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+{"id": "pulmo2$$$ed66933c-0507-4838-8b90-3e3328daf222", "contents": "It might be worth putting dyspnea in a clinical context. Like pain, dyspnea can occur across a number of pathological conditions. It is the cardinal symptom of lung disease, but it is highly prevalent in heart diseases as well\u2014in fact it is a more common sign of myocardial infarction in women than the classical symptom of chest pain that is\u00a0more prevalent in men."}
+{"id": "pulmo2$$$116f070e-6849-4ded-b300-6139c518706b", "contents": "Dyspnea is also a strong predictor of mortality in most heart and lung diseases. As well as cardiopulmonary conditions, dyspnea is also prevalent in other conditions that affect breathing or metabolism, and (see figure 18.1) it is prevalent during end-stage disease where it is as common as pain and forms a significant problem for end-of-life care. Despite its prevalence there are few options for treating this symptom. Unlike pain, there are no specific drugs to reduce this sensation."}
+{"id": "pulmo2$$$f5d49a8e-7472-47f2-aa2e-2ae15bf3322c", "contents": "So now let us look at the distinguishable sensations that the term dyspnea encompasses and begin to understand how they differ neurologically (see figure 18.2)."}
+{"id": "pulmo2$$$971f0265-da9a-4606-aaea-3f064a1f4859", "contents": "Effort to breathe: The first form of dyspnea is the sensation of work or effort to breathe. The healthy individual is usually unaware of the effort they\u00a0are putting into breathing until breathing is significantly increased, such as during exercise when ventilation and work of breathing rises. The sensation of the work or effort to breathe is not particularly uncomfortable. If you jogged down the street now you might become more aware of the effort to breathe, but are not disturbed by it."}
+{"id": "pulmo2$$$e6fc31fa-4351-4dd2-bccd-ff4a91ad3da8", "contents": "An increase in motor drive is required to activate more tension or movement in any skeletal muscle, including the respiratory muscles. And like other skeletal muscles, such as limb muscles, we believe that the sensation of effort comes from a perception of that increased motor drive. Sensory information from the activated muscles, in our case the respiratory muscles, is thought to generate the sensation of work."}
+{"id": "pulmo2$$$133ab222-0225-4d54-bcd5-18c6b4070b00", "contents": "Getting laboratory subjects to report work and effort separately is very difficult, so for our purposes right now, we are grouping what might be two sensations together as one."}
+{"id": "pulmo2$$$a9e094a8-293b-450f-ba3a-bca93185329f", "contents": "Chest tightness: The next form of dyspnea is primarily reported by asthmatic patients during bronchoconstriction. Similar to the sensation of work and effort, tightness was originally thought to arise from the increase in respiratory muscle activity associated with a rise in resistive work of breathing.\u00a0But in 2002 we showed that \u201ctightness\u201d\u00a0was unrelated to respiratory effort by removing respiratory muscle activity of bronchoconstricted asthmatics with mechanical ventilation. When we did this, \u201ctightness\u201d\u00a0persisted, despite the respiratory muscles being inactive. So what does cause tightness? The next best, but so far unproven, alternative is that inflammation of the airways associated with an asthma attack leads to activation of airway irritant (or rapidly adapting) receptors, the afferent activity from which is perceived centrally as tightness."}
+{"id": "pulmo2$$$52ae02da-d9e8-4763-989e-d5354904f7ee", "contents": "Air hunger: Air hunger is arguably the most complex and clinically important form. \u201cAir hunger\u201d\u00a0is the sensation of suffocation and can be described as a \u201cdesperate urge to breathe.\u201d\u00a0You may have experienced this sensation at the end of a prolonged breath-hold, and it is the unpleasantness of air hunger that made you resume breathing. \u201cAir hunger\u201d\u00a0is a warning signal that ventilation is insufficient and blood gases are becoming deranged; given the immediate importance of maintaining constant blood gases, air hunger is perhaps our most important homeostatic signal, and it has been referred to as the \u201csuffocation alarm.\u201d\u00a0The mechanisms underlying air hunger are still unclear, but again, they were once thought to involve the respiratory muscle motor and sensory signals and detection of a disparity between them\u2014that is, the brain perceived that the respiratory muscles were not achieving the work they had been commanded to do. This hypothesis was developed in the sixties and still persists in texts today; however, it is wrong. In two separate labs, one at Harvard University and the other in Australia, pulmonary physiologists completely paralyzed each other to remove all motor activity; when they inhaled carbon dioxide, they still felt air hungry, suggesting the respiratory muscle signals were not essential to generate air hunger. So where does air hunger come from?"}
+{"id": "pulmo2$$$72bffedf-aac4-414b-a6c7-eea6e2e282ec", "contents": "We see air hunger arise when PaCO2 rises, when PaO2 falls, or when arterial pH decreases. These changes are detected by chemoreceptors that reflexly increase the drive to breathe from the brainstem. While we are not usually aware of our reflex breathing drive, we think that once this drive increases to a critical level, a signal is sent upward that is perceived as air hunger."}
+{"id": "pulmo2$$$1453b6a2-caa4-4494-848f-1a198da08ae0", "contents": "So any signals to the brainstem respiratory networks that increase the drive to breathe are likely to promote air hunger, and these influences may not all be chemical (see figure 18.3). For example, emotions such as anxiety increase the drive to breathe, and this is a pertinent point with clinical ramifications that we will return to."}
+{"id": "pulmo2$$$7690de05-839f-42ba-a0b7-de654894948f", "contents": "Likewise, any influences that reduce the drive to breathe also have a tendency to reduce air hunger (see figure 18.3). Perhaps the most interesting example of this is the effect of pulmonary stretch receptor activity. Pulmonary stretch receptors are mechanoreceptors in the airways that respond to lung inflation. Although this pulmonary afferent activity is thought to have little effect on the control of breathing in man, it reduces the drive to breathe in other species as part of the Hering\u2013Breuer reflex. What we see in humans is that lung inflation, and presumably an increase in pulmonary stretch receptor firing, profoundly reduces air hunger, even in the absence of any blood gas improvements."}
+{"id": "pulmo2$$$a9f22713-e80c-40c9-ac82-38c879c982a5", "contents": "This is easy to demonstrate to yourself by holding your breath; during the breath-hold CO2\u00a0will gradually accumulate in your bloodstream and you will feel a gradually increasing urge to breathe that will become increasingly more uncomfortable to a point when it is intolerable and you must begin breathing again. That first big breath you take does not return your arterial CO2\u00a0to normal, but despite this you get great relief from air hunger by taking it, probably because that big breath stretched the lung and caused a rapid increase of stretch receptor activity to the brainstem."}
+{"id": "pulmo2$$$d3edc83e-0deb-4917-8aeb-ee3ced677ae0", "contents": "So air hunger is really affected by a balance of influences:\u00a0those that increase the drive to breathe (such as hypercapnia and hypoxia) promote air hunger, while inhibitory influences on the drive to breathe tend to promote comfort (see figure 18.4)."}
+{"id": "pulmo2$$$8f30f95b-215b-436b-9512-3ae10768618b", "contents": "There are other elements that should be considered when dealing with the air-hungry patient. Probably because of its homeostatic importance, the sensation of air hunger is very effective at getting attention and producing fear and anxiety. Recent comparisons of attentive and emotional impacts suggest air hunger is perceived as much more threatening and worrisome than pain at equivalent intensities. (Ironically we routinely ask about patients\u2019 pain, but rarely about their air hunger.)"}
+{"id": "pulmo2$$$fb7adc11-d772-4195-b5da-be301bfab084", "contents": "This emotional impact of air hunger is reflected in the regions of the brain\u00a0that are consistently seen to be activated in recent functional brain imaging studies (see figure 18.5). The amygdala, anterior insula, and anterior cingulate are all persistently seen to activate during air hunger, and all are either associated with the brain\u2019s fear network or generation of emotional responses. The activation of the anterior insula is also interesting as this phylogenically old part of the cortex also responds to other homeostatic imbalances, such as thirst, hunger for food, and pain. Although air hunger itself is unpleasant, it is these emotional components that produce air hunger\u2019s profoundly negative effect on patients\u2019 quality of life and makes end-of-life distressing for both the patient and their loved ones. We will come back to the\u00a0impact of emotional responses in a moment."}
+{"id": "pulmo2$$$4b7a8014-6af3-445b-b4be-e857a0bc111a", "contents": "So there we are\u2014three different forms of dyspnea, with separate neural mechanisms. That said, it is unlikely that a patient will ever walk into your office and tell you they have \u201cdyspnea,\u201d\u00a0or pinpoint which form of dyspnea they have. But\u00a0taking an interest in the subtleties of your patients\u2019 comments may not be a purely academic exercise either. More likely they are likely to use descriptors like those shown in table 18.1. These descriptors that use more common, everyday language have been related to each form of dyspnea. Knowing which form or forms of dyspnea the patient is experiencing can help in diagnosis as the different causes of dyspnea\u00a0(like those listed in figure 18.1)\u00a0can produce different levels of each form. For example, chest tightness is much more commonly reported by asthmatics, whereas patients with chronic obstructive pulmonary disease tend to use descriptors more related to effort to breathe\u00a0and\u00a0air hunger."}
+{"id": "pulmo2$$$12aa1d7b-d9ba-4fcb-889e-d4973fa700f7", "contents": "Table 18.1: Patient descriptors for the three different forms of dyspnea."}
+{"id": "pulmo2$$$5a0b5c38-5d23-49af-be59-525bac0623e2", "contents": "While the different forms of dyspnea have been investigated, described, and now explored as their potential as diagnostic tools, the emotional impact of dyspnea is only now receiving more attention. The most immediate complication caused by the emotional component is the potential for a positive feedback loop to form between air hunger and the anxiety it generates.\u00a0The anxiety that air hunger produces results in an increased drive to breathe;\u00a0in turn this increased drive to breathe causes the air hunger to increase, which leads to more anxiety and so on (figure 18.6)."}
+{"id": "pulmo2$$$c02eb73c-f5b5-4ccd-8113-3e904d9ae87f", "contents": "Behavioral effects of dyspnea: This cycle can be entered into by different types of patients;\u00a0those with cardiopulmonary disease enter the cycle at the point of the air hunger, whereas patients with anxiety disorders can enter the cycle at this point and can experience significant air hunger even with apparently perfectly normal lung and heart function. On a more long-term basis the quality of life of air-hungry patients can be diminished by another positive feedback scenario that can produce \u201crespiratory cripples\u201d\u00a0of cardiopulmonary patients. The air hunger produced by the underlying disease worsens during exertion, so makes\u00a0exercising uncomfortable. This frequently results in patients avoiding exercise, perhaps starting with taking an elevator instead of the stairs, or driving to the grocery store when previously they might have walked."}
+{"id": "pulmo2$$$0701b412-5140-4761-96ac-7ad79d1b62d8", "contents": "This reduction in exercise leads to cardiac deconditioning, which in turn makes the air hunger worse and leads to further avoidance of exercise. Along with the progression of the disease, this cycle may leave the patient out-of-breath while simply sitting in a chair."}
+{"id": "pulmo2$$$ff30a35d-ec49-4a2b-8402-f685ad7483bb", "contents": "The patient\u2019s quality of life becomes severely diminished as their life is ruled by dyspnea that prevents them from leaving the house, interacting with children or grandchildren, and performing simple activities that used to bring enjoyment, such as gardening, wood-working, walking, and more. This reduced quality of life can potentially lead to depression, and the emotional response to dyspnea may be exacerbated."}
+{"id": "pulmo2$$$3fa222a8-44f6-40e4-9700-b4c786fbd3df", "contents": "So what can be done to relieve the patient\u2019s air hunger and the associated anxiety? Well, despite its prevalence, the treatment of dyspnea is decades behind the treatment of pain. For too long the approach to treating dyspnea has been to treat the underlying disease with the expectation that the dyspnea will go away.\u00a0This is true and a perfect course of action for many conditions, but for many diseases that produce dyspnea we have ineffective cures, such as emphysema, lung cancer, and pulmonary fibrosis. How do we make the 49 percent\u00a0of terminally ill patients who suffer with dyspnea at the end of life more comfortable?"}
+{"id": "pulmo2$$$96bf1610-7ea3-41bb-83c4-4fe808ffa128", "contents": "Opioids: A common practice is to use opioids, but the mechanism of how they might work and indeed their overall efficacy has been disputed. There are a number of routes for how\u00a0morphine may act, if it indeed does so. Opioids may have a direct inhibitory effect on the central networks that generate air hunger, or\u00a0at higher dose concentrations they may reduce air hunger indirectly by causing respiratory depression\u2014that is, they tackle air hunger at what we think to be its source. Alternatively, opioids may reduce the affective or emotional component of dyspnea (i.e., the patient may perceive air hunger, but simply is not\u00a0as bothered by it). Recent work from Harvard University suggests that morphine has a direct effect on both the sensory and affective components of air hunger independent of its effect on ventilatory drive."}
+{"id": "pulmo2$$$acd95dde-e94e-456d-b79c-aaf7cda0accb", "contents": "Anxiolytics: As the emotional component of air hunger is so strong, the fear and anxiety produced can be treated in the absence of any specific drug to treat the air hunger itself. Use of anxiolytics drugs has also produced mixed results that may be complicated by the patient\u2019s underlying condition, and whether the type of anxiolytic causes ventilatory depression."}
+{"id": "pulmo2$$$98681128-282c-4676-af4c-e9237fc4b75c", "contents": "Furosemide: Although there is currently no drug that specifically tackles air hunger, there is a growing body of evidence that inhaled furosemide (the loop diuretic) reduces air hunger by sensitizing pulmonary stretch receptors, meaning they fire more for any given lung volume. This amplifies the stretch receptors\u2019 inhibitory effect on air hunger described earlier, by fooling the brain into thinking the lungs are at a greater volume than they really are."}
+{"id": "pulmo2$$$d4f7d731-abe8-4b12-9515-b817f4c6a042", "contents": "Nonpharmaceutical alternatives: A nonpharmaceutical alternative is to simply cool the patient\u2019s face with a fan or wet cloth. This facial cooling initiates the \u201cdiving reflex\u201d\u00a0via the trigeminal nerve. One component of the diving reflex is to reduce ventilatory drive at the brainstem\u2014an ideal response if one is heading underwater."}
+{"id": "pulmo2$$$2f2f59dd-03fc-41e1-b326-987748de2c35", "contents": "This inhibition of ventilatory drive is likely responsible for the moderate reduction in air hunger seen with facial cooling."}
+{"id": "pulmo2$$$7276f9ff-0abe-46ec-add8-1d0160bf075e", "contents": "Rehabilitation and desensitization: While dyspnea can be addressed by other methods than those briefly described here, few have been shown to work consistently or effectively. On a more long-term basis, breathing training and pulmonary rehabilitation appear to help patients overcome exacerbations of their disease or even reduce chronic air hunger, but both require patient cooperation and compliance and may have limited effect in severe disease. What can be taken from the literature is that the treatment of dyspnea is in desperate need of more attention. For a symptom that is so common and has such an impact on patients, dyspnea is a clinical issue that is woefully underaddressed."}
+{"id": "pulmo2$$$709e47ee-7a91-414c-81cc-5c3752c06c47", "contents": "American Thoracic Society Committee on Dyspnea. \u201cAn Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea.\u201d American Journal of Respiratory and Critical Care Medicine 185, no. 4: 435\u201352. https://doi.org/10.1164/rccm.201111-2042ST."}
+{"id": "pulmo2$$$d5f1a15f-0fcf-40e5-aa89-9237e2b68c6a", "contents": "Banzett, Robert B., Robert W. Lansing, and Andrew P. Binks. \u201cAir Hunger: A Primal Sensation and a Primary Element of Dyspnea.\u201d Comprehensive Physiology 11, no. 2 (April 2021): 1449\u201383. https://doi.org/10.1002/cphy.c200001."}
+{"id": "pulmo2$$$eaf7bcbf-edca-4466-9a42-b46c6949eff1", "contents": "In this chapter we will have a look at the regions of the nervous system that control breathing and how they interact or override each other."}
+{"id": "pulmo2$$$45109a72-ff09-4e18-a1a0-2ed04fe649a5", "contents": "It has long been known that the brainstem contains critical centers for the control of breathing. These regions produce what is often referred to as the reflex drive to breathe, or brainstem drive to breathe. Despite its critical nature for survival, this involuntary motor drive that operates the respiratory muscles is barely understood."}
+{"id": "pulmo2$$$595fcd21-2569-4627-86c5-5d68eb0636ed", "contents": "What we will do here is summarize some basic information to create a coherent and accurate overview."}
+{"id": "pulmo2$$$e86d1c9f-5259-49bb-b6f4-405933b1bf97", "contents": "The reflex drive to breathe is a typical reflex arch, with receptors in the vasculature and lung reporting to a central controller in the brainstem that implements its effects via the respiratory muscles. What is different from\u00a0most simple reflexes is that the controller is rather complex and can be thought of as a central hub that integrates inputs from multiple sources."}
+{"id": "pulmo2$$$d4768435-0fdd-4197-8f2a-aab985042149", "contents": "Many visceral sensors supplying the controller in the brainstem send their afferent signals via the glossopharyngeal and vagus nerves to the nucleus tractus solitaries, or NTS. This input station is part of an anatomically indistinct region on the dorsal surface of the medulla, called the dorsal respiratory group or DRG. The DRG connects to motor neurons that lead to the inspiratory muscles."}
+{"id": "pulmo2$$$b610698c-7867-40bf-9f03-839655118614", "contents": "These DRG (figure 17.1) neurons show ramp-like bursts of activity that cause inspiratory muscle contraction to induce inspiration, then stop, allowing the inspiratory muscles to relax and passive exhalation to begin. This intermittent ramp of activity can be modulated by input from the sensors or other regions of the central nervous system, but it is not spontaneous; rather this activity is initiated by another respiratory pacemaker. It was this pacemaker that eluded physiologists for decades."}
+{"id": "pulmo2$$$d8b83920-c9e5-4c00-94ef-666420f6e650", "contents": "On the other side of medulla is the ventral respiratory group (figure 17.1), which has been known for a long time to contain circuits that contribute to the control of breathing within its rostral, intermediate, and caudal regions. Within the intermediate region a cluster of neurons called the pre-B\u00f6tzinger complex (figure 17.1) with apparently spontaneous activity is currently thought to be the respiratory pacemaker. The pre-b\u00f6tzinger complex is likely responsible for the activity of the DRG inspiratory neurons to produce the ramping activity."}
+{"id": "pulmo2$$$5964420c-b5bc-46f6-9eda-53aa0a34e0cc", "contents": "The ventral respiratory group\u00a0also contains neurons with inspiratory-related activity and connections to the inspiratory motor neurons. It is better known for its expiratory neurons, however, which\u00a0are capable of activating the expiratory muscles when expiration must become active rather than remain passive. During quiet resting breathing, these expiratory neurons remain dormant."}
+{"id": "pulmo2$$$c90b1cb4-2cce-4fac-aff5-e33efe169340", "contents": "This medullary circuitry can be influenced by other brainstem centers thought to be responsible for fine-tuning the breathing rhythm."}
+{"id": "pulmo2$$$54677cd2-0ea5-437f-a884-bdf43ab1c066", "contents": "The Apneustic center in the lower pons (figure 17.1) excites the inspiratory neurons and prolongs the ramp activity they produce; this inevitably produces a prolonged inspiratory period. Higher up in the pons is the Pneumotaxic center (figure 17.1), which\u00a0acts as an off switch for inspiratory neurons;\u00a0thus it regulates inspiratory volume and indirectly influences the rate of breathing, tending to increase it. This is a very basic overview of the breathing circuitry that is capable of generating inspiration\u00a0and active expiration when needed. But these centers take information and direction from other neural influences, including chemoreceptors, receptors in the lung, and higher brain centers.\u00a0We will look at the latter two now."}
+{"id": "pulmo2$$$131d0e8e-0e90-43eb-bd29-2da7eadc4a8f", "contents": "The brainstem drive to breathe can be modulated from above and from below. The literature about whether these influences increase or decrease the drive to breathe is often confused, perhaps because of the wide range of experiments performed and the different species used. We will have a look at some of the most consistent and clinically pertinent aspects here, starting in the lung and three populations of intrapulmonary neural receptors."}
+{"id": "pulmo2$$$b9b6f27e-0866-410e-b07c-8c8539553429", "contents": "Pulmonary stretch receptors\u00a0are mechanoreceptors found in airway walls and smooth muscle. As their name suggests, they respond to expansion of the lung, and their afferent activity to the brainstem increases with lung volume, as figure 17.2 shows. Upon arrival at the NTS the PSR activity tends to inhibit inspiratory neurons and can stop inspiratory activity completely in other species (the Hering\u2013Breuer reflex). However, their influence on the control of breathing in humans is weak, and while they might not contribute to the control of breathing in man, they likely influence respiratory sensations, such as shortness of breath."}
+{"id": "pulmo2$$$9a879c60-0390-4150-b2e0-feb665277246", "contents": "Irritant receptors are found in the airway epithelium and are ideally placed to perform their role of detecting harmful substances entering the lungs, such as noxious gases, particulates, and even cold air. They generally have an inhibitory influence on the drive to breathe, perhaps as an attempt to limit the amount of noxious substance entering the lung. Other components to their defensive strategies are bronchoconstriction and induction of the cough reflex. Their response to inflammatory mediators also suggests they may play a role in asthma."}
+{"id": "pulmo2$$$0d90f985-2aad-4750-9b34-83804b15cdcf", "contents": "J-receptors, or Juxtacapillary receptors, are found at the junction of the pulmonary capillaries and alveoli. These receptors respond to increases in interstitial pressure so are likely to play a role in the response to pulmonary edema. Their effect on the drive to breathe can be regarded as excitatory as they cause an increase in breathing rate as part of the J-reflex, which includes cardiac components and is intended to prevent over-exercising and cardiopulmonary collapse. As such the J-receptors may also contribute to generating the sensation of shortness of breath."}
+{"id": "pulmo2$$$c259f790-0487-49a7-a758-669eee1efafa", "contents": "These\u00a0three pulmonary receptor groups are the three that usually appear in textbooks, perhaps because of their clinical pertinence, but perhaps because we know most about these. Others exist, and details can be found in other sources. We will now focus briefly on the influence of higher centers on breathing, and these are generally all positive (i.e., cause an increase in breathing). Cortical influences are numerous and undefined, that collectively they produce what is referred to as the wakeful drive to breath. The extent of cortical influence is best illustrated by sleep, when the higher brain is unconscious and any wakeful drive is removed. During sleep breathing is significantly reduced\u2014enough so that arterial PCO2\u00a0is several mmHg higher than during wakefulness. This suggests that cortical influences on breathing are enough to cause a lower PaCO2\u00a0than would be determined by chemoreflexes alone."}
+{"id": "pulmo2$$$39d62e67-bec0-4e7e-af31-d09054aac299", "contents": "More specific influences from higher centers include emotions; anger, anxiety, sadness, happiness, and sexual arousal all influence the drive and pattern of breathing. This is perhaps best exemplified by emotionally driven sighs or the frankly bizarre activity of laughter. But the list of higher center influences does not stop there;\u00a0indeed it is\u00a0likely that we still yet do not\u00a0know where it stops. Changes in light changes breathing, a sudden loud sound changes breathing,\u00a0doing a mathematical problem changes breathing\u2026 and so on. And unfortunately for clinicians and pulmonary physiologists, the act of measuring breathing\u00a0changes breathing. So it is likely that all those textbook numbers for normal respiratory rate and depth are all too high, as telling someone you are going to measure their breathing usually causes them to hyperventilate."}
+{"id": "pulmo2$$$586782ef-9a4f-4ff2-a0f7-601efb0c851d", "contents": "Breathing is also a rare incidence of being able to voluntarily control a normally reflex activity (e.g., we can willfully override reflex breathing to perform speech or a breath-hold). In fact, we have as precise control over our respiratory muscles as we have control over the muscles in our hands. Humans maybe be exclusive in this respect because of our elaborate speech, but again, this is another unknown. However, eventually reflex breathing will always reclaim its command over breathing\u2014as anyone who has performed a prolonged breath-hold will know."}
+{"id": "pulmo2$$$c9b06272-d486-4a78-a571-8018c1ba6ce2", "contents": "So we have seen that at the heart of the control of breathing there is a pacemaker establishing a basic rhythm and depth of breathing, but this is influenced by numerous other factors from both the lung and higher brain. These influences adjust breathing via the brainstem to produce respiratory responses to the environment and\u00a0changes in emotional state, and contribute to efficient and appropriate levels of ventilation."}
+{"id": "pulmo2$$$4b40d226-7425-49f8-b741-e4f66e18c57a", "contents": "It perhaps comes as no surprise that the major influence on the reflex drive to breathe comes from the homeostatic need to match ventilation with metabolic demand and maintain blood O2, CO2, and pH within narrow ranges. The chemoreflexes are therefore capable of\u00a0sensing changes in arterial oxygen, carbon dioxide, and pH, modifying the activity of the brainstem respiratory centers and affecting an appropriate change in alveolar ventilation. These reflexes all act as classical negative feedback circuits and are capable of maintaining despite large changes in O2\u00a0consumption and CO2\u00a0production by metabolizing tissue."}
+{"id": "pulmo2$$$ec911790-4994-421d-95fb-f8cb2839638c", "contents": "Before getting into the details of the chemoreceptors, let us take a quick overview of the basic circuitry of the chemoreflexes (figure 17.3). There are two sets of sensors in our circuit:\u00a0the peripheral chemoreceptors that are in the vasculature, and the central chemoreceptors that are found on the surface of the brainstem. The central chemoreceptors are capable of detecting changes in arterial CO2, while the peripheral chemoreceptors respond to changes in CO2, O2, and arterial pH."}
+{"id": "pulmo2$$$621a5b3a-b03b-456f-8755-29de9f879f11", "contents": "Upon excitation by changes in blood gas values, the receptors fire back to the reflex\u2019s controller, the respiratory centers in the brainstem. This results in an increase in reflex ventilatory drive\u00a0and a greater motor signal to the respiratory muscles. This produces an increase in alveolar ventilation that corrects the blood gas disturbances and stops the chemoreceptors from firing."}
+{"id": "pulmo2$$$14e4f4f0-e774-4f43-852e-b59d08bff992", "contents": "With that basic circuit in mind, let us now look more closely at the chemoreceptors and the ventilatory responses they can induce."}
+{"id": "pulmo2$$$b7f684d1-4ed5-4149-8ea1-c6198879fb0d", "contents": "We will start with the central chemoreceptors. The central chemoreceptors are comprised of chemosensitive neurons on the ventral surface of the medulla found close to the entry points of the glossopharyngeal and vagus nerves (coincidentally these are the nerves bringing in afferent information from the peripheral chemoreceptors and the pulmonary mechanoreceptors)."}
+{"id": "pulmo2$$$0795dcc1-1692-44cd-a472-fe878343915c", "contents": "Although the central chemoreceptors do not respond to hypoxemia and only respond to rises in arterial CO2, their activity accounts for about 80 percent\u00a0of the hypercapnic ventilatory response. Given the critical importance of maintaining a normal PaCO2, these are considered the most important chemoreceptors for minute-by-minute regulation of ventilation. Ironically they do not respond to CO2\u00a0directly, but rather to changes in pH of the cerebrospinal fluid (CSF)."}
+{"id": "pulmo2$$$65c5fe4d-2b9c-4e95-bb01-2949d3470676", "contents": "This complication comes from the fact that the central chemoreceptors are not exposed to the blood, but rather are behind the blood brain barrier\u00a0and bathed in CSF. Hydrogen ions and bicarbonate cannot pass through the blood brain barrier, but CO2\u00a0can. Once through the blood brain barrier, CO2\u00a0forms carbonic acid in the reaction that is very familiar to you. It is the hydrogen ion from the dissociated carbonic acid that stimulates the chemoreceptors. So the central chemoreceptors respond to a rise in arterial CO2\u00a0via a change in CSF pH. Because there is little protein in the CSF, there is little buffering capability, and pH changes here tend to be greater than in the blood where plasma proteins are plentiful. This makes the central chemoreceptors quite sensitive and partly explains their substantial role in CO2\u00a0control."}
+{"id": "pulmo2$$$43102078-7420-47e1-ac1f-8ee18dc62425", "contents": "Prolonged exposure to high CO2, such as in chronic lung disease, can lead to a rise in CSF bicarbonate. This bicarbonate buffers hydrogen ions and reduces the sensitivity of the central chemoreceptors. This partly explains why the hypercapnic ventilatory response diminishes over time in chronic lung patients, such as those with COPD."}
+{"id": "pulmo2$$$53bcaa8e-3968-4dd6-af8f-0b7263f68ef2", "contents": "The peripheral chemoreceptors are directly exposed to arterial blood and are capable of responding to changes in CO2, O2, and pH. There are two populations of chemoreceptive cells in the vasculature (see figure 17.4). One population is found in the aortic arch\u00a0and is referred\u00a0to as the aortic bodies. These are wired into the brainstem through afferent fibers that project to and join the vagus nerve. The other chemoreceptor is comprised of the carotid bodies, found in the bifurcation of the common carotid arteries. These connect to the brainstem through the carotid sinus and the glossopharyngeal nerves. The carotid bodies are by far the most important in humans, with the aortic bodies contributing very little to any ventilatory response."}
+{"id": "pulmo2$$$105e0bd6-ef24-40ab-8c61-0cb33135cca7", "contents": "Although the carotid bodies play little role in reflex response to CO2, their response to hypercapnia is more rapid than the central chemoreceptors and so they are capable of breath-by-breath regulation and responding to abrupt changes in arterial PCO2. More importantly the peripheral chemoreceptors are entirely responsible for the response to hypoxia. The mechanism as to how these receptors work is unclear, but cells within the carotid bodies have very high metabolic rates and receive a proportionately high blood flow. It is likely that a decline in oxygen interrupts their metabolism and reduces their inhibitory interaction on neurotransmitter-filled neighboring cells, allowing excitation of the carotid sinus nerve.\u00a0Their response to a decline in blood oxygen is far from linear. A decline in PO2\u00a0below 100 mmHg causes little change in\u00a0action potential firing, but the rate of firing rapidly increases at PO2s below 50. This is reflected in the hypoxic ventilatory response illustrated in the graph in figure 17.5."}
+{"id": "pulmo2$$$7d454584-4e63-4a14-bc6f-e71196169e7b", "contents": "Because of this, the hypoxic ventilatory response normally plays little role in the control of breathing in humans. The hypoxic ventilatory response becomes more significant at altitude when inspired PO2\u00a0is low, or more pertinently in lung disease, where alveolar ventilation or gas exchange is compromised."}
+{"id": "pulmo2$$$439b2a3b-9500-414a-aa44-02adc653c5fd", "contents": "The hypercapnic ventilatory response (figure 17.6) is much more influential on breathing in humans on a normal day-to-day basis. The response is very linear, with a rise in PCO2\u00a0producing a proportionate rise in ventilation, driven of course primarily by the central chemoreceptors, but also contributed to by\u00a0the afferent activity of the peripheral receptors."}
+{"id": "pulmo2$$$b4e8594d-4342-429e-a1d3-29deb926f070", "contents": "The central and peripheral chemoreceptors keep arterial PCO2\u00a0within very fine limits, primarily because of CO2\u2018s effect on pH. Alveolar ventilation rapidly increases with even a moderate rise in arterial CO2, but can completely stop (apnea) if arterial CO2\u00a0falls below normal (~40 mmHg). The wakeful drive to breathe tends to keep CO2\u00a0a little lower than the set-point of the chemoreceptors\u2014a point illustrated during sleep, when the brainstem has complete control of breathing and PaCO2\u00a0is seen to rise a few mmHg."}
+{"id": "pulmo2$$$64b429be-4d21-4cce-b4be-01fbc2ba73c4", "contents": "The hypercapnic ventilatory response\u00a0adapts to chronically elevated arterial CO2, such as in severe lung disease. Here we not only see the CSF increase its buffering capacity with increased bicarbonate, but we also see the chemoreceptors change their set-point. It is not uncommon to see COPD patients with arterial PCO2s above 60."}
+{"id": "pulmo2$$$a7b008bd-dbb5-41e3-9c1e-334d7f944f71", "contents": "Finally, the hypoxic and hypercapnic ventilatory responses are not independent, and when they are both present at the same time a potentiation is seen (i.e., the response to hypoxic and hypercapnia is greater than the sum of the two individual responses)."}
+{"id": "pulmo2$$$f5c85927-3e75-41d5-a3dc-748f9aab2b25", "contents": "The hypoxic ventilatory response we have just looked at was measured at an alveolar PCO2\u00a0of 35.8 mmHg. If the same test is performed at higher PCO2s (figure 17.7), then the hypoxic ventilatory response is much greater, as shown by these upwardly shifted lines when alveolar PCO2\u00a0is set to 43.7 mmHg and 48.7 mmHg."}
+{"id": "pulmo2$$$4b57208b-e130-430c-bd66-a47e7bc49def", "contents": "Likewise, the hypercapnic ventilatory response is exaggerated in the presence of hypoxia (see figure 17.8). The hypercapnic ventilatory response we have just looked at was measured at a \u201cnormal\u201d\u00a0alveolar PO2\u00a0of 110 mmHg. If the hypercapnic response is measured in the presence of hypoxia, then the curve shifts upward, as shown by\u00a0the upper lines when alveolar PO2 is reduced to 47 mmHg and 37 mmHg. This potentiation likely comes from the peripheral chemoreceptors, whose firing rate is potentiated in the presence of both stimuli. Consequently, when a patient is both hypoxic and hypercapnic, then they are likely to have a very high drive to breathe, and when this occurs they are likely to feel very short of breath\u2014the topic of the last chapter."}
+{"id": "pulmo2$$$d1eb2ee4-c45e-4b70-bebb-601f16788991", "contents": "The chemoreflexes modulate breathing to maintain constant arterial blood gases and pH. These reflexes are initiated by central sensors that respond to hypoxia and peripheral sensors that respond to hypercapnia, hypoxia, and changes in arterial pH. Together these sensors can maintain arterial blood gases within narrow ranges despite large changes in oxygen consumption and CO2\u00a0production associated with changes in metabolic rate."}
+{"id": "pulmo2$$$114c8441-5da7-4816-9a98-ebe7006695e0", "contents": "Levitsky, Michael G. \u201cChapter 9: Control of Breathing.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$73bce2fb-98ad-41f3-8101-4bf9af7e048d", "contents": "West, John B. \u201cChapter 8: Control of Ventilation\u2014How Gas Exchange Is Regulated.\u201d In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012."}
+{"id": "pulmo2$$$b8d4a9c3-0d94-4647-88e2-309c65d3b974", "contents": "Widdicombe, John G., and Andrew S. Davis. \u201cChapter 8\u201d and \u201cChapter 9.\u201d In Respiratory Physiology. Baltimore: University Park Press, 1983."}
+{"id": "pulmo2$$$db0a65e0-e669-4647-b737-5a183e68a90c", "contents": "The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the \u201cglobin\u201d\u00a0part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2\u00a0and also hydrogen ions\u2014a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish\u00a0the molecule\u2019s gas carrying ability."}
+{"id": "pulmo2$$$b3772caa-6325-41b5-beea-7c431fd6d4b3", "contents": "The heme component of hemoglobin is an iron-containing porphyrin molecule capable of binding with oxygen. Each of the four polypeptide chains contains a heme molecule, meaning that each hemoglobin molecule is capable of transporting four oxygen molecules. It is\u00a0also worth noting that binding of oxygen to the heme molecule induces a conformational change that results in oxyhemoglobin having some different behaviors and indeed color to deoxyhemoglobin. We will look at some of these differences in behavior later on."}
+{"id": "pulmo2$$$305cc335-e478-4f77-85c3-749b48edc277", "contents": "It is\u00a0also worth reviewing hemoglobin\u2019s home here as well\u2014the red blood cell (RBC). The red blood cell\u2019s classic biconcave shape provides a large surface area for gas exchange and also means that no hemoglobin molecule inside is very far from the edge of the cell, cutting down on the diffusion distance of gases. The cell is also very flexible, making it capable of squeezing through narrow and twisting capillaries so that its walls and those of the capillary may be in\u00a0close contact and again diffusion distances are reduced."}
+{"id": "pulmo2$$$396c63b3-8995-41de-a103-31ebc88c8ab7", "contents": "Each RBC is capable of holding up to 250 million hemoglobin molecules, so consequently is capable of holding one billion oxygen molecules; as such the RBC fulfills its primary role of oxygen transport well. This oxygen transport system fails in anemias that result in either too few red blood cells\u00a0or too little hemoglobin in each cell (or both). Now let us look at the behavior of hemoglobin."}
+{"id": "pulmo2$$$b3a2853f-4d49-466c-b233-b1e3ad132937", "contents": "The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent\u00a0saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin,\u00a0telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin\u2019s affinity for oxygen over a range of PO2."}
+{"id": "pulmo2$$$240bd48e-3307-4e02-a6c4-3980b6721979", "contents": "First\u00a0let us put the curve in a physiological context. The alveolar PO2\u00a0is around 100 mmHg. This means that as blood passes the alveoli and is exposed to this PO2, then oxygen saturation becomes close to 100 percent, about 98 percent. The first important physiological feature of this curve is that PO2\u00a0can fall a considerably long way before it has an impact on oxygen saturation. So, taking time to look at the numbers on the graph, let us say, for example, that a patient begins to hypoventilate and alveolar PO2\u00a0falls to 70 mmHg; while this is a considerable fall in PO2, the saturation will only fall a few percentage points, and PO2\u00a0must\u00a0fall to 50 before significant loss of saturation, or desaturation, occurs. Below 50, however, notice how the curve rapidly steepens, and now for a small change in PO2, we get a large desaturation."}
+{"id": "pulmo2$$$57274494-19e2-4442-a9f6-72dc7f08e65a", "contents": "This steep section of the curve is therefore clinically critical. If your patient\u2019s saturation monitor reads 83 percent\u00a0what should spring into your mind is it that such a low saturation puts the patient onto the steep part of the curve. It will now take only a small further decline in alveolar PO2\u00a0to have a profound effect on saturation, unlike at the top and flat section of the curve where small changes in alveolar PO2\u00a0have very little effect on saturation."}
+{"id": "pulmo2$$$ae59bbfa-2b77-438a-a039-3640d3f50564", "contents": "So what is the advantage of having such a steep curve at lower PO2s? Let us look at the physiological situation again. We have\u00a0already said that the alveolar PO2\u00a0of 100 results in a saturation close to 100 percent (i.e., at the lung the hemoglobin\u00a0has a high affinity for oxygen and becomes fully saturated)."}
+{"id": "pulmo2$$$9db43d4c-5e74-4450-aeb0-f34c80abd999", "contents": "At the tissue, however, we want hemoglobin\u00a0to lose its affinity for oxygen and release some to the metabolizing cells. At the tissue the local PO2\u00a0is much lower, around 40, because of the oxygen consumption by the tissue. At the lower PO2, hemoglobin\u2019s affinity for oxygen falls, and it will lose some of its oxygen to the tissue and saturation will fall. This is ideal, as now our oxygen carrier is capable of releasing oxygen where it is\u00a0needed."}
+{"id": "pulmo2$$$5b86e2bb-12a9-4a32-80fa-554e0dcae3ee", "contents": "If tissue PO2\u00a0falls even lower, such as when metabolic rate is high, then more oxygen will be released by hemoglobin as its affinity for oxygen declines with the lower tissue PO2. Therefore the delivery system for oxygen is intrinsically tied to metabolic rate."}
+{"id": "pulmo2$$$56b865af-bc70-47ec-8696-ba94d1f42869", "contents": "The shape of this curve makes hemoglobin a remarkable molecule\u2014able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3."}
+{"id": "pulmo2$$$fc79ef8e-374a-45ad-b458-bf2beabb7f8e", "contents": "The metabolic rate of tissue determines its oxygen demand, with more active\u00a0tissue requiring hemoglobin to relinquish more oxygen. So there are several other factors, beyond low local PO2, that are associated with active tissue that cause hemoglobin to reduce its affinity for oxygen and therefore release it. Tissue with a high metabolic rate tends to have (1) higher temperature, (2) high PCO2, and (3) lower pH. We can look at the effect of each of these factors on the saturation curve."}
+{"id": "pulmo2$$$2bb04c75-d144-4a6c-9c8e-4498ac2e1887", "contents": "Shifts with temperature: Figure 16.4\u00a0shows the saturation curve at difference tissue temperatures. The curve we have just looked at was at 38\u00baC. Notice that as temperature is reduced, the curve shifts to the left, but more importantly (physiologically) when temperature increases then the curve shifts to the right. Let us look at what this means in terms of hemoglobin\u2019s affinity for oxygen (follow the numbers on the graph again). As before, we will assume that our tissue PO2\u00a0is 40 mmHg, and at normal temperatures this results in a saturation of about 70 percent."}
+{"id": "pulmo2$$$da148794-5848-490d-b6cf-40af24935c19", "contents": "Now at the same PO2\u00a0but a higher temperature (e.g., 43\u00baC) the hemoglobin\u00a0O2\u00a0saturation falls to a little over 50 percent, meaning that more oxygen has been relinquished to the tissue (i.e., an increase in temperature reduces hemoglobin\u2019s affinity for oxygen)."}
+{"id": "pulmo2$$$211cabf9-d406-4501-9908-849d3790c833", "contents": "Shifts with CO2: We see a similar situation with a rise in PCO2, shown in figure 16.5\u00a0with the saturation curve at different PCO2s. At a normal arterial PCO2\u00a0(40 mmHg) we get the same saturation\u00a0curve that we saw previously. But if PCO2 is raised, such as in the locality of highly active tissue (e.g., 80 mmHg), then the curve shifts rightward. Again this means that hemoglobin\u2019s affinity is lowered at equivalent PO2 and more oxygen is released, resulting in a lower saturation."}
+{"id": "pulmo2$$$b7dca429-0ab1-4cc0-8453-0f8954dbb0b6", "contents": "Shifts with pH: Finally, the same is true for changes in pH, shown in figure 16.6\u00a0with the curve at different pHs. When pH falls, as in active tissue, then the curve shifts rightward from its normal position at normal pH (7.4). Again, this result\u00a0describes a lowered affinity for oxygen, so at equivalent levels of PO2 more oxygen is released when the hemoglobin enters a low pH environment (e.g., 7.2 shown on figure 16.6). Obviously pH and PCO2 are related, and their effect on hemoglobin\u00a0binding is known as the Bohr effect."}
+{"id": "pulmo2$$$586eb5e0-d3bf-4f95-8cd4-ded1f58d5fad", "contents": "One last factor that causes this rightward shift is 2,3 diphosphoglycerate, or DPG. DPG is an end product of RBC metabolism, and as it increases inside the cell it reduces hemoglobins, affinity for oxygen. Elevated DPG levels are associated with chronic hypoxia, such as experienced at altitude\u00a0or more pertinently in the presence of chronic lung disease. Conversely, DPG levels are lower in stored blood, so transfused blood may have a problem giving up its oxygen."}
+{"id": "pulmo2$$$1fef71c1-4e58-4c5b-a2dd-2ff64270fa82", "contents": "All these factors mean that hemoglobin will deliver more oxygen to busy tissue."}
+{"id": "pulmo2$$$3a1b9676-8f37-4ed5-a186-1380b218d734", "contents": "Total oxygen carriage: So far we have discussed oxygen transport in terms of hemoglobin only. But despite its lack of solubility, some oxygen can dissolve into the plasma. Realistically this is a very small amount at physiological partial pressures (i.e. at an alveolar PO2 of 100 mmHg only a fraction of a milliliter of oxygen will dissolve into the blood, as figure 16.7 shows)."}
+{"id": "pulmo2$$$4fb823cf-5ec6-4af0-be80-d21a46d8957e", "contents": "Obviously this amount of oxygen is completely inadequate to support metabolism and illustrates the need for hemoglobin. But this minute amount when added to the O2 combined to the hemoglobin makes up the total O2 content of the blood. When calculating the oxygen content of the blood we must consider both of these compartments\u2014hemoglobin and plasma (figure 16.8)."}
+{"id": "pulmo2$$$69c1fbb3-0b29-4514-8c8a-c0863b81c461", "contents": "To calculate the arterial oxygen content (CaO2) let us\u00a0first look at the factors affecting the majority of the O2\u00a0(i.e., that carried by hemoglobin)."}
+{"id": "pulmo2$$$69c2b43e-592a-46b1-96c1-da3fe9945ea7", "contents": "(1)\u00a0This will be determined by the amount of hemoglobin\u00a0in the blood (measured in mg/dL). So let us start building the equation."}
+{"id": "pulmo2$$$33932dfc-4b2a-4a78-9760-aba3490f8456", "contents": "Equation 16.1"}
+{"id": "pulmo2$$$d456d8cd-fad4-4ca1-98be-4008fb1eaa32", "contents": "[latex]C_aO_2 = Hb (mg/dL)...[/latex]"}
+{"id": "pulmo2$$$b5b2dd19-2d9a-4a24-8cf8-f07cb3669f6c", "contents": "(2)\u00a0Second,\u00a0we must\u00a0consider the oxygen carrying capacity of Hb, which is 1.34 mL O2/gm Hb. So we multiply the amount of Hb\u00a0by its carrying capacity."}
+{"id": "pulmo2$$$58c0c348-28c4-421e-a673-d53c692e9c56", "contents": "Equation 16.2"}
+{"id": "pulmo2$$$84fd4d16-1c87-49dc-af8f-00fbbd924a75", "contents": "[latex]C_aO_2 = Hb (mg/dL) \\times 1.34\\, O_2/gmHb...[/latex]"}
+{"id": "pulmo2$$$fb6453fd-b83c-4d3f-8ff2-ab30dd947845", "contents": "(3)\u00a0But that carrying capacity might not have been reached by all the Hb (i.e., the Hb may not be fully saturated). So to account for this, we multiply by the saturation (SaO2)."}
+{"id": "pulmo2$$$7a55c7b8-49eb-41b1-bdaa-390a39806795", "contents": "Equation 16.3"}
+{"id": "pulmo2$$$30941166-4918-4c1d-a080-a78d798357d6", "contents": "[latex]C_aO_2 = Hb (mg/dL) \\times 1.34\\, O_2/gmHb \\times S_aO_2...[/latex]"}
+{"id": "pulmo2$$$957b8eb3-a276-49c1-a654-407f3a583575", "contents": "(4)\u00a0So far that takes care of the O2\u00a0associated with Hb (normally about 98 percent\u00a0of the total). Now we must add the O2\u00a0in plasma to the equation. We do this by measuring the PaO2\u00a0and multiplying it by a solubility coefficient (0.003 mL O2/mmHg/dL) to convert it\u00a0from a partial pressure to milliliters. Removing the units makes this long but simple equation a little easier to understand. It has two components, representing the two compartments for O2\u00a0carriage."}
+{"id": "pulmo2$$$cf6cbe39-934e-4e9f-9bdc-4e65f86ad420", "contents": "Equation 16.4"}
+{"id": "pulmo2$$$8e138379-435d-4053-a62f-7d8fcdd0fe86", "contents": "[latex]C_aO_2 = (Hb \\times 1.34 \\times S_aO_2) + (P_aO_2 \\times 0.003)[/latex]"}
+{"id": "pulmo2$$$286888cb-8929-4ded-b263-66f1cfff7b2d", "contents": "The plasma component is usually inconsequential, but may become more important when blood is exposed to an elevated alveolar PO2, such as during oxygen or hyperbaric therapy."}
+{"id": "pulmo2$$$4cb10e9b-4aca-4b40-bea4-f60cbbaac50e", "contents": "So to summarize, as oxygen\u2019s lack of solubility means metabolic demands cannot be met by dissolved oxygen alone, the vast majority of oxygen is transported by hemoglobin, a molecule that is beautifully designed to pick up oxygen at the lung and release oxygen in proportion to the tissue\u2019s demand. We will see more of hemoglobin\u2019s sophistication when we address CO2\u00a0carriage."}
+{"id": "pulmo2$$$d9051fb8-839a-427f-beac-fc950efbeb58", "contents": "Unlike oxygen, carbon dioxide is soluble enough that it does not\u00a0need a protein carrier like oxygen needs hemoglobin to enter and exit plasma. However, this does not\u00a0necessarily mean that CO2\u00a0transport is simple. The complication this time is\u00a0that free dissolved CO2\u00a0forms carbonic acid, which can threaten pH homeostasis. So most CO2\u00a0is not transported in the dissolved form. Most (approximately 70 percent) of the CO2\u00a0that emerges from metabolizing tissue is converted to bicarbonate with the help of enzymes within red blood cells. We will look at this more closely in a moment. About 15\u201325 percent\u00a0is transported on hemoglobin."}
+{"id": "pulmo2$$$ef098572-d2cf-48dd-8034-55012e836418", "contents": "Carbon dioxide can bind to the terminal amine groups of hemoglobin\u2019s polypeptide chains forming carbaminohemoglobin. It is\u00a0worth noting a couple of points about this. First,\u00a0CO2\u00a0does not compete with oxygen to bind to Hb\u2014the binding sites are completely different and hemoglobin can hold both CO2\u00a0and O2\u00a0at the same time. Second, deoxyhemoglobin is a better carrier of CO2\u00a0than oxyhemoglobin is; consequently at the tissue where hemoglobin is losing its oxygen it is becoming a more efficient CO2\u00a0transporter. This is known as the Haldane effect."}
+{"id": "pulmo2$$$f013bd7f-7123-4533-a857-58d2c7ecd296", "contents": "A little CO2\u00a0combines with water to produce carbonic acid, the dissociated hydrogen form that must be buffered by plasma proteins, such as albumin."}
+{"id": "pulmo2$$$9af068ba-0fe2-4c0e-aac6-8af1be71c06e", "contents": "Seventy percent of the CO2 enters red blood cells, and once inside a familiar reaction occurs (equation 16.5). The CO2\u00a0binds with water in the cytoplasm, producing carbonic acid, which then dissociates into a hydrogen ion and a bicarbonate ion."}
+{"id": "pulmo2$$$4f6aba57-0379-4278-ae69-eab956a84a3b", "contents": "This reversible reaction is accelerated by the enzyme\u00a0carbonic anhydrase and is driven rapidly to the right by the high concentration of CO2\u00a0at the tissue."}
+{"id": "pulmo2$$$7989eb2f-4279-470b-a4a4-98f5f7e69e82", "contents": "The hydrogen ion produced helps shift the oxygen saturation curve to the right and so promotes further release of oxygen to the tissue. Hemoglobin then serves yet another purpose by buffering the proton with its polypeptide chains. Deoxyhemoglobin is a better proton acceptor than oxyhemoglobin, so as the hemoglobin loses its oxygen at the tissue it becomes a better pH buffer.\u00a0This reduces the amount of hydrogen ion on the right side of our equation and moves the equation to the right, promoting the conversion of more CO2."}
+{"id": "pulmo2$$$d8839c18-7062-4e13-b4f2-9ad0cc6058b4", "contents": "Equation 16.5"}
+{"id": "pulmo2$$$ce63434c-8f96-4e2f-8362-b545fcf90d39", "contents": "High concentrations of CO2 at the tissue push this equation right to produce bicarbonate."}
+{"id": "pulmo2$$$abd5629c-c673-4e9a-8df0-aa831db05237", "contents": "The bicarbonate ion is pumped out of the cell, but without intervention this would leave the inside of the cell too positively charged as the negative charge of the bicarbonate is lost. To maintain electroneutrality the bicarbonate is exchanged for a chloride ion; this process is referred to as the chloride shift. The formation of bicarbonate at the tissue is summarized in figure 16.9."}
+{"id": "pulmo2$$$fc091c03-7cae-437e-a615-41436e19bee0", "contents": "The CO2\u00a0now travels through the bloodstream as bicarbonate toward\u00a0the lungs. At the lungs the process is basically reversed. The partial pressure of CO2\u00a0at the lungs is low;\u00a0consequently our equation is driven toward\u00a0the left-hand side as CO2\u00a0leaves toward\u00a0the low alveolar PCO2\u00a0(equation 16.6)."}
+{"id": "pulmo2$$$215659fb-025a-4e62-a33c-af3b48508e3a", "contents": "Equation 16.6"}
+{"id": "pulmo2$$$70d42d98-ce38-4c12-9f5b-cd34e4fcc912", "contents": "High bicarbonate and low CO2\u00a0at the lung force the equation leftward."}
+{"id": "pulmo2$$$b186eeeb-b127-4a4e-aa75-ac5446c366c5", "contents": "The high alveolar PO2\u00a0also promotes the leftward movement\u2014binding of oxygen to hemoglobin makes hemoglobin a less effective proton binder so it loses the proton and raises the amount of substrate on the right-hand side and thereby promotes reformation of CO2. The Haldane effect is also reversed\u2014as hemoglobin gains oxygen at the lung it loses its affinity for CO2\u00a0and releases it into the plasma. This raises plasma PCO2\u00a0and promotes diffusion of CO2\u00a0into the alveoli for expulsion."}
+{"id": "pulmo2$$$43f2b04d-f366-4f0b-87d5-ffafb597f78b", "contents": "Likewise the chloride shift is reversed and bicarbonate reenters the cell as chloride is pumped back out."}
+{"id": "pulmo2$$$9116d612-5ccb-474a-8573-3bf4b72b4eda", "contents": "All these moves\u00a0help promote the right-to-left direction of our now infamous equation and the re-forming of CO2. Alveolar ventilation gets rid of the re-formed CO2\u00a0to the atmosphere, maintaining the alveolar PCO2\u00a0at relatively low levels and the direction of the equation right-to-left. The reformation of CO2\u00a0at the lungs is summarized in figure 16.10."}
+{"id": "pulmo2$$$d819d8c4-d693-44d1-8d35-4c4d37acecb7", "contents": "So, for want of a better name, we can also draw a CO2\u00a0dissociation or saturation curve, as is shown in figure 16.11. The graph shows the CO2\u00a0concentration in blood across a wide range of PCO2\u00a0and shows the effect of Hb O2\u00a0saturation on CO2\u00a0carriage. The CO2\u00a0dissociation curve is unlike the oxygen saturation curve and is virtually linear (i.e., the higher the PCO2, the higher the CO2\u00a0content of the blood); there is no plateau to the curve as we saw with O2\u00a0transport. The ramification of this is that the lower the alveolar PCO2, the lower the blood PCO2, and the higher the alveolar PCO2, the higher the blood PCO2. It is\u00a0a very simple relationship that ends with the obvious statement that the more you breathe, the lower arterial CO2\u00a0becomes. It is worth reminding ourselves here that this is not a relationship seen with oxygen that is limited by the capacity of hemoglobin (breathing more does not necessarily result in more oxygen in the bloodstream). The other aspect to note here is the effect of hemoglobin\u2019s oxygen saturation on carbon dioxide carriage. This has clinical ramifications, so we will look at this more closely."}
+{"id": "pulmo2$$$1a3609d2-2c4e-42a8-8d0c-313f22cb6f86", "contents": "When deoxygenated, hemoglobin\u2019s structure promotes binding of CO2\u00a0and buffering of protons by the polypeptide chains. So when O2\u00a0saturation is zero, the CO2\u00a0and proton carrying capability of Hb is high. As already mentioned, this means that when Hb is in its deoxygenated form at the tissue, its CO2 carrying ability is increased."}
+{"id": "pulmo2$$$b8b21369-d788-4de9-8042-8259b1d039cf", "contents": "When we get to the lung, however, the Hb is exposed to the high alveolar PO2\u00a0and oxygen binds to the heme sites and becomes saturated; this causes a conformational change, and the CO2\u00a0and proton carrying ability is reduced. So conveniently CO2\u00a0release is promoted at the lung."}
+{"id": "pulmo2$$$da0e740b-9ae7-4eaa-8b46-ed5cadf7fa9c", "contents": "Although CO2\u00a0is highly soluble, very little of it can be transported as dissolved CO2\u00a0in plasma because of its effect on pH. The majority is converted to bicarbonate in red blood cells and transported in plasma, while about 25 percent\u00a0is transported bound to hemoglobin."}
+{"id": "pulmo2$$$4ed813be-9b8e-460b-bafa-7979fda65ba0", "contents": "Levitsky, Michael G. \u201cChapter 7: Transport of Oxygen and Carbon Dioxide in the Blood.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$d6a16cf9-d059-46b3-b7e2-0261a878af63", "contents": "West, John B. \u201cChapter 6: Gas Transport by the Blood\u2014How Gases Are Moved to the Peripheral Tissues.\u201d In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012."}
+{"id": "pulmo2$$$eebcdd0d-d4a0-48ea-b604-9534d41496ed", "contents": "Widdicombe, John G., and Andrew S. Davis. \u201cChapter 6.\u201d In Respiratory Physiology. Baltimore: University Park Press, 1983."}
+{"id": "pulmo2$$$279562ba-f525-4412-9982-1e9c07d279bb", "contents": "There are two circulatory networks that normally form shunts. The bronchial circulation, that supplies\u00a0the bronchi, empties its venous blood into the pulmonary veins, thereby sending slightly deoxygenated blood back toward the left heart and into the systemic arterial system. Likewise a very small portion of the coronary venous blood is returned to the left ventricle (through the thebesian veins) and thereby bypasses the lung completely before going back in the systemic circulation."}
+{"id": "pulmo2$$$e26d0d11-466b-4a31-bc87-c83397920658", "contents": "These two wayward circulations and the imperfect V/Q matching in the lung serve to suppress arterial oxygen saturation."}
+{"id": "pulmo2$$$2028df86-7d26-41d1-939e-4531335de8be", "contents": "Shunts can also be created by abnormal physiology or anatomy. There are several heart structural defects that allow blood from the right heart to enter the systemic circulation and bypass the lungs altogether; one common example is a patent foramen ovale where the incomplete atrial septum between the right and left heart allows deoxygenated venous blood to directly enter the arterial circulation, bypassing, or \u201cshunting,\u201d\u00a0past the lungs."}
+{"id": "pulmo2$$$7598457c-5eb4-41de-ac46-a98cdc3b4539", "contents": "In pulmonary disease, areas of the lung may not receive ventilation (e.g., as airways are blocked or collapsed). Perfusion to these areas is therefore wasted as no gas exchange takes place; effectively a right\u2013left physiological shunt has formed, and V/Q approaches zero (i.e., low V and normal Q)."}
+{"id": "pulmo2$$$abce3b74-063f-4823-b158-aa4d975f190e", "contents": "There is a quick and easy way to detect whether a shunt is contributing to a patient\u2019s low arterial PO2 by giving a patient 100 percent\u00a0O2\u00a0to breathe. The blood passing through capillaries that are exposed to the 100 percent\u00a0O2\u00a0becomes fully saturated. However, any shunted blood never \u201csees\u201d\u00a0the high PO2\u00a0and consequently stays at venous PO2. When the two routes rejoin and the blood mixes, it remains below 100 percent\u00a0(i.e., the alveolar\u2013arterial PO2\u00a0difference is not abolished by the 100 percent\u00a0O2, and it never can be as long as the shunt exists)."}
+{"id": "pulmo2$$$4ebe9b5f-9a81-497d-b977-d939be39cada", "contents": "Because even a small shunt can have a large effect on arterial PO2, it is critical to determine the size of a shunt should one be suspected. Figure 15.1 shows the lungs with blood passing through as normal (QC), while some bypasses the heart (QS) and is shunted back into the systemic circulation. The size of a shunt (QS) is expressed as the percentage of total blood (QT\u00a0in figure 15.1) (i.e., QS/QT). We will look now at how this is calculated from oxygen concentration. First, let us\u00a0see what we know."}
+{"id": "pulmo2$$$e553ad86-e664-4ecf-bbb2-9dd8e5e5bf63", "contents": "We can measure the oxygen concentration of the venous system (CVO2\u00a0in figure 15.2) and can assume that the shunted blood, having performed no gas exchange, will have the same oxygen concentration. We can also measure the oxygen concentration in the arterial system (CaO2\u00a0in figure 15.2), and if we assume that all the blood that passed\u00a0through the gas exchange capillaries in the lungs equilibrated with the alveolar PO2, we can use the alveolar gas equation to determine the capillary oxygen concentration (CCO2\u00a0in figure 15.2)."}
+{"id": "pulmo2$$$4068ac99-f409-4266-b009-a69d11e354ad", "contents": "So know we can use these oxygen concentrations to work out the percentage of shunted blood."}
+{"id": "pulmo2$$$f36e6b61-b7bc-468a-86ba-0fcf894754a2", "contents": "Now let us\u00a0combine our flow and oxygen concentration and think in terms of absolute oxygen contents in each part of our diagram. (Critical point: The absolute oxygen content is the product of the blood volume and oxygen concentration.)\u00a0So now thinking of absolute oxygen contents, let us\u00a0generate a first basic equation (equation 15.1) with what we know\u2014the amount of oxygen in our flow going back to the left heart (QT) equals the oxygen from the pulmonary capillaries, plus that from the shunt."}
+{"id": "pulmo2$$$affef48c-01e8-43fd-acbd-4ded7294567f", "contents": "Equation 15.1"}
+{"id": "pulmo2$$$edf017e4-f8e9-4b25-b8fa-9b71a438769e", "contents": "Let us\u00a0build on that and put some values in place. The amount of oxygen arriving back in the arterial side must equal the volume of blood multiplied by the arterial oxygen concentration (QT\u00a0x CaO2), as shown in figure 15.3. And we know that this amount of O2\u00a0must be the sum of that from the capillaries, and that from the shunt."}
+{"id": "pulmo2$$$9ec0dd8c-8545-409c-9501-82b35955ff9d", "contents": "The amount of oxygen from the shunt is calculated as shunt flow multiplied by the venous oxygen concentration (QS\u00a0x CVO2), as shown in figure 15.3."}
+{"id": "pulmo2$$$ad5e9778-4a18-4fb1-a97f-baef972211e6", "contents": "The amount of oxygen going through the pulmonary capillaries can be described as the total volume minus the shunt volume (QT\u2212QS) multiplied by the capillary oxygen concentration (figure 15.3)."}
+{"id": "pulmo2$$$94eb27ac-ad53-47da-bbf1-abc30fb76ada", "contents": "Let us\u00a0put those terms into our basic equation (equation 15.2)."}
+{"id": "pulmo2$$$d71780b8-6e76-4c41-910d-38a5d7cd3e17", "contents": "Equation 15.2"}
+{"id": "pulmo2$$$ed82d5ed-4717-4069-bb0a-103cb5c09a82", "contents": "So at this point we might panic, thinking that we have no measure of flow (Q) for any of these variables, that we only have oxygen concentrations from our blood gases and alveolar gas equation. But panic not. Through the magic of mathematics we can rearrange this equation (15.2) to eliminate our flows (Qs) and be left with an equation that meets our objective of QS/QT."}
+{"id": "pulmo2$$$805a35eb-cf3d-439b-849f-8ebbc99c7e24", "contents": "The shunt equation (equation 15.3) describes the proportion of total perfusion that is passing through the shunt. This is the equation worth remembering: the portion of blood going through the shunt is the difference between the capillary and arterial O2\u00a0concentrations, divided by the difference between the capillary and venous oxygen concentrations."}
+{"id": "pulmo2$$$14293145-d6be-46c1-a68d-59db028c08cf", "contents": "Equation 15.3"}
+{"id": "pulmo2$$$efedbfe6-ffb4-4984-a786-71e19e339f21", "contents": "[latex]Q_T \\times C_aO_2 = [(Q_T - Q_S) \\times C_CO_2] + [Q_S \\times C_VO_2][/latex]"}
+{"id": "pulmo2$$$ef2c2a52-3094-4f18-9d77-7dde38a95528", "contents": "Let us\u00a0look at an example to put this in context. We have a patient with normal lungs, but a right\u2013left shunt is present. We find out that his arterial blood O2\u00a0concentration is 18 mL\u00a0and venous is 14. Capillary oxygen concentration is calculated to be 20 mL/100 mL. Now we plug the numbers in the equation and see that the proportion of blood going through the shunt is a third, or 33 percent."}
+{"id": "pulmo2$$$0c34cf89-7201-4c16-9be7-82f5cfb00ddf", "contents": "So to recap, small pulmonary shunts exist\u00a0even in the normal cardiopulmonary system, but abnormal shunts can arise from a number of different pathological causes. Although the presence of a shunt is relatively easy to detect, it is important to calculate its size, which is also a relatively easy process."}
+{"id": "pulmo2$$$c0f16823-bf43-4645-9269-c51c6ce26d14", "contents": "Levitsky, Michael G. \u201cChapter 5: Ventilation\u2013Perfusion Relationships.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$4a3745c2-5916-41da-b111-3377965154c7", "contents": "West, John B. \u201cChapter 5: Ventilation\u2013Perfusion Relationships\u2014How Matching of Gas and Blood Determines Gas Exchange.\u201d In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012."}
+{"id": "pulmo2$$$5867bf01-6acb-4d92-bac8-5e75bde55544", "contents": "This chapter will describe how the alveolar\u2013arterial PO2 difference is calculated and what assumptions can be made from it."}
+{"id": "pulmo2$$$4ef36793-42e1-48cb-be98-c099eb0e004a", "contents": "Before you start, a quick reminder that an uppercase A refers to alveolar and lowercase to arterial."}
+{"id": "pulmo2$$$3fb6de3d-2dcc-42c8-b6d5-1c6e1447a3c9", "contents": "Obviously to measure the alveolar\u2013arterial PO2 difference, we need to know both the alveolar and arterial PO2s. The arterial PO2 is routinely measured as part of a blood gas panel, along with arterial PCO2. However, from your understanding of V/Q distribution across the lung, you might appreciate that the measurement of a \u201ctypical\u201d\u00a0alveolar PO2 is difficult, and it must\u00a0be calculated as an estimate of the whole lung. This is the role of the alveolar gas equation, and we will\u00a0look at it now, not just because it may appear on your board exams, but primarily because of its clinical importance. As there are several forms of the equation, we will take the easy way out and use the simplest one (figure 14.1), which is accurate for the vast majority of cases you will\u00a0ever see."}
+{"id": "pulmo2$$$8ac3033a-fb35-44e7-b15d-9dfe3b1c441b", "contents": "The alveolar gas equation estimates whole lung alveolar PO2 as the inspired PO2 minus the arterial PO2 divided by the respiratory exchange ratio. For those interested in the derivation of the equation, more detailed sources are available. But here, we will just look at the factors involved and try and make this simpler to commit to memory (which I suggest you do)."}
+{"id": "pulmo2$$$c1cb1316-ad14-4e9d-9200-95813f1cab5f", "contents": "First let us\u00a0look at arterial PCO2; this measurement is included in a blood gas panel so will be readily available to you. The alveolar gas equation really needs\u00a0the alveolar PCO2, but since CO2 is so soluble then we assume that equilibration has taken place and PaCO2 and PACO2 are the same, and we use the number we have at the bedside."}
+{"id": "pulmo2$$$fec7dd78-3deb-4a84-ac34-a0ac874d5940", "contents": "Now let us\u00a0look at R, or the respiratory exchange ratio. The respiratory exchange ratio describes how much CO2 is produced per unit of oxygen consumed. (Perhaps you can see why we are using this in conjunction with the arterial PCO2; we are relating CO2 production as a proxy measurement of oxygen consumption.)\u00a0When utilizing carbohydrate as a fuel (the most common situation) there are eight CO2 molecules produced for every ten oxygen molecules burnt, so R is generally 0.8. Lastly, there is\u00a0the inspired PO2. Generally, breathing room air at sea level this will be ~150 mmHg. But it is\u00a0important to note that this might change in the clinic if the patient is given oxygen therapy."}
+{"id": "pulmo2$$$a11d47d3-cfc1-4902-951d-3a237d759ce8", "contents": "So this simple form of the alveolar gas equation\u00a0really has two basic halves: the amount of oxygen taken into the alveoli (PIO2), and a reflection of the amount that is taken out (PaCO2/R) to supply metabolism."}
+{"id": "pulmo2$$$ad307632-7613-4526-acfd-c6fa2fd331c7", "contents": "You will find more complex and accurate forms of this equation, but for the vast majority of situations this one is perfectly adequate and is considerably easier to remember, particularly when some of the numbers we plug in are frequently the same. If we look at normal values (equation 14.1), we see that our equation gets us close to what we have learned\u00a0to be a normal alveolar PO2. Inspired PO2 at sea level and room air is 150 mmHg, we will\u00a0assume R is 0.8, and a normal arterial PCO2 is 40 mmHg. Here is the alveolar gas\u00a0equation with normal values:"}
+{"id": "pulmo2$$$57501364-ceb6-4ed3-942d-91dfd9ecb79b", "contents": "Equation 14.1"}
+{"id": "pulmo2$$$54177776-ab01-416b-bf60-6e2a9729bdfb", "contents": "[latex]P_AO_2 = 150 - \\frac{40}{0.8} = 100[/latex]"}
+{"id": "pulmo2$$$14dfdb57-bc28-4d38-b6e0-80b8f5bca562", "contents": "Now let us\u00a0see the clinical use of\u00a0being able to determine alveolar PO2\u00a0and thus calculate any alveolar\u2013arterial PO2 difference."}
+{"id": "pulmo2$$$54b86832-28f0-44d8-9f50-93ffe1c47774", "contents": "Not only knowing what the\u00a0alveolar and arterial PO2s are, but by how much they differ can\u00a0tell\u00a0us\u00a0where a problem\u00a0in the process of gas exchange might be occurring. So the PAO2\u2013PaO2 difference has great diagnostic value.\u00a0Let us\u00a0return to our schematic of a lung with a ventilated and perfused lung unit and look at a few scenarios, starting with the normal state."}
+{"id": "pulmo2$$$d8a4e1cb-8727-4554-8087-372ab3bdca8f", "contents": "Normal lung: With a well-ventilated and perfused lung (figure 14.2),\u00a0alveolar PO2 is normal, and when there are\u00a0no problems with diffusion across the membrane into an adequately perfused blood vessel, arterial PO2 is normal as well. Thus the difference between alveolar and arterial PO2 is minimal and normal, and in reality for a young healthy person is no more than 5\u201310 mmHg (note, however, this difference increases with age)."}
+{"id": "pulmo2$$$dfadaa83-f3cc-4495-8e0f-68e356600a1a", "contents": "Hypoventilation: Now let us\u00a0look at a case of where the alveolus is inadequately ventilated (figure 14.3): perhaps a patient has been given a high enough dose of opioid for pain relief and it has\u00a0caused respiratory depression, so the patient no longer breathes enough to achieve sufficient gas exchange. This will lead to a decline in alveolar PO2\u00a0and consequently a fall in arterial PO2 as well. However, because the alveolar and arterial PO2s have both decreased, then the difference between the two of them remains the same. So we see low alveolar PO2, low arterial PO2, but a normal A\u2013a PO2 difference."}
+{"id": "pulmo2$$$d84525ab-d131-4bb7-9b3c-544e0c7734e9", "contents": "Impaired diffusion: Now let us\u00a0look at a patient with a diffusion abnormality\u2014perhaps some pathological process has caused thickening of the alveolar membranes. Here the alveolus is still\u00a0adequately ventilated, so alveolar PO2 remains high or at least the same (figure 14.4). But although blood is passing the ventilated region, the thickened membranes prevent diffusion of oxygen into the blood, and arterial PO2 does not equilibrate and so is lower. As a consequence, the A\u2013a difference increases. So this scenario results in a normal alveolar PO2, a low arterial PO2, and\u00a0an increased difference between the two."}
+{"id": "pulmo2$$$25cefbc3-5776-4459-9216-f5542ac0cc03", "contents": "Inadequate perfusion: Now let us\u00a0look at a last scenario where perfusion has been stopped, perhaps by a pulmonary embolus (figure 14.5). Ventilation still reaches the region, but there is no perfusion; this is a form of V/Q mismatch. Alveolar PO2 remains normal because\u00a0air still reaches the region, but with no perfusion and therefore no gas exchange arterial PO2 will fall. This, again, results in an increased A\u2013a PO2 difference."}
+{"id": "pulmo2$$$26823ba2-cc36-4772-85fc-cd9e4662d428", "contents": "So what you should see from the summary in table 14.1 is that all three abnormalities cause a decrease in arterial PO2, so all three patients are likely to present with low arterial saturations. But when blood gases are taken and the alveolar\u2013arterial PO2 difference is calculated, then one or more of our abnormalities could be ruled out. If there is an increased difference, you know it is\u00a0not hypoventilation. If there is no\u00a0increase in A\u2013a difference,\u00a0you know it is\u00a0neither a diffusion problem nor a V/Q mismatch."}
+{"id": "pulmo2$$$1957c11e-4181-43fe-b281-d4aa73370133", "contents": "These examples to illustrate the point are rather specific, but generally knowing the alveolar and\u00a0arterial PO2s and calculating A\u2013a PO2 difference allows you to distinguish whether a decline in arterial PO2 is due to a problem getting oxygen down into the lung, or a problem getting oxygen from lung to blood. So the alveolar equation is a simple equation, but it forms a powerful tool."}
+{"id": "pulmo2$$$08ea33e3-9037-448b-b892-3f528da57fff", "contents": "Table 14.1: Summary of Alveolar-arterial PO2 difference."}
+{"id": "pulmo2$$$0b3f01fc-f893-4c2a-ba14-78f6613e445c", "contents": "Levitsky, Michael G. \u201cChapter 3: Alveolar Ventilation.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$509a40fa-b90e-40ce-bed4-0b2b31390f8b", "contents": "PAO2=150\u2212400.8=100"}
+{"id": "pulmo2$$$3148f82d-716f-4a5b-8855-6205d071af92", "contents": "400.8"}
+{"id": "pulmo2$$$31736771-63ab-4cf7-af41-e14e28195276", "contents": "0.8"}
+{"id": "pulmo2$$$ef7d1b93-3a1e-49fe-8e36-f72ffeb5d196", "contents": "Let us\u00a0start with a description of the ideal situation, where ventilation to alveoli is matched with the perfusion, then we will see how the lung does not quite achieve this."}
+{"id": "pulmo2$$$20443118-b1a8-481e-b40b-fabc2cdacdae", "contents": "This is what we would expect if the lung were perfect, with uniform distribution of ventilation and perfusion to all regions and a V/Q of 1 in all regions."}
+{"id": "pulmo2$$$1266c3d9-2603-4ab5-a23b-c4c09c575487", "contents": "The lung is not a perfect organ, however, and ventilation and perfusion are not equally distributed, and the lung as a whole only achieves an average V/Q of 0.8, which is close to our ideal of 1, but not quite there. Consequently, by the time the blood has passed the alveoli and regrouped in the pulmonary veins, the PO2 of the blood is less than alveolar. This alveolar\u2013arterial PO2 difference is caused by the less-than-perfect matching of V and Q across the lung; but it is\u00a0not all the lung\u2019s fault, as venous blood that has been through the bronchial and a small section of the coronary circulation (and therefore is deoxygenated) is mixed into the vessels returning to the left heart, which brings down arterial saturation as well. The mixing-in of bronchial and coronary circulations and the less-than-ideal V/Q in the lung as a whole is the reason why your saturation monitors do not\u00a0read 100 percent, but normal oxygen saturation is considered as 96\u201398 percent."}
+{"id": "pulmo2$$$85f0f70d-8677-4678-bea9-07259ce001f8", "contents": "When V and Q are matched (V/Q =\u00a01): Atmospheric PO2 is diluted as it descends the airways to give an alveolar PO2 of 100 mmHg, and alveolar PCO2 is 40 mmHg. The blood returning from the tissue has a diminished PO2 of 40 mmHg and a raised PCO2 of 45 mmHg. As this blood passes the alveolus, oxygen moves into the bloodstream down its pressure gradient and CO2 moves into the alveolus down its pressure gradient. As ventilation and perfusion are\u00a0matched then equilibrium is reached and the blood leaves with arterial gas tensions that are the same as alveolar tensions (figure 13.2)."}
+{"id": "pulmo2$$$ae9928fc-ebed-484b-9d0e-f106637f0444", "contents": "When V = 0: Now let us look at another and extreme situation, where ventilation (V) is zero so our V/Q is zero (zero divided by anything is zero)."}
+{"id": "pulmo2$$$2004592f-936b-4a32-8de4-acb4a232cda9", "contents": "This situation is clinically possible\u00a0as airways can collapse or become blocked with a mucus plug. Without any ventilation the gas tensions inside the alveolus rapidly equilibrate with the returning venous blood, so alveolar gas tensions end up as a PO2 of 40 mmHg and a PCO2 of 45 mmHg. The venous gas tensions, never having been exposed to a ventilated alveolus, now circulate into the arterial system, and arterial PO2 becomes 40 mmHg and PCO2 becomes 45 mmHg there as well (figure 13.3)."}
+{"id": "pulmo2$$$3daf23a3-a6fa-4dd2-ad9f-81f3a8ecaa97", "contents": "When Q = 0: Now let us go to the other extreme, where perfusion is zero and ventilation is normal (V/Q goes to infinity). Again, this can occur in reality should a pulmonary vessel become blocked by an embolus. In this scenario V/Q becomes infinity\u2014anything divided by zero is infinity. With no perfusion, no gas exchange occurs in this alveolus, and as it is still being ventilated then the alveolar gas tensions equilibrate with the atmosphere (figure 13.4)."}
+{"id": "pulmo2$$$6b17964d-6a5d-4fb4-a079-5ebef1888fa2", "contents": "So going from these extremes of V/Q as zero, passing through the ideal of V/Q of 1 to a V/Q of infinity, we get a range of alveolar gas tensions going from venous gas tensions when V/Q is zero to atmospheric gas tensions when V/Q is infinite."}
+{"id": "pulmo2$$$3eb035cf-cde4-46d0-9c3b-0f04bc73270a", "contents": "This range of alveolar gas tensions is represented by the ventilation\u2013perfusion line (figure 13.5). This graph takes a minute to come\u00a0to grips with, so let us\u00a0break it down. The axes of the graph show alveolar PO2 on the X and\u00a0alveolar PCO2 on the Y. The plot shows the range of V/Q ratios we have just discussed, ranging from zero when there is perfusion but no ventilation, to infinity when there is ventilation but no perfusion. Looking at figure 13.5 more carefully will confirm our numbers. When ventilation and perfusion are present and V/Q is 1, then our alveolar PO2 is 100 mmHg, and the alveolar PCO2 is 40 mmHg\u2014just as we have seen."}
+{"id": "pulmo2$$$010a8427-3fa7-44e2-a0c4-21eefc77ebb8", "contents": "If we stop ventilation and go to a V/Q of zero, we again see that the alveolar gas tensions become equal to venous values, with alveolar PO2 at 40 mmHg and PCO2 at 45 mmHg."}
+{"id": "pulmo2$$$80e28412-7783-4aa2-afe4-4cad6fd00f7a", "contents": "And finally, when we stop perfusion and V/Q becomes infinite, then alveolar PO2 becomes 150 mmHg\u00a0and PCO2 becomes zero (i.e., equilibrates with the atmosphere)."}
+{"id": "pulmo2$$$03247534-2826-4442-8fe8-28952a8e8147", "contents": "In summary, the ventilation\u2013perfusion line show the effect of changing V/Q on alveolar gases. Reduce V/Q toward zero and the alveolar gas tensions tend toward\u00a0venous gas tensions. Increase V/Q toward infinity and the alveolar gas tensions get closer to atmospheric partial pressures."}
+{"id": "pulmo2$$$1c4edfae-a845-4cd5-9160-2be7aa42254b", "contents": "The importance of understanding this becomes apparent when we see that V/Q changes across the structure of the lung, and if V/Q changes, then alveolar partial pressures change to."}
+{"id": "pulmo2$$$e5452abd-5a2f-41b6-b3c6-9ef659cd2265", "contents": "Let us look at the distribution of V/Q across the lung and why it changes from apex to base."}
+{"id": "pulmo2$$$c8a75611-c00c-4f33-9054-51f0832f74fe", "contents": "As you should understand, ventilation increases down the lung so is greatest at the base, and perfusion follows the same pattern\u2014all due to the effects of gravity. But the increase in ventilation down the lung structure is not equal to the increase in perfusion, as can be seen in figure 13.6. You can see here that perfusion is higher than ventilation at the base; it\u00a0falls off much more rapidly as the lung is ascended, so it ends up being lower than ventilation at the apex."}
+{"id": "pulmo2$$$2255125b-cca4-4f0c-9fc5-f6bcab3bd4c8", "contents": "This means there is a range of ventilation\u2013perfusion ratios up the height of the lung (figure 13.6, maroon\u00a0plot). At the base perfusion is higher than ventilation, so V/Q is less than 1, while toward\u00a0the apex V/Q rises and becomes greater than\u00a01. At about the level of the third rib, V/Q is perfect (yay!) as ventilation and perfusion are matched, seen here at\u00a0the points the lines cross. This range of V/Q results in the previously mentioned whole lung average of 0.8."}
+{"id": "pulmo2$$$71bbd182-2263-4cb5-b087-6aa5f841cd42", "contents": "As you should appreciate from understanding the ventilation\u2013perfusion line, this range of V/Q across the lung results in a range of alveolar gas partial pressures across the lung. The apical alveoli, being relatively overventilated (or underperfused, whichever way you would\u00a0like to think about it), have a high V/Q and consequently have partial pressures closer to atmospheric partial pressures. On the other extreme, the basal alveoli are relatively underventilated (or overperfused, your choice) and so have a low V/Q, tending toward zero; thus their partial pressures are closer to venous values (figure 13.7)."}
+{"id": "pulmo2$$$3392289c-1e53-4468-8cc4-bf80c8823b52", "contents": "In between these two extremes is a progressive range, so what we see is that alveolar PO2 declines down the lung while alveolar PCO2 rises. As you might imagine, having a range of alveolar gas tensions down the lung has ramifications for gas exchange and particularly for oxygen saturation. This inequality in V/Q resulting in differences in alveolar PO2 is substantial enough to suppress arterial oxygen saturation\u2014and contribute to your oxygen saturation meter never reading 100 percent. Let us see why."}
+{"id": "pulmo2$$$3f5defb8-c9c9-4403-bd5c-80eab935516d", "contents": "The difference in alveolar PO2 from apex to base is as high as 40 mmHg, as is reflected in this figure. The apical alveoli have a high PO2\u00a0(shown in figure 13.8 as 132 mmHg), primarily due to their poor perfusion and relatively high ventilation and thus high V/Q. This produces a high diffusion gradient from 132 mmHg in the apical alveoli, to 40 mmHg in the apical blood. Consequently, what blood does go to the apex becomes fully saturated before it heads back toward the left heart."}
+{"id": "pulmo2$$$f4dbeadd-5730-41ed-9fbe-7bef557b245f", "contents": "Down at the base, however, V/Q is low because of the high perfusion and relatively low ventilation. Consequently the PO2 in basal alveoli tend toward venous values, shown in figure 13.8 as 89 mmHg. This lower alveolar PO2 means a diminished diffusion gradient\u00a0(from 89 in the alveoli to 40 mmHg in the blood), and combined with a shift down the hemoglobin saturation curve (more on this\u00a0later), this means blood leaving the basal alveoli may not be completely saturated with oxygen."}
+{"id": "pulmo2$$$cc40646b-880c-45d8-b6b3-f871e00f52bb", "contents": "When the blood from the apex and base mix on their journey back to the left heart, the outcome is that the combined oxygen saturation is less than 100 percent, about 97 percent. It is worth making perhaps an obvious but critical point here. The blood from the apex is exposed to a substantially higher PO2\u00a0and becomes 100 percent\u00a0saturated (i.e., it cannot take on any more O2 as it is at its full oxygen carrying capacity). There is no way that it can pick up extra to compensate for the blood coming from basal alveoli, which are not at capacity."}
+{"id": "pulmo2$$$640a915e-d9b3-432a-a1da-e6e3361d4808", "contents": "The same is not true for CO2 though. Because of its high solubility, CO2 transport does not rely on a transporter protein like hemoglobin; the transfer of CO2 is really dependent on the diffusion gradient present. So at the apex the lower alveolar PCO2 (slightly less than 30 mmHg looking at our V/Q line) generates a larger diffusion gradient with venous blood, and more CO2 is transferred out the blood, meaning that it can compensate for the low diffusion gradient (perhaps only a few mmHg) that occurs between the alveoli and blood at the lung\u2019s base."}
+{"id": "pulmo2$$$3aeac80e-d966-43bc-aa51-84f9ad55e318", "contents": "As a study exercise it may be worthwhile for you to go back to the ventilation\u2013perfusion line and calculate the diffusion gradients for oxygen and carbon dioxide between the alveoli and venous blood at different heights in the lung. I urge you to come\u00a0to grips with this concept as it is highly pertinent to respiratory disease and can explain clinical-related changes in blood gases."}
+{"id": "pulmo2$$$763cc107-131b-4180-9eb7-abc2a42d3dfc", "contents": "The take-home message, however, is that even the normal lung is not perfect and has an average V/Q ratio of 0.8, rather than the ideal of 1, and this slight matching of ventilation and perfusion contributes to the arterial saturation being slightly less than 100 percent, but has little effect on arterial CO2. If respiratory disease increases the mismatch, this effect on oxygen saturation can become more pronounced, but the lung has a defense mechanism for this."}
+{"id": "pulmo2$$$5ba36db2-9526-4010-9983-6e6b3bd379b3", "contents": "In an attempt to maintain V/Q close to 1 and prevent V/Q mismatching, the pulmonary vasculature has an unusual response to hypoxia. While the systemic vasculature responds to local hypoxia with a vasodilation to bring more blood to the area, the pulmonary vasculature constricts in the presence of low oxygen to shunt blood away from hypoxic regions."}
+{"id": "pulmo2$$$612b5220-0f54-4d23-a7ec-030ebc728c48", "contents": "Let us\u00a0look at a common scenario that might occur in a patient with chronic bronchitis. Figure 13.9 represents two regions of the lung. One region becomes blocked by a mucus plug, and ventilation to that region goes to zero."}
+{"id": "pulmo2$$$4e716cd7-2a3d-4ff9-8152-0575cceb89ae", "contents": "The alveolar partial pressures will rapidly equilibrate to venous pressures, and desaturated blood goes back to the left heart from this region while the local region around this area becomes mildly hypoxic. The pulmonary vasculature responds to the hypoxia by vasoconstricting, reducing the perfusion to the unventilated region and helping to rematch the V/Q ratio in this region (i.e., low ventilation is matched with low perfusion). In common sense terms, there is no point sending pulmonary blood to an unventilated region, so the hypoxia-driven vasoconstriction prevents this from happening."}
+{"id": "pulmo2$$$b29ea3de-4ed5-4b0f-a6bd-6dcf00852fdf", "contents": "The distensibility of the pulmonary vasculature means that the blood is shunted to unconstricted vessels (i.e., those supplying ventilated regions). Thus the lung has its own inherent mechanism to optimize V/Q and promote the most effective gas exchange possible."}
+{"id": "pulmo2$$$4fde109e-5932-4163-af9e-a45beb0d6c49", "contents": "The unusual response of the pulmonary vasculature is demonstrated in figure 13.10, showing how as alveolar PO2 falls (as occurs with a decline in alveolar ventilation) then blood flow falls\u2014and likewise, the more oxygen in the alveolus, the more pulmonary perfusion it receives."}
+{"id": "pulmo2$$$3be15f81-0c88-4ce4-83c2-19c9b755f4da", "contents": "This effect is driven by a hypoxia-sensitive potassium channel found on the albeit sparse smooth muscle of the pulmonary arterioles. This channel is normally open and allows the exit of potassium, which in turn keeps the inside of the muscle cell polarized. When exposed to hypoxia the channel closes, and the outward potassium current stops, allowing the muscle cell\u2019s membrane potential to rise and consequently depolarize to cause a contraction."}
+{"id": "pulmo2$$$a3a54ece-31f1-40de-ac3e-9f1e54b27e27", "contents": "So to summarize, the ratio of ventilation and perfusion changes across the lung, and this affects the alveolar and consequently arterial gas tensions from those regions. While the lung does not reach the ideal V/Q ratio,\u00a0it is capable of shunting pulmonary blood flow away from unventilated areas to optimize gas exchange."}
+{"id": "pulmo2$$$736d22e3-bd4e-497c-bf9a-992a06cc406d", "contents": "Widdicombe, John G., and Andrew S. Davis. \u201cChapter 7.\u201d In Respiratory Physiology. Baltimore: University Park Press, 1983."}
+{"id": "pulmo2$$$ea2fb480-27e3-4171-a770-1b37db5c154e", "contents": "We will start by revisiting the equation dealt with in the previous chapter in the context of four different clinical scenarios."}
+{"id": "pulmo2$$$16446bf3-460e-4969-b016-96c12cf45a27", "contents": "Case #1,\u00a0normal: In the normal situation an increase in tissue metabolism leads to a rise in arterial CO2, pushing the equation to the right and causing a rise in hydrogen ion concentration and a consequent fall in pH. Both the rise in CO2 and fall in pH stimulate breathing. This increase in alveolar ventilation leads to a fall in arterial CO2, pushing the equation back left and lowering hydrogen ions back to normal."}
+{"id": "pulmo2$$$fdc2ed6d-8799-410e-a703-6503d5741b98", "contents": "Equation 12.1"}
+{"id": "pulmo2$$$db23bf0b-5b23-44b6-9224-f9cbe64672a2", "contents": "Case #2, metabolic acidosis: CO2 is by no means the only source of hydrogen ions in the system. Most metabolic pathways result in acidic by-products, and the pulmonary, renal, and buffering systems are generally battling to raise blood and tissue pH back from their tendency to turn acidic. The rise in hydrogen ions resulting from metabolic processes is referred to as metabolic acidosis. The fall in pH stimulates an increase in respiration, which in turn causes a fall in CO2, and the lower CO2 drives the equation to the left, reducing the number of H+\u00a0and thereby raising pH back to normal. Here the pulmonary system has compensated for a metabolic process, and this is referred to as respiratory compensation of metabolic acidosis. The patient may now have a normal blood pH, but the CO2 will be low. In summary, all the pulmonary system has done is get rid of one source of hydrogen ions (carbonic acid derived from dissolved CO2)\u00a0to compensate for another source of hydrogen ions it cannot do anything about (most metabolically driven acids are nonvolatile\u00a0(i.e., do not\u00a0vaporize into a gas the lungs can get rid of))."}
+{"id": "pulmo2$$$77c2cd90-c65f-4988-81d6-8df953baee37", "contents": "The advantage of the pulmonary system being involved in pH regulation is that it is quick\u2014a few larger breaths and arterial PCO2 can be dropped significantly. So the pulmonary system is adept at minute-by-minute (or breath-by-breath) regulation of pH that copes admirably with short-term changes in pH. It is\u00a0worth noting here that metabolic alkalosis can be reversed by reducing or even stopping breathing, allowing CO2 to accumulate in the arterial blood and lowering pH back to normal."}
+{"id": "pulmo2$$$6ec8ba64-b3ae-4b7f-9a63-bd327d915ad9", "contents": "The disadvantage to using the pulmonary system for compensation is that it can only mediate its effect via CO2. So any metabolic acids are eventually dealt with by the renal system, which, although much slower, is capable of excreting any nonvolatile metabolic acids. So through a combination of rapid pulmonary CO2 expulsion and slower but more versatile renal function, pH is normally maintained within a tight range even in the face of large metabolic changes. The kidney also has the advantage of being able to modify bicarbonate levels, which we will see the importance of when we look at the buffering systems in a moment."}
+{"id": "pulmo2$$$d1e8a073-5819-4d14-9074-f6714dad77f8", "contents": "It is worth noting here, especially for the chemists and biochemists among you, that although equation 12.1\u00a0is a reversible reaction, it is open at both ends\u2014the lung being able to expel or retain CO2 at one end and the kidneys being able to retain or expel hydrogen ions and bicarbonate at the other."}
+{"id": "pulmo2$$$35815c54-9b81-433e-a563-dbe456ff07e0", "contents": "Case #3, respiratory acidosis: Given its capability to influence pH, failure of the lung to expel an appropriate amount of CO2 can lead to deviations in pH. Let us\u00a0take a case of severe lung disease, say COPD, for example. The disease has diminished the ability of the lung to expel CO2, so arterial PCO2 rises, pushing the equation to the right and causing a fall in pH, referred to as respiratory acidosis. This acid must be immediately buffered until kidney function can be modified to begin secreting the excess hydrogen ions and even produce more bicarbonate to replenish the buffering system, a process referred to as metabolic compensation of respiratory acidosis."}
+{"id": "pulmo2$$$e8008f82-c1bf-49b5-baaa-22b25e12ee7f", "contents": "Case #4, respiratory alkalosis: Likewise, if ventilation is inappropriately high with respect to CO2 production, such as during a period of hyperventilation, then too much CO2 will be lost and pH will fall. The alkalosis must\u00a0be immediately buffered to avoid deleterious effects. Over the longer term the kidney can lower the raised pH by reabsorbing hydrogen ions and even excreting bicarbonate buffer\u2014again this is termed metabolic compensation\u2014but this time for an alkalosis caused by an inappropriate respiratory response."}
+{"id": "pulmo2$$$f72b4585-52c0-47fd-b96e-a0b5a1b90050", "contents": "Although the lung\u2019s ability to expel CO2\u00a0and the kidney\u2019s ability to excrete or absorb hydrogen ions allow close regulation of pH, their responses alone are not sufficient to prevent immediate local changes in pH at the tissue. This is the role of the buffering systems."}
+{"id": "pulmo2$$$26fd6b87-32ee-4b2c-905a-70eb6d98a77e", "contents": "Buffering systems are chemicals within tissue and the blood that have the ability to absorb either hydrogen ions and/or hydroxyl ions. Once these ions are removed from solution (albeit temporarily) then their effect on pH is diminished. We will deal with buffers in the context of acids, as this is the most common physiological situation."}
+{"id": "pulmo2$$$23345a9c-842f-4ed1-9cba-d40edcb25547", "contents": "If you need an analogy for the function of buffers, imagine them as a chemical mop\u2014they soak up the hydrogen ions and stop them from making a cellular mess, but the hydrogen ions, although contained, remain in the system. It is the role of the lungs and kidneys to \u201crinse the mop\u201d\u00a0and get rid of the hydrogen ions from the system."}
+{"id": "pulmo2$$$c8b8ae17-d07a-493a-8cd3-fde32c396473", "contents": "We will deal with the bicarbonate system as it involves the respiratory system and is also the major extracellular buffer."}
+{"id": "pulmo2$$$087c802c-0b68-42ec-91de-d6259e279fe8", "contents": "Bicarbonate buffering: A buffering system consists of a weak base\u00a0capable of absorbing a strong acid and a weak acid capable of absorbing a strong base. As such, the bicarbonate system involves two components:\u00a0sodium bicarbonate (a weak base) and carbonic acid (a weak acid). Let us look at how it works and put it in the context of the lungs."}
+{"id": "pulmo2$$$47bf8a28-4a36-4e0e-bda2-f27a32c33c45", "contents": "First let us see how a weak acid (carbonic acid) deals with a strong base, in this example, sodium hydroxide (equation 12.2)."}
+{"id": "pulmo2$$$fb3546a9-0983-4009-8e9d-b3e78e90523c", "contents": "Equation 12.2"}
+{"id": "pulmo2$$$e1ad139f-7978-4608-af1b-7556856d401e", "contents": "Sodium hydroxide is a strong base as it rapidly dissociates into a hydroxyl ion and a sodium ion."}
+{"id": "pulmo2$$$42d94e92-061d-4871-904d-04f77c63046d", "contents": "Equation 12.3"}
+{"id": "pulmo2$$$4f3f5a69-ba8f-4549-bab4-292beee0959b", "contents": "The hydroxyl ion is the potential threat to physiological function so must be buffered. This is achieved by the carbonic acid dissociating into a hydrogen ion and bicarbonate (a process you are familiar with)."}
+{"id": "pulmo2$$$ae4e6579-5e24-4f67-9987-4717f457a4fe", "contents": "These dissociated ions now bind to form new partnerships as water and sodium hydroxide (a weak base) (equation 12.4)."}
+{"id": "pulmo2$$$d8b408f0-bc3e-4c6b-89dc-dd5e878b648c", "contents": "Equation 12.4"}
+{"id": "pulmo2$$$9a350d0c-5c12-4a60-acb7-3a67266b34f6", "contents": "So there are a couple of things to notice here beyond watching the ions move and form new components. First, the buffering process has taken a situation with the threat from a strong base (NaOH)\u00a0and toned it down to a situation with a weak base (NaHCO3); the problem has not gone away, it has\u00a0just been reduced (or buffered). Second, you will see that both of the components of the bicarbonate system, carbonic acid and sodium bicarbonate, appear in the equation\u2014we have just shifted from one to the other."}
+{"id": "pulmo2$$$878bc0ce-7107-4a1f-a019-df3dfb03e34b", "contents": "Let us look at the opposite situation to see what happens when the buffering system is faced with a strong acid. This time a strong acid (hydrochloric acid) is faced with our weak base (sodium bicarbonate) (equation 12.5)."}
+{"id": "pulmo2$$$2063bd6a-3edb-41e1-a16e-ef606250eee3", "contents": "Equation 12.5"}
+{"id": "pulmo2$$$db76f4fe-e2d4-4d0f-aaf5-6965c23db3c9", "contents": "The hydrochloric acid rapidly dissociates into a hydrogen ion and a chloride ion. The hydrogen ion now threatens physiological function and must\u00a0be buffered."}
+{"id": "pulmo2$$$1eb1aeae-594e-4ea9-88f7-bf0383796b62", "contents": "Our weak base dissociates into sodium and bicarbonate ions. Again our ions recombine, this time to produce harmless sodium chloride and carbonic acid (equation 12.6)."}
+{"id": "pulmo2$$$ebc2054b-30a6-4459-91da-c8118b19aa8f", "contents": "Equation 12.6"}
+{"id": "pulmo2$$$f1801785-6c58-4deb-a6e9-aaf2058defcf", "contents": "Notice again we have reduced but not removed the threat as we have gone from the presence of a strong acid to a weak one. Also notice that our two components in the bicarbonate system appear in the equation, and we have switched from one to the other. This should now make you realize that these two components are part of a reversible equation, and this reversible equation, even after the addition of sodium to one end, should look rather familiar (equation 12.7)."}
+{"id": "pulmo2$$$1f5c6336-a2f1-4085-85fc-3a8130d66321", "contents": "Equation 12.7"}
+{"id": "pulmo2$$$adb8de3f-e965-4d79-a6ba-0cea0eccc889", "contents": "[latex]CO_2 + H_2O \\leftrightarrow {\\color{red}{H_2CO_3}} \\leftrightarrow H^+ + HCO_{3-} + Na^+ \\leftrightarrow \\color{blue}{NaHCO_3}[/latex]"}
+{"id": "pulmo2$$$5e09f7f8-0d8f-4c2e-bdec-e19540e63114", "contents": "As CO2 is at one end of the equation you should appreciate how alveolar ventilation can influence the bicarbonate buffering system."}
+{"id": "pulmo2$$$0896e08a-3c5a-4299-9cee-dcfa6cd5fa6c", "contents": "Because of their critical role in maintaining blood pH, bicarbonate ions are routinely measured along with arterial blood gases. Knowing what the blood pH, arterial CO2, and bicarbonate levels are provides a very powerful and commonly used diagnostic measure allowing us not only to determine the pH status of the patient, but also the source of the problem and whether the renal or pulmonary systems are achieving compensation. Because of its power and common use, we are going to go through some fundamentals, and I am\u00a0afraid that means looking at the bane of many a medical student: the Henderson\u2013Hasselbalch equation. For those with a background in chemistry you might skip the next section, but for the rest of us, we are going to go through this step-by-step."}
+{"id": "pulmo2$$$81b98d6e-3e75-4f0c-a0ac-278ce9a2df5c", "contents": "What we will see is how the balance of bicarbonate and hydrogen ions determines pH, and how both of these ions can be influenced by the kidneys and lungs to keep pH constant."}
+{"id": "pulmo2$$$760a718a-a216-4a37-8c6f-f0f1b36a2fa5", "contents": "First, we will take the central and most important part of the infamous equation, discarding the more innocuous ends."}
+{"id": "pulmo2$$$0e6291a7-0d8a-4714-91b8-042149345179", "contents": "Equation 12.8"}
+{"id": "pulmo2$$$52b0910e-66e7-4ea7-b808-7bf235ca5f09", "contents": "This central portion describes the dissociation of carbonic acid into hydrogen and bicarbonate ions. But because carbonic acid is a weak acid, this dissociation is incomplete\u2014some carbonic acid staying whole, some dissociating into the ions. The level of dissociation is described by the dissociation constant (K\u2019), which really is the ratio of the concentrations of dissociated components to carbonic acid (equation 12.9)."}
+{"id": "pulmo2$$$1fb66582-ac9a-4976-adee-7dc6671c87ff", "contents": "Equation 12.9"}
+{"id": "pulmo2$$$79c07495-44ad-4277-a808-17d821c6fd99", "contents": "Because we are interested in calculating the pH, however, we are more interested in the amount of hydrogen ions, so rearranging this equation for hydrogen ion concentration we see the hydrogen ion concentration is the dissociation constant, multiplied by the ratio of carbonic acid and bicarbonate (equation 12.10)."}
+{"id": "pulmo2$$$2f9e7dda-eeab-4d6a-9d3f-2ce41e59725e", "contents": "Equation 12.10"}
+{"id": "pulmo2$$$882d5f35-6e05-4327-a5a9-f749b464cacd", "contents": "This equation theoretically would allow us to now determine hydrogen concentration and therefore pH, but there are some practical problems for us, the first of which is that the instability of carbonic acid means we cannot measure its concentration. So we have to use a proxy measure. The amount of carbonic acid is determined by the amount of carbon dioxide, as can be seen in the equation that is\u00a0so familiar to you\u2014the greater the amount of CO2, the more carbonic acid."}
+{"id": "pulmo2$$$7a32bc29-717f-41f0-b1e0-869a9ea58d5a", "contents": "Equation 12.11"}
+{"id": "pulmo2$$$9cab90f6-802a-4357-8093-bbe7a798e746", "contents": "So after accounting for the dissociation constant of carbonic acid and CO2 and water, we can simply replace carbonic acid concentration with concentration of CO2 (equation 12.12)."}
+{"id": "pulmo2$$$73357170-0c41-4678-be54-1f9ce98a2ba6", "contents": "Equation 12.12"}
+{"id": "pulmo2$$$59a53658-cafa-4506-b401-90cf7fa4e992", "contents": "We then bump into our next practical problem: our equation now has CO2 concentration in it, but clinically we do not\u00a0measure CO2\u00a0as a concentration (as in mmols), but as a partial pressure. So our next and nearly final step is to convert CO2 concentration to CO2 partial pressure, and we do this by multiplying the partial pressure (our measured value) by the solubility coefficient of carbon dioxide,\u00a0which happens to be 0.03 mmol/mmHg. Our equation thus now can be completed using our adjusted PCO2 (equation 12.13)."}
+{"id": "pulmo2$$$5fb23906-ec05-4145-9fb9-c4f11c07fff7", "contents": "Equation 12.13"}
+{"id": "pulmo2$$$c999d1c1-a354-40fb-b948-062118219ced", "contents": "[latex]H^+ = K' \\times \\displaystyle\\frac{0.03 \\times PCO_2}{HCO_3-}[/latex]"}
+{"id": "pulmo2$$$f01aca0b-94fd-463c-9c40-200c25366d18", "contents": "Our equation as it is now allows us to calculate hydrogen ion concentration, but we need pH, so we have to make a conversion. Because pH is the negative logarithm of hydrogen concentration, we express everything in the negative log form. And because the negative log of the dissociation constant is referred to as pK, then we can simplify our equation one more step (equation 12.14)."}
+{"id": "pulmo2$$$141e4cc0-2e0f-4828-bcdb-f9f036ce8025", "contents": "Equation 12.14"}
+{"id": "pulmo2$$$216a3094-2d61-4371-bf6e-103ac215c266", "contents": "[latex]pH = pK - log \\displaystyle\\frac{0.03 \\times PCO_2}{HCO_3-}[/latex]"}
+{"id": "pulmo2$$$2bfd10e7-0293-44d7-ac18-adc347b19bf0", "contents": "To make our equation simple to use, we now get rid of the negative log, and so get the following (equation 12.15):"}
+{"id": "pulmo2$$$f11ae011-4301-4ba2-8d2b-90254aa2216f", "contents": "Equation 12.15"}
+{"id": "pulmo2$$$19b76e70-9f12-4e25-88c0-d410b90fcfc9", "contents": "[latex]pH = pK + log \\displaystyle\\frac{HCO_3-}{0.03 \\times PCO_2}[/latex]"}
+{"id": "pulmo2$$$3797eedb-d09c-4039-a6cc-625e57295f26", "contents": "We know that the pK of the bicarbonate system happens to be 6.1, so substituting this into the equation we end up with the Henderson\u2013Hasselbalch equation (equation 12.16)."}
+{"id": "pulmo2$$$374bd71e-dd8c-4003-b290-defe7784b4a4", "contents": "First, the equation shows that if CO2 rises then pH falls, and because\u00a0CO2 is under the influence of alveolar ventilation, this explains how the alveolar ventilation can now control pH. It also shows that if bicarbonate increases then pH increases, and equally if bicarbonate falls then pH falls. Because the bicarbonate concentration can be modified either way by the kidneys, the equation also shows how the kidneys can modify pH (equation 12.16)."}
+{"id": "pulmo2$$$c957205f-7a9a-4194-9e95-686b2e6ca388", "contents": "Equation 12.16"}
+{"id": "pulmo2$$$534628eb-7f64-4af9-936f-53fa3556ec28", "contents": "[latex]pH = 6.1 + log \\displaystyle\\frac{HCO_3-}{0.03 \\times PCO_2}[/latex]"}
+{"id": "pulmo2$$$7231703f-c12d-40db-a20b-d4f56c76d129", "contents": "The involvement of these two major physiological systems in this equation make the bicarbonate system a very powerful buffer, particularly when considering that there is an unlimited source of CO2 and therefore bicarbonate supplied by the metabolism."}
+{"id": "pulmo2$$$eba6def9-d3b1-42ff-988e-505a304594b8", "contents": "But more importantly it shows that pH is actually determined by the ratio of bicarbonate and CO2 and that both are equally important. This fact is critical to appreciate as it forms the basis of understanding the compensation mechanisms we dealt with earlier. This is why I put you through this derivation. So for example, if a rise in CO2 (such as in lung disease) is accompanied by an equal rise in bicarbonate (generated by the kidney), then the ratio between the two remains the same and therefore pH remains the same. Likewise, if during a fall in CO2 the kidneys excrete bicarbonate, then pH can be kept constant. So before we finish, let us show you that the equation actually works by plugging in some numbers."}
+{"id": "pulmo2$$$623e363a-f06c-41a1-9e07-3e6021a946c4", "contents": "Example #1: Let us start with normal values, a PCO2 of 40 mmHg and a bicarbonate of 24, and plug these into the equation. This comes to 6.1 plus the log of 20, which is 6.1 plus 1.3, or 7.4 (i.e., normal arterial pH)."}
+{"id": "pulmo2$$$292a3a0b-56ea-4fc7-b1e6-037b80f9073c", "contents": "Equation 12.17"}
+{"id": "pulmo2$$$4c240ea9-ce0f-437e-ae45-67be7bc2935e", "contents": "[latex]pH = 6.1 + log \\displaystyle\\frac{24}{(0.03 \\times 40)} = 6.1 + log(20) = 6.1 + 1.3 = 7.4[/latex]"}
+{"id": "pulmo2$$$05de98cb-e574-4d49-8bb8-febbd72b82a9", "contents": "Example #2: Now let us look at a case of acute lung failure that has caused a rise in arterial PCO2, but has not\u00a0persisted long enough for the kidney to respond\u00a0and compensate. PCO2 has risen to 50 mmHg, and bicarbonate has not changed. Our calculation now goes to 6.1 plus the log of 16, which is 6.1 plus 1.2, and pH has fallen to 7.3."}
+{"id": "pulmo2$$$4f9ee187-3846-4527-b265-95d683d74cba", "contents": "Equation 12.18"}
+{"id": "pulmo2$$$e535cbc4-78e5-40b0-9939-1f4f5aae5327", "contents": "[latex]pH = 6.1 + log \\displaystyle\\frac{24}{(0.03 \\times 50)} = 6.1 + log(16) = 6.1 + 1.2 = 7.3[/latex]"}
+{"id": "pulmo2$$$8b40b76c-60f6-4500-8590-209c9ece66cc", "contents": "We now have three numbers that can give a meaningful clinical interpretation. The low pH indicates the patient is in acidosis. The raised PCO2 suggests that this is respiratory acidosis, and the unchanged bicarbonate suggests no metabolic compensation has taken place."}
+{"id": "pulmo2$$$4847b373-58a8-45de-bfd3-46682622abae", "contents": "Example #3: Now let us return to our patient thirty-six\u00a0hours later when we have given the kidney a chance to respond. The patient\u2019s PCO2 remains at 50 because of the persistent lung problem, but the kidney has raised the bicarbonate to 30. Now our equation becomes 6.1 plus the log of 20, or 6.1 plus 1.3, and pH is 7.4\u2014apparently normal."}
+{"id": "pulmo2$$$f804c3e7-30d1-4ff6-9344-fcbefcaee359", "contents": "Equation 12.19"}
+{"id": "pulmo2$$$86bd34ca-e88b-4435-8806-83fa52171c85", "contents": "[latex]pH = 6.1 + log \\displaystyle\\frac{30}{(0.03 \\times 50)} = 6.1 + log(20) = 6.1 + 1.3 = 7.4[/latex]"}
+{"id": "pulmo2$$$7926b4fc-57c6-4f45-9af9-cba923d699fc", "contents": "But when we look at all three numbers we see that the patient is far from normal: the pH is okay\u00a0only because the kidneys have raised bicarbonate to match the raised CO2 and keep the ratio the same. So we now have a respiratory acidosis with metabolic compensation."}
+{"id": "pulmo2$$$d40c9d57-bc43-4fb6-9f0e-e3553ce1f145", "contents": "So although it has\u00a0been a long journey through this chapter you should now be able to interpret blood gas values to determine whether a patient is in acidosis or alkalosis and whether or not compensation is present. I strongly recommend writing the Henderson\u2013Hasselbalch equation as a formula in Excel so that you can plug in CO2 and bicarbonate values and see what happens to pH. By repeatedly interpreting blood gas values and pH, determining the status of a patient will rapidly become second nature."}
+{"id": "pulmo2$$$e82a61a5-e5c5-483d-924a-4ac5dafa4cb7", "contents": "H+=K\u2032\u00d70.03\u00d7PCO2HCO3\u2212"}
+{"id": "pulmo2$$$3706f7af-3861-4a03-8216-2ad249cd8ff0", "contents": "0.03\u00d7PCO2HCO3\u2212"}
+{"id": "pulmo2$$$ef98bd66-f9b0-4324-a4ce-b4b086292b6f", "contents": "0.03\u00d7PCO2"}
+{"id": "pulmo2$$$4be474bd-b88e-4780-ad20-7e277ccd2627", "contents": "0.03"}
+{"id": "pulmo2$$$7b7262cf-655e-4df9-a510-3d303f3af6b4", "contents": "pH=pK\u2212log0.03\u00d7PCO2HCO3\u2212"}
+{"id": "pulmo2$$$f9c9695b-fb6b-4941-bd36-de97e862f136", "contents": "pH=pK+logHCO3\u22120.03\u00d7PCO2"}
+{"id": "pulmo2$$$a869269b-a999-4192-8dc9-82b12a7ba6a6", "contents": "HCO3\u22120.03\u00d7PCO2"}
+{"id": "pulmo2$$$6ddbaaf9-7a2a-4b9b-8d74-b774941c7136", "contents": "pH=6.1+logHCO3\u22120.03\u00d7PCO2"}
+{"id": "pulmo2$$$55f3492c-55b5-44d4-ad06-036d952ff6e5", "contents": "6.1"}
+{"id": "pulmo2$$$b8954cf1-75b5-4256-9528-49af358c6e3d", "contents": "pH=6.1+log24(0.03\u00d740)=6.1+log(20)=6.1+1.3=7.4"}
+{"id": "pulmo2$$$1ce19981-006a-4f64-97c8-50dc2200621c", "contents": "24(0.03\u00d740)=6.1+log(20)=6.1+1.3=7.4"}
+{"id": "pulmo2$$$a50c81b1-4a7f-47be-baa9-fa3da579493a", "contents": "24(0.03\u00d740)"}
+{"id": "pulmo2$$$708c86ec-800a-44e5-aef2-8f0148e50215", "contents": "(0.03\u00d740)"}
+{"id": "pulmo2$$$d4014eb0-33ed-48d6-bbef-e19beaf2f4c0", "contents": "1.3"}
+{"id": "pulmo2$$$f68310d5-2dbe-469d-8a0e-847c99ecfd27", "contents": "7.4"}
+{"id": "pulmo2$$$4385d215-fc84-4427-bcce-26cf8e7c8143", "contents": "pH=6.1+log24(0.03\u00d750)=6.1+log(16)=6.1+1.2=7.3"}
+{"id": "pulmo2$$$132ce581-bc38-4038-a3fe-51470dad698b", "contents": "24(0.03\u00d750)=6.1+log(16)=6.1+1.2=7.3"}
+{"id": "pulmo2$$$5633a829-9b2f-4382-a22a-8bd3b01dacef", "contents": "24(0.03\u00d750)"}
+{"id": "pulmo2$$$d7fa266f-a818-4027-98fd-e173f1de9787", "contents": "(0.03\u00d750)"}
+{"id": "pulmo2$$$04d9fa4f-c088-4e9c-8c66-41689fd640a9", "contents": "1.2"}
+{"id": "pulmo2$$$71fd15d4-890b-4da9-873c-7c200bd81a65", "contents": "7.3"}
+{"id": "pulmo2$$$9665794a-c243-4bbc-bdbc-eb738773735b", "contents": "pH=6.1+log30(0.03\u00d750)=6.1+log(20)=6.1+1.3=7.4"}
+{"id": "pulmo2$$$1b9cb9c6-b06e-41ce-a263-2ec6ffa6ab3b", "contents": "30(0.03\u00d750)=6.1+log(20)=6.1+1.3=7.4"}
+{"id": "pulmo2$$$4809f530-daa0-49a3-83c0-f1a87d50fdca", "contents": "30(0.03\u00d750)"}
+{"id": "pulmo2$$$40fb1d75-909e-4706-94bf-a755b197701e", "contents": "The reason control of arterial CO2 is so critical is that it influences arterial pH. Too much CO2\u00a0in the blood and acidosis arises, while too little raises pH to produce an alkalosis. Any deviation from a set point pH of around 7.4 can be highly dangerous as changes in pH rapidly generate changes in protein shape and function. As enzymes, membrane transporters, channels, and more\u00a0start to lose function, then cellular and systemic function rapidly deteriorates. With its high metabolic rate and critical need to maintain control over its membrane potential, the nervous system is usually the first to suffer when pH changes."}
+{"id": "pulmo2$$$ab1f69bb-3518-440c-be06-d94cfd9339df", "contents": "So we now need to look at the relationships between CO2, arterial pH, and alveolar ventilation. Before starting this chapter you should be completely happy that you have an understanding of pH and what constitutes a weak or a strong acid and reversible reactions."}
+{"id": "pulmo2$$$444c6908-4fdf-4e77-a8a1-725ea0d3fc03", "contents": "Active cells produce CO2 through their anerobic and aerobic metabolic pathways. This CO2 rapidly combines with water in the cytoplasm or plasma to produce carbonic acid. Carbonic acid is a weak acid, meaning that some but not all of it dissociates onto a hydrogen ion and bicarbonate ion. Both these molecules are critical players in the maintenance of pH, and this equation explains why CO2 influences arterial pH."}
+{"id": "pulmo2$$$2f97cccc-a65a-4109-9659-c9222c851228", "contents": "Equation 11.1"}
+{"id": "pulmo2$$$6798f346-3c4c-4f92-b7fd-0403b6a90749", "contents": "It is well worth committing this equation to memory and ensuring you have a good understanding of it as it is not only crucial in pulmonary pH regulation, but you will also see this equation again in renal physiology, gastrointestinal\u00a0physiology, and other systems. I would\u00a0argue that this is the most important equation in physiology. But let us\u00a0look at it in terms of respiratory gases and the pulmonary system."}
+{"id": "pulmo2$$$4d741c84-caf4-456b-9b55-2651796fe020", "contents": "It is\u00a0critical to understand that this equation is reversible, so it really describes a balance. If CO2 at the tissue rises, the reaction is driven to the right, and consequently the amount of hydrogen ion is increased and pH falls. Conversely, if CO2 falls, then the reaction is driven to the left, so hydrogen ion concentration falls and pH rises. Because the lung has the ability to control the expulsion rate of CO2 from blood, the lung also has the ability to influence pH."}
+{"id": "pulmo2$$$e8b1f474-d1d6-4505-94a7-32b6d66c9105", "contents": "Let us\u00a0look at the most common physiological scenario: a rise in metabolic rate causes an increase in the production of CO2 by the tissue. This, of course, pushes our equation to the right, and more hydrogen ions are\u00a0produced. Because of buffering and the way CO2 is transported in the blood (discussed later on), the rise of PCO2 and fall of pH in venous blood is usually minimal, but both of these factors are enough to stimulate\u00a0an increase in ventilation."}
+{"id": "pulmo2$$$f472c339-e0ef-4ba8-81c0-bbf486ffa7f5", "contents": "This increase in ventilation (more specifically, alveolar ventilation) reduces the alveolar PCO2. This, along with a raised level of CO2 in the venous blood, steepens the diffusion gradient from blood to alveolus. Consequently more CO2 is transferred to the airways and expelled. This lowers blood CO2, driving our equation back toward the left, lowering hydrogen ion concentration and returning pH back to normal."}
+{"id": "pulmo2$$$a5729fda-c754-4b15-9b80-3293c218447f", "contents": "Because of the importance of maintaining normal CO2 (and thereby pH), alveolar ventilation exponentially increases with decreasing pH. Put simply, the ventilation control mechanisms use negative feedback reflexes to generate the appropriate level of ventilation to keep CO2 and pH constant. Put even more simply, CO2 is a source of acid, and the more you breathe the more CO2 you lose, so pH rises with increased ventilation."}
+{"id": "pulmo2$$$1acbeb2a-c1ab-432b-8db2-7bc5de617280", "contents": "So now you should be able to predict what will happen to blood pH with a change in PCO2, and what the ventilatory response should be to maintain pH at a constant level."}
+{"id": "pulmo2$$$0f1a94cd-f1a5-4b03-ab36-ea7ded411cd8", "contents": "These basic principles form the foundation to understanding common and serious clinical situations of metabolic and respiratory acidosis and alkalosis, and how compensation normally prevents deviation from a safe but narrow pH range."}
+{"id": "pulmo2$$$c7f4c268-560a-4009-8867-a730d1d4a684", "contents": "Levitsky, Michael G. \u201cChapter 8: Acid\u2013Base Balance.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$57cab8eb-6850-4704-96d8-014e274a3499", "contents": "Before looking at the unique situations that influence movement of fluid into and out of the capillary and alveoli, we will briefly review the usual Starling\u2019s forces that influence fluid movement between a capillary and the surrounding tissue."}
+{"id": "pulmo2$$$6036b1e3-b9cd-41d6-955c-72034e28f6fe", "contents": "First we will look at the balance of hydrostatic forces across the walls of a capillary as it travels through tissue. Being closest to the pumping heart, the hydrostatic pressure at the arterial end is relatively high, and likely much higher than the hydrostatic force in the interstitial space. This forms a hydrostatic pressure gradient that water moves down and out of the capillary into the tissue."}
+{"id": "pulmo2$$$63a10440-961c-4c4d-a8e0-f49994c4ed6b", "contents": "This exit of water from the capillary leaves behind a greater concentration of plasma proteins. This causes the colloid osmotic pressure to progressively rise down the capillary, and thus begins to establish an osmotic gradient with a tendency to drag water back into the capillary from the tissue.\u00a0This, and the progressive\u00a0drop in capillary hydrostatic pressure due to the fluid loss to the tissue and increasing distance from the heart, means most of the exuded fluid returns back to the capillary at the venous end down a hydrostatic and osmotic gradient."}
+{"id": "pulmo2$$$c5a76667-c7ea-4886-8541-d73bf8cfcd3e", "contents": "The only other variable to consider here is the permeability of the capillary\u2019s endothelium and other membranes. Pulmonary capillaries are continuous and therefore normally leak relatively little, but exposure to toxins or inflammatory mediators can cause permeabilization\u00a0of the capillary endothelium and increase outward fluid movement, just like\u00a0a capillary in the systemic circulation."}
+{"id": "pulmo2$$$cc3ba682-7d67-4567-beb4-5d47ff2bcd24", "contents": "Unlike the systemic capillaries, though, the pulmonary capillaries are exposed to airway and alveolar forces that can influence fluid movement."}
+{"id": "pulmo2$$$46c21060-f9f5-47a0-bd0c-6cb65bf54647", "contents": "Alveolar surface tension caused by the fluid lining of the internal alveolus wall not only drags the alveolar walls inward, but can also cause entry of fluid from the capillary and interstitium into the airspace. Excessive fluid accumulation can produce interstitial or alveolar edema, edema in the alveoli being much more serious as it interferes with gas exchange."}
+{"id": "pulmo2$$$f0baf849-e326-4ec8-93bb-514e7233bd5f", "contents": "Because\u00a0all cardiac output travels through the pulmonary circulation, it is\u00a0ideally suited to host the enzymes needed to perform metabolic functions on blood components."}
+{"id": "pulmo2$$$c6e65db3-efe0-4c75-aea2-22ddbed0900a", "contents": "We will deal with only a few here as it is more effective to address each metabolic pathway in context of its function, rather than merely because of the location in which it occurs."}
+{"id": "pulmo2$$$a0a2175b-9e8d-44cd-914c-9d802cc9a705", "contents": "ACE: Perhaps the lung\u2019s most well-known metabolic role is to host the angiotensin-converting enzyme (or ACE). This enzyme is responsible for converting angiotensin I (released during periods of hypotension) to angiotensin II, a powerful vasoconstrictor that helps raise blood pressure. The same enzyme also inactivates 80 percent\u00a0of circulating bradykinin (a potent vasodilator)."}
+{"id": "pulmo2$$$37f8cdc0-2060-4076-88d8-9f72c303515e", "contents": "Serotonin: Other circulating substances that are controlled by the lung include serotonin, as the lung is the major site for removing serotonin from the circulation. The lung stores the serotonin, rather than breaking it down, and even transfers it to platelets who use serotonin in their hemostatic role."}
+{"id": "pulmo2$$$d48f6563-76cf-4d0e-94ea-3da171ab0196", "contents": "Arachidonic acid: The lung is also involved in the metabolism of arachidonic acid, which is worth dealing with here as well because\u00a0not only are the products of this metabolism vasoactive, they can also influence airway smooth muscle\u00a0and cause bronchoconstriction. In brief, arachidonic acid is produced by the action of a phospholipase on membrane-bound phospholipids. The arachidonic acid can then follow one of two pathways (figure 10.1): to produce leukotrienes, which\u00a0are involved in the inflammatory response and can cause bronchoconstriction, or\u00a0to produce prostaglandins and thromboxane through the action of cyclooxygenases. The relevance for us here is that these alternative pathways explain why some asthmatics are sensitive to aspirin and bronchoconstrict when they take aspirin. Aspirin inhibits cyclooxygenase\u00a0and thus blocks one of these pathways. Consequently there is more substrate, arachidonic acid, available for the alternate pathway and so more leukotrienes are produced, in response to which\u00a0the hypersensitive airways of the asthmatic bronchoconstrict."}
+{"id": "pulmo2$$$300e0c14-dff2-4bad-bcac-eb32a8f0d68b", "contents": "So from this chapter you should be able to determine the direction of fluid movement into and out of the pulmonary capillaries given the Starling and lung forces involved, and appreciate that the lung plays other relatively small but significant metabolic roles."}
+{"id": "pulmo2$$$405afb7b-5d31-4d56-b756-36329df0d2fa", "contents": "Levitsky, Michael G. \u201cChapter 10: Nonrespiratory Functions of the Lung.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$9cfd8d5d-3721-4961-8c24-8b2bba6b0e82", "contents": "West, John B. \u201cChapter 4: Blood Flow and Metabolism\u2014How the Pulmonary Circulation Removes Gas from the Lung and Alters Some Metabolites.\u201d In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012."}
+{"id": "pulmo2$$$2d656643-3fd1-43fc-96ee-10525d50b3a7", "contents": "The pulmonary circulation takes all cardiac output from the right heart via the pulmonary arteries. Thus, even at rest it has a tremendous blood flow \u2013 about 5 liters per minute, just the same as the systemic circulation. This volume enters a vast array of vessels that penetrate all the lung structure \u2013 so much so that the complete lung structure is visible from the cast of the pulmonary vasculature in figure 9.1."}
+{"id": "pulmo2$$$203cf211-dc4b-4b38-8067-a5e2bc9c8686", "contents": "Main arteries follow a similar branching pattern to the bronchial tree until the terminal bronchioles are reached. This anatomical arrangement allows perfusion to follow the ventilation. Upon reaching the terminal bronchioles the vessels divide into a vast array of capillaries\u00a0that wrap around the respiratory ducts and alveoli to form the respiratory zone of the lungs."}
+{"id": "pulmo2$$$71adf9d0-36ec-43e0-a596-d39992c60ac8", "contents": "The density of the capillary beds is so great that individual capillaries can loose their distinct anatomy as can be seen in this electron micrograph where the capillaries are seen to form more sheet-like structures around where the alveoli would be. A common analogy for this is the capillaries look more like a floor of a parking garage with pillars for support but mainly open space \u2013 rather (figure 9.3) than the distinct tubes seen in other circulations."}
+{"id": "pulmo2$$$d0577b04-fbad-40d6-a316-b00097d55971", "contents": "The capillary beds converge into small veins after traveling over the alveolar surfaces, and these small veins then collect into four pulmonary veins that lead back to the left heart. This is an unusual example of veins carrying blood with arterial gas pressures."}
+{"id": "pulmo2$$$4a245151-c7e3-4f86-a18b-ec19ffdc9e6f", "contents": "Despite receiving the same blood volume per minute as the systemic circulation the pulmonary circulation is a low-pressure system. Systolic pressure is normally only 25 mmHg, compared to 120 in the systemic circulation, diastolic is 8, compared to 80 and mean pulmonary artery pressure is only 15. These numbers are well worth remembering."}
+{"id": "pulmo2$$$e736cb28-7cdf-4455-993e-4b5f2ffa34ab", "contents": "So how can this one circulation receive so much volume (the complete cardiac output) and yet remain at such low pressure? The first reason is the vast size of the capillary beds. As figure 9.4 suggests, the much higher density of pulmonary capillary beds than that seen in the systemic circulation allows pressure to dissipate much more quickly."}
+{"id": "pulmo2$$$b3758842-3c66-487d-ab1b-6fa24991e892", "contents": "The pulmonary arteries show different characteristic to their systemic counterparts as well.\u00a0The walls of a pulmonary arterioles are thin\u00a0compared to systemic arterioles. They also lack\u00a0the smooth muscle layer seen in the systemic arteriole. In fact pulmonary arterioles look much more like systemic veins and they are often mistaken for such in biopsy or dissection. With little smooth muscle it\u2019s clear that these vessels have little role in controlling the distribution of blood flow \u2013 a vital role of their systemic counterparts. As the pulmonary circulation receives all cardiac output, all the time, such precise control isn\u2019t required."}
+{"id": "pulmo2$$$36e1ecec-46eb-4a1f-9188-93fae0ef19ae", "contents": "The thin walls and lack of smooth muscle also make the pulmonary arterioles highly compliant and so they behave much more like veins in their pressure response \u2013 extending when pressure increases. This gives the pulmonary arteriole system a rather unique pressure-resistance relationship that we\u2019ll look at in a moment."}
+{"id": "pulmo2$$$d733e2c5-3e4a-4418-a68f-e424ee6e64cc", "contents": "This low pressure and compliant system also means that the right heart has much less work to perform to generate its output. In fact the right ventricle has about a tenth of the work of the left heart to move exactly the same blood volume. Hence the structure and work capacity of the right heart is so much smaller than the left \u2013 something worth bearing in mind if disease causes changes in the\u00a0pulmonary vasculature that in turn causes the\u00a0less substantial right heart to work harder and undergo hypertrophy"}
+{"id": "pulmo2$$$6325a5d6-c907-458f-84da-8cb60a279adc", "contents": "As we have just seen, with little smooth muscle and a compliant wall, the arterioles act more like veins. As pulmonary arterial pressure rises, the resistance of the pulmonary circulation falls, as seen in figure 9.4, and this occurs for\u00a0several reasons."}
+{"id": "pulmo2$$$2bbb86e4-449d-4278-ad09-1990a2d8b684", "contents": "Unlike systemic arterioles there is little autoregulation by the pulmonary arterioles, so the pulmonary arterioles do not actively vasoconstrict when stretched by high pressure. Instead, they passively distend, thereby reducing their resistance with increasing resistance."}
+{"id": "pulmo2$$$e559d206-42f3-4699-bd6c-3b0df3ae3c3c", "contents": "A rise in pulmonary pressure not only distends vessels but initiates flow through otherwise unused, or dormant, vessels, particularly those closer to the apex of the lung (we will see why later on). With more vessels recruited, the total cross-sectional area of used vessels increases and total resistance falls."}
+{"id": "pulmo2$$$3ec59c37-13fa-479f-8c93-87d98c5f6443", "contents": "But there are other and more complex peculiarities of the pulmonary circulation that determine its resistance\u2026"}
+{"id": "pulmo2$$$18ebdcaa-ba5a-453f-8caa-380515f09552", "contents": "Another unique characteristic of the pulmonary circulation is that it is exposed to the changing pressures in the airways and alveoli. It is also involved in the fiber network that generates radial traction. Consequently pulmonary vessels can be expanded or compressed in a way no other circulation is."}
+{"id": "pulmo2$$$3f0e9c13-9090-4942-9128-184922b0e4e5", "contents": "To explain these phenomena we have to divide the pulmonary circulation into two subdivisions, the alveolar vessels and the extra-alveolar vessels (figure 9.5). These two vessel types behave differently, so we will deal with them separately."}
+{"id": "pulmo2$$$30c04fba-638c-4161-875c-e9c874074e28", "contents": "Alveolar vessels: These are primarily the capillaries and small vessels in close contact with the alveoli. Consequently they are exposed to the alveolar pressures. First,\u00a0the surface tension within the alveolus that is tending to pull the alveolus closed also pulls on the vessels between alveoli, tending to pull it open as neighboring alveoli pull inward on themselves, and play tug-of-war with the vessel walls in between, extending them and causing a decrease in vascular resistance."}
+{"id": "pulmo2$$$a6908a5d-de72-4643-9dbd-7c05bae9db4a", "contents": "Alternatively, when alveolar pressure increases (e.g., at high lung volumes), the raised alveolar pressure can compress the vessels running over its surface, causing an increase in vascular resistance."}
+{"id": "pulmo2$$$33efc853-5de8-41ff-8faa-0de4b021fdf1", "contents": "Extra-alveolar vessels: By definition these vessels are not in contact with the alveoli, so they are not exposed to the same alveolar forces. These are exposed to the intrapleural forces, however, so as we saw airways opening during inspiration when intra-pleural pressure falls, these extra-alveolar vessels are also pulled open during inspiration by radial traction, and their resistance consequently falls as lung volume increases."}
+{"id": "pulmo2$$$41d6d59f-fe3d-411a-a0c2-66ac80e86083", "contents": "The summation of these forces (alveolar pressure, surface tension, and radial traction) means that pulmonary vasculature resistance has a complex relationship with lung volume."}
+{"id": "pulmo2$$$79ac47de-cbee-4e67-902e-326cf326ff5a", "contents": "Vascular resistance at low lung volumes: At low lung volumes (figure 9.6, gray zone on the left), you should know that intra-pleural pressure is less negative because the lung recoil is less. With less negative pressure to hold open the extra-alveolar vessels via radial traction,\u00a0these tend to narrow and vasculature resistance becomes relatively high."}
+{"id": "pulmo2$$$c8eb161e-6df3-439e-b207-ca61bd6a145b", "contents": "Vascular resistance at medium lung volumes: As lung volume increases (figure 9.6, tan zone in the middle), the intrapleural pressure becomes more negative. Radial or parenchymal traction now begins to pull the extra-alveolar vessels open, and as they become wider, vascular resistance falls. Common sense would tell you that this effect would increase with continually larger lung volumes, and one might expect that vascular resistance would continue to decrease as lung volume increased. But this is evidently not the case."}
+{"id": "pulmo2$$$662a01db-ceb5-4631-8916-57168017e69f", "contents": "Vascular resistance at high lung volumes: With further increases in lung volume (figure 9.6, pink zone on the right), vascular resistance rises. At high lung volumes the alveoli are enlarging, and this causes the capillaries running around them to stretch. As the capillaries stretch, they\u00a0narrow\u2014a little like how a piece of latex tubing narrows when it is\u00a0stretched. This narrowing of a large number of capillaries overcomes the radial traction effect on the extra-alveolar vessels, and there is a net increase in vascular resistance."}
+{"id": "pulmo2$$$689ce975-ea30-416b-844d-fd839fcb438f", "contents": "So vascular resistance and lung volume are related with an inverted bell-shaped relationship. Now let us\u00a0look at the forces that determine the distribution of blood flow across the lung structure."}
+{"id": "pulmo2$$$ebf14881-b887-46d5-aa4b-57d239510c35", "contents": "You may recall that gravity affected the distribution of ventilation by generating the gradient of intrapleural pressures down the lung\u2014most negative at the apex, less negative at the base."}
+{"id": "pulmo2$$$3e7ca2e1-e790-4b9f-b380-ae003c217ec6", "contents": "We see a similar distribution of blood flow in the lung as well, as figure 9.7\u00a0shows with blood flow being greater at the base of the lung than it is at the apex. Again this is simply due to gravity. Gravity pushes against the blood rising from heart level, hence the base is better perfused than the apex. Because of this, gravity is responsible for matching the level of perfusion and ventilation up the lung; both are high at the bottom, and both are low at the apex. This is advantageous, as well ventilated areas need more perfusion for efficient gas exchange, and likewise there is little point in sending large amounts of pulmonary blood to poorly ventilated areas. The relationship between ventilation and perfusion (known as the V/Q ratio) that gravity establishes is not quite ideal, however, and we will see the ramifications of this less-than-perfect relationship later on. There are also other forces affecting the distribution of perfusion as well, and we can look at them now."}
+{"id": "pulmo2$$$af9961ed-cb89-4f06-8d40-6eec104904ca", "contents": "We now have to consider the relationship of the pressures in these three systems, arterial, alveolar and venous, at different heights of the lung. Many of the following principles have already been dealt with, but we can put them together to look at how they affect perfusion distribution."}
+{"id": "pulmo2$$$2147c739-e5c8-44a6-8df7-943fe01fe7a2", "contents": "Zone 1: At the top of the lung the arterial pressure is relatively low because this is the furthest vertical distance from the heart. In the same zone, as you know, the alveoli here are extended by the low (more negative) intrapleural pressure at the apex. These extended alveoli tend to compress the surrounding capillaries, and the lack of arterial pressure to push past the extended alveolus means blood flow through capillary beds in zone 1\u00a0may be relatively low. It is certainly a pronounced effect in patients\u00a0undergoing positive pressure ventilation where alveolar pressure may exceed arterial pressure and stop blood flow at the apex altogether. This\u00a0phenomenon of ventilated but underperfused alveoli is referred to as alveolar dead space, as without adequate perfusion, gas exchange is compromised."}
+{"id": "pulmo2$$$2d0d3094-4f38-436c-bcb2-df7ad18adeb7", "contents": "Zone 2: In zone 2\u00a0we are lower down the lung, and at this point arterial pressure is higher (closer proximity to the heart) and the alveoli are less extended, but venous pressure remains less than alveolar pressure. So flow in zone 2\u00a0is determined by the difference between arterial and alveolar pressures."}
+{"id": "pulmo2$$$12a2f3dd-f3c3-42b2-a3e2-d5e47261a51b", "contents": "Zone 3: Dropping further down the lung to the base, the arterial and venous pressure have both risen as the column of fluid (blood) above them is greater at this point, and now both are above the now smaller alveolar pressure (near the base the intrapleural pressure is less negative). Consequently the flow through the capillary bed in zone 3\u00a0is determined by the arterial\u2013venous pressure difference, just as it is in the systemic circulation."}
+{"id": "pulmo2$$$2afa1608-c9b0-4550-82bb-63d310167368", "contents": "(There can at times be a fourth zone, which appears only at low lung volumes. At low lung volumes tissue at the base of the lung can be compressed, and this compression can collapse the extra-alveolar vessels.)"}
+{"id": "pulmo2$$$e8c397b8-78a9-4660-b617-1d4f664f890a", "contents": "So when considering flow through a systemic capillary bed we only have to think about the arterial and venous pressures, the pulmonary circulation throws us a curve ball by adding alveolar pressures into the mix that produce these perfusion zones."}
+{"id": "pulmo2$$$8df720cc-9a89-4b3e-aae3-53bb6fb0914a", "contents": "If systemic tissue becomes hypoxic then local arterioles open to allow more blood flow and increase oxygen delivery. The opposite is true for the pulmonary circulation where the response to local hypoxia is vasoconstriction."}
+{"id": "pulmo2$$$464ab310-a3d2-47ba-a61a-4ff9574d7a11", "contents": "First, remember that the bronchial circulation provides oxygen and nutrients to the pulmonary itself, and this behaves as all other systemic circulations. But the pulmonary circulation is for gas exchange. So if an area of the lung has become hypoxic (i.e., has a low oxygen partial pressure), this is indicative of that area having insufficient ventilation."}
+{"id": "pulmo2$$$50c601f1-cfb5-4ee9-abb0-0fc7de209eae", "contents": "If there is little ventilation going to that area then there is little point sending perfusion to it. So the little smooth muscle there is in the pulmonary vasculature contracts to constrict the vessel when hypoxia is present. The blood follows the path of least resistance and thereby goes to vessels that are open (i.e., to areas where ventilation is maintaining a higher PO2)."}
+{"id": "pulmo2$$$9b54c899-a7bc-41ae-9f38-770b14694999", "contents": "Because of its unique role in gas exchange, rather than supplying local tissue, and the pressures that are present in the lung beyond vasculature pressure, plus the different vasculature structure, the pulmonary circulation has some unusual characteristics. These produce unique blood flow patterns in response to lung volume, gravity, and the need to match ventilated areas with adequate perfusion."}
+{"id": "pulmo2$$$5bbf18cb-720e-433f-a97c-7a9a17affa5c", "contents": "Levitsky, Michael G. \u201cChapter 4: Blood Flow to the Lung.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$58f3e187-02d3-4794-a834-033ae16daf9b", "contents": "Widdicombe, John G., and Andrew S. Davis. \u201cChapter 5.\u201d In Respiratory Physiology. Baltimore: University Park Press, 1983."}
+{"id": "pulmo2$$$ea085c56-bcc8-4188-83d6-9514a3d788c6", "contents": "Identifying whether deranged blood gases are due to diffusion or perfusion limitations can help in the diagnosis of an underlying pathological issue, so we will look at them here."}
+{"id": "pulmo2$$$463fa892-1416-4654-be18-50ff142f7f54", "contents": "If a sufficient diffusion gradient exists across a membrane, then the rate of transfer of gas is primarily dependent on the properties of the membrane (see the left side of the figure 8.1). The transfer of gas in this case is referred to as a diffusion limitation."}
+{"id": "pulmo2$$$3c95b469-429c-4487-826d-731547875baa", "contents": "If gas starts to accumulate on the other side of the membrane, however, the pressure gradient will dissipate and transfer rates become limited (right side of figure 8.1). This is referred to as a perfusion limitation, as it is indicative of low blood flow that is insufficient to \u201cwash away\u201d\u00a0transferred gas, keep blood gas partial pressure low, and maintain the diffusion gradient."}
+{"id": "pulmo2$$$6c66fe37-5877-45a5-8184-401b37c5900c", "contents": "We can illustrate these diffusion and perfusion limitations with the behavior of two nonphysiological gases transferring from the alveolus to the bloodstream."}
+{"id": "pulmo2$$$2e41ac57-5da4-462e-a1ea-a28cb636db14", "contents": "Carbon monoxide is well known for its affinity for hemoglobin. When CO passes across the membrane it rapidly binds to hemoglobin and is thus removed from solution. This removal from solution maintains the pressure gradient across the membrane. So with a maintained pressure gradient the major impediment to CO transfer is diffusion across the membrane. Therefore CO transfer is referred to as diffusion limited and dependent on the properties of the membrane. (Consequently CO is used in diffusion limitation testing (DLCO) in pulmonary function labs.)"}
+{"id": "pulmo2$$$79366767-25f0-4533-89cb-10bcd3076920", "contents": "Nitrous oxide, alternatively, does not\u00a0bind with hemoglobin at all, so its arterial partial pressure rises rapidly as it stays in solution. So maintaining the pressure gradient is dependent on how quickly the transferred nitrous oxide is washed away by blood flow. Because of this, nitrous oxide is referred to as perfusion limited."}
+{"id": "pulmo2$$$984378f8-8885-440a-93fe-2ed0658d9617", "contents": "So while our two nonphysiological gases provide good examples of diffusion and perfusion limitations, let us\u00a0see how oxygen behaves."}
+{"id": "pulmo2$$$5112588e-a1a8-4d11-ab6b-ec9e9a12b260", "contents": "The blood partial pressure of CO rises very little along the capillary as it is rapidly binding to hemoglobin (Hb)\u00a0(figure 8.2), the pressure gradient is maintained, and the CO is only limited by the membrane; it exhibits diffusion limitation."}
+{"id": "pulmo2$$$fcb04a87-d9cf-452a-bfc9-9e25aede1a08", "contents": "The blood partial pressure of nitrous oxide, alternatively, rapidly rises (figure 8.2), and the transfer of NO becomes reliant on the rate of perfusion to maintain the gradient and gas transfer\u00a0(i.e., it is\u00a0perfusion limited)."}
+{"id": "pulmo2$$$07c87127-f693-453f-bb01-92a16e7f2c7d", "contents": "The results for O2\u00a0fall much closer to the perfusion limitation (NO) line than the diffusion limitation line (figure 8.2, O2\u00a0normal). Oxygen binds to hemoglobin so the arterial PO2\u00a0does\u00a0not rise as quickly as nitrous oxide, but the binding of O2\u00a0is so much less than carbon monoxide it actually demonstrates more perfusion, rather than diffusion limitation."}
+{"id": "pulmo2$$$7c077748-f7da-4e48-82c8-e8c12aa90d58", "contents": "The transfer of O2\u00a0is also hampered by having to start off at venous partial pressures (40 mmHg), compared to our test gases that start off at zero. Consequently the initial pressure gradient is less. Despite this, the arterial partial pressure of oxygen equilibrates with alveolar pressures within 0.25 seconds (i.e., a third of the distance around the capillary). With the blood still having another 0.5 seconds in the capillary, this provides a large reserve time."}
+{"id": "pulmo2$$$a832895e-d2aa-49dd-8fc7-669911a24b06", "contents": "This reserve time is often eaten into in some disease states (figure 8.2, abnormal); if for example a diffusion problem arises, such as thickening of the membrane, then that extra 0.5 seconds, or last 2/3 seconds of the transit time around the alveolus, can still allow alveolar and arterial PO2s to equilibrate. The patient may still show normal oxygen pressures until they exercise, during which the velocity of pulmonary blood flow increases and transit time is reduced; you can see from figure 8.2 if transit time is reduced to 0.5 seconds then arterial PO2\u00a0will not equilibrate with alveolar values in the abnormal lung."}
+{"id": "pulmo2$$$00d5d42c-2cac-4631-a847-74fc82e3cfce", "contents": "While in the normal state the transfer of oxygen is perfusion limited, in lung diseases that affect the surface area or membrane thickness of the gas exchange surface, the transfer of oxygen may become diffusion limited. Being able to measure the transfer of gas into the blood provides a valuable diagnostic tool. This is what we will look at here, not only because of its clinical pertinence, but also because it summarizes some physiological principles."}
+{"id": "pulmo2$$$5a6530c6-b883-4dc9-9634-21639f6c6958", "contents": "The gas used to test the\u00a0diffusion capacity of the lung is carbon monoxide. Why? Because as you have seen, carbon monoxide is diffusion limited, so any change in membrane characteristics will affect its movement into the bloodstream. So fundamentally, we will have the patient inhale a little carbon monoxide and hold their breath for a few seconds. During the breath-hold some CO will move into the bloodstream\u2014the greater the disease (diffusion limitation), the more will stay in the lung. As the patient breathes out,\u00a0the exhaled carbon monoxide (i.e., that not transferred) is measured. The difference between the amount inhaled and the amount returned in the exhalation is the amount that crossed into the blood. The more CO that comes back in the exhalation, the less that crossed into the blood and the worse diffusion limitation is."}
+{"id": "pulmo2$$$c56b5d78-a406-4e4f-aaee-34714643e722", "contents": "The transfer factor is primarily dictated by the factors within Fick\u2019s law of diffusion. Because we cannot independently measure membrane area and thickness, we lump these terms and the diffusion coefficient of the gas we are interested in into one term, the diffusing capacity of the lung, or DL\u00a0(equations below)."}
+{"id": "pulmo2$$$224fdfcb-baee-4d17-9dde-868ee8e881a6", "contents": "Equation 8.1"}
+{"id": "pulmo2$$$a8d30229-e745-4fb9-a152-e2675774464c", "contents": "Equation 8.2"}
+{"id": "pulmo2$$$25642507-f496-4380-8e93-2566b49d6a8b", "contents": "Equation 8.3"}
+{"id": "pulmo2$$$68e63b92-cda8-4a3e-b2b2-6d3eff583dc2", "contents": "Equation 8.4"}
+{"id": "pulmo2$$$0b0b7401-8a9a-49d6-b8f2-da909601e4ba", "contents": "In the lab test, we are specifically looking at the transfer, or flow, of CO across the membrane, and if we rearrange this equation for transfer factor we see the transfer factor is the flow of CO divided by the pressure gradient of CO (equation 8.4). We can assume that the arterial partial pressure of CO is zero, so our equation for transfer factor ends up as the flow, or transfer, of CO across the membrane, divided by the alveolar partial pressure of CO."}
+{"id": "pulmo2$$$6a153cc7-d489-47f4-b8b1-eb69a95e082f", "contents": "But the movement of gases such as CO, and more physiologically important, oxygen, is also determined by the rate of binding with hemoglobin when it gets into the bloodstream. So our transfer factor has to contain an additional term to account for this. The rate of binding to hemoglobin is determined by two factors; first,\u00a0the affinity of the gas for hemoglobin, denoted here by theta, and second, by the amount of hemoglobin present in the capillary, denoted as Vc, or capillary volume."}
+{"id": "pulmo2$$$ca9a9fb1-8932-4866-a277-090804daf777", "contents": "Equation 8.5"}
+{"id": "pulmo2$$$9d4fa9a6-e062-4ba6-8391-4a4909541b16", "contents": "So now if we rename our initial value of DL\u00a0that described the factors associated with the membrane as DM and add our term to account for binding with hemoglobin (equation 8.5), the sum of these two gives a more complete description of transfer, or DL. This more complete term now reflects that the transfer of gas is not solely dependent on membrane properties."}
+{"id": "pulmo2$$$125930a1-e498-4bcd-b7b9-a1906ed993e2", "contents": "This provides a relatively simple and powerful diagnostic technique to assess disease stage and reduced function of the lung as a gas exchange organ."}
+{"id": "pulmo2$$$111ccdb1-28e8-416f-9d22-c1ec31f466ce", "contents": "So we have seen the two major factors that affect the rate of gas transfer across the lung:\u00a0the rate of diffusion that is determined by the characteristics of the membrane (as described in Fick\u2019s law of diffusion), and also the rate of perfusion, which involves the rate of blood flow, volume, and binding affinity with hemoglobin. Diffusion limitation is really a description of the impediment caused by the membrane with a constant partial pressure gradient; and perfusion limitation describes whether the partial pressure gradient is being maintained."}
+{"id": "pulmo2$$$7ee7bd78-ee76-462c-8326-3223973d9968", "contents": "Levitsky, Michael G. \u201cChapter 6: Diffusion of Gases and Interpretation of Pulmonary Function Tests.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$7098f0e3-8f6c-4a7f-8bb9-019917fbc96e", "contents": "West, John B. \u201cChapter 3: Diffusion\u2014How Gas Gets Across the Blood\u2013Gas Barrier.\u201d In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012."}
+{"id": "pulmo2$$$83eef49d-f1b3-4248-908d-fe1c99a681e8", "contents": "Widdicombe, John G., and Andrew S. Davis. \u201cChapter 4.\u201d In Respiratory Physiology. Baltimore: University Park Press, 1983."}
+{"id": "pulmo2$$$94a2e555-32f9-4cc7-8f5b-ef7daead5687", "contents": "Before we do that though, we need to be able to calculate the units of measurement we use when describing gas exchange. When referring to gas exchange we are really referring to diffusion of gases down their concentration gradient, but rather than use concentrations, we use partial pressures."}
+{"id": "pulmo2$$$83d5f78d-9abb-48e8-b071-bef116366b8f", "contents": "Partial pressures describe what proportion of the total pressure is exerted by a particular component of a mixed gas. Let us\u00a0look at the specific situation we are interested in to illustrate this description."}
+{"id": "pulmo2$$$d82456a7-eec8-4a00-acb8-976db3f8f866", "contents": "Atmospheric pressure at sea level is 760 mmHg. This pressure is generated by the collisions of all the molecules with each other and other objects. At high altitude there are fewer molecules, so fewer collisions, and hence atmospheric pressure is lower."}
+{"id": "pulmo2$$$a630d4b8-fca5-42f2-b5b5-7435455e5bc6", "contents": "Now looking at the composition of our atmosphere we know that 79 percent\u00a0is nitrogen, 20.9 percent\u00a0is oxygen, and some trace gases collectively get us to 100 percent. Now let us\u00a0calculate a partial pressure. If 79 percent\u00a0of the atmosphere is nitrogen, then 79 percent\u00a0of our atmospheric pressure is generated by the collisions by nitrogen molecules. Likewise 20.9 percent\u00a0of the atmospheric pressure is due to oxygen, so to calculate the partial pressure of oxygen (PO2) we simply multiply atmospheric pressure (PB) by the percentage of oxygen, which means our atmosphere has a partial pressure of oxygen of 159 mmHg."}
+{"id": "pulmo2$$$271b75fb-b62c-4dfb-8a5e-c125c2c035f6", "contents": "[latex]PO_2 = 20.9\\% \\times 760\\:mmHg = 159\\:mmHg[/latex]"}
+{"id": "pulmo2$$$6bcbe39a-d68e-4fea-8188-d9c23f4383ab", "contents": "Although related, we are more interested in the PO2\u00a0at the gas exchange surface\u2014that is the alveolar PO2\u00a0denoted as PAO2\u00a0(note the uppercase A; lowercase refers to arterial PO2\u00a0(i.e.,\u00a0PaO2)). This value differs significantly from atmospheric PO2\u00a0at about 100 mmHg. So why the drop of nearly 60 mmHg from atmospheric PO2?"}
+{"id": "pulmo2$$$e05798d0-51c0-4eaf-9124-90ebfc0b3dbf", "contents": "To calculate alveolar PO2\u00a0we need to account for the water vapor that is added to the inspired air as it enters the airways. This is equivalent to\u00a0adding another gas and must be accounted for. Water vapor exerts a pressure of 47 mmHg. Subtracting this from our atmospheric pressure, our total gaseous pressure is 713 mmHg;\u00a0multiplying this by our fraction of inspired O2\u00a0(FiO2\u00a0is merely the percentage (fraction) of oxygen inspired), we see our alveolar PO2\u00a0is theoretically 149.7 mmHg (i.e., ~150 mmHg)."}
+{"id": "pulmo2$$$58d7a984-0b05-480d-a977-641d70b4ff44", "contents": "[latex]P_AO_2 = 20.9\\% \\times (760 - 47) = 149.7\\:mmHg\\:or \\sim 150\\:mmHg[/latex]"}
+{"id": "pulmo2$$$d78ff3df-9ffa-46b9-b14f-8135c3c1a230", "contents": "If we understand that there will be mixing with air remaining from the previous breath, the real PAO2\u00a0is 100 mmHg (however, we will see this varies across the regions of the lung)."}
+{"id": "pulmo2$$$08e5a60b-4262-4849-8300-e592f290d3d6", "contents": "So how does this value relate to gas exchange in the lung? The venous blood PO2\u00a0(PVO2), returning from the systemic tissue where oxygen has been consumed, is 40 mmHg (see figure 7.1). This blood passes the gas exchange surface, and a pressure gradient of 60 mmHg allows oxygen to move into the pulmonary blood. By the time the blood has passed\u00a0the alveolus, arterial PO2\u00a0will have equilibrated with the alveolar PO2\u00a0and will also be 100 mmHg. These numbers are well worth committing to memory."}
+{"id": "pulmo2$$$ed53b093-27bf-4647-99ec-a32df33bc45a", "contents": "The other critical values we need to address here are the partial pressures of CO2\u00a0(see figure 7.2). Venous blood returning from the tissue has a PCO2\u00a0of 45 mmHg, compared to alveolar PCO2\u00a0that is 40 mmHg. This pressure gradient of 5 mmHg is enough to allow blood to equilibrate with the alveolus, and so arterial PCO2\u00a0is 40 mmHg.\u00a0Again, these numbers are worth remembering."}
+{"id": "pulmo2$$$80f14e98-6d0d-46d5-a094-2dd9f1a23aa6", "contents": "A much smaller diffusion gradient is needed for CO2 because CO2\u00a0is much more soluble than oxygen, a factor\u00a0among\u00a0others that is\u00a0included in Fick\u2019s law of diffusion."}
+{"id": "pulmo2$$$785844a4-2f7f-40fb-bc0c-231169e46107", "contents": "Fick\u2019s law of diffusion (equation 7.1) describes all the factors that influence the transfer of gas (or flow, V) across a membrane."}
+{"id": "pulmo2$$$4245e993-555f-4e26-97d2-7104b69edf40", "contents": "Equation 7.1"}
+{"id": "pulmo2$$$8dca1687-82b4-49ca-8ea5-b76ac65f54e1", "contents": "We will look at each factor in the equation and see how it relates to the physiology of the lung."}
+{"id": "pulmo2$$$c111fe31-7355-4c6d-b8a8-3f2d0a641894", "contents": "Pressure gradient (P1\u2212P2): The higher the pressure gradient, the greater the transfer of gas, and the pressure gradient must be maintained for gas exchange to continue. The maintenance of the gradient is achieved by adequate ventilation to the alveolus to refresh the alveolar gases, and adequate perfusion to flush oxygen away from the gas exchange surface and supply more CO2. We will look at the importance of matching ventilation and perfusion in chapter 13."}
+{"id": "pulmo2$$$30613f0f-6fb1-4313-ab7e-de7303b85abb", "contents": "Other factors in Fick\u2019s\u00a0law are fairly obvious and are reflected in the lung\u2019s structure."}
+{"id": "pulmo2$$$3ca943e1-d69f-4558-ab75-d578a5cbb04c", "contents": "Surface area (A): The greater the surface area available for exchange, the greater the exchange. The lung has a surface area of 100 m2, which is more than adequate to maintain sufficient gas transfer, even during maximal exercise."}
+{"id": "pulmo2$$$c3b32db8-11df-4ba0-9a25-673c9629e987", "contents": "Membrane thickness (T): The thickness of the membrane that gas has to cross also determines the rate of transfer; the thinner the membrane, the more rapid the transfer. The gas exchange membrane in the lung is approximately a 0.3 um thick\u2014and poses little opposition to gas movement."}
+{"id": "pulmo2$$$002b493a-4e40-49b3-b65a-ac4294846cb9", "contents": "Diffusion constant (D): The last variable is the diffusion constant of the gases in question, which for us are O2 and CO2. The important issue here is that CO2 is much more soluble (x 20) than O2\u00a0and so has\u00a0a much greater diffusion constant; hence it transfers across the membrane much more readily and does not\u00a0need the large pressure gradient like the relatively insoluble oxygen (5 mmHg compared with 60 mmHg)."}
+{"id": "pulmo2$$$5599cd0a-f222-443d-8220-ec940bec4498", "contents": "Some of these factors can change in lung disease and can result in decreased gas exchange and so result in deranged blood gases. Loss of surface area occurs in diseases, such as emphysema, that destroy the lung architecture, and cause a loss of gas transfer. Likewise, any disease that causes thickening of the alveolar membrane, such as pulmonary fibrosis, increases the distance for, and resistance to, gas transfer. If ventilation or perfusion of the gas exchange surface fails\u2014for example, a mucus plug blocking an airway or a pulmonary embolus blocking a vessel\u2014then the pressure gradient across the membrane is lost and gas exchange is reduced compared to the ideal situation of ventilation and perfusion being matched."}
+{"id": "pulmo2$$$da7da9ee-69af-494c-bef6-64c3e1342329", "contents": "After this chapter you should be able to calculate the alveolar partial pressure of a gas at any atmospheric pressure and relate it to the rate of gas exchange."}
+{"id": "pulmo2$$$ba6d348e-7679-420a-8bdb-a3ca3d680d28", "contents": "You should also now understand the different factors that contribute to the rate of gas exchange described in Fick\u2019s law of diffusion and be able to appreciate how they might change in disease."}
+{"id": "pulmo2$$$5d2625dd-c00f-406e-89b7-bf17e3d042c0", "contents": "PO2=20.9%\u00d7760mmHg=159mmHg"}
+{"id": "pulmo2$$$7e8e8e0e-3038-405c-8d7a-fd9238de44aa", "contents": "20.9"}
+{"id": "pulmo2$$$5ebd5f2f-5746-4bbc-a036-3921e85c3205", "contents": "PAO2=20.9%\u00d7(760\u221247)=149.7mmHgor\u223c150mmHg"}
+{"id": "pulmo2$$$2417ccf9-6f8c-41eb-8afa-8fd9f8f8b13b", "contents": "149.7"}
+{"id": "pulmo2$$$e125ba2f-6da8-4e10-bea6-e132c5f31f62", "contents": "Although this phenomenon is present in the healthy lung, we will see how it is exacerbated in certain disease states and how this exacerbation can be detected by common pulmonary function tests."}
+{"id": "pulmo2$$$6443f20b-c2ba-4f2a-912d-b820480b48dc", "contents": "First, let us\u00a0look at the forces involved during a normal, passive expiration."}
+{"id": "pulmo2$$$b41f13e9-f936-4f36-a5cf-fb0da07ecd91", "contents": "For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about \u22128 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open."}
+{"id": "pulmo2$$$b2595d16-3472-4347-8652-8a5041e897ec", "contents": "The elastic forces of the alveolus wall exert an inward force of about +10 cm H2O. This results in a net force of +2 cm H2O in the alveolus, and a gradient between this positive pressure is established between the alveolus and the atmosphere outside the lung. That means that along the airway toward\u00a0the mouth there is a gradient of progressively decreasing pressure to zero (shown in maroon)."}
+{"id": "pulmo2$$$4d8eebf9-c2a1-4fc0-af77-1f63bd8d903f", "contents": "Importantly in this example of passive expiration the airway pressure is greater than the pleural pressure along the whole length of the airway toward the mouth. Along with the radial traction provided by the surrounding parenchymal tissue, this favorable transmural pressure gradient helps keep the airway open during expiration."}
+{"id": "pulmo2$$$85336abb-ae09-42b1-8f3d-90c22ce05bb5", "contents": "Now let us\u00a0look at what happens if expiration is forceful, or active, rather than passively relying on lung recoil."}
+{"id": "pulmo2$$$6141bd45-9a97-4ead-8439-2dddc888dac7", "contents": "In a forced expiration (see figure 6.2) the intrapleural pressure can become positive (as much as 120 cm H2O), but in this example we will say it is\u00a025 cm H2O. This positive pressure in the pleural cavity comes from the chest wall and diaphragm now \u201cpushing\u201d\u00a0the pleural membranes together and compressing the lung."}
+{"id": "pulmo2$$$8b63e01d-2e8d-46d0-90ae-dad23f3025c1", "contents": "Again, we have the elastic forces of the alveolus generating an inward force (still +10 cm H2O), and when summed with the now positive intrapleural forces, we end up with an alveolar pressure of +35 cm H2O."}
+{"id": "pulmo2$$$2aefa857-cbcc-430c-96cb-ba4ef825fd3d", "contents": "Again, a pressure gradient between the alveolus and the atmosphere is established (again shown in maroon), but this time there is a fundamental difference caused by the larger intrapleural pressure."}
+{"id": "pulmo2$$$8da683bb-c7ee-4f58-b005-bf64671bdced", "contents": "At some point along the airway, as airway pressure is decreasing, the intrapleural pressure exceeds airway pressure (in this example it is 25 cm H2O). At this \u201cchoke\u201d\u00a0point (arrows pointing toward airway in figure 6.2), the airway can become compressed or even collapse."}
+{"id": "pulmo2$$$480559ff-b1ff-40db-8773-ae708a2320e6", "contents": "This\u00a0effect is somewhat reduced by the radial traction of the parenchyma, but airway compression occurs even in the healthy normal lung, and the greater the effort of expiration (i.e., the more positive the intrapleural pressure), the greater degree airways compress and compression occurs closer to the alveoli (i.e., further up the pressure gradient in the airway)."}
+{"id": "pulmo2$$$e843288a-9a88-4e3a-b197-33a90f9c8ed9", "contents": "If airways are already narrowed, as in obstructive lung diseases such as asthma, or parenchymal traction is lost, such as in emphysema, dynamic airway compression occurs to a greater extent. In these obstructive diseases the increased airway resistance results in the patient having to forcefully expire to overcome the increased resistance of the narrowed airways. This promotes airway compression and leads to air being trapped behind the choke point, causing hyperinflation (breathing at an elevated lung volume)."}
+{"id": "pulmo2$$$f1570577-d8ed-42e9-afb5-85e530a4feb6", "contents": "This airway compression or any other increase in airway resistance can be demonstrated by a common pulmonary function test, the flow-volume loop."}
+{"id": "pulmo2$$$2d0afc3b-7842-421e-810c-7315aa2dca00", "contents": "Flow-volume loops are briefly discussed in context of the relevant physiology. Figure 6.3 shows a normal flow-volume loop. Note that the volume axis seems to be the wrong way around; this is because expired volume and flow are generally more useful, so the plot has expiratory flow as positive and lung volume orientated for expiration. While breathing on a spirometer, the patient begins to breathe in from residual volume (bottom half of maroon line). As inspiration continues, lung volume increases (moves toward the y-axis) and airflow increases (moves downward). The patient continues inhaling until they are at total lung capacity (or TLC)."}
+{"id": "pulmo2$$$3c648ba2-73e4-47f5-b712-da0d0aea9f7f", "contents": "They then exhale as hard and as fast as they can, forcefully emptying the lung as quickly as possible. During forced exhalation of the first liter or so, expiratory flow rapidly increases until it reaches peak expiratory flow; this is the first clinically pertinent measure. After this point expiratory flow begins an exponential decline; as lung volume continues to decrease, so does the flow rate until flow reaches zero when the lung is emptied (at residual volume)."}
+{"id": "pulmo2$$$ef8ca426-319c-46e9-8681-ab7bb5b4aa47", "contents": "The rate of this decline in flow rate is also an important clinical measure and brings together a couple of important physiological points:"}
+{"id": "pulmo2$$$76b0deb9-f98e-4fd6-afdf-0e3793be0296", "contents": "Although there are a number of measurements that are calculated from this forced exhalation, two are most commonly reported. First, the total volume that is expelled from the lung is referred to as the forced vital capacity (FVC). The forced expiratory volume that is expelled from the lung in the first second of expiration is referred to as FEV1. The ratio of these two values, known as FEV1/FVC, describes the percentage of lung volume that can be emptied in one second and is a useful indicator of airway resistance. A normal FEV1/FVC is 90 percent\u00a0or higher, meaning over 90 percent\u00a0of vital capacity can be emptied from the lung within a second. This value is dependent on age, gender, and body size, but commonly used predicted values take\u00a0these variables into account when assessing for disease."}
+{"id": "pulmo2$$$6eae07de-134e-4157-b1f9-2c21589e94f1", "contents": "The loop produced by a patient with chronic obstructive lung disease, or COPD, looks very different (gray\u00a0line in figure 6.4). With disease causing airway narrowing, the peak expiratory flow is significantly reduced, and the decay in expiratory flow as lung volume declines is much more pronounced as the narrowed airways can be easier to collapse due to a lower starting radius and/or loss of radial traction."}
+{"id": "pulmo2$$$a9447d8a-043e-40ac-9a3d-eaf68ecb640f", "contents": "This means that FEV1\u00a0is significantly reduced, but FVC may remain unchanged\u00a0(i.e., the lung volume is the same, but it takes longer to empty). An FEV1/FVC significantly less than 90 percent\u00a0is indicative of obstructive disease. Notice that the inspiratory loop of the COPD patient appears normal, illustrating the effect of increasingly negative intrapleural pressure, increasing lung volume and radial traction on airway resistance."}
+{"id": "pulmo2$$$b1f7270f-a1a0-42ea-840c-1b10afdbc09d", "contents": "Alternatively, diseases that restrict lung expansion (figure 6.5), such as pulmonary fibrosis, demonstrate a reduced lung volume, where FVC is substantially reduced, but FEV1\u00a0may not be significantly affected;\u00a0in fact it is not uncommon for FEV1/FVC to increase to about normal in restricted diseases, but this is of course due to a decline in FVC rather than a rise in FEV1. Notice also that the inspiratory loop is affected, with volumes being reduced here as well."}
+{"id": "pulmo2$$$bfae96d4-8f73-47a3-bc15-1e4a8b89fe16", "contents": "A flow-volume loop is a quick, cheap, and powerful diagnostic measure, but it is highly dependent on the patient performing a forced expiration to encourage\u00a0dynamic compression and peak flows\u00a0be obtained so that any airway abnormalities can be seen. This is why you may hear a pulmonary function technologist (PFT)\u00a0shouting encouragement to a patient as you walk past the lab."}
+{"id": "pulmo2$$$c2a28e29-e429-433c-aa9c-20fdfa1e6ad4", "contents": "So we have dealt with a couple of relatively complex issues in this chapter, particularly the interaction between intrapleural pressure and airway pressure during forced or active expirations and how airways can become compressed."}
+{"id": "pulmo2$$$b1f3896b-28a3-48a5-a578-79d067745772", "contents": "We have also looked at the use of flow-volume loops to determine the degree of airway obstruction and to distinguish between obstructive and restrictive disorders."}
+{"id": "pulmo2$$$e3fd9346-74ee-4550-ac3d-c10b889a9616", "contents": "West, John B. \u201cChapter 7: Mechanics of Breathing\u2014How the Lung Is Supported and Moved.\u201d In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012."}
+{"id": "pulmo2$$$f3d82c09-4fa4-4232-b7c2-ca82c3f0e4d6", "contents": "Widdicombe, John G., and Andrew S. Davis. \u201cChapter 3.\u201d In Respiratory Physiology. Baltimore: University Park Press, 1983."}
+{"id": "pulmo2$$$2abbd8fc-bc45-4021-95f3-7cc764fb7854", "contents": "The first factor we must consider when thinking about airflow is the type of flow that is occurring."}
+{"id": "pulmo2$$$90b7c113-9453-48ab-af12-da3e977c0466", "contents": "The most efficient form of flow is laminar\u00a0(i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls\u00a0and those in the middle moving fastest (figure 5.1)."}
+{"id": "pulmo2$$$185f8384-ae77-4ecc-8216-cf9651f31397", "contents": "When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high."}
+{"id": "pulmo2$$$78016837-1b1e-4b72-9459-159a81636088", "contents": "In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above\u2014mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3)."}
+{"id": "pulmo2$$$d8c9a412-74b3-47d6-9885-10a68f3195dc", "contents": "For our purposes though we are going to look at the factors that affect flow when it is laminar\u2014the dominant form of flow in the majority of airways. These factors are described by Poiselle\u2019s equation. We will now break down Poiselle\u2019s equation in relation to flow of air down airways. Although initially an intimidating equation, there are some things we can generally ignore."}
+{"id": "pulmo2$$$329ee30f-0280-4186-a272-76cda4611f6d", "contents": "Equation 5.1"}
+{"id": "pulmo2$$$5e3fb3a7-a053-4acc-86e9-d182ddf86042", "contents": "First, Poiselle says that flow decreases when length of the tube increases; because the airways have constant length, we do not have to worry about it."}
+{"id": "pulmo2$$$61591784-2605-49b6-90c8-7235cba59477", "contents": "Then there is the viscosity of the gas. This is not usually a concern either when breathing humidified air at a constant biological temperature. It does become important when breathing other gas mixtures, however, such as a helium/oxygen blend that has a lower viscosity and is given to respiratory patients or deep water divers to increase flow. But we will assume it is another constant. Pi (\u03c0) is also a constant."}
+{"id": "pulmo2$$$a5a1a5d4-c643-4a7a-b174-3e51a5e3e4e9", "contents": "So the two remaining variables are the important ones to understand. The pressure differential created by expansion and relaxation of the lung generates a proportional flow, and we have dealt with this in previous chapters."}
+{"id": "pulmo2$$$5213b635-ab48-405e-8029-e5110cb26cfc", "contents": "What we will look at more closely now is airway radius as this has a profound effect on flow. Radius is critical for two main reasons. First\u00a0it is variable, as the caliber of an airway changes with lung volume and by the action of airway smooth muscle. Second, it has a very powerful effect on flow; as you can see in Poiselle\u2019s equation, radius is to the fourth power. This means a small increase in radius has a large effect on flow. For example, if the radius of an airway is doubled from 1 mm to 2 mm, the flow rate through the tube increases sixteenfold, which of course is two\u00a0to the fourth power (i.e.,\u00a02x2x2x2). The inverse is of course true\u2014halve the radius and flow reduces sixteenfold."}
+{"id": "pulmo2$$$ebe62cb3-d7dd-46a2-9281-1ebc290a834a", "contents": "So far we have couched everything in terms of flow, but really we need to look at airway resistance. Because resistance is simply the reciprocal (or opposite) of flow, we can flip Poiselle\u2019s equation upside down to describe resistance, and we now see that a reduction in radius (r) causes a large increase in resistance (R)."}
+{"id": "pulmo2$$$d563dc7e-7fa3-4742-9a9d-0fe9c19a3eac", "contents": "Equation 5.2"}
+{"id": "pulmo2$$$c7af50f6-2c05-47d3-9087-5b1f80d3fccb", "contents": "So with radius having such a powerful effect on airway resistance we would expect that the early and larger generations of airways would offer the least resistance to flow, and resistance would increase as we descended deeper into the lung to the smaller and later airway generations. Figure 5.4\u00a0shows the opposite is true\u2014that airway resistance decreases as the airway generations are descended. This is because the total cross-sectional area increases with each generation\u2014while the early and large airways are wide, they are few. The lower and smaller airways are much more numerous, and so collectively they have a greater cross-sectional area and therefore offer less resistance."}
+{"id": "pulmo2$$$b1b161a6-1bb8-45d6-88e1-70fe35847671", "contents": "The highest point of resistance is actually the midsize bronchioles. There are a couple of clinically important points to make here:"}
+{"id": "pulmo2$$$cbb7a36b-87fc-4845-9394-57c7374d4733", "contents": "The airways without cartilaginous support significantly change their radius when the lung expands\u00a0due to the radial traction. In brief, parenchymal fibers tethered to the alveoli and exterior of the airways allow the airways to be pulled open by the expanding alveoli when lung volume increases (illustrated in figure 5.5)."}
+{"id": "pulmo2$$$16bcda72-2e9a-413f-ae1d-b5d369159840", "contents": "This increase in airway diameter means that airway resistance falls as lung volume increases. This is demonstrated by figure 5.6; as lung volume increases, then airway resistance falls exponentially."}
+{"id": "pulmo2$$$ce71d882-d522-4f75-9d9c-d0057c48fede", "contents": "The inverse is also true, that as lung volume decreases, airway radius declines. This may happen to a sufficient extent to allow small airways to collapse. It is worth noting here that respiratory patients frequently breathe at higher lung volumes. While there are mechanical reasons for this that we will discover in the next chapter, the higher lung volume may at least improve airway conductance (although it carries many other disadvantages)."}
+{"id": "pulmo2$$$7fbedb37-b1a1-4e8e-9b75-3174278e913b", "contents": "As well as the lung volume effect, the tone of airway smooth muscle is also a powerful determinant\u00a0of airway radius\u00a0and therefore resistance. The muscle is arranged in a ring pattern around the airway circumference. Contraction of the smooth muscle causes bronchoconstriction, decreasing the airway radius. Relaxation of the smooth muscle allows bronchodilation."}
+{"id": "pulmo2$$$b6fab127-b070-4907-b6f1-c7e002e1f264", "contents": "Airway smooth muscle is under the control of the autonomic nervous system. Parasympathetic release of acetylcholine causes activation of muscarinic receptors. This causes a rise in intracellular calcium that activates the smooth muscle. Muscle is relaxed by sympathetic stimulation of \u03b22\u00a0adrenergic receptors. These \u03b22\u00a0receptors are the target of bronchodilator drugs, such as albuterol, that resolve the inappropriate contraction of smooth muscle seen in the hypersensitive airways of asthmatics."}
+{"id": "pulmo2$$$21f8a7bc-59af-4aeb-a2e7-6f804effab65", "contents": "The bronchoconstrictive pathway is utilized by the irritant reflex that is initiated by airway wall receptors detecting the arrival of inspired particulates. This defensive reflex results in bronchoconstriction, presumably to limit the entry of more particulates."}
+{"id": "pulmo2$$$711d35bf-e5b0-4935-a96e-0fc4dc439037", "contents": "A number of inflammatory mediators also cause\u00a0bronchoconstriction and probably play a significant role in the bronchoconstriction of asthma (which frequently also involves airway inflammation)."}
+{"id": "pulmo2$$$58667a67-1b20-472a-ad8b-cb483a27c09a", "contents": "Low airway PCO2\u00a0also has a direct stimulatory effect on airway smooth muscle and a bronchoconstrictive effect. This is presumably to shunt air to other regions of the lung and away from regions where overventilation caused the low PCO2."}
+{"id": "pulmo2$$$e9f4b749-54a9-484b-8c35-4c8a005ea450", "contents": "So now you should be able to understand how the type of flow, airway radius, lung volume, and\u00a0autonomic nervous system all influence airway resistance and so can either oppose or\u00a0promote the flow of air in the lung."}
+{"id": "pulmo2$$$ccf522d3-ed2e-4e8f-951d-b5f59bf4614f", "contents": "Levitsky, Michael G. \u201cChapter 2: Mechanics of Breathing.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$a51c7485-ccc2-408b-b8e4-81a967726da8", "contents": "Before we look at ventilation distribution we need to understand a little more about lung structure. Although the lung is composed of individual components, such as the alveoli within distinct ascini, the airways, and the blood vessels, the parenchymal tissue between these components helps form the mechanical structure of the lung."}
+{"id": "pulmo2$$$be8b78cd-0195-4b08-b835-d711e5910ebf", "contents": "In brief, collagenous and elastic fibers run the length of the large airways and into the lobes forming the axial network. Fibers beneath the pleura and within the septal spaces between the lobes form a peripheral network, and finally thin fibers surrounding the alveoli within the lobes form the septal network. Together these networks form a fibrous \u201cweb\u201d of the lung (figure 4.1)."}
+{"id": "pulmo2$$$05b86415-fa0a-4fd9-bcd2-ac5248007ef1", "contents": "Functionally what this means is that movement of one lung structure is transferred to others. As the lung inflates these fibrous connections have a significant impact on lung function and the pulmonary vasculature. Expanding alveoli pull on fibers that are attached to neighboring airways and blood vessels and, indeed, other alveoli."}
+{"id": "pulmo2$$$e6b3312f-2269-4d95-a367-9aa35274f3d4", "contents": "The expanding lung volume tends to pull open airways and blood vessels, lowering the resistance of both as inspiration continues, as is illustrated in figure 4.2."}
+{"id": "pulmo2$$$e09c9161-fc78-4197-acb5-13e6b2517377", "contents": "Radial traction (sometimes called parenchymal traction) is an important component of the lung\u2019s mechanical behavior, and it means that lung volume has an effect on airway and vascular resistance."}
+{"id": "pulmo2$$$7fac62a3-dcfc-4f2a-9ed3-f2ad58606fce", "contents": "More important for us now though is the understanding that the lung is highly connected within itself. And it is\u00a0a good thing\u00a0that it is\u00a0these fiber networks transfer changes in pleural pressure from the lung periphery to its center; without the networks, only the alveoli at the periphery of the lung would expand when pleural pressure became negative during inspiration."}
+{"id": "pulmo2$$$b86a276d-3ccd-419d-80d8-19a1ed9b8520", "contents": "It also means that the effects of gravity are transferred to the lung as a single unit, and we will look at that now."}
+{"id": "pulmo2$$$37d203a4-7994-4997-9a6d-f7c0e178c7b7", "contents": "The lung hangs in the thorax supported by the trachea and the surface tension adhering its outer surface to the inside of the thoracic cavity. Gravity obviously tends to pull the lung downward, and this pull has an unequal effect on alveoli at different heights of the lung."}
+{"id": "pulmo2$$$0d6fedce-9752-4d68-81b5-7494c5f5e736", "contents": "Alveoli at the apex (top) of the lung have a substantial amount of lung tissue below them for gravity to act on,\u00a0so there is a large force pulling the lung away from the pleural space here and hence at the top of the lung intrapleural pressure is more negative. As we descend down the lung the mass below each point becomes less and less, so the pull on the pleural space declines, and we see intrapleural pressure become less and less negative."}
+{"id": "pulmo2$$$d88f06b7-a07c-477f-a356-9b5556a97395", "contents": "Simply because of gravity, therefore, we have a distribution of intrapleural pressures. As you know from the previous chapter, intrapleural pressure determines alveolus size (figure 4.3). So at the apex of the lung alveoli tend to be large because of the more negative intrapleural pressure, while at the base, alveoli are less extended because of the less negative intrapleural pressure.\u00a0If an analogy would help, look at this slinky being held up (figure 4.4). The coils near the top of it are pulled far apart because of the weight of the slinky below the top. As you travel down the slinky the coils are less and less extended as less and less weight below pulls on them. The lung acts just the same;\u00a0alveoli at the top are extended at rest, while those at the base have a smaller volume."}
+{"id": "pulmo2$$$9e36424f-a1ab-4191-8732-63f704c81294", "contents": "This has ramifications on where air entering the lung goes and how ventilation is distributed across the lung (more on the implications of this in chapter 13). Alveoli at the apex of the lung are already extended and therefore have limited capacity to take in more air;\u00a0their resting volume is also close to the flat part of the compliance curve (figure 4.3), so they are more difficult to inflate. The smaller alveoli at the base of the lung, however, still have a greater capacity for expansion, and the smaller resting volume places them on the steeper section of the compliance curve;\u00a0consequently they are easier to inflate, and air takes the path of least resistance."}
+{"id": "pulmo2$$$18e21582-f8de-47df-b66f-013595cc7781", "contents": "Because of this, the alveoli at the apex of the lung rapidly fill to capacity on inspiration, and the vast majority of inspired air descends toward\u00a0the base toward\u00a0the more compliant and less extended alveoli. This uneven distribution of ventilation is something we will return to when we address other learning objectives, so it is worth understanding."}
+{"id": "pulmo2$$$c97d9bb0-e9af-41df-a403-3810771f74cb", "contents": "The distribution of ventilation is also effected by lung volume, and at low lung volumes the apex of the lung is actually better ventilated than the base\u2014again, this is due to changes in alveolar compliance."}
+{"id": "pulmo2$$$61698af8-8f5e-423c-b912-4307c8078a9d", "contents": "As the lung is emptied below functional residual capacity, that is below the normal point that expiration ends, the recoil of the lung is reduced and therefore intrapleural pressure becomes progressively less negative (or more positive if that is the way you would\u00a0like to think of it). Compared to the normal resting volume we just dealt with, at low lung volumes the intrapleural pressure may be up to \u22124 cm H2O\u00a0(compared to \u221210). This pushes the apical alveoli down on to the steep part of the compliance curve, and therefore they are easier to inflate."}
+{"id": "pulmo2$$$f471b51b-53e8-4a5c-8be6-104466a4f6cc", "contents": "The intrapleural pressure at the base of the lung may actually become positive at low lung volumes. Now that force that tended to open up alveoli is actually a force that tends to compress alveoli. In our example here the intrapleural reaches 3.5 cm H2O, a force that may lead to airway compression and thereby reduce ventilation to the basal alveoli. This intrapleural pressure will certainly place these alveoli on the very flat\u00a0and therefore noncompliant section of the compliance curve and make them difficult to inflate because of the surface tension and small radius effect we have discussed previously."}
+{"id": "pulmo2$$$51c22bee-8d26-45c5-b56d-5e272b4882ca", "contents": "Ventilation is unevenly distributed across the lung because of the range of intrapleural pressures that are established down the lung by gravity. At normal lung volumes the base of the lung is better ventilated than the apex."}
+{"id": "pulmo2$$$34c1cc59-112f-438a-969f-fc135a5ae24c", "contents": "At low lung volumes this relationship is reversed as intrapleural pressures at the base of the lung become compressive, reducing the compliance of basal alveoli, while the compliance of apical alveoli is increased."}
+{"id": "pulmo2$$$6122ed24-6881-4243-b127-64fd05cdb94a", "contents": "Widdicombe, John G., and Andrew S. Davis. \u201cChapter 1.\u201d In Respiratory Physiology. Baltimore: University Park Press, 1983."}
+{"id": "pulmo2$$$6ba80913-757c-4bf2-9fae-0abce683e342", "contents": "First let us\u00a0look at lung volumes. This trace from a spirometer (figure 3.1) shows the change in lung volume as a patient breathes normally and then performs some specific maneuvers."}
+{"id": "pulmo2$$$ac8ec9e3-516a-425c-b7ce-a82558e6e9e2", "contents": "Let us\u00a0work through the trace from left to right. The initial part of the trace shows resting or \u201ctidal\u201d\u00a0breathing. The amount of volume inspired during each breath is referred to as tidal volume."}
+{"id": "pulmo2$$$f67812e4-2a8d-4331-bec3-b0fae9916f7f", "contents": "Once a normal expiration is complete, however, the lung is far from empty, and when instructed, this patient (figure 3.1) breathes out as far as they can; this excess that comes out the lung is referred to as the expiratory reserve volume."}
+{"id": "pulmo2$$$dc56756d-41ee-4ec8-b969-4573065f4b6b", "contents": "Even at this point, however, some air remains in the lung, and this is referred to as residual volume. Even with maximal efforts, this volume cannot be exhaled, so at no point can the lung be fully emptied. This also means that residual volume can never be measured with a spirometer."}
+{"id": "pulmo2$$$f288c178-32e1-4731-8af8-c03a67151b63", "contents": "Our patient (figure 3.1) returns to normal tidal breathing for two breaths before taking a full breath in, filling the lungs as much as they can. This extra volume into the lung after a normal tidal inspiration is referred to as inspiratory reserve volume. Related to\u00a0this volume is the inspiratory capacity, which is the volume that can be taken into the lung after a normal expiration; inspiratory capacity is a useful clinical measurement that we will return to when we deal with some disease states."}
+{"id": "pulmo2$$$8763a675-1a95-47e8-9ccf-01a538f10261", "contents": "Another clinically valuable measurement is vital capacity, which is the volume of air that our patient can move out of the lung after a full inspiration, that is, the total lung capacity, minus the residual volume (remember: residual volume\u00a0cannot be expelled). Forced vital capacity is a common measure taken in pulmonary function testing, and this is simply the volume that can be expelled from total lung capacity during a forceful expiration. The importance of this maneuver being forced will be dealt with when we look at airway compression (chapter 6)."}
+{"id": "pulmo2$$$f9e309dc-7742-4d89-91f5-00041b8b6a6d", "contents": "While the volumes we have just seen measured by spirometry in the pulmonary function lab provide valuable clinical information, we need to now look at some physiological variables that are also critical for our understanding of lung function and disease."}
+{"id": "pulmo2$$$68b1385e-fd77-4886-a987-7a43f6cc9f83", "contents": "As you have seen, the volume of air inspired during a normal breath is tidal volume, and the size of this is dependent on body size, but in the example here is listed as 500 mL (a good approximation). Not all this 500 mL\u00a0reaches the gas exchange surfaces in the respiratory zone, however, as some never gets further than the conducting zone (i.e., it stays in the anatomical dead space). From chapter 1 we know that this dead space has a volume of 150 mL,\u00a0so the amount of air reaching the alveoli in the respiratory zone is our tidal volume (500 mL), minus the dead space volume, so alveolar volume is 350 mL."}
+{"id": "pulmo2$$$8193e390-06e1-4d2e-b7ef-d1f349a3c8bb", "contents": "This brings us to an important point of clarification. Minute ventilation (denoted as Ve) is the volume of air exchanged in the lung within a minute. This is analogous to cardiac output, the volume of blood pumped by the heart in a minute. As such, minute ventilation is the average tidal volume (VT) multiplied by the number of breaths taken in a minute (RR)."}
+{"id": "pulmo2$$$e3c8077b-c703-4e84-9cd8-ca4328c7e75e", "contents": "Equation 3.1"}
+{"id": "pulmo2$$$d7b20370-3cc9-4e56-8211-5b1064e3ce09", "contents": "So if respiratory rate is 10 bpm and tidal volume is 500 mL, minute ventilation is 5,000 mL."}
+{"id": "pulmo2$$$0fe8cf12-ee11-477b-91fc-153382912cd4", "contents": "Equation 3.2"}
+{"id": "pulmo2$$$ec2e7604-bc85-4c48-b6e8-1d2ee48175b1", "contents": "Physiologically more important, however, is the alveolar minute ventilation (VA) that accounts for the \u201cwasted\u201d\u00a0ventilation that never reached a gas exchange surface but remained in the anatomical dead space. So the calculation for VA is"}
+{"id": "pulmo2$$$cc6f9246-3b61-4f24-96fb-cfa80f6019a4", "contents": "Equation 3.3"}
+{"id": "pulmo2$$$6b97a405-83a4-4da1-b864-00f13ec9449a", "contents": "where VD\u00a0is the anatomical dead space (approximately 150 mL). So for our previous example, alveolar minute ventilation is"}
+{"id": "pulmo2$$$7e881735-623c-4d4e-adbf-7a3a8be20017", "contents": "Equation 3.4"}
+{"id": "pulmo2$$$4f0e51a2-b584-48a8-b20e-1f41f292d9c4", "contents": "describing only the volume of air that reached the respiratory zone."}
+{"id": "pulmo2$$$86aade39-a50e-4e6e-8c61-efa554b7c295", "contents": "So far the involvement of anatomical dead space might seem academic, as it remains constant. But let us consider a different breathing pattern (as often occurs in disease states)."}
+{"id": "pulmo2$$$c028ddf4-66e2-475f-a128-70862da12d38", "contents": "In our example above minute ventilation is 5,000 mL, but accounting for dead space we see that alveolar minute ventilation is 3,500 mL. Now let us consider another breathing pattern\u2014one typical of a patient with restrictive lung disease where tidal volume is reduced and respiratory rate is increased. With a tidal volume of 250 mL\u00a0and rate of 20, the minute ventilation remains the same, 5,000 mL."}
+{"id": "pulmo2$$$7d3f3158-f721-4cc8-bb5a-037202006657", "contents": "Equation 3.5"}
+{"id": "pulmo2$$$59d9cbc6-11cd-4fbe-bb3c-94b27f90374b", "contents": "But\u00a0calculating alveolar minute ventilation we see that a greater proportion of the reduced tidal volume is consumed by dead space."}
+{"id": "pulmo2$$$63e82b96-e727-4cc3-bcf3-1c951420b92c", "contents": "Equation 3.6"}
+{"id": "pulmo2$$$1c16b300-39ec-49c1-bfc7-5a2dc76d4d07", "contents": "So despite maintaining the same minute ventilation, the second patient\u2019s alveolar minute ventilation is reduced by 1,500 mL, which is significant given that this is the volume of air going to the gas exchange surfaces."}
+{"id": "pulmo2$$$37c67bfc-e104-4064-89dc-96788fcfaf6a", "contents": "This partially explains why increases in ventilation are initially achieved by increases in tidal volume; as shown in figure 3.2, as tidal volume increases during exercise intensity (represented by oxygen uptake) until it reaches a plateau. Only when this plateau is reached are further increases in minute ventilation\u00a0achieved by increasing respiratory rate."}
+{"id": "pulmo2$$$f9badee4-82c4-4073-9f76-7490c77f53b7", "contents": "So why not keep increasing tidal volume? At higher lung volumes the elastic limit of the lung is approached, and it\u00a0takes more energy (muscular force) to expand, so it is more efficient and the work of breathing is less if the rate of breathing is increased to achieve higher levels of minute ventilation. This brings us to our next topic, lung compliance."}
+{"id": "pulmo2$$$eb090bbf-c764-42ea-a0e8-7f58725e4d00", "contents": "Lung compliance is a description of how easy the lung is to inflate, more specifically, how much volume will change for a given pressure differential. Figure 3.3 shows a typical and normal lung compliance curve. The lower line shows how volume changes as intrapleural pressure becomes more negative (as the chest wall and diaphragm expand the thorax). The upper curve is the compliance of the lung during expiration, and it is clearly different; this is an example of hysteresis, meaning that the relationship depends on direction, and we will see why this exists later."}
+{"id": "pulmo2$$$bf688c7a-ae87-4784-bff0-a4fc4b6648af", "contents": "You will notice at low lung volumes the slope of the compliance curve (figure 3.3) is shallower, meaning that it takes a relatively large pressure change to cause an increase in volume. This tells us at low lung volumes the lung is less distensible, or has low compliance."}
+{"id": "pulmo2$$$4568b50b-5850-4ce8-87d7-3a44de82dbfb", "contents": "If we start to breathe at a higher lung volume, the slope of the curve is steeper, meaning that for a similar change in pressure there is a greater change in volume\u00a0(i.e., the lung is more compliant)."}
+{"id": "pulmo2$$$938ef1ff-989b-4d01-8605-5f387607d321", "contents": "If we start breathing at a higher lung volume still, closer to total lung capacity, we see the slope of the compliance curve flatten out again, showing that at the lung volumes the compliance of the lung is low."}
+{"id": "pulmo2$$$8a48fba0-bb2d-407f-98e1-170502f90531", "contents": "As you might imagine, the normal range for breathing is in the middle range where the slope is steep and the lung compliant. This corresponds to an intrapleural pressure range of \u22125 to \u221210 cm H2O, which you should know is the normal range of intrapleural pressures during tidal breathing. This means we normally breathe at a lung volume at which the lung is most compliant and therefore takes less work to inflate."}
+{"id": "pulmo2$$$d16ea004-19ec-4b3b-9a78-420bddc6679f", "contents": "Too low a lung volume and compliance falls and work of breathing increases, likewise during breathing at high lung volumes, another contributing reason for\u00a0why tidal volume plateaus during exercise."}
+{"id": "pulmo2$$$451b76e9-589e-4a74-bfc0-49991bb084ef", "contents": "So now let us look at why compliance is low at high and low lung volumes, starting with the cause of low lung compliance at low volumes."}
+{"id": "pulmo2$$$b3fcd35a-6d91-4bc7-b257-ff73349fa7b3", "contents": "Low compliance at low volumes\u2014Surface tension: The reason why the lung takes more pressure to inflate at low volumes is surface tension. As mentioned in chapter 1 the alveoli have a thin layer of fluid lining their inner surface. As we saw in the pleural space, this causes surface tension. Unlike the surface tension in the pleural space, in the alveoli surface tension is a disadvantage."}
+{"id": "pulmo2$$$ca8faa42-d2ec-4bae-952e-07edccef8f5d", "contents": "Surface tension is generated as water molecules cluster together to reduce their exposure to the gas in the alveolar space. As they gather together they drag the alveolar wall with them, producing a force that tends to pull the alveolar walls inward. The alveolar pressure opposes this force and should prevent the alveolus from collapsing (figure 3.4)."}
+{"id": "pulmo2$$$da746387-5ed7-484c-bf0b-c88bcb2f1276", "contents": "The relationship between these two opposing forces is described by Laplace\u2019s law that states the outward (alveolar) pressure needed to oppose the inwardly directed tension is proportionate to the tension (obviously), but also inversely related to the radius of the alveolus\u00a0(i.e., the smaller the radius, the greater the inwardly acting force)."}
+{"id": "pulmo2$$$3509f1ca-8ecc-4ad2-b9cf-3eff570619b3", "contents": "This explains why compliance is low at low\u00a0lung volumes. At low lung volumes the alveoli are smaller and\u00a0thus have a smaller radius. Laplace\u2019s law states that with a low radius the pressure needed to overcome the inward force will be greater, explaining why a larger alveolar (outward) pressure is needed to inflate the alveolus from a low starting volume."}
+{"id": "pulmo2$$$036a0fe8-5632-4d81-bf4b-f27259dbb8ed", "contents": "As lung volume increases, and thus alveolar radius increases, the pressure needed to overcome the inward acting force becomes less and the compliance of the lung increases. This explains why compliance is improved at the normal operating range of lung volumes."}
+{"id": "pulmo2$$$000e0120-8738-495c-8cd9-a9f3b7a795c5", "contents": "This also explains the hysteresis of the compliance curve. During expiration as alveoli are becoming progressively smaller, the inwardly acting force generated by surface tension becomes progressively greater. This phenomenon consequently assists expiration and contributes to expiration being a passive process."}
+{"id": "pulmo2$$$da35cdea-8870-4095-b7fa-9c77d9540a3e", "contents": "Low compliance at high lung volumes\u2014Elastic limit: At high lung volumes the alveolar radius has increased further, suggesting that compliance should be further improved as the effect of surface tension will be much less. But surface tension is not the only factor involved, and the compliance curve flattens here, meaning a greater pressure is needed to achieve a volume change at high lung volumes. The low compliance at high lung volumes is caused by another phenomenon altogether. At high lung volumes expansion of the lung becomes limited by the elastic limit of the lung, a little like trying to further stretched an already stretch elastic band\u2014it is harder to do."}
+{"id": "pulmo2$$$8484b092-d7eb-44a1-b241-2fecb31ef15e", "contents": "So with surface tension causing problems at low lung volumes\u00a0and tissue elastic limit causing problems at high lung volumes, the compliance curve is steepest (i.e., most favorable) in the middle, as mentioned before, which is the operating volume of the lung. These principles are summarized in figure 3.5."}
+{"id": "pulmo2$$$29a73de0-3529-4d42-9213-a65ad7fce041", "contents": "Improving lung compliance with surfactant: So after that information on how surface tension is a problem for the lung, we now have to look at how it could be so much worse if the lung did not\u00a0protect itself."}
+{"id": "pulmo2$$$4e9740cc-c080-4ddb-8640-dac07d5ffc9a", "contents": "Despite it having an effect, particularly at low lung volumes, the lung actually reduces the effect of alveolar surface tension by releasing \u201csurfactant,\u201d\u00a0a molecule that disrupts surface tension. In brief, the surfactant molecule (dipalmitoyl phosphatidylcholine) has a similar structure to the phospholipids that make up cell membranes with a hydrophobic end and a hydrophilic end, allowing it to surround water and repel it\u00a0at the same time, thus breaking up the interaction between water molecules. So as surfactant significantly reduces surface tension, it thereby increases lung compliance and the risk of alveolar collapse. It also helps keep the air space dry, as excessive surface tension tends to draw water into the space from the capillaries and interstitial spaces."}
+{"id": "pulmo2$$$fdc63085-2513-4355-8ded-f5d0c9698671", "contents": "Surfactant is released onto the alveolar inner surface by Type II alveolar cells (recall Type I cells are those making up the alveolar wall). Type II cells produce surfactant at a high rate\u00a0and thus demand a constant and generous blood flow; therefore any condition that disrupts this blood supply will cause surfactant concentrations to decline and therefore put the alveolus at risk of collapse as surface tension is allowed to increase."}
+{"id": "pulmo2$$$08ca76c6-e7cf-44d2-ac4f-713cf0644d61", "contents": "A good illustration of the effect of surfactant is respiratory distress syndrome of the newborn. The underdeveloped lungs of infants born prematurely (at about twenty-eight\u00a0weeks), cannot produce sufficient surfactant. Alveoli rapidly collapse (known as atelectasis), and pulmonary edema develops because of the excessive surface tension in the alveolar walls."}
+{"id": "pulmo2$$$3265bb73-23ce-4e55-b347-c6a6e3d0f4a2", "contents": "Widdicombe, John G., and Andrew S. Davis. \u201cChapter 2.\u201d In Respiratory Physiology. Baltimore: University Park Press, 1983."}
+{"id": "pulmo2$$$5b7cdf1c-6e3e-4689-a4b4-001b0e7d0b85", "contents": "Before we get into the details of how we breathe in, let me make sure we are all on the same page by going right back to basics, so bare with me or skip ahead if you are happy with pressure, volume, and flow."}
+{"id": "pulmo2$$$9e430d7f-a263-41b5-819a-5d6f57a475d3", "contents": "To get air to move into the lungs we need to generate a pressure differential;\u00a0that is the pressure inside the lungs must be lower than the pressure outside\u00a0(i.e., atmospheric pressure), so that air moves down the pressure gradient into the lungs."}
+{"id": "pulmo2$$$2a56dfa9-1088-4e0d-8a05-7d0dae7eabe3", "contents": "The low pressure inside the lungs is generated by increasing lung volume; bigger volume means fewer molecules in the same space, and therefore lower pressure (go back and revisit Boyle\u2019s law if needed)."}
+{"id": "pulmo2$$$700a30d9-cdcb-4a22-934d-dbb9221c27e8", "contents": "The basis of inspiration is lowering lung pressure below atmospheric pressure, so that atmospheric pressure pushes air down the airways until pressure equilibrates. So the fundamental first step is, how do we increase lung volume?"}
+{"id": "pulmo2$$$f0582f89-5080-4d8c-973f-c82797cb93ae", "contents": "To understand the mechanics of breathing we have to deal with two concepts:\u00a0first how the action of the respiratory muscles increases thoracic volume, and second\u00a0(and more complex) we need to understand the interaction of the lungs and the thoracic wall."}
+{"id": "pulmo2$$$cf71568f-25a9-4c48-880c-f5fdda101c9b", "contents": "Let us deal with the respiratory muscles and expansion of the thorax first."}
+{"id": "pulmo2$$$2e10d819-9c0e-4ff8-97ba-e2aa7cfc6a63", "contents": "The muscle that generates the greatest change in thoracic volume (and thereby the greatest contribution to breathing) is the diaphragm (figure 2.1). Separating the thoracic and abdominal cavities, this sheetlike muscle forms a dome shape in the relaxed state that encroaches into the thorax. This sheet is formed of three sections, the anterior portion originating at the ribs and sternum, and the posterior portion originating on the vertebrae. These are connected by the central portion that is comprised of a tendon sheet."}
+{"id": "pulmo2$$$8b500a6a-6ed6-49c0-a989-611c6fd54a2f", "contents": "It is\u00a0worth a quick reminder that while controlling a visceral organ and performing a homeostatic function, the diaphragm and the other respiratory muscles are skeletal muscle and have the force-generation characteristics of such. As well as being under reflex control, it can also be controlled voluntarily (such as during speech)."}
+{"id": "pulmo2$$$6630b073-10dd-4a89-9b32-1f911273bc20", "contents": "Activation of the phrenic nerve stimulates\u00a0the diaphragm and generates inspiration. Upon stimulation the contracting diaphragm flattens out, descending toward the abdomen. As it does so the thoracic volume increases, and consequently thoracic pressure falls. When thoracic pressure falls below atmospheric pressure, air moves down the generated pressure gradient and enters the lung. Note that this increase in thoracic volume comes at the expense of the abdominal volume, and abdominal contents can be compressed during inspiration. The diaphragm may descend as much as 10 cm, but a descent of 1 cm is sufficient to provide tidal breathing (figure 2.2)."}
+{"id": "pulmo2$$$9b4271e3-76cb-47d8-9449-ce65ba432fd8", "contents": "When phrenic nerve activity stops, the diaphragm relaxes and returns to its resting dome-like position; this is aided by the recoil of the expanded lung and the decompression of the abdominal contents. The return to the resting position reduces thoracic volume\u00a0and increases thoracic pressure above atmospheric pressure\u00a0and air exits the lung down the reversed pressure gradient."}
+{"id": "pulmo2$$$218f33db-878e-4e96-a7ae-8fea0a27b6ff", "contents": "During inspiration the thoracic volume is also increased by the action of the external intercostal muscles. Controlled by the intercostal nerve, contraction of the external intercostals causes the rib cage to rise upward and outward, resulting in an expansion of the thoracic volume in addition to the action of the diaphragm. This action is generated by the oblique positioning of the external intercostals between the ribs,\u00a0and the sternum and upper ribs are stabilized\u00a0by simultaneous activation of the scalenus muscles."}
+{"id": "pulmo2$$$a1515008-08ab-4670-a844-d743bdd8e6e5", "contents": "During periods of high ventilatory need (or drive) other muscles can contribute to expansion of the rib\u00a0cage (figure 2.3). These \u201caccessory\u201d\u00a0muscles assist the external intercostals and include the sternocleidomastoids, the scalenes, and the pectoralis minor. All of these groups allow for a greater thoracic expansion and thus a greater lung volume. Recognizing that a patient is using these muscles to breath is a useful clinical sign; use of these muscles during rest is highly indicative of a raised respiratory effort to cope with an underlying and probably significant problem."}
+{"id": "pulmo2$$$26844539-30f0-458f-ba5e-1090747c25a6", "contents": "Expiration is generally simpler. The elastic tissue of the lung has been expanded during inspiration, and a little like letting go of a stretch elastic band, the lungs recoil when the inspiratory muscles relax. This recoil reduces lung volume and\u00a0increases lung pressure above atmospheric pressure and air exits the lung. Depending on the final lung volume achieved during inspiration, recoil of the chest wall may\u00a0also contribute to expiration."}
+{"id": "pulmo2$$$519a542a-f7b9-46fe-b36b-95775d34ba1b", "contents": "So during quiet resting breathing, expiration is passive, relying on the expenditure of the stored, potential energy in the elastic lung tissue. However, when ventilation needs to be increased, such as during exercise, this process is too slow, and this passive process needs some active help in order to increase the rate of breathing. Activation of the internal intercostal muscles draws the rib cage downward to reduce thoracic volume. Thoracic volume is further decreased by contraction of muscles surrounding the abdomen; these increase abdominal pressure and help push the diaphragm upward (figure 2.4)."}
+{"id": "pulmo2$$$b79578ea-4f17-4d85-a425-ccef0537b748", "contents": "Now having dealt with the expansion of the thoracic cage, we should look at the relationship between the thoracic wall and the lungs and how the lungs and the inside of the thorax are adhered to each other so when the thoracic wall moves the lungs follow."}
+{"id": "pulmo2$$$5fcde448-c4dd-4364-9f75-8234b4d7ccea", "contents": "The inside of the thoracic cavity is lined with a membrane, the parietal pleura. The outside of the lungs are lined with a membrane called the visceral pleura. The space between these membranes, the pleural cavity or pleural space, is filled with pleural fluid (figure 2.5). Normally there is only 5\u201310 mL\u00a0of pleural fluid to cover all the lung\u2019s external surface. So the fluid layer and the intra-pleural space is extremely thin. When a thin layer of fluid is trapped between two surfaces it exerts surface tension and holds the two surfaces together; if you\u2019ve ever been doing the washing up and trapped a layer of water between too dinner plates you\u2019ll have noticed its difficult to pry\u00a0the plates apart.\u00a0It is similar for the pleural membranes, and it is\u00a0this surface tension that holds the outside of the lungs to the inside of the thorax. We will deal with surface tension in more detail in a later chapter."}
+{"id": "pulmo2$$$9a164c3c-d73e-457a-8d69-06f6aa3c6a12", "contents": "We have mentioned the pressure inside the lungs, but now we have to think about the pressure inside the pleural space\u2014called intra-pleural pressure. Even at normal, resting lung volumes the elastic tissue in the lungs is already somewhat stretched, so the lungs have a tendency to recoil, pulling inward. The chest wall, alternatively, has a tendency to spring outward. These opposing movements are prevented by the surface tension in the pleural space and cause a negative intrapleural pressure, that is below atmospheric pressure."}
+{"id": "pulmo2$$$4f7752a8-2faa-45cb-ab9f-36a375757362", "contents": "We should now consider what happens to intrapleural and airway pressures during the breathing cycle. First, let us\u00a0look at the pressures and volumes before inspiration begins (figure 2.6). The intrapleural pressure is slightly negative (\u22125 cm H2O) due to the recoil of the lung and outward spring of the chest wall. Before the breath starts lung volume is considered zero and flow is also zero\u00a0(i.e., volume has not changed and there is\u00a0no movement of air in the airways). Alveolar pressure, the pressure inside the lungs, is also zero, really meaning it is equal to atmospheric pressure."}
+{"id": "pulmo2$$$be8d9cc7-fde3-4e7d-91dd-b6426638caed", "contents": "Look at what happens (figure 2.6) when the respiratory muscles are activated to increase thoracic volume and achieve a breath in. As the thoracic wall moves outward and the diaphragm descends, thoracic volume and therefore lung volume increases. More tension is generated in the stretching elastic tissue of the lungs as the lung expands\u2014and just like stretching an elastic band, the recoil force increases, and the stretching lung now pulls back harder on the pleural space. This causes the intrapleural pressure to become even more negative (\u22128 cm H2O)."}
+{"id": "pulmo2$$$00c543a1-17f7-4f9a-b450-3f05758900fe", "contents": "This increase in lung volume (and referring back to Boyle\u2019s law,\u00a0the pressure of a gas tends to decrease as the volume of the container increases)\u00a0causes a decrease in pressure in the lung. This is reflected in a decrease in alveolar pressure."}
+{"id": "pulmo2$$$fdffa40a-6b58-4b16-8891-34463a849827", "contents": "This drop in alveolar pressure generates a pressure differential between the airways and the atmosphere outside\u2014the atmospheric pressure now being greater than the reduced airway pressure causes the flow of air into the airways and toward the alveoli."}
+{"id": "pulmo2$$$6f11a9b3-494e-4ff8-8809-20a8917f1621", "contents": "Now let us look at these pressures during expiration. At the end of inspiration the lungs are stretched and the recoil force is high. When the activity of the inspiratory muscles stops, the recoil of the lung is unopposed and the lung recoils (a little like letting go of that stretched elastic band). Therefore, in quiet breathing, the process of breathing out is normally passive\u00a0and relies on the potential energy stored in the lungs\u2019 elastic tissue."}
+{"id": "pulmo2$$$f733002d-db88-4551-bac3-5e617da255e0", "contents": "As the lung recoils and returns toward\u00a0its resting position, the intrapleural pressure becomes less negative and the volume decreases, resulting in a rise in alveolar pressure, as described by Boyle\u2019s law. This rise in alveolar pressure means the pressure gradient is reversed, with pressure inside the lung becoming greater than atmospheric pressure. This reversed pressure differential causes the flow of air from the airways toward the outside\u2014and expiration is achieved."}
+{"id": "pulmo2$$$72cefa2a-7f84-4d03-a27d-2a7be6d25a22", "contents": "As already mentioned, this is a passive process that relies on lung recoil, and the expiratory muscles remain inactive during quiet breathing. However, when there is a greater ventilatory demand, such as during exercise or lung disease, the respiratory system cannot wait for this passive and relatively slow process to occur, so the expiratory muscles are activated and thoracic volume (and therefore lung volume) is reduced actively much more quickly; this may cause intrapleural pressure to go positive as the thoracic wall actively pushes on the intrapleural space (and the lungs). This positive pleural pressure during active expiration can have significant ramifications in diseased lungs that we will see later on."}
+{"id": "pulmo2$$$338eec0f-6210-47e2-815e-4cb6f22fc67a", "contents": "West, John B. \u201cChapter 2: Ventilation\u2014How Gas Gets to the Alveoli.\u201d In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012."}
+{"id": "pulmo2$$$3c8b34ab-c9f8-4728-8aad-518dd91e7284", "contents": "We will see how blood gases are monitored and maintained through neurochemical control of lung expansion and relaxation to achieve the appropriate level of alveolar ventilation. Factors that affect the\u00a0degree of gas exchange between the lung and blood will be discussed, along with the coordination of ventilation and perfusion of the lung. Finally, we will see how oxygen and carbon dioxide are transported in the bloodstream to and from tissue and the mechanisms that ensure appropriate delivery and a stable blood gas environment.\u00a0Before we begin, however, we will look at the functional anatomy of the lung and how the lung is well designed to perform its primary role and defend itself from the external environment."}
+{"id": "pulmo2$$$57f4f53d-d33e-4c7e-873d-33f33788ea22", "contents": "As the only internal organ exposed to the external environment, the lung needs special protection from particles or pathogens that could be transported down the airways with inhaled air.\u00a0The first line of defense is the nasal cavity, which is lined with a ciliated epithelial, dispersed\u00a0within which are\u00a0goblet cells producing mucus (figure 1.2). This mucus forms\u00a0a sticky layer on top\u00a0of the epithelial surface and\u00a0traps inhaled particles, bacteria, or other potential pathogens. The mucus is\u00a0then moved by the\u00a0cilia back toward the pharynx where it can be coughed or spat out."}
+{"id": "pulmo2$$$f288bfbb-d2c9-4f26-bd73-b9cc05195f26", "contents": "The inhaled air also must be warmed and humidified before it reaches the gas exchange surfaces,\u00a0otherwise the relatively cold and dry air would cause evaporation of the thin water layer\u00a0lining the gas exchange surfaces that\u00a0is essential for allowing gases to dissolve and\u00a0diffuse\u00a0into or out of the pulmonary bloodstream. This warming and humidification is achieved by transfer of heat and water from blood in the highly vascularized nasal cavity (figure 1.3)."}
+{"id": "pulmo2$$$696f5302-3baf-4605-87e5-ffa601be665d", "contents": "The second line of defense (which becomes more important when breathing through the mouth) is the lining of the trachea. Again, this is covered with a ciliated epithelium with mucus-producing goblet cells (figure 1.2). As in the\u00a0nasal cavity, particles and potential pathogens are\u00a0trapped in the mucus layer and cilia move the mucus up toward\u00a0the mouth for expulsion.\u00a0The trachea and larynx also contain\u00a0sensory nerve endings (rapidly adapting receptors, nicknamed \u201cirritant receptors\u201d) that respond to the arrival of particles on the epithelial surface and initiate the cough reflex and propel the offending particles out of the airway (see more in chapter 17)."}
+{"id": "pulmo2$$$e9c72af1-ff8b-4aae-b16e-1c90f7d65f86", "contents": "The airways, or bronchial tree (figure 1.4), consist\u00a0of a series of branching tubes that become narrower and\u00a0shorter\u00a0but more numerous\u00a0as they descend into the lung."}
+{"id": "pulmo2$$$d54cb433-447c-4fc8-a471-77d0133a64ab", "contents": "The trachea bifurcates into the primary bronchi, left and right, transporting air into the left and right lungs, respectively. The primary bronchi consequently divide into lobar (or secondary) bronchi, the number of which correspond to the number of lobes in each lung. The lobar bronchi then divide into segmental (or tertiary) bronchi to supply the segments of each lobe. This bifurcation process continues to the terminal bronchioles. This initial section of the bronchial tree is referred to as the conducting zone as its role is to transfer air to the gas exchange surfaces (figure 1.4). As no gas exchange takes place here, these airways constitute the anatomical dead space and have\u00a0a volume of approximately 150 mL."}
+{"id": "pulmo2$$$f02e387e-e075-4b37-b9b6-a610e5f32c9b", "contents": "Each terminal bronchiole then divides into numerous respiratory bronchioles, the walls of which may contain some alveoli and are therefore capable of some gas exchange; this is the transition to the respiratory zone of the lung and the onset of gas exchange (figure 1.4). The respiratory zone becomes firmly established when terminal bronchioles divide into alveolar ducts that are fundamentally tubes lined\u00a0with alveoli. These alveolar ducts then terminate in alveolar sacs. The portion of lung distal to each terminal bronchiole forms an anatomical unit called the acinus. Although only a few millimeters long, collectively\u00a0these acini make\u00a0up the respiratory zone and form the vast majority of the lung\u2019s volume."}
+{"id": "pulmo2$$$7c524b3e-db2b-48a2-bf84-86e51af527a1", "contents": "Airflow down the bronchial tree is caused by the generation of a pressure differential when lung volume is expanded by contraction of the respiratory muscles (more on this in chapter\u00a02). Inspired air first enters the airways of the\u00a0conducting zone, which while having the largest diameter airways also has the fewest; consequently the total cross-sectional area of the\u00a0conducting zone\u00a0is relatively low. With a large volume of air passing through a low cross-sectional area, the velocity of air in the\u00a0conducting zone\u00a0is high and is moving by \u201cbulk flow\u201d generated by the pressure differential (like water through a hose) until it reaches the terminal bronchioles and the end of the\u00a0conducting zone."}
+{"id": "pulmo2$$$63a3d858-bef4-4104-bfc5-25dc72d5b028", "contents": "When this air enters the\u00a0respiratory zone, it slows rapidly. This is due to the enormous total cross-sectional area of the airways in the\u00a0respiratory zone\u2014while the airways are much narrower here, they are far more numerous. The final transfer of the gases through the\u00a0respiratory zone\u00a0is therefore achieved by diffusion; the rate of diffusion is so rapid and the distances so short that concentration differences are abolished within a second."}
+{"id": "pulmo2$$$6a95a121-4333-4cfb-bb85-7dfaf892f9dd", "contents": "As an aside, this deceleration of the air at the terminal bronchioles means any particles that have been able to descend this deep are frequently deposited here. This has ramifications for disease and also delivery of inhaled medications."}
+{"id": "pulmo2$$$ba772aac-d906-41ac-a41f-012f852e38ff", "contents": "Gases that have diffused to the respiratory zone find themselves in an ideal environment for gas exchange. We will deal with gas exchange in more detail later (chapter 7), but you should appreciate that the essential components for efficient gas exchange are all present in the lung."}
+{"id": "pulmo2$$$b007a1b0-21ac-42ed-bc9d-b2aab0db116e", "contents": "A large surface area is generated by the 500 million alveoli, and while each alveolus only has a diameter of 0.3 mm, collectively they produce a total gas exchange surface of 100\u00a0m2\u2014about the surface area of a tennis court."}
+{"id": "pulmo2$$$c0c5c417-5ff6-472c-a25f-5ad889382fc3", "contents": "The membranes that gases transfer across are very thin and pose little opposition. In brief, oxygen entering the alveolus only has to cross the squamous cell of the alveolus wall, a very thin basement membrane, and then the squamous cell of the capillary wall to get into the pulmonary circulation. The total distance can be as low as 0.2 micrometers. This degree of thinness also makes these membranes prone to damage."}
+{"id": "pulmo2$$$389b6c13-b75d-4d7c-b994-a2cd8388bdac", "contents": "As well as the alveolus receiving air (that is being ventilated), the other essential component for gas exchange is blood flow. This is provided by the pulmonary circulation and consists of all cardiac output coming from the right heart. The pulmonary circulation forms very dense networks of capillaries surrounding each alveolus, so much so that the alveoli can be imagined as being washed over with blood."}
+{"id": "pulmo2$$$7e4649c8-2ea2-4feb-8341-0aca3e7d30b8", "contents": "These characteristics make the lung a highly efficient exchange organ between the environment and the circulation, which is ideal for the transfer of O2\u00a0into the bloodstream and, just as importantly, CO2 out. It also allows some drugs to be delivered by inhalation, but also has the potential to allow noxious substances into the bloodstream. Likewise, changes in any of these characteristics of the lung in disease, such as loss of surface area in emphysema\u00a0or membrane thickening in pulmonary fibrosis, can severely diminish gas exchange."}
+{"id": "pulmo2$$$bb13387c-a557-4bd6-8b04-3e30d6d82916", "contents": "Levitsky, Michael G. \u201cChapter 1: Function and Structure of the Respiratory System.\u201d In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018."}
+{"id": "pulmo2$$$9faee6ea-d9bf-4b11-a3d3-8561cb811717", "contents": "West, John B. \u201cChapter 1: Structure and Function\u2014How the Architecture of the Lung Subserves Its Function.\u201d In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012."}
+{"id": "pulmonary$$$97ebdeb2-7d1f-4119-99ac-a7f7f9ebbb77", "contents": "To get warmed up, let us\u00a0start with the simplest one, pleurisy."}
+{"id": "pulmonary$$$7009c4e3-0b80-4c44-887c-8b2524aa62db", "contents": "Pleurisy is synonymous with pleuritis and refers to inflammation of the pleural membranes that may be accompanied by pleural exudate or may remain \u201cdry.\u201d Inflammation of the membranes may be mild and transient due to common conditions such as bacterial or viral infection, or it may be severe and chronic and indicative of more serious conditions, such as lupus and rheumatoid arthritis."}
+{"id": "pulmonary$$$407a2c51-13bf-4dda-a164-eb5fbdd989df", "contents": "The inflammation causes thickening of the membranes that may cause them to impinge on the pleural space. Prolonged inflammation leads to an accumulation of pleural macrophages, and these in turn initiate a proliferation of fibrocytes. The inflammatory process may prevent the membranes from moving freely, and in some patients the two inflamed membranes sliding against each other can produce an audible pleural friction rub, which sounds like leather rubbing against leather or walking on fresh snow. The hallmark symptom of a pleural rub is sudden onset chest pain associated with inhalation and cough."}
+{"id": "pulmonary$$$7c6236df-56f7-4a85-b6fc-d15fcacccc79", "contents": "In\u00a0prolonged pathological conditions, the membranes may adhere, and calcium deposits can appear in old pleural fibrosis and are often associated with chronic conditions such as asbestosis. When significant, this level of fibrosis may restrict respiratory movement."}
+{"id": "pulmonary$$$0def0019-efda-4bf8-be84-5b336770125a", "contents": "In our description of pleurisy we eluded to our next pleural disorder,\u00a0pleural effusion. The normally small amount of pleural fluid is sufficient to lubricate the movement of the lungs and is not detectable on x-ray without specialized radiography. Pleural effusion is the abnormal accumulation of fluid in the pleural space and is easily detectable. As with the formation of\u00a0fluid accumulation in any part of the body, a normal fluid level in the pleural space is dependent on a balanced rate of formation and reabsorption. In pleural effusion, this balance is lost."}
+{"id": "pulmonary$$$902fd1dd-cadc-4a50-8f63-14d5cccf816f", "contents": "Initially it was thought that pleural fluid was formed by hydrostatic pressure in capillaries in the parietal membrane pushing fluid into the pleural space, and the fluid was then absorbed by capillaries in the visceral membrane. However, there is mounting evidence to show that reabsorption is actually performed by the lymph vessels in the parietal membrane. The low hydrostatic pressure and large capacity of these vessels helps maintain the normal, small volume of pleural fluid. Pleural effusion can be caused by:"}
+{"id": "pulmonary$$$efd6567f-5f5c-4501-bbea-0cacb9da552d", "contents": "For example, pleural effusion in cardiac pulmonary edema occurs as fluid leaks across the visceral pleura from the lung."}
+{"id": "pulmonary$$$d24c3129-0e09-4597-aba0-f501519a0c12", "contents": "Two broad classifications exist, transudate and exudate, so let us\u00a0compare them now (summary in table 9.1)."}
+{"id": "pulmonary$$$15308720-28b8-4057-8aba-0d06e11d901b", "contents": "Transudative effusion occurs when there is a disturbance in the Starling\u2019s forces influencing fluid movement across the capillary. As such transudate can be caused by an increase in hydrostatic force pushing fluid out of the capillary, such as in congestive heart failure, or a decrease in the plasma oncotic pressure retaining fluid in the capillary, such as in kidney or liver disease. This results in a transudate with low specific gravity, protein concentration, and cell count."}
+{"id": "pulmonary$$$7cff022c-a76f-4a82-b17e-f78a5fdd876d", "contents": "Exudative effusion is caused by increased capillary permeability, such as that caused by the inflammatory process. Relate this back to your understanding of exudative pleurisy (figure 9.1). As larger molecules can exit the leaky capillaries, exudative effusion has a higher specific gravity, higher protein concentration, and likely a higher cell count."}
+{"id": "pulmonary$$$1e0b031d-9c50-4863-b745-92487d68f087", "contents": "Table 9.1:\u00a0Comparison of transudative and exudative pleural effusions."}
+{"id": "pulmonary$$$d28a84a9-71ac-4502-8ece-95fa5e2224ec", "contents": "The manifestation of pleural effusion varies with the quantity of fluid accumulation and the time line. Symptoms may in fact be absent when the effusion is small. In the case of exudative pleurisy, an initial rub pain may disappear as exudate accumulates and separates the rubbing pleural surfaces."}
+{"id": "pulmonary$$$d575ecdb-955c-4b19-916f-a59a4460db7f", "contents": "As the effusion volume increases the patient is likely to experience dyspnea and physical exam will\u00a0more likely include dullness to percussion and absence of breath sounds as the effusion forms a fluid pillow around the lung."}
+{"id": "pulmonary$$$2b911b0a-c25c-424a-9007-658fd882bfdd", "contents": "As the severity of the effusion increases the patient will be severely short of breath, and the risk of the effusion pushing mediastinal structures to the contralateral side becomes significant and urgent (figure 9.1) as even mild displacement of the mediastinum can reduce cardiac output and produce hypotension. More significant displacement can become life threatening."}
+{"id": "pulmonary$$$6a213ac2-3232-4642-b5ea-84dc3b2e1882", "contents": "As we have already mentioned, the pleural fluid\u2019s composition can provide a great deal of information about the underlying mechanism. We have already mentioned the ability to distinguish between an exudate and a transudate by analysis of the fluid. But gross inspection of the fluid can be revealing before lab tests are ready."}
+{"id": "pulmonary$$$39e4babc-3e32-4837-a9aa-93149918524f", "contents": "Fluid drawn through thoracentesis that appears clear and straw colored (figure 9.2) is likely to be transudate. The clarity of the fluid relates to a low protein content reflecting intact capillaries, and you should be looking for disturbances in Starling\u2019s forces. Lab results can confirm the integrity of the capillary beds. Clinically the pleural fluid\u2019s protein content and lactate dehydrogenase concentration are used and are expressed as a ratio with the patient\u2019s plasma concentrations. Light\u2019s criteria set diagnostic thresholds for these ratios to determine transudative or exudative effusions."}
+{"id": "pulmonary$$$c7344b21-2aa5-4a33-9e99-55431504c570", "contents": "The higher protein of exudative effusion gives the fluid a more turbid or cloudy appearance, and high protein content may even give the fluid a foamy head (figure 9.2). Further lab analysis of the composition and cell content of the exudate can help determine the underlying cause of the leak.\u00a0For example, presence of polymorphonuclear leukocytes is highly suggestive of pyrogenic infection, whereas predominance of lymphocytes is indicative of TB or malignancy."}
+{"id": "pulmonary$$$fc06e3ad-477c-4c24-8714-7e8253b62da5", "contents": "Presence of lysed red blood cells will give the fluid a red turbid appearance (figure 9.2) and is indicative of trauma or malignancy, and again will require further investigation. If a malignancy has penetrated the lymphatics, such as the thoracic duct, the resultant chylous exudate will have a milky appearance."}
+{"id": "pulmonary$$$55dda68d-a0fb-4804-8f51-27432e0a7d33", "contents": "A purulent fluid (figure 9.2) is indicative of infection within the pleural space and culturing the fluid will allow the pathogen to be determined. When pleural fluid is grossly purulent or contains pyogenic organisms we refer to this as pleural empyema. The most common route of entry for organisms is from underlying\u00a0pneumonia or lung abscess, or through penetrative surgery or chest wound. The patient usually presents with fever and other manifestations of bacterial infection."}
+{"id": "pulmonary$$$c7166aaa-f88c-45d5-8fb8-aea658aa589c", "contents": "Normally the negative pressure inside the pleural space opposes the lung\u2019s recoil and holds the lung surface to the interior of the thorax. If the pleural membranes are disrupted this subatmospheric or negative pressure is lost and the lung can recoil, or collapse. This is a\u00a0pneumothorax."}
+{"id": "pulmonary$$$c2586289-886f-4131-85d6-2457ba18e76c", "contents": "The causal events of losing the negative pleural pressure divide pneumothoraces into one of two categories:\u00a0spontaneous or traumatic. (A third category exists, artificial pneumothorax, which was\u00a0intentionally induced as part of procedures that are very rarely used today.)"}
+{"id": "pulmonary$$$38f879f0-5ff6-43f0-95ec-fc890ff997cc", "contents": "Spontaneous pneumothorax occurs in the absence of accidental or intentional trauma. When it occurs in otherwise healthy individuals it is usually the fault of anatomy and occurs mostly\u00a0in tall, thin individuals with a long and narrow chest. If you compare the\u00a0two body morphs in figure 9.3, the tall, thin torso has a lot of lung mass hanging below a relatively small apical section of pleural membrane compared to the other torso."}
+{"id": "pulmonary$$$df047406-e161-4f2b-b683-a315a1315378", "contents": "The proportionately greater weight of lung per unit surface area at the apex increases the risk that bulla form (figure 9.4), then rupture\u00a0causing loss of pleural\u00a0membrane adhesion."}
+{"id": "pulmonary$$$0fe5da22-93a8-4711-8d35-5624a9f89b5f", "contents": "The most common cause of spontaneous pneumothorax in pulmonary patients is a ruptured bleb or bulla. These thin-walled, air-filled cavities are found near the pleural surface, particularly in cases of emphysema. In the past, TB was thought to be the most common cause of pneumothorax as its destructive path encroached on the pleural space."}
+{"id": "pulmonary$$$e8f8516a-c8ad-4295-b55f-73cb46039a26", "contents": "Traumatic pneumothorax is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as\u00a0thoracentesis, pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura."}
+{"id": "pulmonary$$$fab6752f-0cd2-4f94-b1d6-360dba928893", "contents": "is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as"}
+{"id": "pulmonary$$$e45fe667-2ec7-4033-8c5e-04c092a2b507", "contents": ", pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura."}
+{"id": "pulmonary$$$a204c5c6-7a42-4146-a852-8691884ffd56", "contents": "The pneumothorax is readily identified with translucency on the affected side. The pathophysiology of a pneumothorax (figure 9.5) leads to hypoxia and hypercapnia in the affected lung through changes in perfusion and ventilation. Perfusion to the affected side is markedly reduced as the vasoconstrictive response to local hypoxia and the loss of radial traction to vessels profoundly increases vascular resistance. Consequently, perfusion shifts to the contralateral and unaffected lung. Similarly ventilation to the collapsed lung is minimal as airspaces are collapsed and airway resistance is very high, but the chemoreceptive reflexes increase ventilation to the unaffected lung where resistance is normal. Because perfusion and ventilation are shifted to the normal lung, V/Q mismatching may be compensated to some degree and severe hypoxemia may be avoided. When pneumothorax occurs patients usually describe a rapid onset of dyspnea and initial sudden sharp pain. The pain often then transitions into a dull ache."}
+{"id": "pulmonary$$$40ccba21-8fb6-4af3-aba0-bff1653d3e37", "contents": "Tension pneumothorax may arise if the disruption to the pleural is such that the injury acts like a valve. During inspiration when thoracic pressure falls air enters the airways\u00a0and also the thoracic cavity via the injury. During expiration when the thoracic pressure increases, the wound closes, stopping the air that entered the thoracic cavity from leaving. So with each inspiration more air enters while little or none leaves during the subsequent expiration. The accumulating volume can begin to push the heart and mediastinum to the contralateral side. This may severely affect cardiac output and rapidly become life threatening."}
+{"id": "pulmonary$$$c8ef4a3e-bc72-41a2-832a-f0993ef52345", "contents": "These CT scans in figure 9.6 shows a spontaneous pneumothorax (left panel) and a tension pneumothorax (right panel) with significant shift of the mediastinum over the contralateral hemithorax. So now you should be able to distinguish between the causes and mechanisms of these pleural disorders and determine their effects on pulmonary and cardiac function."}
+{"id": "pulmonary$$$34b024cb-5165-4749-a052-0d8070d763e3", "contents": "Husain, Aliya N. \u201cChapter 15: The Lung.\u201d In Robbins and Cotran Pathologic Basis of Disease, 9th ed., edited by Vinay Kumar, Abul K. Abbas, and John C. Aster. Philadelphia: Saunders, an imprint of Elsevier Inc., 2015."}
+{"id": "pulmonary$$$a8850dcf-5c61-474b-b4f7-bdb65edf15a6", "contents": "West, John B. \u201cChapter 5: Restrictive Diseases.\u201d In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008."}
+{"id": "pulmonary$$$69f961c0-969d-40e6-8ade-b643ff59d2c7", "contents": "The lung is no different from\u00a0any other organ in that it is susceptible to disorders of the immune system. One might argue that it is surprising that the lung does not\u00a0encounter more problems, given the lung\u2019s exposure to the environment and the myriad\u00a0antigens it encounters. Before we start looking at a few specific disorders, let us\u00a0quickly review the four mechanisms through which the immune system might disrupt lung tissue."}
+{"id": "pulmonary$$$1a94ccb8-a877-481c-afba-6bd5bbb2d630", "contents": "A type 1 reaction, or immediate hypersensitivity\u00a0(table\u00a08.1), is a result of overexpression of IgE (table\u00a08.1). When an antigen binds to the overexpressed IgE on the surface of mast cells, the cell releases histamine and leukotrienes that in turn induce an inappropriate or exaggerated inflammatory response. Allergic asthma is an example of a type 1 reaction."}
+{"id": "pulmonary$$$49e8b3ef-78fa-49c0-a782-676e724ef6a7", "contents": "A type 2 reaction, or antibody-dependent cytotoxic reaction (table\u00a08.1), is the result of a circulating antibody reacting with a component of a cell or tissue. The formation of this inappropriate immune complex results in the cell or tissue being flagged for attack by the immune system. Goodpasture\u2019s syndrome is an example of a type 2 reaction."}
+{"id": "pulmonary$$$ecded636-8864-4e2e-bc01-b7de6a6d0a42", "contents": "A type 3 reaction, or immune complex reaction (table\u00a08.1), is the result of an immune complex forming either locally or circulating from elsewhere and then depositing itself in tissue; the immune complex then instigates an immune system attack that involves the tissue. Pulmonary vasculitis can be caused by type 3 immune disorders."}
+{"id": "pulmonary$$$fadbb58c-ba27-41aa-a219-2148de5e68ee", "contents": "Lastly, a type 4 reaction, or cell-mediated hypersensitivity (table\u00a08.1), is caused by a population of hypersensitive T cells whose response to an antigen is exaggerated and leads to the proliferation of that\u00a0cell population and the release of lymphokines to induce an inflammatory response. While this pattern is the same as the normal response to many infections, the magnitude of the response is inappropriate and can lead to\u00a0pathological changes, such as allergic alveolitis."}
+{"id": "pulmonary$$$cc18c6f4-da00-49e1-8ade-6b079c139b8e", "contents": "Table 8.1:\u00a0Types of immune mechanisms involved in lung tissue injury."}
+{"id": "pulmonary$$$5a3578ba-82c1-4463-b782-2ce0d7d29268", "contents": "With those mechanisms defined, let us\u00a0look at some specific disorders."}
+{"id": "pulmonary$$$513c66e1-b30f-47a0-804e-ced6ad9b3808", "contents": "In the acute phase, lymphocytes and macrophages infiltrate the alveolar walls and loose granulomas can form. The presence of multi-nucleated giant cells (figure 8.2), are helpful in diagnosis, but more typical is a dramatic rise in lymphocyte count in BAL fluid, particularly CD8+ cells."}
+{"id": "pulmonary$$$da5f7d98-82bc-43e0-a76b-cdd2a83989b1", "contents": "In the subacute phase\u00a0there is evidence of interstitial thickening and the onset of fibrosis can be seen. Involvement of the bronchioles is seen with evidence of chronic bronchiolitis.\u00a0The chronic form is marked by significant fibrosis (figure 8.3), to the extent it is indistinguishable from pulmonary fibrosis with distinctive fibrotic patterns and all the hallmarks of restrictive lung disease."}
+{"id": "pulmonary$$$82e72dd8-37aa-46e6-9f8e-d4af6a758814", "contents": "How hypersensitivity pneumonitis presents is somewhat dependent on the form of exposure the patient had."}
+{"id": "pulmonary$$$e2f9d8e0-f40a-4675-87b5-a9ce46016902", "contents": "With brief but heavy exposure, an acute presentation of pneumonitis will present with\u00a0fever, malaise, cough, and dyspnea. Physical exam confirms the fever and tachypnea and cyanosis can reflect the severity of the response. Bibasilar rales are often present, but unless a type 1 hypersensitivity arises then wheeze is usually absent (but you might note here that concurrent allergenic asthma is not beyond the realms of possibility). This acute form usually resolves within a couple of days, but can reoccur when the patient is exposed to the causal agent again."}
+{"id": "pulmonary$$$9534c8bf-8a47-49c8-b624-35f5e7524840", "contents": "When exposure is light but prolonged, the onset of hypersensitivity pneumonitis is more insidious and clinically challenging. The patient will describe a slowly progressive cough and developing dyspnea, also weakness and weight loss. This form of onset is common with continuous exposure to organic dust. With this longer time line the patient is not usually aware of the symptom\u2019s relation to occupation and exposure persists until diffuse pulmonary fibrosis is established. At this point the signs and symptoms are related to respiratory insufficiency."}
+{"id": "pulmonary$$$92c213eb-a541-4823-8fdd-39f460143f1e", "contents": "Lupus erythematosus is a type 3 reaction. Autoantibodies are formed against cell components, particularly the nucleus and its associated proteins. The most common antibodies found are against single\u2013\u00a0or double\u2013stranded DNA. About 70 percent\u00a0of SLE patients have lung involvement that can be either acute or chronic."}
+{"id": "pulmonary$$$a4e79593-235f-4368-8a83-505add623aa5", "contents": "The acute form is referred to as lupus pneumonitis, and its signs and symptoms mimic bacterial pneumonia. It can have a rapidly progressive course with acute pleuritic chest pain\u00a0and can lead to respiratory failure. The inflammation it involves can disrupt pulmonary capillaries and lead to hemorrhage. Patients with SLE are highly susceptible to infection, so diagnosis of an SLE patient should distinguish between respiratory tract infection and changes directly related to lupus. Changes in lupus come as flares followed by remission, and there are a number of triggers for flares including:"}
+{"id": "pulmonary$$$a963a7f7-ee87-4a98-b028-be212f62d59d", "contents": "The chronic form can progress insidiously with no symptoms or physical findings, and so it frequently it goes unrecognized until later stages of the disease. The later stages are marked with the appearance of progressive fibrosis. This is evident in the\u00a0chest x-rays in figure 8.4\u00a0showing the appearance of diffuse fibrosis over a twenty-month period in a young SLE patient. The fibrosis produces reduced\u00a0lung volumes and basilar atelectasis may also occur. The increased recoil of the lung can also produce an elevated and weakened diaphragm. There may also be pleural involvement with effusions arising that are normally bilateral and small."}
+{"id": "pulmonary$$$c48b9516-2cb6-4fe5-92f6-604b85200655", "contents": "More famous for its effect on the joints, rheumatoid disease can also affect the lungs and pleura. Rheumatoid factors that generate rheumatoid disease continue to be investigated, but\u00a0in brief, they are antibodies generated against gamma globulins. Pleural and pulmonary lesions are probably the result of local immune complex\u2013mediated reactions associated with high levels of circulating rheumatoid factors."}
+{"id": "pulmonary$$$04d7b4aa-886a-4536-98ed-070284e4bd95", "contents": "Up to 50 percent\u00a0of rheumatoid patients show pulmonary or pleural manifestations, with pleural involvement being more common and\u00a0most frequently manifested as pleural effusion (figure 8.5). The effusate tends to have low glucose, and this finding is useful for diagnosis. Pleural and pulmonary manifestations of rheumatoid disease are more common in male patients."}
+{"id": "pulmonary$$$ede6027d-fb5a-4e30-9117-95507266dd44", "contents": "Pulmonary involvement shows as either diffuse or nodular lesions (figure 8.6). The diffuse lesions are\u00a0similar to those seen in idiopathic pulmonary fibrosis. The nodular lesions are variable in size and number and usually do not\u00a0cause symptoms. They are known as necrobiotic nodules and are capable of cavitating. Bronchiolitis obliterans organizing pneumonia and bronchiectasis have also been seen in rheumatoid disease."}
+{"id": "pulmonary$$$42a08419-43ef-4114-bb9f-0f12c3b4dfa6", "contents": "It should be noted here that some drugs used to treat difficult rheumatoid arthritis, such as gold preparations, methotrexate, and penicillamine, are toxic to the lung and can produce their own pulmonary lesions."}
+{"id": "pulmonary$$$cb8e1a9f-2a82-4a89-b17c-a1610c12363b", "contents": "Also known as scleroderma, progressive systemic sclerosis primarily affects the blood vessels and connective tissue and likely has an autoimmune mechanism. The result is dysregulation of fibroblasts and uncontrolled collagen formation. The disease can affect many organs and tissues, and pulmonary manifestations are common."}
+{"id": "pulmonary$$$1c381b39-cda0-46b1-83e7-0ef197c5085c", "contents": "The most common pulmonary findings are interstitial fibrosis, bronchiolar dilation, and pleural fibrosis, as well as the vascular changes that are seen in other organs. These changes produce dyspnea, cough, and basilar rales. The vascular changes can produce pulmonary hypertension that may lead to cor pulmonale."}
+{"id": "pulmonary$$$46f49161-5bd8-4b1a-bce3-e07a1097b217", "contents": "The radiographic findings\u00a0are similar to pulmonary fibrosis with the early stage of the disease showing fine reticular patterning that progresses to honeycombing in the late stage of the disease (figure 8.7). These changes are mostly found in the lower lung fields. As you might expect, the disease has restrictive characteristics along with diffusion abnormalities that produce hypoxemia during\u00a0exercise."}
+{"id": "pulmonary$$$bdc02467-c4ab-42d3-959c-6b0c22fd235a", "contents": "Polymyositis is an autoimmune disease that attacks striated muscle through a cell-mediated mechanism, but can also affect other organ systems, including the lung."}
+{"id": "pulmonary$$$3b291a83-50c1-498a-a5ca-d3ec4c152236", "contents": "There is some direct involvement with\u00a0development of bronchiolitis obliterans organizing pneumonia (BOOP) and chronic interstitial pneumonitis and fibrosis. But\u00a0the most frequent respiratory complications are a result of the respiratory muscles and muscles involved with swallowing becoming affected. Poor control of swallowing and inability to generate effective cough promote aspiration and retention of airway secretions. This is a recipe for bronchopneumonia\u2014and this ends up being the most common form of death. Infection risk is often increased by the patient taking large doses of corticosteroids or immunosuppressive drugs to address the disease."}
+{"id": "pulmonary$$$18cc338a-ebb8-4172-ab25-10a0067cd924", "contents": "To summarize, the immunological responses to inhaled particles, localized immune responses, and systemic immunological disease can produce pulmonary manifestations that are generally related to acute and then chronic inflammatory responses. The distinguishing features and pulmonary manifestations are summarized in table 8.2."}
+{"id": "pulmonary$$$8e232397-5b37-4af4-ad5a-bcf6c313532f", "contents": "Table 8.2:\u00a0Summary of immune and systemic disorders that affect the lung."}
+{"id": "pulmonary$$$c95fa1fa-f9e3-450e-b56a-ad2feb79761c", "contents": "Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. \u201cChapters 13\u201314.\u201d In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978."}
+{"id": "pulmonary$$$46cbc4df-cf41-4ebf-99e9-0d40ac274b65", "contents": "Table 8.1:\u00a0Types of immune mechanisms involved in lung tissue injury. Includes Immune mechanism \u2013 type 1 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism \u2013 type 2 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism \u2013 type 3 by Kindred Grey from Internet archive (CC BY 4.0), and Immune mechanism \u2013 type 4 by Kindred Grey from Internet archive (CC BY 4.0).Figure 8.1: Acute phase of hypersensitivity pneumonitis. Mutleysmith. 2012. CC BY-SA 3.0. From WikimediaCommons."}
+{"id": "pulmonary$$$135b6718-449f-4a77-b8d5-731b7a7b5b9c", "contents": "About 90 percent\u00a0of PEs are caused by deep vein thrombi, but at least one of three main predisposing factors (Virchow\u2019s triad)\u00a0are present in a case of PE:"}
+{"id": "pulmonary$$$128585f5-b225-4d9f-9d7e-0936c134ceaf", "contents": "Abnormal vessel walls: Damage to the inner wall of veins causes adherence of blood platelets and activation of clotting factors. Similarly inflammation or trauma of the vein or surrounding area can lead to a risk of local clotting."}
+{"id": "pulmonary$$$55e13d6c-43b2-49b5-b0d3-5960b0cf3b6d", "contents": "Venous stasis: Venous stasis appears to be the most important factor in thrombus formation, and cases of PE are often preceded by periods of immobility (top tip: a USMLE\u00a0question with a long-haul flight in the stem should raise the PE flag). But other causes of disrupted venous blood flow can elevate the risk."}
+{"id": "pulmonary$$$1bd5b401-9a57-4794-9b36-57eae7a373c0", "contents": "Hypercoagulability: Any condition that increases coagulability elevates the risk of PE, and most are due to trauma of some form or another or an elevated inflammatory state such as cancer or the postsurgery state. Birth control pills predispose the patient to thromboembolic disease so thereby also increase the risk of PE."}
+{"id": "pulmonary$$$6a3a9432-5ad0-4334-a824-8d3ad6ddd2f8", "contents": "The pathophysiology and clinical severity of PE depend on the number and size of the emboli, so clinical manifestations can be highly variable. In fact, PE is suspected to be much more common than previously thought because of improved detection techniques revealing more small and asymptomatic cases."}
+{"id": "pulmonary$$$4d0d3628-5138-4854-a44d-ba58dcd8838c", "contents": "Small emboli that can travel\u00a0further into the vasculature may cause occlusion of relatively small areas of the lung, but with these areas receiving no perfusion and still being ventilated V/Q becomes inappropriately high. Not being able to pass the occlusion, blood will be diverted to other areas of the lung, and consequently cause them to be overperfused, lowering V/Q."}
+{"id": "pulmonary$$$d640376a-ecdb-4c83-8343-613efd368b53", "contents": "Depending on the size and number of emboli, these V/Q mismatches can produce\u00a0a widening alveolar\u2013arterial PO2\u00a0difference and lead to hypoxemia."}
+{"id": "pulmonary$$$6a590143-e548-4a81-9811-77266509fd09", "contents": "With larger emboli that occlude larger vessels there will not only be a larger impact on gas exchange, but also a more increase in pulmonary vascular resistance. The extreme \u00a0(and thankfully rare) case\u00a0is a \u201csaddle\u201d embolus that is large enough to\u00a0straddle the bifurcation of the pulmonary trunk, obstruct the left and right pulmonary arteries, and lead to immediate\u00a0hemodynamic collapse.\u00a0In lesser cases,\u00a0pulmonary hypertension will overwhelm the thin myocardium of the right ventricle, and as pulmonary arterial pressure approaches right ventricle pressure then cardiac output will fall. This will exaggerate the hypoxemia and cause the pulmonary vasculature to perform its normal vasoconstrictive response to low oxygen tensions that in turn worsens the pulmonary hypertension (summarized in figure 7.1)."}
+{"id": "pulmonary$$$b6c06c73-33d6-4676-a8a9-9d5c8ec1bf3d", "contents": "Pulmonary infarction, however, is rare, occurring in only 10 percent\u00a0of PE cases. The lung tissue is supplied by the bronchial circulation so can usually survive the embolism in the pulmonary circulation unless there is preexisting cardiac disease."}
+{"id": "pulmonary$$$d0ce662e-8d5d-405f-8e7d-b7f8d24379a4", "contents": "The clinical manifestations of PE vary\u00a0widely, from asymptomatic when emboli are small or few, to sudden death when they are large or numerous."}
+{"id": "pulmonary$$$b6c9dbed-4067-4944-a3a9-3f53dbf12971", "contents": "Signs of DVT may precede PE cases, such as leg pain, venous swelling, or warm skin over the thrombus site, but these are present in less than half of patients. Once instigated, the presenting symptom of PE is usually dyspnea but can also include chest pain. There can be clinical clues in the dyspnea as it has a rapid onset and is disproportionate to any initial clinical findings. The nature of its onset also tends to generate significant anxiety. Chest pain can start as anginal but then become more pleuritic."}
+{"id": "pulmonary$$$a83aa3ad-12e5-42ec-88f7-9ec3557150fe", "contents": "Hemoptysis is less common but an important symptom. In severe cases involving massive PE tachypnea, tachycardia and cyanosis are usually present."}
+{"id": "pulmonary$$$c57159d5-62f7-43e4-8af9-290d57a70f62", "contents": "Because of the mechanical and metabolic strain on the heart, cardiac manifestations, including arrhythmia, acute cor pulmonale, or signs of cardiac failure or shock, may be detected with\u00a0an\u00a0increased difference between alveolar and arterial PO2s."}
+{"id": "pulmonary$$$1893bfc2-8422-4729-a3ed-19ebc7de8e7d", "contents": "The chest x-ray will appear normal, unless there are complications such as pleural effusion, atelectasis, or pulmonary infarction. CT angiography is used to detect the presence of a PE when suspicion is high. When suspicion is lower,\u00a0labs will include a\u00a0D-dimer\u00a0test (a protein fragment\u00a0produced by a dissolving clot), which, if negative, can help rule out the presence of a PE, but if positive would require further investigation (e.g., CT angiography) for confirmation."}
+{"id": "pulmonary$$$682f75a3-5287-4893-b258-f8c47679450f", "contents": "Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. \u201cChapter 21.\u201d In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978."}
+{"id": "pulmonary$$$99ef9463-cb8b-4725-b750-3a5bfddf0607", "contents": "West, John B. \u201cChapter 6: Vascular Diseases.\u201d In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008."}
+{"id": "pulmonary$$$cc05c711-e485-49f6-b7d0-98f4edb46105", "contents": "Four major types of bronchogenic carcinoma can be distinguished by histology, epidemiology, clinical features, and prognosis. They are:"}
+{"id": "pulmonary$$$2c4b095c-1962-4a38-bb39-11b4df914910", "contents": "Squamous cell cancer accounts for about one-third of all lung cancers and is more common in men. It is pathologically characterized by keratin formation between cells and the development of large, well-outlined islands of cancer cells. It is usually centrally located and associated with the main bronchi. Metastasis tends to be local, affecting the surrounding areas and lymph nodes."}
+{"id": "pulmonary$$$642f8c65-9e6d-4e5e-b739-5d8733fdee5c", "contents": "Adenocarcinoma also accounts for about one-third of cases but is the most common lung cancer in women. The lesion has a glandular structure and may produce mucin. This is usually a peripheral lesion and distant metastasis is common."}
+{"id": "pulmonary$$$837940c9-02fc-4c10-87a0-f1b1d8a03509", "contents": "Large cell is less common and is seen in about 10 percent\u00a0of cases, most of whom are male. The diagnosis is made by cell size, which is large and easily distinguished from squamous cell cancer or adenocarcinoma. The lesions can be anywhere in the lung but are often found in the periphery. This is a fast-growing cancer and so is frequently diagnosed at a later disease stage."}
+{"id": "pulmonary$$$a57a9a27-05f6-41c2-b9e1-cd5de525f8d1", "contents": "The previous three types of cancer are\u00a0collectively known as non-small cell lung cancer. Alternatively, small cell cancer is found in about 15 percent\u00a0of cases. It is less predominant in men, and incidence in women is rising. The small cells have an oat-like appearance, and the most common small cell cancer is known as oat cell carcinoma and the lesions frequently have endocrine function. Originating in the main bronchi this cancer spreads very quickly into other thoracic and extrathoracic sites, and this form carries a very poor prognosis."}
+{"id": "pulmonary$$$57fec407-a47f-41cf-a8a1-5e48c3670f1a", "contents": "The characteristics of these forms of lung cancer are summarized in table 6.1."}
+{"id": "pulmonary$$$56b5f3ed-7941-4317-9144-71ab189085ac", "contents": "Table 6.1:\u00a0Summary of forms of lung cancer."}
+{"id": "pulmonary$$$d34dcb43-d5bb-43a5-a675-20a43c43d204", "contents": "The signs and symptoms can be variable and diverse depending on the location, type, size, and rapidity of growth. Patients may even be asymptomatic when the lesion is found on chest x-ray or with bronchoscope."}
+{"id": "pulmonary$$$51c38948-4396-4f5a-b997-bb40f22f0dc6", "contents": "The most common symptom is cough, but unfortunately the patient, likely being a smoker, may be accustomed to cough and not think anything of it. Bloody sputum occurs in only about half of patients and is a frequent cause for them seeking medical advice, and severe hemoptysis is uncommon."}
+{"id": "pulmonary$$$6ff06d00-15aa-4d3a-9574-871ab4f18cb5", "contents": "Chest pain is fairly common and ranges from a mild ache or feeling of heaviness, to severe and unremitting. Pain does not necessarily indicate pleural or chest wall involvement, although significant steady pain is more indicative of this complication."}
+{"id": "pulmonary$$$4edb3231-5a6a-4444-9c9b-b8e352550942", "contents": "Dyspnea may arise as the tumor obstructs a major airway or causes a large pleural effusion, but it can also be due to underlying bronchopulmonary disease."}
+{"id": "pulmonary$$$e4bfe82d-3803-4ffe-919f-997f2394bc42", "contents": "Physical exam is likely to be normal in the early stages of the disease, but as the cancer progresses the exam usually reveals signs associated with either bronchial obstruction or a consequence of metastasis. Bronchial obstruction can lead to wheeze or other modified breath sounds, atelectasis, down-stream pneumonia, or pleural effusion. Paraneoplastic syndromes associated with the cancer can cause disruption to other systems and lead to characteristic weight loss, muscle wasting, and digital clubbing."}
+{"id": "pulmonary$$$92f391cb-397f-42ca-8027-6aeabc48b471", "contents": "Chest x-ray is usually only capable of detecting advanced cancer stages, and therefore is not the best screening tool. Low-dose CT screening can be used to detect early stages of disease before symptoms arise and is advised for patients\u00a0between fifty to eighty years old with a twenty-pack-per-year smoking history or who have quit smoking in the past fifteen\u00a0years.\u00a0Once the disease is established, however, the x-ray\u2019s findings can either be direct detection of a mass, or a\u00a0secondary consequence of the mass; therefore they are quite variable (figure 6.1)."}
+{"id": "pulmonary$$$d412e5db-7af7-4ded-98bd-d3838d618392", "contents": "Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. \u201cChapter 20.\u201d In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978."}
+{"id": "pulmonary$$$5b90a401-f907-458e-acb6-06e6ef81186f", "contents": "Table 6.1: Summary of forms of lung cancer. Includes Squamous Cell Carcinoma Lung 40x by Calicut\u00a0Medical\u00a0College\u00a0from WikimediaCommons (CC BY-SA 4.0), Papillary adenocarcinoma of the lung \u2014 intermed mag by Nephron from WikimediaCommons (CC BY-SA 3.0), Large cell carcinoma of the lung by The Armed Forces Institute of Pathology (AFIP) from WikimediaCommons (Public domain), and Lung small cell carcinoma (1) by core needle biopsy by KGH from WikimediaCommons (CC BY-SA 3.0)."}
+{"id": "pulmonary$$$56cdcda8-5410-4a9a-b9e0-4b3903d27c1a", "contents": "There are about two hundred thousand cases of ARDS in the United States\u00a0each year. Each case starts with an initial insult to the lung parenchyma and there are numerous examples of this instigating event, but the most common of these (and therefore worth remembering) are sepsis, pulmonary aspiration, and thoracic trauma. The insult can arrive from the airway, such as in pulmonary aspiration or smoke inhalation, or can arrive from the bloodstream, as in a fat embolism or blood-born pathogen."}
+{"id": "pulmonary$$$01bbc814-2276-4901-bc9f-9f07e914f0f3", "contents": "Regardless of the insult\u2019s route or indeed form, the ensuing pathological events are similar and lead to the same alteration of the lungs. What is initiated is a defensive inflammatory response, and what results is vascular endothelial and alveolar epithelial damage and a leaky alveolar capillary membrane."}
+{"id": "pulmonary$$$b002921a-3855-45f1-bd5a-3d96e9e69018", "contents": "The process is summarized in figure 5.2."}
+{"id": "pulmonary$$$81fd3fe0-f6b1-4b2f-8f8b-91243a4d8699", "contents": "1.\u00a0Exudative: The first six to seven\u00a0days comprise the exudative phase that begins with edema appearing in the interstitial walls seen here by the widened alveolar septum. Cellular debris can also be seen in the airspaces, and this can continue with the formation\u00a0of the hyaline membranes that coat the alveolar surface (figure 5.3)."}
+{"id": "pulmonary$$$d97bee38-539e-41c2-88f9-d40dec596de6", "contents": "2.\u00a0Proliferative: In the early proliferative stage,\u00a0there is increased cell infiltration and squamous metaplasia with proliferation of type II cells (figure 5.4), and these mitotic type II cells have a \u201chob-nail\u201d\u00a0like appearance over a time line of weeks. The infiltrating cells include fibroblasts that begin laying down collagen."}
+{"id": "pulmonary$$$b43019e3-eb73-4f55-8900-49b4367dafee", "contents": "3.\u00a0Fibrotic: Without resolution the patient may enter the third stage, fibrotic stage, that occurs over months (figure 5.5). This\u00a0stage occurs much later and is a consequence of unresolved chronic inflammation. Diffuse fibrosis permanently obliterates normal lung architecture and may form cysts."}
+{"id": "pulmonary$$$bca299ce-c242-4db3-a09d-fe0e59b21c40", "contents": "We start with initial lung injury leading to alveolarcapillary leaking. As we have seen, this leads to the airspace edema and hyaline membrane formation."}
+{"id": "pulmonary$$$b87eec7f-9f61-4c00-838d-5a163aebf10b", "contents": "The lack of gas exchange from affected areas produces a right\u2013left shunt and hypoxemia will result. This produces dyspnea, the major symptom of ARDS."}
+{"id": "pulmonary$$$b1e93c93-2590-4e21-8d02-3e16493195df", "contents": "But the disruption caused by the inflammatory process also leads to other pathophysiological issues. The loss of type II cells causes surfactant production to decline. This of course reduces lung compliance, and the resultant increase in the work of breathing contributes to the patient\u2019s dyspnea."}
+{"id": "pulmonary$$$7136c68b-396a-4e35-9b14-9e06025e19e2", "contents": "But we are still not done. The fibrin clots forming obstructions in the lung microvasculature lead to V/Q mismatches, and these contribute to the hypoxemia. The obstructed vasculature also produces pulmonary hypertension, which is exacerbated by the vasculature\u2019s response to the hypoxia."}
+{"id": "pulmonary$$$4d0fb6e4-a76c-4d8b-a501-8e8dd45920f3", "contents": "The onset of dyspnea usually occurs within one to two\u00a0days after the initial injury, and as tachypnea arises, this symptom progressively worsens. Cough is common and may produce blood-tinged sputum. Findings on chest exam may be surprisingly scant, but some bronchial breath sounds and crackles may be heard."}
+{"id": "pulmonary$$$899da8e7-7c71-4f23-9158-a61a1da39096", "contents": "As cyanosis becomes apparent, minute ventilation and dyspnea continue to increase\u00a0and the patient will likely become distressed."}
+{"id": "pulmonary$$$ce745529-8ee6-4ec7-8b21-bd5fce8cf006", "contents": "A high ventilatory rate driven by the hypoxemia can produce hypocapnia and a respiratory alkalosis. The arterial pH can be complicated by the underlying disorder, and it is not uncommon for a mixed acid\u2013base disorder to occur with concurrent respiratory alkalosis and metabolic acidosis. At the onset of respiratory failure arterial CO2\u00a0will rise and produce a respiratory acidosis."}
+{"id": "pulmonary$$$f8616bb2-6c63-4fc9-bf8a-9bcd12f1a732", "contents": "Radiographic findings are an essential part of diagnosing the ARDS patient and will show diffuse bilateral interstitial and airspace densities caused by the edema (figure 5.7). Normal heart and vessel size and absence of pleural effusion distinguish ARDS from cardiogenic pulmonary edema. Although the x-ray gives the appearance of diffuse edema, high-resolution CT often shows that the process is heterogeneous and patchy. This heterogeneity is reflected by remnant patchy fibrosis if the patient recovers; however, the mortality rate for ARDS is around 50 percent."}
+{"id": "pulmonary$$$b66d19ed-4bac-409b-900e-56e1916f41a5", "contents": "So now you should have a clear understanding that after an initial insult to the lung an exaggerated and perpetual inflammatory response leads to the destruction of the alveolar\u2013capillary interface. The resulting edema and hyaline membrane formation produces severe hypoxemia and a critically ill patient."}
+{"id": "pulmonary$$$a657cac1-87c9-4a34-a8b2-a3d673f6934b", "contents": "Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. \u201cChapter 27.\u201d In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978."}
+{"id": "pulmonary$$$5351bcef-c613-420f-a998-817912cb0590", "contents": "West, John B. \u201cChapter 8: Respiratory Failure.\u201d In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008."}
+{"id": "pulmonary$$$2bf2097e-c952-4e61-bdc7-c018fed73a0c", "contents": "Before we start taking about diseases affecting the lung interstitium, let us\u00a0remind ourselves of what it is."}
+{"id": "pulmonary$$$5a2ecb16-7483-4ecc-9625-a5985a2879c5", "contents": "The interstitial tissue, sometimes referred to as parenchyma, surrounds\u00a0the alveolar and capillary structures and contributes to the mechanical behavior of the lungs. The interstitium is extremely thin between the alveoli and capillaries, and forms the basement membrane through which gas exchange occurs. On the parenchymal\u00a0side of the capillaries the interstitium is more substantial and is more involved in fluid exchange. There is also substantial amounts of interstitial tissue in the spaces around major vessels and airways, and it also makes up the interlobular septa."}
+{"id": "pulmonary$$$485f64ad-fa63-4fbf-8b74-59c779f369f8", "contents": "Now we will look at the generalized mechanism of interstitial lung disease (figure 4.1). It is\u00a0worth noting that the numerous conditions that the term ILD encompasses have subtle differences in mechanism and manifestations, and these differences are what we will deal with elsewhere."}
+{"id": "pulmonary$$$6288be73-5e03-483d-8f33-eb75f593ae7e", "contents": "Generally though, ILD\u00a0starts with an initial insult to the lung (#1, figure 4.1); the type of insult is a major contributor to the different ILD conditions. (It probably will not be what is depicted in figure 4.1, but if it was, it might lead to the inflammatory condition of tiefitis.)"}
+{"id": "pulmonary$$$0d6d0d01-0c63-4bba-ae16-38598ec0bebd", "contents": "There is then a response by neutrophils and alveolar macrophages (#2, figure 4.1). The macrophage response seems particularly important to the development of ILD. Release of cytokines (#3, figure 4.1) attracts other inflammatory cells, and the arrival of polymorphonuclear leukocytes and lymphocytes play an important role in disease instigation. These cells release cytokines, enzymes, and toxic oxygen radicals that damage and destroy local tissue. Released growth factors, such as TGF-Beta, instigate\u00a0the transition of mesenchymal cells to fibroblasts."}
+{"id": "pulmonary$$$0930cfa0-06e6-4970-8ec3-ce8ab0031868", "contents": "It is worth noting at this point that some forms of ILD are caused by an exaggerated immune reaction\u2014either through an allergic-like response, or a direct immune disorder."}
+{"id": "pulmonary$$$b95bc8bc-346f-4fba-875a-8acf17538a8e", "contents": "The destruction of tissue and activity of a growing number of fibroblasts results in the inflamed interstitium becoming fibrosed with excess connective tissue, particularly collagen (#4, figure 4.1)."}
+{"id": "pulmonary$$$0c71ff29-d3ba-42a8-8fce-844052080d90", "contents": "These changes in structure dramatically change the functional and mechanical properties of the tissue. The changes also tend to follow a characteristic pattern, although, as you might imagine, different conditions have subtle differences in pattern."}
+{"id": "pulmonary$$$2f7dba2a-3d57-4504-8aab-3a738a53efd2", "contents": "The action of fibroblasts laying down connective tissue, combined with the destruction of alveolar and capillary structures, leads to a widening of airspaces with thick collagenous and infiltrated walls (figure 4.2A and 4.2B), which are a functionally significant departure from the ideal structure for gas exchange."}
+{"id": "pulmonary$$$6ca2500b-8328-4fa4-8dff-737e70c8af8d", "contents": "The thickened basement membrane poses\u00a0a significant obstacle to the transfer of gases, and the dense connective tissue stiffens the lung and thereby reduces its compliance. Combined with loss of capillary beds and airspace surface area,\u00a0gas exchange is reduced."}
+{"id": "pulmonary$$$caac64f9-dba5-4e86-981f-0c9bc3eb92d9", "contents": "At the end of the disease the lung takes on a characteristic honeycomb appearance, and \u201cground glass\u00a0opacities\u201d\u00a0are a hallmark sign on CT images (figure 4.2C). These morphological changes lead to pathophysiological consequences that are shared by most forms of the disease, as all cause varying degrees of\u00a0interstitial inflammation and connective tissue deposition."}
+{"id": "pulmonary$$$3c042458-99fe-4f55-985d-09fb29fe1eae", "contents": "The first major issue is the reduced diffusion capacity of the involved areas, and all ILD patients demonstrate a reduced transfer factor, or DLCO (figure 4.3)."}
+{"id": "pulmonary$$$34939227-a8c9-4d82-8cdf-b7a470753c69", "contents": "Because of the heterogenous distribution of the disease, and the involvement of the pulmonary circulation, severe V/Q abnormalities arise throughout the lung. This and the reduced diffusion capacity result in hypoxemia. In the chronic disease state this may lead to cor pulmonale (figure 4.3)."}
+{"id": "pulmonary$$$5f0a5066-7816-41f8-bb4b-d3e9611df59f", "contents": "The reduction in lung compliance leads to a reduced lung volume. This is easily detected with spirometry as shown by the inner plot of the flow-volume loop in figure 4.3. Because\u00a0FEV1\u00a0and FVC are both reduced, the ratio frequently remains the same or may even rise; as such FEV1/FVC is a poor indicator of restrictive disease."}
+{"id": "pulmonary$$$f1ec629d-7d66-4592-a222-c5466b6cea6d", "contents": "The reduced lung volume and compliance results in a characteristic rapid, shallow breathing pattern as the patient tries to maintain alveolar ventilation (figure 4.3). However, while avoiding unnecessary increases in the work of breathing by not trying to over-expand the noncompliant lung, the rapid shallow breathing proportionally increases dead space ventilation."}
+{"id": "pulmonary$$$c60ff515-57cc-465c-890f-8733b6745c07", "contents": "The reduction in tidal volume, combined with a raised hypoxic drive to breathe, results in the cardinal symptom of ILD, which is dyspnea (figure 4.3)."}
+{"id": "pulmonary$$$5e1f063f-f1c0-4dae-8e69-7164d4942037", "contents": "The correlation of dyspnea and disease stage is closer in ILD than any other respiratory disease. The onset is insidious, appearing first during exercise, and it likely contributes to the other major complaints of weakness and fatigue. The dyspnea gets progressively worse until it can be debilitating."}
+{"id": "pulmonary$$$f791e25d-b16b-4201-94be-727765967b11", "contents": "Inflammation and excitation of pulmonary receptors leads to a nonproductive and persistent cough, and upon examination patients will have limited chest expansion and demonstrate the characteristic breathing pattern of restrictive lung disease."}
+{"id": "pulmonary$$$359b4715-62df-4b4d-8d03-da46801bf029", "contents": "Hallmark lung sounds are fine crackles, commonly found at the base of the lung, and may appear louder than expected because of increased transmission through denser than normal tissue."}
+{"id": "pulmonary$$$a577d412-0202-4478-96a2-acb4b15fac20", "contents": "At later stages of the disease the patient shows signs of the prolonged hypoxemia with digital clubbing and cyanosis."}
+{"id": "pulmonary$$$ed9376b6-c726-4557-947d-0005c1a4e3cf", "contents": "Our major subcategory is idiopathic interstitial pneumonia (figure 4.4), or IIP, and this is divided again into six\u00a0more useful categories that can be distinguished by history, time line, and histological changes. We will deal with these categories in this section, but it might be noted that usual interstitial pneumonia, still frequently called idiopathic pulmonary fibrosis, is the only one that remains untreatable, and early differentiation from the other forms is critical (figure 4.4)."}
+{"id": "pulmonary$$$08ab9220-0913-4a7d-8109-9a3caba0c7a8", "contents": "Interstitial lung diseases can also be induced by numerous different environmental causes that produce nuanced conditions that are distinguishable by environmental and social history (figure 4.4) as well as specific histological features."}
+{"id": "pulmonary$$$27ff98b6-20f0-436a-8d91-d312ab01dd09", "contents": "The characteristics of usual interstitial pneumonia have been covered in the \u201cBasis of ILD\u201d\u00a0section, so let us\u00a0start looking at the pathophysiological and clinical features of the other broader disease categories."}
+{"id": "pulmonary$$$50787a16-ae6e-4bba-a29d-10236766ba20", "contents": "We can deal with the first two together as both share common characteristics and are potentially the same disease occurring in different anatomical locations. Desquamative interstitial pneumonia and respiratory bronchiolitis\u2013associated ILD are both smoking related and are relatively uncommon."}
+{"id": "pulmonary$$$91e53081-b90c-49bc-a7fb-9984fb280b67", "contents": "The histological hallmark is accumulation of numerous smoker\u2019s macrophages in the airspaces (figure 4.5) or the first- and second-order respiratory bronchioles. These macrophages have a characteristic brown pigmentation. In desquamative interstitial pneumonia the airspaces are the primary site of involvement, whereas a\u00a0respiratory bronchiolitis\u2013associated ILD sees more involvement of the bronchioles (as the name suggests). The alveolar septum may be thickened with infiltrate and there may be mild peribronchilor or alveolar fibrosis, but this does not result in a honeycomb pattern seen in usual interstitial pneumonia."}
+{"id": "pulmonary$$$59bb848d-4092-487d-adf4-e5a25c7cadcf", "contents": "These ILDs\u00a0are more prevalent in men, and are usually found in the fifth decade of life and after thirty-pack years. They are marked by the gradual and insidious onset of dyspnea, but lung reductions are usually minimal with both forms. The response to corticosteroid therapy and smoking cessation is good in about 80 percent\u00a0of patients who remain stable or improve."}
+{"id": "pulmonary$$$17bb1651-8d8a-4b45-afc2-efd30c082a87", "contents": "While the development of most interstitial lung diseases is slow and insidious, the hallmark of diffuse alveolar damage is rapid, occurring in a matter of days and often in previously healthy individuals. The manifestation of the disease is similar to acute respiratory distress syndrome, and in fact it has been suggested that DAD is a form of\u00a0ARDS."}
+{"id": "pulmonary$$$c57682e2-8ace-4639-8dc6-8b0d318ccbd1", "contents": "The start is marked by a brief exudative phase with fluid entering the airspaces, but the following organizing or proliferative phase is what is usually seen by the time a biopsy is taken and where the similarities to ARDS are seen. The alveolar septa are thickened due to the interstitial edema and the septa may collapse or appose each other (figure 4.7). There is marked infiltration of the interstitial and airspaces by inflammatory cells, and type II cells proliferate. The destruction of the alveolar structure leaves a sludgy hyaline membrane of debris. Thrombi in small arteries may also be apparent."}
+{"id": "pulmonary$$$686812e2-4e59-41f6-b99c-c0510409912e", "contents": "Should the patient survive (about 50 percent\u00a0do not) the healing phase can show recovery of the alveolar structure with varying degrees of fibrosis. Many patients return to normal lung function, but a few show a progressive fibrotic process that resembles idiopathic pulmonary fibrosis."}
+{"id": "pulmonary$$$85e07c4e-5535-4942-9ac3-4df19764c6c7", "contents": "Without biopsy, DAD is usually differentiated from other forms of interstitial disease by its rapid onset, but this can be confused with acute exacerbations of other diseases. However, the uniform pattern of damage in real DAD is representative of a single time line."}
+{"id": "pulmonary$$$4f4b5176-7c16-47a4-b394-6d43d48321aa", "contents": "Our next disease is at least courteous enough to only have one name, nonspecific interstitial pneumonia (NSIP), but irritatingly, it has three groups that are determined by the degree of either interstitial inflammation or\u00a0fibrosis. Group 1 is primarily inflammation, group 2 involves inflammation and fibrosis, and group 3 is primarily fibrosis. The differences in groups are most clearly seen looking at the extremes\u2014group 1 shows\u00a0the puffy alveolar septa infiltrated with lymphocytes (left panel, figure 4.8), whereas group 3\u00a0shows a matrix of fibrosis that can be distinguished from usual interstitial pneumonia by the absence of fibroblastic foci and a homogenous onset and distribution (right panel, figure 4.8). As its name suggests, the distinguishing feature of nonspecific interstitial pneumonia is the lack of features that determine it to be something else. If that sounds a bit wishy-washy, take solace in the fact that even experts argue over its classification."}
+{"id": "pulmonary$$$f2b66fec-7e69-4784-9992-536c85ba1f51", "contents": "The presence of lymphocytes in biopsy and bronchoalveolar lavage fluid suggests the involvement of the immune system in the pathogenesis of nonspecific interstitial pneumonia. This is supported by the occurrence of NSIP in immune diseases such as HIV infection\u00a0and several connective tissue disorders including polymyositis, rheumatoid arthritis, and systemic sclerosis. Our understanding of the pathological mechanisms is still evolving."}
+{"id": "pulmonary$$$94cbfa4e-dc95-405c-9469-5c5a0ac83543", "contents": "Our final major classification is cryptogenic organizing pneumonia (COP). This form of interstitial disease affects the distal bronchioles, respiratory bronchioles, and alveoli, but the primary site of injury is usually the alveolar walls."}
+{"id": "pulmonary$$$474b1b0f-a8b8-4fca-b7ce-0b84ca99c8dd", "contents": "The hallmark of COP is an excessive proliferation of granulation tissue made of collagen-embedded fibroblasts and myofibroblasts that starts in the alveolar space. These plugs of fibrotic tissue may extend\u00a0from one alveolus to another via the pores of Kohn and give rise to a characteristic butterfly pattern. The pathogenesis is an initial alveolar injury, with plasma proteins leaking into the alveolar lumen that is followed by recruited fibroblasts depositing connective tissue with the lumen itself. These fibrotic lesions show a homogenous time line and movement to the distal airways, but are actually reversible, which is in contrast of the lesions seen in usual interstitial pneumonia. In COP the lung architecture is maintained, probably through more thorough regulation of angiogenesis and apoptosis than that seen in usual interstitial pneumonia (UIP)."}
+{"id": "pulmonary$$$78dd4afc-a302-48c5-9219-af147740fc68", "contents": "The onset of COP is marked with dyspnea and dry cough (as with most ILDs), and it has a moderate time line of a couple of months, after which symptoms subside. History is again important to determine the initial insult, and potential culprits include connective tissue disease, new medications, or exposure to therapeutic radiation, fumes, or dusts."}
+{"id": "pulmonary$$$7aabfb20-1e7d-4953-a924-49592b48b60f", "contents": "Now we will look at several specific forms of interstitial disease that are related to occupational exposure. While these forms of ILD have some distinguishing factors, the importance of taking a good history cannot be understated."}
+{"id": "pulmonary$$$32228d49-8d1c-4271-8ef0-75cbf93cb15f", "contents": "Silicosis is related to exposure to silica that occurs frequently in occupations such as stone cutting, foundry work, and mining. Cutting or breaking stone can produce crystalline silica, and when less than 5 microns in diameter, it becomes respirable. When particle size is between 1 and 3\u00a0microns, it can reach the alveoli."}
+{"id": "pulmonary$$$b52f3881-27ab-47c1-bb26-ec221d70d180", "contents": "The formation of silicosis can be acute with heavy brief exposure (often seen in sandblasters), or chronic and insidious with more prolonged lighter exposures. The process is initiated with alveolar macrophages engulfing the crystals. In response they release cytokines to attract lymphocytes, neutrophils, and fibroblasts\u2014and a familiar story of tissue destruction and laying down of collagen begins. (You might note at this point that engulfing silica in vitro has been shown to damage macrophages,\u00a0causing them to release their intracellular enzymes, which may contribute to the destructive mechanism in vivo.)"}
+{"id": "pulmonary$$$f072a2a0-20f4-4d5a-9f7a-84901c47f894", "contents": "The pattern of collagen deposition is distinct, with silicotic nodules forming with concentric fibers producing a whirled pattern (figure 4.10). These nodules are distributed throughout the lung but are more common in the upper lobes and perihilar area (figure 4.11). They tend to be surrounded by distorted lung tissue that may show emphysematous changes. Ongoing disease coalescence of the nodules produces irregular masses of noncaseating granulomas. This progressive massive fibrosis can be helped with concurrent TB or atypical mycobacterial disease where caseating granulomas may also be present. Likewise silicosis may impair the macrophage response to TB. It causes contraction of the upper lobes and may lead to emphysema\u00a0in the lower lobes, sometimes with large bullous changes. The pathophysiology of silicosis is summarized in figure 4.12."}
+{"id": "pulmonary$$$db3a7449-a665-414c-9338-2d9268f62327", "contents": "After an insidious, asymptomatic beginning, the main symptom of silicosis is dyspnea, with or without cough (cough is likely generated by concurrent smoking). The dyspnea is progressive but other symptoms that occur are often due to secondary, superimposed infection making repeated bacteriological studies important."}
+{"id": "pulmonary$$$c2584430-2397-44fb-b8f1-d1715a340a30", "contents": "The pathophysiology of silicosis is summarized in figure 4.12."}
+{"id": "pulmonary$$$2ab10898-0cbd-4b8b-a680-b16e2a09947a", "contents": "There are a number of pulmonary manifestations arising from exposure to asbestos. Previously used in the construction and manufacturing industries, the occurrence of related illness led to legislation to restrict its use. However, demolition or renovation of asbestos-containing buildings can still lead to air-born asbestos exposure. The pulmonary manifestations include pulmonary fibrosis, bronchogenic carcinoma, pleural effusion, pleural fibrosis, and mesothelioma. We will deal with the pulmonary fibrosis\u00a0here and what is known as asbestosis."}
+{"id": "pulmonary$$$9164de85-0de6-4f9f-a42d-86c789adf3cc", "contents": "The disease course (summarized in figure 4.13) is similar to that described for silicosis.\u00a0Asbestos fibers arrive in the alveoli and macrophages initiate an inflammatory response. Note that the arrival of neutrophilic leukocytes and their release of cytokines and oxygen radicals seem to play a significant role. Short fibers can be phagocytized and removed, but larger fibers persist in the airway and\u00a0perpetuate the inflammatory reaction, promoting fibrosis."}
+{"id": "pulmonary$$$20b818f5-a04d-473e-a4cf-a17b43be300c", "contents": "Histologically, these fibers can been seen as asbestos bodies, or ferruginous bodies, as they are coated with iron-containing protein (figure 4.14)."}
+{"id": "pulmonary$$$7d14e285-f52b-478d-a30d-2ae3074fbc5a", "contents": "Fibrosis ensues, but in contrast to silicosis, asbestos-related fibrosis is nonnodular and mostly involves\u00a0the lower lung fields and frequently includes pleural thickening."}
+{"id": "pulmonary$$$60ca387f-32f1-45fc-9f1e-42ea6f6a1e59", "contents": "The extent of fibrosis is highly variable, from thickened alveolar septum to complete destruction of the alveolar spaces. In the advanced disease honeycomb lung can be observed with CT. Radiography of later-stage disease shows reticular interstitial markings in the lower lung fields (left panel, figure 4.15). Pleural changes are also more common. Rounded atelectasis may occur after a pleural effusion has been reabsorbed and caused a section of the airway to become trapped. A rounded atelectasis is indicated by the arrow in figure 4.15, and care should be taken not to mistake this for a neoplasm. Abestosis\u00a0is a risk factor for the development of\u00a0mesothelioma and should be considered for patients working in \u201cat-risk\u201d\u00a0environments or occupations."}
+{"id": "pulmonary$$$57b439a5-0b86-4157-85f8-33afd87605ff", "contents": "CWP arises after prolonged exposure to coal dust. While drilling through rock the miner may be susceptible to silicosis, but prolonged and heavy exposure to aerosolized carbon (that is not\u00a0usually fibrogenic in lesser exposures) can result in its own distinct condition. Even then it can take ten to twelve years of underground exposure to develop."}
+{"id": "pulmonary$$$830ca7d1-c3ed-4807-978c-783dda3ba844", "contents": "Again we see the process start with phagocytosis of the coal dust by macrophages after the mucocillary escalator is overwhelmed. The macrophages launch their inflammatory process, and tissue damage is caused by the resultant cytokine bloom and oxygen radical and enzyme release. Fibroblasts form reticulin networks, but there is no significant collagen deposition. Aggregates of reticulin fibers, macrophages, and dust form coal macules (figure 4.16). The coal macules appear as black spots in lung sections\u00a0and give rise to the condition\u2019s nickname of \u201cblack lung.\u201d"}
+{"id": "pulmonary$$$486e98a7-1b80-4b9d-8880-2ac7031ec1ac", "contents": "The coal macules are associated with dilation of the respiratory bronchioles that can manifest as focal centrilobar emphysema (figure 4.16). This is referred to as simple CWP, whereas the less common, complicated form involves progressive\u00a0massive fibrosis, usually in the upper lobes, as in silicosis. However, in CWP these lesions are black and relatively homogenous, where as in silicosis they are a conglomeration of intersecting nodules. Figure 4.17\u00a0shows a large black fibrotic lesion destroying the perihilar lung parenchyma."}
+{"id": "pulmonary$$$5e78f8d0-ca02-4c2d-8811-44c02d710618", "contents": "Clinical manifestations are often complicated by concurrent cigarette smoking that may alone explain the frequency of chronic bronchitis in CWP patients. The simple form can be asymptomatic, but the complicated form produces dyspnea and\u00a0signs of respiratory failures, pulmonary hypertension, and cor pulmonale."}
+{"id": "pulmonary$$$18d67239-f8dd-44ba-a54a-bd7b25e8113a", "contents": "The last occupational disorder we will look at is berylliosis, or chronic beryllium disease (CBD), that occurs after exposure to beryllium, a metal used in manufacturing. Here the start to our story is a little different. Beryllium arrives in the airway and there is a hypersensitization of T cells. On subsequent exposures the T cells proliferate\u2014the bronchoalveolar lavage (BAL) fluid of berylliosis patients is rich in sensitized CD4+ cells."}
+{"id": "pulmonary$$$a71e1a5a-4ba3-4599-97ec-a55e8d32aa1e", "contents": "Now we return to our pattern:\u00a0the abundant CD4+ cells release proinflammatory cytokines and granulomatous fibrosis occurs (figure 4.18). The granulomas (figure 4.19) are indistinguishable from those caused by sarcoidosis (which are also caused by CD4+ cells), and many CBD patients may be misdiagnosed as sarcoidosis cases, so appropriate history taking is paramount. Usually CBD involves greater interstitial inflammation, but the most definitive diagnosis comes from the beryllium lymphocyte proliferation test. The test involves exposing lymphocytes from the patient\u2019s blood or BAL fluid to different concentrations of beryllium and assaying their proliferation."}
+{"id": "pulmonary$$$793e99c6-587d-4319-b0be-1b2bd3dbae63", "contents": "Susceptibility to becoming hypersensitized appears to have a significant genetic component. Why the process continues after exposure has stopped is unclear, but possibilities include a fundamental T cell disorder, or the fact that the insoluble beryllium causes apoptosis of macrophages, leading\u00a0them to release a previously phagocytized beryllium load."}
+{"id": "pulmonary$$$be30c734-8a28-4d0d-9a91-b90bf3f61f50", "contents": "As the disease progresses, radiographic findings show that the granuoles can become more organized to produce fibrous nodules that may begin to impact lung function. The immune system involvement can produce hilar lymphadenopathy, and common later signs include interstital fibrosis and pleural thickening."}
+{"id": "pulmonary$$$d740c2b8-6c64-41b1-b581-e7cb38c70dc9", "contents": "So there is a selection of interstitial lung diseases that, while sharing the pathophysiological manifestations of restrictive lung disease, can be distinguished through good history taking or identifying distinct histological features."}
+{"id": "pulmonary$$$99cfc116-0672-4e5d-a968-44f58a5d1a46", "contents": "Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. \u201cChapters 12\u201315.\u201d In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978."}
+{"id": "pulmonary$$$e61c8ba1-f3e6-4190-862a-754314aecd49", "contents": "Acute bronchitis often originates from a migrating upper airway infection, and hence the usual\u00a0candidates for a URI are the pathogens associated with acute bronchitis, and most are viral\u00a0but can include mycoplasma infection. Acute bronchitis can be caused by bacteria, but it is usually an opportunistic secondary infection by resident bacteria taking advantage of a weakened airway. Regardless of the pathogen, let us\u00a0look at the sequence of pathophysiological events in acute bronchitis (figure 3.1)."}
+{"id": "pulmonary$$$21f621b2-758a-44b4-b393-a22b8bf3f997", "contents": "First the bronchial mucus membranes become inflamed. Taking a careful history\u00a0can help you distinguish infectious causes from other instigators of airway inflammation, such as physical or chemical insults or an allergic response.\u00a0The inflammation will initially produce a dry cough, but within two to three\u00a0days bronchial secretions will be established,\u00a0the cough will become productive, and rales can be heard over the site of the infection, which constitutes the clinical diagnosis."}
+{"id": "pulmonary$$$6038d957-953a-4829-b401-c34b0d6d4459", "contents": "The inflamed airways may also become hyperreactive, and this may compound any concurrent allergic response or existing asthma resulting in bronchospasm and wheeze. See figure 3.1 for a summary."}
+{"id": "pulmonary$$$1de3847d-9228-4391-8a1e-61fb82d789a5", "contents": "Penetrating deeper into the airway a pathogen can cause acute infectious bronchiolitis. By far the most common culprit is respiratory syncytial virus (RSV). This is the most common cause of lower airway infection in children under one year old and is estimated to cause more infant deaths than any other pathogen with the exception of malaria. While it can affect adults,\u00a0it usually occurs only in the elderly and immunosuppressed patients."}
+{"id": "pulmonary$$$97215dbd-07f2-492e-a63c-bbcefb6af430", "contents": "Infection starts in the nasopharynx and then progresses to the epithelium of the bronchioles that appears particularly susceptible to RSV infection. Immune cells are called to the area, but the predominant feature of the infection is the sloughing of the bronchiolar epithelium and the appearance of syncytial giant cells in the airway lumen, as seen in the insert of the histology slide in figure 3.2. With anatomically smaller bronchioles, infants are susceptible to this epithelial sludge blocking the airway. The hallmark of the infection reflects the obstructive nature of the disease with hyperinflation."}
+{"id": "pulmonary$$$bd8e5ef5-b7b4-44f2-a158-2026b0e84aba", "contents": "The young patient will likely present with a recent history of cough and hallmarks of shortness of breath such as use of accessory muscles. A scattered wheeze is likely, and in severe cases the child develops an expiratory grunt."}
+{"id": "pulmonary$$$ee55f954-65e9-4b0a-b623-926f13541b01", "contents": "Unresolved the RSV can spread to type 1 and 2 pneumocytes through cell-to-cell transmission. There is a high incidence of apnea associated with RSV infection, presumably due to the virus activating defensive reflexes associated with the larynx."}
+{"id": "pulmonary$$$fba594d9-9875-4ed1-bfdf-0b867f9bafbe", "contents": "Now we will look at the consequences of infection of the terminal airways and what is\u00a0referred to as pneumonia. Although pneumonia can result from infection by one of any number of pathogens, we will first look at a generalized pathophysiological mechanism."}
+{"id": "pulmonary$$$ecb4cda9-73d9-465b-a415-9e0b6f0a0216", "contents": "The pathogen arrives in the alveolar space causing activation of alveolar macrophages and recruitment of neutrophils from the bloodstream. These first responder cells release cytokines to attract more neutrophils and hyperpermeabilize the vasculature. Consequently the airspace becomes congested with pathogens, neutrophils, and exudate and incapable\u00a0of being ventilated (figure 3.3). This produces V/Q mismatching in the effected area and the potential for the establishing of\u00a0intrapulmonary shunts."}
+{"id": "pulmonary$$$86998207-255c-4311-928a-b83dfc103fff", "contents": "The infection may not be retained by the airway structure and can penetrate the pleural space, in which case an effusion is likely."}
+{"id": "pulmonary$$$505daa00-9d90-4d25-8a91-46ff01fb9606", "contents": "The pneumonia-causing pathogen can often be found in blood analysis but the patient remains asymptomatic, but if the infection becomes more established significant signs and symptoms of bacteremia arise."}
+{"id": "pulmonary$$$ac6216e8-fbc9-4370-bd3e-fa476d4658c9", "contents": "An infection may lead to necrotized tissue and formation of an abscess in the lung. The prevalence of this is mostly dependent on the pathogen; for example, a tuberculosis infection is famous for causing walled-off abscesses (or granuloma) that try to contain the mycobacterium. These processes are summarized in figure 3.4."}
+{"id": "pulmonary$$$95934a74-2855-452b-a2a3-432867c22907", "contents": "The causes of pneumonia are many, but so are the ways in which they are classified. Pneumonias are distinguished by:"}
+{"id": "pulmonary$$$438437fe-a071-4091-80c8-08aa789c5d34", "contents": "Typical or atypical pneumonia: We can start at arguably the least clinically helpful classification, the microscopic location. Pneumonias can be either typical or atypical. Typical pneumonium involves the presence of pathogens and immune cells in the airspace, whereas atypical has the pathogen and inflammatory response within the alveolar walls and interstitium (table 3.1). The site is\u00a0usually dictated by the mode of the pathogen, with typical pneumonia being bacterial\u00a0and atypical being caused by virus or mycobacterium that are capable of entering cells."}
+{"id": "pulmonary$$$7477bdfc-7b61-4dd0-8ac9-02a4d17ba85a", "contents": "The two forms can have different signs and symptoms with typical pneumonia having a more rapid onset and atypical being more gradual. Both can be associated with fever, but extrapulmonary features such as headache, joint and muscle pain, and nausea are more characteristic of atypical pneumonia. Because of the location of the pathogen; typical pneumonia is associated with a productive cough, whereas the cough of atypical pneumonia is dry, as summarized in table 3.1."}
+{"id": "pulmonary$$$713d6958-5764-43d4-a923-64346f755f53", "contents": "On x-ray\u00a0the atypical pneumonia shows more diffuse patchy markings associated with the infiltrated interstitium, whereas an x-ray of typical pneumonia\u00a0shows lobar opacities caused by consolidated airspaces (table 3.1)."}
+{"id": "pulmonary$$$5a6ebf85-4f36-4a26-a717-15cc3f95e5f6", "contents": "Table 3.1:\u00a0Comparison of typical and atypical pneumonia."}
+{"id": "pulmonary$$$0f23faf8-323b-4cd4-a086-1dd7be010e57", "contents": "Bronchopneumonia or lobar pneumonia: The next classification is based on the infection\u2019s gross\u00a0location\u2014whether it occurs in a bronchiolocentric pattern to produce bronchopneumonia, or whether the consolidation occurs in continuous airspaces to occupy a lobe to produce lobar pneumonia. Bronchopneumonia will produce distinct areas of infiltrate, and the chest x-ray will reflect this with opacities following the effected airways (table 3.2). Lobar pneumonia will involve dense consolidation outlining the whole lobe and the possibility of air brochograms as air-filled bronchi are surrounded by the infiltrated, more dense alveoli (table 3.2). Bronchopneumonia is usually bilateral, whereas lobar pneumonia tends to be unilateral. However, both can exist in the same patient, as is the case in the example x-ray in table 3.2."}
+{"id": "pulmonary$$$294ad406-c7b4-453e-bd20-61bb68dc8f51", "contents": "Table 3.2:\u00a0Comparison of bronchopneumonia and lobar pneumonia."}
+{"id": "pulmonary$$$f58ce162-f3dc-48b1-b302-4c9c8ca5e5f4", "contents": "Hospital-acquired or community-acquired pneumonia: The last classification relates to the setting in which the infection was acquired, either out in the community or during hospitalization. This classification can provide clues to identifying the pathogen involved. By far the most common cause of community-acquired pneumonia is Streptococcus pneumoniae. Other pathogens can be responsible but tend to affect only those with an underlying condition or characteristic; they are listed in table 3.3\u00a0with the usual instigating issue in parentheses. Legionella-related pneumonia requires exposure to laced water droplets, and mycoplasma infection tends to affect young\u00a0adults living in close quarters, such as military barracks or college dorms. Lastly, and more uncommonly, the pneumonia may be caused by a viral infection."}
+{"id": "pulmonary$$$cccfb2b1-fc1f-4bcd-a743-378ffee040c7", "contents": "Hospital-acquired pneumonia is defined as occurring\u00a0at least three\u00a0days after hospitalization. Unlike community-acquired pneumonias the pathogen is frequently a gram-negative bacteria or staphylococci that normally would not be able to become established in the lung. However, the hospitalized patient\u2019s weakened state of health, state of consciousness, exposure to poor sterile technique for intubation, or antibiotic therapy can provide these listed pathogens an opportunity (table 3.3)."}
+{"id": "pulmonary$$$0eee94c8-8250-407c-8983-8b44a16ee7c7", "contents": "Table 3.3: Comparison of community- and hospital-acquired pneumonias."}
+{"id": "pulmonary$$$44ac7006-eea1-4c80-bcbc-e9f4d17676a1", "contents": "The clinical findings depend on the severity of the infection and underlying cause. Onset can be abrupt or gradual, and is\u00a0often preceded by upper airway symptoms and associated with malaise, fever, or chills. As the infection progresses cough is established and chest pain and dyspnea can develop."}
+{"id": "pulmonary$$$d866b20e-d26c-4af9-8875-a2252d6ed55e", "contents": "As the infection progresses expectoration increases and can be purulent or even blood tinged. Mental confusion can arise particularly in elderly or alcoholic patients. If there is multiple lobe involvement then dyspnea can become severe and cyanosis may arise as intrapulmonary shunts become established and more significant. The hypoxemia can be accompanied by hypocapnia as the patient hyperventilates due to the hypoxic drive to breathe."}
+{"id": "pulmonary$$$716a2dfa-d8d8-4d23-9414-09f8dc804adf", "contents": "Chest exams can have variable findings\u00a0but may include poor respiratory excursion. The consolidated lung fields result in dullness to percussion and a reduction in breath sounds and increase in tactile fremitus. Inspiratory crackles may be heard.\u00a0With continued progression arterial hypoxia worsens and arterial CO2\u00a0falls due to hyperventilation."}
+{"id": "pulmonary$$$c3db54b1-55df-4ecf-ada2-dbb18f992feb", "contents": "Chest x-ray allows the areas of consolidation to be seen, but typically there is no volume loss, which allows pneumonia to be distinguished from atelectasis (although pneumonia and atelectasis can co-occur). Particularly in the case of a typical pneumonia the complete blood count (CBC)\u00a0panel will show an elevated white blood cell count. See table 3.4\u00a0for summary."}
+{"id": "pulmonary$$$426b3711-f442-4cbd-befa-21ac65108c0c", "contents": "Table 3.4: Summary of the clinical findings of pneumonia."}
+{"id": "pulmonary$$$643821d1-ed82-48c7-93e1-ebc504ed1987", "contents": "Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. \u201cChapter 3.\u201d In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978."}
+{"id": "pulmonary$$$85c596d0-c0f5-467f-b2ce-39e772dc507b", "contents": "Table 3.1: Comparison of typical and atypical pneumonia. Includes Case 1 by Bell, D., Hacking, C., et al. from https://doi.org/10.53347/rID-68496\u00a0(CC BY-NC-SA 3.0), Acute pneumonia \u2013 i \u2014 low mag by Nephron from WikimediaCommons (CC BY-SA 3.0), Case 2 by Paks, M., Knipe, H., et al. from https://doi.org/10.53347/rID-27535 (CC BY-NC-SA 3.0), and image 1 by Dr Patsy Lill from University of South Carolina School of Medicine\u2019s\u00a0Microbiologybook.org (Fair use)."}
+{"id": "pulmonary$$$b3d33b15-a961-4fcf-90af-d04139c33ca5", "contents": "Table 3.2: Comparison of bronchopneumonia and lobar pneumonia. Includes Bronchopneumonia by Kindred Grey from Internet archive (CC BY 4.0), Lobar pneumonia by Kindred Grey from Internet archive (CC BY 4.0), X-ray of bronchopneumonia by Franquet T., Chung J.H. from WikimediaCommons (CC BY 4.0), Case 3 by Paks, M., Knipe, H., et al. from https://doi.org/10.53347/rID-26886\u00a0(CC BY-NC-SA 3.0)."}
+{"id": "pulmonary$$$7d48f651-5ec9-4c8c-8c1d-f8ac28654b61", "contents": "As with most URIs the common\u00a0cold is caused by a viral infection, and although there are several different viral candidates for causing a common cold, the pathophysiological mechanism and symptoms are the same regardless of the type. This is because it is the innate immune response, rather than the direct infection, that is responsible for most of the symptoms."}
+{"id": "pulmonary$$$93234398-69a1-4864-9f54-5418cb35f91b", "contents": "Looking at the sequence of events involved in \u201cgetting a cold\u201d\u00a0(figure 2.2), we start with delivery of the pathogen to the upper airway and inoculation. The most common modes of delivery are hand-to-nose or hand-to-mouth contact or inhalation of aerosolized nasal fluid produced from a sneeze of an infected person. The causal virus is rarely found in saliva, so infection is spread from snot not spit."}
+{"id": "pulmonary$$$d37b6aa6-f48f-4625-b3a4-2ecdb13824d4", "contents": "Once in the upper airway, and if the pathogen can breach the innate defenses here (mucus and the mucociliary escalator), the virus attaches to, and then enters, the epithelial cells. In response, the invaded epithelial cells release cytokines to instigate an immune response. The primary cytokine released in this scenario is IL-8, which\u00a0causes the attraction and accumulation of polymorphonuclear cells (PMN)."}
+{"id": "pulmonary$$$c2e4bd97-d89a-432b-bfb7-ebacb05d761c", "contents": "It is the substantial increase in PMN cells that is responsible for most of the symptoms of a common cold\u2014runny nose, postnasal drip, and other signs of epithelial inflammation."}
+{"id": "pulmonary$$$88424554-821d-4fd4-a30b-408bce446a9b", "contents": "By far the most common cause of the common cold is the rhinovirus, followed by coronavirus and influenza, then less frequently by parainfluenza respiratory syncytial virus (RSV), and then rarely by adenovirus or enterovirus (table 2.1)."}
+{"id": "pulmonary$$$3569c1e2-50a7-4653-83e2-246fef266886", "contents": "Table 2.1: The viral pathogens."}
+{"id": "pulmonary$$$e77d6cb6-3b21-4d89-afcf-f5d3ac3b7693", "contents": "Seasonal differences (table 2.1) in the prevalence of these pathogens might help you identify the causal agent, but as the viral infections are self-limiting it is more important to ensure there is no bacterial involvement."}
+{"id": "pulmonary$$$9beb875c-6f9f-4efd-ba79-b48cb3ecb649", "contents": "A viral infection can progress and cause more specific conditions than a cold, and these are identified by their location."}
+{"id": "pulmonary$$$24c1986f-c27f-4396-9450-53a6f5faec95", "contents": "Rhinosinusitis is most commonly caused by a viral infection, and despite popular belief\u00a0is only rarely associated with a concurrent bacterial infection in adults. The lining of the nasal and sinus cavities becomes inflamed, again as a result of the immune response rather than a direct effect of the virus. The congestion can be painful, but symptoms can be treated\u00a0with over-the-counter analgesics. Like the common cold, the condition is self-limiting and normally resolves in seven to ten\u00a0days."}
+{"id": "pulmonary$$$710ca630-de22-4dc6-8c76-46bd170c4ab2", "contents": "When the pharynx is involved the local inflammation will cause the patient to\u00a0present with a sore throat and a hoarse voice. Pharyngitis is most commonly caused by viral infection, but more serious bacterial infections (e.g., Streptococcus) should be considered. The two infection types are easily distinguished with tonsillar exudate and petechial mottling of the soft palate being present in a bacterial infection, but absent in a viral infection. Treatment of viral pharyngitis is limited to symptom relief, and antibiotics should be avoided."}
+{"id": "pulmonary$$$52964135-ef76-4376-b7cf-88a0dbf15328", "contents": "Involvement of the larynx and subglottic airway will produce croup. There are numerous causes of croup\u00a0and subclassifications depending on the region involved. Viral croup, like other forms, involves inflammation of the larynx that causes the airway to narrow. Edematous airway walls form an upper airway obstruction that produces stridor. Stridor is a crow-like airway sound, and the phase of breathing that it appears in can be helpful in determining the site of obstruction. Stridor during inspiration is indicative of airway collapse above the vocal cords (i.e., extrathoracic), and expiratory stridor suggests a tracheal or bronchial obstruction (i.e., intrathoracic). The constriction of the airway can be seen on x-ray when severe and the narrowing produces a characteristic \u201csteeple\u201d\u00a0sign in the trachea (see figure 2.3)."}
+{"id": "pulmonary$$$64087e6b-fc24-4968-804b-febccb8669fb", "contents": "The induction of upper airway infection by bacteria is similar to that by virus with droplet inhalation or hand-to-mouth or nose contact. Cell adherence is usually promoted by bacterial properties, but it is\u00a0bacterial toxins that instigate the signs and symptoms of infection rather than the innate immune system. We will now cover four bacteria that are capable of causing an upper airway infection."}
+{"id": "pulmonary$$$ebfbe95b-bedd-4fac-ac1f-5c74fd78055d", "contents": "The pathogenic mechanisms of Group A Streptococcus are poorly understood\u2014partly because of the numerous and complex ways it interacts with its human host. Its coat protects it from phagocytosis, antibody binding, and opsonization. It is capable of releasing a cocktail of cell-lysing toxins as well as pyrogenic exotoxins that:"}
+{"id": "pulmonary$$$22b5f3a0-0ae4-4e40-ad22-f6114b7ea720", "contents": "In terms of the upper airway it is the leading cause of tonsillopharyngitis in both adults and children. A sore throat may be accompanied by fever, headache, and vomiting. Inflamed tonsils and uvula\u00a0may be coated in exudates, and palatal petechiae (figure 2.4) may be be present as well as\u00a0a scarlatiniform rash. Symptoms resolve in three to five\u00a0days, but antibiotic therapy should be used to reduce the risk of complications that include peritonsillar cellulitis, otitis media, sinusitis, and even acute rheumatic fever."}
+{"id": "pulmonary$$$eb7578ba-a236-4c00-a201-cbae2fe28bd9", "contents": "After inoculation, C. diphtheriae releases diphtheria exotoxin and enters the cell by exploiting a membrane receptor. Once inside, the exotoxin inactivates elongation factor 2, halting protein production and causing cell death. Occurrence of diphtheria is now rare in developed countries because of vaccination programs, but infection produces sore throat, swelling of cervical lymph glands, and low-grade fever. Most cases are tonsillopharyngeal where a pseudomembrane and exudate (figure 2.5) is produced that can spread to other areas. In severe cases the spread can lead to the bull neck of diphtheria (figure 2.5) as swelling and pseudomembranes accumulate and swallowing can become difficult. If the infection becomes systemic, cardiac, neural, and renal issues may arise, including myocarditis, local neuropathies, and in severe cases renal failure."}
+{"id": "pulmonary$$$aeb4da5c-5a33-4f95-b93b-47cae4dd7543", "contents": "After inhalation, B.\u00a0pertussis attaches to airway cells through a variety of adhesion molecules. The organism then releases\u00a0cytotoxins that cause loss of protective respiratory cells and promote microaspiration and a distinct and prolonged cough. Pertussis\u2019s nickname of whooping cough comes from the distinct inspiratory noise. The paroxysmal stage of pertussis (that involving cough) can last between two and ten\u00a0weeks, and this prolongation is likely due to the bacteria penetrating deeper regions of the lung (the cytotoxins have been found in alveolar macrophages). The disease can be life threatening to infants, but widespread vaccinations started in the forties dramatically reduced its incidence."}
+{"id": "pulmonary$$$92187996-cc71-4081-aaa9-5aeafdc2f8e2", "contents": "The outer coat of the H. influenzae contains several proteins that attach to upper airway cells and specifically promote pharyngeal and the middle ear\u00a0colonization. The outer coat also acts as an endotoxin and elicits a potent inflammatory response to produce the symptoms of the infection. Prior to routine vaccination, vascular invasion by the pathogen could produce metastatic foci including meningitis, septic arthritis, osteomyelitis, and cellulitis. Today, while upper airway infection can lead to pneumonia, the incidence of bacteremia is low."}
+{"id": "pulmonary$$$c9d5fd5e-55d3-44b1-94eb-4c180bbf3596", "contents": "Thomas, Micah, and Paul A. Bomar. Upper Respiratory Tract Infection. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK532961, CC BY 4.0."}
+{"id": "pulmonary$$$fc7ec5d0-c678-4556-971c-1fdf56177f67", "contents": "There are numerous underlying mechanisms of asthma (figure 1.1), and they may not be exclusive or independent within the same patient."}
+{"id": "pulmonary$$$5257cee7-51ab-414b-b5ce-f379a71ee95f", "contents": "We will also look at how exercise and certain pharmacological agents can produce asthma."}
+{"id": "pulmonary$$$fbf759df-934f-4ba5-9987-deb818c57280", "contents": "Allergenic asthma: Most allergic asthma is caused by the presence of an excessive amount of IgE (the hallmark antibody of an allergy). Formation of an immune complex between the antigen and the overexpressed IgE results in binding to surface receptors on mast cells and basophilic granulocytes,\u00a0of which there are plenty in the lung. The IgE receptor binding results in the release of a cocktail of proinflammatory and airway-active substances. Some of these, including histamine and cytokines that attract eosinophils and neutrophils, are stored in vesicles of mast cells shown in figure 1.2. Others are produced on demand, including leukotrienes, and are derivatives of arachidonic acid (we will return to this later)."}
+{"id": "pulmonary$$$9403cfd2-ebde-42f9-a224-89717149c0c8", "contents": "The results of this cocktail\u2019s release are the hallmarks of asthma:"}
+{"id": "pulmonary$$$63c4f3fd-ee46-4636-86bd-254ef135edf6", "contents": "The timeline\u00a0from the exposure to the antigen to asthmatic response is not straightforward. A response may occur within minutes (\u201cearly response\u201d), or\u00a0hours later (\u201clate response\u201d). Some patients show only an early response, some only a late one, and some show both in a \u201cdual\u201d\u00a0response. The late response may correspond to the arrival of leucocytes in response to the initial release of cytokines. It may also be due to a\u00a0mild stimulus arriving later in an airway that was sensitized earlier."}
+{"id": "pulmonary$$$5ae6e870-08ae-4364-8f65-65722fd3bbf1", "contents": "Cholinergic asthma:\u00a0Because\u00a0it is open to the external environment, the airway has defensive, vagal reflexes (figure 1.3). An inappropriate exaggeration of some of these may lead to asthma. The basic reflex arch that ends with a cholinergic response begins with stimulation of airway irritant receptors in the epithelium. An afferent signal to the brainstem instigates an efferent signal to cause airway smooth muscle contraction and mucus secretion by glandular cells. The reflex also stimulates mast cells to release their cocktail, which includes histamine."}
+{"id": "pulmonary$$$302d3114-64ae-41b8-8183-aca19772daa3", "contents": "The released histamine stimulates the airway receptors, setting up the potential for a positive feedback loop and perpetuating the cycle of bronchoconstriction and secretion. The histamine also\u00a0stimulates bronchoconstriction through its direct action on the smooth muscle as well as sensitizing the smooth muscle to further vagal stimulation. These processes are summarized in figure 1.3."}
+{"id": "pulmonary$$$3fd37337-9e1e-405b-a12d-12309bb29ada", "contents": "The cholinergic response may help produce an asthmatic response to another stimulus that normally would not have produced\u00a0one\u00a0(i.e., it may play a part in the hypersensitivity of the asthmatic airways). Likewise, the presence of an infection, particularly a viral infection,\u00a0may place the airway in a proinflammatory state."}
+{"id": "pulmonary$$$8a63cccf-ca7b-410b-a20c-45c4d45b3743", "contents": "Neural airway control may also contribute to the high prevalence of nocturnal asthma, as during rest when the airways are predominantly under parasympathetic control. But other factors\u00a0(summarized in figure 1.4) may contribute:"}
+{"id": "pulmonary$$$7fb4e653-c7a8-4681-b61d-029242e94098", "contents": "Exercise-induced asthma: Although exercise is associated with increased airway caliber, it can also induce asthma. Increased airway flow to meet the increased metabolic demand of exercise results in loss of fluid and heat from airway surfaces. This leaves the peribronchial fluid in a hypertonic state and causes excitation of the irritant airway receptors, which\u00a0leads to release of the mast cells\u2019 cocktail."}
+{"id": "pulmonary$$$65f28ac8-49a8-498c-b6bb-2bfa734c1f6e", "contents": "Exercise-induced asthma is more prevalent in cold (i.e. dry air) where water loss will be higher, so occurs more in sports such as cross-country skiing than swimming in a warm humid environment. Bronchoconstriction usually occurs when exercise stops\u2014when the protective effect of sympathetic activity to the airway smooth muscles ceases."}
+{"id": "pulmonary$$$a09ded15-2746-415c-a59c-bbbda3c9bb0e", "contents": "Drug-induced asthma: There are several pharmaceutical and food products that can promote asthma, including tartrazine (a yellow food coloring) and sulfides used as food preservatives. Additionally,\u00a010 to 20 percent\u00a0of asthmatics are sensitive to aspirin."}
+{"id": "pulmonary$$$210444a3-7639-4c7d-a3c6-2ccacaada374", "contents": "Recall that some of the on-demand components of the mast cell\u2019s cocktail were derived from arachidonic acid.\u00a0There are two pertinent pathways in which arachidonic acid is used:\u00a0the lipoxygenase pathway and the cyclooxygenase pathway (figure 1.5). The first leads to the production of leukotrienes, which are potent bronchoconstrictors. The second leads to the production of prostaglandins and thromboxane. Normally the distribution of arachidonic acid down these pathways is balanced to meet demand. However, NSAIDS such as aspirin are COX 2 inhibitors and block the cyclooxygenase route, leaving more substrate for the lipoxygenase pathway and production of leukotrienes (figure 1.5) with their bronchoconstrictive effect."}
+{"id": "pulmonary$$$6455b9cb-3f00-467a-9e70-4d28360886e5", "contents": "Environmental/occupational asthma: As the airway is open to the environment, it is susceptible to inhaled substances that can cause sensitization; there are over two hundred\u00a0substances known to cause asthma, both organic and inorganic. Some common ones are listed below."}
+{"id": "pulmonary$$$047df8a3-3958-4a52-a01f-7b69cc7475ff", "contents": "Table 1.1: Some of the most common environmental causes of asthma. Taking a\u00a0pulmonary history should include asking about potential environmental exposures."}
+{"id": "pulmonary$$$5b3bd0da-eb35-4624-b0a3-d90f9074bb62", "contents": "Determining whether airway hypersensitivity is due to environmental factors is complicated by\u00a0widely varying latency periods. Short latency periods can be as brief as twenty-four\u00a0hours and are associated with vapor or smoke exposure that does not cause an immunological response. Longer latency periods that may last years are more commonly associated with an immunological response to large particles that act like antigens."}
+{"id": "pulmonary$$$e0159ef2-2eec-4bae-836c-8c9b1b80a7dc", "contents": "The situation is further confused by occupation-related responses, which often cause the airway to become more sensitive to some of the other causes of asthma covered here. This\u00a0makes\u00a0the role of an environmental factor more difficult to determine."}
+{"id": "pulmonary$$$097ec5df-dd0e-408e-a729-5850a903e263", "contents": "With numerous and maybe concurrent mechanisms, what does asthma look like in the airway?\u00a0The normal lumen of the airway has a relatively lower resistance, as depicted in panel A of figure 1.6, but in mild asthma the lumen is narrowed (thereby raising resistance to airflow) through swelling of the airway wall, contraction of airway smooth muscle, and blockage (or plugging) of the airway by increased mucus secretion (figure 1.6B). This worsens in more severe asthma until the lumen can be extremely narrow (figure 1.6C) or even completely blocked."}
+{"id": "pulmonary$$$c47f79de-4ee0-4513-8306-9f155e88c752", "contents": "Other characteristics of asthma include the presence of eosinophillic that infiltrate into the airway walls. The eosinophil enzymes also leave a telltale sign: Charcot\u2013Leyden crystals, as shown in the circled area\u00a0of figure 1.7A."}
+{"id": "pulmonary$$$65a1b979-d155-41e2-9cca-a8018cbe9cb8", "contents": "The sputum of the asthmatic may also contain Curshman\u2019s spirals (figure 1.7B), which\u00a0are casts of small bronchioles consisting of mucus and shed epithelial cells. However, Curshman\u2019s spirals are not exclusive to asthma."}
+{"id": "pulmonary$$$92854127-014f-41fd-a517-c1814b0aafbb", "contents": "With persistent asthma the airway undergoes remodeling (figure 1.8), with thickening of the airway wall and basement membrane, enlarged submucosal glands, and hypertrophy and hyperplasia of airway smooth muscle."}
+{"id": "pulmonary$$$4580d001-127d-4038-bcb0-87a588b04fb0", "contents": "One useful diagnostic element\u00a0of asthma is its episodic or acute behavior. However, as patients may\u00a0be asymptomatic between attacks, the severity of asthma can be difficult to determine without performing bronchial challenge tests."}
+{"id": "pulmonary$$$9749b941-584e-42d8-944a-ef58e9aff4ed", "contents": "The characteristic signs of asthma progress and vary with declining FEV1 (summarized in figure 1.9). Most attacks start with mild wheezing and coughing, which progress with the severity of attack. The location and form of sensations vary between patients, but most asthmatics complain of chest tightness. This sensation is more commonly reported by asthmatics than other pulmonary patients, so it is a useful diagnostic sign."}
+{"id": "pulmonary$$$48ac981b-61b0-4a77-b2f4-33fd1bcebd77", "contents": "As airway resistance increases, the accessory muscles are deployed to maintain sufficient airflow through the narrowing airways, and the patient experiences an increased effort to breathe.\u00a0Increased expiratory efforts produce dynamic airway collapse and lead to hyperinflation. Further decreases in airway caliber result in insufficient alveolar ventilation and deranged blood gases. The sensation reported at this point is air hunger.\u00a0Once the patient is severely\u00a0bronchoconstricted, delivery of inhaled therapies is much more difficult, and mechanical ventilation to support the respiratory muscles becomes complicated.\u00a0Other signs present during a severe attack are raised heart (tachycardia) and breathing\u00a0(tachypnea) rates as well as a paradoxical pulse (i.e., a rise in blood pressure during expiration)."}
+{"id": "pulmonary$$$663afe60-899e-40ce-a85c-3fca6c6c6eb1", "contents": "The typical chest x-ray of an\u00a0asthmatic (figure 1.10) shows hyperlucent lung fields, evidence of hyperinflation and peribronchial infiltrate, and perhaps areas of atelectasis. However, the chest x-ray is not particularly effective at distinguishing asthma from some other obstructive disorders."}
+{"id": "pulmonary$$$2c66bf8c-8e8b-48d9-b6b6-1f58a75dc8bf", "contents": "Although chronic bronchitis and emphysema have different underlying pathologies, they frequently have the same root\u00a0cause and are often found together in a patient. In brief, chronic bronchitis is associated with an increase in mucus production, while emphysema involves disruption of the lung structure."}
+{"id": "pulmonary$$$a71a0984-5f66-4bcf-b5f3-2dbcfcdd20dd", "contents": "The relative role of chronic bronchitis in COPD has diminished since the Clean Air Act reduced atmospheric sulphur dioxide, but with 90 percent\u00a0of COPD caused by cigarette smoking there is still plenty of bronchitis and emphysema to treat\u2014at enormous cost to the health system from\u00a0over eight\u00a0million hospitalizations a year that are\u00a0mostly paid for by Medicare. The COPD patient tends to be older and\u00a0poorer and will likely have comorbidities, the most common of which is hypertension. What is perhaps more disturbing is that of the most common causes of death, COPD is the only one whose incidence continues to rise."}
+{"id": "pulmonary$$$5388bea8-f0ed-4ba6-ae0f-cdc4a122d9af", "contents": "We will now look at the underlying mechanisms of COPD. Despite the fact it is usually composed of some elements of both chronic bronchitis and\u00a0emphysema, we will deal with each separately for the sake of simplicity."}
+{"id": "pulmonary$$$c7b77aef-bf23-437e-9c38-10f3e5de0d04", "contents": "Chronic bronchitis is clinically defined as a persistent and productive cough that lasts for at least three\u00a0months per\u00a0year for two consecutive years."}
+{"id": "pulmonary$$$416a3eeb-8aba-4a5b-b5d7-0ca3490bffeb", "contents": "Chronic bronchitis arises from\u00a0chronic exposure to bronchial irritants, the most common of which is tobacco smoke. These irritants initiate the release of cytokines from airway epithelial cells and macrophages that result in a cascade of responses (summarized in figure 1.11)."}
+{"id": "pulmonary$$$ba022a1a-fb87-493e-bdf6-facc52b46271", "contents": "Neutrophils, lymphocytes, and macrophages are attracted to the irritated airway, and their presence is maintained through increased expression of cell adhesion molecules on the airway walls. These immune cells lead to acute airway wall inflammation that narrows the airway, and if chronic, can lead to tissue damage. The cytokines released by these cells also sensitize airway irritant receptors, which exacerbates the response to future irritant exposure."}
+{"id": "pulmonary$$$b5129469-dd40-4ea7-9332-cf7ed356411a", "contents": "Mucus production increases, and the glands themselves may also release cytokines that further exacerbate the inflammatory response. The mucus also contributes to airway narrowing, and mucus plugs may form that completely block bronchioles."}
+{"id": "pulmonary$$$25da24f2-ae7b-400c-9da9-c66259b49f04", "contents": "Mesenchymal cells transition into fibroblasts as part of the inflammatory response, and their chronic presence leads to the deposition of fibrotic tissue."}
+{"id": "pulmonary$$$4f1e1d33-20b5-47bb-a322-14f0cda5f106", "contents": "Collectively these responses to the irritants result in a narrowed airway that is (1) hypersensitive, (2) fibrosed, and (3) blocked by excessive secretions."}
+{"id": "pulmonary$$$54cd4ac6-6907-4268-9406-ca5c0f5c7c9d", "contents": "Continued exposure to irritants leads to other chronic changes beyond\u00a0fibrosis. With excessive stimulation, the size and number of mucus glands increases. The size of mucosal glands is used as a diagnostic test, and the Reid index describes what proportion of the submucosa is spanned by a gland\u2014in the normal airway a normal gland spans less than 40 percent\u00a0of the submucosa\u2019s depth, but in chronic bronchitis this exceeds 50 percent\u00a0(figure 1.12)."}
+{"id": "pulmonary$$$ad01645b-127f-4836-9e86-73e40913b9dd", "contents": "In conjunction with an increased mucus production capacity, the airway has a reduced mucus clearance capability with airway remodeling, including squamous metaplasia replacing normal ciliated columnar epithelium (figure 1.13). The mucus escalator is also\u00a0compromised by a decline in function of the remaining cilia with exposure to cigarette smoke."}
+{"id": "pulmonary$$$d7cd9b07-d0a5-4899-bcc0-30d05cabb18e", "contents": "These changes result in an airway that produces more mucus and is less capable of removing it. The static mucus not only causes airway plugging, but can also promote infections that lead to episodic and characteristic exacerbation of COPD symptoms."}
+{"id": "pulmonary$$$d0fdcfa1-6dc9-494a-b681-9e5ac098fbed", "contents": "The signs and symptoms of chronic bronchitis depend on the level of airway obstruction and the consequent decline in lung function (summarized in figure 1.14)."}
+{"id": "pulmonary$$$2954d908-e93e-4674-b0c9-0975d6cf9fb2", "contents": "As with many pulmonary diseases, the onset can be insidious. Small airway damage may be present but undetectable with normal spirometry, while the patient becomes accustomed to and tolerates a persistent productive cough. However, with continued irritant exposure, this initial simple bronchitis progresses."}
+{"id": "pulmonary$$$08a74477-a8f1-4b48-ab90-84cbe7259665", "contents": "Secretions continue to worsen and peribronchiolar fibrosis marks the onset of obstructive bronchitis that is reflected by significant expiratory airflow limitation. At this point the patient may have tolerated years of productive cough\u00a0and experienced frequent chest infections related to poor mucus clearance. COPDers are particularly susceptible to Haemophilus influenza and Streptococcus pneumoniae. The sputum is abundant and capable of plugging significant numbers of airways and may be blood tinged; COPD is the most common cause of hemoptysis. Airways may demonstrate hyperreactivity and mimic\u00a0an asthmatic response."}
+{"id": "pulmonary$$$27931927-1824-4817-a27b-c32536ca3786", "contents": "The onset of dyspnea is insidious and is usually first experienced during exertion\u2014leading the patient to avoid exercise, which in turn leads to deconditioning and a worsening of the symptom. Lung sounds include wheezes and rales, the rales often clearing after cough."}
+{"id": "pulmonary$$$2d83191b-b693-4cca-b87f-54e3eaed3a93", "contents": "With worsening airway flow limitation expiration becomes prolonged and may be incomplete due to airway collapse that leads to characteristic hyperinflation."}
+{"id": "pulmonary$$$0fa93e3c-8ee7-41c9-9d8d-e1eb7473e407", "contents": "Mucus plugging and airway closure leads to areas of V/Q abnormalities through the lung, and localized areas of hypoxia can lead to pulmonary vasoconstriction. When significant regions of the lung are vasoconstricted, pulmonary vascular resistance can rise enough to induce right-sided heart failure."}
+{"id": "pulmonary$$$e05298ae-d73f-4d8e-ac5c-1a8da3dd5ecf", "contents": "With continued progression of the disease, blood gases become deranged as insufficient alveolar ventilation is achieved. As the disease approaches its end stage, the patient experiences dyspnea at rest until respiratory failure occurs and the patient is hypoxemic and hypercarbic."}
+{"id": "pulmonary$$$3f0a580f-86e2-435d-b0e4-caa5108fb91d", "contents": "Emphysema, a possible second component to COPD, involves permanent enlargement of airspaces distal to the terminal bronchioles and destruction of alveolar walls, as is evident in figure 1.15."}
+{"id": "pulmonary$$$92d7a511-da4d-461c-abdb-666c0aea2745", "contents": "The pattern of airspace destruction varies with underlying cause and revolves around the acinus (figure 1.16), the functional unit of the lung comprised of the terminal airways and the alveoli that collectively make up the respiratory zone of the lung. In its broadest classification, emphysema can take on either a centriacinar or panacinar distribution (figure 1.16). In centriacinar emphysema, the respiratory duct is affected while the distal alveoli are mostly unaffected. This is more commonly found in the upper lung fields and associated with smoking and the concurrent presence of chronic bronchitis."}
+{"id": "pulmonary$$$693063c9-85f7-4633-8cb5-7d1b00c1cbcf", "contents": "This pathology slide in figure 1.15\u00a0illustrates this pattern of tissue destruction with isolated areas of damage, surrounded by relatively normal alveolar structure."}
+{"id": "pulmonary$$$a390d983-31fe-4f9e-a25a-8c31c79eb96b", "contents": "Panacinar emphysema, as the name suggests, involves the entire acinus (figure 1.16), and the alveolar structure is more involved creating large airspaces that occur throughout the lung. This is evident in the pathology slide in figure 1.16\u00a0that shows much more uniform damage than the centriacinar example. Panacinar emphysema is much less common and is the pattern of destruction associated with alpha-1 antitrypsin deficiency, which we will deal with in a moment."}
+{"id": "pulmonary$$$e21ed96a-346e-493e-986c-6f00e6c6eb04", "contents": "So having seen the morphology of emphysema, we will look at how this damage occurs."}
+{"id": "pulmonary$$$b097a932-7fa1-4947-8e11-bafa3186560d", "contents": "The normal structure of alveoli and respiratory ducts consists of type 1 and type 2 pneumocytes with elastic fibers that contribute to the structure\u2019s mechanical behavior. Emphysema involves the loss of these parenchymal fibers."}
+{"id": "pulmonary$$$0fa0b53b-3f87-4efd-b6a0-387c8245a5ae", "contents": "The presence of irritants, such as cigarette smoke, causes oxidization and the dysfunction of antiprotease enzymes. Without their inhibitory action, the activity of proteases increases and causes the destruction of local tissue. One of these proteases is elastase, whose elevated activity leads to irreparable loss of parenchymal fibers."}
+{"id": "pulmonary$$$459fd924-7a3d-4a28-81ac-df7382c9d225", "contents": "Elastase is also released by neutrophils and macrophages that arrive in response to the inflammatory cascade caused by the inhaled smoke. This causes further destruction of elastin fibers."}
+{"id": "pulmonary$$$dc111024-3189-4be2-ad9d-918c626fa685", "contents": "The pathogenesis of emphysema (figure 1.17) might be summarized as an imbalance between the activities of antiproteases and proteases. Antiproteases are suppressed, and proteases are elevated."}
+{"id": "pulmonary$$$881ad255-a783-48fa-994c-2231712d0f30", "contents": "The emphysema in about 1 percent\u00a0of COPD patients is caused by a genetic lack of alpha-1 anti-trypsin. Even without tobacco use, these patients have an antiprotease/protease imbalance that results in loss of elastin and collagen and produces the panacinar emphysema shown previously (figure 1.16). If an alpha1-anti-trypsin patient does smoke, this imbalance is worsened and emphysema may develop by their late twenties."}
+{"id": "pulmonary$$$0e44cc30-7e48-4ce3-b0b4-d2e00966239a", "contents": "The loss of the elastic tissue and alveolar structure produces several pathophysiological changes in lung mechanics and function that result in typical clinical signs."}
+{"id": "pulmonary$$$7d8c96ce-9924-4387-94a1-80d055ee2d40", "contents": "Lung recoil is the opposing force to the chest wall\u2019s tendency to spring outward. The loss of elastin reduces lung recoil and the chest wall can move outward, producing a characteristic \u201cbarrel-chest\u201d\u00a0(figure 1.18)."}
+{"id": "pulmonary$$$87a017cc-f379-4643-98f9-aa8f53dbf94b", "contents": "The lack of recoil also means that passive expiration\u00a0is ineffective and active expiration must\u00a0be employed. The positive pleural pressure associated with active expiration enhances dynamic airway collapse that leads to gas trapping and characteristic hyperinflation (figure 1.18). To prevent this, the emphysema patient may adopt pursed lip breathing to maintain airway pressure during expiration that props open the airways."}
+{"id": "pulmonary$$$5742c7ee-8ee9-444a-9662-df0710c7f307", "contents": "The hyperinflation and nonuniform tissue damage can lead to a heterogenous distribution of ventilation and V/Q abnormalities that diminish gas exchange. Gas exchange will also be diminished by the enlargement of airspaces, reducing available surface area (figure 1.18)."}
+{"id": "pulmonary$$$871edbd3-de1f-4969-ac90-c77d04e4fc7d", "contents": "The deterioration of gas exchange and lung mechanics worsens as more lung becomes involved, and the stage of the disease, and any concurrent chronic bronchitis, is classified by the level of airway flow limitation\u00a0(e.g.,\u00a0FEV1/FVC)."}
+{"id": "pulmonary$$$048065e5-22d3-4ca8-acae-021631ba02ca", "contents": "It might also be worth noting here that COPD can produce or be associated with a number of comorbidities;\u00a0we have already mentioned hypertension, but pulmonary artery disease, coronary heart disease, heart failure, lung cancer, and malnutrition may\u00a0contribute to a low quality of life that is typically associated with COPD. This in\u00a0turn may contribute to the high incidence of anxiety disorders and depression experienced by COPD patients."}
+{"id": "pulmonary$$$446ba93b-2d1f-45e0-9927-2200ddcc767c", "contents": "Cystic fibrosis (CF) is an inherited disorder that affects the exocrine glands of not only the lungs, but also the pancreas, intestines, and bile ducts. We will focus only on the pulmonary aspects here and see how CF produces an obstructive lung disease."}
+{"id": "pulmonary$$$cc3aa53a-178f-4cde-88eb-5fa08e0edb7e", "contents": "Cystic fibrosis affects the composition of the fluid lining the airways. Changes in this fluid lead to serious sequelae that dramatically shorten life expectancy. Even with modern therapy, many CF patients only live until their thirties\u00a0or early forties, and some still die in infancy."}
+{"id": "pulmonary$$$fe7d98ff-0733-4afe-8ed2-012c4841b697", "contents": "There are two hypotheses about the pathophysiological mechanism of CF:\u00a0the low volume and the high salt. We will focus only on the low volume hypothesis as there is increasing evidence to support this and emerging evidence against the high salt hypothesis."}
+{"id": "pulmonary$$$436e0f88-184e-4ef8-83a7-8ff24e16d8aa", "contents": "Control of the airway fluid relies on the action of ion channels in the apical membranes of epithelial cells, and there are two channels to focus on:\u00a0CFTR and ENaC. The CFTR channels let chloride out of the cell, while the ENaC lets sodium in (top panel, figure 1.19)."}
+{"id": "pulmonary$$$92c3a7db-46c2-4254-a908-437e66526269", "contents": "This exchange helps maintain a healthy fluid layer in the airway, but fails in CF because of a nonfunctioning CFTR channel (right\u00a0panel, figure 1.19)."}
+{"id": "pulmonary$$$db961fb6-7ee8-42ad-9b6a-50252109c9f1", "contents": "There are numerous mutations that are known to produce a dysfunctional CFTR channel, but 70 percent\u00a0of CF cases are due to the delta-F-508 mutation (so named as the mutation leads to a deletion of phenylalanine at position 508 of the CFTR protein). This is a Mendelian recessive trait, and CF occurrence is 1 in 2,500 live births."}
+{"id": "pulmonary$$$db063a96-38f8-483f-b708-339a80edfada", "contents": "So what are the consequences of CFTR dysfunction? Chloride ends up being trapped inside the cell (bottom panel, figure 1.19), and this leads to a greater influx of sodium through the ENaC down its electrochemical gradient, leaving a higher concentration of salt inside the cells that pulls water in from the airway lumen. The low fluid volume in the airway results in:"}
+{"id": "pulmonary$$$a720ab5f-669c-4f95-9082-c5872f7f154a", "contents": "This combination severely impacts mucus clearance (thicker, heavier mucus with compromised cillary escalator). The defective CFTR channel therefore results in mucus retention and airway obstruction. This in turn leads to reduced alveolar ventilation and repeated infections. The two most common culprits for infection in CF are Staphylococcus aureus and Pseudomonsa aeruginosa. Normal functional CFTR appears to suppress P. aeruginosa, perhaps explaining its prevalence in cystic fibrosis where it can be found in the sputum of almost all CF patients."}
+{"id": "pulmonary$$$abc7971b-13c4-4067-9a5a-7665cfa7f8e2", "contents": "The consequences of repeated infection are a mixture of serious conditions and pathologies including atelectasis, pneumonia, bronchiectasis, and other structural abnormalities of the airways (figure 1.20)."}
+{"id": "pulmonary$$$0d167435-239a-41d7-9361-89ba1424b20c", "contents": "The findings of CF obviously include the results of other effected organs, such as the pancreas. But nowadays these are more easily addressed, and it is pulmonary involvement that still proves critical. The onset of pulmonary involvement is variable and may be weeks or years after birth."}
+{"id": "pulmonary$$$1dd450c4-c78b-4e97-aae4-77b0aeec4455", "contents": "Findings progress with progressive airway damage (figure 1.21), but start with cough that may be dry at first but transitions to productive to expel the copious, viscous mucus. With poor mucus clearance, the patient experiences repeated infections that exacerbate symptoms at each stage of the disease."}
+{"id": "pulmonary$$$6d6d09c5-8305-4eb8-9cb4-2713e9900058", "contents": "CF patients usually have an abnormal sinus x-ray and evidence of chronic sinusitis as well as a high occurrence of nasal polyps."}
+{"id": "pulmonary$$$8f15251e-c619-47d8-b829-86276075121b", "contents": "With increasing and irreversible airway damage, the patients begins to experience dyspnea, and the damage may lead to hemoptysis, spontaneous pneumothorax, and a barrel chested appearance.\u00a0Signs of prolonged pulmonary dysfunction appear as the disease progresses, such as finger clubbing, cyanosis, and cor pulmonale (right-sided heart failure caused by lung disease).\u00a0As the patient approaches respiratory failure the accessory muscles are deployed. Patients succumb to the respiratory failure or an overwhelming infection."}
+{"id": "pulmonary$$$65d7b0a8-11a4-4885-af6f-25d2bf1e9767", "contents": "Because\u00a0CF also affects sweat gland function, the sweat test remains a standard diagnostic with a chloride level greater than 60 mEq/L being indicative of CF. This test is more reliable in children than adults, who may have developed other conditions that affect the composition of sweat."}
+{"id": "pulmonary$$$9f26e820-60de-49c3-bf18-3b819e96857d", "contents": "Chest x-rays show (figure 1.22) signs of hyperinflation associated with gas trapping and the hallmarks of any other complications that the CF has induced. These are viewed more clearly with the common use of high-resolution computed tomography (HRCT)(figure 1.23) to determine the type and extent of damage that may include bronchiectasis and mucus impactions."}
+{"id": "pulmonary$$$b23a55bf-50a0-48a9-930e-2c99087daa92", "contents": "Spirometry detects the airway obstruction and hyperinflation that produce a low vital capacity and high residual volume."}
+{"id": "pulmonary$$$63e29543-59b0-4f8e-a93b-d4dd2a24df97", "contents": "This section will address bronchiectasis, a form of airway obstruction that is often a manifestation of chronic airway inflammation. Bronchiectasis involves a permanent dilation of a bronchi or bronchiole\u2014think of bronchiectasis as the airway equivalent of an aneurysm."}
+{"id": "pulmonary$$$5087adaa-b775-4acc-b424-fac0e5a412c4", "contents": "A bronchiectasis starts with a section of airway wall becoming inflamed (figure 1.24), disrupting and weakening its structure. This weakening leads to a permanent dilation of the airway that impairs the clearance of secretion. Because the airway is inflamed, the amount of secretion may be significant and it begins to accumulate."}
+{"id": "pulmonary$$$72b427b6-7cf6-41a2-a298-ee8f69387133", "contents": "The stagnant secretion promotes a secondary infection that leads to further inflammation, wall disruption, and dilation. Thus the airway has entered a vicious cycle that causes the dilation and retention of mucus to perpetuate (figure 1.24)."}
+{"id": "pulmonary$$$3b0e3f15-bb01-4e8b-9eb4-5a773362a5ae", "contents": "The establishing of a bronchiectasis has an initial\u00a0phase leading to persistent inflammation, desquamation (which worsens the mucus clearance), and the ulceration. In what is probably a familiar story, the continued inflammation leads to fibrosis in the chronic phase of development, and this can lead to airway destruction and perhaps the condition of bronchiolitis obliterans."}
+{"id": "pulmonary$$$f428b662-610b-4f62-8621-6d3f4a454180", "contents": "There are some common culprits for initiating bronchiectasis (figure 1.25). Most start with either a decline in mucus clearance and the associated inflammation or damage to the airway wall."}
+{"id": "pulmonary$$$1eadf609-f7b9-4fd9-a3d2-599321b3bb81", "contents": "About 50 percent\u00a0of bronchiectasis cases are associated with cystic fibrosis where the genetic condition causes production of copious, thick mucus that is difficult to clear and often results in infection (commonly caused by Staphylococcus aureus)."}
+{"id": "pulmonary$$$21b1bf7f-bbf0-4bb6-92c1-c5a3b2272546", "contents": "Conditions causing cillary dyskinesia, as seen in Kartagener\u2019s syndrome, also disrupt\u00a0the mucocillary escalator."}
+{"id": "pulmonary$$$81114ed9-a389-4422-9698-34946e4a2b4c", "contents": "Another common cause of bronchiectasis is an allergy to Aspergillus fumigatus, a common fungus. In hypersensitive or immune-compromised individuals, chronic exposure can lead to allergic bronchopulmonary aspiragillosis."}
+{"id": "pulmonary$$$d35443aa-6694-4620-9ecf-6c8d4a9eb6c4", "contents": "Bronchiectasis can be initiated in the vicinity of tuberculosis or other necrotizing infections that damage and weaken airway walls."}
+{"id": "pulmonary$$$952f8828-37b3-4834-a902-a380893228f9", "contents": "Obstruction of the bronchioles or bronchi by inhaled foreign objects, tumors, or compacted mucus can also initiate bronchiectasis through local inflammation and by preventing mucus clearance. The dilation of the airway can be worsened further by distal atelectasis that produces a negative pressure around the affected airway."}
+{"id": "pulmonary$$$ac939b98-dff5-4043-9842-1069b2af1ff1", "contents": "As you might have gather by now, repeated local infection or inflammation has the potential to initiate bronchiectasis, so it is perhaps not surprising that with the advent of high resolution computed tomography (CT) imaging, bronchiectasis has also been found\u00a0in association with AIDS, transplant rejection, and rheumatoid lung disease."}
+{"id": "pulmonary$$$04f9aefe-9a2e-4d2a-87d6-5f8b1b94232f", "contents": "The outcomes of bronchiectasis\u00a0are seen in the\u00a0histology slide in figure 1.26, with the affected airway lumen filled with mucus and pus, and the airway walls exhibiting fibroglandular tissue and infiltration by inflammatory cells (outer red circle)."}
+{"id": "pulmonary$$$aa4b374a-8833-4dd4-8069-844da9e21e7a", "contents": "The gross view (right panel, figure 1.26) shows severely dilated bronchi and noticeable\u00a0thickening of their walls."}
+{"id": "pulmonary$$$ee2a56dd-bf2a-4bec-846d-e142501aa5a8", "contents": "There are different forms of bronchiectasis; these are classified by their shape (figure 1.27)."}
+{"id": "pulmonary$$$6fbaaa0c-eb4e-4a4f-af24-e98089ffce9c", "contents": "A bronchiectasis can be cylindrical, varicose (also known as fusiform), or cystic (also known as saccular). The\u00a0shape is relevant to their effect on the efficacy of coughing; cylindrical form has\u00a0very little effect on cough\u2019s ability to clear mucus, whereas varicose and cystic forms tend to disproportionately collapse during cough and reduce its effectiveness at moving mucus up the airway."}
+{"id": "pulmonary$$$9b95f1a0-8db6-4189-993e-9db465dcd585", "contents": "As shown\u00a0in figure 1.28 an x-ray shows the presence of bronchiectasis, but it\u00a0can be difficult to ascertain the form. High resolution CT (figure 1.28) is better at determining the form and has all but replaced the much more invasive bronchography, which\u00a0involves instillation of radiopaque medium into the tracheobronchial tree."}
+{"id": "pulmonary$$$40cf67f9-f2f5-4f16-9935-fbb7f928762f", "contents": "Where the bronchiectasis occurs in the lung is somewhat dependent on the cause. The segmental and subsegmental bronchi are the airway types most commonly affected, and the basilar segments of the lower lobes are the most frequent region in the lung. The second most common locations are the right middle lobe and lingual segments, while bronchiectasis caused by primary tuberculosis (TB)\u00a0and other infections tend to occur in the upper lung fields where the infection is located (see figure 1.29)."}
+{"id": "pulmonary$$$d5c4f82c-5276-4294-802a-0338ebfbb119", "contents": "So, how does bronchiectasis present, and what are the results of diagnostic tests?"}
+{"id": "pulmonary$$$5e65bc8e-27c1-4d20-b621-19cbb49f66bf", "contents": "The initial complaint is usually a persistent cough with copious expectoration. The amount of mucus the cough produces varies and can be as high as several hundred milliliters\u00a0per day, particular when the dependent airways are involved. However, it is\u00a0worth noting here that\u00a0bronchiectasis in the upper lobes (usually associated with infection)\u00a0may be dry with little or no mucus expectoration."}
+{"id": "pulmonary$$$937f0cac-75b1-4750-b24a-1102b5b8155a", "contents": "Generally though there is mucopurulent expectorate, and if it is associated with an anerobic infection it will likely have a foul odor. Sputum smears are loaded with white blood cells and can contain both gram-positive and -negative organisms."}
+{"id": "pulmonary$$$a107792c-c797-481e-aa49-75245f1a3990", "contents": "The patient will likely have a history of recurrent pneumonia, the site of the pneumonia being consistent with locality of the bronchiectasis."}
+{"id": "pulmonary$$$625e0746-b32e-4849-bf71-4250bb7116a0", "contents": "The expectorate may also contain blood. The degree and frequency of hemoptysis is variable and unpredictable, but occasionally it can be massive and life threatening."}
+{"id": "pulmonary$$$cf6b7f64-2bf3-4cc9-8ff1-0ff2a604ccd0", "contents": "The standard diagnostic tests may not be helpful in early stages, but typical signs appear with worsening airway involvement. In the early stages the patient will likely appear normal on a physical exam and have normal spirometry and arterial blood gas values. With more significant bronchiectasis, rales and rhonchi over the affected site can be heard."}
+{"id": "pulmonary$$$c3d3baf9-f5f9-45b0-92f5-3092c6460159", "contents": "Later signs with long-standing bronchiectasis include finger clubbing, but this is not exclusive to the condition."}
+{"id": "pulmonary$$$32463f67-8faa-40ef-b65c-da948ae39c76", "contents": "A chest x-ray will show\u00a0the peribronchial fibrosis and any atelectasis. But, as mentioned earlier, a high-resolution CT is much more effective at determining the degree and type of airway changes."}
+{"id": "pulmonary$$$cbb9aaad-105e-4a3e-ac67-3afc2bac6e48", "contents": "Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. \u201cChapters 8\u201311.\u201d In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978."}
+{"id": "pulmonary$$$2fae69a4-a520-4df1-b51b-916b71d658bf", "contents": "West, John B. \u201cChapter 4: Obstructive Diseases.\u201d In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1", "contents": "Pulmonology  ( / \u02cc p \u028c l m \u0259 \u02c8 n \u0252 l \u0259 d\u0292 i / ,  / \u02cc p \u028a l m \u0259 \u02c8 n \u0252 l \u0259 d\u0292 i / , from  Latin   pulm\u014d, -\u014dnis  \"lung\" and the  Greek  suffix  -\u03bb\u03bf\u03b3\u03af\u03b1   -log\u00eda  \"study of\"),  pneumology  ( / n \u028a \u02c8 m \u0252 l \u0259 d\u0292 i ,   n j \u028a -/ , built on Greek \u03c0\u03bd\u03b5\u03cd\u03bc\u03c9\u03bd  pne\u00fam\u014dn  \"lung\") or  pneumonology [ 1 ]  ( / n \u028a m \u0259 n \u02c8 \u0252 l \u0259 d\u0292 i ,   n j \u028a -/ ) is a  medical specialty  that deals with  diseases  involving the  respiratory tract . [ 2 ]  It is also known as  respirology ,  respiratory medicine , or  chest medicine  in some countries and areas."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2", "contents": "Pulmonology is considered a branch of  internal medicine , and is related to  intensive care medicine . Pulmonology often involves managing patients who need life support and  mechanical ventilation . Pulmonologists are specially trained in diseases and conditions of the  chest , particularly  pneumonia ,  asthma ,  tuberculosis ,  emphysema , and complicated chest infections. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3", "contents": "Pulmonology/respirology departments work especially closely with certain other specialties:  cardiothoracic surgery  departments and  cardiology  departments."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4", "contents": "One of the first major discoveries relevant to the field of pulmonology was the discovery of  pulmonary circulation . Originally, it was thought that  blood  reaching the right side of the  heart  passed through small 'pores' in the  septum  into the left side to be oxygenated, as theorized by  Galen ; however, the discovery of pulmonary circulation disproves this theory, which had previously been accepted since the 2nd century. Thirteenth-century  anatomist  and  physiologist   Ibn Al-Nafis  accurately theorized that there was no 'direct' passage between the two sides ( ventricles ) of the heart. He believed that the blood must have passed through the  pulmonary artery , through the lungs, and back into the heart to be  pumped  around the body. This is believed by many to be the first scientific description of pulmonary circulation. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5", "contents": "Although pulmonary medicine only began to evolve as a medical specialty in the 1950s,  William Welch  and  William Osler  founded the 'parent' organization of the  American Thoracic Society , [ 5 ]  the National Association for the Study and Prevention of  Tuberculosis . [ 6 ]  The care, treatment, and study of tuberculosis of the lung is recognised as a discipline in its own right,  phthisiology . [ 7 ]  When the specialty did begin to evolve, several discoveries were being made linking the respiratory system and the measurement of arterial blood gases, attracting more and more physicians and researchers to the developing field. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_6", "contents": "Surgery  of the respiratory tract is generally performed by specialists in  cardiothoracic surgery [ 9 ]  (or  thoracic surgery ), [ 10 ]  though minor procedures may be performed by pulmonologists. Pulmonology is closely related to critical care medicine [ 11 ]  when dealing with patients who require mechanical ventilation. As a result, many pulmonologists are certified to practice critical care medicine in addition to pulmonary medicine. There are fellowship programs that allow physicians to become board certified in pulmonary and critical care medicine simultaneously.  Interventional pulmonology  is a relatively new field within pulmonary medicine [ 12 ]  that deals with the use of procedures such as  bronchoscopy [ 13 ]  and pleuroscopy to treat several pulmonary diseases. [ 14 ]  Interventional pulmonology is increasingly recognized as a specific medical specialty. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_7", "contents": "The pulmonologist begins the diagnostic process with a general review focusing on:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_8", "contents": "Physical diagnostics [ 19 ]  are as important as in other fields of  medicine ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_9", "contents": "As many  heart diseases  can give pulmonary signs, [ 20 ]  a thorough cardiac investigation is usually included."}
+{"id": "WikiPedia_Pulmonology$$$corpus_10", "contents": "Pulmonary clinical procedures include the following pulmonary tests and procedures: [ 21 ] [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_11", "contents": "Major surgical procedures on the heart and lungs are performed by a  thoracic surgeon . [ 28 ]  Pulmonologists often perform specialized procedures to get samples from the inside of the chest or inside of the lung. They use radiographic techniques to view vasculature of the lungs and heart to assist with diagnosis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_12", "contents": "Medication  is the most important treatment of most diseases of pulmonology, either by inhalation ( bronchodilators  and  steroids ) or in oral form ( antibiotics ,  leukotriene antagonists ). A common example being the usage of  inhalers  in the treatment of inflammatory lung conditions such as  asthma  or  chronic obstructive pulmonary disease .  Oxygen therapy [ 29 ]  is often necessary in severe respiratory disease ( emphysema  and  pulmonary fibrosis ). When this is insufficient, the patient might require  mechanical ventilation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_13", "contents": "Pulmonary rehabilitation [ 30 ]  has been defined as a multidimensional continuum of services directed to persons with pulmonary disease and their families, usually by an interdisciplinary team of specialists, with the goal of achieving and maintaining the individual's maximum level of independence and functioning in the community. Pulmonary rehabilitation [ 31 ]  is intended to educate the patient, the family, and improve the overall quality of life and  prognosis  for the patient. Interventions can include exercise, education, emotional support, oxygen, noninvasive mechanical ventilation, optimization of airway secretion clearance, promoting compliance with medical care to reduce numbers of exacerbations and hospitalizations, and returning to work and/or a more active and emotionally satisfying life. These goals are appropriate for any patients with diminished respiratory reserve whether due to obstructive or intrinsic pulmonary diseases (oxygenation impairment) or neuromuscular weakness (ventilatory impairment).  A pulmonary rehabilitation team [ 32 ]  may include a rehabilitation physician, a pulmonary medicine specialist,  physician assistant  and allied health professionals including a rehabilitation  nurse , a  respiratory therapist , a  speech-language pathologist , a  physical therapist , an  occupational therapist , a  psychologist , and a  social worker  among others. Additionally, breathing games are used to motivate children to perform pulmonary rehabilitation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_14", "contents": "In the  United States , pulmonologists are physicians who, after receiving a medical degree ( MD  or  DO ), complete  residency  training in  internal medicine , followed by at least two additional years of subspeciality  fellowship  training in pulmonology. [ 33 ]  After satisfactorily completing a fellowship in pulmonary medicine, the physician is permitted to take the board certification examination in pulmonary medicine. After passing this exam, the physician is then board certified as a pulmonologist. Most pulmonologists complete three years of combined subspecialty fellowship training in pulmonary medicine and critical care medicine."}
+{"id": "WikiPedia_Pulmonology$$$corpus_15", "contents": "In the  United States , pediatric pulmonologists [ 34 ]  are  physicians  who, after receiving a medical degree (MD, DO, MBBS, MBBCh, etc.), complete residency training in  pediatrics , followed by at least three additional years of subspeciality fellowship training in pulmonology. Pediatric pulmonologists treat diseases of the airways, lungs, respiratory mechanics and aerodigestive system."}
+{"id": "WikiPedia_Pulmonology$$$corpus_16", "contents": "Pulmonologists are involved in both clinical and basic research of the  respiratory system , ranging from the anatomy of the  respiratory epithelium  to the most effective treatment of  pulmonary hypertension . Scientific research also takes place to look for causes and possible treatment in diseases such as  pulmonary tuberculosis  and  lung cancer ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_17", "contents": "Acute inhalation injury  may result from frequent and widespread use of household cleaning agents and industrial gases (including  chlorine  and  ammonia ). The airways and lungs receive continuous first-pass exposure to non-toxic and irritant or toxic gases via inhalation. Irritant gases are those that, on inhalation, dissolve in the water of the respiratory tract  mucosa  and provoke an inflammatory response, usually from the release of acidic or alkaline radicals. [ 1 ] [ 2 ]   Smoke ,  chlorine ,  phosgene ,  sulfur dioxide ,  hydrogen chloride ,  hydrogen sulfide ,  nitrogen dioxide ,  ozone , and  ammonia  are common irritants."}
+{"id": "WikiPedia_Pulmonology$$$corpus_18", "contents": "Depending on the type and amount of irritant gas inhaled, victims can experience symptoms ranging from minor respiratory discomfort to acute airway and lung injury and even death. A common response cascade to a variety of irritant gases includes  inflammation ,  edema  and epithelial  sloughing , which if left untreated can result in scar formation and pulmonary and airway remodeling. Currently, mechanical ventilation remains the therapeutic mainstay for pulmonary dysfunction following acute inhalation injury."}
+{"id": "WikiPedia_Pulmonology$$$corpus_19", "contents": "Smoke inhalation  injury, either by itself but more so in the presence of body surface burn, can result in severe lung-induced morbidity and mortality. [ 3 ]  The most common cause of death in burn centers is now respiratory failure. The  September 11 attacks  in 2001 and  forest fires  in  U.S. states  such as  California  and  Nevada  are examples of incidents that have caused smoke inhalation injury. [ 4 ] [ 5 ]  Injury to the lungs and airways is not only due to deposition of fine  particulate   soot  but also due to the gaseous components of smoke, which include phosgene,  carbon monoxide , and sulfur dioxide."}
+{"id": "WikiPedia_Pulmonology$$$corpus_20", "contents": "Chlorine  is a relatively common gas in industry with a variety of uses. It is used to disinfect water as well as being a part of the sanitation process for sewage and industrial waste. Chlorine is also used as a bleaching agent during the production of paper and cloth. Many household cleaning products, including  bleach , contain chlorine. Given the volume and ease of chlorine for industrial and commercial use, exposure could occur from an accidental spill or a deliberate attack. The  National Institute for Occupational Safety and Health  recommends that a person wear splash proof goggles, a face shield and a respirator mask when working in the vicinity of chlorine gas. Because chlorine is a gas at room temperature, most exposure occurs via inhalation. Exposure may also occur through skin or eye contact or by ingesting chlorine-contaminated food or water. Chlorine is a strong oxidizing element causing the hydrogen to split from water in moist tissue, resulting in nascent oxygen and hydrogen chloride that cause corrosive tissue damage. Additionally oxidation of chlorine may form  hypochlorous acid , which can penetrate cells and react with cytoplasmic proteins destroying cell structure. [ 6 ] [ 7 ]  Chlorine\u2019s odor provides early warning signs of exposure but causes olfactory fatigue or adaptations, reducing awareness of exposure at low concentrations. With increased exposure, symptoms may progress to labored respirations, severe coughing, chest tightness, wheezing, dyspnea, and bronchospasm associated with a decrease in oxygen saturation level. . [ 8 ]  Severe exposure may result in  changes in upper and lower airways resulting in an acute lung injury, which may not be present until several hours after exposure. A recent chlorine gas leak in  Pune ,  India , landed 20 individuals in the hospital. [ 9 ]  Though that was an accidental exposure, chlorine gas has been used as a weapon of warfare since  World War I , most recently in  2007 in Iraq . [ 10 ] [ 11 ] [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_21", "contents": "Phosgene , notably used as a   chemical weapon  during World War I, is also used as an industrial reagent and building block in  synthesis  of  pharmaceuticals  and other  organic compounds . Because of safety issues, phosgene is almost always produced and consumed within the same plant and extraordinary measures are made to contain this gas. In low concentrations, phosgene\u2019s odor resembles freshly cut hay or grass. Because of this, the gas may not be noticed and symptoms may appear slowly. Phosgene directly reacts with  amine ,  sulfhydryl , and  alcohol   groups , adversely affecting cell macromolecules and metabolism. The direct toxicity to the cells leads to an increase in capillary permeability. [ 12 ] [ 13 ]  Furthermore, when phosgene hydrolyzes it forms  hydrochloric acid , which can damage the cell surface and cause cell death in the  alveoli  and  bronchioles . The hydrochloric acid triggers an inflammatory response that attracts neutrophils to the lungs, which causes  pulmonary edema . [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_22", "contents": "Ammonia  is generally used in household cleaning products, as well as on farms and in some industrial and commercial locations, and this makes it easy for accidental or deliberate exposure to occur. [ 15 ] [ 16 ] [ 17 ]  Ammonia interacts with moist surfaces to form  ammonium hydroxide , which causes  necrosis  of tissues. Exposure to high concentrations can cause bronchiolar and alveolar edema and airway destruction resulting in respiratory distress or failure. Although ammonia has a pungent odor, it also causes olfactory fatigue or adaptation, reducing awareness of prolonged exposure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_23", "contents": "Sulfur mustard , commonly known as mustard gas, was used as a chemical weapon in World War I and more recently in the  Iran\u2013Iraq War . Sulfur mustard is a vesicant  alkylating agent  with strong cytotoxic, mutagenic, and carcinogenic properties. After exposure, victims show skin irritations and blisters. [ 18 ] [ 19 ]  This agent also causes  respiratory tract   lesions ,  bone marrow depression , and eye damage, the epithelial tissues of these organs being predominately affected. Inhalation of high doses of this gas causes lesions in the larynx, trachea, and large bronchi with inflammatory reactions and necrosis. The alkylating agent affects more the upper parts of the respiratory tract, and only intensely exposed victims showed signs like bronchiolitis obliterans in the distal part. Secondary effects of sulfur mustard exposure lead to chronic lung diseases such as chronic bronchitis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_24", "contents": "A common exposure involves accidental mixing of household ammonia with cleansers containing bleach, causing the irritant gas  monochloramine  to be released."}
+{"id": "WikiPedia_Pulmonology$$$corpus_25", "contents": "Methyl isocyanate  is an intermediate chemical in the production of  carbamate   pesticides  (such as carbaryl, carbofuran, methomyl, and aldicarb). [ 20 ] [ 21 ]  It has also been used in the production of rubbers and adhesives. As a highly toxic and irritating material, it is hazardous to human health, and was involved in the  Bhopal disaster \u2014which killed nearly 8,000 people initially and approximately 17,000 people in total. [ 21 ]  When inhaled the vapor produces a direct inflammatory effect on the respiratory tract."}
+{"id": "WikiPedia_Pulmonology$$$corpus_26", "contents": "Respiratory damage is related to the concentration of the gas and its solubility. Irritant gas exposures predominantly affect the airways, causing  tracheitis , bronchitis, and  bronchiolitis . Other inhaled agents may be directly toxic (e.g.  cyanide ,  carbon monoxide ), or cause harm simply by displacing oxygen and producing  asphyxia  (e.g. methane, carbon dioxide). The effect of inhaling irritant gases depends on the extent and duration of exposure and on the specific agent [ 22 ] [ 23 ] [ 24 ]  Chlorine, phosgene, sulfur dioxide, hydrogen chloride, hydrogen sulfide, nitrogen dioxide, ozone, and ammonia are among the most important irritant gases. Hydrogen sulfide is also a potent cellular toxin, blocking the  cytochrome  system and inhibiting cellular respiration. More water-soluble gases (e.g. chlorine, ammonia, sulfur dioxide, hydrogen chloride) dissolve in the upper airway and immediately cause mucous membrane irritation, which may alert people to the need to escape the exposure. Permanent damage to the upper respiratory tract, distal airways, and lung parenchyma occurs only if escape from the gas source is impeded. Less soluble gases (e.g. nitrogen dioxide, phosgene, ozone) may not dissolve until they are well into the respiratory tract, often reaching the lower airways. [ 25 ]  These agents are less likely to produce early warning signs (phosgene in low concentrations has a pleasant odor), are more likely to cause severe bronchiolitis, and often have a lag of \u2265 12 h before symptoms of pulmonary edema develop."}
+{"id": "WikiPedia_Pulmonology$$$corpus_27", "contents": "Acute lung injury  (ALI), also called non-cardiogenic pulmonary edema, is characterized by the abrupt onset of significant hypoxemia and diffuse pulmonary infiltrates in the absence of cardiac failure. The core pathology is disruption of the capillary-endothelial interface: this actually refers to two separate barriers \u2013 the endothelium and the basement membrane of the alveolus. [ 26 ] [ 27 ] [ 28 ] [ 29 ]  In the acute phase of ALI, there is increased permeability of this barrier and protein rich fluid leaks out of the capillaries. There are two types of alveolar epithelial cells \u2013 Type 1 pneumocytes represent 90% of the cell surface area, and are easily damaged. Type 2 pneumocytes are more resistant to damage, which is important as these cells produce surfactant, transport ions and proliferate and differentiate into Type 1 cells. The damage to the endothelium and the alveolar epithelium results in the creation of an open interface between the lung and the blood, facilitating the spread of micro-organisms from the lung systemically, stoking up a systemic inflammatory response. Moreover, the injury to epithelial cells handicaps the lung\u2019s ability to pump fluid out of airspaces. Fluid filled airspaces, loss of surfactant, microvascular thrombosis and disorganized repair (which leads to fibrosis) reduces resting lung volumes (decreased compliance), increasing ventilation-perfusion mismatch, right to left shunt and the work of breathing. In addition, lymphatic drainage of lung units appears to be curtailed\u2014stunned by the acute injury\u2014which contributes to the build-up of extravascular fluid. Some patients rapidly recover from ALI and have no permanent sequelae. Prolonged inflammation and destruction of pneumocytes leads to fibroblastic proliferation, hyaline membrane formation, tracheal remodeling and lung fibrosis. This fibrosing alveolitis may become apparent as early as five days after the initial injury. Subsequent recovery may be characterized by reduced  physiologic reserve , and increased susceptibility to further lung injuries. Extensive microvascular thrombosis may lead to pulmonary hypertension, myocardial dysfunction and systemic hypotension."}
+{"id": "WikiPedia_Pulmonology$$$corpus_28", "contents": "Clinically, the most serious and immediate complication is  acute respiratory distress syndrome  (ARDS), which usually occurs within 24 hours. [ 30 ] [ 31 ] [ 32 ]  Those with significant lower airway involvement may develop bacterial infection. Importantly, victims suffering body surface burn and smoke inhalation are the most susceptible. Thermal injury combined with inhalation injury compromises pulmonary function, producing microvascular hyperpermeability that leads to a significant increase in lung lymph flow and pulmonary edema. The terrorist attack on the World Trade Center on September 11, 2001 left many people with impaired lung function. [ 33 ] [ 34 ] [ 35 ]  A study of firefighters and EMS workers enrolled in the FDNY WTC Medical Monitoring and Treatment Program, whose lung function was tested prior to 9/11, documented a steep decline in lung function in the first year after 9/11. [ 33 ]  A new study that includes a thousand additional workers shows that the declines have persisted over time. [ 34 ]  Prior to 9/11, 3% of firefighters had below-normal lung function, one year after 9/11 nearly 19% did, and six years later it stabilized at 13%. Ten to 14 days after acute exposure to some agents (e.g. ammonia, nitrogen oxides, sulfur dioxide, mercury), some patients develop  bronchiolitis obliterans  progressing to ARDS.  Bronchiolitis obliterans with organized pneumonia  can ensue when granulation tissue accumulates in the terminal airways and alveolar ducts during the body's reparative process. A minority of these patients develop late pulmonary fibrosis. Also at enhanced risk are persons with co-morbidities. Several studies report that both aged persons and smokers are especially vulnerable to the adverse effects of inhalation injury."}
+{"id": "WikiPedia_Pulmonology$$$corpus_29", "contents": "Specific pretreatments, drugs to prevent chemically induced lung injuries due to respiratory airway toxins, are not available. Analgesic medications, oxygen, humidification, and ventilator support currently constitute standard therapy. In fact, mechanical ventilation remains the therapeutic mainstay for acute inhalation injury. [ 36 ]   [ 37 ]  The cornerstone of treatment is to keep the PaO2 > 60 mmHg (8.0 kPa), without causing injury to the lungs with excessive O2 or volutrauma. Pressure control ventilation is more versatile than volume control, although breaths should be volume limited, to prevent stretch injury to the alveoli. Positive end-expiratory pressure (PEEP) is used in mechanically ventilated patients with ARDS to improve oxygenation. Hemorrhaging, signifying substantial damage to the lining of the airways and lungs, can occur with exposure to highly corrosive chemicals and may require additional medical interventions. Corticosteroids are sometimes administered, and bronchodilators to treat bronchospasms. Drugs that reduce the inflammatory response, promote healing of tissues, and prevent the onset of pulmonary edema or secondary inflammation may be used following severe injury to prevent chronic scarring and airway narrowing. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_30", "contents": "Although current treatments can be administered in a controlled hospital setting, many hospitals are ill-suited for a situation involving mass casualties among civilians. Inexpensive positive-pressure devices that can be used easily in a mass casualty situation, and drugs to prevent inflammation and pulmonary edema are needed. Several drugs that have been approved by the FDA for other indications hold promise for treating chemically induced pulmonary edema. These include \u03b22-agonists, dopamine, insulin, allopurinol, and non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. Ibuprofen is particularly appealing because it has an established safety record and can be easily administered as an initial intervention. [ 36 ]  Inhaled and systemic forms of \u03b22-agonists used in the treatment of asthma and other commonly used medications, such as  insulin ,  dopamine , and  allopurinol  have also been effective in reducing pulmonary edema in animal models but require further study. A recent study documented in the  AANA Journal  discussed the use of volatile anesthetic agents, such as  sevoflurane , to be used as a bronchodilator that lowered peak airway pressures and improved oxygenation. [ 36 ] [ 39 ]  Other promising drugs in earlier stages of development act at various steps in the complex molecular pathways underlying pulmonary edema. Some of these potential drugs target the inflammatory response or the specific site(s) of injury. Others modulate the activity of ion channels that control fluid transport across lung membranes or target surfactant, a substance that lines the air sacs in the lungs and prevents them from collapsing. Mechanistic information based on toxicology, biochemistry, and physiology may be instrumental in determining new targets for therapy. Mechanistic studies may also aid in the development of new diagnostic approaches. Some chemicals generate metabolic byproducts that could be used for diagnosis, but detection of these byproducts may not be possible until many hours after initial exposure. Additional research must be directed at developing sensitive and specific tests to identify individuals quickly after they have been exposed to varying levels of chemicals toxic to the respiratory tract."}
+{"id": "WikiPedia_Pulmonology$$$corpus_31", "contents": "Currently there are no clinically approved agents that can reduce pulmonary and airway cell dropout and avert the transition to pulmonary and /or airway fibrosis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_32", "contents": "Given the constant threat of bioterrorist related events, there is an urgent need to develop pulmonary protective and reparative agents that can be used by first responders in a mass casualty setting. Use in such a setting would require administration via a convenient route for e.g. intramuscular via epipens. [ 36 ]  Other feasible routes of administration could be inhalation and perhaps to a lesser extent oral \u2013 swallowing can be difficult in many forms of injury especially if accompanied by secretions or if victim is nauseous. A number of in vitro and in vivo models lend themselves to preclinical evaluation of novel pulmonary therapies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_33", "contents": "In vitro, exposure of human bronchial epithelial cells or human pulmonary alveolar epithelial cells to agents such as  hydrogen peroxide  or bleach produces a time and toxin-dose-dependent decrease in cellular viability. [ 40 ] [ 41 ] [ 42 ]  Cells exposed to these agents demonstrate significant ATP depletion, DNA damage, and lipid peroxidation, followed by death allowing for evaluation of novel cytoprotective agents. Potential tissue reparative agents can be evaluated in vitro by determining their effects on stimulation of pulmonary and airway epithelial cell proliferation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_34", "contents": "Test articles passing muster in vitro can be evaluated in a number of in vivo models (usually in mice) of ALI including chlorine inhalation,  intratracheal instillation  of  bleomycin  and in transforming growth factor \u03b21 (TGF \u03b21) overexpressing transgenic mice exposed to high dose doxycycline. [ 43 ] [ 44 ] [ 45 ] [ 46 ] [ 47 ] [ 48 ] [ 49 ]  Acute exposure to high concentrations of chlorine gas induces pathological and functional changes in the lungs of rodents. Histological changes consist of epithelial necrosis and detachment, increase in the area of smooth muscle, epithelial regeneration and mucous cell hyperplasia. [ 46 ]  Most of these abnormalities resolve with time. Functional changes (increased RL and/or bronchial responsiveness to inhaled methacholine) last for mean intervals of 3 and 7 days after exposure, but can persist up to 30 and 90 days, respectively. The functional changes are related to the overall abnormal airway epithelial damage and there is a significant correlation between RL and bronchoalveolar lavage ( BAL) neutrophilia. Bleomycin is an antineoplastic antibiotic drug isolated in 1966 from the actinomycete Streptomyces verticillus. Bleomycin forms a complex with oxygen and metals such as Fe2+, leading to the production of oxygen radicals, DNA breaks, and ultimately cell death. [ 44 ] [ 45 ]  Doxycycline driven overexpression of TGF \u03b21 in the lungs of transgenic mice result in a time-dependent inflammatory response characterized by massive infiltration of F4/80+ monocytic/macrophage-like cells and a wave of apoptotic pulmonary cell death. Mice that survive this initial onslaught go on to demonstrate an increase in lung collagen content, and decreased lung compliance. [ 48 ] [ 49 ]  A large animal model of ALI is the ovine model of body surface burn + heated smoke inhalation. [ 50 ] [ 51 ]  It has been established that combined burn and smoke inhalation injury impairs hypoxic pulmonary vasoconstriction (HPV), the vasoconstrictive response to hypoxia, thereby mismatching ventilation with perfusion. Gas exchange is affected by increases in the dispersion of both alveolar ventilation and cardiac output because bronchial and vascular functions are altered by injury-related factors, such as the effects of inflammatory mediators on airway and vascular smooth muscle tone. As a rule of thumb, all these models are characterized by high mortality, inflammation of the airways and pulmonary parenchyma, edema and flooding of the alveolar spaces by a proteinaceous exudate, sloughing of the airway and pulmonary epithelium, scarring and transition to airway and pulmonary remodeling."}
+{"id": "WikiPedia_Pulmonology$$$corpus_35", "contents": "Airway pressure release ventilation  ( APRV ) is a  pressure control   mode of mechanical ventilation  that utilizes an  inverse ratio ventilation  strategy.  APRV is an applied  continuous positive airway pressure  (CPAP) that at a set timed interval releases the applied pressure. Depending on the ventilator manufacturer, it may be referred to as BiVent. This is just as appropriate to use, since the only difference is that the term APRV is copyrighted. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_36", "contents": "Airway pressure release ventilation was described initially by Stock and Downs in 1987 [ 2 ] [ 3 ]  as a  continuous positive airway pressure  (CPAP) with an intermittent release phase.  APRV begins at a pressure higher than the baseline pressure and follows with a deflation to accomplish tidal ventilation. [ 4 ]   Fundamentally APRV is a time-cycled alternant between two levels of positive airway pressure, with the main time on the high level and a brief expiratory release to facilitate ventilation. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_37", "contents": "Based on clinical and experimental data, airway pressure release ventilation is indicated in patients with  acute lung injury , [ 6 ] [ 7 ]   acute respiratory distress syndrome [ 8 ] [ 9 ]  and  atelectasis [ 1 ]  after major surgery"}
+{"id": "WikiPedia_Pulmonology$$$corpus_38", "contents": "This is a type of  inverse ratio ventilation . [ 9 ]  The exhalation time (T low ) is shortened to usually less than one second to maintain alveoli inflation.  Fundamentally this is a continuous pressure with a brief release.  APRV is currently the most efficient, conventional mode for lung protective ventilation. [ 10 ] [ 11 ] [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_39", "contents": "Settings are sometimes brand specific and the term for the individual settings may differ, however generally the settings listed here are a fundamental explanation of the purpose of the settings within the APRV mode."}
+{"id": "WikiPedia_Pulmonology$$$corpus_40", "contents": "Mean airway pressure  on APRV is calculated by this formula: [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_41", "contents": "Different perceptions of this mode may exist around the globe. While 'APRV' is common to users in  North America , a very similar mode, biphasic positive airway pressure ( BIPAP ), was introduced in Europe. [ 13 ]   The term APRV has also been used in American journals where, from the ventilation characteristics, BIPAP would have been the appropriate terminology. [ 14 ]  To further confusion, BiPAP is a registered trade-mark for a noninvasive ventilation mode in a specific ventilator (Respironics Inc.). Other names (BILEVEL, DUOPAP, BIVENT) have been created for legal reasons. Although similar in modality, these terms describe how a mode is intended to inflate the lung, rather than defining the characteristics of synchronization or the way spontaneous breathing efforts are supported. [ 8 ] [ 15 ]   Concern has been raised about the amount of mechanical power applied to the lung during APRV and the risk of ergotrauma, especially in pulmonary ARDS."}
+{"id": "WikiPedia_Pulmonology$$$corpus_42", "contents": "APRV is used by many brands and models of mechanical ventilators under different names.  Most names are copyrighted as trademarks and do not represent  nomenclature of mechanical ventilation  but may be referred to clinically by the brand name. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_43", "contents": "Some of these names include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_44", "contents": "Daoud EG, Farag HL, Chatburn RL (2012). \"Airway pressure release ventilation: what do we know?\".  Respir Care .  57  (2):  282\u2013 92.  doi : 10.4187/respcare.01238 .  PMID \u00a0 21762559 .  S2CID \u00a0 16294092 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_45", "contents": "This is a list of  allergies , which includes the  allergen , potential reactions, and a brief description of the cause where applicable."}
+{"id": "WikiPedia_Pulmonology$$$corpus_46", "contents": "Many substances can cause an allergic reaction when in contact with the human  integumentary system ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_47", "contents": "Alveolar pressure  ( P alv ) is the pressure of  air  inside the  lung   alveoli . When the  glottis  is opened and no air is flowing into or out of the lungs, alveolar pressure is equal to the atmospheric pressure, that is, zero  cmH 2 O . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_48", "contents": "During  inhalation , the increased volume of  alveoli  as a result of  lung  expansion decreases the intra-alveolar pressure to a value below atmospheric pressure about -1 cmH 2 O. This slight negative pressure is enough to move 500 ml of air into the lungs in the 2 seconds required for inspiration. At the end of inspiration, the alveolar pressure returns to atmospheric pressure (zero cmH 2 O). [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_49", "contents": "During  exhalation , the opposite change occurs. The lung alveoli collapse before air is expelled from them. The alveolar pressure rises to about +1\u00a0cmH 2 O. This forces the 500 ml of inspired air out of the lung during the 2\u20133 seconds of expiration. By the end of expiration, the pressure drops gradually and becomes atmospheric again. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_50", "contents": "The  Apnea\u2013Hypopnea Index  or  Apnoea\u2013Hypopnoea Index  ( AHI ) is an index used to indicate the severity of  sleep apnea . It is represented by the number of  apnea  and  hypopnea  events per hour of sleep. Apnea is the complete absence of airflow through your nose and mouth. Hypopnea is a partial collapse of your airway, limiting breathing. Apneas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation to be considered. Combining AHI and  oxygen desaturation  gives an overall sleep apnea severity score that evaluates both the number of sleep breathing disruptions and the degree of oxygen desaturation (low oxygen level in the blood) during said disruptions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_51", "contents": "The AHI is calculated by dividing the number of apnea events by the number of hours of sleep. The AHI values for adults are categorized as: [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_52", "contents": "For children, because of their different physiology, an AHI in excess of 1 is considered abnormal. Underage pediatric patients presenting with AHI of 2 or greater will often be referred for treatment. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_53", "contents": "The Apnea-Hypopnea Index has been criticized for being too simplistic to accurately rate apnea and hypopnea events for their severity. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_54", "contents": "In one study, mean apnea-hypopnea duration and not AHI was found to be associated with worse hypertension. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_55", "contents": "One long apnea event is clearly worse than the same period broken up into shorter multiple events, with breathing between events, yet it would have the lower AHI."}
+{"id": "WikiPedia_Pulmonology$$$corpus_56", "contents": "This  medical  diagnostic article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_57", "contents": "This  respiratory system  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_58", "contents": "Atelectotrauma ,  atelectrauma ,  cyclic atelectasis  or  repeated alveolar collapse and expansion  ( RACE ) are medical terms for the damage caused to the lung by  mechanical ventilation  under certain conditions. When parts of the lung  collapse  at the end of expiration, due to a combination of a diseased lung state and a low  functional residual capacity , then reopen again on inspiration, this repeated collapsing and reopening causes  shear stress  which has a damaging effect on the  alveolus . [ 1 ] [ 2 ]  Clinicians attempt to reduce atelectotrauma by ensuring adequate  positive end-expiratory pressure (PEEP)  to maintain the alveoli open in expiration. This is known as  open lung ventilation .  High frequency oscillatory ventilation (HFOV)  with its use of 'super  CPAP ' is especially effective in preventing atelectotrauma since it maintains a very high  mean airway pressure (MAP) , equivalent to a very high PEEP. Atelectotrauma is one of several means by which mechanical ventilation may damage the lungs leading to  ventilator-associated lung injury . The other means are  volutrauma ,  barotrauma ,  rheotrauma  and  biotrauma . Attempts have been made to combine these factors in an all encompassing term:  mechanical power ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_59", "contents": "This  pulmonology  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_60", "contents": "The  Bachelor of Science in Respiratory Care  ( BSRC or BScRC ) is a four-year  academic degree  in the science and principles of  respiratory care , granted by a  tertiary education   university  or similarly accredited school. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_61", "contents": "In the United States one is eligible to sit for the  NBRC-WRE  licensing examination to become a  Registered Respiratory Therapist  after graduating from either a two-year program with an  associate degree  or from a four-year program with a bachelor's degree, the bachelor's degree prepares  respiratory practitioners  for a professional role away from the bedside with coursework in science, research, leadership, and informatics. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_62", "contents": "Students awarded a Bachelor of Science in Respiratory Care are qualified to sit for the three credentialing examinations  NBRC-ELE ,  NBRC-WRE , and  NBRC-CSE  and apply for licensure as a  Registered Respiratory Therapist ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_63", "contents": "Baritosis  is a  benign  type of  pneumoconiosis , which is caused by long-term exposure to the dust of insoluble compounds of  barium , such as ground  baryte  ore."}
+{"id": "WikiPedia_Pulmonology$$$corpus_64", "contents": "The disease may develop after few months of exposure. Barium compounds have a high  radio-opacity . Extremely dense, discrete small  opacities  of 2\u20134\u00a0mm diameter, sometimes of a star-like configuration, are seen on the  radiograph . Their distribution is uniform. When they are very numerous, superimposition may give the impression of confluency, but this does not seem to occur in reality. The hilar  lymph nodes  can be very opaque but not enlarged. After cessation of exposure, there is a gradual clearing of the opacities."}
+{"id": "WikiPedia_Pulmonology$$$corpus_65", "contents": "In some cases, it is  asymptomatic . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_66", "contents": "The particles of barium compounds can be seen as opaque shadows on the chest  X-rays  of people with baritosis. However, being a benign condition, it neither interferes with lung function nor causes symptoms other than a mild cough. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_67", "contents": "After exposure to barium compounds dust ceases, the X-ray abnormalities gradually resolve. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_68", "contents": "Once diagnosis has been confirmed, the most effective treatment is to eliminate exposure to barium compounds dust. When a persistent cough is present,  expectorants  may be prescribed to help cough out the sputum and particles of barium compounds.  Cough suppressants  and/or  NSAIDs  may be used to help reduce irritation and inflammation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_69", "contents": "Although the term has occasionally been used in other ways, in medical literature  biotrauma  is usually defined as a severe inflammatory response produced in the lungs of patients who breathe by means of a  mechanical ventilator  for a long period of time. [ 1 ]   The term was coined in a 1998 paper by L. N. Tremblay and A. S. Slutsky, titled  Ventilator-induced injury: from  barotrauma  to biotrauma . [ 2 ]   The message of that paper was that  barotrauma  caused by pressure differentials is only one of several types of lung damage that a ventilator can produce."}
+{"id": "WikiPedia_Pulmonology$$$corpus_70", "contents": "This  medical  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_71", "contents": "Blood gas tension  refers to the  partial pressure  of  gases  in  blood . [ 1 ]  There are several significant purposes for measuring gas tension. [ 2 ]  The most common gas tensions measured are  oxygen  tension (P x O 2 ),  carbon dioxide  tension (P x CO 2 ) and  carbon monoxide  tension (P x CO). [ 3 ]  The subscript  x  in each symbol represents the source of the gas being measured: \" a \" meaning  arterial , \" A \" being  alveolar , \" v \" being  venous , and \" c \" being  capillary . [ 3 ]   Blood gas tests  (such as  arterial blood gas  tests) measure these partial pressures."}
+{"id": "WikiPedia_Pulmonology$$$corpus_72", "contents": "P a O 2  \u2013 Partial pressure of oxygen at sea level (160\u00a0 mmHg  in the atmosphere, 21% of standard atmospheric pressure of 760\u00a0mmHg) in  arterial blood  is between 75\u00a0mmHg and 100\u00a0mmHg. [ 4 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_73", "contents": "P v O 2  \u2013 Oxygen tension in  venous blood  at sea level is between 30\u00a0mmHg and 40\u00a0mmHg. [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_74", "contents": "Carbon dioxide is a by-product of food metabolism and in high amounts has toxic effects including:  dyspnea ,  acidosis  and  altered consciousness . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_75", "contents": "P a CO 2  \u2013 Partial pressure of carbon dioxide at sea level in arterial blood is between 35 mmHg and 45 mmHg. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_76", "contents": "P v CO 2  \u2013 Partial pressure of carbon dioxide at sea level in venous blood is between 40 mmHg and 50 mmHg. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_77", "contents": "P a CO  \u2013 Partial pressure of CO at sea level in arterial blood is approximately 0.02. It can be slightly higher in smokers and people living in dense urban areas."}
+{"id": "WikiPedia_Pulmonology$$$corpus_78", "contents": "The partial pressure of gas in blood is significant because it is directly related to   gas exchange , as the driving force of   diffusion  across the   blood gas barrier  and thus blood  oxygenation . [ 10 ]   When used alongside the  pH  balance of the blood, the P a CO 2  and  HCO \u2212 3  (and  lactate ) suggest to the health care practitioner which interventions, if any, should be made. [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_79", "contents": "The constant, 1.36, is the amount of oxygen (ml at 1 atmosphere) bound per gram of  hemoglobin . The exact value of this constant varies from 1.34 to 1.39, depending on the reference and the way it is derived. S a O 2  refers to the percent of arterial hemoglobin that is saturated with oxygen. The constant 0.0031 represents the amount of oxygen dissolved in plasma per mm Hg of partial pressure. The dissolved-oxygen term is generally small relative to the term for hemoglobin-bound oxygen, but becomes significant at very high P a O 2  (as in a  hyperbaric chamber ) or in severe  anemia . [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_80", "contents": "This is an estimation and does not account for differences in temperature, pH and concentrations of 2,3 DPG. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_81", "contents": "A  blood gas test  or  blood gas analysis   tests blood  to measure  blood gas tension values , it also measures  blood pH , and the level and  base excess  of  bicarbonate . The source of the  blood  is reflected in the name of each test;  arterial blood  gases come from  arteries ,  venous blood  gases come from  veins  and capillary blood gases come from  capillaries . [ 1 ]  The  blood gas tension  levels of  partial pressures  can be used as indicators of ventilation,  respiration  and oxygenation. Analysis of paired arterial and venous specimens can give insights into the aetiology of acidosis in the newborn. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_82", "contents": "Blood samples  for testing are taken from arterial blood by a  radial artery puncture , and from venous blood by  venipuncture . Samples of  capillary blood  are taken using a  lancet  and  capillary action . Samples from capillaries from either the earlobe or the fingertip can be used to predict the  arterial partial pressure of carbon dioxide , and the  blood's pH .  Samples from the earlobe are seen to be a more appropriate site for the prediction of the  arterial partial pressure of oxygen . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_83", "contents": "Blood gas tests also  measure the levels  of  bicarbonate  and of standard bicarbonate, of  base excess , of  oxygen saturation , and of pH. An  arterial blood gas test  is more often used. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_84", "contents": "Blood gas tests can be used in the  diagnosis  of a number of  acidosis  conditions such as  lactic ,  metabolic , and  respiratory acidosis ,  diabetic ketoacidosis , and also of  respiratory alkalosis . [ 1 ]  Particularly, umbilical cord blood gas analysis can give an indication of preceding fetal hypoxic stress. In combination with other clinical information, normal paired arterial and venous cord blood gas results can usually provide a robust defence against a suggestion that an infant had an intrapartum  hypoxic-ischaemic  event. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_85", "contents": "Abnormal results may be due to a wide range of diseases, including poisoning and trauma as well as lung, kidney, or metabolic diseases. Drug overdose and uncontrolled diabetes may be determined from abnormal results. [ 4 ]  Head or neck injuries or other injuries that affect breathing can also lead to abnormal results. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_86", "contents": "Chest drains  are  surgical drains  placed within the  pleural space  to facilitate removal of unwanted substances ( air ,  blood ,  fluid , etc.) in order to preserve  respiratory functions  and  hemodynamic  stability.  Some chest drains may utilize a  flutter valve  to prevent retrograde flow, but those that do not have physical valves employ a  water trap seal  design, often aided by continuous  suction  from a  wall suction  or a  portable vacuum pump ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_87", "contents": "The active maintenance of an intrapleural negative pressure via chest drains builds the basis of  chest drain management , as an intrapleural pressure lower than the surrounding  atmosphere  allows easier  lung  expansion and thus better  alveolar   ventilation  and  gas exchange ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_88", "contents": "The so-called \"central vacuum\" was the first sub-atmospheric pressure device available. Sub-atmospheric pressure of around 100\u00a0cm of water column was historically generated at a central location in the hospital. This \"central vacuum\" was available throughout the entire hospital, as it was proved via a tubing system. It was referred to as \"wall suction\". [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_89", "contents": "Reduction  valves  that reduce the negative pressure to a therapeutically reasonable range were commercially available later. Due to this, multi-chamber suction \u2013 the use of three-chamber systems \u2013 was developed. In the 1960s, the first pumps (Emerson-Pump) were available. These and other systems launched later generated a fixed \"negative pressure\". These pumps couldn't compensate for an inadequate position of the collection chamber of a siphon. Since 2008, an electronically driven and regulated system is available, generating a \"negative pressure\" on demand."}
+{"id": "WikiPedia_Pulmonology$$$corpus_90", "contents": "External  suction  (previously referred to as active suction) is used to create a sub-atmospheric pressure at the tip of a  catheter . As the atmospheric pressure is lower compared to the  intrapleural  pressure, the lack of external suction (which was previously referred to as passive suction) is used to drain air and fluids. [ 1 ]  Traditional drainage systems are not able to suction sub-atmospheric pressure in the pleural space. These systems only allow for a regulation of pressure via the system itself but cannot regulate sub-atmospheric pressure in the pleural space. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_91", "contents": "Two different principles are used in chest drainage management: The Heber-Drain principle and the  B\u00fclau -Drain principle.\nThe \"Heber-Drain\" is based on the Heber principle, which uses hydrostatic pressure to transfer fluid from the chest to a collection canister. It produces permanent passive suction. As the Heber drain is a classical  gravity  drain, the canister must be placed below chest level to be active. The difference in height between the floor and the patient bed determines the resultant sub-atmospheric pressure. With a difference, for example, of 70\u00a0cm in height, a pressure of minus 70\u00a0cm of water is created. A water seal component is always combined with a Heber-Drain."}
+{"id": "WikiPedia_Pulmonology$$$corpus_92", "contents": "The \"B\u00fclau-Drain\" is based on the B\u00fclau principle and creates a permanent passive suction within a closed system that is based on the Heber-Drain principle. The  pulmonologist  Gotthard B\u00fclau (1835-1900) used this system in 1875 for the first time for the treatment of  pleural empyema . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_93", "contents": "This type of drainage is mainly used in  cardiac surgery .  Mediastinal  drains are placed behind the  sternum  and/or next to the heart. The main indication in these cases is the monitoring of post-operative bleeding. Whether these drains are used with active suction or not depends on factors such as personal preference and experience of the physician, individual patient-related factors etc... [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_94", "contents": "Drainage of the  pericardium  can be achieved by puncture (transcutaneously) or surgically. In the first case, small-bore  catheters  not suitable for the drainage of blood (e.g. hemopericard) are used. Pericardial drains are mostly used with the help of gravity. As a pericardial drain is placed surgically, a largo bore drain is used with a decreased probability of clogging. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_95", "contents": "The simplest system that is sufficient for chest drainage is a one-chamber system. It uses either a Heber-drain or an active suction source and comprises a single collection canister. For active or passive air evacuation, a water seal component is attached. To ensure that all air is sucked out when using a Heber-drain, manual support might be needed. To prevent a  pneumothorax  or  subcutaneous emphysema  when the patient is not able to breathe out or cough out surplus air, the height between the patient bed and the ground might need adjustment.\nAs air leaks are not always easy to observe, some one-chamber systems are limited when it comes to the treatment of huge air leaks, especially when the patient produces a lot of foam."}
+{"id": "WikiPedia_Pulmonology$$$corpus_96", "contents": "In a two-chamber system air and fluid are directed to a first collection canister.  Gravity  keeps the fluid in the first canister, whereas air is directed into a second canister. The air can either actively or passively be released via a water seal. Two-chamber systems are mainly used for patients with huge air leaks. These patients often produce foam due to protein rich  surfactant  that might enter the tubing toward the patient. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_97", "contents": "Early three-chamber systems used an extra glass bottle filled with water as a third water- vacuometer  chamber in addition to a two-chamber system. The sub-atmospheric pressure was controlled with a pipe. The higher the pipe depth, the lower the generated pressure in the  pleural space.  These systems were used in times of the central vacuum and are not used anymore as they caused accidents and were not very ease to use. The mechanics of these systems depended on high flows (20l/min) for the system to be considered active."}
+{"id": "WikiPedia_Pulmonology$$$corpus_98", "contents": "In modern portable, digital chest drainage systems, the collection chamber is integrated into the system. During the suction process, fluid will be collected in the chamber and air discharged into the  atmosphere . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_99", "contents": "Digital chest drainage systems have many advantages compared to traditional, analogue systems:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_100", "contents": "Electronic systems do not apply permanent suction but monitor the patient very closely and are activated when needed. On average, after an uncomplicated  lobectomy , an electronic pump is active for 90 minutes within 2.5 days."}
+{"id": "WikiPedia_Pulmonology$$$corpus_101", "contents": "A  chest tube  (also  chest drain ,  thoracic catheter ,  tube thoracostomy  or  intercostal drain ) is a  surgical drain  that is inserted through the  chest wall  and into the  pleural space  or the  mediastinum . The insertion of the tube is sometimes a lifesaving procedure. The tube can be used to remove clinically undesired substances such as air ( pneumothorax ), [ 1 ]  excess fluid ( pleural effusion  or  hydrothorax ),  blood  ( hemothorax ),  chyle  ( chylothorax ) or  pus  ( empyema ) from the intrathoracic space. An intrapleural chest tube is also known as a  B\u00fclau drain  or an  intercostal catheter  (ICC), and can either be a thin, flexible silicone tube (known as a \"pigtail\" drain), or a larger, semi-rigid,  fenestrated  plastic tube, which often involves a  flutter valve  or  underwater seal ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_102", "contents": "The concept of  chest drainage  was first advocated by  Hippocrates  when he described the treatment of  empyema  by means of incision, cautery and insertion of metal tubes. [ 2 ]  However, the technique was not widely used until the influenza epidemic of 1918 to evacuate post-pneumonic empyema, which was first documented by Dr. C. Pope, on a 22-month-old infant. [ 3 ]  The use of chest tubes in postoperative thoracic care was reported in 1922, [ 4 ]  and they were regularly used post-thoracotomy in  World War II , though they were not routinely used for emergency tube  thoracostomy  following acute trauma until the  Korean War . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_103", "contents": "Medical uses of chest tube are as follows: [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_104", "contents": "Contraindications to chest tube placement include refractory  coagulopathy  and presence of a diaphragmatic hernia, as well as  hepatic hydrothorax . [ 7 ]  Additional contraindications include scarring in the pleural space (adhesions)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_105", "contents": "Complications that are sometimes associated with chest tubes include the potential for clogging, air leaks, infection,  hemorrhage , re-expansion  pulmonary edema . Injury to the  liver ,  spleen  or  diaphragm  is also possible if the tube is placed behind (inferior) to the  pleural cavity  or is mispositioned. Injuries to the thoracic  aorta  and  heart  can also occur. [ 5 ] [ 8 ]  The rate of complications of chest tubes inserted for trauma-related treatment needs has been estimated at approximately 19%. [ 9 ]  The rate of complications is variable and other estimations have been made that share a rate of closer to 40%. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_106", "contents": "Complications that arise while the chest tube is being inserted or within the first day of the insertional procedure include a risk of injury to organs near the insertional site. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_107", "contents": "Complications that arise after the tube has been inserted for one day or longer include the potential for tube blockages (obstruction), air leaks, kinking, or entrapment in the lung fissure once the lung has been expanded. Chest tube clogging can lead to retained blood around the heart and lungs that can contribute to complications and increase mortality. [ 11 ]  A common complication after thoracic surgery that arises within 30\u201350% of patients are air leaks.  If a chest tube clogs when there is an air leak the patient will develop a pneumothorax.  This can be life-threatening. [ 12 ]  Here, digital  chest drainage systems  can provide real time information as they monitor  intra-pleural  pressure and air leak flow, constantly. [ 13 ]   Keeping vigilant about chest tube clogging is imperative for the team taking care of the patient in the early postoperative period."}
+{"id": "WikiPedia_Pulmonology$$$corpus_108", "contents": "Minor complications include a subcutaneous  hematoma  or  seroma , anxiety, shortness of breath, and cough (after removing large volume of fluid). In most cases, the chest tube related pain goes away after the chest tube is removed, however, chronic pain related to chest tube induced scarring of the intercostal space is not uncommon. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_109", "contents": "Subcutaneous emphysema  indicates backpressure created by undrained air, often caused by a clogged chest tube or insufficient negative pressure. [ citation needed ]   If a person has subcutaneous emphysema, it is likely their chest tube is not draining and consideration should be given if it should be unclogged or another tube should be placed so that the air leaking from the lung can be adequately drained."}
+{"id": "WikiPedia_Pulmonology$$$corpus_110", "contents": "Problems keeping the site clean or with sterilizing instruments can lead to infections. [ 10 ]  When chest tubes are placed due to either blunt or penetrating trauma, antibiotics may decrease the risks of infectious complications. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_111", "contents": "There is also a risk of complications after the chest tube has been removed. [ 10 ]  Potential complications include problems with re-sealing the chest that can lead to trapped air or if a  foreign object  is retained in the chest after the procedure. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_112", "contents": "Chest tubes are commonly made from clear plastics like  PVC  and soft  silicone . Chest tubes are made in a range of sizes measured by their external diameter from 6 Fr to 40 Fr. Chest tubes, like most catheters, are measured in  French catheter scale . For adults, 20 Fr to 40 Fr (6.7 to 13.3mm external diameter) are commonly used, and 6 Fr to 26 Fr for children. Conventional chest tubes feature multiple drainage fenestrations in the section of the tube which resides inside the patient, as well as distance markers along the length of the tube, and a radiopaque stripe which outlines the first drainage hole. [ 5 ]  Chest tubes are also provided in right angle, trocar, flared, and tapered configurations for different drainage needs. As well, some chest tubes are coated with  heparin  to help prevent thrombus formation, though the effect of this is disputed. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_113", "contents": "Chest tube have an end hole (proximal, toward the patient) and a series of side holes.  The number of side holes is generally 6 on most chest tubes.  The length of tube that has side holes is the effective drainage length (EDL).  In chest tubes designed for pediatric heart surgery, the EDL is shorter, generally by only having 4 side holes. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_114", "contents": "Channel style chest drains, also called Blake drains, are so-called  silastic  drains made of silicone and feature open flutes that reside inside the patient. Drainage is thought to be achieved by capillary action, allowing the fluids to travel through the open grooves into a closed cross section, which contains the fluid and allows it to be suctioned through the tube. [ 18 ]   Though these chest tubes are more expensive than conventional ones, they are theoretically less painful. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_115", "contents": "A  chest drainage  system is typically used to collect chest drainage (air, blood, effusions). Most commonly, drainage systems use three chambers which are based on the three-bottle system. The first chamber allows fluid that is drained from the chest to be collected. The second chamber functions as a \"water seal\", which acts as a one way valve allowing gas to escape, but not reenter the chest. Air bubbling through the water seal chamber is usual when the patient coughs or exhales but may indicate, if continual, a pleural or system leak that should be evaluated critically. It can also indicate a leak of air from the lung. The third chamber is the suction control chamber. The height of the water in this chamber regulates the negative pressure applied to the system. A gentle bubbling through the water column minimizes evaporation of the fluid and indicates that the suction is being regulated to the height of the water column. In this way, increased wall suction does not increase the negative pressure of the system. Newer drainage systems eliminate the water seal using a mechanical check-valve, and some also use a mechanical regulator to regulate the suction pressure. Systems which employ both these are dubbed \"dry\" systems, whereas systems that retain the water seal but use a mechanical regulator are called \"wet-dry\" systems. Systems which use a water seal and water column regulator are called \"wet\" systems. Dry systems are advantageous as tip-overs of wet systems can spill and mix with blood, mandating the replacement of the system. Even newer systems are smaller and more ambulatory so the patient can be sent home for drainage if indicated. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_116", "contents": "The free end of the tube is usually attached to an underwater seal, below the level of the chest. This allows the air or fluid to escape from the pleural space, and prevents anything returning to the chest. Alternatively, the tube can be attached to a  flutter valve . This allows patients with  pneumothorax  to remain more mobile. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_117", "contents": "More recently digital or  electronic chest drainage systems  have been introduced. An onboard motor is used as vacuum source along with an integrated suction control canister and water seal. These systems monitor the patient and will alert if the measured data are out of range. Due to the digital control of the negative pressure, the system is able to objectively quantify the presence of a pleural or system leak. Digital drainage systems allow clinicians to mobilize patients early, even for those on continuous suction, which is difficult to accomplish with the traditional water-seal system under suction. [ 12 ] [ 21 ]  Application of such systems can also lead to a reduction in complications. [ 22 ] [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_118", "contents": "It can be inserted in an area described as the \"safe zone\", which is a region bordered by the lateral border of pectoralis major, a horizontal line inferior to the axilla, the anterior border of latissimus dorsi and a horizontal line superior to the nipple. [ 24 ]   This should translate to the tube being inserted into the fifth intercostal space slightly anterior to the mid axillary line. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_119", "contents": "Chest tubes are usually inserted under  local anesthesia . The skin over the area of insertion is first cleansed with  antiseptic  solution, such as iodine, before  sterile  drapes are placed around the area. The local anesthetic is injected into the skin and down to the muscle, and after the area is numb a small incision is made in the skin and a passage made through the skin and muscle into the chest. The tube is placed through this passage. If necessary, patients may be given additional  analgesics  for the procedure. Once the tube is in place it is sutured to the skin to prevent it falling out and a dressing applied to the area. Once the drain is in place, a  chest radiograph  will be taken to check the location of the drain. The tube stays in for as long as there is air or fluid to be removed, or risk of air gathering."}
+{"id": "WikiPedia_Pulmonology$$$corpus_120", "contents": "Chest tubes can also be placed using a trocar, which is a pointed metallic bar used to guide the tube through the chest wall. This method is less popular due to an increased risk of iatrogenic lung injury. Placement using the  Seldinger technique , in which a blunt guidewire is passed through a needle (over which the chest tube is then inserted) has been described."}
+{"id": "WikiPedia_Pulmonology$$$corpus_121", "contents": "Protocols to maintain chest tube patency by preventing chest tube clogging are necessary."}
+{"id": "WikiPedia_Pulmonology$$$corpus_122", "contents": "The placement technique for postoperative drainage (e.g.  cardiac surgery ) differs from the technique used for emergency situations. At the completion of open cardiac procedures, chest tubes are placed through separate stab incisions, typically near the inferior aspect of the sternotomy incision. In some instances multiple drains may be used to evacuate the mediastinal, pericardial, and pleural spaces. The drainage holes are placed inside the patient and the chest tube is passed out through the incision. Once the tube is in place, it is sutured to the skin to prevent movement. The chest tube is then connected to the drainage canister using additional tubing and connectors and connected to a suction source, typically regulated to -20\u00a0cm of water. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_123", "contents": "After suturing,  dressings  are applied for hygienical reasons covering the wound. First, a y-slit  compress  is used around the tube. Second, a compress (10 x 10\u00a0cm) is placed on top and finally an  adhesive plaster  is added in a way that tension is avoided. A bridle rein is recommended to fix the tube to the skin. This tape bridge will prevent the tube from moving backwards and the possibility to cause clogging. It also prevents pain as it reduces tension on the fixation stitch. Alternatively, a large adhesive plaster that functions like a tape bridge may be used. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_124", "contents": "Chest tubes should be kept free of dependent loops, kinks, and obstructions which may prevent drainage. [ 27 ]  In general, chest tubes are not clamped except during insertion, removal, or when diagnosing air leaks. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_125", "contents": "Chest tube clogging with blood clots of fibrinous material is common. When this occurs, it can result in retained blood around the heart or lungs that can lead to complications such as hematoma that needs to be drained, effusions, empyema, or, in the long term, fibrothorax.  Thus its critical to maintain chest tube patency.   Manual manipulation, often called milking, stripping, fan folding, or tapping, of chest tubes is commonly performed to clear chest tube obstructions. However these approaches are controversial.  No conclusive evidence has demonstrated that any of these techniques are more effective than the others, and no method has shown to improve chest tube drainage. [ 28 ]  Furthermore, chest tube manipulation has proved to increase negative pressure, which may be detrimental, and painful to the patient. [ 28 ]  For these reasons, many hospitals do not allow these types of manual tube manipulations. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_126", "contents": "One option is active chest tube clearance without breaking the sterile field.  According to a consensus of multiple experts in cardiac surgery, anesthesia and critical care in 2019 the ERAS Guidelines for Perioperative Care recommends active clearance of chest tubes to prevent retained blood and other complications. [ 30 ]  Makeshift efforts such as open chest tube clearing that involves breaking the sterile environment separating the chest tube from the drainage canister tubing to suction it out should not be performed. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_127", "contents": "The chest tube can only be removed when the subject clinical condition is stable, the lungs are fully aerated as seen on chest X-ray, chest tube drainage is less than 200 cc per day, and there is no air leak into the lungs pleura. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_128", "contents": "In December 2018 the  European Respiratory Journal  published correspondences that raise the possibility of improving mobility as well as patient outcomes by placing a chest tube more optimally. [ 33 ] [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_129", "contents": "Curschmann's spirals  are a microscopic finding in the  sputum  of asthmatics. They are spiral-shaped mucus plugs from subepithelial mucous gland ducts of bronchi. They may occur in several different lung diseases [ 1 ]  and may refer to parts of the  desquamated   epithelium  seen in lavages from asthmatic patients. [ 2 ]  These microscopic casts are named after German physician  Heinrich Curschmann  (1846-1910). They are often seen in association with  creola bodies  and  Charcot-Leyden crystals . They are elongated microscopic mucous casts from small bronchi and are often found in sputum samples from patients with bronchial asthma. They can be stretched out to a length of around 2\u00a0cm and can sometimes be longer. They have a central core that may be ensheathed in cell debris and mucus. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_130", "contents": "Cystic fibrosis\u2013related diabetes  ( CFRD ) is diabetes specifically caused by  cystic fibrosis , a genetic condition. Cystic fibrosis related diabetes mellitus (CFRD) develops with age, and the median age at diagnosis is 21 years. [ 1 ]  It is an example of  type 3c diabetes  \u2013 diabetes that is caused by damage to the  pancreas  from another disease or condition. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_131", "contents": "CFRD shares features of both  type 1 diabetes  and  type 2 diabetes . The primary cause of CFRD is insulin deficiency due to pancreatic scarring. CFRD patients are typically young and are not obese, and lack metabolic syndrome features. The cause of CFRD is not autoimmune. [ 3 ]  CFRD patients can also have insulin resistance, but ketosis is rare. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_132", "contents": "The endocrine pancreatic function deterioration appears to be secondary to  chronic pancreatitis  and subsequent scarring associated with CF. [ 4 ]  The thick mucus caused by CF is considered to block the pancreatic ducts causing chronic pancreatitis. The failure of the Chloride channel leads to less salt and water in the mucus. It is also probable that the failed Chloride channel leads to high Chloride levels within cells which leads to increased cations (esp potassium and calcium) in those cells. This may also lead to abnormal functioning of the  Islets of Langerhans Cells , the insulin producing endocrine glands of the  pancreas . Inflammation of the surrounding exocrine pancreatic cells is considered to affect the Islet cells but abnormal intracellular electrolytes may be a better explanation as to why CF persons (pwCF) have a high incidence of  diabetes . Abnormal intracellular Electrolytes may also the reason pwCF have a high incidence of Adrenal failure, osteoporosis and Hyperparathyroidism. Muscle function is also likely to be affected including heart muscle function. Research is needed into Intracellular electrolytes in pwCF."}
+{"id": "WikiPedia_Pulmonology$$$corpus_133", "contents": "CFRD occurs in some 20% of adolescents and 40\u201350% of adults affected by CF. [ 3 ]  Though rare in children, it has been described in CF patients of all ages, including infants. Beginning in the teenage years, CFRD has an annual incidence of ~3%, and may be more common in females. It is associated with more severe CF gene mutation types. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_134", "contents": "As survival of CF patients has steadily increased in past decades, CFRD is an increasingly common \u2013 and currently the most common \u2013 complication of CF. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_135", "contents": "In some individuals, the  effect of oxygen on chronic obstructive pulmonary disease  is to cause increased  carbon dioxide retention ,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_136", "contents": "In individuals with chronic obstructive pulmonary disease and similar lung problems, the clinical features of oxygen toxicity are due to high  carbon dioxide  content in the blood ( hypercapnia ). [ 1 ]  This leads to drowsiness (narcosis),  deranged acid-base balance  due to  respiratory acidosis , and death. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_137", "contents": "Many people with  chronic obstructive pulmonary disease  have a low partial pressure of oxygen in the blood and high  partial pressure of carbon dioxide . Treatment with supplemental oxygen may improve their well-being; alternatively, in some this can lead to the adverse effect of elevating the carbon dioxide content in the blood ( hypercapnia ) to levels that may become toxic. [ 3 ] [ 4 ]  With normal lung function, a stimulation to take another breath occurs when a patient has a slight rise in PaCO 2 . The slight rise in PaCO 2  stimulates the respiratory centre in the brain, creating the impulse to take another breath. In some patients with a chronically high level of PaCO 2 , such as those with COPD, the stimulus and drive to breathe is caused by a decrease in PaO 2 . This is called a  hypoxic drive . Thus, when  oxygen is administered  to patients with known CO 2  retention, patients need to be watched for signs of  hypoventilation , a decreased level of consciousness, and  apnea . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_138", "contents": "In individuals with chronic obstructive pulmonary disease who receive supplemental oxygen, carbon dioxide accumulation may occur through two main mechanisms: [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_139", "contents": "In people with chronic obstructive pulmonary disease, carbon dioxide toxicity can be prevented by careful control of the supplemental oxygen. In those with an acute exacerbation of COPD, hypoxic pulmonary vasoconstriction can improve gas exchange, and so just enough oxygen is given to maintain an  oxygen saturation  of 88%\u201392%. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_140", "contents": "In respiratory medicine, a  flutter valve  (also  Pneumostat valve , and  Heimlich  valve ) is a one-way  check valve  used to prevent airflow back into a  chest tube , and usually is applied to drain air from a  pneumothorax . [ 1 ]  The design of the flutter valve features a rubber sleeve in a plastic case, where the rubber sleeve is arranged so that when air flows through the valve the sleeve opens and allows the outwards airflow from the body of the patient; however, when the airflow is reversed, the rubber sleeve closes and halts backwards airflow into the body of the patient."}
+{"id": "WikiPedia_Pulmonology$$$corpus_141", "contents": "The construction of the flutter valve enables it to function as a one-way valve allowing airflow, or the flow of a fluid, in only one direction along the drainage tube. The end of the drainage tube is placed inside the chest cavity of the patient \u2014 into the air mass or into the fluid mass to be drained from the thorax. The flutter valve is placed in the appropriate orientation (designed so that the valve can only be connected in the appropriate orientation) and the  pneumothorax  is thus evacuated from the chest of the patient. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_142", "contents": "Usage of the flutter valve presents potential problems such as clogging of the chest tube, which might provoke the recurrence of the  pneumothorax  or the  subcutaneous emphysema , which can lead to  empyema . Another potential problem leaks of fluid, which are resolved with a small chest-drain; or with a sputum-trap attached to the valve, to function as a reservoir of the draining fluid. Flutter valves (Pneumostat valves) allow patients to ambulate more easily and patients may be able leave the hospital in certain instances. The traditional chest tube collection box often requires a longer hospital stay. Additional to the Heimlich valve, a  chest-drainage management  system, which typically enables the application of vacuum, and the quantification of the effluent; however, a drainage-management system is much a larger apparatus with more tubing, which encumbers the patient."}
+{"id": "WikiPedia_Pulmonology$$$corpus_143", "contents": "Fraction of inspired oxygen  ( F I O 2 ), correctly denoted with a capital  I , [ 1 ]  is the molar or volumetric fraction of  oxygen  in the inhaled gas. Medical patients experiencing difficulty breathing are provided with oxygen-enriched air, which means a higher-than-atmospheric  F I O 2 . Natural air includes 21% oxygen, which is equivalent to  F I O 2  of 0.21. Oxygen-enriched air has a higher  F I O 2  than 0.21; up to 1.00 which means 100% oxygen.  F I O 2  is typically maintained below 0.5 even with mechanical ventilation, to avoid  oxygen toxicity , [ 2 ]  but there are applications when up to 100% is routinely used."}
+{"id": "WikiPedia_Pulmonology$$$corpus_144", "contents": "Often used in  medicine , the  F I O 2  is used to represent the percentage of oxygen participating in gas-exchange.  If the barometric pressure changes, the  F I O 2  may remain constant while the  partial pressure  of oxygen changes with the change in barometric pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_145", "contents": "P A O 2 ,  P E O 2 , and  P I O 2  are the partial pressures of oxygen in alveolar, expired, and inspired gas, respectively, and  \u2060 V D / V t \u2060  is the ratio of physiologic dead space over tidal volume."}
+{"id": "WikiPedia_Pulmonology$$$corpus_146", "contents": "In medicine, the  F I O 2  is the assumed percentage of oxygen concentration participating in  gas exchange  in the  alveoli . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_147", "contents": "The  F I O 2  is used in the  APACHE II  (Acute Physiology and Chronic Health Evaluation II) severity of disease classification system for  intensive care unit  patients. [ 4 ]  For  F I O 2  values equal to or greater than 0.5, the  alveolar\u2013arterial gradient  value should be used in the APACHE II score calculation. Otherwise, the  Pa O 2  will suffice. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_148", "contents": "The ratio between  partial pressure  of  oxygen  in  arterial blood  ( PaO2 ) and  F I O 2  is used as an indicator of  hypoxemia  per the American-European Consensus Conference on  lung injury .  A high  F I O 2  has been shown to alter the ratio of P a O 2 / F I O 2 . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_149", "contents": "The ratio of  partial pressure arterial oxygen  and fraction of inspired oxygen, known as the  Horowitz index  or  Carrico index , is a comparison between the oxygen level in the blood and the oxygen concentration that is breathed. This helps to determine the degree of any problems with how the lungs transfer oxygen to the blood. [ 5 ]  A sample of arterial blood is collected for this test. [ 6 ]  With a normal P a O 2  of 60\u2013100\u00a0mmHg and an oxygen content of  F I O 2  of 0.21 of room air, a normal P a O 2 / F I O 2  ratio ranges between 300 and 500\u00a0mmHg. A P a O 2 / F I O 2  ratio less than or equal to 200\u00a0mmHg is necessary for the diagnosis of  acute respiratory distress syndrome  by the  AECC criteria . [ 7 ]  The more recent Berlin criteria defines mild  ARDS  at a ratio of less than 300\u00a0mmHg."}
+{"id": "WikiPedia_Pulmonology$$$corpus_150", "contents": "A P a O 2 / F I O 2  ratio less than or equal to 250\u00a0mmHg is one of the minor criteria for severe  community acquired pneumonia  (i.e., possible indication for inpatient treatment)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_151", "contents": "A P a O 2 / F I O 2  ratio less than or equal to 333\u00a0mmHg is one of the variables in the  SMART-COP  risk score for intensive respiratory or vasopressor support in community-acquired pneumonia."}
+{"id": "WikiPedia_Pulmonology$$$corpus_152", "contents": "The  alveolar air equation  is the following formula, used to calculate the partial pressure of alveolar gas:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_153", "contents": "Functional residual capacity  ( FRC ) is the  volume  of air present in the  lungs  at the end of passive  expiration . [ 1 ]  At FRC, the opposing elastic recoil forces of the lungs and  chest wall  are in equilibrium and there is no exertion by the  diaphragm  or other respiratory muscles. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_154", "contents": "FRC is the sum of  expiratory reserve volume  (ERV) and residual volume (RV) [ 2 ]  and measures approximately 3000 mL in a 70\u00a0kg, average-sized male. [ 1 ] [ 2 ]  It cannot be estimated through  spirometry , since it includes the residual volume. In order to measure RV precisely, one would need to perform a test such as  nitrogen washout ,  helium dilution  or  body plethysmography . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_155", "contents": "Positioning plays a significant role in altering FRC.\u00a0It is highest when in an upright position and decreases as one moves from upright to supine/prone or Trendelenburg position. The greatest decrease in FRC occurs when going from 60\u00b0 to totally supine at 0\u00b0.\u00a0There is no significant change in FRC as position changes from 0\u00b0 to Trendelenburg of up to \u221230\u00b0. However, beyond \u221230\u00b0, the drop in FRC is considerable. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_156", "contents": "A lowered or elevated FRC is often an indication of some form of  respiratory disease . In  restrictive diseases , the decreased total lung capacity leads to a lower FRC. In turn in  obstructive diseases , the FRC is increased. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_157", "contents": "For instance, in  emphysema , FRC is increased, because the lungs are more  compliant  and the equilibrium between the inward recoil of the lungs and outward recoil of the chest wall is disturbed. As such, patients with emphysema often have noticeably broader chests due to the relatively unopposed outward recoil of the chest wall.  Total lung capacity  also increases, largely as a result of increased functional residual capacity. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_158", "contents": "Obese and pregnant patients will have a lower FRC in the supine position due to the added tissue weight opposing the outward recoil of the chest wall thus reducing chest wall compliance. In pregnancy, this starts at about the fifth month and reaches 10-20% decrease at term. [ 6 ]  FRC tends to increase with aging due to changes in the static recoil of the lungs. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_159", "contents": "The predicted value of FRC was measured for large populations and published in several references. [ 8 ] [ 9 ] [ 10 ] [ 11 ]  FRC was found to vary by a patient's age, height, and sex. Functional residual capacity is directly proportional to height and indirectly proportional with obesity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_160", "contents": "The  LOINC  code is 19843-2 [ 12 ]  and the  SNOMED CT  concept is 65825000. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_161", "contents": "High-frequency ventilation  (HFV) is a type of  mechanical ventilation  which utilizes a  respiratory rate  greater than four times the normal value [ 1 ]  (>150 (V f ) breaths per minute) and very small  tidal volumes . [ 2 ] [ 3 ]   High frequency ventilation is thought to reduce  ventilator-associated lung injury  (VALI), especially in the context of  Acute respiratory distress syndrome  (ARDS) and  acute lung injury  (ALI). [ 2 ]  This is commonly referred to as  lung protective ventilation . [ 4 ]  There are different types of high-frequency ventilation. [ 2 ]  Each type has its own unique advantages and disadvantages. The types of HFV are characterized by the delivery system and the type of exhalation phase."}
+{"id": "WikiPedia_Pulmonology$$$corpus_162", "contents": "High-frequency ventilation may be used alone, or in combination with conventional mechanical ventilation. In general, those devices that need conventional mechanical ventilation do not produce the same lung protective effects as those that can operate without tidal breathing. Specifications and capabilities will vary depending on the device manufacturer."}
+{"id": "WikiPedia_Pulmonology$$$corpus_163", "contents": "With  conventional ventilation  where tidal volumes (V T ) exceed  dead space  (V DEAD ), gas exchange is largely related to bulk flow of gas to the  alveoli . With high-frequency ventilation, the tidal volumes used are smaller than anatomical and equipment dead space and therefore alternative mechanisms of gas exchange occur. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_164", "contents": "High-frequency jet ventilation (HFJV) minimizes movement of the thorax and abdomen and facilitates surgical procedures where even slight motion from spontaneous or intermittent  positive pressure ventilation  may significantly affect the duration and success of the procedure (for example  atrial fibrillation  ablation). HFJV does NOT allow: setting specific tidal volume, sampling  ETCO2  (and because of this, frequent ABGs are required to measure  PaCO2 ). In HFJV a jet is applied with a set driving pressure, followed by passive exhalation for a very short period before the next jet is delivered, creating \"auto-PEEP\" (called pause pressure by the jet ventilator). [ 3 ]  The risk of excessive breath-stacking leading to  barotrauma  and  pneumothorax  is low but not zero."}
+{"id": "WikiPedia_Pulmonology$$$corpus_165", "contents": "In HFJV exhalation is passive (depends on passive lung and chest-wall recoil) whereas in HFOV gas movement is caused by in-and-out movement of the \u201cloudspeaker\u201d  oscillator  membrane.\u00a0 Thus in HFOV both inspiration and expiration are actively caused by the oscillator, and passive exhalation is not allowed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_166", "contents": "In the UK, the Mistral or Monsoon jet ventilator (Acutronic Medical Systems) is most commonly used.  In the United States the Bunnell LifePulse jet ventilator is most commonly used."}
+{"id": "WikiPedia_Pulmonology$$$corpus_167", "contents": "HFJV is provided by the  Bunnell  Life Pulse High-Frequency Ventilator.  HFJV employs an endotracheal tube adaptor in place for the normal 15\u00a0mm ET tube adaptor. A high pressure \"jet\" of gas flows out of the adaptor and into the airway. This jet of gas occurs for a very brief duration, about 0.02 seconds, and at high-frequency: 4-11 hertz. Tidal volumes \u2264 1 ml/Kg are used during HFJV. This combination of small tidal volumes delivered for very short periods of time creates the lowest possible distal airway and alveolar pressures produced by a mechanical ventilator. Exhalation is passive. Jet ventilators utilize various I:E ratios\u2014between 1:1.1 and 1:12\u2014to help achieve optimal exhalation. Conventional mechanical breaths are sometimes used to aid in reinflating the lung. Optimal PEEP is used to maintain alveolar inflation and promote ventilation-to-perfusion matching. Jet ventilation has been shown to reduce ventilator induced lung injury by as much as 20%.  Usage of high-frequency jet ventilation is recommended in neonates and adults with severe lung injury. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_168", "contents": "The Bunnell Life Pulse High-Frequency Ventilator is indicated for use in ventilating critically ill infants with  pulmonary interstitial emphysema  (PIE). Infants studied ranged in birth weight from 750 to 3529 grams and in  gestation age  from 24 to 41 weeks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_169", "contents": "The Bunnell Life Pulse High-Frequency Ventilator is also indicated for use in ventilating\ncritically ill infants with  respiratory distress syndrome  (RDS) complicated by pulmonary air leaks who are, in the opinion of their physicians, failing on  conventional ventilation . Infants of this description studied ranged in birth weight from 600 to 3660 grams and in  gestational age  from 24 to 38 weeks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_170", "contents": "The adverse side effects noted during the use of high-frequency ventilation include those\ncommonly found during the use of conventional positive pressure ventilators. These adverse effects include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_171", "contents": "High-frequency jet ventilation is contraindicated in patients requiring tracheal tubes smaller than 2.5\u00a0mm ID."}
+{"id": "WikiPedia_Pulmonology$$$corpus_172", "contents": "Settings that can be adjusted in HFJV include 1) inspiratory time, 2) driving pressure, 3) frequency, 4) FiO2, and 5) humidity.\u00a0 Increases in FiO2, inspiratory time, and frequency improve oxygenation (by increasing \"auto-PEEP\" or pause pressure), while an increase in driving pressure and a decrease in frequency improve ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_173", "contents": "The peak inspiratory pressure (P IP ) window displays the average P IP . During startup a P IP  sample is taken with every inhalation cycle and is averaged with all other samples taken over the most recent ten-second period. After regular operation begins, samples are averaged over the most recent twenty-second period."}
+{"id": "WikiPedia_Pulmonology$$$corpus_174", "contents": "The value displayed in the \u0394 P  (pressure difference) window represents the difference between the P IP  value and the PEEP value."}
+{"id": "WikiPedia_Pulmonology$$$corpus_175", "contents": "The servo pressure display indicates the amount of pressure the machine must generate\ninternally in order to achieve the P IP  appearing in the servo-display.  Its value can range from 0\u201420 psi (0\u2014137.9  kPa ).  If the P IP  sensed or approximated at the distal tip of the tracheal tube deviates from the desired P IP , the machine automatically generates more or less internal pressure in an attempt to compensate for the change. The servo-pressure display keeps the  operator  informed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_176", "contents": "The servo display is a general clinical indicator of changes in the  compliance  or  resistance  of the patient's lungs, as well as loss of lung volume due to tension  pneumothorax ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_177", "contents": "In High-frequency oscillatory ventilation (HFOV) the airway is pressurized to a set mean airway pressure (called continuous lung-distending pressure) through an adjustable expiratory valve.\u00a0 Small pressure oscillations delivered at a very high rate are superimposed by the action of a \u201cloudspeaker\u201d oscillator membrane. HFOV is often used in premature neonates with respiratory distress syndrome who fail to oxygenate appropriately with lung-protective settings of conventional ventilation.\u00a0 It has also been used in ARDS in adults, but two studies (the OSCAR and OSCILLATE trials) showed negative results for this indication."}
+{"id": "WikiPedia_Pulmonology$$$corpus_178", "contents": "Parameters that can be set in HFOV includes the continuous lung-distending pressure, oscillation amplitude and frequency, I:E ratio (positive-oscillation/negative-oscillation ratio), fresh gas flow (called bias flow), and FiO2.\u00a0 Increases in continuous lung-distending pressure and FiO2 will improve oxygenation.\u00a0 Increases in amplitude or fresh gas flow and decreases in frequency will improve ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_179", "contents": "HFPV  \u2014 High-frequency percussive ventilation combines HFV plus time cycled, pressure-limited controlled mechanical ventilation (i.e., pressure control ventilation, PCV)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_180", "contents": "HFPPV  \u2014 High-frequency positive pressure ventilation is rarely used anymore, having been replaced by high-frequency jet, oscillatory and percussive types of ventilation. HFPPV is delivered through the  endotracheal tube  using a conventional ventilator whose frequency is set near its upper limits.  HFPV began to be used in selected centres in the 1980s. It is a hybrid of conventional  mechanical ventilation  and high-frequency oscillatory ventilation.  It has been used to salvage patients with persistent  hypoxemia  when on conventional mechanical ventilation or, in some cases, used as a primary modality of ventilatory support from the start. [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_181", "contents": "HFFI  \u2014 High Frequency Flow Interruption is similar to high-frequency jet ventilation but the gas control mechanism is different. Frequently a rotating bar or ball with a small opening is placed in the path of a high pressure gas. As the bar or ball rotates and the opening lines-up with the gas flow, a small, brief pulse of gas is allowed to enter the airway. Frequencies for HFFI are typically limited to maximum of about 15 hertz."}
+{"id": "WikiPedia_Pulmonology$$$corpus_182", "contents": "High-frequency ventilation (active)  \u2014 HFV-A is notable for the active exhalation mechanic included.  Active exhalation means a negative pressure is applied to force volume out of the lungs.  The CareFusion 3100A and 3100B are similar in all aspects except the target patient size.  The 3100A is designed for use on patients up to 35 kilograms and the 3100B is designed for use on patients larger than 35 kilograms."}
+{"id": "WikiPedia_Pulmonology$$$corpus_183", "contents": "High-frequency oscillatory ventilation was first described in 1972 [ 8 ]  and is used in neonates and adult patient populations to reduce lung injury, or to prevent further lung injury. [ 9 ]  HFOV is characterized by high respiratory rates between 3.5 and 15  hertz  (210 - 900 breaths per minute) and having both inhalation and exhalation maintained by active pressures.  The rates used vary widely depending upon patient size, age, and disease process.  In HFOV the pressure oscillates around the constant distending pressure (equivalent to mean airway pressure [MAP]) which in effect is the same as  positive end-expiratory pressure  (PEEP). Thus gas is pushed into the lung during inspiration, and then pulled out during expiration. HFOV generates very low tidal volumes that are generally less than the dead space of the lung.  Tidal volume is dependent on endotracheal tube size, power and frequency. Different mechanisms (direct bulk flow - convective, Taylorian dispersion,  Pendelluft  effect, asymmetrical velocity profiles, cardiogenic mixing and molecular diffusion) of gas transfer are believed to come into play in HFOV compared to normal mechanical ventilation. It is often used in patients who have refractory hypoxemia that cannot be corrected by normal mechanical ventilation such as is the case in the following disease processes: severe ARDS, ALI and other oxygenation diffusion issues.  In some neonatal patients HFOV may be used as the first-line ventilator due to the high susceptibility of the premature infant to lung injury from conventional ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_184", "contents": "The vibrations are created by an electromagnetic valve that controls a piston. The resulting vibrations are similar to those produced by a stereo speaker. The height of the vibrational wave is the amplitude. Higher amplitudes create greater pressure fluctuations which move more gas with each vibration. The number of vibrations per minute is the frequency. One Hertz equals 60 cycles per minute. The higher amplitudes at lower frequencies will cause the greatest fluctuation in pressure and move the most gas."}
+{"id": "WikiPedia_Pulmonology$$$corpus_185", "contents": "Altering the\u00a0% inspiratory time (T %i ) changes the proportion of the time in which the vibration or sound wave is above the baseline versus below it. Increasing the\u00a0% Inspiratory Time will also increase the volume of gas moved or tidal volume. Decreasing the frequency, increasing the amplitude, and increasing the\u00a0% inspiratory time will all increase tidal volume and eliminate CO 2 . Increasing the tidal volume will also tend to increase the mean airway pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_186", "contents": "The bias flow controls and indicates the rate of continuous flow of humidified blended gas through the patient circuit.  The control knob is a 15-turn pneumatic valve which increases flow as it is turned."}
+{"id": "WikiPedia_Pulmonology$$$corpus_187", "contents": "The mean pressure adjust setting adjusts the mean airway pressure (P AW ) by controlling the resistance of the airway pressure control valve.  The mean airway pressure will change and requires the mean pressure adjust to be adjusted when the following settings are changed:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_188", "contents": "During high-frequency oscillatory ventilation (HFOV), P AW  is the primary variable affecting oxygenation and is set independent of other variables on the oscillator. Because distal airway pressure changes during HFOV are minimal, [ 10 ] [ 11 ]  the P AW  during HFOV can be viewed in a manner similar to the  PEEP  level in conventional ventilation. [ 12 ]  The optimal P AW  can be considered as a compromise between maximal lung recruitment and minimal overdistention."}
+{"id": "WikiPedia_Pulmonology$$$corpus_189", "contents": "The mean pressure limit controls the limit above which proximal P AW  cannot be increased by setting the control pressure of the pressure limit valve.  The mean pressure limit range is 10-45 cmH 2 O."}
+{"id": "WikiPedia_Pulmonology$$$corpus_190", "contents": "The power setting is set as amplitude to establish a measured change of pressure (\u0394P).  Amplitude/Power is a setting which determines the amount of power that is driving the oscillator piston forward and backward resulting in an air volume ( tidal volume ) displacement.  The effect of the amplitude on the \u0394P that it is changed by the displacement of the oscillator piston and hence the oscillatory pressure (\u0394P).  The power setting interacts with P AW  conditions existing within the patient circuit to produce the resulting \u0394P."}
+{"id": "WikiPedia_Pulmonology$$$corpus_191", "contents": "The percent of inspiratory time is a setting which determines the percent of cycle time the piston is traveling toward (or at its final inspiratory position).  The inspiratory percent range is 30\u201450%."}
+{"id": "WikiPedia_Pulmonology$$$corpus_192", "contents": "The frequency setting is measured in hertz (hz).  The control knob is a 10-turn clockwise-increasing potentiometer covering a range of 3\u00a0Hz to 15\u00a0Hz.  The set frequency is displayed on a digital meter on the face of the ventilator.  One Hertz is (-/+5%) equal to 1 breath per second, or 60 breaths per minute (e.g., 10\u00a0Hz = 600 breaths per minute).  Changes in\nfrequency are inversely proportional to the amplitude and thus delivered  tidal volume ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_193", "contents": "Oscillation trough pressure is the instantaneous pressure within the HFOV circuit following the oscillating piston reaching its complete negative deflection."}
+{"id": "WikiPedia_Pulmonology$$$corpus_194", "contents": "Transtracheal jet ventilation  refers to a type of high-frequency ventilation, low  tidal volume  ventilation provided via a laryngeal catheter by specialized ventilators that are usually only available in the operating room or intensive care unit. This procedure is occasionally employed in the operating room when a difficult airway is anticipated.  Such as  Treacher Collins syndrome ,  Robin sequence , head and neck  surgery  with supraglottic or glottic obstruction). [ 13 ] [ 14 ] [ 15 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_195", "contents": "Hyperinflation therapy  ( HIT ) is a very common [ 1 ]  therapy performed on patients who have some sort of respiratory distress.  The therapy involves applying volumes greater than normal to reinflate the collapsed alveoli in the lungs.  There are many different techniques used to administer hyperinflation therapy. [ 2 ]   The  respiratory therapist  typically decides which method is best for each patient. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_196", "contents": "A  hyperoxia test  is a test that is performed\u2014usually on an infant\u2014to determine whether the patient's  cyanosis  is due to lung disease or a problem with blood circulation. It is performed by measuring the  arterial blood gases  of the patient while they breathe room air, then re-measuring the blood gases after the patient has breathed 100% oxygen for 10 minutes. [ 1 ] :141 [ 2 ] :141 [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_197", "contents": "If the cause of the cyanosis is poor oxygen saturation by the lungs, allowing the patient to breathe 100% oxygen will augment the lungs' ability to saturate the blood with oxygen, and the  partial pressure  of oxygen in the arterial blood will rise (usually above 150\u00a0 mmHg [ 3 ] ). However, if the lungs are healthy and already fully saturating the blood that is delivered to them, then supplemental oxygen will have no effect, and the partial pressure of oxygen will usually remain below 100\u00a0mmHg. [ 3 ]  In this case, the cyanosis is most likely due to blood that moves from the systemic veins to the systemic arteries via a  right-to-left shunt  without ever going through the lungs. [ 1 ] :141"}
+{"id": "WikiPedia_Pulmonology$$$corpus_198", "contents": "This  pediatrics  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_199", "contents": "This  cardiovascular system  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_200", "contents": "Hypoxia  is a condition in which the body or a region of the body is deprived of adequate  oxygen  supply at the  tissue  level. [ 1 ]  Hypoxia may be classified as either  generalized , affecting the whole body, or  local , affecting a region of the body. [ 2 ]  Although hypoxia is often a  pathological  condition, variations in  arterial  oxygen concentrations can be part of the normal  physiology , for example, during strenuous  physical exercise ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_201", "contents": "Hypoxia differs from  hypoxemia  and anoxemia, in that hypoxia refers to a state in which oxygen present in a tissue or the whole body is insufficient, whereas hypoxemia and anoxemia refer specifically to states that have low or no  oxygen in the blood . [ 3 ]  Hypoxia in which there is complete absence of oxygen supply is referred to as  anoxia ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_202", "contents": "Hypoxia can be due to external causes, when the breathing gas is hypoxic, or internal causes, such as reduced effectiveness of gas transfer in the lungs, reduced capacity of the blood to carry oxygen, compromised general or local  perfusion , or inability of the affected tissues to extract oxygen from, or metabolically process, an adequate supply of oxygen from an adequately oxygenated blood supply."}
+{"id": "WikiPedia_Pulmonology$$$corpus_203", "contents": "Generalized hypoxia occurs in healthy people when they ascend to  high altitude , where it causes  altitude sickness  leading to potentially fatal complications:  high altitude pulmonary edema  ( HAPE ) and  high altitude cerebral edema  ( HACE ). [ 4 ]   Hypoxia also occurs in healthy individuals when breathing inappropriate mixtures of gases with a low oxygen content, e.g., while  diving underwater , especially when using malfunctioning closed-circuit  rebreather  systems that control the amount of oxygen in the supplied air. Mild, non-damaging  intermittent hypoxia  is used intentionally during  altitude training  to develop an athletic performance adaptation at both the systemic and cellular level. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_204", "contents": "Hypoxia is a common  complication  of  preterm birth  in newborn infants. Because the  lungs  develop late in  pregnancy , premature infants frequently possess underdeveloped lungs. To improve blood oxygenation, infants at risk of hypoxia may be placed inside  incubators  that provide warmth,  humidity , and supplemental oxygen. More serious cases are treated with  continuous positive airway pressure  (CPAP)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_205", "contents": "Hypoxia exists when there is a reduced amount of oxygen in the tissues of the body. Hypoxemia refers to a reduction in arterial oxygenation below the normal range, regardless of whether gas exchange is impaired in the lung, arterial oxygen content (C a O 2  \u2013 which represents the amount of oxygen delivered to the tissues) is adequate, or tissue hypoxia exists. [ 6 ]  The classification categories are not always mutually exclusive, and hypoxia can be a consequence of a wide variety of causes."}
+{"id": "WikiPedia_Pulmonology$$$corpus_206", "contents": "Intermittent hypoxic training  induces mild generalized hypoxia for short periods as a training method to improve sporting performance. This is not considered a medical condition. [ 14 ]  Acute cerebral hypoxia leading to blackout can occur during  freediving . This is a consequence of prolonged voluntary apnea underwater, and generally occurs in trained athletes in good health and good physical condition. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_207", "contents": "Hypoxia may affect the whole body, or just some parts."}
+{"id": "WikiPedia_Pulmonology$$$corpus_208", "contents": "The term  generalized hypoxia  may refer to hypoxia affecting the whole body, [ 16 ]  or may be used as a synonym for  hypoxic hypoxia , which occurs when there is insufficient oxygen in the breathing gas to oxygenate the blood to a level that will adequately support normal metabolic processes, [ 8 ] [ 13 ] [ 7 ]  and which will inherently affect all perfused tissues."}
+{"id": "WikiPedia_Pulmonology$$$corpus_209", "contents": "The symptoms of generalized hypoxia depend on its severity and acceleration of onset.\nIn the case of  altitude sickness , where hypoxia develops gradually, the symptoms include  fatigue ,  numbness  / tingling of  extremities ,  nausea , and  cerebral hypoxia . [ 17 ] [ 18 ]  These symptoms are often difficult to identify, but early detection of symptoms can be critical. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_210", "contents": "In severe hypoxia, or hypoxia of very rapid onset,  ataxia , confusion, disorientation,  hallucinations , behavioral change, severe  headaches , reduced level of consciousness,  papilloedema ,  breathlessness , [ 17 ]   pallor , [ 20 ]   tachycardia , and  pulmonary hypertension  eventually leading to the late signs  cyanosis ,  slow heart rate ,  cor pulmonale , and  low blood pressure  followed by  heart failure  eventually leading to  shock  and  death . [ 21 ] [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_211", "contents": "Because  hemoglobin  is a darker red when it is not bound to oxygen ( deoxyhemoglobin ), as opposed to the rich red color that it has when bound to oxygen ( oxyhemoglobin ), when seen through the skin it has an increased tendency to reflect blue light back to the eye. [ 23 ]  In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may appear 'cherry red' instead of cyanotic. [ 24 ]  Hypoxia can cause  premature birth , and injure the liver, among other deleterious effects. [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_212", "contents": "Hypoxia that is localized to a region of the body, such as an organ or a limb. is usually the consequence of  ischemia , the reduced perfusion to that organ or limb, and may not necessarily be associated with general hypoxemia. A locally reduced perfusion is generally caused by an increased resistance to flow through the blood vessels of the affected area."}
+{"id": "WikiPedia_Pulmonology$$$corpus_213", "contents": "Ischemia is a restriction in blood supply to any tissue, muscle group, or organ, causing a shortage of oxygen. [ 27 ] [ 28 ]   Ischemia is generally caused by problems with  blood vessels , with resultant damage to or dysfunction of tissue i.e. hypoxia and  microvascular dysfunction . [ 29 ] [ 30 ]  It also means local hypoxia in a given part of a body sometimes resulting from  vascular occlusion  such as  vasoconstriction ,  thrombosis , or  embolism . Ischemia comprises not only insufficiency of oxygen, but also reduced availability of  nutrients  and inadequate removal of  metabolic wastes . Ischemia can be a partial (poor  perfusion ) or total blockage."}
+{"id": "WikiPedia_Pulmonology$$$corpus_214", "contents": "Compartment syndrome is a condition in which increased pressure within one of the body's  anatomical compartments  results in insufficient blood supply to  tissue  within that space. [ 31 ] [ 32 ]  There are two main types:  acute  and  chronic . [ 31 ]  Compartments of the leg or arm are most commonly involved. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_215", "contents": "If tissue is not being perfused properly, it may feel cold and appear pale; if severe, hypoxia can result in  cyanosis , a blue discoloration of the skin. If hypoxia is very severe, a tissue may eventually become gangrenous."}
+{"id": "WikiPedia_Pulmonology$$$corpus_216", "contents": "Any living tissue can be affected by hypoxia, but some are particularly sensitive, or have more noticeable or notable consequences."}
+{"id": "WikiPedia_Pulmonology$$$corpus_217", "contents": "Cerebral hypoxia is hypoxia specifically involving the brain. The four categories of cerebral hypoxia in order of increasing severity are: diffuse cerebral hypoxia (DCH), focal cerebral ischemia,  cerebral infarction , and global cerebral ischemia. Prolonged hypoxia induces  neuronal  cell death via  apoptosis , resulting in a hypoxic brain injury. [ 34 ] [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_218", "contents": "Oxygen deprivation  can be hypoxic (reduced general oxygen availability) or ischemic (oxygen deprivation due to a disruption in blood flow) in origin. Brain injury as a result of oxygen deprivation is generally termed hypoxic injury.  Hypoxic ischemic encephalopathy  (HIE) is a condition that occurs when the entire brain is deprived of an adequate oxygen supply, but the deprivation is not total. While HIE is associated in most cases with oxygen deprivation in the neonate due to  birth asphyxia , it can occur in all age groups, and is often a complication of  cardiac arrest . [ 36 ] [ 37 ] [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_219", "contents": "Although corneal hypoxia can arise from any of several causes, it is primarily attributable to the prolonged use of  contact lenses . [ 39 ]   The corneas are not perfused and get their oxygen from the atmosphere by diffusion. Impermeable contact lenses form a barrier to this  diffusion , and therefore can cause damage to the corneas. Symptoms may include irritation, excessive tearing and  blurred vision . The sequelae of corneal hypoxia include punctate  keratitis ,  corneal neovascularization  and epithelial microcysts. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_220", "contents": "Intrauterine hypoxia, also known as fetal hypoxia, occurs when the fetus is  deprived  of an adequate supply of  oxygen .  It may be due to a variety of reasons such as  prolapse  or  occlusion  of the  umbilical cord ,  placental infarction , maternal diabetes (prepregnancy or  gestational diabetes ) [ 40 ]  and  maternal smoking .  Intrauterine growth restriction  may cause or be the result of hypoxia.  Intrauterine hypoxia can cause cellular damage that occurs within the  central nervous system  (the brain and spinal cord). This results in an increased mortality rate, including an increased risk of  sudden infant death syndrome  (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as  epilepsy ,  attention deficit hyperactivity disorder ,  eating disorders  and  cerebral palsy . [ 41 ] [ 42 ] [ 43 ] [ 44 ] [ 45 ] [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_221", "contents": "Tumor hypoxia is the situation where  tumor  cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironements in solid tumors are a result of available oxygen being consumed within 70 to 150 \u03bcm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. The severity of hypoxia is related to tumor types and varies between different types. Research has shown that the level of oxygenation in hypoxic tumor tissues is poorer than normal tissues and it is reported somewhere between 1%\u20132% O2. [ 47 ]  In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism.  Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior. [ 48 ] [ 49 ]  Tumour hypoxia is usually associated with highly malignant tumours, which frequently do not respond well to treatment. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_222", "contents": "In acute exposure to hypoxic hypoxia on the  vestibular system  and the visuo-vestibular interactions, the gain of the  vestibulo-ocular reflex  (VOR) decreases under mild hypoxia at altitude. Postural control is also disturbed by hypoxia at altitude, postural sway is increased, and there is a correlation between hypoxic stress and  adaptive tracking  performance. [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_223", "contents": "Arterial oxygen tension can be measured by blood gas analysis of an arterial blood sample, and less reliably by  pulse oximetry , which is not a complete measure of circulatory oxygen sufficiency. If there is insufficient blood flow or insufficient hemoglobin in the blood (anemia), tissues can be hypoxic even when there is high arterial oxygen saturation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_224", "contents": "Oxygen passively diffuses in the lung  alveoli  according to a concentration gradient, also referred to as a  partial pressure  gradient. Inhaled air rapidly reaches saturation with water vapour, which slightly reduces the partial pressures of the other components. Oxygen diffuses from the inhaled air to  arterial  blood, where its partial pressure is around 100\u00a0mmHg (13.3\u00a0kPa). [ 58 ]  In the blood, oxygen is bound to hemoglobin, a protein in  red blood cells . The binding capacity of hemoglobin is influenced by the  partial pressure  of oxygen in the environment, as described by the  oxygen\u2013hemoglobin dissociation curve . A smaller amount of oxygen is transported in solution in the blood. [ 59 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_225", "contents": "In systemic tissues, oxygen again diffuses down a concentration gradient into cells and their  mitochondria , where it is  used to produce energy  in conjunction with the breakdown of  glucose ,  fats , and some  amino acids . [ 60 ]  Hypoxia can result from a failure at any stage in the delivery of oxygen to cells. This can include low partial pressures of oxygen in the breathing gas, problems with diffusion of oxygen in the lungs through the interface between air and blood, insufficient available hemoglobin, problems with blood flow to the end user tissue, problems with the breathing cycle regarding rate and volume, and physiological and mechanical  dead space .\nExperimentally, oxygen diffusion becomes  rate limiting  when arterial oxygen partial pressure falls to 60\u00a0mmHg (5.3\u00a0kPa) or below. [ clarification needed ] [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_226", "contents": "Almost all the oxygen in the blood is bound to hemoglobin, so interfering with this carrier molecule limits oxygen delivery to the perfused tissues. Hemoglobin increases the oxygen-carrying capacity of blood by about 40-fold, [ 62 ]  with the ability of hemoglobin to carry oxygen influenced by the partial pressure of oxygen in the local environment, a relationship described in the oxygen\u2013hemoglobin dissociation curve. When the ability of hemoglobin to carry oxygen is degraded, a hypoxic state can result. [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_227", "contents": "Ischemia, meaning insufficient blood flow to a tissue, can also result in hypoxia in the affected tissues. This is called 'ischemic hypoxia'. Ischemia can be caused by an  embolism , a  heart attack  that decreases overall blood flow, trauma to a tissue that results in damage reducing perfusion, and a variety of  other causes . A consequence of insufficient blood flow causing local hypoxia is  gangrene  that occurs in  diabetes . [ 64 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_228", "contents": "Diseases such as  peripheral vascular disease  can also result in local hypoxia. Symptoms are worse when a limb is used, increasing the oxygen demand in the active muscles. Pain may also be felt as a result of increased hydrogen ions leading to a decrease in blood pH ( acidosis ) created as a result of  anaerobic metabolism . [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_229", "contents": "G-LOC , or g-force induced loss of consciousness, is a special case of ischemic hypoxia which occurs when the body is subjected to high enough acceleration sustained for long enough to lower cerebral blood pressure and circulation to the point where  loss of consciousness  occurs due to cerebral hypoxia. The human body is most sensitive to longitudinal acceleration towards the head, as this causes the largest hydrostatic pressure deficit in the head. [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_230", "contents": "This refers specifically to hypoxic states where the arterial content of oxygen is insufficient. [ 67 ]  This can be caused by alterations in  respiratory drive , such as in  respiratory alkalosis , physiological or pathological shunting of blood, diseases interfering in lung function resulting in a  ventilation-perfusion mismatch , such as a  pulmonary embolus , or alterations in the partial pressure of oxygen in the environment or lung alveoli, such as may occur at altitude or when diving. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_231", "contents": "Common disorders that can cause respiratory dysfunction include trauma to the head and spinal cord, nontraumatic acute myelopathies, demyelinating disorders, stroke,  Guillain\u2013Barr\u00e9 syndrome , and  myasthenia gravis . These dysfunctions may necessitate mechanical ventilation. Some chronic neuromuscular disorders such as motor neuron disease and muscular dystrophy may require ventilatory support in advanced stages. [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_232", "contents": "Carbon monoxide  competes with oxygen for binding sites on hemoglobin molecules. As carbon monoxide binds with hemoglobin hundreds of times tighter than oxygen, it can prevent the carriage of oxygen. [ 68 ] \nCarbon monoxide poisoning can occur acutely, as with smoke intoxication, or over a period of time, as with cigarette smoking. Due to physiological processes, carbon monoxide is maintained at a resting level of 4\u20136 ppm. This is increased in urban areas (7\u201313 ppm) and in smokers (20\u201340 ppm). [ 69 ]   A carbon monoxide level of 40 ppm is equivalent to a reduction in hemoglobin levels of 10 g/L. [ 69 ] [ note 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_233", "contents": "Carbon monoxide has a second toxic effect, namely removing the  allosteric shift  of the oxygen dissociation curve and shifting the foot of the curve to the left. [ clarification needed ]   In so doing, the hemoglobin is less likely to release its oxygen at the peripheral tissues. [ clarification needed ] [ 62 ]  Certain  abnormal hemoglobin variants  also have higher than normal affinity for oxygen, and so are also poor at delivering oxygen to the periphery. [ clarification needed ] [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_234", "contents": "Atmospheric pressure reduces with altitude  and proportionally, so does the oxygen content of the air. [ 70 ]  The reduction in the partial pressure of inspired oxygen at higher altitudes lowers the oxygen saturation of the blood, ultimately leading to hypoxia. [ 70 ]  The clinical features of altitude sickness include: sleep problems, dizziness, headache and oedema. [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_235", "contents": "The  breathing gas  may contain an insufficient partial pressure of oxygen. Such situations may lead to unconsciousness without symptoms since carbon dioxide levels remain normal and the human body senses pure hypoxia poorly. Hypoxic breathing gases can be defined as mixtures with a lower oxygen fraction than air, though gases containing sufficient oxygen to reliably maintain consciousness at normal sea level atmospheric pressure may be described as normoxic even when the oxygen fraction is slightly below normoxic. Hypoxic breathing gas mixtures in this context are those which will not reliably maintain consciousness at sea level pressure. [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_236", "contents": "One of the most widespread circumstances of exposure to hypoxic breathing gas is ascent to altitudes where the ambient pressure drops sufficiently to reduce the partial pressure of oxygen to hypoxic levels. [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_237", "contents": "Gases with as little as 2% oxygen by volume in a helium diluent are used for deep  diving  operations. The ambient pressure at 190  msw  is sufficient to provide a partial pressure of about 0.4 bar, which is suitable for  saturation diving . As the divers are  decompressed , the breathing gas must be oxygenated to maintain a breathable atmosphere. [ 72 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_238", "contents": "It is also possible for the breathing gas for diving to have a dynamically controlled oxygen partial pressure, known as a  set point , which is maintained in the breathing gas circuit of a  diving rebreather  by addition of oxygen and diluent gas to maintain the desired oxygen partial pressure at a safe level between hypoxic and hyperoxic at the ambient pressure due to the current depth. A malfunction of the control system may lead to the gas mixture becoming hypoxic at the current depth. [ 73 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_239", "contents": "A special case of hypoxic breathing gas is encountered in deep freediving where the partial pressure of the oxygen in the lung gas is depleted during the dive, but remains sufficient at depth, and when it drops during ascent, it becomes too hypoxic to maintain consciousness, and the diver  loses consciousness  before reaching the surface. [ 15 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_240", "contents": "Hypoxic gases may also occur in industrial, mining, and firefighting environments. Some of these may also be toxic or narcotic, others are just asphyxiant. Some are recognisable by smell, others are odourless."}
+{"id": "WikiPedia_Pulmonology$$$corpus_241", "contents": "Inert gas asphyxiation may be deliberate with use of a  suicide bag . Accidental death has occurred in cases where concentrations of nitrogen in controlled atmospheres, or methane in mines, has not been detected or appreciated. [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_242", "contents": "Hemoglobin's function can also be lost by chemically oxidizing its iron atom to its ferric form.  This form of inactive hemoglobin is called  methemoglobin  and can be made by ingesting sodium nitrite [ 75 ] [ unreliable medical source? ]  as well as certain drugs and other chemicals. [ 76 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_243", "contents": "Hemoglobin plays a substantial role in carrying oxygen throughout the body, [ 62 ]  and when it is deficient,  anemia  can result, causing 'anaemic hypoxia' if tissue oxygenation is decreased.  Iron deficiency  is the most common cause of anemia. As iron is used in the synthesis of hemoglobin, less hemoglobin will be synthesised when there is less iron, due to insufficient intake, or poor absorption. [ 63 ] :\u200a997\u201399"}
+{"id": "WikiPedia_Pulmonology$$$corpus_244", "contents": "Anemia is typically a chronic process that is compensated over time by increased levels of red blood cells via upregulated  erythropoetin . A chronic hypoxic state can result from a poorly compensated anaemia. [ 63 ] :\u200a997\u201399"}
+{"id": "WikiPedia_Pulmonology$$$corpus_245", "contents": "Histotoxic hypoxia (also called histoxic hypoxia) is the inability of cells to take up or use oxygen from the bloodstream, despite physiologically normal delivery of oxygen to such cells and tissues. [ 77 ]  Histotoxic hypoxia results from tissue poisoning, such as that caused by  cyanide  (which acts by inhibiting  cytochrome oxidase ) and certain other  poisons  like  hydrogen sulfide  (byproduct of sewage and used in leather tanning). [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_246", "contents": "Tissue hypoxia from low oxygen delivery may be due to low haemoglobin concentration (anaemic hypoxia), low cardiac output (stagnant hypoxia) or low haemoglobin saturation (hypoxic hypoxia). [ 79 ]  The consequence of oxygen deprivation in tissues is a switch to anaerobic metabolism at the cellular level. As such, reduced systemic blood flow may result in increased serum lactate. [ 80 ]  Serum lactate levels have been correlated with illness severity and mortality in critically ill adults and in ventilated neonates with respiratory distress. [ 80 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_247", "contents": "All vertebrates must maintain oxygen homeostasis to survive, and have evolved physiological systems to ensure adequate oxygenation of all tissues. In air breathing vertebrates this is based on lungs to acquire the oxygen, hemoglobin in red corpuscles to transport it, a vasculature to distribute, and a heart to deliver. Short term variations in the levels of oxygenation are sensed by chemoreceptor cells which respond by activating existing proteins, and over longer terms by regulation of gene transcription. Hypoxia is also involved in the pathogenesis of some common and severe pathologies. [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_248", "contents": "The most common causes of death in an aging population include myocardial infarction, stroke and cancer. These diseases share a common feature that limitation of oxygen availability contributes to the development of the pathology. Cells and organisms are also able to respond adaptively to hypoxic conditions, in ways that help them to cope with these adverse conditions. Several systems can sense oxygen concentration and may respond with adaptations to acute and long-term hypoxia. [ 81 ] \nThe systems activated by hypoxia usually help cells to survive and overcome the hypoxic conditions.  Erythropoietin , which is produced in larger quantities by the kidneys under hypoxic conditions, is an essential hormone that stimulates production of red blood cells, which are the primary transporter of blood oxygen, and glycolytic enzymes are involved in anaerobic ATP formation. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_249", "contents": "Hypoxia-inducible factors (HIFs) are  transcription factors  that respond to decreases in available oxygen in the cellular environment, or hypoxia. [ 82 ] [ 83 ]  The HIF signaling cascade mediates the effects of hypoxia on the cell. Hypoxia often keeps cells from  differentiating . However, hypoxia promotes the  formation of blood vessels , and is important for the formation of a  vascular system  in  embryos  and tumors. The hypoxia in  wounds  also promotes the migration of  keratinocytes  and the restoration of the  epithelium . [ 84 ]  It is therefore not surprising that HIF-1 modulation was identified as a promising treatment paradigm in wound healing. [ 85 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_250", "contents": "Exposure of a tissue to repeated short periods of hypoxia, between periods of normal oxygen levels, influences the tissue's later response to prolonged ischaemic exposure. Thus is  known as  ischaemic preconditioning , and it is known to occur in many tissues. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_251", "contents": "If oxygen delivery to cells is insufficient for the demand (hypoxia), electrons will be shifted to  pyruvic acid  in the process of  lactic acid fermentation .  This temporary measure (anaerobic metabolism) allows small amounts of energy to be released.  Lactic acid build up (in tissues and blood) is a sign of inadequate mitochondrial oxygenation, which may be due to hypoxemia, poor blood flow (e.g., shock) or a combination of both. [ 86 ]  If severe or prolonged it could lead to cell death. [ 87 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_252", "contents": "In humans, hypoxia is detected by the peripheral chemoreceptors in the  carotid body  and  aortic body , with the carotid body chemoreceptors being the major mediators of reflex responses to hypoxia. [ 88 ]  This response does not control ventilation rate at normal P O 2 , but below normal the activity of neurons innervating these receptors increases dramatically, so much as to override the signals from central chemoreceptors in the  hypothalamus , increasing P O 2  despite a falling P CO 2 [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_253", "contents": "In most tissues of the body, the response to hypoxia is  vasodilation . By widening the blood vessels, the tissue allows greater perfusion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_254", "contents": "By contrast, in the  lungs , the response to hypoxia is vasoconstriction. This is known as  hypoxic pulmonary vasoconstriction , or \"HPV\", and has the effect of redirecting blood away from poorly ventilated regions, which helps match perfusion to ventilation, giving a more even oxygenation of blood from different parts of the lungs. [ 81 ]  In conditions of hypoxic breathing gas, such as at high altitude, HPV is generalized over the entire lung, but with sustained exposure to generalized hypoxia, HPV is suppressed. [ 89 ] \nHypoxic ventilatory response (HVR) is the increase in  ventilation  induced by hypoxia that allows the body to take in and transport lower concentrations of oxygen at higher rates.  It is initially elevated in lowlanders who travel to high altitude, but reduces significantly over time as people  acclimatize . [ 4 ] [ 90 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_255", "contents": "When the pulmonary capillary pressure remains elevated chronically (for at least 2 weeks), the lungs become even more resistant to pulmonary edema because the lymph vessels expand greatly, increasing their capability of carrying fluid away from the interstitial spaces perhaps as much as 10-fold. Therefore, in patients with chronic  mitral stenosis , pulmonary capillary pressures of 40 to 45\u00a0mm Hg have been measured without the development of lethal pulmonary edema. [ 91 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_256", "contents": "There are several potential physiologic mechanisms for hypoxemia, but in patients with chronic obstructive pulmonary disease ( COPD ),  ventilation/perfusion  (V/Q) mismatching is most common, with or without alveolar hypoventilation, as indicated by arterial carbon dioxide concentration. Hypoxemia caused by V/Q mismatching in COPD is relatively easy to correct, and relatively small flow rates of supplemental oxygen (less than 3 L/min for the majority of patients) are required for long term  oxygen therapy  (LTOT). Hypoxemia normally stimulates ventilation and produces dyspnea, but these and the other signs and symptoms of hypoxia are sufficiently variable in COPD to limit their value in patient assessment. Chronic alveolar hypoxia is the main factor leading to development of cor pulmonale \u2014 right ventricular hypertrophy with or without overt right ventricular failure \u2014 in patients with COPD. Pulmonary hypertension adversely affects survival in COPD, proportional to resting mean pulmonary artery pressure elevation. Although the severity of airflow obstruction as measured by forced expiratory volume tests  FEV1  correlates best with overall prognosis in COPD, chronic hypoxemia increases mortality and morbidity for any severity of disease. Large-scale studies of long term oxygen therapy in patients with COPD show a  dose\u2013response relationship  between daily hours of supplemental oxygen use and survival. Continuous, 24-hours-per-day oxygen use in appropriately selected patients may produce a significant survival benefit. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_257", "contents": "The brain has relatively high energy requirements, using about 20% of the oxygen under resting conditions, but low reserves, which make it specially vulnerable to hypoxia. In normal conditions, an increased demand for oxygen is easily compensated by an increased cerebral blood flow. but under conditions when there is insufficient oxygen available, increased blood flow may not be sufficient to compensate, and hypoxia can result in brain injury. A longer duration of cerebral hypoxia will generally result in larger areas of the brain being affected. The  brainstem ,  hippocampus  and  cerebral cortex  seem to be the most vulnerable regions. Injury becomes irreversible if oxygenation is not soon restored. Most cell death is by  necrosis  but delayed  apoptosis  also occurs. In addition, presynaptic neurons release large amounts of glutamate which further increases Ca 2+  influx and causes catastrophic collapse in postsynaptic cells. Although it is the only way to save the tissue, reperfusion also produces reactive oxygen species and inflammatory cell infiltration, which induces further cell death. If the hypoxia is not too severe, cells can suppress some of their functions, such as protein synthesis and spontaneous electrical activity, in a process called  penumbra , which is reversible if the oxygen supply is resumed soon enough. [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_258", "contents": "Parts of the heart are exposed to ischemic hypoxia in the event of occlusion of a coronary artery. Short periods of ischaemia are reversible if reperfused within about 20 minutes, without development of necrosis, but the phenomenon known as  stunning  is generally evident. If hypoxia continues beyond this period, necrosis propagates through the myocardial tissue. [ 81 ]  Energy metabolism in the affected area shifts from mitochondrial respiration to anaerobic glycolysis almost immediately, with concurrent reduction of effectiveness of contractions, which soon cease. Anaerobic products accumulate in the muscle cells, which develop acidosis and osmotic load leading to cellular edema. Intracellular Ca2+ increases and eventually leads to cell necrosis. Arterial flow must be restored to return to aerobic metabolism and prevent necrosis of the affected muscle cells, but this also causes further damage by  reperfusion injury . Myocadial stunning has been described as \"prolonged postischaemic dysfunction of viable tissue salvaged by reperfusion\", which manifests as temporary contractile failure in oxygenated muscle tissue. This may be caused by a release of reactive oxygen species during the early stages of reperfusion. [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_259", "contents": "As tumors grow, regions of relative hypoxia develop as the oxygen supply is unevenly utilized by the tumor cells. The formation of new blood vessels is necessary for continued tumor growth, and is also an important factor in metastasis, as the route by which cancerous cells are transported to other sites. [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_260", "contents": "Hypoxia can present as acute or chronic."}
+{"id": "WikiPedia_Pulmonology$$$corpus_261", "contents": "Acute presentation may include  dyspnea  (shortness of breath) and  tachypnea  (rapid, often shallow, breathing). Severity of symptom presentation is commonly an indication of severity of hypoxia. Tachycardia (rapid pulse) may develop to compensate for low arterial oxygen tension.  Stridor  may be heard in upper airway obstruction, and  cyanosis  may indicate severe hypoxia. Neurological symptoms and organ function deterioration occur when the oxygen delivery is severely compromised. In moderate hypoxia, restlessness, headache and confusion may occur, with coma and eventual death possible in severe cases. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_262", "contents": "In chronic presentation, dyspnea following exertion is most commonly mentioned. Symptoms of the underlying condition that caused the hypoxia may be apparent, and can help with differential diagnosis. A productive cough and fever may be present with lung infection, and leg edema may suggest heart failure. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_263", "contents": "Lung  auscultation  can provide useful information. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_264", "contents": "An  arterial blood gas test  (ABG) may be done, which usually includes measurements of oxygen content, hemoglobin, oxygen saturation (how much of the hemoglobin is carrying oxygen), arterial partial pressure of oxygen (P a O 2 ), partial pressure of carbon dioxide (P a CO 2 ), blood pH level, and bicarbonate (HCO 3 ) [ 92 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_265", "contents": "X-rays  or  CT scans  of the chest and airways can reveal abnormalities that may affect ventilation or perfusion. [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_266", "contents": "A  ventilation/perfusion scan , [ 96 ]  also called a V/Q lung scan, is a type of  medical imaging  using  scintigraphy  and  medical isotopes  to evaluate the circulation of air and blood within a patient's  lungs , [ 97 ] [ 98 ]  in order to determine the ventilation/perfusion ratio. The ventilation part of the test looks at the ability of air to reach all parts of the lungs, while the perfusion part evaluates how well blood circulates within the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_267", "contents": "Pulmonary function testing [ 95 ]  may include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_268", "contents": "Treatment will depend on severity and may also depend on the cause, as some cases are due to external causes and removing them and treating acute symptoms may be sufficient, but where the symptoms are due to underlying pathology, treatment of the obvious symptoms may only provide temporary or partial relief, so differential diagnosis can be important in selecting definitive treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_269", "contents": "Hypoxemic hypoxia: Low oxygen tension in the arterial blood (P a O 2 ) is generally an indication of inability of the lungs to properly oxygenate the blood. Internal causes include hypoventilation, impaired alveolar diffusion, and pulmonary shunting. External causes include hypoxic environment, which could be caused by low ambient pressure or unsuitable breathing gas. [ 8 ]  Both acute and chronic hypoxia and hypercapnia caused by respiratory dysfunction can produce neurological symptoms such as encephalopathy, seizures, headache,  papilledema , and  asterixis . [ 54 ]  Obstructive sleep apnea syndrome may cause morning headaches [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_270", "contents": "Circulatory Hypoxia: Caused by insufficient perfusion of the affected tissues by blood which is adequately oxygenated. This may be generalised, due to cardiac failure or hypovolemia, or localised, due to infarction or localised injury. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_271", "contents": "Anemic Hypoxia is caused by a deficit in oxygen-carrying capacity, usually due to low hemoglobin levels, leading to generalised inadequate oxygen delivery. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_272", "contents": "Histotoxic Hypoxia (Dysoxia) is a consequence of cells being unable to utilize oxygen effectively. A classic example is cyanide poisoning which inhibits the enzyme cytochrome C oxidase in the mitochondria, blocking the use of oxygen to\u00a0make ATP. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_273", "contents": "Critical illness  polyneuropathy  or  myopathy  should be considered in the intensive care unit when patients have difficulty coming off the ventilator. [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_274", "contents": "Prevention can be as simple as  risk management  of  occupational exposure  to hypoxic environments, and commonly involves the use of environmental monitoring and personal protective equipment. Prevention of hypoxia as a predictable consequence of medical conditions requires prevention of those conditions. Screening of demographics known to be at risk for specific disorders may be useful."}
+{"id": "WikiPedia_Pulmonology$$$corpus_275", "contents": "To counter the effects of high-altitude diseases, the body must return arterial P a O 2  toward normal.  Acclimatization , the means by which the body adapts to higher altitudes, only partially restores P O 2  to standard levels.  Hyperventilation , the body's most common response to high-altitude conditions, increases alveolar P O 2  by raising the depth and rate of breathing. However, while P O 2  does improve with hyperventilation, it does not return to normal. Studies of miners and astronomers working at 3000 meters and above show improved alveolar P O 2  with full acclimatization, yet the P O 2  level remains equal to or even below the threshold for continuous oxygen therapy for patients with  chronic obstructive pulmonary disease  (COPD). [ 100 ]  In addition, there are complications involved with acclimatization.  Polycythemia , in which the body increases the number of red blood cells in circulation, thickens the blood, raising the risk of blood clots. [ 101 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_276", "contents": "In high-altitude situations, only oxygen enrichment or compartment pressurisation can counteract the effects of hypoxia. Pressurisation is practicable in vehicles, and for emergencies in ground installations. By increasing the concentration of oxygen in the at ambient pressure, the effects of lower barometric pressure are countered and the level of arterial P O 2  is restored toward normal capacity. A small amount of supplemental oxygen reduces the equivalent altitude in climate-controlled rooms. At 4000\u00a0m, raising the oxygen concentration level by 5% via an oxygen concentrator and an existing ventilation system provides an altitude equivalent of 3000\u00a0m, which is much more tolerable for the increasing number of low-landers who work in high altitude. [ 102 ]  In a study of astronomers working in Chile at 5050\u00a0m, oxygen concentrators increased the level of oxygen concentration by almost 30 percent (that is, from 21 percent to 27 percent). This resulted in increased worker productivity, less fatigue, and improved sleep. [ 100 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_277", "contents": "Oxygen concentrators  are suited for high altitude oxygen enrichment of climate-controlled environments. They require little maintenance and electricity, utilise a locally available source of oxygen, and eliminate the expensive task of transporting oxygen cylinders to remote areas. Offices and housing often already have climate-controlled rooms, in which temperature and humidity are kept at a constant level. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_278", "contents": "Treatment and management depend on circumstances. For most high altitude situations the risk is known, and prevention is appropriate. At low altitudes hypoxia is more likely to be associated with a medical problem or an unexpected contingency, and treatment is more likely to be provided to suit the specific case. It is necessary to identify persons who need oxygen therapy, as supplemental oxygen is required to treat most causes of hypoxia, but different oxygen concentrations may be appropriate. [ 103 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_279", "contents": "Treatment will depend on the cause of hypoxia. If it is determined that there is an external cause, and it can be removed, then treatment may be limited to support and returning the system to normal oxygenation. In other cases a longer course of treatment may be necessary, and this may require supplemental oxygen over a fairly long term or indefinitely."}
+{"id": "WikiPedia_Pulmonology$$$corpus_280", "contents": "There are three main aspects of oxygenation treatment: maintaining patent airways, providing sufficient oxygen content of the inspired air, and improving the diffusion in the lungs. [ 8 ]  In some cases treatment may extend to improving oxygen capacity of the blood, which may include volumetric and circulatory intervention and support,  hyperbaric oxygen therapy  and treatment of intoxication."}
+{"id": "WikiPedia_Pulmonology$$$corpus_281", "contents": "Invasive ventilation may be necessary or an elective option in surgery. This generally involves a positive pressure ventilator connected to an endotracheal tube, and allows precise delivery of ventilation, accurate monitoring of F i O 2 , and positive end-expiratory pressure, and can be combined with anaesthetic gas delivery. In some cases a  tracheotomy  may be necessary. [ 8 ]  Decreasing metabolic rate by reducing body temperature lowers oxygen demand and consumption, and can minimise the effects of tissue hypoxia, especially in the brain, and therapeutic hypothermia based on this principle may be useful. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_282", "contents": "Where the problem is due to respiratory failure. it is desirable to treat the underlying cause. In cases of pulmonary edema, diuretics can be used to reduce the oedems.  Steroids  may be effective in some cases of interstitial lung disease, and in extreme cases,  extracorporeal membrane oxygenation  (ECMO) can be used. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_283", "contents": "Hyperbaric oxygen  has been found useful for treating some forms of localized hypoxia, including poorly perfused trauma injuries such as  Crush injury,  compartment syndrome , and other acute traumatic ischemias. [ 104 ] [ 105 ]  It is the definitive treatment for severe  decompression sickness , which is largely a condition involving localized hypoxia initially caused by inert gas embolism and inflammatory reactions to extravascular bubble growth. [ 106 ] [ 107 ] [ 108 ]  It is also effective in  carbon monoxide poisoning [ 109 ]  and  diabetic foot . [ 110 ] [ 111 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_284", "contents": "A prescription renewal for home oxygen following hospitalization requires an assessment of the patient for ongoing hypoxemia. [ 112 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_285", "contents": "Prognosis is strongly affected by cause, severity, treatment, and underlying pathology."}
+{"id": "WikiPedia_Pulmonology$$$corpus_286", "contents": "Hypoxia leading to reduced capacity to respond appropriately, or to loss of consciousness, has been implicated in incidents where the direct cause of death was not hypoxia. This is recorded in underwater diving incidents, where drowning has often been given as cause of death, high altitude mountaineering, where exposure, hypothermia and falls have been consequences, flying in unpressurized aircraft, and aerobatic maneuvers, where loss of control leading to a crash is possible."}
+{"id": "WikiPedia_Pulmonology$$$corpus_287", "contents": "Hypoxia is a common disorder but there are many possible causes. [ 8 ]  Prevalence is variable. Some of the causes are very\u00a0common, like pneumonia or chronic obstructive pulmonary disease; some are quite\u00a0rare like hypoxia due to cyanide poisoning. Others, like reduced oxygen tension at high altitude, may be regionally distributed or associated with a specific demographic. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_288", "contents": "Generalized hypoxia is an occupational hazard in several high-risk occupations, including firefighting, professional diving, mining and underground rescue, and flying at high altitudes in unpressurised aircraft."}
+{"id": "WikiPedia_Pulmonology$$$corpus_289", "contents": "Potentially life-threatening hypoxemia is common in critically ill patients. [ 113 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_290", "contents": "Localized hypoxia may be a complication of diabetes, decompression sickness, and of trauma that affects blood supply to the extremities."}
+{"id": "WikiPedia_Pulmonology$$$corpus_291", "contents": "Hypoxia due to underdeveloped lung function is a common complication of premature birth. In the United States, intrauterine hypoxia and birth asphyxia were listed together as the tenth leading cause of neonatal death. [ 114 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_292", "contents": "Silent hypoxia (also known as happy hypoxia) [ 115 ] [ 116 ]  is generalised  hypoxia that does not coincide with  shortness of breath . [ 117 ] [ 118 ] [ 119 ]  This presentation is known to be a complication of  COVID-19 , [ 120 ] [ 121 ]  and is also known in  atypical pneumonia , [ 122 ]  altitude sickness, [ 123 ] [ 124 ] [ 125 ]  and  rebreather  malfunction accidents. [ 126 ] [ 127 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_293", "contents": "The 2019  Nobel Prize in Physiology or Medicine  was awarded to  William G. Kaelin Jr. ,  Sir Peter J. Ratcliffe , and  Gregg L. Semenza  in recognition of their discovery of cellular mechanisms to sense and adapt to different oxygen concentrations, establishing a basis for how oxygen levels affect physiological function. [ 128 ] [ 129 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_294", "contents": "The use of the term  hypoxia  appears to be relatively recent, with the first recorded use in scientific publication from 1945. Previous to this the term  anoxia  was extensively used for all levels of oxygen deprivation. Investigation into the effects of lack of oxygen date from the mid 19th century.\n [ 130 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_295", "contents": "Hypoxia is formed from the Greek roots \u03c5\u03c0o (hypo), meaning under, below, and less than, and o\u03be\u03c5 (oxy), meaning acute or acid, which is the root for oxygen. [ 130 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_296", "contents": "Interventional pulmonology  ( IP , also called  interventional pulmonary medicine ) is a maturing  medical sub-specialty  from its parent specialty of  pulmonary medicine . It deals specifically with minimally invasive  endoscopic  and percutaneous procedures for diagnosis and treatment of  neoplastic  as well as  non-neoplastic diseases  of the airways, lungs, and pleura. Many IP procedures constitute efficacious yet less invasive alternatives to  thoracic surgery ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_297", "contents": "Before the advent of  optical fibers  and advances in  anesthesiology , interventional pulmonary procedures were mostly limited to foreign body retrieval via rigid bronchoscopy.  Gustav Killian  (June 2, 1860 \u2013 February 24, 1921), a German laryngologist, performed foreign body retrievals from bronchial passages using a rigid  laryngoscope /bronchoscope whereas in the United States,  Chevalier Jackson  (1865 \u2013 1958) was the first to use the rigid  bronchoscope . [ 1 ]  Later, Swedish internist  Hans-Christian Jacobaeus  first introduced  thoracoscopy  in a 1910 paper published in the journal  M\u00fcnch med Wochenschr , before Japanese thoracic surgeon  Shiketo Ikeda  (1925 \u2013 2001) introduced the fiberoptic bronchoscope in the late 20th century. [ 2 ] [ 3 ]  Jean-Francois Dumon from France is credited with modernizing rigid bronchoscopy in the late 20th century by introducing a novel non-metallic airway stent made of silicone, appropriately named the Dumon stent. [ 4 ]  Together, these developments laid the foundation for most of today\u2019s interventional pulmonary techniques."}
+{"id": "WikiPedia_Pulmonology$$$corpus_298", "contents": "In 1978, Kopen Wang and colleagues at  Johns Hopkins Hospital  described the use of transbronchial needle aspiration (TBNA) through a rigid bronchoscope to diagnose a paratracheal  mediastinal mass . [ 5 ]  Following the advent of  endobronchial ultrasound  (EBUS), which first became available in the early 21st century, EBUS-TBNA swiftly replaced  mediastinoscopy  as the first-line in mediastinal  staging  for lung cancer. [ 6 ]  With these developments, interventional pulmonology became much more firmly established on the map of distinct subspecialties."}
+{"id": "WikiPedia_Pulmonology$$$corpus_299", "contents": "In 1992, the Association for Bronchology and Interventional Pulmonology (AABIP) was formed as a representative society of interventional pulmonologists based in North America. [ 7 ]  This organization also publishes a journal, namely the  Journal of Bronchology and Interventional Pulmonology . [ 8 ]  The World Association for Bronchology was founded by Dr. Ikeda in 1978 and renamed as the World Association for Bronchology and Interventional Pulmonology (WABIP) in 2010. [ 9 ]  It holds a biennial scientific meeting known as the World Congress for Bronchology and Interventional Pulmonology. The Association for Interventional Pulmonology Program Directors (AIPPD), dedicated to the advancement of IP education in the United States, was created in 2012. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_300", "contents": "In addition to basic bronchoscopic and pleural procedures that are performed by a general pulmonologist, an interventional pulmonologist may perform the following advanced procedures:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_301", "contents": "For purposes of formal training in interventional pulmonology, dedicated training programs only became available in the early 21st century. The first dedicated program was a 12-month advanced fellowship offered by Dr. Beamis at  Lahey Clinic  in  Boston . [ 11 ]  Currently, there are over 30 IP  fellowship  programs across the country. [ 10 ]  However, training programs have varied considerably in terms of the breadth and depth of procedural training that they offer. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_302", "contents": "To address the issue of inconsistent IP training across fellowship programs, representative members from five professional organizations (AABIP, AIPPD, ACCP, ATS, and APCCMPD) jointly published a list of minimum standards required by July 2019 in order for IP fellowship programs to receive formal accreditation from the AABIP and AIPPD. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_303", "contents": "To be eligible for this fellowship, applicants must first complete a three-year fellowship in pulmonary &  critical care medicine . Most of these programs select one to two fellow(s) per year, applying though the Interventional Pulmonary Fellow Application Service (IPFAS\u00a9). As with most other medical specialties and subspecialties across the United States, applicants are matched to programs through the  National Resident Matching Program  (NRMP, or the \u201cMatch\u201d). [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_304", "contents": "In  physiology ,  intrapleural pressure  refers to the pressure within the  pleural cavity . Normally, the pressure within the pleural cavity is slightly less than the  atmospheric pressure , which is known as  negative pressure . [ 1 ]  When the pleural cavity is damaged or ruptured and the intrapleural pressure becomes greater than the atmospheric  pressure,  pneumothorax  may ensue."}
+{"id": "WikiPedia_Pulmonology$$$corpus_305", "contents": "Intrapleural pressure is different from intrathoracic pressure. The  thoracic cavity  is the space that includes the pleura, lungs, and heart, while the pleural space is only the space between the  parietal pleura  and  visceral pleura  surrounding lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_306", "contents": "Intrapleural pressure depends on the ventilation phase, atmospheric pressure, and the volume of the intrapleural cavity. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_307", "contents": "At rest, there is a negative intrapleural pressure. This provides a  transpulmonary pressure , causing the lungs to expand. If humans didn't maintain a slightly negative pressure even when exhaling, their lungs would collapse on themselves because all the air would rush towards the area of lower pressure. Intra-pleural pressure is sub-atmospheric. This is due to the  recoil of the chest and lungs  away from each other."}
+{"id": "WikiPedia_Pulmonology$$$corpus_308", "contents": "M\u00fcller's maneuver  can temporarily but significantly decrease the intrapleural pressure. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_309", "contents": "The relationship between the intra-pulmonary pressure and intra-pleural pressure is that the pressure becomes more negative during inspiration and allows air to get sucked in ( Boyle's law )  P  vs  V  relationship and during expiration, the pressure becomes less negative (Note: still less than atmospheric pressure, also take note of the  partial pressure of carbon dioxide ) and the air is given out. The only difference between the pressures is that intra-pleural pressure is more negative than intra-pulmonary pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_310", "contents": "Factors affecting are:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_311", "contents": "Physiological effects:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_312", "contents": "Pathological effects:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_313", "contents": "A person breathing at rest inhales and exhales approximately half a liter of air during each respiratory cycle, which is called  tidal volume.  The respiratory rate is directly affected by the concentration of carbon dioxide in the blood.  Lungs do not collapse after forceful respiration because of the  residual volume. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_314", "contents": "Latent hypoxia  is a condition where the oxygen content of the lungs and arterial blood is sufficient to maintain consciousness at a raised ambient pressure, but not when the pressure is reduced to normal atmospheric pressure. It usually occurs when a  diver  at depth has a lung gas and blood oxygen concentration that is sufficient to support consciousness at the pressure at that depth, but would be insufficient at surface pressure. This problem is associated with  freediving blackout  and the presence of  hypoxic breathing gas  mixtures in  underwater breathing apparatus , particularly in  diving rebreathers ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_315", "contents": "The term latent hypoxia strictly refers to the situation while the potential victim is at depth, still conscious, and not yet hypoxic, but is also loosely applied to the consequential blackout, which is a form of hypoxic blackout also referred to as  blackout of ascent  or deep water blackout, though deep water blackout is also used to refer to the final stage of  nitrogen narcosis . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_316", "contents": "The minimum tissue and vascular partial pressure of oxygen which will maintain consciousness is about 20 millimetres of mercury (27\u00a0mbar). [ 2 ]  This is equivalent to approximately 30 millimetres of mercury (40\u00a0mbar) in the lungs. [ 3 ]  Approximately 46\u00a0ml/min oxygen is required for brain function. This equates to a minimum arterial oxygen partial pressure (P a O 2 ) of 29 millimetres of mercury (39\u00a0mbar) at 868\u00a0ml/min cerebral flow. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_317", "contents": "An ascent blackout, or deep water blackout, is a loss of consciousness caused by  cerebral hypoxia  on ascending from a deep freedive (breath-hold dive), typically of ten metres or more when the swimmer does not necessarily experience an urgent need to breathe and has no other obvious medical condition that might have caused it, [ 4 ] [ 5 ] [ 6 ] [ 7 ]  or from a dive using underwater breathing apparatus while using a breathing gas which has too low an oxygen fraction to support consciousness at the surface. Breath-hold victims typically black out close to the surface, sometimes even as they break surface, and have been seen to approach the surface without apparent distress only to sink away. Breath-hold victims are usually established practitioners of deep breath-hold diving, are fit, strong swimmers and have not experienced problems before. Blackout by this mechanism may occur even after surfacing from depth and breathing has commenced if the inhaled oxygen has not yet reached the brain and may be referred to as a surface blackout. [ 8 ]  Divers ascending using breathing apparatus typically ascend at slower ascent rates to avoid decompression sickness, and the depth at which consciousness is lost tends to follow the oxygen partial pressure of the breathing gas."}
+{"id": "WikiPedia_Pulmonology$$$corpus_318", "contents": "The partial pressure of oxygen in the air or other breathing gas mixture in the lungs controls the oxygen loading of blood. A critical P O 2  of 30 millimetres of mercury (40\u00a0mbar) in the lungs will sustain consciousness when breathing is resumed after a breath-hold dive. This is about 4% oxygen in the lungs and 45% oxygen saturation of the arterial blood. At 30\u00a0msw (4 bar), 2% by volume oxygen in the lung gas gives a P O 2  of 60 millimetres of mercury (80\u00a0mbar). At 10\u00a0msw (2 bar), for the same 2% oxygen, the P O 2  would be 30 millimetres of mercury (40\u00a0mbar), i.e. marginal. At the surface the same 2% oxygen drops to 15 millimetres of mercury (20\u00a0mbar), ignoring metabolic use. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_319", "contents": "The usual consequence, if the airway is not protected, is drowning. A breath-hold diver who has blacked out and has been promptly returned to the surface, will usually regain consciousness within seconds. While the diver is still unconscious underwater, they are at high risk of drowning. While unconscious the diver has lost voluntary bodily control, but still has protective reflexes that protect the airway. One of these is  laryngospasm , which closes the  larynx , to preventing water from entering the lungs. If the diver has reached the surface, and the divers face is kept above water, when the laryngospasm relaxes spontaneous breathing will often resume. [ 9 ]  The laryngospasm will eventually relax, and if the diver is still underwater then water will enter the airway and may reach the lungs which will cause complications if resuscitation is successful, and  secondary drowning  is possible. [ 9 ]  The time between loss of consciousness and death varies considerably depending on a number of factors but can be as little as two and a half minutes. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_320", "contents": "If the diver's airway is protected by a full-face mask or diving helmet, the immediate risk is death by asphyxiation, which can occur within a few minutes of cessation of breathing. If the diver sinks and the pressure increases sufficiently, the gas may become capable of supporting consciousness again, but the problem of latent hypoxia remains until a higher oxygen content gas is provided. If the diver is on surface supply, a prompt switch of gases may be sufficient to restore consciousness, and this may also apply to a scuba diver if immediate and appropriate action is taken by another diver. Immediate surfacing of a hypoxic diver using underwater breathing apparatus presents the risk of  decompression illness  from  lung barotrauma  or  decompression sickness , and the risk depends on the  pressure exposure history  of the diver."}
+{"id": "WikiPedia_Pulmonology$$$corpus_321", "contents": "Risk of latent hypoxia leading to blackout and further complications depends on the mode of diving in use."}
+{"id": "WikiPedia_Pulmonology$$$corpus_322", "contents": "The diver who has lost consciousness due to latent hypoxia is already hypoxic, and should be brought to the surface as soon as possible, while protecting the airway. There are no contraindications to immediate surfacing for a breath-hold diver, and the mouth and nose may be blocked to prevent involuntary aspiration of water. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_323", "contents": "The first priority is ventilation at the earliest possible opportunity, and in many cases this may be sufficient. If ventilation with sufficient oxygenation is achieved promptly, and there has been no aspiration of water it is quite possible that no further treatment will be needed. If there is a delay the prognosis deteriorates rapidly. CPR may be necessary. Aspiration of water may require hospitalisation for observation, and if necessary, treatment for complications due to water in the lungs. Treatment is generally as for drowning. Supplementary oxygen is generally recommended. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_324", "contents": "Lobectomy  means  surgical excision of a lobe . This may refer to a lobe of the  lung [ 1 ]  (also simply called a  lobectomy ), a lobe of the  thyroid  ( hemithyroidectomy ), a lobe of the  brain  (as in  anterior temporal lobectomy ), or a lobe of the  liver  ( hepatectomy )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_325", "contents": "A lobectomy of the lung is performed in early-stage non-small cell  lung cancer  patients. [ 2 ] [ 3 ]  It is not performed on patients that have lung cancer that has spread to other parts of the body. Tumor size, type, and location are major factors as to whether a lobectomy is performed. This can be due to cancer or smoking.  Lung lobectomies are performed on patients as young as eleven or twelve who have no cancer or smoking history, but have conditions from birth or early childhood that necessitate the operation. [ 4 ] [ 5 ]  Such patients will have reduced lung capacity which tends to limit their range of activities through life.  They often need to use inhalers on a daily basis, and are often classified as being  asthmatic . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_326", "contents": "The  lung allocation score  (LAS) is a numerical value used by the  United Network for Organ Sharing  (UNOS) to assign relative priority for distributing donated  lungs  for  transplantation  within the  United States . The lung allocation score takes into account various measures of a patient's health in order to direct donated organs towards the patients who would best benefit from a  lung transplant . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_327", "contents": "The LAS system replaces the older method within the United States of allocating donated lungs strictly on a  first-come, first-served  basis, according to  blood type  compatibility and distance from the donor hospital. The older method is still used for patients under the age of 12. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_328", "contents": "The LAS system is still being evaluated and revised. [ 1 ]  The reason for this continuing analysis is the need to balance on one hand the desire to help those patients in direct need, versus the statistical likelihood of the patient to survive the procedure, as well as the post-operative risks of  infection  and  transplant rejection . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_329", "contents": "The lung allocation score is calculated from a series of formulas that take into account the statistical probability of a patient's survival in the next year without a transplant, and the projected length of survival post-transplant. A raw allocation score, summarizing all of the above values, is calculated, and finally this score is normalized to obtain the actual LAS, which has a range from 0 to 100. Higher lung allocation scores indicate the patient is more likely to benefit from a lung transplant."}
+{"id": "WikiPedia_Pulmonology$$$corpus_330", "contents": "The post-transplant survival measure is one-year survival after  transplantation of the lungs . Factors used to predict it include  FVC ,  ventilator  use, age,  creatinine ,  NYHA class  and diagnosis. [ 3 ]  It is used for calculation of  transplant benefit  by subtracting another variable called  waitlist urgency measure  from it. The final lung allocation score, which is meant to reflect the overall transplant benefit, incorporates this element as well. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_331", "contents": "There are many factors that are used to calculate the lung allocation score: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_332", "contents": "UNOS requires that the various medical results must be current, i.e. obtained within the last six months, or the relevant factor is assigned a zero value. Exceptions can be made if a patient is deemed unable to complete a test due to his or her current condition. In such a case, the physician must obtain permission from the UNOS Lung Review Board to submit a reasonable estimate of how the patient would perform. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_333", "contents": "In certain instances, a physician may petition the UNOS Lung Review Board to modify a patient's assigned LAS if it is felt that a patient's particular circumstances are not adequately represented by the regular LAS calculation system. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_334", "contents": "The lung allocation score is an important part of the recipient selection process, but other factors are also considered. Patients who are under the age of 12 are still given priority based on how long they have been on the transplant waitlist. The length of time spent on the list is also the deciding factor when multiple patients have the same lung allocation score. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_335", "contents": "A lung from a 16-year-old donor would first be offered to the person in the age group 12\u201317 with the highest lung allocation score and matching blood type in the vicinity of the transplant center. If there no suitable recipient in that age group, it would next be offered to the highest LAS-scoring candidate who is under 12 years of age. Finally, it would be offered to the highest LAS-scoring person of age 18 or older. If there is no suitable candidate within the area, the lung may be offered to someone farther away, within certain time and distance constraints."}
+{"id": "WikiPedia_Pulmonology$$$corpus_336", "contents": "Mandatory minute ventilation  ( MMV ) (also called  minimum minute ventilation ) is a  mode of mechanical ventilation  which requires the operator to determine what the appropriate minute ventilation for the patient should be and the ventilator then monitors the patient's ability to generate this volume.  If the calculation suggests the volume target will not be met, supplemental breaths are delivered at the targeted volume to achieve the desired minute ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_337", "contents": "Mandatory minute ventilation is a  volume control  mode of ventilation and a derivative of  intermittent mandatory ventilation . [ 1 ]  Mandatory minute ventilation allows spontaneous breathing with automatic adjustments of mandatory ventilation to meet the patient\u2019s preset minimum minute volume requirement. If the patient maintains the minute volume settings for VT x f, no mandatory breaths are delivered. If the patient's minute volume is insufficient, mandatory delivery of the preset tidal volume will occur until the minute volume is achieved.  The method for monitoring whether or not the patient is meeting the required minute ventilation (V E ) is different per ventilator brand and model, but generally there is a window of time being monitored and a smaller window being checked against that larger window."}
+{"id": "WikiPedia_Pulmonology$$$corpus_338", "contents": "MMV is an optimal mode for weaning in neonatal and pediatric populations and has been shown to reduce long term complications related to mechanical ventilation. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_339", "contents": "Redirect to:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_340", "contents": "In  medicine ,  mechanical power  is a measure of the amount of  energy  imparted to a patient by a  mechanical ventilator . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_341", "contents": "While in many cases mechanical ventilation is a life-saving or life-preserving intervention, it also has the potential to cause harm to the patient via  ventilator-associated lung injury . A number of stresses may be induced by the ventilator on the patient's lung. These include  barotrauma  caused by pressure,  volutrauma  caused by distension of the lungs,  rheotrauma  caused by fast-flowing delivery of gases and  atelectotrauma  resulting from repeated collapse and re-opening of the lung."}
+{"id": "WikiPedia_Pulmonology$$$corpus_342", "contents": "The purpose of  mechanical power  is to provide a quantity which can account for all of these stresses and therefore predict the amount of lung injury which is likely to be seen in the patient."}
+{"id": "WikiPedia_Pulmonology$$$corpus_343", "contents": "There is no agreed upon equation for Mechanical Power."}
+{"id": "WikiPedia_Pulmonology$$$corpus_344", "contents": "Medical gas therapy  is a treatment involving the administration of various gases. It has been used in medicine since the use of  oxygen therapy . [ 1 ]  Most of these gases are drugs, including oxygen. [ 2 ]   Many other gases, collectively known as  factitious airs , were explored for medicinal value in the late eighteenth century. In addition to oxygen, medical gases include nitric oxide (NO), and helium-O2 mixtures (Heliox). Careful considerations and close monitoring needed when medical gases are in use. For the purpose of this article only gas mixtures are described."}
+{"id": "WikiPedia_Pulmonology$$$corpus_345", "contents": "Nitric oxide is a substance that our body produces in its every cell and in its every organ. It has a number of functions. It take part in vasodilation, platelet inhibition, immune regulation, enzyme regulation, and neurotransmission."}
+{"id": "WikiPedia_Pulmonology$$$corpus_346", "contents": "Inhaled  nitric oxide  is a gas that is inhaled. [ 1 ]  It was initially described in 1987 as an \"endothelial-derived relaxing factor\" and has since been used to treat pulmonary disorders. [ 3 ]  It works by relaxing  smooth muscle  to widen (dilate)  blood vessels , especially in the lungs. [ 1 ]   Inhaled nitric oxide selects only pulmonary smooth muscles. There will be no effect or minimal effect of inhaled nitric oxide on  atelectatic  or fluid-filled lung. [ 3 ]   It improves oxygenation and decreases  pulmonary hypertension . [ 4 ]  Nitric oxide is used together with a  mechanical ventilator  to treat  respiratory failure  in  premature infants . [ 1 ]   In adults nitric oxide can be used in treating pulmonary hypertension with  acute respiratory distress syndrome . Thanks to the possible clinical successful outcomes of nitric oxide treatment patients can avoid need for  extracorporeal membrane oxygenation  treatment. The  U.S. Food and Drug Administration  has been approved the use of nitric oxide in term and near-term (greater than 34 weeks' gestation age) neonates with hypoxic respiratory failure with clinical or echocardiographic evidence of pulmonary hypertension.  [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_347", "contents": "Nitric oxide must not be used in neonates who depend on right-to-left shunting of blood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_348", "contents": "Dose needed to achieve desired effect but avoid toxicity and adverse effects in neonates and adults is relatively low. Usually it is 5-20 ppm (parts per million).  [ 6 ]  Regular  arterial blood gas  tests needed to assess the response to the therapy and signs of toxicity. Improvement in partial pressure of oxygen (PO2) and oxygen saturation would be indication of positive response to the nitric oxide therapy.  If there is an evidence that nitric oxide works the same dose would be used till the hypoxemia and pulmonary hypertension resolved. When the hypoxemia and pulmonary hypertension resolved titration or slowly weaning of the nitric oxide initiates. Abrupt discontinuation of nitric oxide may lead to compromised oxygenation and pulmonary hypertension may rebound.  [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_349", "contents": "Methemoglobins  level in the blood increases with the use of nitric oxide. Methemoglobin is abnormal form of molecule which can not carry oxygen. Methemoglobin turns blood brown. Other medications can produce methemoglobin too. Monitoring of methemoglobin needed when nitric oxide is in use."}
+{"id": "WikiPedia_Pulmonology$$$corpus_350", "contents": "Nitric oxide with oxygen ( O 2 ) in combination produces another by-product  chemical compound   nitrogen dioxide  ( NO 2 ). The higher the oxygen concentration and nitric oxide therapy duration and lower ventilator flow rate the higher amount of  NO 2  will be produced.  NO 2  is toxic and its level should always be monitored in nitric oxide therapies. High level of  NO 2  can lead to cell damage, hemorrhage,  pulmonary edema ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_351", "contents": "Use of nitric oxide in patients with left heart failure or congestive heart failure may lead to pulmonary edema or worsen pulmonary edema."}
+{"id": "WikiPedia_Pulmonology$$$corpus_352", "contents": "Three US scientist - Robert F. Furchgott, PhD, Louis J. Ignarro, PhD, and Ferid Murad, MD, PhD won  Nobel Prize in Physiology and Medicine  for their discovery of nitric oxide role in cardiovascular and nervous systems in 1998. [ 8 ]  Even though the nitric oxide effects on the body known for more than 25 years the clinical use is still in a development."}
+{"id": "WikiPedia_Pulmonology$$$corpus_353", "contents": "In medicine,  Heliox  generally refers to a mixture of 21% O 2  (the same as  air ) and 79% He, although other combinations are available."}
+{"id": "WikiPedia_Pulmonology$$$corpus_354", "contents": "Heliox generates less airway resistance than air and thereby requires less mechanical energy to  ventilate  the lungs. [ 9 ]  \"Work of Breathing\" is reduced. It does this by two mechanisms:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_355", "contents": "The dry air on the Earth we inhale consists of 78.8% nitrogen, 20.95% oxygen and 0.93% argon. Heliox therapy is substitution of nitrogen with helium. Helium itself has no pharmacological value, it does not react in the body. Its only purpose is to make the flow less turbulent and help oxygen to get into the lungs. Less turbulent flow requires less work to breathe."}
+{"id": "WikiPedia_Pulmonology$$$corpus_356", "contents": "Helium  (He) is colorless, odorless, tasteless, and inert noble gas. Helium is second lightest gas after hydrogen.  [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_357", "contents": "Heliox has a similar  viscosity  to air but a significantly lower  density  (0.5\u00a0g/L versus 1.2\u00a05g/L at  STP ). Flow of gas through the  airways  comprises  laminar flow , transitional flow and  turbulent flow . The tendency for each type of flow is described by the  Reynolds number .  Heliox 's low density produces a lower  Reynolds number  and hence higher probability of laminar flow for any given airway.  Laminar flow  tends to generate less resistance than turbulent flow."}
+{"id": "WikiPedia_Pulmonology$$$corpus_358", "contents": "In the small airways where flow is laminar, resistance is proportional to gas  viscosity  and is not related to  density  and so  heliox  has little effect. The  Hagen\u2013Poiseuille equation  describes laminar resistance. In the large airways where flow is turbulent, resistance is proportional to density, so Heliox has a significant effect."}
+{"id": "WikiPedia_Pulmonology$$$corpus_359", "contents": "Heliox has been used medically since the early 1930s. It was the mainstay of treatment in acute  asthma  before the advent of  bronchodilators . Currently, heliox is mainly used in conditions of large airway narrowing (upper airway obstruction from tumors or foreign bodies and  vocal cord dysfunction ). There is also some use of heliox in conditions of the medium airways ( croup , asthma and  chronic obstructive pulmonary disease )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_360", "contents": "Patients with these conditions may develop a range of symptoms including  dyspnea  (breathlessness),  hypoxemia  (below-normal oxygen content in the arterial blood) and eventually a weakening of the respiratory muscles due to  exhaustion , which can lead to  respiratory failure  and require  intubation  and  mechanical ventilation . Heliox may reduce all these effects, making it easier for the patient to breathe. [ 11 ]  Heliox has also found utility in the weaning of patients off mechanical ventilation, and in the nebulization of inhalable drugs, particularly for the elderly. [ 12 ]  Research has also indicated advantages in using helium\u2013oxygen mixtures in delivery of  anaesthesia . [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_361", "contents": "Heliox side effect is that inhaled helium change voice. Speech will sound high pitched. This effect is caused by low density gas passing through the vocal cords. The effect is reversible."}
+{"id": "WikiPedia_Pulmonology$$$corpus_362", "contents": "Modes of mechanical ventilation  are one of the most important aspects of the usage of  mechanical ventilation . The mode refers to the method of inspiratory support. In general, mode selection is based on  clinician  familiarity and institutional preferences, since there is a paucity of evidence indicating that the mode affects clinical outcome.  The most frequently used forms of volume-limited mechanical ventilation are intermittent mandatory ventilation (IMV) and continuous mandatory ventilation (CMV). [ 1 ]  There have been substantial changes in the  nomenclature of mechanical ventilation  over the years, but more recently it has become standardized by many respirology and pulmonology groups. [ 2 ] [ 3 ]   Writing a mode is most proper in all capital letters with a dash between the control variable and the strategy (i.e. PC-IMV, or VC-MMV etc.)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_363", "contents": "The taxonomy is a logical classification system based on 10 maxims of ventilator design [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_364", "contents": "Pressure = (Elastance \u00d7 Volume) + (Resistance \u00d7 Flow)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_365", "contents": "Volume control (VC) means that both volume and flow are preset prior to inspiration. In other words, the right hand side of the equation of motion remains constant while pressure changes with changes in elastance and resistance. Pressure control (PC) means that inspiratory pressure is preset as either a constant value or it is proportional to the patient's inspiratory effort. In other words, the left-hand side of the equation of motion remains constant while volume and flow change with changes in elastance and resistance. Time control (TC) means that, in some rare situations, none of the main variables (pressure, volume, or flow) are preset. In this case only the inspiratory and expiratory times are preset."}
+{"id": "WikiPedia_Pulmonology$$$corpus_366", "contents": "Patient triggering means starting inspiration based on a patient signal independent of a machine trigger signal. Machine triggering means starting inspiratory flow based on a signal from the ventilator, independent of a patient trigger signal. Patient cycling means ending inspiratory time based on signals representing the patient determined components of the equation of motion, (ie, elastance or resistance and including effects due to inspiratory effort). Flow cycling is a form of patient cycling because the rate of flow decay to the cycle threshold is determined by patient mechanics.  Machine cycling means ending inspiratory time independent of signals representing the patient determined components of the equation of motion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_367", "contents": "Set-point: A targeting scheme for which the operator sets all the parameters of the pressure waveform (pressure control modes) or volume and flow waveforms (volume control modes). Dual: A targeting scheme that allows the ventilator to switch between volume control and pressure control during a single inspiration. Bio-variable: A targeting scheme that allows the ventilator to automatically set the inspiratory pressure or tidal volume randomly to mimic the variability observed during normal breathing. Servo: A targeting scheme for which inspiratory pressure is proportional to inspiratory effort. Adaptive: A targeting scheme that allows the ventilator to automatically set one target (eg, pressure within a breath) to achieve another target (eg, average tidal volume over several breaths). Optimal: A targeting scheme that automatically adjusts the targets of the ventilatory pattern to either minimize or maximize some overall performance characteristic (eg, minimize the work rate done by the ventilatory pattern). Intelligent: A targeting scheme that uses artificial intelligence programs such as  fuzzy logic , rule based  expert systems , and  artificial neural networks ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_368", "contents": "The \"primary breath\" is either the only breath there is (mandatory for CMV and spontaneous for CSV) or it is the mandatory breath in IMV. The targeting schemes can be represented by single, lower case letters: set-point = s, dual = d, servo = r, bio-variable = b, adaptive = a, optimal = o, intelligent = i. \nA tag is an abbreviation for a mode classification, such as PC-IMVs,s. Compound tags are possible, eg, PC-IMVoi,oi."}
+{"id": "WikiPedia_Pulmonology$$$corpus_369", "contents": "Step 1: Identify the primary breath control variable. If inspiration starts with a preset inspiratory pressure, or if pressure is proportional to inspiratory effort, then the control variable is pressure. If inspiration starts with a preset tidal volume and inspiratory flow, then the control variable is volume. If neither is true, the control variable is time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_370", "contents": "Step 2: Identify the breath sequence. Determine whether trigger and cycle events are patient or machine determined. Then, use this information to determine the breath sequence."}
+{"id": "WikiPedia_Pulmonology$$$corpus_371", "contents": "Step 3: Identify the targeting schemes for the primary breaths and (if applicable) secondary breaths."}
+{"id": "WikiPedia_Pulmonology$$$corpus_372", "contents": "Mode Name: A/C Volume Control ( Covidien  PB 840): [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_373", "contents": "Mode Name: SIMV Volume Control Plus ( Covidien  PB 840): [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_374", "contents": "Mechanical ventilation machines are available with both invasive modes (such as  intubation ) and non-invasive modes (such as  BPAP ).  Invasive has to do with the insertion of medical devices or tubes internal to the patient, while non-invasive is completely external to the patient, as for example in using a tightly fitting mask or other device that covers the patient's nose and mouth."}
+{"id": "WikiPedia_Pulmonology$$$corpus_375", "contents": "A basic distinction in mechanical ventilation is whether each breath is initiated by the patient (assist mode) or by the machine (control mode). Dynamic hybrids of the two (assist-control modes) are also possible, and control mode without assist is now mostly obsolete."}
+{"id": "WikiPedia_Pulmonology$$$corpus_376", "contents": "Airway pressure release ventilation  is a time-cycled alternant between two levels of positive airway pressure, with the main time on the high level and a brief expiratory release to facilitate ventilation. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_377", "contents": "Airway pressure release ventilation is usually utilized as a type of inverse ratio ventilation.  The exhalation time (T low ) is shortened to usually less than one second to maintain alveoli inflation.  In the basic sense, this is a continuous pressure with a brief release.  APRV currently the most efficient conventional mode for lung protective ventilation. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_378", "contents": "Different perceptions of this mode may exist around the globe. While 'APRV' is common to users in  North America , a very similar mode, biphasic positive airway pressure (BIPAP), was introduced in Europe. [ 7 ]   The term APRV has also been used in American journals where, from the ventilation characteristics, BIPAP would have been perfectly good terminology. [ 8 ]  But BiPAP(tm) is a trademark for a noninvasive ventilation mode in a specific ventilator (Respironics Inc.)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_379", "contents": "Other manufacturers have followed with their own brand names (BILEVEL, DUOPAP, BIVENT). Although similar in modality, these terms describe how a mode is intended to inflate the lung, rather than defining the characteristics of synchronization or the way spontaneous breathing efforts are supported."}
+{"id": "WikiPedia_Pulmonology$$$corpus_380", "contents": "Intermittent mandatory ventilation has not always had the synchronized feature, so the division of modes were understood to be SIMV (synchronized) vs IMV (not-synchronized). Since the  American Association for Respiratory Care  established a  nomenclature of mechanical ventilation  the \"synchronized\" part of the title has been dropped and now there is only IMV."}
+{"id": "WikiPedia_Pulmonology$$$corpus_381", "contents": "Mandatory minute ventilation (MMV) allows spontaneous breathing with automatic adjustments of mandatory ventilation to the meet the patient's preset minimum minute volume requirement. If the patient maintains the minute volume settings for V T  x f, no mandatory breaths are delivered. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_382", "contents": "If the patient's minute volume is insufficient, mandatory delivery of the preset tidal volume will occur until the minute volume is achieved.  The method for monitoring whether or not the patient is meeting the required minute ventilation (V E ) differs by ventilator brand and model, but, in general, there is a window of monitored time, and a smaller window checked against the larger window (i.e., in the Dr\u00e4ger Evita\u00ae line of mechanical ventilators there is a moving 20-second window, and every 7 seconds the current tidal volume and rate are measured) to decide whether a mechanical breath is needed to maintain the minute ventilation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_383", "contents": "MMV is an optimal mode for weaning in neonatal and pediatric populations and has been shown to reduce long-term complications related to mechanical ventilation. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_384", "contents": "Pressure-regulated volume control is an Assist Controlled Ventilation (ACV) based mode.  Pressure-regulated volume control utilizes pressure-limited, volume-targeted, time-cycled breaths that can be either ventilator- or patient-initiated."}
+{"id": "WikiPedia_Pulmonology$$$corpus_385", "contents": "The peak inspiratory pressure delivered by the ventilator is varied on a breath-to-breath basis to achieve a target tidal volume that is set by the clinician."}
+{"id": "WikiPedia_Pulmonology$$$corpus_386", "contents": "For example, if a target tidal volume of 500 mL is set but the ventilator delivers 600 mL, the next breath will be delivered with a lower inspiratory pressure to achieve a lower tidal volume.  Though PRVC is regarded as a hybrid mode because of its tidal-volume (VC) settings and pressure-limiting (PC) settings fundamentally PRVC is a pressure-control mode with adaptive targeting."}
+{"id": "WikiPedia_Pulmonology$$$corpus_387", "contents": "Continuous positive airway pressure  (CPAP) is a non-invasive positive pressure mode of respiratory support. CPAP is a continuous pressure applied to keep the  alveoli  open and not fully deflate.  This mechanism for maintaining inflated alveoli helps increase partial pressure of oxygen in arterial blood, an appropriate increase in CPAP increases the PaO 2 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_388", "contents": "Automatic positive airway pressure  (APAP) is a form of CPAP that automatically tunes the amount of pressure delivered to the patient to the minimum required to maintain an unobstructed airway on a breath-by-breath basis by measuring the resistance in the patient's breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_389", "contents": "Bilevel positive airway pressure  (BPAP) is a mode used during  non-invasive ventilation  (NIV).  First used in 1988 by Professor Benzer in Austria, [ 10 ]  it delivers a preset inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP).  BPAP can be described as a Continuous Positive Airway Pressure system with a time-cycle change of the applied CPAP level. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_390", "contents": "CPAP/APAP, BPAP, and other non-invasive ventilation modes have been shown to be effective management tools for  chronic obstructive pulmonary disease ,  acute respiratory failure ,  sleep apnea , etc. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_391", "contents": "Often BPAP is incorrectly referred to as \"BiPAP\". BiPAP is the name of a portable ventilator manufactured by  Respironics Corporation ; it is just one of many ventilators that can deliver BPAP."}
+{"id": "WikiPedia_Pulmonology$$$corpus_392", "contents": "BPAP has been shown to be useful in reducing mortality and reducing the need for endotracheal intubation when used in people with  chronic obstructive pulmonary disease  (COPD). [ 13 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_393", "contents": "The term  active  refers to the ventilator's forced expiratory system.  In a HFV-A scenario, the ventilator uses pressure to apply an inspiratory breath and then applies an opposite pressure to force an expiratory breath.  In high-frequency oscillatory ventilation (sometimes abbreviated HFOV) the oscillation bellows and piston force positive pressure in and apply negative pressure to force an expiration. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_394", "contents": "The term  passive  refers to the ventilator's non-forced expiratory system.  In a HFV-P scenario, the ventilator uses pressure to apply an inspiratory breath and then returns to atmospheric pressure to allow for a passive expiration.  This is seen in High-Frequency Jet Ventilation, sometimes abbreviated HFJV. Also categorized under High Frequency Ventilation  is High Frequency Percussive Ventilation, sometimes abbreviated HFPV. With HFPV it utilizes an open circuit to deliver its subtidal volumes by way of the patient interface known as the Phasitron."}
+{"id": "WikiPedia_Pulmonology$$$corpus_395", "contents": "Volume guarantee an additional parameter available in many types of ventilators that allows the ventilator to change its inspiratory pressure setting to achieve a minimum tidal volume.  This is utilized most often in neonatal patients who need a pressure controlled mode with a consideration for volume control to minimize  volutrauma ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_396", "contents": "Positive end expiratory pressure  (PEEP) is pressure applied upon expiration.  PEEP is applied using either a valve that is connected to the expiratory port and set manually or a valve managed internally by a mechanical ventilator."}
+{"id": "WikiPedia_Pulmonology$$$corpus_397", "contents": "PEEP is a pressure that an exhalation has to bypass, in effect causing  alveoli  to remain open and not fully deflate.  This mechanism for maintaining inflated alveoli helps increase partial pressure of oxygen in arterial blood, and an increase in PEEP increases the PaO 2 . [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_398", "contents": "Pressure support is a spontaneous mode of ventilation also named  Pressure Support Ventilation  (PSV). The patient initiates every breath and the ventilator delivers support with the preset pressure value. With support from the ventilator, the patient also regulates their own  respiratory rate  and their  tidal volume ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_399", "contents": "In Pressure Support, the set inspiratory pressure support level is kept constant and there is a decelerating flow. The patient triggers all breaths. If there is a change in the mechanical properties of the lung/thorax and patient effort, the delivered tidal volume will be affected. The user must then regulate the pressure support level to obtain desired ventilation. [ 17 ] [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_400", "contents": "Pressure support improves oxygenation, [ 19 ]  ventilation and decreases work of breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_401", "contents": "Also see adaptive support ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_402", "contents": "Flow-controlled ventilation (FCV) is an entirely dynamic ventilation mode, without pauses, with continuous and stable gas flows during both inspiration and expiration, aiming for linear changes in both volume and pressure. [ 20 ]  FCV is an invasive ventilation mode but, unlike Volume- and pressure controlled modes, it does not rely on a passive expiration created by collapse of the thoracic wall and elastic recoil of the lungs. A high resistant breathing circuit inhibits a passive expiration and therewith allows to fully control and stabilize the expiration flow. FCV creates an inspiration by generating a stable flow from a set End-expiratory pressure (EEP) to a set Peak pressure. Then a stable expiratory flow is created by suctioning. [ 21 ]  This expiratory flow rate is preferably similar to the inspiratory flow, aiming for an I:E ratio of 1:1.0, to minimize energy dissipation in the lungs. [ 22 ] [ 23 ]  FCV\u00ae is a more efficient ventilation as compared to conventional modes, [ 24 ] [ 25 ] [ 26 ] [ 27 ] [ 28 ]  allows ventilation through even small lumens (~2 \u2013 10\u00a0mm ID) [ 29 ] [ 30 ]  and results in less applied mechanical power. [ 31 ] [ 32 ]  FCV was invented by Professor Dr. med. Dietmar Enk. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_403", "contents": "Negative-pressure ventilation stimulates (or forces) breathing by periodic application of partial vacuum (air pressure reduced below ambient pressure), applied externally to the patient's torso\u2014specifically, chest and abdomen\u2014to assist (or force) the chest to expand, expanding the lungs, resulting in voluntary (or involuntary)  inhalation through the patient's airway. [ 33 ] [ 34 ] [ 35 ] [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_404", "contents": "Various \"negative pressure ventilators\" (NPVs) have been developed to serve this function\u2014most famously the \" Iron lung ,\" a tank in which the patient lays, with only their head exposed to ambient air, while air pressure on the remainder of their body, inside the tank, is varied by pumping, to stimulate chest and lung expansion and contraction. Though not in wide use today, NPVs were the principal forms of hospital and long-term mechanical ventilation in the first half of the 20th century, and remain in limited use today. [ 33 ] [ 34 ] [ 35 ] [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_405", "contents": "Adaptive Support Ventilation (ASV) is the only commercially available mode that uses optimal targeting. This ventilation mode was invented and subsequently patented in 1991 by Dr. Fleur Tehrani  [ 38 ] [ 39 ] [ 40 ]  In this positive pressure mode of ventilation, the frequency and tidal volume of breaths of a patient on the ventilator are automatically adjusted and optimized to mimic natural breathing, stimulate spontaneous breathing, and reduce weaning time. In the ASV mode, every breath is synchronized with patient effort if such an effort exists, and otherwise, full mechanical ventilation is provided to the patient. [ 41 ] [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_406", "contents": "Automatic Tube Compensation (ATC) is the simplest example of a computer-controlled targeting system on a ventilator. It is a form of servo targeting."}
+{"id": "WikiPedia_Pulmonology$$$corpus_407", "contents": "The goal of ATC is to support the resistive work of breathing through the artificial airway"}
+{"id": "WikiPedia_Pulmonology$$$corpus_408", "contents": "Neurally Adjusted Ventilatory Assist (NAVA) is adjusted by a computer (servo) and is similar to ATC but with more complex requirements for implementation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_409", "contents": "In terms of patient-ventilator synchrony, NAVA supports both resistive and elastic work of breathing in proportion to the patient's inspiratory effort"}
+{"id": "WikiPedia_Pulmonology$$$corpus_410", "contents": "Proportional assist ventilation (PAV) is another servo targeting based mode in which the ventilator guarantees the percentage of work regardless of changes in  pulmonary compliance  and resistance. [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_411", "contents": "The ventilator varies the tidal volume and pressure based on the patient's work of breathing.  The amount it delivers is proportional to the percentage of assistance it is set to give."}
+{"id": "WikiPedia_Pulmonology$$$corpus_412", "contents": "PAV, like NAVA, supports both restrictive and elastic work of breathing in proportion to the patient's inspiratory effort."}
+{"id": "WikiPedia_Pulmonology$$$corpus_413", "contents": "Liquid ventilation  is a technique of mechanical ventilation in which the lungs are insufflated with an oxygenated  perfluorochemical  liquid rather than an oxygen-containing gas mixture. The use of perfluorochemicals, rather than nitrogen, as the inert carrier of oxygen and carbon dioxide offers a number of theoretical advantages for the treatment of acute lung injury, including:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_414", "contents": "Despite its theoretical advantages, efficacy studies have been disappointing and the optimal clinical use of LV has yet to be defined. [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_415", "contents": "In total liquid ventilation (TLV), the entire lung is filled with an oxygenated PFC liquid, and a liquid tidal volume of PFC is actively pumped into and out of the lungs. A specialized apparatus is required to deliver and remove the relatively dense, viscous PFC tidal volumes, and to extracorporeally oxygenate and remove carbon dioxide from the liquid. [ 45 ] [ 46 ] [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_416", "contents": "In partial liquid ventilation (PLV), the lungs are slowly filled with a volume of PFC equivalent or close to the FRC during gas ventilation. The PFC within the lungs is oxygenated and carbon dioxide is removed by means of gas breaths cycling in the lungs by a conventional gas ventilator. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_417", "contents": "Mucoactive agents  are a class of chemical agents that aid in the clearance of  mucus  or  sputum  from the upper and lower airways, including the  lungs ,  bronchi , and  trachea . Mucoactive drugs include expectorants, mucolytics, mucoregulators, and mucokinetics. These medications are used in the treatment of respiratory diseases that are complicated by the oversecretion or  inspissation  of mucus. These drugs can be further categorized by their  mechanism of action . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_418", "contents": "Mucoactive agents \u2014 expectorants \u2014include mucolytics, secretolytics and mucokinetics (also called secretomotorics)  [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_419", "contents": "Alternatively, attacking the affinity between secretions and the biological surfaces is another avenue, which is used by  abhesives  and  surfactants . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_420", "contents": "Any of these effects could improve airway clearance during coughing. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_421", "contents": "In general, clearance ability is hampered by the bonding to surfaces (stickiness) and by the  viscosity  of mucous secretions in the lungs. In turn, the viscosity is dependent upon the concentration of  mucoprotein  in the secretions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_422", "contents": "Mucolytics, secretolytics and secretomotorics are different types of medication, yet they are intended to promote drainage of mucus from the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_423", "contents": "An expectorant (from the Latin  expectorare , to expel or banish) works by signaling the body to increase the amount or hydration of secretions, resulting in more, yet clearer, secretions and lubricating the irritated respiratory tract. [ 4 ] \nOne mucoactive agent,  guaifenesin , has  anxiolytic  and muscle-relaxing properties. It is commonly available in cough syrups and also as sustained-release tablets."}
+{"id": "WikiPedia_Pulmonology$$$corpus_424", "contents": "Mucolytics can dissolve thick mucus and are usually used to help relieve respiratory difficulties. They do this by breaking down the chemical bonds between molecules in the mucus. [ 5 ]  This in turn can lower the viscosity by altering the  mucin -containing components. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_425", "contents": "An expectorant increases bronchial secretions and mucolytics help loosen thick bronchial secretions. Expectorants reduce the thickness or viscosity of bronchial secretions, thus increasing mucus flow that can be removed more easily through coughing. Mucolytics break down the chemical structure of mucus molecules. The mucus becomes thinner and can be removed more easily through coughing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_426", "contents": "Mucoactive drugs include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_427", "contents": "The  multiple inert gas elimination technique  (MIGET) is a medical technique used mainly in  pulmonology  that involves measuring the concentrations of various  infused ,  inert gases  in mixed  venous blood ,  arterial blood , and expired gas of a subject. The technique quantifies true  shunt ,  physiological dead space ventilation , ventilation versus blood flow ( V A /Q ) ratios, and  diffusion  limitation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_428", "contents": "Hypoxemia  is generally attributed to one of four processes:  hypoventilation , shunt (right to left),  diffusion limitation , and ventilation/perfusion ( V A /Q ) inequality. [ 1 ]  Moreover, there are also \"extrapulmonary\" factors that can contribute to fluctuations in arterial PO 2 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_429", "contents": "There are several measures of hypoxemia that can be assessed, but there are various limitations associated with each. It was for this reason that the MIGET was developed, to overcome the shortcomings of previous methods. [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_430", "contents": "Steady-state  gas exchange in the  lungs  obeys the principles of  conservation of mass . [ 6 ]   This leads to the ventilation/perfusion equation for  oxygen :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_431", "contents": "and for  carbon dioxide :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_432", "contents": "where:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_433", "contents": "For the purposes of utilizing the MIGET, the equations have been generalized for an  inert gas  (IG):"}
+{"id": "WikiPedia_Pulmonology$$$corpus_434", "contents": "Assuming diffusion equilibration is complete for the inert gas, dropping the subscript IG, and substituting the blood-gas  partition coefficient  ( \u03bb ) renders:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_435", "contents": "Rearranging:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_436", "contents": "This equation is the foundation for the MIGET, and it demonstrates that the fraction of inert gas not eliminated from the blood via the lung is a function of the partition coefficient and the  V A /Q  ratio.  This equation operates under the presumption that the lung is perfectly homogenous.  In this model, retention ( R ) is measured from the ratio  \u2060 \n \n \n \n \n P \n \n A \n \n \n \n / \n \n \n P \n \n v \n \n \n \n \n {\\displaystyle P_{A}/P_{v}} \n \n \u2060 .  Stated mathematically:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_437", "contents": "From this equation, we can measure the levels of each inert gas retained in the blood.  The relationship between retention (R) and  \u2060 \n \n \n \n \n V \n \n A \n \n \n \n / \n \n Q \n \n \n {\\displaystyle V_{A}/Q} \n \n \u2060  can be summarized as follows:  As  \u2060 \n \n \n \n \n V \n \n A \n \n \n \n / \n \n Q \n \n \n {\\displaystyle V_{A}/Q} \n \n \u2060  for a given  \u03bb  increases,  R  decreases; however, this relationship between  \u2060 \n \n \n \n \n V \n \n A \n \n \n \n / \n \n Q \n \n \n {\\displaystyle V_{A}/Q} \n \n \u2060  and  R  is the most obvious at values of  \u2060 \n \n \n \n \n V \n \n A \n \n \n \n / \n \n Q \n \n \n {\\displaystyle V_{A}/Q} \n \n \u2060  between ten times higher and lower than a gas's  \u03bb .  Beyond this, however, it is possible to measure the concentrations of the inert gases in the expired gas from the subject.  The ratio of the mixed expired concentration to the mixed venous concentration has been termed excretion ( E ) and describes the ventilation to regions of varying  \u2060 \n \n \n \n \n V \n \n A \n \n \n \n / \n \n Q \n \n \n {\\displaystyle V_{A}/Q} \n \n \u2060 .  When taken together:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_438", "contents": "When observing a collection of alveoli in which PO 2  and PCO 2  are uniform, local alveolar ventilation and local blood flow define  \u2060 \n \n \n \n \n V \n \n A \n \n \n \n / \n \n Q \n \n \n {\\displaystyle V_{A}/Q} \n \n \u2060 :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_439", "contents": "From these equations it can be deduced that to have knowledge of either retention or excretion implies knowledge of the other.  Moreover, a similar understanding exists for the relationship between the distribution of blood flow and the distribution of ventilation. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_440", "contents": "The data produced by the MIGET is an approximation of the distribution of  \u2060 \n \n \n \n \n V \n \n A \n \n \n \n / \n \n Q \n \n \n {\\displaystyle V_{A}/Q} \n \n \u2060  ratios across the entire lung.  It has been estimated that nearly 100,000 gas exchange units exist in the human lung; [ 7 ]  this could lead to a theoretical maximum of VA/Q compartments as high as 100,000, in that case."}
+{"id": "WikiPedia_Pulmonology$$$corpus_441", "contents": "Many terms are used in  mechanical ventilation , some are specific to brand, model, trademark and  mode of mechanical ventilation . [ 1 ]   There is a standardized  nomenclature of mechanical ventilation  that is specific about nomenclature related to modes, but not settings and variables. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_442", "contents": "Terms are now split into acronyms of CONTROL VARIABLE + BREATH SEQUENCE + TARGETING SCHEME.  As in PC-CMV, Pressure Controlled Continuous Mandatory Ventilation. The term trigger (commonly flow or pressure) denotes the criteria that starts inspiration and cycle denotes the criteria that stops it. \nThe target variable should not be confused with the cycle variable or the control variable. The target variable only sets an upper limit for pressure, volume or flow."}
+{"id": "WikiPedia_Pulmonology$$$corpus_443", "contents": "The physical parameter that controls the breath in accordance with the equation of motion"}
+{"id": "WikiPedia_Pulmonology$$$corpus_444", "contents": "Pressure = Elastance*Volume + Resistance*Flow"}
+{"id": "WikiPedia_Pulmonology$$$corpus_445", "contents": "Volume controlled ventilation is ventilation where both volume and flow are controlled by the ventilator. Normally, flow is set to a fixed amount, meaning volume increases linearly over time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_446", "contents": "Any mode that relies on flow to control inspiration falls under the VC- category."}
+{"id": "WikiPedia_Pulmonology$$$corpus_447", "contents": "Pressure controlled ventilation is where pressure as a function of time is controlled by the ventilator. Normally, pressure is set to a specific amount for a specific breath duration, letting volume and flow vary according to patient demands."}
+{"id": "WikiPedia_Pulmonology$$$corpus_448", "contents": "Any mode that relies on pressure to deliver a breath falls under the PC- category."}
+{"id": "WikiPedia_Pulmonology$$$corpus_449", "contents": "Rarely breaths can be purely time controlled. An example is  intrapulmonary percussive ventilation . Here only time is set by the operator and pressure and flow change obeying the equation of motion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_450", "contents": "Commonly known as \u201cAssist/Control\u201d; CMV is a breath sequence for which spontaneous breaths are not possible between mandatory breaths because every patient trigger signal in the trigger window produces a machine cycled inspiration (i.e., a mandatory breath). Machine triggered mandatory breaths may be delivered at a preset rate. Therefore, in contrast to IMV, the mandatory breath frequency may be higher than the set frequency but never below it. In some pressure controlled modes on ventilators with an active exhalation valve, spontaneous breaths may occur during mandatory breaths, but the defining characteristic of CMV is that spontaneous breaths are not permitted between mandatory breaths. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_451", "contents": "IMV is a form of ventilation where the ventilator delivers mandatory breaths, but spontaneous breaths are possible between mandatory breaths. Mandatory breaths can be delivered at a set frequency (with spontaneous breaths occurring in between), or can be delivered whenever breath volume per minute falls below a set point. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_452", "contents": "Continuous Spontaneous Ventilation  \u2014  CSV  is a breath sequence for which all breaths are spontaneous.\nTerms no longer in use:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_453", "contents": "Mandatory Breath  is a breath type during mechanical ventilation for which inspiration is machine triggered and/or machine cycled."}
+{"id": "WikiPedia_Pulmonology$$$corpus_454", "contents": "Spontaneous Breath s are a breath type for which inspiration is both patient triggered and patient cycled. Applies to assisted or unassisted breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_455", "contents": "Assisted ventilation  or assisted breath references ventilation (or breath) for which a machine provides some or all of the  work of breathing ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_456", "contents": "Patient triggered breath  \u2014 A breath that is initiated by the patient, independent of ventilator settings for frequency."}
+{"id": "WikiPedia_Pulmonology$$$corpus_457", "contents": "Autotriggering  \u2014 Autotriggering is the unintended initiation of breath delivery by the ventilator, e.g., by an external disturbance such as movement of the breathing tube or an inappropriate trigger sensitivity setting."}
+{"id": "WikiPedia_Pulmonology$$$corpus_458", "contents": "The following are terms that are included in  modes of mechanical ventilation  but are not yet included in the standardized nomenclature."}
+{"id": "WikiPedia_Pulmonology$$$corpus_459", "contents": "Normocapnia  or  normocarbia  is a state of normal  arterial   carbon dioxide  pressure, usually about 40 mmHg."}
+{"id": "WikiPedia_Pulmonology$$$corpus_460", "contents": "Within the medical field of  respiratory therapy ,  Open lung ventilation  is a strategy that is utilized by several  modes of mechanical ventilation  to combine low tidal volume and applied  PEEP  to maximize recruitment of alveoli.  The low  tidal volume  aims to minimize alveolar overdistention and the PEEP minimizes cyclic atelectasis.  Working in tandem the effects from both decrease the risk of  ventilator-associated lung injury ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_461", "contents": "Some clinical trials indicate that open lung ventilation may improve mortality, other clinically important outcomes, and oxygenation. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_462", "contents": "Open lung ventilation is generally well tolerated. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_463", "contents": "A universally accepted protocol for open lung ventilation has not been established. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_464", "contents": "Peak inspiratory pressure  ( P IP ) is the highest level of pressure applied to the  lungs  during  inhalation . [ 1 ]   In  mechanical ventilation  the number reflects a positive pressure in centimeters of water pressure (cm H 2 O).  In normal breathing, it may sometimes be referred to as the  maximal inspiratory pressure  (M IPO ), which is a negative value. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_465", "contents": "Peak inspiratory pressure increases with any airway resistance. Factors that may increase P IP  include increased secretions, bronchospasm, biting down on ventilation tubing, and decreased lung compliance. P IP  should never be chronically higher than 40 cm H 2 O unless the patient has acute respiratory distress syndrome. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_466", "contents": "Permissive hypercapnia  is  hypercapnia  (i.e. high concentration of  carbon dioxide  in blood) in  respiratory insufficient  patients in which  oxygenation  has become so difficult that the optimal mode of  mechanical ventilation  (with oxygenation in mind) is not capable of exchanging enough carbon dioxide. Carbon dioxide is a  gaseous  product of the  body's   metabolism  and is normally expelled through the  lungs ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_467", "contents": "In  acute respiratory distress syndrome  (ARDS), decreasing the tidal volume on the ventilator (usually 6-8 mL/kg) to 4-6 mL/kg may decrease  barotrauma  by decreasing ventilatory peak airway pressures and leads to improved respiratory recovery.  Hypercapnia (increased pCO 2 ) sometimes needs to be tolerated in order to achieve these lower tidal volumes. The permissive hypercapnia leads to respiratory acidosis which might have negative side effects, but given that the patient is in ARDS, improving ventilatory function is more important."}
+{"id": "WikiPedia_Pulmonology$$$corpus_468", "contents": "Since  hypoxemia  is a major life-threatening condition and hypercapnia is not, one might choose to accept the latter. Hence the term, \"permissive hypercapnia.\""}
+{"id": "WikiPedia_Pulmonology$$$corpus_469", "contents": "Symptoms of early hypercapnia (i.e. where PaCO 2  is elevated but not extremely so) include flushed skin, full  pulse ,  extrasystoles , muscle twitches, hand flaps, and possibly a raised  blood pressure . In severe hypercapnia (generally PaCO 2  greater than 10  kPa  or 75  mmHg ), symptomatology progresses to disorientation,  panic ,  hyperventilation ,  convulsions ,  unconsciousness , and eventually  death ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_470", "contents": "Mechanical ventilation using high tidal volume (VT) and transpulmonary pressure can damage the lung, causing ventilator-induced lung injury. Permissive hypercapnia, a ventilatory strategy for acute respiratory failure in which the lungs are ventilated with a low inspiratory volume and pressure, has been accepted progressively in critical care for adult, pediatric, and neonatal patients requiring mechanical ventilation and is one of the central components of current protective ventilatory strategies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_471", "contents": "Phthisiology  is the care, treatment, and study of  tuberculosis  of the  lung . It is therefore considered a specialisation within the area of  pulmonology . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_472", "contents": "The term derives from the designation by  Hippocrates  of phthisis ( Greek  \u03c6\u03b8\u03af\u03c3\u03b9\u03c2) meaning \" consumption \"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_473", "contents": "This  medical treatment \u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_474", "contents": "Pneumothorax ex vacuo  is a rare type of  pneumothorax  which forms adjacent to an  atelectatic lobe . [ 1 ]  It is seen preferentially with atelectasis of the right upper lobe and is the result of rapid atelectasis producing an abrupt decrease in the intrapleural pressure with subsequent release of  nitrogen  from pleural  capillaries ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_475", "contents": "Treatment consists of  bronchoscopy  rather than chest tube drainage.  Radiographically , pneumothorax ex vacuo is suggested when an atelectatic lobe or lung, particularly right upper lobe atelectasis, is surrounded by a focal pneumothorax. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_476", "contents": "\"Trapped lung\" presents in the same way as pneumothorax ex vacuo and can occur in patients with visceral pleural thickening and following drainage of an effusion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_477", "contents": "Precision cut lung slices  or  PCLS  refer to thin sections of lung tissue that are prepared with high precision and are typically used for experimental purposes in the field of respiratory research. [ 1 ]  These slices are utilized to study various aspects of lung physiology, pathology, and pharmacology, providing researchers with a valuable tool for investigating lung diseases and testing the effects of drugs on lung tissue. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_478", "contents": "Precision cut lung slices are prepared using specialized equipment called  Vibratomes , ensuring that the tissue remains viable and retains its structural and functional characteristics, making them ideal for a wide range of experimental applications. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_479", "contents": "The history of Precision-cut Lung Slices (PCLS) dates back to the 1920s when scientists first explored tissue slices for studying organ metabolism and toxicology. Initially, manual slicing of tissues, such as the liver, led to significant variability in thickness and limited viability. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_480", "contents": "A critical advancement occurred in the 1940s when Stadie and Riggs introduced a  microtome  equipped with a thin razor blade, reducing thickness variability to about 5%. These improved slices became known as precision-cut tissue slices. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_481", "contents": "Creating PCLS posed unique challenges due to the lung's intricate structure. In the 1980s, Placke and Fisher achieved a breakthrough by infusing heated liquid agarose into the airways of hamster and rat lungs, preventing airway and alveolar collapse during slicing. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_482", "contents": "Creating Precision-cut Lung Slices (PCLS) is a meticulous process that involves several essential steps. The use of vibratomes is crucial in ensuring the production of precise and high-quality lung slices for research purposes. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_483", "contents": "The basic steps involved in preparing PCLS using vibratomes include: [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_484", "contents": "Ensuring the viability of Precision-cut Lung Slices (PCLS) during ex vivo maintenance presents several challenges. Typically, PCLS are submerged in culture medium within multi-well plates, simulating tissue culture conditions at 37\u00a0\u00b0C, 5% CO2, and 95\u2013100% air humidity. [ 9 ]  The culture medium is refreshed daily and optimized with essential nutrients, enabling viable PCLS to be maintained for up to 14 days, a significant improvement compared to previous reports of only 3\u20135 days. [ 10 ]  Additionally, the inclusion of antibiotics like penicillin and streptomycin helps prevent pathogen contamination from the outset of culture. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_485", "contents": "While in culture, PCLS retain their viability, normal metabolic activity, tissue integrity, and responsiveness to stimuli such as lipopolysaccharide (LPS). [ 10 ]  However, it's important to note that extended culture periods may lead to some changes in PCLS function. For instance, although human PCLS can contract in response to methacholine, the secretion of LPS-induced TNF-\u03b1, while maintained, may diminish over time. [ 12 ]  Furthermore, long-term cultivation can result in the loss of certain cell populations, such as pneumocytes and lymphocytes, as well as the degradation of connective tissue fibers. These changes may contribute to decreased sensitivity of cultured PCLS to external stimuli. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_486", "contents": "In practice, PCLS can maintain comparable viability and tissue homeostasis for 1 to 3 days, though extended periods can be achieved with optimized culture conditions. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_487", "contents": "Precision-cut lung slices find extensive use in a variety of experimental applications in the field of respiratory research. Some of the key areas where PCLS are employed include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_488", "contents": "In the pursuit of understanding and developing treatments for asthma, researchers have explored various models, including animal models like mice and rats, to mimic different aspects of the condition. While these animal models have contributed to our knowledge, they come with limitations, particularly in terms of translatability to humans. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_489", "contents": "To address these limitations and enhance our understanding of asthma, researchers have turned to human Precision-cut Lung Slices (PCLS) obtained from both healthy and diseased individuals as a valuable ex vivo tool. [ 15 ]  PCLS derived from healthy and asthmatic lungs exhibit altered responses to various stimuli, including bronchoconstriction and hyperresponsiveness, which closely resemble those observed in patients and various animal models. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_490", "contents": "Moreover, PCLS from individuals with asthma have been shown to display significantly increased airway inflammation and hyperresponsiveness when stimulated by factors such as rhinovirus. [ 16 ]  These PCLS also exhibit elevated gene expression related to asthma pathogenesis, including genes like Il25, Tslp, and Il13. [ 17 ]  These findings align with observations in asthmatic patients, indicating that PCLS models provide a promising platform for asthma research. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_491", "contents": "While no in vivo models fully encompass all aspects of clinical COPD pathology, certain animal models, such as those involving cigarette smoke exposure, elastase-induced emphysema, and LPS challenge, have yielded valuable insights. For instance, exposing guinea pigs or mice to cigarette smoke can reproduce key features of human COPD, including emphysema, small airway remodeling, and pulmonary hypertension. However, this model typically manifests mild emphysema and requires months to develop. [ 18 ]  In contrast, delivering elastase to the lungs of mice rapidly induces an emphysematous phenotype, allowing for controlled disease severity by adjusting elastase dose, administration route, and duration. [ 19 ]  It's worth noting that the  physiological relevance  of elastase and LPS models is debatable due to differences in underlying mechanisms. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_492", "contents": "The use of Precision-cut Lung Slices (PCLS) from in vivo models has proven particularly valuable in modeling COPD. For instance, PCLS obtained from smoke-exposed mice have shown elevated expression of chemokines when stimulated with viral mimics or influenza A virus. [ 21 ]  Murine PCLS have also demonstrated that Influenza A infection and cigarette smoke can impair bronchodilator responsiveness to \u03b22-adrenoceptor agonists. Future studies employing PCLS from COPD patients hold the potential to enable both functional and phenotypic immune cell characterization, facilitating a more comprehensive understanding of molecular mechanisms underlying disease heterogeneity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_493", "contents": "Precision-cut Lung Slices (PCLS) have proven effective in studying the early stages of lung fibrosis in IPF. When exposed to TGF-\u03b21 and cadmium chloride, both human and rat PCLS have displayed relevant pathohistological changes commonly observed in the early phases of lung fibrosis. These changes include the upregulation of critical pro-fibrotic genes, increased thickness of alveolar septa, and abnormal activation of pulmonary cells. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_494", "contents": "Recent advancements in research have led to the establishment of an ex vivo human PCLS model specifically focused on early-stage fibrosis. This model involves exposing PCLS to a combination of pro-fibrotic growth factors and signaling molecules, including TGF-\u03b21, TNF-\u03b1, platelet-derived growth factor-AB, and lysophosphatidic acid. [ 23 ]  This approach offers a pathway to investigate the underlying mechanisms of early IPF and assess novel therapies. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_495", "contents": "Researchers are actively evaluating novel treatments for IPF using PCLS. For example, caffeine, which inhibits TGF-\u03b2-induced increases in pro-fibrotic gene expression, has shown promise by significantly reducing fibrosis in PCLS from bleomycin-treated mice. Additionally, targeting PI3K signaling has emerged as a promising anti-fibrotic treatment strategy, as demonstrated using PCLS derived from IPF patients. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_496", "contents": "The use of PCLS in IPF research holds great potential for understanding the disease's early stages, testing innovative therapies, and uncovering novel treatment strategies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_497", "contents": "Precision-cut Lung Slices (PCLS) have been instrumental in studying the body's innate responses to viral and, to a lesser extent, bacterial challenges. This system has shed light on which cells become infected within the intact lung, offering insights distinct from in vitro air-liquid interface cultures. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_498", "contents": "Studies by Goris et al. have revealed variations in the infectability of different cell types within the lung. For instance, bovine parainfluenza virus infection was observed primarily in cells beneath the lung epithelium within the PCLS system. [ 26 ] [ 27 ]  Importantly, this suggests that the epithelium, when in its natural physiological structure, resists infection. Similar findings were reported by Kirchhoff et al. [ 28 ]  These studies emphasize the significance of studying cells within their physiological environment, considering cell associations and structural architecture. Such interactions not only affect infectability but also shape the system's response to infection."}
+{"id": "WikiPedia_Pulmonology$$$corpus_499", "contents": "The PCLS system serves as a valuable tool for understanding inflammatory responses. It has been employed to investigate the innate response to bacterial wall components like LPS and to conduct complex mixed infection studies involving multiple viruses or viral and bacterial co-infections. This approach enables precise analysis of immune responses to each stimulus. In simpler models, PCLS have been used to assess the impact of LPS on the innate immune response, testing the effects of various immunomodulators on innate signaling. [ 29 ] [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_500", "contents": "Furthermore, the ability to obtain slices from diseased lungs, such as those affected by conditions like COPD and asthma, provides a robust model for studying how respiratory diseases influence infectivity and host responses. This is particularly relevant for diseases like COPD and asthma, which have links to pathogen-induced exacerbations."}
+{"id": "WikiPedia_Pulmonology$$$corpus_501", "contents": "PCLS research in infection and inflammation enhances our understanding of immune responses, paving the way for insights into disease mechanisms and potential therapeutic strategies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_502", "contents": "Precision-cut Lung Slices (PCLS) play a crucial role in evaluating novel therapeutic targets for asthma, especially as tolerance to conventional treatments like glucocorticoids and \u03b22-receptor agonists becomes more common. Researchers have increasingly focused on targets relevant to asthma pathogenesis, and PCLS have become a valuable tool for evaluating these targets as potential therapeutics. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_503", "contents": "For instance, studies have shown that inhibiting histone deacetylase with trichostatin A can alleviate airway constriction in human PCLS and simultaneously reduce airway hyperresponsiveness in antigen-challenged mice. [ 31 ]  Additionally, activating soluble guanylate cyclase in airway smooth muscle using riociguat and cinaciguat analogs has been found to induce bronchodilation in normal human PCLS and reverse airway hyperresponsiveness in allergic asthmatic mice, restoring normal lung function. [ 30 ] [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_504", "contents": "The use of PCLS in drug development is expanding further, with specific agonists or inhibitors targeting bitter-taste receptors, peroxisome proliferator-activated receptor (PPAR) \u03b3, phosphoinositide-3 kinase (PI3K), BK channels, and spleen tyrosine kinase (Syk) all undergoing investigation within this context. [ 30 ] [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_505", "contents": "PCLS research contributes significantly to the development of innovative therapeutic strategies for asthma, addressing the evolving challenges of treatment resistance. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_506", "contents": "Precision-cut Lung Slices (PCLS) offer several distinct advantages that make them invaluable tools in respiratory research. They excel in preserving the intricate lung architecture, maintaining essential tissue structures like small airways, respiratory parenchyma, structural and immune cell populations, and connective tissue. [ 34 ]  The cellular composition within PCLS closely mirrors that of intact lungs, retaining the organization of structural and immune cells. [ 35 ] [ 36 ]  However, it's important to note that specific cell types' distribution may vary among slices due to regional variability within the lung, especially in the presence of non-uniform disease-related changes. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_507", "contents": "In certain contexts, PCLS can be considered as \"mini\" lungs. [ 38 ]  While lacking a recruitable immune system, PCLS provide a unique opportunity to correlate cell-specific functions with organ physiology. They exhibit complex responses to challenges and stimuli, such as airway contraction and immune responses, shedding light on disease mechanisms and treatment evaluations. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_508", "contents": "PCLS have found applications in a wide range of respiratory research areas, including asthma, COPD, idiopathic pulmonary fibrosis, allergies, infections, and toxicology studies. Researchers have harnessed the advantages of PCLS to model and study these prominent respiratory diseases, facilitating insights and translational relevance to human disease. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_509", "contents": "Precision-cut Lung Slices (PCLS) provide valuable insights into lung physiology and pathology, but they do have limitations. Firstly, PCLS represent a static \"snapshot\" of lung tissue at the time of excision, lacking access to the dynamic, recruitable immune system present in living organisms. This limitation hinders the full understanding of immune responses within the lung. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_510", "contents": "Furthermore, lung tissue is inherently heterogeneous, with variations in epithelial integrity, immune cell populations, and responses to stimulation across different lung regions. When studying diseases, such as respiratory conditions, this heterogeneity can complicate data interpretation, requiring careful statistical analysis to account for variability between slices. [ 41 ] [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_511", "contents": "PCLS have a limited ability to fully replicate the intricate and dynamic immune responses observed in living organisms. They cannot recruit non-resident immune cells, and their viability is restricted to approximately two weeks. [ 43 ]  While they can capture initial signals induced by pathogens, they cannot fully mimic the complex immune responses seen in a living lung. [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_512", "contents": "Another limitation is that PCLS are typically used as static systems and do not replicate the natural breathing motion of the lung. [ 45 ]  This is particularly relevant when studying diseases like ventilator-induced lung injury, where mechanical stress from ventilation plays a crucial role. Attempts to stretch or deform PCLS have been made to simulate mechanical dynamics, but accurately replicating these processes remains a challenge. [ 46 ] [ 47 ] [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_513", "contents": "Administering treatments in PCLS can be challenging because the entire slice is bathed in the compound or stimulant of interest. This poses difficulties in translating findings to inhaled or systemic applications in vivo, making dosing and translation  [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_514", "contents": "Administering treatments in PCLS can be challenging because the entire slice is bathed in the compound or stimulant of interest. This poses difficulties in translating findings to inhaled or systemic applications in vivo, making dosing and translation complex. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_515", "contents": "Pulmonary agenesis  is an inborn lung underdevelopment that is rare and potentially lethal. [ 1 ]  The disorder is caused by a complete developmental arrest of the primitive lung during  embryonic  life, and it is often associated with other developmental defects. [ 2 ]  Bilateral and unilateral pulmonary agenesis are classified, depending on whether one side of the lung or both sides are affected.  Bilateral pulmonary agenesis  is lethal, while the mortality rate of unilateral pulmonary agenesis is higher than 50%. [ 3 ]  Depending on the severity, the symptom ranges from none to various respiratory complaints. [ 4 ]  It is detectable prenatally, however, its nonspecific clinical features act as the obstacle for diagnosing. [ 2 ]  The exact cause of pulmonary agenesis is still obscure. However, theories have been raised regarding the vascular,  iatrogenic , viral and genetic causes of pulmonary agenesis in an attempt to explain the pathogenesis of the disorder. [ 5 ]  In most cases of pulmonary agenesis, surgical resection is performed to remove the malformed lobe or the entire defected lung of the patient depending on the severity of the respiratory impairment. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_516", "contents": "Pulmonary agenesis is the complete absence of lung tissue, including bronchial tree,\u00a0lung parenchyma, and supporting vasculatures. [ 7 ]  The only remaining part is rudimentary bronchus. [ 7 ]  Hence, the affected areas lose their function of gas exchange. [ 7 ]  This malformation is thought to involve the proliferation arrest of lung buds during embryo development, while the causes are still debatable. In many cases, it is associated with the occurrence of other inborn malformations. [ 7 ]  The estimated prevalence of pulmonary agenesis is 34/1,000,000 live births, with a slightly higher possibility in the female population. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_517", "contents": "Two types of pulmonary agenesis are classified based on the severity of underdevelopment: bilateral and unilateral pulmonary agenesis. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_518", "contents": "Bilateral pulmonary agenesis means that both sides of the lung are absent, its occurrence is rare compared to unilateral pulmonary agenesis. [ 9 ]  The fetus loses the ability to do gas exchange post-delivery, and is hence incompatible with life after birth. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_519", "contents": "The severity of unilateral pulmonary agenesis varies depending on the area of tissue affected, being either a single lobe or a whole lung. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_520", "contents": "The clinical features varies in individuals from asymptomatic to various respiratory complaints. [ 4 ]  The occurrences of symptoms also vary from infant stage to childhood, teenager, and adult life. [ 4 ]  Frequently seen clinical features includes  dyspnea , respiratory distress, recurrent pulmonary infections, and limited exercise tolerance. [ 4 ]  Rapid heartbeat,  cyanosis , chest asymmetry, dullness may also be present. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_521", "contents": "Lung function is significantly affected in cases of pulmonary agenesis, demonstrated by reduction in forced expiratory volume and forced vital capacity. [ 4 ]  This reduction in  total lung volume  sets limits on patients\u2019 exercise tolerance, and contribute to shortness of breath after exercises. [ 4 ]  The retention of bronchial secretions often leads to recurrent pulmonary infections, adding to damage in lung function, hence causing respiratory stress. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_522", "contents": "Considering the fact that a large proportion of mortality cases of pulmonary agenesis are partly due to the presence of associated malformations, it is common to find other  congenital anomalies  associated with this type of disorder. Although some cases of bilateral pulmonary agenesis were reported as an isolated finding, most cases of pulmonary agenesis are associated with other anomalies, especially in the  gastrointestinal ,  genitourinary  and  ocular  systems. Frequently associated congenital anomalies include  tracheal stenosis ,  esophageal atresia ,  tracheoesophageal fistula ,  bronchogenic cysts ,  patent ductus arteriosus ,  tetralogy of Fallot  and anomalies of the  great vessels . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_523", "contents": "Although pulmonary agenesis, aplasia and hypoplasia are lethal congenital disorders all resulting from underdevelopment of lungs, pulmonary agenesis and aplasia differ from  pulmonary hypoplasia  in their underlying cause. [ 12 ]  Unlike  pulmonary hypoplasia  which in most cases result from the incomplete development of lung during  prenatal development , [ 13 ]  pulmonary agenesis and  aplasia  result from a complete developmental arrest of the primitive lung during  embryonic  life. [ 12 ]  The difference between pulmonary agenesis and aplasia is that pulmonary agenesis has complete absence of lung tissue, airways, and lung vessels while pulmonary aplasia has complete absence of lung tissue and lung vessels, but have some incompletely developed short airways. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_524", "contents": "Whether the  disorder  is bilateral or unilateral depends on the stage in which the arrest occurs during the embryonic stage of lung development. [ 12 ]  The earlier the occurrence of developmental arrest, the more severe the defect and the more likely that the agenesis will be bilateral. [ 12 ]  Bilateral pulmonary agenesis is highly rare and it is caused by the complete failure in the development of  respiratory primordium , [ 11 ]  the primary structure developed in the earliest stage of embryonic development that gives rise to the entire  respiratory tract . [ 15 ]  In this case, the absence of lung buds or pleural cavities is observed, [ 11 ]  thus making the case of bilateral pulmonary agenesis highly lethal."}
+{"id": "WikiPedia_Pulmonology$$$corpus_525", "contents": "On the other hand, unilateral pulmonary agenesis is caused by the imbalance in the development of  lung buds . Either one side of the lung fails completely, leading to pulmonary aplasia, or one side of the lung is underdeveloped, leading to  dysplasia  or  hypoplasia . [ 11 ]  These defects occur during the early stage of lung development, although not as early as bilateral pulmonary agenesis, when  respiratory primordium  bifurcates into right and left primitive  lung buds  at the end of the fourth week of  gestation . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_526", "contents": "Although the exact cause of the disorder remains obscure, theories have been advanced throughout history to explain the  pathogenesis  of lung agenesis. [ 16 ]  Based on an  in vitro  experiment done in rats, researchers observed lung aplasia in animals that were fed with a diet deficient in  vitamin A . [ 17 ]  From the result of this experiment, a theory was raised that  vitamin A deficiency  during  pregnancy  may cause pulmonary agenesis. Some authors have suggested vascular cause of pulmonary agenesis similar to the causes for intestinal atresia [ 16 ]  and others suggested  Iatrogenic  and  viral  factors as potential causes of pulmonary agenesis. [ 16 ]   Genetic  cause for pulmonary agenesis has also been raised. It has been said that the gene responsible for the cause of pulmonary agenesis may have variable expressivity and penetrance. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_527", "contents": "The symptoms of pulmonary agenesis are unspecific, and their occurrence varies between individuals. [ 2 ]  These factors increased the difficulty for physicians to diagnose. So, there is a considerable time delay for the disease to be diagnosed, though it's capable of detection since birth or even prenatally. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_528", "contents": "Prenatal diagnosis of pulmonary agenesis is yet to be reached satisfaction, due to the technical difficulties in differentiating this disorder with other malformation. [ 2 ]  Only a few cases of reported cases are diagnosed before birth. [ 2 ]   Prenatal sonographic evaluation , also known as  Biophysical profile  is frequently used for prenatal testing. High frequency of associated abnormalities (see the section - \"Associated Abnormalities\" for details) may also lead to suspicion of pulmonary agenesis. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_529", "contents": "2\u2010dimensional color Doppler imaging \u00a0could visually capture the blood flow, hence determine the existence of pulmonary vasculature. [ 2 ]  It is also a frequently used technique for pulmonary agenesis diagnosis. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_530", "contents": "Congenital diaphragmatic hernia (CDH), in this case, the upward displacement of the diaphragm and abdominal organs, is a possible clinical outcome detectable before birth. [ 7 ]  The displacement is caused by organ herniation occupying the empty space in the chest wall, while this space is created by the absence of lung tissue. [ 7 ]  However, it's important to note that a list of other disorders could also be the cause of CDH. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_531", "contents": "Several techniques are frequently involved in the diagnosis of pulmonary agenesis after birth:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_532", "contents": "The treatment is dependent on the severity of respiratory impairment and the underlying  etiology  of the disorder. [ 13 ]  In most cases, surgical resection is performed to remove the nonfunctioning  lobe  or the entire defected lung. [ 13 ]  Removing the malformed part of the lung helps reduce symptoms and chances of  lung infection . [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_533", "contents": "In the past, patients underwent  pulmonary plombage  to render the empty hemithorax. [ 18 ]   Plombage , also known as  extraperiosteal or extrapleural pneumonolysis , is a historical treatment procedure for cavity  tuberculosis  of upper lobes of lungs used between the 1930s and 1950s. [ 19 ]  During the operation, a cavity is created by the  intrathoracic  placement of inert materials, commonly  Lucite (acrylic) balls ,  ping pong balls ,  oils ,  rubber sheets ,  paraffin wax , and  gauze . [ 19 ]  As a result, the mediastinal and skeletal shift toward the volume loss side. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_534", "contents": "Recent approach involves the implantation of  tissue expander  either via open  thoracotomy  or  thoracoscopically  in an attempt to shift the mediastinum back to its anatomical location. [ 20 ]  Such surgical procedure involving the implantation of  tissue expander  for treating pulmonary agenesis was first reported in Berlin, Germany which was then followed by reports from Bordeaux, France and Verona, Italy. [ 20 ]  The main focus of the treatment procedure is to preserve the remaining functional  tissue [ 13 ]  and prevent significant  musculoskeletal disfigurement  that may arise as a side effect of  tissue expander implantation , as the  mediastinal  and  skeletal  shift towards the volume-loss side. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_535", "contents": "If the defect is extensive but there is a chance for the  fetus  to live, an  exo-utero intrapartum treatment (EXIT)  may be performed to salvage the potential life. [ 18 ]   EXIT  technique involves partial delivery of a baby through an  incision  in the  uterus  while remaining attached to their mother's  placenta . [ 19 ]  Such procedure is necessary for babies who require airway support so that they are provided with a functioning airway before they are detached from their mother's  placenta . [ 19 ]  The  EXIT  procedure is used to perform  lung resection  for babies with extensive lung defects in a relatively stabilized condition after birth. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_536", "contents": "Prognosis of pulmonary agenesis depends on the degree of pulmonary involvement during the  embryonic stage  of lung development, as well as the patient's history of  pulmonary infections  and the presence of associated anomalies. [ 18 ]  The majority of patients diagnosed with bilateral pulmonary agenesis die in  utero  or within the first few hours after birth. [ 22 ]  Numerous cases of bilateral pulmonary agenesis, where both lungs have been affected, have been reported previously. [ 19 ]  On the other hand, the  hypertrophy  of the remaining lung to compensate for the lost lung is common in the case of unilateral pulmonary agenesis. [ 22 ]  However, the  mortality rate  still exceeds 50%. Most causes of death are because of the presence of associated anomalies and malformations, which are common for pulmonary agenesis especially involving right-sided defects. Those suffering right-sided defects normally have poorer prognosis than those with left-sided defects, partly because the right side of the lung is usually more prone to infection considering the  standard anatomical position  of right  bronchus , and also because cases with right-sided lung disorders have shown higher association rates with other anomalies. [ 18 ]  In fact, it has been suggested that right-sided defects produce a more severe  mediastinal shift , distorting the  trachea  and  great vessels . [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_537", "contents": "Pulmonary agenesis was a confusing term before Boyden's classification was published. Before that, the term agenesis was used frequently when reporting cases related to underdeveloped lungs, regardless of the degree of the underdevelopment. [ 1 ]  In 1955, Boyden classified pulmonary agenesis into 3 groups: agenesis, aplasia, and hypoplasia, which has been adopted by most researchers nowadays. [ 1 ]  As a clarification, the term \u201cpulmonary agenesis\u201d in this Wikipedia page will only be referring to the agenesis in Boyden's classification, hence the information contained may not be valid for pulmonary aplasia or hypoplasia unless specifically mentioned. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_538", "contents": "Pulmonary capillary hemangiomatosis  ( PCH ) is a disease affecting the blood vessels of the lungs, where abnormal capillary proliferation and venous fibrous intimal thickening result in progressive increase in vascular resistance. [ 1 ]  It is a rare cause of  pulmonary hypertension , and occurs predominantly in young adults. [ 2 ] [ 3 ]  Together with  pulmonary veno-occlusive disease , PCH comprises WHO Group I' causes for pulmonary hypertension. Indeed, there is some evidence to suggest that PCH and pulmonary veno-occlusive disease are different forms of a similar disease process. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_539", "contents": "Nonspecific symptoms like fatigue, coughing, chest pain, and shortness of breath are what define clinical features. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_540", "contents": "At least some cases appear to be due to mutations in the eukaryotic translation initiation factor 2-alpha kinase 4 ( EIF2AK4 ) gene. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_541", "contents": "This condition has been reported in patients with  Ehlers Danlos syndrome , [ 7 ]  and  scimitar syndrome . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_542", "contents": "Pulmonary artery hypertension, which manifests as enlarged pulmonary arteries, is a common imaging characteristic of pulmonary capillary hemangiomatosis. Additionally, as pulmonary artery hypertension worsens, typical CT imaging findings of right ventricular hypertrophy, leftward interventricular septum bowing, right atrial enlargement, and reflux of IV contrast into the inferior vena cava and hepatic veins can indicate secondary right heart dysfunction. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_543", "contents": "The only definitive treatment for this condition currently is  lung transplantation . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_544", "contents": "Imatinib  may be of use. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_545", "contents": "Epoprostenol  does not appear to be of use. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_546", "contents": "The prevalence of this disease is estimated to be < 1/million. [ 11 ]  The usual age at presentation is between 20 and 40 but it has been reported in the newborn. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_547", "contents": "This condition was first described in 1978. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_548", "contents": "Median survival without treatment is 3 years. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_549", "contents": "This condition has been reported in cats. [ 15 ]  and dogs. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_550", "contents": "A  pulmonary infiltrate  is a substance denser than  air , such as  pus ,  blood , or  protein , which lingers within the  parenchyma  of the lungs. [ 1 ]  Pulmonary infiltrates are associated with  pneumonia ,  tuberculosis , [ citation needed ]  and  sarcoidosis . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_551", "contents": "Pulmonary infiltrates can be observed on a  chest radiograph . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_552", "contents": "Pulmonary interstitial emphysema  ( PIE ) is a collection of  air  outside of the normal air space of the  pulmonary alveoli , found instead inside the  connective tissue  of the peribronchovascular sheaths, interlobular septa, and  visceral pleura . (This supportive tissue is called the pulmonary interstitium.) This collection of air develops as a result of alveolar and terminal bronchiolar rupture. Pulmonary interstitial emphysema is more frequent in premature infants who require  mechanical ventilation  for severe lung disease.  Infants with pulmonary interstitial emphysema are typically recommended for admission to a  neonatal intensive care unit ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_553", "contents": "Pulmonary interstitial emphysema is a concern in any of the following:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_554", "contents": "Pulmonary interstitial emphysema is created when air bursts or ruptures through tissue from the alveoli and  bronchioles  into the perivascular tissue of the lung."}
+{"id": "WikiPedia_Pulmonology$$$corpus_555", "contents": "A chest X ray may show a \"salt and pepper\" appearance due to the linear lucencies that are present."}
+{"id": "WikiPedia_Pulmonology$$$corpus_556", "contents": "Different treatments have been used to manage pulmonary interstitial emphysema with variable success. Admission/transfer to a  neonatal intensive care unit  (NICU) is common and expected for patients with PIE. Treatments include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_557", "contents": "Pulmonary interstitial emphysema often resolves gradually and may take 2\u20133 weeks. [ 2 ]   For longer durations of PIE the length of time of mechanical ventilation needed may increase and the incidence of  bronchopulmonary dysplasia  becomes higher. Some infants may develop chronic lobar emphysema, which may require surgical  lobectomies . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_558", "contents": "The prevalence of pulmonary interstitial emphysema widely varies with the population studied. In a 1987 study 3% of infants admitted to the  neonatal intensive care unit  (NICU) developed pulmonary interstitial emphysema. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_559", "contents": "Studies reflecting international frequency demonstrated that 2-3% of all infants in NICUs develop pulmonary interstitial emphysema. [ 4 ] [ 5 ]   When limiting the population studied to premature infants, this frequency increases to 20-30%, with the highest frequencies occurring in infants weighing fewer than 1000 g. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_560", "contents": "Respiratory Care Week  is a week set to honor and recognize  respiratory therapists . Respiratory Care Week is celebrated internationally but most notably in  Canada  and the  United States . Respiratory Care Week is usually the last full week of October. [ 1 ]  United States President Ronald Reagan proclaimed the first week dedicated to honoring respiratory therapists in 1982. Originally November 7 through November 13, 1982 [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_561", "contents": "last full week of October (Sunday through Saturday)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_562", "contents": "The  respiratory disturbance index  ( RDI )\u2014or  respiratory distress Index \u2014is a formula used in reporting  polysomnography  (sleep study) findings.  Like the  apnea-hypopnea index  (AHI), it reports on respiratory distress events during sleep, but unlike the AHI, it also includes  respiratory-effort related arousals  (RERAs). [ 1 ]  RERAs are arousals from  sleep  that do not technically meet the definitions of  apneas  or  hypopneas , but do in some way disrupt breathing during sleep and cause respiratory symptoms that may cause an arousal."}
+{"id": "WikiPedia_Pulmonology$$$corpus_563", "contents": "A RERA is characterized by increasing respiratory effort such as  dyspneas  (and thus decreasing esophageal pressures) for 10 seconds or more leading to an arousal from sleep, but one that does not fulfill the criteria for a hypopnea or apnea. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_564", "contents": "The gold standard method for measuring RERAs is  esophageal manometry , as recommended by the  American Academy of Sleep Medicine  (AASM). However, esophageal manometry is uncomfortable for patients, may disrupt sleep and is impractical to use in most  sleep centers ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_565", "contents": "Some research studies have found that a high RDI was significantly  correlated  with  excessive daytime sleepiness , and that this correlation was stronger than that for the frequency of  oxygen saturation  decreases below 85%, but other studies have found only a weak and unreliable correlation. [ 3 ]  More recent studies have found more impressive outcomes of methods in treating patients with RERAs and respiratory events that satisfy the definition of hypopneas in all aspects other than reduction of oxygen saturation levels. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_566", "contents": "The  American Academy of Sleep Medicine  uses RDI to determine the severity of  Obstructive Sleep Apnea  according to the following range: 5\u201314.9 for mild, 15\u201329.9 for moderate, and 30+ for severe, similar to the one used in the AHI. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_567", "contents": "The formula to assessing the RDI is = (RERAs + Hypopneas + Apneas) X 60 / TST (in minutes).  That is, RDI means the average number of episodes of obstructive apnea, hypopnea, and respiratory event-related arousal per hour of sleep. [ 7 ]  (TST is \"total sleep time\".)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_568", "contents": "Respiratory sounds , also known as  lung sounds  or  breath sounds , are the specific sounds generated by the movement of air through the  respiratory system . [ 1 ]  These may be easily audible or identified through  auscultation  of the respiratory system through the  lung fields  with a  stethoscope  as well as from the spectral characteristics of lung sounds. [ 2 ]  These include normal breath sounds and added sounds such as  crackles ,  wheezes ,  pleural friction rubs ,  stertor , and  stridor ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_569", "contents": "Description and classification of the sounds usually involve auscultation of the inspiratory and expiratory phases of the breath cycle, noting both the pitch (typically described as low (\u2264200\u00a0Hz), medium or high (\u2265400\u00a0Hz))  and intensity (soft, medium, loud or very loud) of the sounds heard. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_570", "contents": "Normal breath sounds are classified as vesicular, bronchovesicular, bronchial or tracheal based on the anatomical location of auscultation. [ 4 ] [ 3 ]  Normal breath sounds can also be identified by patterns of sound duration and the quality of the sound as described in the table below: [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_571", "contents": "posteriorly in-between the scapulae"}
+{"id": "WikiPedia_Pulmonology$$$corpus_572", "contents": "Common types of abnormal breath sounds include the following: [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_573", "contents": "Pectoriloquy ,  egophony  and  bronchophony  are tests of  auscultation  that utilize the phenomenon of  vocal resonance . [ 3 ]  Clinicians can utilize these tests during a physical exam to screen for pathological lung disease. For example, in  whispered pectoriloquy , the person being examined whispers a two syllable number as the clinician listens over the  lung fields . The whisper is not normally heard over the lungs, but if heard may be indicative of  pulmonary consolidation  in that area. This is because sound travels differently through denser (fluid or solid) media than the air that should normally be predominant in lung tissue. In egophony, the person being examined continually speaks the English long-sound \"E\" ( /i/ ). The lungs are usually air filled, but if there is an abnormal solid component due to infection, fluid, or tumor, the higher frequencies of the \"E\" sound will be diminished. This changes the sound produced, from a long \"E\" sound to a long \"A\" sound ( /e\u026a/ )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_574", "contents": "In 1957, Robertson and Coope proposed the two main categories of adventitious (added) lung sounds. Those categories were \"Continuous\" and \"Interrupted\" (or non-continuous). [ 12 ]  In 1976, the International Lung Sound Association simplified the sub-categories as follows:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_575", "contents": "Several sources will also refer to \"medium\" crackles, as a crackling sound that seems to fall between the coarse and fine crackles. Crackles are defined as discrete sounds that last less than 250 ms, while the continuous sounds (rhonchi and wheezes) last approximately 250 ms. Rhonchi are usually caused by a stricture or blockage in the upper airway. These are different from  stridor ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_576", "contents": "Mansy, H. A.; Royston, T. J.; Balk, R. A.; Sandler, R. H. (2002). \"Pneumothorax detection using computerised analysis of breath sounds\".  Medical & Biological Engineering & Computing .  40  (5):  526\u2013 532.  doi : 10.1007/BF02345450 .  PMID \u00a0 12452412 .  S2CID \u00a0 7413897 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_577", "contents": "A  respiratory driven protocol  is an algorithmic medical process applied by  respiratory practitioners  as an extension of the physician. [ 1 ]   Respiratory-driven protocols are implemented in hospitals for treatment of people suffering from  asthma ,  bronchiolitis , and other respiratory illness.  Respiratory-driven protocols are most widely applied in intensive-care units. [ 2 ]   Respiratory practitioners are not utilized globally, [ 3 ]  so most application of respiratory practitioners as physician-extenders in this fashion is in the  United States . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_578", "contents": "Respiratory practitioners applying respiratory-driven protocols was initially designed and has been since shown to reduce patient cost and improve overall patient outcomes. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_579", "contents": "Respiratory-driven protocols have been shown to decrease hospital stays and improve overall outcomes in pediatric populations requiring respiratory intervention such as mechanical ventilation. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_580", "contents": "Rheotrauma  is a medical term for the harm caused to a patient's lungs by high gas flows as delivered by  mechanical ventilation . [ 1 ] [ 2 ] [ 3 ]  Although mechanical ventilation may prevent death of a patient from the  hypoxia  or  hypercarbia  which may be caused by  respiratory failure , it can also be damaging to the lungs, leading to  ventilator-associated lung injury . [ 4 ]  Rheotrauma is one of the ways in which mechanical ventilation may do this, alongside  volutrauma ,  barotrauma ,  atelectotrauma  and  biotrauma . Attempts have been made to combine all of the mechanical forces caused by the ventilator on the patient's lungs in an all encompassing term:  mechanical power ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_581", "contents": "The  SensorMedics High-Frequency Oscillatory Ventilator  is a patented  high-frequency  (>150  R f )  mechanical ventilator  designed and manufactured by SensorMedics Corp. of  Yorba Linda, California . After a series of acquisitions, Vyaire Medical, Inc. marketed the product as 3100A/B HFOV Ventilators. [ 1 ]  Model 3100 (later 3100A) received premarket approval from the United States  Food and Drug Administration  (FDA) in 1991 for treatment of all forms of  respiratory failure  in  neonatal  patients. [ 2 ]  In 1995, it received pre-market approved for Pediatric Application with no upper weight limit for treating selected patients failing on conventional ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_582", "contents": "The 3100A model is used for infants and children under 35 kilograms (<35\u00a0kg). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_583", "contents": "The 3100B model is used for all other people weighing more than 35 kilograms. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_584", "contents": "Adjusting bias flow affects mean P aw . Lowering bias flow may decrease the work of breathing and facilitate weaning."}
+{"id": "WikiPedia_Pulmonology$$$corpus_585", "contents": "This control sets the mean airway pressure, directly affecting lung volume and oxygenation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_586", "contents": "The initial setting is slightly higher than the mean airway pressure for conventional ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_587", "contents": "Piston displacement is controlled by the power setting. Power changes ventilation and thereby changes blood  PaCO2  levels."}
+{"id": "WikiPedia_Pulmonology$$$corpus_588", "contents": "Start with a power of 2.0 and adjust for chest wiggle to the umbilicus."}
+{"id": "WikiPedia_Pulmonology$$$corpus_589", "contents": "T i%  is the percentage of time allotted for inspiration. Once this value is set, it rarely needs to be changed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_590", "contents": "Frequency  (R f ) is the number of breaths in one second, expressed in hertz (hz). One hertz is equal to 60 breaths per minute (R f ) ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_591", "contents": "Since neither the 3100A or the 3100B measure actual tidal volumes, it is impossible to wean with precision; [ 4 ]  as a result, some clinicians find it problematic to use these machines for oscillatory ventilation. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_592", "contents": "Smoke inhalation  is the breathing in of  harmful fumes  (produced as by-products of  combusting  substances) through the  respiratory tract . [ 1 ]  This can cause smoke inhalation injury (subtype of  acute inhalation injury ) which is damage to the  respiratory tract  caused by  chemical  and/or heat exposure, as well as possible systemic toxicity after smoke inhalation. [ 2 ] [ 3 ] [ 4 ]  Smoke inhalation can occur from fires of various sources such as residential, vehicle, and wildfires. Morbidity and mortality rates in fire victims with burns are increased in those with smoke inhalation injury. [ 3 ] [ 4 ]  Victims of smoke inhalation injury can present with cough, difficulty breathing, low oxygen saturation, smoke debris and/or burns on the face. [ 2 ] [ 5 ]  Smoke inhalation injury can affect the upper respiratory tract (above the larynx), usually due to heat exposure, or the lower respiratory tract (below the larynx), usually due to exposure to toxic fumes. [ 2 ] [ 4 ] [ 6 ] [ 5 ]  Initial treatment includes taking the victim away from the fire and smoke, giving 100% oxygen at a high flow through a face mask (non-rebreather if available), and checking the victim for injuries to the body. [ 5 ] [ 6 ]  Treatment for smoke inhalation injury is largely supportive, with varying degrees of consensus on benefits of specific treatments. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_593", "contents": "The  U.S. Fire Administration  reported almost 1.3 million fires in 2019 causing 3,704 deaths and almost 17,000 injuries. [ 7 ]  Residential fires were found to be most often cooking related and resulted in the highest amount of deaths when compared to other fire types such as vehicle and outdoor fires. [ 7 ]  It has been found that men have higher rates of fire-related death and injury than women do, and that African American and American Indian men have higher rates of fire-related death and injury than other ethnic and racial groups. The age group with the highest rate of death from smoke inhalation is people over 85, while the age group with the highest injury rate is people of ages 50\u201354. [ 7 ]  Some reports also show increased rates of death and injury in children, due to their lower physical and mental capabilities. [ 2 ] [ 4 ]  In 2019, the overall U.S. national fire death rate was 10.7 people per million population and the injury rate was 50.6 people per million population. [ 7 ]  According to the U.S. Fire Administration, the deaths in the United States that were caused by a fire fluctuated over the past 10 years. The administration recorded the increase of deaths between 2012 and 2021, and concluded an increase of 18% per million. [ 8 ]  Smoke inhalation injury is the most common cause of death in fire victims. [ 2 ]  Fire victims with both burns to their body and smoke inhalation injury have increased mortality rate and length of hospital stay compared to those with burns alone. [ 2 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_594", "contents": "Some of the signs and symptoms of smoke inhalation injury include recent fire exposure followed by cough, wheezing, stridor, confusion, difficulty breathing, low oxygen saturation, smoke debris (especially on face and/or in saliva), burns (especially of the face), singed facial or nose hairs, and/or hoarse voice. [ 2 ] [ 6 ]  A careful history can be helpful in determining where the fire occurred and therefore, what chemical fumes could have been inhaled with accompanying systemic toxicities. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_595", "contents": "Smoke inhalation injury can lead to respiratory complications ranging from minor to major.  Acute Respiratory Distress Syndrome  (ARDS) is a relatively delayed complication of smoke inhalation injury caused by chemical fumes inducing an inflammatory response in the lung tissue, especially the small air sacs known as alveoli where critical gas exchange occurs. [ 2 ] [ 3 ] [ 4 ]  Another potential complication is swelling of the upper airway from both heat and chemical damage, and can become profound enough to obstruct breathing. The onset of airway swelling can be relatively delayed making it difficult to intubate later on, thus endotracheal intubation should be considered early in certain patients. [ 2 ] [ 6 ]  Other possible complications include pneumonia, vocal cord damage and/or dysfunction, and tracheal stenosis (usually delayed). [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_596", "contents": "Inhalation of chemical toxins produced by combusting materials can cause damage to tissues of both the upper (above larynx) and lower respiratory tract (below larynx). Damage to lower airways, air sacs, and lung tissue is due to an inflammatory cascade in response to the noxious chemicals which causes a variety of downstream effects such as increased secretions and exudative material thus clogging the airways and/or air sacs, collapse of air sacs ( atelectasis ), vascular permeability leading to  pulmonary edema  (fluid in the lungs),  bronchoconstriction , activation of the  coagulation cascade , and impaired function of the  mucociliary escalator . [ 2 ] [ 3 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_597", "contents": "Inhalation of hot fumes can cause thermal damage to tissues, usually limited to the upper respiratory tract (above larynx). Damage in this location can result in sloughing of the damaged tissue and swelling, both of which can cause obstruction of the respiratory tract, ulceration, increased secretions, and redness ( erythema ). [ 2 ] [ 3 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_598", "contents": "Systemic toxicity can occur from inhalation of chemical compounds produced as byproducts of combustion in a fire. [ 2 ] [ 3 ] [ 4 ] [ 6 ]   Carbon monoxide poisoning  is the most common systemic toxicity after smoke inhalation, and can cause organ failure from lack of oxygen (often  heart attack ). [ 2 ] [ 4 ] [ 6 ]   Carbon monoxide  is a common byproduct of combusting substances in fires and is colorless and odorless. It has a much higher binding affinity for hemoglobin compared to oxygen and thus can block oxygen from binding to  hemoglobin , causing  hypoxia . Additionally, carbon monoxide decreases the ability of oxygen to dissociate from hemoglobin to diffuse into tissues, thus causing hypoxia. [ 4 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_599", "contents": "According to the  New York Times , a recent study claims that smoke inhalation can also cause  lung cancer . While cigarettes are proven to cause cancer, as well as inhaling second hand smoke from a cigarette, the article notes that a cigarette is filtered. In contrast, inhaling wild fire smoke due to the harmful substances found in the air. For example, smoke from burning trees and gardens will present different dangers than smoke from burning houses, cars or electronics. A study published in 2019 recorded firefighters who worked for 25 years, an average of 7 weeks per year,  increase their risk of lung cancer by 8 to 26 percent due to the amount of smoke they have been exposed to on duty. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_600", "contents": "First responders often take the victim away from the fire and smoke, give 100% oxygen at high flow through a face mask (non-rebreather if available), assess level of consciousness, and check the victim for burns and/or injuries to the body for initial care. [ 4 ]  Upper respiratory tract injury due to heat exposure often results in swelling. Intubation should be considered early given that the swelling can have a slow, delayed onset but once present, will make intubation very difficult. [ 2 ] [ 4 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_601", "contents": "Lower respiratory tract injury due to exposure to noxious fumes often consists of supportive measures such as intubation and ventilator support if indicated, suctioning of the airways ( pulmonary hygiene ), and other supportive measures. [ 5 ] [ 6 ]  Intravenous fluids are a mainstay in treatment of fire victims with extensive burns to the body, however, there are differing perspectives on the risks/benefits of IV fluids in fire victims with both burns and smoke inhalation injury due to the potential worsening of pulmonary edema with large amounts of IV fluids typically given in burn victims. [ 4 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_602", "contents": "Other treatments with differing perspectives and study findings on utility in smoke inhalation injury include nebulized  bronchodilators  (such as  beta-2-agonists ), IV  corticosteroids , nebulized  corticosteroids , nebulized  epinephrine , nebulized  heparin , and nebulized  N-acetylcysteine . [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_603", "contents": "Carbon monoxide poisoning is initially treated with high flow 100% oxygen. Hyperbaric oxygen therapy can be considered but there are differing views on its clinical benefit in terms of outcomes. [ 2 ] [ 4 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_604", "contents": "Products with systemic effects are mainly asphyxiating gases, such as carbon monoxide and cyanides. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_605", "contents": "Carbon monoxide (\u0421\u041e), which is absorbed by the lungs, diffuses into the capillaries and dissolves in the plasma and erythrocytes, binding to haemoglobin. As its affinity is more than 200 times that of oxygen, the amount of oxygen bound to haemoglobin is reduced, leading to anoxia. [ 11 ]  In addition, carbon monoxide released at the tissue level binds to mitochondrial enzyme systems, resulting in the inability of cells to utilise oxygen. When exposed to excess CO, one of the body's natural reactions is to breathe faster. This further increases the CO level in the blood, eventually leading to cardiac arrest."}
+{"id": "WikiPedia_Pulmonology$$$corpus_606", "contents": "Once the cyanide ion (CN-) enters the bloodstream, it diffuses into body cells. [ 12 ]  It binds to the trivalent iron of mitochondrial cytochrome oxidase, causing its inhibition and hence tissue anoxia. The metabolism shifts towards anaerobic metabolism, leading to an increase in lactacidemia."}
+{"id": "WikiPedia_Pulmonology$$$corpus_607", "contents": "There are many  modes of mechanical ventilation . [ 1 ]  In  medicine ,  mechanical ventilation  is a method to mechanically assist or replace spontaneous  breathing ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_608", "contents": "A breath by breath trigger, limit, cycling (TLC) classification of the common modes of ventilation. (V = ventilator; P = patient) [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_609", "contents": "Thickened fluids and thickened drinks  are often used for people with  dysphagia , a disorder of swallowing function. [ 1 ]  The thicker consistency makes it less likely that individuals will  aspirate  while they are drinking. Individuals with difficulty swallowing may find that liquids cause coughing, spluttering, or even aspiration, and that thickening drinks enables them to swallow safely. Patients may be advised to consume thickened liquids after being  extubated ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_610", "contents": "Liquid thickness may be measured by two methods, with a  viscometer  or by line spread test."}
+{"id": "WikiPedia_Pulmonology$$$corpus_611", "contents": "There are several levels of consistency/viscosity and these have historically varied by country, although the launch of the International Dysphagia Diet Standardisation Initiative (IDDSI) [ 2 ]  aims to remove this variation. According to the IDDSI, the thickness of a drink can be tested by measuring the amount that pours out of a 10ml syringe in 10 seconds. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_612", "contents": "Patients who have a restriction on thin liquids should avoid milk shakes, ice cream, popsicles, and Jell-O, as these melt into thin liquids in the mouth."}
+{"id": "WikiPedia_Pulmonology$$$corpus_613", "contents": "There are multiple commercial  thickeners  on the market for thickening liquids. Vendors also offer pre-thickened liquids such as water, juice, and milk in individual serving sized cartons. Some commercial thickeners use modified maize starch, which helps support hydration and nutritional levels, while others use  xanthan gum ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_614", "contents": "There is no good evidence that thickening liquids reduces pneumonia in dysphagia (swallowing problems) and it may be associated with poorer hydration and with an adverse effect on quality of life. [ 4 ] [ 5 ]  Thicker consistencies may also be associated with pharyngeal residue and perhaps with an increased risk of severe pneumonia if aspirated. [ 6 ] [ 7 ]   Concern has been expressed that patients receiving modified texture diets, such as thickened liquids are not receiving adequate information about the pros and cons and are not as result giving valid  informed consent . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_615", "contents": "A  thoracostomy  is a small incision of the  chest wall , [ 1 ]  with maintenance of the opening for  drainage . [ 2 ]  It is most commonly used for the treatment of a  pneumothorax . This is performed by physicians, paramedics, and nurses usually via  needle thoracostomy  or an incision into the chest wall with the insertion of a  thoracostomy tube  (chest tube) or with a hemostat and the provider's finger (finger thorocostomy). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_616", "contents": "When air, blood, or other fluids accumulate in the  pleural cavity  it may be drained by thoracostomy. [ 1 ]  Whereas air in this space ( pneumothorax ) may be released by  needle thoracostomy , other substances require drainage with a  thoracostomy tube . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_617", "contents": "There are no absolute  contraindications  to thoracostomy. There are relative contraindications (such as  coagulopathies ); however, in an emergency setting these are outweighed by the necessity to re-inflate a collapsed lung by draining fluid/air from the space around the lung. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_618", "contents": "The standard location for thoracostomy is the triangle of safety. This is an anatomical triangle. The borders of which are; the anterior border of the  latissimus dorsi , the lateral border of the  pectoralis major muscle , a line superior to the horizontal level of the  nipple  (or 5th intercostal space), with the apex being below, or at, the  axilla . [ 5 ]   A primary skin incision is made superiorly to the rib to avoid the neurovascular supply that runs inferiorly to the rib. [ 1 ]  This should be around 4-5cm long. [ 1 ]  The clinician will tunnel through the subcutaneous tissue and muscle using forceps to reach the pleural. [ 1 ]   Further blunt dissection is used to carefully penetrate the pleural cavity.  A finger is then inserted into this hole, the finger is swept to feel for lung adhesions to the rib cage and to feel for an inflating lung. [ 1 ]  This cavity is where a hemothorax or pneumothorax would accumulate. A finger thoracostomy as described here can be the first step in inserting an intercostal chest drain.  At this point, a chest tube can be inserted and connected to a one way wale to allow continuous drainage. A Roman sandal tie and U-Stitch are done to secure the chest tube and to ensure that removal of the tube will not produce another pneumothorax. Chest x-ray is performed post-procedure to confirm placement and to check for resolution of the pneumothorax/hemothorax. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_619", "contents": "Rare complications are mostly due to placement technique, inexperience of the interventionist, and emergent vs. elective circumstances. The most common complications are recurrent pneumothorax (incomplete recovery, but an expected course), infection, and organ injury (due to mechanical damage). [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_620", "contents": "Esophageal injury is rare. If saliva and chyme contents drain from the chest tube, that should raise suspicion of esophageal injury. The main treatment of esophageal injury is surgical repair. The stomach is also rarely injured. Proper technique and not using a  trocar  during the procedure decreases the risk of this from occurring. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_621", "contents": "Time of useful consciousness  ( TUC ), also  effective performance time  ( EPT ), is defined as the amount of time an individual is able to function effectively (e.g. perform  flying  duties) in an environment of inadequate  oxygen  supply. [ 1 ]  It is the period of time from the interruption of the oxygen supply or exposure to an oxygen-poor environment to the time when useful function is lost, and the individual is no longer capable of taking proper corrective and protective action. It is not the time to total  unconsciousness . At the higher altitudes, the TUC becomes very short; considering this danger, the emphasis is on prevention rather than cure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_622", "contents": "For orbital altitudes and above, that is, direct exposure to space, 6\u20138 seconds of consciousness is expected. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_623", "contents": "There are many individual variations of  hypoxia , even within the same person.  Generally,  old age  tends to reduce the efficiency of the pulmonary system, and can cause the onset of hypoxia symptoms sooner. [ 3 ]   Smoking  drastically reduces oxygen intake efficiency, and can have the effect of reducing tolerance by 1,000\u20132,000 metres (3,300\u20136,600\u00a0ft). [ 4 ]  Hypoxia can be produced in a  hypobaric chamber .  This can be useful for identifying individual symptoms of hypoxia, along with rough estimates of the altitude that causes problems for each person.  Identifying symptoms is often helpful for self-diagnosis in order to realize when altitude should be reduced."}
+{"id": "WikiPedia_Pulmonology$$$corpus_624", "contents": "The table below shows average TUCs as documented by the  Federal Aviation Administration ; a rapid ascent results in a lower TUC. [ 5 ]  The TUCs for any given individual may differ significantly from this.  Aerobic exercise  during the TUC period will reduce the TUCs considerably; so will exercise immediately prior to the TUC as this induces an  oxygen debt  prior to exposure. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_625", "contents": "Tracheal deviation  is a  clinical sign  that results from unequal intrathoracic pressure within the  chest cavity .  It is most commonly associated with traumatic  pneumothorax ,  but can be caused by a number of both acute and chronic health issues, such as  pneumonectomy ,  atelectasis ,  pleural effusion ,  fibrothorax  (pleural fibrosis), or some cancers (tumors within the  bronchi ,  lung , or  pleural cavity ) and certain  lymphomas  associated with the mediastinal lymph nodes."}
+{"id": "WikiPedia_Pulmonology$$$corpus_626", "contents": "In most adults and children, the  trachea  can be seen and felt directly in the middle of the  anterior  (front side) neck behind the  jugular notch  of the  manubrium  and superior to this point as it extends towards the  larynx . However, when tracheal deviation is present, the trachea will be displaced in the direction of less pressure. Meaning, that if one side of the chest cavity has an increase in pressure (such as in the case of a  pneumothorax ) the trachea will shift towards the opposing side. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_627", "contents": "The trachea is the tube that carries air from the throat to the lungs. It is also commonly referred to as the windpipe. The trachea is one of the most important parts of the respiratory system and damage to the trachea can indicate a life-threatening emergency. The normal position of the trachea is straight up and down, running along the center of the front side of the throat. Certain conditions can cause the trachea to shift to one side or the other. This is a medical emergency that requires immediate medical attention to discover the cause of the shift and begin an appropriate course of treatment. There are several causes for a tracheal deviation, and the condition often presents along with difficulty breathing, coughing and abnormal breath sounds. The most common cause of tracheal deviation is a  pneumothorax , which is a collection of air inside the chest, between the chest cavity and the lung. A pneumothorax can be spontaneous, caused by existing lung disease, or by trauma. Treatment varies, depending on the severity of the pneumothorax. Smaller pockets of air tend to dissipate on their own, while larger areas can cause complications and are usually vented by a needle in the chest. As soon as the pneumothorax is treated, the tracheal deviation also will resolve itself. [ 2 ]   A congenital lack of one lung, surgical removal of a lung or pleural fibrosis, which is an inflammation of the lung membranes caused by an infection. As a result of the wide range of causes of tracheal deviation, it is essential to seek medical attention so that an accurate diagnosis can be obtained."}
+{"id": "WikiPedia_Pulmonology$$$corpus_628", "contents": "In children, where trachea is more flexible, it can be displaced by the aortic arch up to 90 degrees. The trachea can also be displaced to the left if the aortic arch lies to the right of the trachea. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_629", "contents": "Since tracheal deviation is a sign as opposed to a condition, treatment is focused on correcting the cause of the finding. In the case of pneumothorax,  thoracentesis  or  chest tube  insertion is performed to relieve the pressure within the affected pleural cavity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_630", "contents": "Understanding Lung Sounds  3rd edition (2002) by  Steven Lehrer  is a book and audio CD that guides the student through the skills of lung  auscultation . It provides a complete overview of lung examination, anatomy, physiology, and pathology. The audio CD presents and explains normal and abnormal lung sounds. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_631", "contents": "Ventilator-associated lung injury  (VALI) is an acute lung injury that develops during  mechanical ventilation  and is termed  ventilator-induced lung injury  (VILI) if it can be proven that the mechanical ventilation caused the acute lung injury. In contrast, ventilator-associated lung injury (VALI) exists if the cause cannot be proven. VALI is the appropriate term in most situations because it is virtually impossible to prove what actually caused the lung injury in the hospital. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_632", "contents": "It is generally regarded, based on animal models and human studies, that  volutrauma  is the most harmful aspect of mechanical ventilation. [ 2 ] [ 3 ] [ 4 ]  This may be regarded as the over-stretching of the airways and alveoli. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_633", "contents": "During mechanical ventilation, the flow of gas into the lung will take the  path of least resistance . Areas of the lung that are collapsed ( atelectasis ) or filled with secretions will be underinflated, while those areas that are relatively normal will be overinflated. These areas will become overdistended and injured. This may be reduced by using smaller tidal volumes. [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_634", "contents": "During positive pressure ventilation, atelectatic regions will inflate, however, the alveoli will be unstable and will collapse during the expiratory phase of the breath ( atelectotrauma ). This repeated alveolar collapse and expansion (RACE) is thought to cause VALI. By opening the lung and keeping the lung open RACE (and VALI) is reduced. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_635", "contents": "Another possible ventilator-associated lung injury is known as  biotrauma . Biotrauma involves the lung suffering injury from any mediators of the inflammatory response or from bacteremia."}
+{"id": "WikiPedia_Pulmonology$$$corpus_636", "contents": "Finally  oxygen toxicity  contributes to ventilator-associated lung injury through several mechanisms including  oxidative stress ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_637", "contents": "Possible reasons for predisposition to VALI include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_638", "contents": "Overdistension of alveoli and cyclic atelectasis ( atelectotrauma ) are the primary causes for alveolar injury during positive pressure  mechanical ventilation .  Severe injury to alveoli causes swelling of the tissues (edema) in the lungs, bleeding of the alveoli, loss of surfactant (decrease in  lung compliance ) and complete alveoli collapse ( biotrauma ). [ 1 ] [ 8 ]  High flow rates are associated with  rheotrauma , high volumes with  volutrauma  and pressures with  barotrauma . Collectively these may be converted into a single unit of  mechanical power . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_639", "contents": "VALI does not need to be distinguished from progressive  ALI /ARDS because management is the same in both. Additionally, definitive diagnosis of VALI may not be possible because of lack of sign or symptoms. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_640", "contents": "Alveolar overdistension is mitigated by using small tidal volumes, maintaining a low plateau pressure, and most effectively by using volume-limited ventilation.  A 2018 systematic review by  The Cochrane Collaboration  provided evidence that low tidal volume ventilation reduced post operative pneumonia and reduced the requirement for both invasive and non invasive ventilation after surgery [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_641", "contents": "Applied  positive end-expiratory pressure  (PEEP) is the principal method used to keep the alveoli open and lessen cyclic atelectasis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_642", "contents": "Open lung ventilation is a ventilatory strategy that combines small tidal volumes (to lessen alveolar overdistension) and an applied PEEP above the low inflection point on the pressure-volume curve (to lessen cyclic atelectasis)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_643", "contents": "High frequency ventilation  is thought to reduce ventilator-associated lung injury, especially in the context of  ARDS  and  acute lung injury . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_644", "contents": "Permissive hypercapnia  and  hypoxaemia  allow the patient to be ventilated at less aggressive settings and can, therefore, mitigate all forms of ventilator-associated lung injury"}
+{"id": "WikiPedia_Pulmonology$$$corpus_645", "contents": "VALI is most common in people receiving mechanical ventilation for acute lung injury or acute respiratory distress syndrome (ALI/ARDS). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_646", "contents": "24 percent of people mechanically ventilated will develop VALI for reasons other than ALI or ARDS. [ 1 ]  The incidence is probably higher among people who already have ALI/ARDS, but estimates vary widely. [ 1 ]  The variable estimates reflect the difficulty in distinguishing VALI from progressive ALI/ARDS. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_647", "contents": "This template is used to identify a  pulmonology  stub. It uses {{ asbox }}, which is a meta-template designed to ease the process of creating and maintaining stub templates."}
+{"id": "WikiPedia_Pulmonology$$$corpus_648", "contents": "Typing  {{Pulmonology-stub}}  produces the message shown at the beginning, and adds the article to the following category:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_649", "contents": "This is a  stub template . A brief explanation of these templates follows; for full details please consult  Wikipedia:Stub ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_650", "contents": "A stub is an article containing only a few sentences of text which is too short to provide encyclopedic coverage of a subject."}
+{"id": "WikiPedia_Pulmonology$$$corpus_651", "contents": "Further information can be found at:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_652", "contents": "New stub templates and categories (collectively \"stub types\") should not be created without prior proposal at  Wikipedia:WikiProject Stub sorting/Proposals . This allows for the proper coordination of all stub types across Wikipedia, and for the checking of any new stub type for possible problems prior to its creation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_653", "contents": "Acute eosinophilic pneumonia  (AEP) is an uncommon, acute-onset form of eosinophilic lung disease which varies in severity. Though poorly understood, the pathogenesis of AEP likely varies depending on the underlying cause which may include smoking, inhalation exposure, medication, and infection. [ 1 ]  In most patients, AEP is idiopathic, or has no known cause. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_654", "contents": "AEP is characterized by airway injury, vascular injury, and the release of IL-33, a pro-inflammatory cytokine. This results in the recruitment of eosinophils, a type of white blood cell, to the lungs with subsequent inflammation and symptoms. Symptoms are nonspecific and include cough, shortness of breath, malaise, myalgia, night sweats, and pleuritic chest pain. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_655", "contents": "While not completely understood, it is thought that AEP may be triggered by offending agents such as smoking, parasites, or fungi that trigger a hypersensitivity reaction. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_656", "contents": "Eosinophilic pneumonia is diagnosed by characteristic imaging and the presence of eosinophils on alveolar lavage, or washing of the lower respiratory system. Eosinophilia, or elevated eosinophils in the blood may be significantly elevated or absent. [ 3 ]   Lung biopsy is usually not necessary for diagnosis. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_657", "contents": "While there is no formal diagnostic criteria, the modified Philit criteria has been used and includes: acute illness with fever for less than 21 month, hypoxemia, diffuse infiltrates in both lungs on imaging, greater than 25% eosinophils in bronchoalveolar lavage fluid (or eosinophils on lung biopsy), and no other known causes of eosinophilic lung disease present. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_658", "contents": "Treatment generally involves removing exposure of the causal agent, if identifiable, and systemic steroid therapy. [ 1 ]  Patients often respond quickly to systemic steroids. [ 1 ]   Relapse of disease is rare. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_659", "contents": "AEP was first described in 1989 by Allen, Pacht, Gadek, and Davis, with eight proposed diagnostic criteria. [ 1 ]  These criteria included: acute febrile illness, hypoxemia, pulmonary infiltrates on imaging, alveolar eosinophils, ruled out infection, ruled out asthma, quick response to steroids, and followed by resolution of disease with no long-term effects. [ 1 ]  Currently there is no agreement on diagnostic criteria for AEP. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_660", "contents": "Bat wing appearance  is a radiologic sign referring to bilateral perihilar lung shadowing seen in frontal chest X-ray and in chest CT. [ 1 ] [ 2 ]  The most common reason for bat wing appearance is the accumulation of oedema fluid in the lungs. [ 3 ]  The batwing sign is symmetrical, usually showing  ground glass appearance  and spares the lung cortices. [ 4 ]   This sign is seen in individuals with  pneumonia , inhalation injuries,  pulmonary haemorrhage ,  sarcoidosis , bronchoalveolar carcinoma and pulmonary alveolar proteinosis. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_661", "contents": "Exhalation delivery systems  ( EDS ) deliver medications to the  internal nose . Developed in 2006, [ 1 ]  EDS devices use the patient's exhaled breath to propel medication, such as steroids, [ 1 ]  into the nasal cavities. The method can deliver medication deeper into the nasal passages than intranasal sprays, [ 1 ]  and at a lower pressure than nasal irrigation methods. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_662", "contents": "Using EDS to deliver  fluticasone  (EDS-FLU) to patients with  nasal polyps  has been shown to reduce the need for surgery. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_663", "contents": "Pediatric Pulmonology  is a monthly  peer-reviewed   medical journal  covering  pediatric pulmonology . It was established in 1985; the  editor-in-chief  is Susanna McColley, MD. According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 3.039, ranking it 36th out of 129 journals in the category \"Pediatrics\" [ 1 ]  and 36th out of 64 in the category \"Respiratory System\". [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_664", "contents": "This article about a  pediatrics   journal  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_665", "contents": "See tips for writing articles about academic journals . Further suggestions might be found on the article's  talk page ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_666", "contents": "Respiratory diseases , or  lung diseases , [ 1 ]  are  pathological  conditions affecting the organs and tissues that make  gas exchange  difficult in  air-breathing  animals. They include conditions of the  respiratory tract  including the   trachea ,  bronchi ,  bronchioles ,  alveoli ,  pleurae ,  pleural cavity , the nerves and  muscles of respiration . Respiratory diseases range from mild and self-limiting, such as the  common cold ,  influenza , and  pharyngitis  to life-threatening  diseases  such as  bacterial pneumonia ,  pulmonary embolism ,  tuberculosis ,  acute asthma ,  lung cancer , [ 2 ]  and  severe acute respiratory syndromes , such as  COVID-19 . [ 3 ]  Respiratory diseases can be classified in many different ways, including by the organ or tissue involved, by the type and pattern of associated signs and symptoms, or by the cause of the disease."}
+{"id": "WikiPedia_Pulmonology$$$corpus_667", "contents": "The study of respiratory disease is known as  pulmonology . A  physician  who specializes in respiratory disease is known as a pulmonologist, a chest medicine specialist, a respiratory medicine specialist, a respirologist or a thoracic medicine specialist."}
+{"id": "WikiPedia_Pulmonology$$$corpus_668", "contents": "Asthma ,  chronic bronchitis ,  bronchiectasis  and  chronic obstructive pulmonary disease  (COPD) are all  obstructive lung diseases  characterised by  airway obstruction . This limits the amount of air that is able to enter alveoli because of constriction of the bronchial tree, due to inflammation. Obstructive lung diseases are often identified because of symptoms and diagnosed with  pulmonary function tests  such as  spirometry . Many obstructive lung diseases are managed by avoiding triggers (such as  dust mites  or  smoking ), with symptom control such as  bronchodilators , and with suppression of inflammation (such as through  corticosteroids ) in severe cases. One common cause of COPD including  emphysema , and chronic bronchitis, is  tobacco smoking , and common causes of  bronchiectasis  include severe infections and  cystic fibrosis . The definitive cause of  asthma  is not yet known. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_669", "contents": "Restrictive lung diseases  are a category of respiratory disease characterized by a loss of  lung compliance , causing incomplete lung expansion and increased lung stiffness, such as in infants with respiratory distress syndrome. [ 5 ]  Restrictive lung diseases can be divided into two categories: those caused by intrinsic factors and those caused by extrinsic factors. [ 6 ]  Restrictive lung diseases yielding from intrinsic factors occur within the lungs themselves, such as  tissue death  due to inflammation or toxins. Conversely, restrictive lung diseases caused by extrinsic factors result from conditions originating from outside the lungs such as  neuromuscular dysfunction  and irregular chest wall movements. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_670", "contents": "Chronic respiratory diseases are long-term diseases of the airways and other structures of the lung. They are characterized by a high inflammatory cell recruitment ( neutrophil ) and/or destructive cycle of  infection , (e.g. mediated by  Pseudomonas aeruginosa ). Some of the most common are  asthma ,  chronic obstructive pulmonary disease , and  acute respiratory distress syndrome . Most chronic respiratory dieseases are not curable; however, various forms of treatment that help dilate major air passages and improve  shortness of breath  can help control symptoms and increase the quality of life. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_671", "contents": "Telerehabilitation for chronic respiratory disease"}
+{"id": "WikiPedia_Pulmonology$$$corpus_672", "contents": "The latest evidence suggests that primary pulmonary rehabilitation and maintenance rehabilitation delivered through telerehabilitation for people with chronic respiratory disease reaches outcomes similar to centre-based rehabilitation. [ 8 ]  While there are no safety issues identified, the findings are based on evidence limited by a small number of studies. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_673", "contents": "Infections can affect any part of the respiratory system. They are traditionally divided into upper respiratory tract infections and lower respiratory tract infections. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_674", "contents": "The upper airway is defined as all the structures connecting the glottis to the mouth and nose. [ 9 ]  The most common  upper respiratory tract infection  is the  common cold . However, infections of specific organs of the upper respiratory tract such as  sinusitis ,  tonsillitis ,  otitis media ,  pharyngitis  and  laryngitis  are also considered upper respiratory tract infections. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_675", "contents": "Epiglottitis  is a bacterial infection of the larynx which causes life-threatening swelling of the  epiglottis  with a mortality rate of 7% in adults and 1% in children. [ 10 ]   Haemophilus influenzae  is still the primary cause even with vaccinations. Also Streptococcus pyogenes can cause epiglottitis. Symptoms include drooling, stridor, difficulty breathing and swallowing, and a hoarse voice. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_676", "contents": "Croup  (Laryngotracheobronchitis) is a viral infection of the  vocal cords  typically lasting five to six days. The main symptom is a barking cough and low-grade  fever . On an X-ray, croup can be recognized by the \"steeple sign\", which is a narrowing of the  trachea . It most commonly occurs in winter months in children between the ages of 3 months and 5 years. A severe form caused by bacteria is called bacterial tracheitis. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_677", "contents": "Tonsillitis  is swelling of the tonsils by a bacterial or viral infection. This inflammation can lead to airway obstruction. From tonsillitis can come a peritonsillar abscess which is the most common upper airway infection and occurs primarily in young adults. It causes swelling in one of the tonsils, pushing the  uvula  to the unaffected side. [ 9 ]  Diagnosis is usually made based on the presentation and examination. Symptoms generally include fever, sore throat, trouble swallowing, and sounding like they have a \"hot potato\" in their mouth. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_678", "contents": "The most common lower respiratory tract infection is  pneumonia , an infection of the lungs which is usually caused by bacteria, particularly  Streptococcus pneumoniae  in Western countries. Worldwide,  tuberculosis  is an important cause of pneumonia. Other pathogens such as  viruses  and fungi can cause pneumonia, for example  severe acute respiratory syndrome ,  COVID-19  and  pneumocystis pneumonia . Pneumonia may develop complications such as a lung abscess, a round cavity in the lung caused by the infection, or may spread to the  pleural cavity . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_679", "contents": "Poor oral care may be a contributing factor to lower respiratory disease, as bacteria from gum disease may travel through airways and into the lungs. [ 14 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_680", "contents": "Primary ciliary dyskinesia  is a genetic disorder causing the cilia to not move in a coordinated manner. This causes chronic respiratory infections, cough, and nasal congestion. This can lead to bronchiectasis, which can cause life-threatening breathing issues. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_681", "contents": "Malignant tumors of the respiratory system, particularly  primary carcinomas of the lung , are a major health problem responsible for 15% of all cancer diagnoses and 30% of all cancer deaths. The majority of respiratory system cancers are attributable to  smoking tobacco . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_682", "contents": "The major  histological  types of respiratory system cancer are: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_683", "contents": "In addition, since many cancers spread via the bloodstream and the entire cardiac output passes through the lungs, it is common for cancer  metastases  to occur within the lung.  Breast cancer  may invade directly through local spread, and through lymph node metastases. After metastasis to the  liver ,  colon cancer  frequently metastasizes to the lung.  Prostate cancer , germ cell cancer and  renal cell carcinoma  may also metastasize to the lung. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_684", "contents": "Treatment of respiratory system cancer depends on the type of cancer. Surgical removal of part of a lung ( lobectomy ,  segmentectomy , or  wedge resection ) or of an entire lung  pneumonectomy ), along with chemotherapy and  radiotherapy , are all used. The chance of surviving lung cancer depends on the cancer stage at the time the cancer is diagnosed, and to some extent on the  histology , and is only about 14\u201317% overall. In the case of metastases to the lung, treatment can occasionally be curative but only in certain, rare circumstances. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_685", "contents": "Benign tumors are relatively rare causes of respiratory disease. Examples of benign tumors are: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_686", "contents": "Pleural cavity diseases include  pleural mesothelioma  which are mentioned above."}
+{"id": "WikiPedia_Pulmonology$$$corpus_687", "contents": "A collection of fluid in the pleural cavity is known as a  pleural effusion . [ 17 ]  This may be due to fluid shifting from the bloodstream into the pleural cavity due to conditions such as congestive heart failure and cirrhosis. [ 17 ]  It may also be due to inflammation of the pleura itself as can occur with infection,  pulmonary embolus , tuberculosis, mesothelioma and other conditions. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_688", "contents": "A  pneumothorax  is a hole in the pleura covering the lung allowing air in the lung to escape into the pleural cavity. The affected lung \"collapses\" like a deflated balloon. A  tension pneumothorax  is a particularly severe form of this condition where the air in the pleural cavity cannot escape, so the pneumothorax keeps getting bigger until it compresses the heart and blood vessels, leading to a life-threatening situation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_689", "contents": "Pulmonary vascular diseases are conditions that affect the  pulmonary circulation . Examples are: [ 18 ] [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_690", "contents": "Pulmonary diseases also impact newborns and the disorders are often unique from those that affect adults."}
+{"id": "WikiPedia_Pulmonology$$$corpus_691", "contents": "Infant respiratory distress syndrome  most commonly occurs in less than six hours after birth in about 1% of all births in the United States. [ 9 ]  The main risk factor is prematurity with the likelihood of it occurring going up to 71% in infants under 750g. [ 19 ]  Other risk factors include infant of a diabetic mother (IDM), method of delivery, fetal asphyxia, genetics,  prolonged rupture of membranes  (PROM), maternal toxemia,  chorioamnionitis , and male sex. The widely accepted pathophysiology of respiratory distress syndrome is it caused by insufficient surfactant production and immature lung and vascular development. The lack of surfactant makes the lungs  atelectatic  causing a ventilation to perfusion mismatch, lowered compliance, and increased air resistance. This causes hypoxia and respiratory acidosis which can lead to  pulmonary hypertension . It has a ground glass appearance on an x-ray. Symptoms can include tachypnea, nasal flaring, paradoxical chest movement, grunting, and subcostal retractions. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_692", "contents": "Bronchopulmonary Dysplasia  is a condition that occurs after birth usually from  mechanical ventilation  and oxygen use. It happens almost exclusively in pre-mature infants and is characterized by the alveoli, and lung vasculature becoming inflamed and damaged. Complications from BPD can follow a patient into adulthood. As a child they may experience learning disabilities, pulmonary hypertension, and hearing problems. As an adult, there is an increased likelihood for asthma and exercise intolerance. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_693", "contents": "Meconium Aspiration Syndrome  occurs in full term or post-term infants who aspirate  meconium . Risk factors include a diabetic mother, fetal hypoxia, precipitous delivery, and maternal high blood pressure. [ 21 ]  Its diagnosis is based on meconium stained amniotic fluid at delivery and staining on the skin, nails, and umbilical cord. Aspiration can cause airway obstruction, air-trapping, pneumonia, lung inflammation, and inactivated surfactant. It presents as patchy atelectasis and hyperinflation on an x-ray with a  pneumothorax  of pneumomediastinum also possible. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_694", "contents": "Persistent Pulmonary Hypertension of the Newborn  (PPHN) is a syndrome that occurs from an abnormal transition to extra-uterine life. It is marked by an elevated pulmonary vascular resistance and vasoconstriction causing a right-to-left shunt of the blood through the  foramen ovale  or  ductus arteriosus . [ 9 ]  There are three main causes of PPHN are parenchymal diseases such as meconium aspiration syndrome, idiopathic, and hypoplastic vasculature like in a diaphragmatic hernia. It will eventually resolve in most infants. [ 22 ]  This is the only syndrome that inhaled nitric oxide is approved for by the FDA. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_695", "contents": "Transient Tachypnea of the Newborn  is caused by the retention of alveolar fluid in the lungs. It commonly occurs in infants who are delivered via  caesarean section  without the onset of labor because absorption of amniotic fluid in the lungs has not yet commenced. Other risk factors are male sex,  macrosomia , multiple gestations, and maternal asthma. It usually presents with tachypnea and increased work of breathing. On an x-ray diffuse infiltrates, interlobar fissures, and sometimes  pleural effusions  can be seen. It is a diagnosis of exclusion because of its similarity to other diseases and frequently CPAP is used to help push the lung fluid into the pulmonary vasculature. [ 9 ] [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_696", "contents": "Pulmonary interstitial emphysema  is the condition of air escaping overdistended alveoli into the pulmonary interstitium. It is a rare disease that occurs most often in premature infants, even though it is possible to appear in adults. [ 25 ]  It often presents as a slow deterioration with the need for increased ventilatory support. Chest x-ray is the standard for diagnosis where it is seen as linear or cystic translucencies extending to the edges of the lungs. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_697", "contents": "Bronchiolitis  is the swelling and buildup of mucus in the bronchioles. It is usually caused by  respiratory syncytial virus  (RSV), which is spread when an infant touches the nose or throat fluids of someone infected. [ 26 ]  The virus infects the cells causing ciliary dysfunction and death. The debris, edema, and inflammation eventually leads to the symptoms. [ 27 ]  It is the most common reason for admission of children under the age of one year. It can present widely from a mild respiratory infection to respiratory failure. Since there is no medication to treat the disease, it is only managed supportively with fluids and oxygen. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_698", "contents": "Respiratory diseases may be investigated by performing one or more of the following tests: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_699", "contents": "Respiratory disease is a common and significant cause of illness and death around the world. In the US, approximately one billion  common colds  occur each year. [ 29 ]   A study found that in 2010, there were approximately 6.8 million emergency department visits for respiratory disorders in the U.S. for patients under the age of 18. [ 30 ]  In 2012, respiratory conditions were the most frequent reasons for hospital stays among children. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_700", "contents": "In the UK, approximately 1 in 7 individuals are affected by some form of chronic lung disease, most commonly  chronic obstructive pulmonary disease , which includes  asthma ,  chronic bronchitis  and  emphysema . [ 32 ] \nRespiratory diseases (including lung cancer) are responsible for over 10% of hospitalizations and over 16% of deaths in Canada. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_701", "contents": "In 2011, respiratory disease with ventilator support accounted for 93.3% of ICU utilization in the United States. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_702", "contents": "Air trapping , also called  gas trapping , is an abnormal retention of air in the  lungs  where it is difficult to exhale completely. [ 1 ]   It is observed in  obstructive lung diseases  such as  asthma , bronchiolitis obliterans syndrome and  chronic obstructive pulmonary diseases  such as  emphysema  and  chronic bronchitis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_703", "contents": "Air trapping is not a diagnosis but is a presentation of an illness, and can be a guide to the appropriate  differential diagnosis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_704", "contents": "Exhaled volumes are measured by a pulmonary function test or simple  spirometry , leading to an elevated  residual volume  and a measurement of forced expiratory volume. Air trapping is often incidentally diagnosed on  computed tomography  (CT) scanning.  On expiratory films, retained hyperlucent gas will be visualised in cases of air trapping. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_705", "contents": "Air trapping represents poorly aerated lung, but on its own is clinically benign. It is a common problem for smokers who dive. On diving the  lung volume  collapses and pushes air into the poorly aerated regions. On arising from a deep depth, these air-trapped areas of lung expand. This places great pressure on the lung tissue which can rupture. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_706", "contents": "Allergies in children , an incidence which has increased over the last fifty years, are overreactions of the immune system often caused by foreign substances or genetics that may present themselves in different ways. [ 1 ]  There are multiple forms of testing, prevention, management, and treatment available if an allergy is present in a child. In some cases, it is possible for children to outgrow their allergies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_707", "contents": "Children affected by allergies in the developed world: [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_708", "contents": "Children in the United States under 18 years of age: [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_709", "contents": "Children in the United Kingdom: [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_710", "contents": "A child's allergy is an immune system reaction to a foreign substance, or allergen, that is considered harmless to most. According to Dr. James Fernandez with the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, \"Genetic and environmental factors work together to contribute to the development of allergies.\" [ 4 ]  Upon contact with an allergen, a child\u2019s immune system produces antibodies which patrol the body for future encounters with the invader. [ 5 ]  During any future encounters, the antibodies release immune system chemicals, such as histamine, that cause allergy symptoms in the nose, lungs, throat, sinuses, ears, eyes, skin, or stomach lining. [ 5 ] [ 6 ]  The development and symptoms of  asthma  can also be triggered by allergies; indoor allergens and indoor  volatile organic compounds , such as formaldehyde, have been known to do so. [ 6 ] [ 7 ] [ 8 ] [ 9 ]  Anthony Durmowicz, M.D., a pediatric pulmonary doctor at the FDA also says that, if a child has both allergies and asthma, \"not controlling the allergies can make asthma worse.\" [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_711", "contents": "Children are already at a higher risk of developing an allergy due to their age. [ 5 ]  \nOther risk factors include: [ 5 ] [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_712", "contents": "Airborne allergens, certain foods, insect stings, medications, and latex or other substances one touches are the most common allergy triggers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_713", "contents": "Examples of airborne allergens include: [ 5 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_714", "contents": "The top 9 food allergens are: [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_715", "contents": "Vitamin D deficiency at the time of birth and exposure to  egg white ,  milk ,  peanut ,  walnut ,  soy ,  shrimp ,  cod fish , and  wheat  makes a child more susceptible to allergies. [ 1 ]   Soy-based infant formula  is associated with allergies in infants. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_716", "contents": "Common drug allergens in children are: [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_717", "contents": "The most common insect bite/sting allergens are: [ 15 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_718", "contents": "Common skin allergens and triggers include: [ 5 ] [ 17 ] [ 11 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_719", "contents": "According to the Mayo Clinic, \u201cAllergy symptoms, which depend on the substance involved, can affect your airways, sinuses and nasal passages, skin, and digestive system.\u201d [ 5 ]  The severity of the following symptoms varies from child to child. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_720", "contents": "The symptoms of indoor and outdoor allergies in children may include: [ 18 ] [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_721", "contents": "Symptoms of indoor allergies can occur year-round but tend to be more troublesome during the winter months when children are inside more often. [ 18 ]  However, outdoor allergies, or seasonal allergies, normally change with the season. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_722", "contents": "The potential symptoms of a food allergy include: [ 10 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_723", "contents": "Possible symptoms of a drug allergy include: [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_724", "contents": "Symptoms of a potential insect bite/sting allergy include: [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_725", "contents": "Symptoms of allergic skin conditions such as atopic dermatitis, or eczema, include: [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_726", "contents": "There are some different ways that can lead allergists to an official diagnosis of an allergy. These methods include: [ 5 ] [ 10 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_727", "contents": "Family medical history can be used to help determine if a child may have an allergy because of genetics. \"Genes are thought to be involved because specific mutations are common among people with allergies and because allergies tend to run in families.\" [ 4 ]  However, it is not the specific allergies that are passed down, just the likelihood of developing allergies. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_728", "contents": "Keeping a diary of the child\u2019s symptoms and possible triggers can help an allergist determine if the child has an allergy or guide decisions for further testing. The possible allergens tracked in this manner include food, skin, indoor and outdoor allergens. Keeping track of when the symptoms appear/the reaction occurs can also help determine the possible triggers, as \"[f]ood allergy symptoms usually develop within minutes to 2 hours after eating the offending food.\" [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_729", "contents": "An elimination diet involves complete avoidance of suspected food allergens for 1\u20132 weeks and readding them to the child\u2019s diet one at a time to watch for symptoms. [ 10 ]  This method, however, may not always be accurate in identifying food allergies because it also works for determining food sensitivities/intolerances, which are different. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_730", "contents": "There are two types of skin tests that are commonly used for diagnosing allergies. The first one done is the skin prick test, which can identify most allergens. [ 4 ]  This test involves pricking a needle through a drop of each control and allergen test solutions into the child\u2019s skin. [ 4 ]  The intradermal test may be done second if no allergen is identified with the skin prick test. [ 4 ]  This test is more sensitive and involves injecting tiny amounts of the control and allergen test solutions into the child\u2019s skin with a needle. [ 4 ]  For either test, any allergies will result with a wheal and flare reaction (swelled center and surrounding circular red area) at the pinprick site. [ 4 ]  For accurate results, any child undergoing either test will need to stop taking any drugs/medications that may suppress a reaction. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_731", "contents": "For children who cannot receive either skin test, the blood test is used to determine \"whether IgE in the person's blood binds to the specific allergen used for the test.\" [ 4 ]  IgE is immunoglobulin E \u2013 the antibody produced by the immune system to protect the body from the \"invader.\" [ 11 ]  A specific allergy can be confirmed if binding occurs with that allergen. [ 4 ] \nProvocative testing for any type of allergen involves directly exposing the child to small but increasing amounts of a suspected allergen. [ 4 ] [ 10 ]  It is done at a doctor\u2019s office by a doctor who can confirm the allergy if a reaction occurs during the test. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_732", "contents": "Provocative testing for any type of allergen involves directly exposing the child to small but increasing amounts of a suspected allergen. [ 4 ] [ 10 ]  It is done at a doctor\u2019s office by a doctor who can confirm the allergy if a reaction occurs during the test. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_733", "contents": "There is no cure for allergies, making the avoidance of allergens one of the most important ways to prevent a reaction. [ 5 ]  Keeping a diary of symptoms, potential triggers, activities, and what helps reduce symptoms is also a helpful form of prevention and management. [ 10 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_734", "contents": "For pet allergies, it may help to keep pet-free zones in the house (bedrooms), give furry friends frequent baths, have kids wash hands after petting and avoid touching their eyes, and use over-the-counter (OTC) allergy medicine to reduce symptoms. [ 18 ]  These OTC allergy medications include antihistamines, such as Benadryl, Claritin, and Allegra, and nasal corticosteroids, such as Flonase and Afrin. [ 20 ]  However, it is important to consult a doctor before taking any new medications. OTC medications may not work for every child, but a doctor may be able to prescribe a different, stronger medication or alternative treatment. [ 6 ]  Immunotherapy in the form of allergy shots is one alternative treatment. [ 6 ]  If the child\u2019s reactions cannot be maintained using these methods, it may be better to find a new home for the pet and get a different one."}
+{"id": "WikiPedia_Pulmonology$$$corpus_735", "contents": "For other indoor allergies, thoroughly clean the house, bedding, and stuffed animals frequently. [ 18 ]  Using special hypoallergenic furniture and covers for bedding, trading carpet for hardwood flooring, dehumidifying, and letting in sunlight may also help with some allergens. [ 18 ]  If present, cockroaches, mice, and rats should be controlled to reduce symptoms as well."}
+{"id": "WikiPedia_Pulmonology$$$corpus_736", "contents": "Outdoor allergy symptoms can be managed by strategically planning outdoor play time, removing shoes and clothes and bathing after playing outside, keeping car and house windows closed and using the air conditioning, planting an allergy-friendly yard for kids, and keeping allergy medicine handy. [ 6 ] [ 19 ]  It may also help to keep leaves and grass clippings away from the house, keep trees and bushes trimmed, and avoid drying clothes on outdoor clotheslines. [ 6 ] [ 19 ]  Allergy shots are another possible means of management/treatment for these allergies as well, if necessary. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_737", "contents": "Reactions to food allergens can also be prevented in multiple ways. One of these ways is avoiding cross contamination of allergens into safe foods. [ 10 ]  Keeping hands/gloves, utensils, surfaces, etc. clean is important. Another effective way to avoid these allergens is to read food labels on everything that has one that may be ingested. [ 10 ]  If a product contains or may contain one of the major nine allergens, the food labels are required to have a special note to inform potential consumers. [ 10 ]  Other preventative measures include informing the child, relatives, babysitters, teachers, and any other care givers of the child\u2019s allergy and ways to avoid/treat it and avoiding any foods that you are unsure of that were made by others. [ 11 ] [ 10 ]  This could be food at school, a restaurant, or any social gathering. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_738", "contents": "For bug bite/sting and skin allergens, using fragrance-free skincare products, keeping the skin moisturized, using insect repellent, and wearing protective clothing are some of the easiest ways to prevent a reaction. [ 16 ]  OTC medications, prescription (steroid) medications and creams, allergy shots, and biologics are also effective ways to manage/treat some skin allergies. [ 5 ] [ 4 ] [ 21 ]  It is also best to avoid scratching any affected area(s) as much as possible. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_739", "contents": "As they get older, some children may outgrow their allergies. [ 10 ]  Others can also be desensitized to an allergen through exposure to the allergen, but this is a process that takes time and is not always necessary or possible. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_740", "contents": "If a child has any severe allergies that may be life-threatening, the Mayo Clinic recommends having the child wear a medical alert bracelet or necklace that would inform others of the allergy if the child was ever unable to communicate. [ 5 ]  It is also crucial to always have an epinephrine auto-injector (EpiPen, etc.) on hand that is not expired. [ 5 ]  Antihistamine medications are also helpful. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_741", "contents": "If the child encounters the allergen and shows signs of anaphylaxis, use the epinephrine auto-injector first, if available, and seek medical help immediately. Antihistamine medication can also help slow the reaction in addition to epinephrine if it has been approved for combination by your doctor. [ 4 ]  Otherwise, call 911 or your other local emergency number immediately for emergency medical help. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_742", "contents": "Allergies , also known as  allergic diseases , are various conditions caused by  hypersensitivity  of the  immune system  to typically harmless substances in the environment. [ 11 ]  These diseases include  hay fever ,  food allergies ,  atopic dermatitis ,  allergic asthma , and  anaphylaxis . [ 1 ]  Symptoms may include  red eyes , an itchy  rash ,  sneezing ,  coughing , a  runny nose ,  shortness of breath , or swelling. [ 12 ]  Note that  food intolerances  and  food poisoning  are separate conditions. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_743", "contents": "Common  allergens  include  pollen  and certain foods. [ 11 ]  Metals and other substances may also cause such problems. [ 11 ]  Food,  insect stings , and medications are common causes of severe reactions. [ 2 ]  Their development is due to both genetic and environmental factors. [ 2 ]  The underlying mechanism involves  immunoglobulin E antibodies  (IgE), part of the body's immune system, binding to an allergen and then to  a receptor  on  mast cells  or  basophils  where it triggers the release of inflammatory chemicals such as  histamine . [ 13 ]  Diagnosis is typically based on a person's  medical history . [ 3 ]  Further testing of the  skin  or blood may be useful in certain cases. [ 3 ]  Positive tests, however, may not necessarily mean there is a significant allergy to the substance in question. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_744", "contents": "Early exposure of children to potential allergens may be protective. [ 5 ]  Treatments for allergies include avoidance of known allergens and the use of medications such as  steroids  and  antihistamines . [ 6 ]  In severe reactions, injectable  adrenaline  (epinephrine) is recommended. [ 7 ]   Allergen immunotherapy , which gradually exposes people to larger and larger amounts of allergen, is useful for some types of allergies such as hay fever and reactions to insect bites. [ 6 ]  Its use in food allergies is unclear. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_745", "contents": "Allergies are common. [ 10 ]  In the developed world, about 20% of people are affected by allergic rhinitis, [ 15 ]  about 6% of people have at least one food allergy, [ 3 ] [ 5 ]  and about 20% have or have had atopic dermatitis at some point in time. [ 16 ]  Depending on the country, about 1\u201318% of people have asthma. [ 17 ] [ 18 ]  Anaphylaxis occurs in between 0.05\u20132% of people. [ 19 ]  Rates of many allergic diseases appear to be increasing. [ 7 ] [ 20 ] [ 21 ]  The word \"allergy\" was first used by  Clemens von Pirquet  in 1906. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_746", "contents": "Many allergens such as dust or pollen are airborne particles. In these cases, symptoms arise in areas in contact with air, such as the eyes, nose, and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, itching, and redness of the eyes. [ 22 ]  Inhaled allergens can also lead to increased production of  mucus  in the  lungs ,  shortness of breath , coughing, and wheezing. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_747", "contents": "Aside from these ambient allergens, allergic reactions can result from foods,  insect stings , and reactions to medications like  aspirin  and  antibiotics  such as  penicillin . Symptoms of food allergy include abdominal pain,  bloating , vomiting,  diarrhea ,  itchy  skin, and  hives . Food allergies rarely cause  respiratory  (asthmatic) reactions, or  rhinitis . [ 24 ]  Insect stings, food,  antibiotics , and certain medicines may produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including the  digestive system , the  respiratory system , and the  circulatory system . [ 25 ] [ 26 ] [ 27 ]  Depending on the severity, anaphylaxis can include skin reactions, bronchoconstriction,  swelling ,  low blood pressure , coma, and death. This type of reaction can be triggered suddenly, or the onset can be delayed. The nature of anaphylaxis is such that the reaction can seem to be subsiding but may recur throughout a period of time. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_748", "contents": "Substances that come into contact with the skin, such as  latex , are also common causes of allergic reactions, known as  contact dermatitis  or eczema. [ 28 ]  Skin allergies frequently cause  rashes , or swelling and inflammation within the skin, in what is known as a \" weal  and flare\" reaction characteristic of hives and  angioedema . [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_749", "contents": "With insect stings, a large local reaction may occur in the form of an area of skin redness greater than 10\u00a0cm in size that can last one to two days. [ 30 ]  This reaction may also occur after  immunotherapy . [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_750", "contents": "The way our body responds to foreign invaders on the molecular level is similar to how our allergens are treated even on the skin. Our skin forms an effective barrier to the entry of most allergens but this barrier cannot withstand everything that comes at it because at the end of the day, it is only our skin. A situation such as an insect sting can breach the barrier and inject  allergen  to the affected spot. When an allergen enters the epidermis or dermis, it triggers a localized allergic reaction which activates the mast cells in the skin resulting in an immediate increase in vascular permeability, leading to fluid leakage and swelling in the affected area. [ 32 ]  Mast-cell activation also stimulates a skin lesion called the wheal-and-flare reaction. [ 33 ]  This is when the release of chemicals from local nerve endings by a nerve axon reflex, causes the  vasodilatations  of surrounding cutaneous blood vessels, which causes redness of the surrounding skin. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_751", "contents": "As a part of the allergy response, our body has developed a secondary response which in some individuals causes a more widespread and sustained edematous response. [ 35 ]  This usually occurs about 8 hours after the allergen originally comes in contact with the skin. When an allergen is ingested, a dispersed form of wheal-and-flare reaction, known as urticaria or hives will appear when the allergen enters the bloodstream and eventually reaches the skin. [ 36 ] [ 37 ]  The way our skin reacts to different allergens gives allergists the upper hand and allows them to test for allergies by injecting a very small amount of an allergen into the skin. [ 38 ]  Even though these injections are very small and local, they still pose the risk of causing systematic anaphylaxis. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_752", "contents": "Risk factors for allergies can be placed in two broad categories, namely  host  and  environmental  factors. [ 40 ]  Host factors include  heredity , sex,  race , and age, with heredity being by far the most significant. However, there has been a recent increase in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to  infectious diseases  during early childhood,  environmental pollution , allergen levels, and  dietary  changes. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_753", "contents": "Dust mite  allergy, also known as house dust allergy, is a  sensitization  and allergic reaction to the droppings of  house dust mites . The allergy is common [ 42 ] [ 43 ]  and can trigger allergic reactions such as asthma,  eczema , or  itching . The mite's gut contains potent digestive enzymes (notably  peptidase 1 ) that persist in their feces and are major inducers of allergic reactions such as  wheezing . The mite's exoskeleton can also contribute to allergic reactions. Unlike  scabies  mites or skin follicle mites, house dust mites do not burrow under the skin and are not parasitic. [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_754", "contents": "A wide variety of foods can cause allergic reactions, but 90% of allergic responses to foods are caused by cow's milk,  soy , eggs, wheat, peanuts,  tree nuts , fish, and shellfish. [ 45 ]  Other food allergies, affecting less than 1 person per 10,000 population, may be considered \"rare\". [ 46 ]  The most common food allergy in the US population is a sensitivity to  crustacea . [ 46 ]  Although  peanut allergies  are notorious for their severity, peanut allergies are not the most common food allergy in adults or children. Severe or life-threatening reactions may be triggered by other allergens and are more common when combined with asthma. [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_755", "contents": "Rates of allergies differ between adults and children. Children can sometimes outgrow peanut allergies.  Egg allergies  affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5. [ 47 ]  The sensitivity is usually to proteins in the  white , rather than the  yolk . [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_756", "contents": "Milk-protein allergies \u2014distinct from  lactose intolerance \u2014are most common in children. [ 49 ]  Approximately 60% of milk-protein reactions are  immunoglobulin E \u2013mediated, with the remaining usually attributable to  inflammation of the colon . [ 50 ]  Some people are unable to tolerate milk from goats or sheep as well as from cows, and many are also unable to tolerate dairy products such as cheese. Roughly 10% of children with a milk allergy will have a reaction to beef. [ 51 ]  Lactose intolerance, a common reaction to milk, is not a form of allergy at all, but due to the absence of an  enzyme  in the  digestive tract . [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_757", "contents": "Those with  tree nut allergies  may be allergic to one or to many  tree nuts , including  pecans ,  pistachios , and  walnuts . [ 48 ]  In addition,  seeds , including  sesame seeds  and  poppy seeds , contain oils in which protein is present, which may elicit an allergic reaction. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_758", "contents": "Allergens can be transferred from one food to another through  genetic engineering ; however, genetic modification can also remove allergens. Little research has been done on the natural variation of allergen concentrations in unmodified crops. [ 53 ] [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_759", "contents": "Latex  can trigger an IgE-mediated cutaneous, respiratory, and systemic reaction. The prevalence of latex allergy in the general population is believed to be less than one percent. In a hospital study, 1 in 800 surgical patients (0.125 percent) reported latex sensitivity, although the sensitivity among healthcare workers is higher, between seven and ten percent. Researchers attribute this higher level to the exposure of healthcare workers to areas with significant airborne latex allergens, such as operating rooms, intensive-care units, and dental suites. These latex-rich environments may sensitize healthcare workers who regularly inhale allergenic proteins. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_760", "contents": "The most prevalent response to latex is an allergic contact dermatitis, a delayed hypersensitive reaction appearing as dry, crusted lesions. This reaction usually lasts 48\u201396 hours. Sweating or rubbing the area under the glove aggravates the lesions, possibly leading to ulcerations. [ 55 ]   Anaphylactic  reactions occur most often in sensitive patients who have been exposed to a surgeon's latex gloves during abdominal surgery, but other  mucosal  exposures, such as dental procedures, can also produce systemic reactions. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_761", "contents": "Latex and banana sensitivity may cross-react. Furthermore, those with latex allergy may also have sensitivities to  avocado , kiwifruit, and chestnut. [ 56 ]  These people often have  perioral  itching and local  urticaria . Only occasionally have these food-induced allergies induced systemic responses. Researchers suspect that the cross-reactivity of latex with banana,  avocado ,  kiwifruit , and  chestnut  occurs because latex proteins are structurally  homologous  with some other plant proteins. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_762", "contents": "About 10% of people report that they are allergic to  penicillin ; however, of that 10%, 90% turn out not to be. [ 57 ]  Serious allergies only occur in about 0.03%. [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_763", "contents": "One of the main sources of human allergies is insects. An allergy to insects can be brought on by bites, stings, ingestion, and inhalation. [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_764", "contents": "Another non-food protein reaction,  urushiol-induced contact dermatitis , originates after contact with  poison ivy ,  eastern poison oak ,  western poison oak , or  poison sumac .  Urushiol , which is not itself a protein, acts as a  hapten  and chemically reacts with, binds to, and changes the shape of  integral membrane proteins  on exposed skin cells. The immune system does not recognize the affected cells as normal parts of the body, causing a  T-cell -mediated  immune response . [ 59 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_765", "contents": "Of these poisonous plants, sumac is the most virulent. [ 60 ] [ 61 ]  The resulting dermatological response to the reaction between urushiol and membrane proteins includes redness, swelling,  papules ,  vesicles ,  blisters , and streaking. [ 62 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_766", "contents": "Estimates vary on the population fraction that will have an immune system response. Approximately 25% of the population will have a strong allergic response to urushiol. In general, approximately 80\u201390% of adults will develop a rash if they are exposed to 0.0050\u00a0mg (7.7 \u00d7 10 \u22125 \u00a0gr) of purified urushiol, but some people are so sensitive that it takes only a molecular trace on the skin to initiate an allergic reaction. [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_767", "contents": "Allergic diseases are strongly  familial ;  identical twins  are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in  non-identical twins . [ 64 ]  Allergic parents are more likely to have allergic children [ 65 ]  and those children's allergies are likely to be more severe than those in children of non-allergic parents. Some allergies, however, are not consistent along  genealogies ; parents who are allergic to peanuts may have children who are allergic to  ragweed . The likelihood of developing allergies is  inherited  and related to an irregularity in the immune system, but the specific  allergen  is not. [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_768", "contents": "The risk of allergic  sensitization  and the development of allergies varies with age, with young children most at risk. [ 66 ]  Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years. [ 66 ]  The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10. [ 67 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_769", "contents": "Ethnicity  may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to  migration . [ 65 ]  It has been suggested that different  genetic loci  are responsible for asthma, to be specific, in people of  European ,  Hispanic ,  Asian , and  African  origins. [ 68 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_770", "contents": "When we think about how different we all look and perceive our surroundings, it becomes unimaginable to think about how different all the ways we are different on the molecular level. Everything from how we react to foreign bodies to how we respond to those bodies and why. This is all because of our genetic markup; our  DNA , which is made up of genes that encode for specific molecules or whole complexes. Due to the variability in responses and how the disease manifests differently in individuals, a clear genetic basis for the predisposition and severity of allergic diseases has not yet been fully established. [ 69 ]  A lot of what causes the allergy is the way our body extremely reacts to the environment so the genes that cause these things are related to regulation of molecules."}
+{"id": "WikiPedia_Pulmonology$$$corpus_771", "contents": "Researchers have worked to characterize genes involved in inflammation and the maintenance of mucosal integrity. The identified genes associated with allergic disease severity, progression, and development primarily function in four areas: regulating inflammatory responses ( IFN-\u03b1 ,  TLR-1 ,  IL-13 ,  IL-4 , IL-5, HLA-G, iNOS), maintaining vascular endothelium and mucosal lining (FLG, PLAUR, CTNNA3, PDCH1, COL29A1), mediating immune cell function (PHF11, H1R, HDC, TSLP, STAT6, RERE, PPP2R3C), and influencing susceptibility to allergic sensitization (e.g., ORMDL3, CHI3L1). [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_772", "contents": "Multiple studies have investigated the genetic profiles of individuals with predispositions to and experiences of allergic diseases, revealing a complex polygenic architecture. Specific genetic loci, such as MIIP, CXCR4, SCML4, CYP1B1, ICOS, and LINC00824, have been directly associated with allergic disorders. [ 71 ]  Additionally, some loci show pleiotropic effects, linking them to both autoimmune and allergic conditions, including PRDM2, G3BP1, HBS1L, and POU2AF1. [ 72 ]  These genes engage in shared inflammatory pathways across various epithelial tissues\u2014such as the skin, esophagus, vagina, and lung\u2014highlighting common genetic factors that contribute to the pathogenesis of asthma and other allergic diseases. [ 73 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_773", "contents": "In atopic patients, transcriptome studies have identified IL-13-related pathways as key for eosinophilic airway inflammation and remodeling. That causes the body to experience the type of airflow restriction of allergic asthma. [ 74 ]  Expression of genes was quite variable: genes associated with inflammation were found almost exclusively in superficial airways, while genes related to airway remodeling were mainly present in endobronchial biopsy specimens. [ 75 ]  This enhanced gene profile was similar across multiple sample sizes \u2013 nasal brushing, sputum, endobronchial brushing \u2013 demonstrating the importance of eosinophilic inflammation, mast cell degranulation and group 3 innate lymphoid cells in severe adult-onset asthma. [ 76 ]  IL-13 is an immunoregulatory cytokine that is made mostly by activated  T-helper 2 (Th2)  cells. [ 77 ]  It is an important cytokine for many steps in B-cell maturation and differentiation, since it increases CD23 and MHC class II molecules, and aids in B-cell isotype switching to IgE. [ 78 ] [ 79 ]  IL-13 also suppresses macrophage function by reducing the release of pro-inflammatory cytokines and chemokines. [ 80 ] [ 81 ]  The more striking thing is that IL-13 is the prime mover in allergen-induced asthma via pathways that are independent of IgE and eosinophils. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_774", "contents": "Allergic diseases are caused by inappropriate immunological responses to harmless  antigens  driven by a  TH2 -mediated immune response. Many bacteria and viruses elicit a  TH1 -mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis was that insufficient stimulation of the TH1 arm of the immune system leads to an overactive TH2 arm, which in turn leads to allergic disease. [ 83 ]  In other words, individuals living in too sterile an environment are not exposed to enough pathogens to keep the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when they are not exposed to this level, the immune system will attack harmless antigens, and thus normally benign microbial objects\u2014like pollen\u2014will trigger an immune response. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_775", "contents": "The hygiene hypothesis was developed to explain the observation that  hay fever  and  eczema , both allergic diseases, were less common in children from larger families, which were, it is presumed, exposed to more infectious agents through their siblings, than in children from families with only one child. [ 85 ]  It is used to explain the increase in allergic diseases that have been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. [ 86 ]  The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents. [ 87 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_776", "contents": "Epidemiological data support the hygiene hypothesis. Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world, and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world. [ 88 ]  Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner. [ 89 ]  The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases. [ 90 ]  The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by  caesarean section  rather than vaginal birth. [ 91 ] [ 92 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_777", "contents": "Chronic  stress  can aggravate allergic conditions. This has been attributed to a T helper 2 (TH2)-predominant response driven by suppression of  interleukin 12  by both the  autonomic nervous system  and the  hypothalamic\u2013pituitary\u2013adrenal axis . Stress management in highly susceptible individuals may improve symptoms. [ 93 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_778", "contents": "Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined. [ 94 ]  Historically, the trees planted in urban areas were predominantly male to prevent litter from seeds and fruits, but the high ratio of male trees causes high pollen counts, a phenomenon that horticulturist Tom Ogren has called \" botanical sexism \". [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_779", "contents": "Alterations in exposure to  microorganisms  is another plausible explanation, at present, for the increase in  atopic allergy . [ 41 ]  Endotoxin exposure reduces release of inflammatory  cytokines  such as  TNF-\u03b1 ,  IFN\u03b3 ,  interleukin-10 , and  interleukin-12  from white blood cells ( leukocytes ) that circulate in the blood. [ 96 ]  Certain microbe-sensing  proteins , known as  Toll-like receptors , found on the surface of cells in the body are also thought to be involved in these processes. [ 97 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_780", "contents": "Parasitic worms  and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine  chlorination  and purification of drinking water supplies. [ 98 ]  Recent research has shown that some common parasites, such as intestinal worms (e.g.,  hookworms ), secrete chemicals into the gut wall (and, hence, the bloodstream) that  suppress  the immune system and prevent the body from attacking the parasite. [ 99 ]  This gives rise to a new slant on the hygiene hypothesis theory\u2014that  co-evolution  of humans and parasites has led to an immune system that functions correctly only in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive. [ 100 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_781", "contents": "In particular, research suggests that allergies may coincide with the delayed establishment of  gut flora  in  infants . [ 101 ]  However, the research to support this theory is conflicting, with some studies performed in China and  Ethiopia  showing an increase in allergy in people infected with intestinal worms. [ 94 ]  Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies. [ 102 ]  It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected  symbiosis  is at work. [ 102 ]  For more information on this topic, see  Helminthic therapy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_782", "contents": "In the initial stages of allergy, a type I hypersensitivity reaction against an allergen encountered for the first time and presented by a professional  antigen-presenting cell  causes a response in a type of immune cell called a  T H 2 lymphocyte , a subset of  T cells  that produce a  cytokine  called  interleukin-4  (IL-4). These T H 2 cells interact with other  lymphocytes  called  B cells , whose role is production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE. Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a kind of  Fc receptor  called  Fc\u03b5RI ) on the surface of other kinds of immune cells called  mast cells  and  basophils , which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage, are sensitized to the allergen. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_783", "contents": "If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule and activates the sensitized cell. Activated mast cells and basophils undergo a process called  degranulation , during which they release  histamine  and other inflammatory chemical mediators ( cytokines ,  interleukins ,  leukotrienes , and  prostaglandins ) from their  granules  into the surrounding tissue causing several systemic effects, such as  vasodilation ,  mucous  secretion,  nerve  stimulation, and  smooth muscle  contraction."}
+{"id": "WikiPedia_Pulmonology$$$corpus_784", "contents": "This results in  rhinorrhea , itchiness, dyspnea, and anaphylaxis. Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis) or localized to specific body systems. Asthma is localized to the respiratory system and eczema is localized to the  dermis . [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_785", "contents": "After the chemical mediators of the acute response subside, late-phase responses can often occur. This is due to the migration of other  leukocytes  such as  neutrophils ,  lymphocytes ,  eosinophils , and  macrophages  to the initial site. The reaction is usually seen 2\u201324 hours after the original reaction. [ 103 ]  Cytokines from mast cells may play a role in the persistence of long-term effects. Late-phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils and are still dependent on activity of T H 2 cells. [ 104 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_786", "contents": "Although  allergic contact dermatitis  is termed an \"allergic\" reaction (which usually refers to type I hypersensitivity), its pathophysiology involves a reaction that more correctly corresponds to a  type IV hypersensitivity  reaction. [ 105 ]  In type IV hypersensitivity, there is activation of certain types of  T cells  (CD8+) that destroy target cells on contact, as well as activated  macrophages  that produce  hydrolytic   enzymes . [ 106 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_787", "contents": "Effective management of allergic diseases relies on the ability to make an accurate diagnosis. [ 107 ]  Allergy testing can help confirm or rule out allergies. [ 108 ] [ 109 ]  Correct diagnosis, counseling, and avoidance advice based on valid allergy test results reduce the incidence of symptoms and need for medications, and improve quality of life. [ 108 ]  To assess the presence of allergen-specific IgE antibodies, two different methods can be used: a skin prick test, or an allergy  blood test . Both methods are recommended, and they have similar diagnostic value. [ 109 ] [ 110 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_788", "contents": "Skin prick tests and blood tests are equally cost-effective, and health economic evidence shows that both tests were cost-effective compared with no test. [ 108 ]  Early and more accurate diagnoses save cost due to reduced consultations, referrals to secondary care, misdiagnosis, and emergency admissions. [ 111 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_789", "contents": "Allergy undergoes dynamic changes over time. Regular allergy testing of relevant allergens provides information on if and how patient management can be changed to improve health and quality of life. Annual  testing  is often the practice for determining whether allergy to milk, egg, soy, and wheat have been outgrown, and the testing interval is extended to 2\u20133 years for allergy to peanut, tree nuts, fish, and crustacean shellfish. [ 109 ]  Results of follow-up testing can guide decision-making regarding whether and when it is safe to introduce or re-introduce allergenic food into the diet. [ 112 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_790", "contents": "Skin testing  is also known as \"puncture testing\" and \"prick testing\" due to the series of tiny punctures or pricks made into the patient's skin. Tiny amounts of suspected allergens and/or their  extracts  ( e.g. , pollen, grass, mite proteins, peanut extract) are introduced to sites on the skin marked with pen or dye (the ink/dye should be carefully selected, lest it cause an allergic response itself). A negative and positive control are also included for comparison (eg, negative is saline or glycerin; positive is histamine). A small plastic or metal device is used to puncture or prick the skin. Sometimes, the allergens are injected \"intradermally\" into the patient's skin, with a needle and syringe. Common areas for testing include the inside forearm and the back."}
+{"id": "WikiPedia_Pulmonology$$$corpus_791", "contents": "If the patient is allergic to the substance, then a visible inflammatory reaction will usually occur within 30\u00a0minutes. This response will range from slight reddening of the skin to a full-blown  hive  (called \"wheal and flare\") in more sensitive patients similar to a  mosquito bite . Interpretation of the results of the skin prick test is normally done by allergists on a scale of severity, with +/\u2212 meaning borderline reactivity, and 4+ being a large reaction. Increasingly, allergists are measuring and recording the diameter of the wheal and flare reaction. Interpretation by well-trained allergists is often guided by relevant literature. [ 113 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_792", "contents": "In general, a positive response is interpreted when the wheal of an antigen is \u22653mm larger than the wheal of the negative control (eg, saline or glycerin). [ 114 ]  Some patients may believe they have determined their own allergic sensitivity from observation, but a skin test has been shown to be much better than patient observation to detect allergy. [ 115 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_793", "contents": "If a serious life-threatening anaphylactic reaction has brought a patient in for evaluation, some allergists will prefer an initial blood test prior to performing the skin prick test. Skin tests may not be an option if the patient has widespread skin disease or has taken  antihistamines  in the last several days."}
+{"id": "WikiPedia_Pulmonology$$$corpus_794", "contents": "Patch testing is a method used to determine if a specific substance causes allergic inflammation of the skin. It tests for delayed reactions. It is used to help ascertain the cause of skin contact allergy or  contact dermatitis . Adhesive patches, usually treated with several common allergic chemicals or skin sensitizers, are applied to the back. The skin is then examined for possible local reactions at least twice, usually at 48 hours after application of the patch, and again two or three days later."}
+{"id": "WikiPedia_Pulmonology$$$corpus_795", "contents": "An allergy  blood test  is quick and simple and can be ordered by a licensed health care provider ( e.g. , an allergy specialist) or general practitioner. Unlike skin-prick testing, a blood test can be performed irrespective of age, skin condition, medication, symptom, disease activity, and pregnancy. Adults and children of any age can get an allergy blood test. For babies and very young children, a single needle stick for allergy blood testing is often gentler than several skin pricks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_796", "contents": "An allergy blood test is available through most  laboratories . A sample of the patient's blood is sent to a laboratory for analysis, and the results are sent back a few days later. Multiple allergens can be detected with a single blood sample. Allergy blood tests are very safe since the person is not exposed to any allergens during the testing procedure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_797", "contents": "The test measures the concentration of specific  IgE antibodies  in the blood.  Quantitative  IgE test results increase the possibility of ranking how different substances may affect symptoms. A rule of thumb is that the higher the IgE antibody value, the greater the likelihood of symptoms. Allergens found at low levels that today do not result in symptoms cannot help predict future symptom development. The quantitative allergy blood result can help determine what a patient is allergic to, help predict and follow the disease development, estimate the risk of a severe reaction, and explain  cross-reactivity . [ 116 ] [ 117 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_798", "contents": "A low total IgE level is not adequate to rule out  sensitization  to commonly inhaled allergens. [ 118 ]   Statistical methods , such as  ROC curves , predictive value calculations, and likelihood ratios have been used to examine the relationship of various testing methods to each other. These methods have shown that patients with a high total IgE have a high probability of allergic sensitization, but further investigation with allergy tests for specific IgE antibodies for a carefully chosen of allergens is often warranted."}
+{"id": "WikiPedia_Pulmonology$$$corpus_799", "contents": "Laboratory methods to measure specific IgE antibodies for allergy testing include  enzyme-linked immunosorbent assay  (ELISA, or EIA), [ 119 ]   radioallergosorbent test  (RAST), [ 119 ]  fluorescent enzyme  immunoassay  (FEIA), [ 120 ]  and  chemiluminescence immunoassay  (CLIA). [ 121 ] [ 122 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_800", "contents": "Challenge testing:  Challenge testing is when tiny amounts of a suspected allergen are introduced to the body orally, through inhalation, or via other routes. Except for testing food and medication allergies, challenges are rarely performed. When this type of testing is chosen, it must be closely supervised by an  allergist ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_801", "contents": "Elimination/challenge tests:  This testing method is used most often with foods or medicines. A patient with a suspected allergen is instructed to modify his diet to totally avoid that allergen for a set time. If the patient experiences significant improvement, he may then be \"challenged\" by reintroducing the allergen, to see if symptoms are reproduced."}
+{"id": "WikiPedia_Pulmonology$$$corpus_802", "contents": "Unreliable tests:  There are other types of allergy testing methods that are unreliable, including  applied kinesiology  (allergy testing through muscle relaxation),  cytotoxicity  testing, urine autoinjection, skin  titration  (Rinkel method), and provocative and neutralization (subcutaneous) testing or sublingual provocation. [ 123 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_803", "contents": "Before a diagnosis of allergic disease can be confirmed, other plausible causes of the presenting symptoms must be considered. [ 124 ]   Vasomotor rhinitis , for example, is one of many illnesses that share symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis. [ 125 ]  Once a diagnosis of  asthma , rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy."}
+{"id": "WikiPedia_Pulmonology$$$corpus_804", "contents": "Giving peanut products early may decrease the risk of allergies while only  breastfeeding  during at least the first few months of life may decrease the risk of  dermatitis . [ 126 ] [ 127 ]  There is no good evidence that a mother's diet during pregnancy or breastfeeding affects the risk of allergies, [ 126 ]  nor is there evidence that delayed introduction of certain foods is useful. [ 126 ]  Early exposure to potential allergens may actually be protective. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_805", "contents": "Fish oil supplementation during pregnancy is associated with a lower risk. [ 127 ]  Probiotic supplements during pregnancy or infancy may help to prevent atopic dermatitis. [ 128 ] [ 129 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_806", "contents": "Management of allergies typically involves avoiding the allergy trigger and taking medications to improve the symptoms. [ 6 ]   Allergen immunotherapy  may be useful for some types of allergies. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_807", "contents": "Several medications may be used to block the action of allergic mediators, or to prevent activation of cells and  degranulation  processes. These include  antihistamines ,  glucocorticoids ,  epinephrine  (adrenaline),  mast cell stabilizers , and  antileukotriene agents  are common treatments of allergic diseases. [ 130 ]   Anticholinergics ,  decongestants , and other compounds thought to impair  eosinophil   chemotaxis  are also commonly used. Although rare, the severity of anaphylaxis often requires  epinephrine  injection, and where medical care is unavailable, a device known as an  epinephrine autoinjector  may be used. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_808", "contents": "Allergen  immunotherapy  is useful for environmental allergies, allergies to insect bites, and asthma. [ 6 ] [ 131 ]  Its benefit for food allergies is unclear and thus not recommended. [ 6 ]  Immunotherapy involves exposing people to larger and larger amounts of allergen in an effort to change the immune system's response. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_809", "contents": "Meta-analyses have found that injections of allergens under the skin is effective in the treatment in allergic rhinitis in children [ 132 ] [ 133 ]  and in asthma. [ 131 ]  The benefits may last for years after treatment is stopped. [ 134 ]  It is generally safe and effective for allergic rhinitis and  conjunctivitis , allergic forms of asthma, and stinging insects. [ 135 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_810", "contents": "To a lesser extent, the evidence also supports the use of  sublingual immunotherapy  for rhinitis and asthma. [ 134 ]  For seasonal allergies the benefit is small. [ 136 ]  In this form the allergen is given under the tongue and people often prefer it to injections. [ 134 ]  Immunotherapy is not recommended as a stand-alone treatment for asthma. [ 134 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_811", "contents": "An experimental treatment,  enzyme potentiated desensitization  (EPD), has been tried for decades but is not generally accepted as effective. [ 137 ]  EPD uses dilutions of allergen and an enzyme,  beta-glucuronidase , to which  T-regulatory lymphocytes  are supposed to respond by favoring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment of  autoimmune diseases , but evidence does not show effectiveness. [ 137 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_812", "contents": "A review found no effectiveness of  homeopathic treatments  and no difference compared with  placebo . The authors concluded that based on rigorous clinical trials of all types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of homeopathic treatments. [ 138 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_813", "contents": "According to the  National Center for Complementary and Integrative Health , U.S., the evidence is relatively strong that  saline nasal irrigation  and  butterbur  are effective, when compared to other  alternative medicine  treatments, for which the scientific evidence is weak, negative, or nonexistent, such as honey, acupuncture, omega 3's, probiotics, astragalus, capsaicin, grape seed extract, Pycnogenol, quercetin, spirulina, stinging nettle, tinospora, or guduchi.\n [ 139 ] [ 140 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_814", "contents": "The allergic diseases\u2014hay fever and asthma\u2014have increased in the Western world over the past 2\u20133 decades. [ 141 ]  Increases in allergic asthma and other atopic disorders in industrialized nations, it is estimated, began in the 1960s and 1970s, with further increases occurring during the 1980s and 1990s, [ 142 ]  although some suggest that a steady rise in sensitization has been occurring since the 1920s. [ 143 ]  The number of new cases per year of atopy in developing countries has, in general, remained much lower. [ 142 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_815", "contents": "Although genetic factors govern susceptibility to atopic disease, increases in  atopy  have occurred within too short a period to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes. [ 142 ]  Several hypotheses have been identified to explain this increased rate. Increased exposure to perennial allergens may be due to housing changes and increased time spent indoors, and a decreased activation of a common immune control mechanism may be caused by changes in cleanliness [ 155 ]  or hygiene, and exacerbated by dietary changes, obesity, and decline in physical exercise. [ 141 ]  The  hygiene hypothesis  maintains [ 156 ]  that high living standards and hygienic conditions exposes children to fewer infections. It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away from  T H 1 type responses, leading to unrestrained T H 2 responses that allow for an increase in allergy. [ 100 ] [ 157 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_816", "contents": "Changes in rates and types of infection alone, however, have been unable to explain the observed increase in allergic disease, and recent evidence has focused attention on the importance of the  gastrointestinal microbial environment . Evidence has shown that exposure to food and  fecal-oral  pathogens, such as  hepatitis A ,  Toxoplasma gondii , and  Helicobacter pylori  (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%, [ 158 ]  and an increased rate of parasitic infections has been associated with a decreased prevalence of asthma. [ 159 ]  It is speculated that these infections exert their effect by critically altering T H 1/T H 2 regulation. [ 160 ]  Important elements of newer hygiene hypotheses also include exposure to  endotoxins , exposure to pets and growing up on a farm. [ 160 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_817", "contents": "Some symptoms attributable to allergic diseases are mentioned in ancient sources. [ 161 ]  Particularly, three members of the Roman  Julio-Claudian dynasty  ( Augustus ,  Claudius  and  Britannicus ) are suspected to have a family history of atopy. [ 161 ] [ 162 ]  The concept of \"allergy\" was originally introduced in 1906 by the  Viennese   pediatrician   Clemens von Pirquet , after he noticed that patients who had received injections of horse serum or smallpox vaccine usually had quicker, more severe reactions to second injections. [ 163 ]  Pirquet called this phenomenon \"allergy\" from the  Ancient Greek  words  \u1f04\u03bb\u03bb\u03bf\u03c2   allos  meaning \"other\" and  \u1f14\u03c1\u03b3\u03bf\u03bd   ergon  meaning \"work\". [ 164 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_818", "contents": "All forms of hypersensitivity used to be classified as allergies, and all were thought to be caused by an improper activation of the immune system. Later, it became clear that several different disease mechanisms were implicated, with a common link to a disordered activation of the immune system. In 1963, a new classification scheme was designed by  Philip Gell  and  Robin Coombs  that described four types of  hypersensitivity reactions , known as Type I to Type IV hypersensitivity. [ 165 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_819", "contents": "With this new classification, the word  allergy , sometimes clarified as a  true allergy , was restricted to type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions involving IgE antibodies. [ 166 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_820", "contents": "A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled  immunoglobulin E  (IgE). IgE was simultaneously discovered in 1966\u201367 by two independent groups: [ 167 ]   Ishizaka 's team at the Children's Asthma Research Institute and Hospital in Denver, USA, [ 168 ]  and by Gunnar Johansson and Hans Bennich in Uppsala, Sweden. [ 169 ]  Their joint paper was published in April 1969. [ 170 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_821", "contents": "Radiometric assays include the  radioallergosorbent test  (RAST test) method, which uses IgE-binding (anti-IgE) antibodies labeled with  radioactive isotopes  for quantifying the levels of IgE antibody in the blood. [ 171 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_822", "contents": "The RAST methodology was invented and marketed in 1974 by Pharmacia Diagnostics AB, Uppsala, Sweden, and the acronym RAST is actually a brand name. In 1989, Pharmacia Diagnostics AB replaced it with a superior test named the ImmunoCAP Specific IgE blood test, which uses the newer fluorescence-labeled technology. [ 172 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_823", "contents": "American College of Allergy Asthma and Immunology  (ACAAI) and the  American Academy of Allergy Asthma and Immunology  (AAAAI) issued the Joint Task Force Report \"Pearls and pitfalls of allergy diagnostic testing\" in 2008, and is firm in its statement that the term RAST is now obsolete:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_824", "contents": "The term RAST became a colloquialism for all varieties of (in vitro allergy) tests.  This is unfortunate because it is well recognized that there are well-performing tests and some that do not perform so well, yet they are all called RASTs, making it difficult to distinguish which is which. For these reasons, it is now recommended that use of RAST as a generic descriptor of these tests be abandoned. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_825", "contents": "The updated version, the ImmunoCAP Specific IgE blood test, is the only specific IgE assay to receive  Food and Drug Administration  approval to quantitatively report to its detection limit of 0.1kU/L. [ 172 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_826", "contents": "The medical speciality that studies, diagnoses and treats diseases caused by allergies is called allergology. [ 173 ] \nAn allergist is a physician specially trained to manage and treat allergies, asthma, and the other allergic diseases. In the United States physicians holding certification by the  American Board of Allergy and Immunology  (ABAI) have successfully completed an accredited educational program and evaluation process, including a proctored examination to demonstrate knowledge, skills, and experience in patient care in allergy and immunology. [ 174 ]  Becoming an allergist/immunologist requires completion of at least nine years of training."}
+{"id": "WikiPedia_Pulmonology$$$corpus_827", "contents": "After completing medical school and graduating with a medical degree, a physician will undergo three years of training in  internal medicine  (to become an internist) or  pediatrics  (to become a pediatrician). Once physicians have finished training in one of these specialties, they must pass the exam of either the  American Board of Pediatrics  (ABP), the  American Osteopathic Board of Pediatrics  (AOBP), the  American Board of Internal Medicine  (ABIM), or the  American Osteopathic Board of Internal Medicine  (AOBIM). Internists or pediatricians wishing to focus on the sub-specialty of allergy-immunology then complete at least an additional two years of study, called a fellowship, in an allergy/immunology training program. Allergist/immunologists listed as ABAI-certified have successfully passed the certifying examination of the ABAI following their fellowship. [ 175 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_828", "contents": "In the United Kingdom, allergy is a subspecialty of  general medicine  or  pediatrics . After obtaining postgraduate exams ( MRCP  or  MRCPCH ), a doctor works for several years as a  specialist registrar  before qualifying for the  General Medical Council  specialist register. Allergy services may also be delivered by  immunologists . A 2003  Royal College of Physicians  report presented a case for improvement of what were felt to be inadequate allergy services in the UK. [ 176 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_829", "contents": "In 2006, the  House of Lords  convened a subcommittee. It concluded likewise in 2007 that allergy services were insufficient to deal with what the Lords referred to as an \"allergy epidemic\" and its social cost; it made several recommendations. [ 177 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_830", "contents": "Low-allergen foods are being developed, as are improvements in skin prick test predictions; evaluation of the atopy patch test, wasp sting outcomes predictions, a rapidly disintegrating epinephrine tablet, and anti- IL-5  for eosinophilic diseases. [ 178 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_831", "contents": "Aluminosis  (also known as  aluminium lung ) is a  restrictive lung disease  caused by exposure to aluminum-bearing  dust . [ 1 ]  Aluminosis is a form of  pneumoconiosis  that can lead to  pulmonary fibrosis . [ 2 ]  First cases of lung damage from aluminium exposure were reported in the 1930s in Germany. It can be detected by using  high-resolution computed tomography . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_832", "contents": "Findings may vary, showing nodular or slightly irregular opacities that may merge into more prominent forms, most frequently in the upper lung fields, sometimes in the lower lung fields, and less frequently a diffuse micro nodular pattern. In severe cases, pulmonary fibrosis with honeycombing was described. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_833", "contents": "Workers exposed to aluminium dust are often involved in industries such as explosives manufacturing where  aluminium powder  is involved, aluminium  welding  and grinding, and bauxite smelting. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_834", "contents": "This article about a medical condition affecting the respiratory system is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_835", "contents": "Anaphylaxis  (Greek:  ana-  'up' +  phylaxis  'guarding') is a serious, potentially fatal  allergic reaction  and  medical emergency  that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. [ 4 ] [ 5 ]  It typically causes more than one of the following: an itchy rash, throat closing due to swelling that can obstruct or stop breathing; severe tongue swelling that can also interfere with or stop breathing;  shortness of breath ,  vomiting , lightheadedness, loss of consciousness,  low blood pressure , and  medical shock . [ 6 ] [ 1 ]  These symptoms typically start in minutes to hours and then increase very rapidly to life-threatening levels. [ 1 ]  Urgent medical treatment is required to prevent serious harm and death, even if the patient has used an  epipen  or has taken other medications in response, and even if symptoms appear to be improving. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_836", "contents": "Common causes include allergies to  insect bites  and stings,  allergies to foods  \u2013 including nuts, milk, fish, shellfish, eggs and some fresh fruits or dried fruits; allergies to sulfites \u2013 a class of food preservatives and a byproduct in some fermented foods like vinegar; allergies to medications \u2013 including some antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin; [ 7 ]  allergy to general anaesthetic (used to make people sleep during surgery); allergy to contrast agents \u2013 dyes used in some medical tests to help certain areas of the body show up better on scans; allergy to  latex  \u2013 a type of rubber found in some rubber gloves and condoms. [ 6 ] [ 1 ]  Other causes can include physical exercise, and cases may also occur in some people due to escalating reactions to simple throat irritation or may also occur without an obvious reason. [ 6 ] [ 1 ]  The mechanism involves the release of inflammatory mediators in a rapidly escalating cascade from certain types of  white blood cells  triggered by either  immunologic  or non-immunologic mechanisms. [ 8 ]  Diagnosis is based on the presenting symptoms and signs after exposure to a potential  allergen  or irritant and in some cases, reaction to physical exercise. [ 6 ] [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_837", "contents": "The primary treatment of anaphylaxis is  epinephrine   injection into a muscle ,  intravenous fluids , then placing the person \"in a reclining position with feet elevated to help restore normal blood flow\". [ 1 ] [ 9 ]  Additional doses of epinephrine may be required. [ 1 ]  Other measures, such as  antihistamines  and  steroids , are complementary. [ 1 ]  Carrying an  epinephrine autoinjector , commonly called an \"epipen\", and identification regarding the condition is recommended in people with a history of anaphylaxis. [ 1 ]  Immediately contacting ambulance / EMT services is always strongly recommended, regardless of any on-site treatment. [ 6 ]  Getting to a doctor or hospital as soon as possible is absolutely required in all cases, even if it appears to be getting better. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_838", "contents": "Worldwide, 0.05\u20132% of the population is estimated to experience anaphylaxis at some point in life. [ 3 ]  Globally, as underreporting declined into the 2010s, the rate appeared to be increasing. [ 3 ]  It occurs most often in young people and females. [ 9 ] [ 10 ]  About 99.7% of people hospitalized with anaphylaxis in the United States survive. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_839", "contents": "The word is derived from  Ancient Greek :  \u1f00\u03bd\u03ac ,  romanized :\u00a0 ana ,  lit. \u2009 'up', and  Ancient Greek :  \u03c6\u03cd\u03bb\u03b1\u03be\u03b9\u03c2 ,  romanized :\u00a0 phylaxis ,  lit. \u2009 'protection'. [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_840", "contents": "Anaphylaxis typically presents many different symptoms over minutes or hours [ 9 ] [ 14 ]  with an average onset of 5 to 30\u00a0minutes if exposure is intravenous and up to 2\u00a0hours if from eating food. [ 15 ]  The most common areas affected include: skin (80\u201390%),  respiratory  (70%),  gastrointestinal  (30\u201345%), heart and  vasculature  (10\u201345%), and central nervous system (10\u201315%) [ 16 ]  with usually two or more being involved. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_841", "contents": "Symptoms typically include generalized  hives ,  itchiness ,  flushing , or  swelling  ( angioedema ) of the affected  tissues . [ 4 ]  Those with angioedema may describe a burning sensation of the skin rather than itchiness. [ 15 ]  Swelling of the tongue or throat occurs in up to about 20% of cases. [ 17 ]  Other features may include a runny nose and swelling of the  conjunctiva . [ 18 ]  The skin may also be  blue tinged  because of  lack of oxygen . [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_842", "contents": "Respiratory symptoms and signs that may be present include  shortness of breath ,  wheezes , or  stridor . [ 4 ]  The wheezing is typically caused by spasms of the  bronchial  muscles [ 19 ]  while stridor is related to upper airway obstruction secondary to swelling. [ 18 ]  Hoarseness, pain with swallowing, or a cough may also occur. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_843", "contents": "While  a fast heart rate  caused by low blood pressure is more common, [ 18 ]  a  Bezold\u2013Jarisch reflex  has been described in 10% of people, where a  slow heart rate  is associated with  low blood pressure . [ 10 ]  A drop in  blood pressure  or  shock  (either  distributive  or  cardiogenic ) may cause the feeling of lightheadedness or  loss of consciousness . [ 19 ]  Rarely very low blood pressure may be the only sign of anaphylaxis. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_844", "contents": "Coronary artery spasm  may occur with subsequent  myocardial infarction ,  dysrhythmia , or  cardiac arrest . [ 3 ] [ 16 ]  Those with underlying coronary disease are at greater risk of cardiac effects from anaphylaxis. [ 19 ]  The coronary spasm is related to the presence of  histamine -releasing cells in the heart. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_845", "contents": "Gastrointestinal symptoms may include severe crampy  abdominal pain , and vomiting. [ 4 ]  There may be confusion, a loss of bladder control or pelvic pain similar to that of  uterine  cramps. [ 4 ] [ 18 ]  Dilation of blood vessels around the brain may cause  headaches . [ 15 ]  A feeling of  anxiety  or of \"impending doom\" has also been described. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_846", "contents": "Anaphylaxis can occur in response to almost any foreign substance. [ 20 ]  Common triggers include  venom  from  insect bites or stings , foods, and  medication . [ 10 ] [ 21 ]  Foods are the most common trigger in children and young adults, while medications and insect bites and stings are more common in older adults. [ 3 ]  Less common causes include: physical factors, biological agents such as  semen ,  latex ,  hormonal  changes, food additives and colors, and topical medications. [ 18 ]  Physical factors such as exercise (known as  exercise-induced anaphylaxis ) or temperature (either hot or cold) may also act as triggers through their direct effects on  mast cells . [ 3 ] [ 22 ] [ 23 ]  Events caused by exercise are frequently associated with cofactors such as the ingestion of certain foods [ 15 ] [ 24 ]  or taking an  NSAID . [ 24 ]  In  aspirin-exacerbated respiratory disease  (AERD), alcohol is a common trigger. [ 25 ] [ 26 ]  During  anesthesia ,  neuromuscular blocking agents ,  antibiotics , and latex are the most common causes. [ 27 ]  The cause remains unknown in 32\u201350% of cases, referred to as \" idiopathic  anaphylaxis.\" [ 28 ]  Six vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal) are recognized as a cause for anaphylaxis, and  HPV  may cause anaphylaxis as well. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_847", "contents": "Many foods can trigger anaphylaxis; this may occur upon the first known ingestion. [ 10 ]   Common triggering foods vary around the world due to cultural cuisine.  In Western cultures, ingestion of or exposure to  peanuts ,  wheat ,  nuts , certain types of  seafood  like  shellfish ,  milk ,  fruit  and  eggs  are the most prevalent causes. [ 3 ] [ 16 ]   Sesame  is common in the Middle East, while rice and  chickpeas  are frequently encountered as sources of anaphylaxis in Asia. [ 3 ]  Severe cases are usually caused by ingesting the allergen, [ 10 ]  but some people experience a severe reaction upon contact. Children can outgrow their allergies.  By age 16, 80% of children with anaphylaxis to milk or eggs and 20% who experience isolated anaphylaxis to peanuts can tolerate these foods. [ 20 ]  Any type of alcohol, even in small amounts, can trigger anaphylaxis in people with AERD. [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_848", "contents": "Any medication may potentially trigger anaphylaxis. The most common are  \u03b2-lactam antibiotics  (such as  penicillin ) followed by  aspirin  and  NSAIDs . [ 16 ] [ 30 ]  Other  antibiotics  are implicated less frequently. [ 30 ]  Anaphylactic reactions to NSAIDs are either agent specific or occur among those that are structurally similar meaning that those who are allergic to one NSAID can typically tolerate a different one or different group of NSAIDs. [ 31 ]  Other relatively common causes include  chemotherapy ,  vaccines ,  protamine  and  herbal  preparations. [ 3 ]  Some medications ( vancomycin ,  morphine ,  x-ray contrast  among others) cause anaphylaxis by directly triggering mast cell  degranulation . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_849", "contents": "The frequency of a reaction to an agent partly depends on the frequency of its use and partly on its intrinsic properties. [ 32 ]  Anaphylaxis to penicillin or  cephalosporins  occurs only after it binds to proteins inside the body with some agents binding more easily than others. [ 15 ]  Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in fewer than one in every 50,000 courses of treatment. [ 15 ]  Anaphylaxis to aspirin and NSAIDs occurs in about one in every 50,000 persons. [ 15 ]  If someone has a reaction to penicillin, his or her risk of a reaction to cephalosporins is greater but still less than one in 1,000. [ 15 ]  The old radiocontrast agents caused reactions in 1% of cases, while the newer lower osmolar agents cause reactions in 0.04% of cases. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_850", "contents": "Venom  from stinging or biting insects such as  Hymenoptera  (ants, bees, and wasps) or  Triatominae  (kissing bugs) may cause anaphylaxis in susceptible people. [ 9 ] [ 33 ] [ 34 ]  Previous reactions that are anything more than a local reaction around the site of the sting, are a risk factor for future anaphylaxis; [ 35 ] [ 36 ]  however, half of fatalities have had no previous systemic reaction. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_851", "contents": "People with  atopic  diseases such as  asthma ,  eczema , or  allergic rhinitis  are at high risk of anaphylaxis from food,  latex , and  radiocontrast agents  but not from injectable medications or stings. [ 3 ] [ 10 ]  One study in children found that 60% had a history of previous atopic diseases, and of children who die from anaphylaxis, more than 90% have asthma. [ 10 ]  Those with  mastocytosis  or of a higher  socioeconomic status  are at increased risk. [ 3 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_852", "contents": "Anaphylaxis is a severe  allergic reaction  of rapid onset affecting many  body systems . [ 5 ] [ 8 ]  It is due to the release of  inflammatory mediators  and  cytokines  from mast cells and  basophils , typically due to an  immunologic reaction  but sometimes non-immunologic mechanism. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_853", "contents": "Interleukin  (IL)\u20134 and IL-13 are cytokines important in the initial generation of antibody and inflammatory cell responses to anaphylaxis. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_854", "contents": "In the immunologic mechanism,  immunoglobulin E  (IgE) binds to the  antigen  (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates  Fc\u03b5RI  receptors on mast cells and basophils. This leads to the release of inflammatory mediators such as  histamine . These mediators subsequently increase the contraction of bronchial  smooth muscles , trigger  vasodilation , increase the leakage of fluid from blood vessels, and cause heart muscle depression. [ 8 ] [ 15 ]  There is also a non-immunologic mechanism that does not rely on IgE, but it is not known if this occurs in humans. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_855", "contents": "Non-immunologic mechanisms involve substances that directly cause the  degranulation  of mast cells and basophils. These include agents such as  contrast medium ,  opioids , temperature (hot or cold), and vibration. [ 8 ] [ 22 ]   Sulfites  may cause reactions by both immunologic and non-immunologic mechanisms. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_856", "contents": "Anaphylaxis is diagnosed on the basis of a person's signs and symptoms. [ 3 ]  When any one of the following three occurs within minutes or hours of exposure to an allergen there is a high likelihood of anaphylaxis: [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_857", "contents": "Skin involvement may include: hives, itchiness or a swollen tongue among others. Respiratory difficulties may include: shortness of breath,  stridor , or low oxygen levels among others. Low blood pressure is defined as a greater than 30% decrease from a person's usual blood pressure. In adults a systolic blood pressure of less than 90 mmHg is often used. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_858", "contents": "During an attack, blood tests for  tryptase  or  histamine  (released from mast cells) might be useful in diagnosing anaphylaxis due to insect stings or medications. However these tests are of limited use if the cause is food or if the person has a normal  blood pressure , [ 3 ]  and they are not  specific  for the diagnosis. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_859", "contents": "There are three main classifications of anaphylaxis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_860", "contents": "Allergy testing  may help in determining the trigger.  Skin allergy testing  is available for certain foods and venoms. [ 20 ]  Blood testing for specific  IgE  can be useful to confirm milk, egg, peanut, tree nut and fish allergies. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_861", "contents": "Skin testing is available to confirm  penicillin  allergies, but is not available for other medications. [ 20 ]  Non-immune forms of anaphylaxis can only be determined by history or exposure to the allergen in question, and not by skin or blood testing. [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_862", "contents": "It can sometimes be difficult to distinguish anaphylaxis from  asthma ,  syncope , and  panic attacks . [ 3 ]  Asthma however typically does not entail itching or gastrointestinal symptoms, syncope presents with pallor rather than a rash, and a panic attack may have flushing but does not have hives. [ 3 ]  Other conditions that may present similarly include:  scrombroidosis  and  anisakiasis . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_863", "contents": "In a person who died from anaphylaxis,  autopsy  may show an \"empty heart\" attributed to reduced venous return from  vasodilation  and redistribution of intravascular volume from the central to the peripheral compartment. [ 38 ]  Other signs are laryngeal edema, eosinophilia in lungs, heart and tissues, and evidence of myocardial hypoperfusion. [ 43 ]  Laboratory findings could detect increased levels of serum  tryptase , increase in total and specific IgE serum levels. [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_864", "contents": "Avoidance of the trigger of anaphylaxis is recommended. In cases where this may not be possible, desensitization may be an option.  Immunotherapy  with  Hymenoptera  venoms is effective at desensitizing 80\u201390% of adults and 98% of children against allergies to  bees ,  wasps ,  hornets ,  yellowjackets , and  fire ants . Oral immunotherapy may be effective at desensitizing some people to certain food including milk, eggs, nuts and peanuts; however, adverse effects are common. [ 3 ]  For example, many people develop an itchy throat, cough, or lip swelling during immunotherapy. [ 44 ]  Desensitization is also possible for many medications, however it is advised that most people simply avoid the agent in question. In those who react to latex it may be important to avoid cross-reactive foods such as avocados, bananas, and potatoes among others. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_865", "contents": "Anaphylaxis is a  medical emergency  that may require  resuscitation  measures such as  airway management ,  supplemental oxygen , large volumes of  intravenous fluids , and close monitoring. [ 9 ]   Passive leg raise  may also be helpful in the emergency management. [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_866", "contents": "Administration of intravenous fluid bolus and epinephrine is the treatment of choice with  antihistamines  used as adjuncts. [ 46 ]  A period of in-hospital observation for between 2 and 24 hours is recommended for people once they have returned to normal due to concerns of biphasic anaphylaxis. [ 10 ] [ 15 ] [ 41 ] [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_867", "contents": "Epinephrine  (adrenaline) (1 in 1,000) is the primary treatment for anaphylaxis with no absolute  contraindication  to its use. [ 9 ]  It is recommended that an epinephrine solution be given  intramuscularly  into the mid anterolateral thigh as soon as the diagnosis is suspected. The injection may be repeated every 5 to 15 minutes if there is insufficient response. [ 9 ]  A second dose is needed in 16\u201335% of episodes with more than two doses rarely required. [ 9 ]  The intramuscular route is preferred over  subcutaneous  administration because the latter may have delayed absorption. [ 9 ] [ 48 ]  It is recommended that after diagnosis and treatment of anaphylaxis, the patient should be kept under observation in an appropriate clinical setting until symptoms have fully resolved. [ 40 ]  Minor adverse effects from epinephrine include  tremors , anxiety, headaches, and  palpitations . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_868", "contents": "People on  \u03b2-blockers  may be resistant to the effects of epinephrine. [ 10 ]  In this situation if epinephrine is not effective intravenous  glucagon  can be administered which has a mechanism of action independent of  \u03b2-receptors . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_869", "contents": "If necessary, it can also be given  intravenously  using a dilute epinephrine solution. Intravenous epinephrine, however, has been associated both with  dysrhythmia  and  myocardial infarction . [ 9 ]   Epinephrine autoinjectors  used for self-administration typically come in two doses, one for adults or children who weigh more than 25\u00a0kg and one for children who weigh 10 to 25\u00a0kg. [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_870", "contents": "Antihistamines  (both  H1  and  H2 ), while commonly used and assumed effective based on theoretical reasoning, are poorly supported by evidence. [ 50 ] [ 51 ]  A 2007  Cochrane  review did not find any good-quality studies upon which to base recommendations [ 51 ]  and they are not believed to have an effect on airway edema or spasm. [ 10 ]   Corticosteroids  are unlikely to make a difference in the current episode of anaphylaxis, but may be used in the hope of decreasing the risk of biphasic anaphylaxis. Their prophylactic effectiveness in these situations is uncertain. [ 41 ]   Nebulized   salbutamol  may be effective for  bronchospasm  that does not resolve with epinephrine. [ 10 ]   Methylene blue  has been used in those not responsive to other measures due to its presumed effect of relaxing smooth muscle. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_871", "contents": "People prone to anaphylaxis are advised to have an allergy action plan. Parents are advised to inform schools of their children's allergies and what to do in case of an anaphylactic emergency. The action plan usually includes use of  epinephrine autoinjectors , the recommendation to wear a  medical alert bracelet , and counseling on avoidance of triggers. [ 52 ]   Immunotherapy  is available for certain triggers to prevent future episodes of anaphylaxis. A multi-year course of subcutaneous  desensitization  has been found effective against stinging insects, while oral desensitization is effective for many foods. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_872", "contents": "In those in whom the cause is known and prompt treatment is available, the prognosis is good. [ 53 ]  Even if the cause is unknown, if appropriate preventive medication is available, the prognosis is generally good. [ 15 ]  Usually death occurs due to either respiratory failure (typically involving  asphyxia ) or cardiovascular complications, such as  cardiovascular shock , [ 8 ] [ 10 ]  with 0.7\u201320% of cases causing death. [ 15 ] [ 19 ]  There have been cases of death occurring within minutes. [ 3 ]  Outcomes in those with exercise-induced anaphylaxis are typically good, with fewer and less severe episodes as people get older. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_873", "contents": "The number of people who get anaphylaxis is 4\u2013100 per 100,000 persons per year, [ 10 ] [ 54 ]  with a  lifetime risk  of 0.05\u20132%. [ 55 ]  About 30% of affected people get more than one attack. [ 54 ]  Exercise-induced anaphylaxis affects about 1 in 2000 young people. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_874", "contents": "Rates appear to be increasing: the numbers in the 1980s were approximately 20 per 100,000 per year, while in the 1990s it was 50 per 100,000 per year. [ 16 ]  The increase appears to be primarily for food-induced anaphylaxis. [ 56 ]  The risk is greatest in young people and females. [ 9 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_875", "contents": "Anaphylaxis leads to as many as 500\u20131,000 deaths per year (2.7 per million) in the United States, 20 deaths per year in the United Kingdom (0.33 per million), and 15 deaths per year in Australia (0.64 per million). [ 10 ]  Another estimate from the United States puts the death rate at 0.7 per million. [ 57 ]  Mortality rates have decreased between the 1970s and 2000s. [ 58 ]  In Australia, death from food-induced anaphylaxis occur primarily in women while deaths due to insect bites primarily occur in males. [ 10 ]  Death from anaphylaxis is most commonly triggered by medications. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_876", "contents": "The conditions of anaphylaxis has been known since ancient times. [ 42 ]  French physician  Fran\u00e7ois Magendie  had described how rabbits were killed by repeated injections of egg albumin in 1839. [ 59 ]  However, the phenomenon was discovered by two French physiologists  Charles Richet  and  Paul Portier . [ 60 ]  In 1901,  Albert I, Prince of Monaco  requested Richet and Portier join him on a scientific expedition around the French coast of the Atlantic Ocean, [ 61 ]  specifically to study on the toxin produced by cnidarians (like  jellyfish  and  sea anemones ). [ 60 ]  Richet and Portier boarded Albert's ship  Princesse Alice II  for ocean exploration to make collections of the marine animals. [ 62 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_877", "contents": "Richet and Portier extracted a toxin called hypnotoxin from their collection of jellyfish (but the real source was later identified as  Portuguese man o' war ) [ 63 ]  and sea anemone ( Actinia sulcata ). [ 64 ]  In their first experiment on the ship, they injected a dog with the toxin in an attempt to immunise the dog, which instead developed a severe reaction ( hypersensitivity ). In 1902, they repeated the injections in their laboratory and found that dogs normally tolerated the toxin at first injection, but on re-exposure, three weeks later with the same dose, they always developed fatal shock. They also found that the effect was not related to the doses of toxin used, as even small amounts in secondary injections were lethal. [ 64 ]  Thus, instead of inducing tolerance ( prophylaxis ) which they expected, they discovered effects of the toxin as deadly. [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_878", "contents": "In 1902, Richet introduced the term  aphylaxis  to describe the condition of lack of protection. He later changed the term to  anaphylaxis  on grounds of  euphony . [ 20 ]  The term is from the  Greek   \u1f00\u03bd\u03ac- ,  ana- , meaning \"against\", and  \u03c6\u03cd\u03bb\u03b1\u03be\u03b9\u03c2 ,  phylaxis , meaning \"protection\". [ 66 ]  On 15 February 1902, Richet and Portier jointly presented their findings before the  Societ\u00e9 de Biologie  in Paris. [ 67 ] [ 68 ]  The moment is regarded as the birth of allergy (the term invented by  Clemens von Pirquet  in 1906) study ( allergology ). [ 68 ]  Richet continued to study on the phenomenon and was eventually awarded the  Nobel Prize in Physiology or Medicine  for his work on anaphylaxis in 1913. [ 62 ] [ 69 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_879", "contents": "There are ongoing efforts to develop  sublingual  epinephrine to treat anaphylaxis. Trials of sublingual epinephrine, currently called AQST-108 (dipivefrin) and sponsored by Aquestive Therapeutics, are in  phase 1 trials  as of December 2021. [ 10 ] [ 70 ]   Subcutaneous injection  of the anti-IgE antibody  omalizumab  is being studied as a method of preventing recurrence, but it is not yet recommended. [ needs update ] [ 3 ] [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_880", "contents": "Anthrax  is an infection caused by the  bacterium   Bacillus anthracis  or  Bacillus cereus  biovar  anthracis . [ 2 ]  Infection typically occurs by  contact with the skin , inhalation, or intestinal absorption. [ 9 ]  Symptom onset occurs between one day and more than two months after the infection is contracted. [ 1 ]  The skin form presents with a small blister with surrounding swelling that often turns into a painless  ulcer  with a black center. [ 1 ]  The inhalation form presents with fever, chest pain, and  shortness of breath . [ 1 ]  The intestinal form presents with diarrhea (which may contain blood), abdominal pains, nausea, and vomiting. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_881", "contents": "According to the U.S.  Centers for Disease Control and Prevention , the first clinical descriptions of  cutaneous anthrax  were given by Maret in 1752 and Fournier in 1769. Before that, anthrax had been described only in historical accounts. The German scientist  Robert Koch  was the first to identify  Bacillus anthracis  as the bacterium that causes anthrax."}
+{"id": "WikiPedia_Pulmonology$$$corpus_882", "contents": "Anthrax is spread by contact with the bacterium's  spores , which often appear in infectious animal products. [ 10 ]  Contact is by breathing or eating or through an area of broken skin. [ 10 ]  It does not typically spread directly between people. [ 10 ]  Risk factors include people who work with animals or animal products, and military personnel. [ 3 ]  Diagnosis can be confirmed by finding antibodies or the toxin in the blood or by  culture  of a sample from the infected site. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_883", "contents": "Anthrax vaccination  is recommended for people at high risk of infection. [ 3 ]  Immunizing animals against anthrax is recommended in areas where previous infections have occurred. [ 10 ]  A two-month course of antibiotics such as  ciprofloxacin ,  levofloxacin  and  doxycycline  after exposure can also prevent infection. [ 5 ]  If infection occurs, treatment is with  antibiotics  and possibly  antitoxin . [ 6 ]  The type and number of antibiotics used depend on the type of infection. [ 5 ]  Antitoxin is recommended for those with widespread infection. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_884", "contents": "A rare disease, human anthrax is most common in Africa and central and southern Asia. [ 11 ]  It also occurs more regularly in  Southern Europe  than elsewhere on the continent and is uncommon in  Northern Europe  and North America. [ 12 ]  Globally, at least 2,000 cases occur a year, with about two cases a year in the United States. [ 8 ] [ 13 ]  Skin infections represent more than 95% of cases. [ 7 ]  Without treatment the risk of death from skin anthrax is 23.7%. [ 5 ]  For intestinal infection the risk of death is 25 to 75%, while respiratory anthrax has a mortality of 50 to 80%, even with treatment. [ 5 ] [ 7 ]  Until the 20th century anthrax infections killed hundreds of thousands of people and animals each year. [ 14 ]  In herbivorous animals infection occurs when they eat or breathe in the spores while grazing. [ 11 ]  Animals may become infected by killing and/or eating infected animals. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_885", "contents": "Several countries have  developed anthrax as a weapon . [ 7 ]  It has been used in biowarfare and bioterrorism since 1914. In 1975, the  Biological Weapons Convention  prohibited the \"development, production and stockpiling\" of biological weapons. It has since been used in bioterrorism. Likely delivery methods of weaponized anthrax include aerial dispersal or dispersal through livestock; notable bioterrorism uses include the  2001 anthrax attacks  and an incident in  1993 by the Aum Shinrikyo group ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_886", "contents": "The English name comes from  anthrax  ( \u1f04\u03bd\u03b8\u03c1\u03b1\u03be ), the  Greek  word for coal, [ 15 ] [ 16 ]  possibly having  Egyptian  etymology, [ 17 ]  because of the characteristic black skin  lesions  people with a cutaneous anthrax infection develop. The central black  eschar  surrounded by vivid red skin has long been recognised as typical of the disease. The first recorded use of the word \"anthrax\" in English is in a 1398 translation of  Bartholomaeus Anglicus 's work  De proprietatibus rerum  ( On the Properties of Things , 1240). [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_887", "contents": "Anthrax was historically known by a wide variety of names, indicating its symptoms, location, and groups considered most vulnerable to infection. They include Siberian plague,  Cumberland disease , charbon, splenic fever, malignant edema, woolsorter's disease and  la maladie de Bradford . [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_888", "contents": "Cutaneous anthrax, also known as hide-porter's disease, is when anthrax occurs on the skin. It is the most common (>90% of cases) and least dangerous form (low mortality with treatment, 23.7% mortality without). [ 20 ] [ 5 ]  Cutaneous anthrax presents as a  boil -like  skin lesion  that eventually forms an  ulcer  with a black center ( eschar ). The black eschar often shows up as a large, painless,  necrotic  ulcer (beginning as an irritating and itchy skin lesion or blister that is dark and usually concentrated as a black dot, somewhat resembling bread mold) at the site of infection. In general, cutaneous infections form within the site of spore penetration two to five days after exposure. Unlike  bruises  or most other lesions, cutaneous anthrax infections normally do not cause pain. Nearby lymph nodes may become infected, reddened, swollen, and painful. A scab forms over the lesion soon, and falls off in a few weeks. Complete recovery may take longer. [ 21 ]  Cutaneous anthrax is typically caused when  B. anthracis  spores enter through cuts on the skin. This form is found most commonly when humans handle infected animals and/or animal products. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_889", "contents": "In December 2009, an outbreak of anthrax occurred among injecting heroin users in the  Glasgow  and  Stirling  areas of Scotland, resulting in 14\u00a0deaths. [ 23 ]  It was the first documented non-occupational human anthrax outbreak in the UK since 1960. [ 23 ]  The source of the anthrax is believed to have been dilution of the heroin with  bone meal  in Afghanistan. [ 24 ]  Injected anthrax may have symptoms similar to cutaneous anthrax, with the exception of black areas, [ 25 ]  and may also cause infection deep into the muscle and spread faster. [ 26 ]  This can make it harder to recognise and treat."}
+{"id": "WikiPedia_Pulmonology$$$corpus_890", "contents": "Inhalation anthrax usually develops within a week after exposure, but may take up to 2 months. [ 27 ]  During the first few days of illness, most people have fever, chills, and fatigue. [ 27 ]  These symptoms may be accompanied by cough, shortness of breath, chest pain, and nausea or vomiting, making inhalation anthrax difficult to distinguish from  influenza  and  community-acquired pneumonia . [ 27 ]  This is often described as the prodromal period. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_891", "contents": "Over the next day or so, shortness of breath, cough, and chest pain become more common, and complaints not involving the chest such as nausea, vomiting, altered mental status, sweats, and headache develop in one-third or more of people. [ 27 ]  Upper respiratory tract symptoms occur in only a quarter of people, and muscle pains are rare. [ 27 ]  Altered mental status or shortness of breath generally brings people to healthcare and marks the fulminant phase of illness. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_892", "contents": "It infects the lymph nodes in the chest first, rather than the lungs themselves, a condition called hemorrhagic  mediastinitis , causing bloody fluid to accumulate in the chest cavity, thereby causing shortness of breath. The second (pneumonia) stage occurs when the infection spreads from the lymph nodes to the lungs. Symptoms of the second stage develop suddenly within hours or days after the first stage. Symptoms include high fever, extreme shortness of breath, shock, and rapid death within 48 hours in fatal cases. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_893", "contents": "Gastrointestinal  (GI) infection is most often caused by consuming anthrax-infected meat and is characterized by diarrhea, potentially with blood, abdominal pains, acute inflammation of the intestinal tract, and loss of appetite. [ 29 ]  Occasional  vomiting of blood  can occur. Lesions have been found in the intestines and in the mouth and throat. After the bacterium invades the gastrointestinal system, it spreads to the bloodstream and throughout the body, while continuing to make toxins. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_894", "contents": "Bacillus anthracis  is a rod-shaped,  Gram-positive , facultative anaerobe [ 31 ]  bacterium about 1 by 9\u00a0\u03bcm in size. [ 2 ]  It was shown to cause disease by  Robert Koch  in 1876 when he took a blood sample from an infected cow, isolated the bacteria, and put them into a mouse. [ 32 ]  The bacterium normally rests in spore form in the soil, and can survive for decades in this state. Herbivores are often infected while grazing, especially when eating rough, irritant, or spiky vegetation; the vegetation has been hypothesized to cause wounds within the gastrointestinal tract, permitting entry of the bacterial spores into the tissues. Once ingested or placed in an open wound, the bacteria begin multiplying inside the animal or human and typically kill the host within a few days or weeks. The spores germinate at the site of entry into the tissues and then spread by the circulation to the lymphatics, where the bacteria multiply. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_895", "contents": "The production of two powerful exotoxins and lethal toxin by the bacteria causes death. Veterinarians can often tell a possible anthrax-induced death by its sudden occurrence and the dark, nonclotting blood that oozes from the body orifices. Most anthrax bacteria inside the body after death are outcompeted and destroyed by anaerobic bacteria within minutes to hours  post mortem , but anthrax vegetative bacteria that escape the body via oozing blood or opening the carcass may form hardy spores. These vegetative bacteria are not contagious. [ 34 ]  One spore forms per vegetative bacterium. The triggers for spore formation are not known, but oxygen tension and lack of nutrients may play roles. Once formed, these spores are very hard to eradicate. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_896", "contents": "The infection of herbivores (and occasionally humans) by inhalation normally begins with inhaled spores being transported through the air passages into the tiny air sacs (alveoli) in the lungs. The spores are then picked up by scavenger cells ( macrophages ) in the lungs and transported through small vessels ( lymphatics ) to the  lymph nodes  in the central chest cavity ( mediastinum ). Damage caused by the anthrax spores and bacilli to the central chest cavity can cause chest pain and difficulty breathing. Once in the lymph nodes, the spores germinate into active bacilli that multiply and eventually burst the macrophages, releasing many more bacilli into the bloodstream to be transferred to the entire body. Once in the bloodstream, these bacilli release three proteins:  lethal factor , edema factor, and protective antigen. The three are not toxic by themselves, but their combination is incredibly lethal to humans. [ 35 ]  Protective antigen combines with these other two factors to form lethal toxin and edema toxin, respectively. These toxins are the primary agents of tissue destruction, bleeding, and death of the host. If antibiotics are administered too late, even if the antibiotics eradicate the bacteria, some hosts still die of toxemia because the toxins produced by the bacilli remain in their systems at lethal dose levels. [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_897", "contents": "Anthrax can enter the human body through the intestines (gastrointestinal), lungs (pulmonary), or skin (cutaneous), and causes distinct clinical symptoms based on its site of entry. [ 13 ]  Anthrax does not usually spread from an infected human to an uninfected human. [ 13 ]  If the disease is fatal to the person's body, its mass of anthrax bacilli becomes a potential source of infection to others and special precautions should be used to prevent further contamination. [ 13 ]  Pulmonary anthrax, if left untreated, is almost always fatal. [ 13 ]  Historically, pulmonary anthrax was called woolsorters' disease because it was an occupational hazard for  people who sorted wool . [ 37 ]  Today, this form of infection is extremely rare in industrialized nations. [ 37 ]  Cutaneous anthrax is the most common form of transmission but also the least dangerous of the three transmissions. [ 9 ]  Gastrointestinal anthrax is likely fatal if left untreated, but very rare. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_898", "contents": "The spores of anthrax are able to survive in harsh conditions for decades or even centuries. [ 38 ]  Such spores can be found on all continents, including Antarctica. [ 39 ]  Disturbed grave sites of infected animals have been known to cause infection after 70 years. [ 40 ]  In one such event, a young boy died from gastrointestinal anthrax due to the thawing of reindeer corpses from 75 years before contact. [ 41 ]  Anthrax spores traveled though groundwater used for drinking and caused tens of people to be hospitalized, largely children. [ 41 ]  Occupational exposure to infected animals or their products (such as skin, wool, and meat) is the usual pathway of exposure for humans. [ 42 ]  Workers exposed to dead animals and animal products are at the highest risk, especially in countries where anthrax is more common. [ 42 ]  Anthrax in  livestock  grazing on open range where they mix with wild animals still occasionally occurs in the U.S. and elsewhere. [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_899", "contents": "Many workers who deal with wool and animal hides are routinely exposed to low levels of anthrax spores, but most exposure levels are not sufficient to produce infection. [ 43 ]  A lethal infection is reported to result from inhalation of about 10,000\u201320,000 spores, though this dose varies among host species. [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_900", "contents": "The lethality of the anthrax disease is due to the bacterium's two principal virulence factors: the  poly-D-glutamic acid capsule , which protects the bacterium from phagocytosis by host neutrophils; and the tripartite protein toxin, called  anthrax toxin , consisting of protective  antigen  (PA),  edema  factor (EF), and lethal factor (LF). [ 44 ]  PA plus LF produces lethal toxin, and PA plus EF produces edema toxin. These toxins cause death and tissue swelling ( edema ), respectively.\nTo enter the cells, the edema and lethal factors use another protein produced by  B. anthracis  called protective antigen, which binds to two surface receptors on the host cell. A cell  protease  then cleaves PA into two fragments: PA 20  and PA 63 . PA 20  dissociates into the extracellular medium, playing no further role in the toxic cycle. PA 63  then oligomerizes with six other PA 63  fragments forming a heptameric ring-shaped structure named a prepore. Once in this shape, the complex can competitively bind up to three EFs or LFs, forming a resistant complex. [ 35 ]  Receptor-mediated endocytosis occurs next, providing the newly formed toxic complex access to the interior of the host cell. The acidified environment within the endosome triggers the heptamer to release the LF and/or EF into the cytosol. [ 45 ]  It is unknown how exactly the complex results in the death of the cell."}
+{"id": "WikiPedia_Pulmonology$$$corpus_901", "contents": "Edema factor is a  calmodulin -dependent  adenylate cyclase . Adenylate cyclase catalyzes the conversion of ATP into  cyclic AMP  (cAMP) and  pyrophosphate . The complexation of adenylate cyclase with  calmodulin  removes calmodulin from stimulating calcium-triggered signaling, thus inhibiting the immune response. [ 35 ]  To be specific, LF inactivates  neutrophils  (a type of phagocytic cell) by the process just described so they cannot phagocytose bacteria. Throughout history, lethal factor was presumed to cause macrophages to make  TNF-alpha  and  interleukin 1 beta  (IL1B). TNF-alpha is a  cytokine  whose primary role is to regulate immune cells, as well as to induce inflammation and  apoptosis  or programmed cell death. Interleukin 1 beta is another cytokine that also regulates inflammation and apoptosis. The overproduction of TNF-alpha and IL1B ultimately leads to  septic shock  and death. However, recent evidence indicates anthrax also targets endothelial cells that line serious cavities such as the  pericardial cavity ,  pleural cavity , and  peritoneal cavity , lymph vessels, and blood vessels, causing vascular leakage of fluid and cells, and ultimately  hypovolemic shock  and septic shock. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_902", "contents": "Various techniques may be used for the direct identification of  B. anthracis  in clinical material. Firstly, specimens may be  Gram stained .  Bacillus  spp. are quite large in size (3 to 4\u00a0\u03bcm long), they may grow in long chains, and they stain Gram-positive. To confirm the organism is  B. anthracis , rapid diagnostic techniques such as  polymerase chain reaction -based assays and  immunofluorescence microscopy  may be used. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_903", "contents": "All  Bacillus  species grow well on 5% sheep blood agar and other routine culture media. Polymyxin-lysozyme-EDTA-thallous acetate can be used to isolate  B. anthracis  from contaminated specimens, and bicarbonate agar is used as an identification method to induce capsule formation.  Bacillus  spp. usually grow within 24 hours of incubation at 35\u00a0\u00b0C, in ambient air (room temperature) or in 5% CO 2 . If bicarbonate agar is used for identification, then the medium must be incubated in 5% CO 2 .  B. anthracis  colonies are medium-large, gray, flat, and irregular with swirling projections, often referred to as having a \" medusa head \" appearance, and are not hemolytic on 5% sheep blood agar. The bacteria are not motile, susceptible to penicillin, and produce a wide zone of lecithinase on egg yolk agar. Confirmatory testing to identify  B. anthracis  includes gamma bacteriophage testing, indirect hemagglutination, and enzyme-linked immunosorbent assay to detect antibodies. [ 47 ]  The best confirmatory precipitation test for anthrax is the  Ascoli  test."}
+{"id": "WikiPedia_Pulmonology$$$corpus_904", "contents": "Precautions are taken to avoid contact with the skin and any fluids exuded through natural body openings of a deceased body that is suspected of harboring anthrax. [ 48 ]  The body should be put in strict quarantine. A blood sample is collected and sealed in a container and analyzed in an approved laboratory to ascertain if anthrax is the cause of death. The body should be sealed in an airtight body bag and incinerated to prevent the transmission of anthrax spores. Microscopic visualization of the encapsulated bacilli, usually in very large numbers, in a blood smear stained with polychrome methylene blue (McFadyean stain) is fully diagnostic, though the culture of the organism is still the gold standard for diagnosis. Full isolation of the body is important to prevent possible contamination of others. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_905", "contents": "Protective, impermeable clothing and equipment such as  rubber gloves , rubber apron, and rubber boots with no perforations are used when handling the body. No skin, especially if it has any wounds or scratches, should be exposed. Disposable personal protective equipment is preferable, but if not available, decontamination can be achieved by autoclaving. Used disposable equipment is burned and/or buried after use. All contaminated bedding or clothing is isolated in double plastic bags and treated as biohazard waste. [ 48 ]  Respiratory equipment capable of filtering small particles, such the US  National Institute for Occupational Safety and Health - and  Mine Safety and Health Administration -approved high-efficiency respirator, is worn. [ 49 ]  By addressing Anthrax from a One Health perspective, we can reduce the risks of transmission and better protect both human and animal populations. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_906", "contents": "The prevention of anthrax from the environmental sources like air, water, & soil is disinfection used by  effective microorganisms  through spraying, and  bokashi mudballs  mixed with effective microorganisms for the contaminated waterways."}
+{"id": "WikiPedia_Pulmonology$$$corpus_907", "contents": "Vaccines against anthrax for use in livestock and humans have had a prominent place in the history of medicine. The French scientist  Louis Pasteur  developed the first effective  vaccine  in 1881. [ 51 ] [ 52 ] [ 53 ]  Human anthrax vaccines were developed by the  Soviet Union  in the late 1930s and in the US and UK in the 1950s. The current FDA-approved US vaccine was formulated in the 1960s. [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_908", "contents": "Currently administered human anthrax vaccines include  acellular   subunit vaccine  (United States) and  live vaccine  (Russia) varieties. All currently used anthrax vaccines show considerable local and general  reactogenicity  ( erythema ,  induration ,  soreness ,  fever ) and serious adverse reactions occur in about 1% of recipients. [ 55 ]  The American product, BioThrax, is licensed by the FDA and was formerly administered in a six-dose primary series at 0, 2, 4 weeks and 6, 12, 18 months, with annual boosters to maintain immunity. In 2008, the FDA approved omitting the week-2 dose, resulting in the currently recommended five-dose series. [ 56 ]  This five-dose series is available to military personnel, scientists who work with anthrax and members of the public who do jobs which cause them to be at-risk. [ 57 ]  New second-generation vaccines currently being researched include  recombinant live vaccines  and  recombinant subunit vaccines . In the 20th century the use of a modern product ( BioThrax ) to protect American troops against the use of anthrax in  biological warfare  was controversial. [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_909", "contents": "Preventive antibiotics are recommended in those who have been exposed. [ 5 ]  Early detection of sources of anthrax infection can allow preventive measures to be taken. In response to the  anthrax attacks of October 2001 , the  United States Postal Service  (USPS) installed biodetection systems (BDSs) in their large-scale mail processing facilities. BDS response plans were formulated by the USPS in conjunction with local responders including fire, police, hospitals, and public health. Employees of these facilities have been educated about anthrax, response actions, and  prophylactic  medication. Because of the time delay inherent in getting final verification that anthrax has been used, prophylactic antibiotic treatment of possibly exposed personnel must be started as soon as possible. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_910", "contents": "Anthrax cannot be spread from person to person, except in the rare case of skin exudates from cutaneous anthrax. [ 59 ]  However, a person's clothing and body may be contaminated with anthrax spores. Effective decontamination of people can be accomplished by a thorough wash-down with  antimicrobial  soap and water. Wastewater is treated with bleach or another antimicrobial agent. [ 60 ]  Effective decontamination of articles can be accomplished by boiling them in water for 30 minutes or longer. Chlorine bleach is ineffective in destroying spores and vegetative cells on surfaces, though  formaldehyde  is effective. Burning clothing is very effective in destroying spores. After decontamination, there is no need to immunize, treat, or isolate contacts of persons ill with anthrax unless they were also exposed to the same source of infection. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_911", "contents": "Early antibiotic treatment of anthrax is essential; delay significantly lessens chances for survival. Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as  fluoroquinolones  ( ciprofloxacin ),  doxycycline ,  erythromycin ,  vancomycin , or  penicillin . FDA-approved agents include ciprofloxacin, doxycycline, and penicillin. [ 61 ]  In possible cases of pulmonary anthrax, early  antibiotic prophylaxis  treatment is crucial to prevent possible death. Many attempts have been made to develop new drugs against anthrax, but existing drugs are effective if treatment is started soon enough. [ 62 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_912", "contents": "In May 2009,  Human Genome Sciences  submitted a  biologic license application  (BLA, permission to market) for its new drug,  raxibacumab  (brand name ABthrax) intended for emergency treatment of inhaled anthrax. [ 63 ]  On 14 December 2012, the US Food and Drug Administration approved raxibacumab injection to treat inhalational anthrax. Raxibacumab is a  monoclonal antibody  that neutralizes toxins produced by  B. anthracis . [ 64 ]  In March 2016, FDA approved a second anthrax treatment using a monoclonal antibody which neutralizes the toxins produced by  B. anthracis .  Obiltoxaximab  is approved to treat inhalational anthrax in conjunction with appropriate  antibacterial  drugs, and for prevention when alternative therapies are not available or appropriate. [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_913", "contents": "Treatment of multi-drug resistant, antibody- or vaccine-resistant Anthrax is also possible.  Legler, et al.  [ 66 ]  showed that pegylated CapD (capsule depolymerase) could provide protection against 5 LD50 exposures to lethal Ames spores without the use of antibiotics, monoclonal antibodies, or vaccines.  The CapD enzyme removes the poly-D-glutamate (PDGA) capsular material from the bacteria, rendering it susceptible to the innate immune responses.  The unencapsulated bacteria can then be cleared."}
+{"id": "WikiPedia_Pulmonology$$$corpus_914", "contents": "Cutaneous anthrax is rarely fatal if treated, [ 69 ]  because the infection area is limited to the skin, preventing the  lethal factor ,  edema  factor, and protective  antigen  from entering and destroying a  vital organ . Without treatment, up to 20% of cutaneous skin infection cases progress to  toxemia  and death. [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_915", "contents": "Before 2001, fatality rates for inhalation anthrax were 90%; since then, they have fallen to 45%. [ 27 ]  People that progress to the  fulminant  phase of inhalational anthrax nearly always die, with one case study showing a death rate of 97%. [ 71 ]  Anthrax meningoencephalitis is also nearly always fatal. [ 72 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_916", "contents": "Gastrointestinal anthrax infections can be treated, but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences."}
+{"id": "WikiPedia_Pulmonology$$$corpus_917", "contents": "Injection anthrax is the rarest form of anthrax, and has only been seen to have occurred in a group of heroin injecting drug users. [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_918", "contents": "Anthrax, a bacterial disease caused by  Bacillus anthracis , can have devastating effects on animals. It primarily affects herbivores such as cattle, sheep, and goats, but a wide range of mammals, birds, and even humans can also be susceptible. Infection typically occurs through the ingestion of spores in contaminated soil or plants. Once inside the host, the spores transform into active bacteria, producing lethal toxins that lead to severe symptoms. Infected animals often exhibit high fever, rapid breathing, and convulsions, and they may succumb to the disease within hours to days. The presence of anthrax can pose significant challenges to livestock management and wildlife conservation efforts, making it a critical concern for both animal health and public health, as it can occasionally be transmitted to humans through contact with infected animals or contaminated products. Infected animals may stagger, have difficulty breathing, tremble, and finally collapse and die within a few hours. [ 73 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_919", "contents": "Globally, at least 2,000 cases occur a year. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_920", "contents": "The last fatal case of natural inhalational anthrax in the United States occurred in California in 1976, when a home weaver died after working with infected wool imported from Pakistan. To minimize the chance of spreading the disease, the body was transported to  UCLA  in a sealed plastic body bag within a sealed metal container for autopsy. [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_921", "contents": "Gastrointestinal anthrax is exceedingly rare in the United States, with only two cases on record. The first case was reported in 1942, according to the Centers for Disease Control and Prevention. [ 75 ]  During December 2009, the New Hampshire Department of Health and Human Services confirmed a case of gastrointestinal anthrax in an adult female. The  CDC  investigated the source and the possibility that it was contracted from an African drum recently used by the woman taking part in a  drum circle . [ 76 ]  The woman apparently inhaled anthrax, in spore form, from the hide of the drum. She became critically ill, but with gastrointestinal anthrax rather than inhaled anthrax, which made her unique in American medical history. The building where the infection took place was cleaned and reopened to the public and the woman recovered. The New Hampshire state epidemiologist, Jodie Dionne-Odom, stated \"It is a mystery. We really don't know why it happened.\" [ 77 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_922", "contents": "In 2007 two cases of cutaneous anthrax were reported in  Danbury, Connecticut . The case involved a maker of traditional African-style drums who was working with a goat hide purchased from a dealer in New York City which had been previously cleared by Customs. While the hide was being scraped, a spider bite led to the spores entering the bloodstream. His son also became infected. [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_923", "contents": "In July 2022, dozens of cattle in a nature park in  Lonjsko Polje , a flood plain by the  Sava  river, died of anthrax and 6 people have been hospitalized with light, skin-related symptoms. [ 79 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_924", "contents": "In November 2008, a drum maker in the United Kingdom who worked with untreated animal skins died from anthrax. [ 80 ]  In December 2009, an outbreak of anthrax occurred among heroin addicts in the  Glasgow  and  Stirling  areas of Scotland, resulting in 14\u00a0deaths. [ 23 ]  The source of the anthrax is believed to have been dilution of the heroin with  bone meal  in Afghanistan. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_925", "contents": "Robert Koch , a German physician and scientist, first identified the bacterium that caused the anthrax disease in 1875 in  Wollstein  (now Wolsztyn, Poland). [ 32 ] [ 81 ]  His pioneering work in the late 19th century was one of the first demonstrations that  diseases could be caused by microbes . In a groundbreaking series of experiments, he uncovered the lifecycle and means of transmission of anthrax. His experiments not only helped create an understanding of anthrax but also helped elucidate the role of microbes in causing illness at a time when debates still took place over  spontaneous generation  versus  cell theory . Koch went on to study the mechanisms of other diseases and won the 1905  Nobel Prize in Physiology or Medicine  for his discovery of the bacterium causing tuberculosis. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_926", "contents": "Although Koch arguably made the greatest theoretical contribution to understanding anthrax, other researchers were more concerned with the practical questions of how to prevent the disease. In Britain, where anthrax affected workers in the wool,  worsted ,  hides , and  tanning  industries, it was viewed with fear.  John Henry Bell , a doctor born & based in  Bradford , first made the link between the mysterious and deadly \"woolsorter's disease\" and anthrax, showing in 1878 that they were one and the same. [ 83 ]  In the early 20th century,  Friederich Wilhelm Eurich , the  German   bacteriologist  who settled in Bradford with his family as a child, carried out important research for the local Anthrax Investigation Board. Eurich also made valuable contributions to a  Home Office  Departmental Committee of Inquiry, established in 1913 to address the continuing problem of industrial anthrax. [ 84 ]  His work in this capacity, much of it collaboration with the factory inspector  G. Elmhirst Duckering , led directly to the  Anthrax Prevention Act  (1919)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_927", "contents": "Anthrax posed a major economic challenge in  France  and elsewhere during the 19th century. Horses, cattle, and sheep were particularly vulnerable, and national funds were set aside to investigate the production of a  vaccine . French scientist  Louis Pasteur  was charged with the production of a vaccine, following his successful work in developing methods that helped to protect the important wine and silk industries. [ 85 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_928", "contents": "In May 1881, Pasteur \u2013 in collaboration with his assistants  Jean-Joseph Henri Toussaint ,  \u00c9mile Roux  and others \u2013 performed a public experiment at  Pouilly-le-Fort  to demonstrate his concept of vaccination. He prepared two groups of 25  sheep , one  goat , and several  cattle . The animals of one group were twice injected with an anthrax vaccine prepared by Pasteur, at an interval of 15 days; the control group was left unvaccinated. Thirty days after the first injection, both groups were injected with a culture of live anthrax bacteria. All the animals in the unvaccinated group died, while all of the animals in the vaccinated group survived. [ 86 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_929", "contents": "After this apparent triumph, which was widely reported in the local, national, and international press, Pasteur made strenuous efforts to export the vaccine beyond France. He used his celebrity status to establish Pasteur Institutes across Europe and Asia, and his nephew,  Adrien Loir , travelled to  Australia  in 1888 to try to introduce the vaccine to combat anthrax in  New South Wales . [ 87 ]  Ultimately, the vaccine was unsuccessful in the challenging climate of rural Australia, and it was soon superseded by a more robust version developed by local researchers  John Gunn  and  John McGarvie Smith . [ 88 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_930", "contents": "The  human vaccine for anthrax  became available in 1954. This was a cell-free vaccine instead of the live-cell Pasteur-style vaccine used for veterinary purposes. An improved cell-free vaccine became available in 1970. [ 89 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_931", "contents": "Anthrax spores can survive for very long periods of time in the environment after release. Chemical methods for cleaning anthrax-contaminated sites or materials may use  oxidizing agents  such as  peroxides ,  ethylene oxide , Sandia Foam, [ 93 ]  chlorine dioxide (used in the  Hart Senate Office Building ), [ 94 ]  peracetic acid, ozone gas, hypochlorous acid, sodium persulfate, and liquid bleach products containing sodium hypochlorite. Nonoxidizing agents shown to be effective for anthrax decontamination include methyl bromide, formaldehyde, and metam sodium. These agents destroy bacterial spores. All of the aforementioned anthrax decontamination technologies have been demonstrated to be effective in laboratory tests conducted by the US EPA or others. [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_932", "contents": "Decontamination techniques for  Bacillus anthracis  spores are affected by the material with which the spores are associated, environmental factors such as temperature and humidity, and microbiological factors such as the spore species, anthracis strain, and test methods used. [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_933", "contents": "A bleach solution for treating hard surfaces has been approved by the EPA. [ 97 ]   Chlorine dioxide  has emerged as the preferred biocide against anthrax-contaminated sites, having been employed in the treatment of numerous government buildings over the past decade. [ 98 ]  Its chief drawback is the need for  in situ  processes to have the reactant on demand."}
+{"id": "WikiPedia_Pulmonology$$$corpus_934", "contents": "To speed the process, trace amounts of a nontoxic  catalyst  composed of iron and tetroamido macrocyclic  ligands  are combined with  sodium carbonate  and  bicarbonate  and converted into a spray. The spray formula is applied to an infested area and is followed by another spray containing  tert-butyl hydroperoxide . [ 99 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_935", "contents": "Using the catalyst method, complete destruction of all anthrax spores can be achieved in under 30 minutes. [ 99 ]  A standard catalyst-free spray destroys fewer than half the spores in the same amount of time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_936", "contents": "Cleanups at a Senate Office Building, several contaminated postal facilities, and other US government and private office buildings, a collaborative effort headed by the  Environmental Protection Agency [ 100 ]  showed decontamination to be possible, but time-consuming and costly. Clearing the Senate Office Building of anthrax spores cost $27\u00a0million, according to the Government Accountability Office. Cleaning the Brentwood postal facility in Washington cost $130\u00a0million and took 26 months. Since then, newer and less costly methods have been developed. [ 101 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_937", "contents": "Cleanup of anthrax-contaminated areas on ranches and in the wild is much more problematic. Carcasses may be burned, [ 102 ]  though often 3 days are needed to burn a large carcass and this is not feasible in areas with little wood. Carcasses may also be buried, though the burying of large animals deeply enough to prevent resurfacing of spores requires much manpower and expensive tools. Carcasses have been soaked in formaldehyde to kill spores, though this has environmental contamination issues. Block burning of vegetation in large areas enclosing an anthrax outbreak has been tried; this, while environmentally destructive, causes healthy animals to move away from an area with carcasses in search of fresh grass. Some wildlife workers have experimented with covering fresh anthrax carcasses with shadecloth and heavy objects. This prevents some scavengers from opening the carcasses, thus allowing the putrefactive bacteria within the carcass to kill the vegetative  B. anthracis  cells and preventing sporulation. This method also has drawbacks, as scavengers such as hyenas are capable of infiltrating almost any exclosure. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_938", "contents": "The experimental site at  Gruinard Island  is said to have been decontaminated with a mixture of formaldehyde and seawater by the Ministry of Defence. [ 103 ]  It is not clear whether similar treatments had been applied to US test sites."}
+{"id": "WikiPedia_Pulmonology$$$corpus_939", "contents": "Anthrax spores have been used as a  biological warfare  weapon. Its first modern incidence occurred when Nordic rebels, supplied by the  German General Staff , used anthrax with unknown results against the  Imperial Russian Army  in Finland in 1916. [ 104 ]  Anthrax was first tested as a biological warfare agent by  Unit 731  of the Japanese Kwantung Army in  Manchuria  during the 1930s; some of this testing involved intentional infection of prisoners of war, thousands of whom died. Anthrax, designated at the time as Agent N, was also investigated by the Allies in the 1940s. [ 105 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_940", "contents": "In 1942, British scientists at  Porton Down  began research on  Operation Vegetarian , an ultimately unused  biowarfare   military operation plan  which called for animal feed pellets containing  linseed  infected with anthrax spores of the  Vollum-14578 strain  to be dropped by air over the countryside of  Nazi Germany . The pellets would be eaten by cattle, which would in turn be eaten by the human population and as such severely disrupt the German war effort. In the same year, bioweapons tests were carried out on the uninhabited  Gruinard Island  in the  Scottish Highlands , with Porton Down scientists studying the effect of anthrax on the island's population of sheep. Ultimately, five million pellets were created, though plans to drop them over Germany using  Royal Air Force  bombers in 1944 were scrapped after the success of  Operation Overlord  and the subsequent Allied liberation of France. All pellets were destroyed using incinerators in 1945. [ 106 ] [ 107 ] [ 108 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_941", "contents": "Weaponized anthrax was part of the US stockpile prior to 1972, when the United States signed the  Biological Weapons Convention . [ 109 ]  President  Nixon  ordered the dismantling of US biowarfare programs in 1969 and the destruction of all existing stockpiles of bioweapons. In 1978\u201379, the  Rhodesian  government used anthrax against cattle and humans during its campaign against rebels. [ 110 ]  The Soviet Union created and stored 100 to 200 tons of anthrax spores at  Kantubek  on  Vozrozhdeniya Island ; they were abandoned in 1992 and destroyed in 2002. [ 111 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_942", "contents": "American military  and  British Army  personnel are no longer routinely vaccinated against anthrax prior to active service in places where biological attacks are considered a threat. [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_943", "contents": "Despite signing the 1972 agreement to end bioweapon production, the government of the Soviet Union had an active bioweapons program that included the production of hundreds of tons of anthrax after this period. On 2 April 1979, some of the over one million people living in Sverdlovsk (now called  Ekaterinburg, Russia ), about 1,370 kilometres (850\u00a0mi) east of Moscow, were exposed to an  accidental release of anthrax  from a biological weapons complex located near there. At least 94 people were infected, of whom at least 68 died. One victim died four days after the release, 10 over an eight-day period at the peak of the deaths, and the last six weeks later. Extensive cleanup, vaccinations, and medical interventions managed to save about 30 of the victims. [ 112 ]  Extensive cover-ups and destruction of records by the  KGB  continued from 1979 until Russian President  Boris Yeltsin  admitted this anthrax accident in 1992.  Jeanne Guillemin  reported in 1999 that a combined Russian and United States team investigated the accident in 1992. [ 112 ] [ 113 ] [ 114 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_944", "contents": "Nearly all of the night-shift workers of a ceramics plant directly across the street from the biological facility (compound 19) became infected, and most died. Since most were men, some  NATO  governments suspected the Soviet Union had developed a sex-specific weapon. [ 115 ]  The government blamed the outbreak on the consumption of anthrax-tainted meat, and ordered the confiscation of all uninspected meat that entered the city. They also ordered all  stray dogs  to be shot and people not have contact with sick animals. Also, a voluntary evacuation and anthrax vaccination program was established for people from 18 to 55. [ 116 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_945", "contents": "To support the  cover-up  story, Soviet medical and legal journals published articles about an outbreak in livestock that caused gastrointestinal anthrax in people having consumed infected meat, and cutaneous anthrax in people having come into contact with the animals. All medical and public health records were confiscated by the KGB. [ 116 ]  In addition to the medical problems the outbreak caused, it also prompted Western countries to be more suspicious of a covert Soviet bioweapons program and to increase their surveillance of suspected sites. In 1986, the US government was allowed to investigate the incident, and concluded the exposure was from aerosol anthrax from a military weapons facility. [ 117 ]  In 1992, President Yeltsin admitted he was \"absolutely certain\" that \"rumors\" about the Soviet Union violating the 1972 Bioweapons Treaty were true. The Soviet Union, like the US and UK, had agreed to submit information to the UN about their bioweapons programs, but omitted known facilities and never acknowledged their weapons program. [ 115 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_946", "contents": "In theory, anthrax spores can be cultivated with minimal special equipment and a first-year collegiate  microbiological  education. [ 118 ] \nTo make large amounts of an  aerosol  form of anthrax suitable for biological warfare requires extensive practical knowledge, training, and highly advanced equipment. [ 119 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_947", "contents": "Concentrated anthrax spores were used for bioterrorism in the  2001 anthrax attacks  in the United States, delivered by mailing postal letters containing the spores. [ 120 ]  The letters were sent to several news media offices and two Democratic senators:  Tom Daschle  of South Dakota and  Patrick Leahy  of Vermont. As a result, 22 were infected and five died. [ 35 ]  Only a few grams of material were used in these attacks and in August 2008, the US Department of Justice announced they believed that  Bruce Ivins , a senior biodefense researcher employed by the United States government, was responsible. [ 121 ]  These events also spawned many  anthrax hoaxes ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_948", "contents": "Due to these events, the US Postal Service installed  biohazard detection systems  at its major distribution centers to actively scan for anthrax being transported through the mail. [ 122 ]  As of 2020, no positive alerts by these systems have occurred. [ 123 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_949", "contents": "In response to the postal anthrax attacks and hoaxes, the United States Postal Service sterilized some mail using gamma  irradiation  and treatment with a proprietary  enzyme  formula supplied by Sipco Industries. [ 124 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_950", "contents": "A scientific experiment performed by a high school student, later published in the  Journal of Medical Toxicology , suggested a domestic  electric iron  at its hottest setting (at least 400\u00a0\u00b0F (204\u00a0\u00b0C)) used for at least 5 minutes should destroy all anthrax spores in a common postal envelope. [ 125 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_951", "contents": "Anthrax is especially rare in dogs and cats, as is evidenced by a single reported case in the United States in 2001. [ 126 ]  Anthrax outbreaks occur in some wild animal populations with some regularity. [ 127 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_952", "contents": "Russian researchers estimate arctic  permafrost  contains around 1.5\u00a0million anthrax-infected reindeer carcasses, and the spores may survive in the permafrost for 105 years. [ 128 ]  A risk exists that  global warming in the Arctic  can thaw the permafrost, releasing anthrax spores in the carcasses. In 2016, an anthrax outbreak in reindeer was linked to a 75-year-old carcass that defrosted during a heat wave. [ 129 ] [ 130 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_953", "contents": "Asthma  is a common  long-term   inflammatory  disease of the  airways  of the  lungs . [ 4 ]  Asthma occurs when  allergens ,  pollen , dust, or other particles, are inhaled into the lungs, causing the bronchioles to constrict and produce mucus, which then restricts  oxygen  flow to the  alveoli . It is characterized by variable and recurring symptoms, reversible  airflow obstruction , and easily triggered  bronchospasms . [ 9 ] [ 10 ]  Symptoms include episodes of  wheezing ,  coughing , chest tightness, and  shortness of breath . [ 3 ]  These may occur a few times a day or a few times per week. [ 4 ]  Depending on the person, asthma symptoms may become worse at night or with exercise. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_954", "contents": "Asthma is thought to be caused by a combination of  genetic  and  environmental factors . [ 3 ]  Environmental factors include exposure to  air pollution  and  allergens . [ 4 ]  Other potential triggers include medications such as  aspirin  and  beta blockers . [ 4 ]  Diagnosis is usually based on the pattern of symptoms, response to therapy over time, and  spirometry  lung function testing. [ 5 ]  Asthma is classified according to the frequency of symptoms of  forced expiratory volume in one second  (FEV 1 ), and  peak expiratory flow rate . [ 11 ]  It may also be classified as  atopic  or non-atopic, where atopy refers to a predisposition toward developing a  type 1 hypersensitivity  reaction. [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_955", "contents": "There is no known cure for asthma, but it can be controlled. [ 4 ]  Symptoms can be prevented by avoiding triggers, such as  allergens  and respiratory  irritants , and suppressed with the use of inhaled  corticosteroids . [ 6 ] [ 14 ]   Long-acting beta agonists  (LABA) or  antileukotriene agents  may be used in addition to inhaled corticosteroids if asthma symptoms remain uncontrolled. [ 15 ] [ 16 ]  Treatment of rapidly worsening symptoms is usually with an inhaled short-acting  beta 2  agonist  such as  salbutamol  and corticosteroids taken by mouth. [ 7 ]  In very severe cases, intravenous corticosteroids,  magnesium sulfate , and hospitalization may be required. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_956", "contents": "In 2019 asthma affected approximately 262 million people and caused approximately 461,000 deaths. [ 8 ]  Most of the deaths occurred in the  developing world . [ 4 ]  Asthma often begins in childhood, [ 4 ]  and the rates have increased significantly since the 1960s. [ 18 ]  Asthma was recognized as early as  Ancient Egypt . [ 19 ]  The word  asthma  is from the Greek  \u1f06\u03c3\u03b8\u03bc\u03b1 ,  \u00e2sthma , which means 'panting'. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_957", "contents": "Asthma is characterized by recurrent episodes of  wheezing ,  shortness of breath ,  chest tightness , and  coughing . [ 21 ]   Sputum  may be produced from the lung by coughing but is often hard to bring up. [ 22 ]  During recovery from an  asthma attack (exacerbation) , the sputum may appear  pus-like  due to high levels of white blood cells called  eosinophils . [ 23 ]  Symptoms are usually worse at night and in the early morning or in response to exercise or cold air. [ 24 ]  Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may react frequently and readily and experience persistent symptoms. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_958", "contents": "A number of other health conditions occur more frequently in people with asthma, including  gastroesophageal reflux disease  (GERD),  rhinosinusitis , and  obstructive sleep apnea . [ 26 ]  Psychological disorders are also more common, [ 27 ]  with  anxiety disorders  occurring in between 16 and 52% and  mood disorders  in 14\u201341%. [ 28 ]  It is not known whether asthma causes psychological problems or psychological problems lead to asthma. [ 29 ]  Current asthma, but not former asthma, is associated with increased all-cause mortality, heart disease mortality, and chronic lower respiratory tract disease mortality. [ 30 ]  Asthma, particularly severe asthma, is strongly associated with development of chronic obstructive pulmonary disease (COPD). [ 31 ] [ 32 ] [ 33 ]  Those with asthma, especially if it is poorly controlled, are at increased risk for  radiocontrast  reactions. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_959", "contents": "Cavities  occur more often in people with asthma. [ 35 ]  This may be related to the effect of  beta 2 -adrenergic agonists  decreasing saliva. [ 36 ]  These medications may also increase the risk of  dental erosions . [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_960", "contents": "Asthma is caused by a combination of complex and incompletely understood environmental and genetic interactions. [ 37 ] [ 38 ]  These influence both its severity and its responsiveness to treatment. [ 39 ]  It is believed that the recent increased rates of asthma are due to changing  epigenetics  ( heritable  factors other than those related to the  DNA sequence ) and a changing living environment. [ 40 ]  Asthma that starts before the age of 12 years old is more likely due to genetic influence, while onset after age 12 is more likely due to environmental influence. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_961", "contents": "Many environmental factors have been associated with asthma's development and exacerbation, including allergens, air pollution, and other environmental chemicals. [ 42 ]  There are some substances that are known to cause asthma in exposed people and they are called  asthmagens . Some common asthmagens include ammonia, latex, pesticides, solder and welding fumes, metal or wood dusts, spraying of isocyanate paint in vehicle repair, formaldehyde, glutaraldehyde, anhydrides, glues, dyes, metal working fluids, oil mists, moulds. [ 43 ] [ 44 ]   Smoking during pregnancy  and after delivery is associated with a greater risk of asthma-like symptoms. [ 45 ]  Low  air quality  from environmental factors such as  traffic pollution  or high  ozone  levels [ 46 ]  has been associated with both asthma development and increased asthma severity. [ 47 ]  Over half of cases in children in the United States occur in areas when air quality is below the  EPA  standards. [ 48 ]  Low air quality is more common in  low-income  and minority communities. [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_962", "contents": "Exposure to indoor  volatile organic compounds  may be a trigger for asthma;  formaldehyde  exposure, for example, has a positive association. [ 50 ]   Phthalates  in certain types of  PVC  are associated with asthma in both children and adults. [ 51 ] [ 52 ]  While exposure to  pesticides  is linked to the development of asthma, a cause and effect relationship has yet to be established. [ 53 ] [ 54 ]  A  meta-analysis  concluded gas stoves are a major risk factor for asthma, finding around one in eight cases in the U.S. could be attributed to these. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_963", "contents": "The majority of the evidence does not support a causal role between  paracetamol  (acetaminophen) or antibiotic use and asthma. [ 56 ] [ 57 ]  A 2014 systematic review found that the association between paracetamol use and asthma disappeared when respiratory infections were taken into account. [ 58 ]  Maternal  psychological stress  during pregnancy is a risk factor for the child to develop asthma. [ 59 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_964", "contents": "Asthma is associated with exposure to indoor allergens. [ 60 ]  Common indoor allergens include  dust mites ,  cockroaches ,  animal dander  (fragments of fur or feathers), and mould. [ 61 ] [ 62 ]  Efforts to decrease dust mites have been found to be ineffective on symptoms in sensitized subjects. [ 63 ] [ 64 ]  Weak evidence suggests that efforts to decrease mould by repairing buildings may help improve asthma symptoms in adults. [ 65 ]  Certain viral respiratory infections, such as  respiratory syncytial virus  and  rhinovirus , [ 20 ]  may increase the risk of developing asthma when acquired as young children. [ 66 ]  Certain other infections, however, may decrease the risk. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_965", "contents": "The  hygiene hypothesis  attempts to explain the increased rates of asthma worldwide as a direct and unintended result of reduced exposure, during childhood, to non-pathogenic bacteria and viruses. [ 67 ] [ 68 ]  It has been proposed that the reduced exposure to bacteria and viruses is due, in part, to increased cleanliness and decreased family size in modern societies. [ 69 ]  Exposure to bacterial  endotoxin  in early childhood may prevent the development of asthma, but exposure at an older age may provoke bronchoconstriction. [ 70 ]  Evidence supporting the hygiene hypothesis includes lower rates of asthma on farms and in households with pets. [ 69 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_966", "contents": "Use of  antibiotics  in early life has been linked to the development of asthma. [ 71 ]  Also, delivery via  caesarean section  is associated with an increased risk (estimated at 20\u201380%) of asthma\u00a0\u2013 this increased risk is attributed to the lack of healthy bacterial colonization that the newborn would have acquired from passage through the birth canal. [ 72 ] [ 73 ]  There is a link between asthma and the degree of affluence which may be related to the hygiene hypothesis as less affluent individuals often have more exposure to bacteria and viruses. [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_967", "contents": "Family history is a risk factor for asthma, with many different genes being implicated. [ 76 ]  If one identical twin is affected, the probability of the other having the disease is approximately 25%. [ 76 ]  By the end of 2005, 25 genes had been associated with asthma in six or more separate populations, including  GSTM1 ,  IL10 ,  CTLA-4 ,  SPINK5 ,  LTC4S ,  IL4R  and  ADAM33 , among others. [ 77 ]  Many of these genes are related to the immune system or modulating inflammation. Even among this list of genes supported by highly replicated studies, results have not been consistent among all populations tested. [ 77 ]  In 2006 over 100  genes  were associated with asthma in one  genetic association  study alone; [ 77 ]  more continue to be found. [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_968", "contents": "Some genetic variants may only cause asthma when they are combined with specific environmental exposures. [ 37 ]  An example is a specific  single nucleotide polymorphism  in the  CD14  region and exposure to  endotoxin  (a bacterial product). Endotoxin exposure can come from several environmental sources including tobacco smoke, dogs, and farms. Risk for asthma, then, is determined by both a person's genetics and the level of endotoxin exposure. [ 75 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_969", "contents": "A triad of  atopic eczema ,  allergic rhinitis  and asthma is called atopy. [ 79 ]  The strongest risk factor for developing asthma is a history of  atopic disease ; [ 66 ]  with asthma occurring at a much greater rate in those who have either  eczema  or  hay fever . [ 80 ]  Asthma has been associated with  eosinophilic granulomatosis with polyangiitis  (formerly known as Churg\u2013Strauss syndrome), an autoimmune disease and  vasculitis . [ 81 ]  Individuals with certain types of  urticaria  may also experience symptoms of asthma. [ 79 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_970", "contents": "There is a correlation between  obesity  and the risk of asthma with both having increased in recent years. [ 82 ] [ 83 ]  Several factors may be at play including decreased respiratory function due to a buildup of fat and the fact that adipose tissue leads to a pro-inflammatory state. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_971", "contents": "Beta blocker  medications such as  propranolol  can trigger asthma in those who are susceptible. [ 85 ]   Cardioselective beta-blockers , however, appear safe in those with mild or moderate disease. [ 86 ] [ 87 ]  Other medications that can cause problems in asthmatics are  angiotensin-converting enzyme inhibitors ,  aspirin , and  NSAIDs . [ 88 ]  Use of acid-suppressing medication ( proton pump inhibitors  and  H2 blockers ) during pregnancy is associated with an increased risk of asthma in the child. [ 89 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_972", "contents": "Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different individuals react to various factors in different ways. [ 90 ]  Most individuals can develop severe exacerbation from a number of triggering agents. [ 90 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_973", "contents": "Home factors that can lead to exacerbation of asthma include  dust , animal  dander  (especially cat and dog hair), cockroach  allergens  and  mold . [ 90 ] [ 91 ]   Perfumes  are a common cause of acute attacks in women and children. Both  viral  and bacterial  infections  of the upper respiratory tract can worsen the disease. [ 90 ]  Psychological  stress  may worsen symptoms\u00a0\u2013 it is thought that stress alters the immune system and thus increases the airway inflammatory response to allergens and irritants. [ 47 ] [ 92 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_974", "contents": "Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school. This might reflect a combination of factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. There is limited evidence to guide possible approaches to reducing autumn exacerbations, but while costly, seasonal  omalizumab  treatment from four to six weeks before school return may reduce autumn asthma exacerbations. [ 93 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_975", "contents": "Asthma is the result of chronic  inflammation  of the  conducting zone  of the airways (most especially the  bronchi  and  bronchioles ), which subsequently results in increased contractability of the surrounding  smooth muscles . This among other factors leads to bouts of narrowing of the airway and the classic symptoms of wheezing. The narrowing is typically reversible with or without treatment. Occasionally the airways themselves change. [ 21 ]  Typical changes in the airways include an increase in  eosinophils  and thickening of the  lamina reticularis . Chronically the airways' smooth muscle may increase in size along with an increase in the numbers of mucous glands. Other cell types involved include  T lymphocytes ,  macrophages , and  neutrophils . There may also be involvement of other components of the  immune system , including  cytokines ,  chemokines ,  histamine , and  leukotrienes  among others. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_976", "contents": "While asthma is a well-recognized condition, there is not one universal agreed-upon definition. [ 20 ]  It is defined by the  Global Initiative for Asthma  as \"a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment\". [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_977", "contents": "There is currently no precise test for the diagnosis, which is typically based on the pattern of symptoms and response to therapy over time. [ 5 ] [ 20 ]  Asthma may be suspected if there is a history of recurrent wheezing, coughing or difficulty breathing and these symptoms occur or worsen due to exercise, viral infections, allergens or air pollution. [ 94 ]   Spirometry  is then used to confirm the diagnosis. [ 94 ]  In children under the age of six the diagnosis is more difficult as they are too young for spirometry. [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_978", "contents": "Spirometry  is recommended to aid in diagnosis and management. [ 96 ] [ 97 ]  It is the single best test for asthma. If the  FEV 1  measured by this technique improves more than 12% and increases by at least 200 millilitres following administration of a  bronchodilator  such as  salbutamol , this is supportive of the diagnosis. It  however may be normal in those with a history of mild asthma, not currently acting up. [ 20 ]  As  caffeine  is a bronchodilator in people with asthma, the use of caffeine before a lung function test may interfere with the results. [ 98 ]   Single-breath diffusing capacity  can help differentiate asthma from  COPD . [ 20 ]  It is reasonable to perform spirometry every one or two years to follow how well a person's asthma is controlled. [ 99 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_979", "contents": "The  methacholine challenge  involves the inhalation of increasing concentrations of a substance that causes airway narrowing in those predisposed. If negative it means that a person does not have asthma; if positive, however, it is not specific for the disease. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_980", "contents": "Other supportive evidence includes: a \u226520% difference in  peak expiratory flow rate  on at least three days in a week for at least two weeks, a \u226520% improvement of peak flow following treatment with either salbutamol, inhaled corticosteroids or prednisone, or a \u226520% decrease in peak flow following exposure to a trigger. [ 100 ]  Testing peak expiratory flow is more variable than spirometry, however, and thus not recommended for routine diagnosis. It may be useful for daily self-monitoring in those with moderate to severe disease and for checking the effectiveness of new medications. It may also be helpful in guiding treatment in those with acute exacerbations. [ 101 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_981", "contents": "Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in one second (FEV 1 ), and  peak expiratory flow rate . [ 11 ]  Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic), based on whether symptoms are precipitated by allergens (atopic) or not (non-atopic). [ 12 ]  While asthma is classified based on severity, at the moment there is no clear method for classifying different subgroups of asthma beyond this system. [ 102 ]  Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research. [ 102 ]  Recently, asthma has been classified based on whether it is associated with type 2 or non\u2013type 2 inflammation. This approach to immunologic classification is driven by a developing understanding of the underlying immune processes and by the development of therapeutic approaches that target type 2 inflammation. [ 103 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_982", "contents": "Although asthma is a chronic  obstructive  condition, it is not considered as a part of  chronic obstructive pulmonary disease , as this term refers specifically to combinations of disease that are irreversible such as  bronchiectasis  and  emphysema . [ 104 ]  Unlike these diseases, the airway obstruction in asthma is usually reversible; however, if left untreated, the chronic inflammation from asthma can lead the lungs to become irreversibly obstructed due to airway remodelling. [ 105 ]  In contrast to emphysema, asthma affects the bronchi, not the  alveoli . [ 106 ]  The combination of asthma with a component of irreversible airway obstruction has been termed the  asthma-chronic obstructive disease (COPD) overlap syndrome (ACOS) . Compared to other people with \"pure\" asthma or COPD, people with ACOS exhibit increased morbidity, mortality and possibly more comorbidities. [ 107 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_983", "contents": "An acute asthma exacerbation is commonly referred to as an  asthma attack . The classic symptoms are  shortness of breath ,  wheezing , and  chest tightness . [ 20 ]  The wheezing is most often when breathing out. [ 109 ]  While these are the primary symptoms of asthma, [ 110 ]  some people present primarily with  coughing , and in severe cases, air motion may be significantly impaired such that no wheezing is heard. [ 108 ]  In children,  chest pain  is often present. [ 111 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_984", "contents": "Signs occurring during an asthma attack include the use of accessory  muscles  of respiration ( sternocleidomastoid  and  scalene muscles  of the neck), there may be a  paradoxical pulse  (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest. [ 112 ]  A  blue colour  of the skin and nails may occur from lack of oxygen. [ 113 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_985", "contents": "In a mild exacerbation the  peak expiratory flow rate  (PEFR) is \u2265200\u00a0L/min, or \u226550% of the predicted best. [ 114 ]  Moderate is defined as between 80 and 200\u00a0L/min, or 25% and 50% of the predicted best, while severe is defined as \u2264\u00a080 L/min, or \u226425% of the predicted best. [ 114 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_986", "contents": "Acute severe asthma , previously known as status asthmaticus, is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and corticosteroids. [ 115 ]  Half of cases are due to infections with others caused by allergen, air pollution, or insufficient or inappropriate medication use. [ 115 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_987", "contents": "Brittle asthma  is a kind of asthma distinguishable by recurrent, severe attacks. [ 108 ]  Type 1 brittle asthma is a disease with wide peak flow variability, despite intense medication. Type 2 brittle asthma is background well-controlled asthma with sudden severe exacerbations. [ 108 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_988", "contents": "Exercise can trigger  bronchoconstriction  both in people with or without asthma. [ 116 ]  It occurs in most people with asthma and up to 20% of people without asthma. [ 116 ]  Exercise-induced bronchoconstriction is common in professional athletes. The highest rates are among cyclists (up to 45%), swimmers, and cross-country skiers. [ 117 ]  While it may occur with any weather conditions, it is more common when it is dry and cold. [ 118 ]  Inhaled beta 2  agonists do not appear to improve athletic performance among those without asthma; [ 119 ]  however, oral doses may improve endurance and strength. [ 120 ] [ 121 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_989", "contents": "Asthma as a result of (or worsened by) workplace exposures is a commonly reported  occupational disease . [ 122 ]  Many cases, however, are not reported or recognized as such. [ 123 ] [ 124 ]  It is estimated that 5\u201325% of asthma cases in adults are work-related. A few hundred different agents have been implicated, with the most common being  isocyanates , grain and wood dust,  colophony ,  soldering flux ,  latex , animals, and  aldehydes . The employment associated with the highest risk of problems include those who  spray paint , bakers and those who process food, nurses, chemical workers, those who work with animals,  welders , hairdressers and timber workers. [ 122 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_990", "contents": "Aspirin-exacerbated respiratory disease  (AERD), also known as  aspirin -induced asthma, affects up to 9% of asthmatics. [ 125 ]  AERD consists of asthma, nasal polyps, sinus disease, and respiratory reactions to aspirin and other  NSAID medications  (such as ibuprofen and naproxen). [ 126 ]  People often also develop loss of smell and most experience respiratory reactions to alcohol. [ 127 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_991", "contents": "Alcohol may worsen asthmatic symptoms in up to a third of people. [ 128 ]  This may be even more common in some ethnic groups such as the  Japanese  and those with aspirin-exacerbated respiratory disease. [ 128 ]  Other studies have found improvement in asthmatic symptoms from alcohol. [ 128 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_992", "contents": "Non-atopic asthma, also known as intrinsic or non-allergic, makes up between 10 and 33% of cases. There is negative skin test to common inhalant allergens. Often it starts later in life, and women are more commonly affected than men. Usual treatments may not work as well. [ 129 ]  The concept that \"non-atopic\" is synonymous with \"non-allergic\" is called into question by epidemiological data that the prevalence of asthma is closely related to the serum IgE level standardized for age and sex (P<0.0001), indicating that asthma is almost always associated with some sort of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of aeroallergens studied (the \"missing antigen(s)\" hypothesis). [ 130 ]  For example, an updated systematic review and meta-analysis of population-attributable risk (PAR) of  Chlamydia pneumoniae  biomarkers in chronic asthma found that the PAR for  C. pneumoniae -specific IgE was 47%. [ 131 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_993", "contents": "Infectious asthma is an easily identified clinical presentation. [ 132 ]  When queried, asthma patients may report that their first asthma symptoms began after an acute lower respiratory tract illness. This type of history has been labelled the \"infectious asthma\" (IA) syndrome, [ 133 ]  or as \"asthma associated with infection\" (AAWI) [ 134 ]  to distinguish infection-associated asthma initiation from the well known association of respiratory infections with asthma exacerbations. Reported clinical prevalences of IA for adults range from around 40% in a primary care practice [ 133 ]  to 70% in a speciality practice treating mainly severe asthma patients. [ 135 ]  Additional information on the clinical prevalence  of IA in adult-onset asthma is unavailable because clinicians are not trained to elicit this type of history routinely, and recollection in child-onset asthma is challenging. A population-based incident case-control study in a geographically defined area of Finland reported that 35.8% of new-onset asthma cases had experienced acute bronchitis or pneumonia in the year preceding asthma onset, representing a significantly higher risk compared to randomly selected controls ( odds ratio  7.2, 95% confidence interval 5.2\u201310). [ 136 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_994", "contents": "Asthma phenotyping and endotyping has emerged as a novel approach to asthma classification inspired by  precision medicine  which separates the clinical presentations of asthma, or asthma phenotypes, from their underlying causes, or asthma endotypes. The best-supported endotypic distinction is the type 2-high/type 2-low distinction. Classification based on type 2 inflammation is useful in predicting which patients will benefit from targeted  biologic therapy . [ 137 ] [ 138 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_995", "contents": "Many other conditions can cause symptoms similar to those of asthma. In children, symptoms may be due to other upper airway diseases such as  allergic rhinitis  and  sinusitis , as well as other causes of airway obstruction including  foreign body aspiration ,  tracheal stenosis ,  laryngotracheomalacia ,  vascular rings , enlarged  lymph nodes  or neck masses. [ 139 ]   Bronchiolitis  and other viral infections may also produce wheezing. [ 140 ]  According to  European Respiratory Society , it may not be suitable to label wheezing preschool children with the term  asthma  because there is lack of clinical data on inflammation in airways. [ 141 ]  In adults,  COPD ,  congestive heart failure , airway masses, as well as drug-induced coughing due to  ACE inhibitors  may cause similar symptoms. In both populations  vocal cord dysfunction  may present similarly. [ 139 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_996", "contents": "Chronic obstructive pulmonary disease  can coexist with asthma and can occur as a complication of chronic asthma. After the age of 65, most people with obstructive airway disease will have asthma and COPD. In this setting, COPD can be differentiated by increased airway neutrophils, abnormally increased wall thickness, and increased smooth muscle in the bronchi. However, this level of investigation is not performed due to COPD and asthma sharing similar principles of management: corticosteroids, long-acting beta-agonists, and smoking cessation. [ 142 ]  It closely resembles asthma in symptoms, is correlated with more exposure to cigarette smoke, an older age, less symptom reversibility after bronchodilator administration, and decreased likelihood of family history of atopy. [ 143 ] [ 144 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_997", "contents": "The evidence for the effectiveness of measures to prevent the development of asthma is weak. [ 145 ]  The  World Health Organization  recommends decreasing risk factors such as tobacco smoke, air pollution, chemical irritants including  perfume , and the number of  lower respiratory infections . [ 146 ] [ 147 ]  Other efforts that show promise include: limiting smoke exposure  in utero ,  breastfeeding , and increased exposure to daycare or large families, but none are well supported enough to be recommended for this indication. [ 145 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_998", "contents": "Early pet exposure may be useful. [ 148 ]  Results from exposure to pets at other times are inconclusive [ 149 ]  and it is only recommended that pets be removed from the home if a person has allergic symptoms to said pet. [ 150 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_999", "contents": "Dietary restrictions during pregnancy or when breastfeeding have not been found to be effective at preventing asthma in children and are not recommended. [ 150 ]  Omega-3 consumption,  Mediterranean diet  and antioxidants have been suggested by some studies to potentially help prevent crises but the evidence is still inconclusive. [ 151 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1000", "contents": "Reducing or eliminating compounds known to sensitive people from the workplace may be effective. [ 122 ]  It is not clear if annual  influenza vaccinations  affect the risk of exacerbations. [ 152 ]  Immunization, however, is recommended by the World Health Organization. [ 153 ]  Smoking bans are effective in decreasing exacerbations of asthma. [ 154 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1001", "contents": "While there is no cure for asthma, symptoms can typically be improved. [ 155 ]  The most effective treatment for asthma is identifying triggers, such as  cigarette smoke , pets or other allergens, and eliminating exposure to them. If trigger avoidance is insufficient, the use of medication is recommended. Pharmaceutical drugs are selected based on, among other things, the severity of illness and the frequency of symptoms. Specific medications for asthma are broadly classified into fast-acting and long-acting categories. [ 156 ] [ 157 ]  The medications listed below have demonstrated efficacy in improving asthma symptoms; however, real world use-effectiveness is limited as around half of people with asthma worldwide remain sub-optimally controlled, even when treated. [ 158 ] [ 159 ] [ 160 ]  People with asthma may remain sub-optimally controlled either because optimum doses of asthma medications do not work (called \"refractory\" asthma) or because individuals are either unable (e.g. inability to afford treatment, poor inhaler technique) or unwilling (e.g., wish to avoid side effects of corticosteroids) to take optimum doses of prescribed asthma medications (called \"difficult to treat\" asthma). In practice, it is not possible to distinguish \"refractory\" from \"difficult to treat\" categories for patients who have never taken optimum doses of asthma medications. A related issue is that the asthma efficacy trials upon which the pharmacological treatment guidelines are based have systematically excluded the majority of people with asthma. [ 161 ] [ 162 ]  For example, asthma efficacy treatment trials always exclude otherwise eligible people who smoke, and smoking diminishes the efficacy of inhaled corticosteroids, the mainstay of asthma control management. [ 163 ] [ 164 ] [ 165 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1002", "contents": "Bronchodilators  are recommended for short-term relief of symptoms. In those with occasional attacks, no other medication is needed. If mild persistent disease is present (more than two attacks a week), low-dose inhaled corticosteroids or alternatively, a  leukotriene antagonist  or a  mast cell stabilizer  by mouth is recommended. For those who have daily attacks, a higher dose of inhaled corticosteroids is used. In a moderate or severe exacerbation, corticosteroids by mouth are added to these treatments. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1003", "contents": "People with asthma have higher rates of  anxiety ,  psychological stress , and  depression . [ 166 ] [ 167 ]  This is associated with poorer asthma control. [ 166 ]   Cognitive behavioural therapy  may improve quality of life, asthma control, and anxiety levels in people with asthma. [ 166 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1004", "contents": "Improving people's knowledge about asthma and using a written action plan has been identified as an important component of managing asthma. [ 168 ]  Providing educational sessions that include information specific to a person's culture is likely effective. [ 169 ]  More research is necessary to determine if increasing preparedness and knowledge of asthma among school staff and families using home-based and school interventions results in long term improvements in safety for children with asthma. [ 170 ] [ 171 ] [ 172 ]  School-based asthma self-management interventions, which attempt to improve knowledge of asthma, its triggers and the importance of regular practitioner review, may reduce hospital admissions and emergency department visits. These interventions may also reduce the number of days children experience asthma symptoms and may lead to small improvements in asthma-related quality of life. [ 173 ]  More research is necessary to determine if  shared decision-making  is helpful for managing adults with asthma [ 174 ]  or if a personalized asthma action plan is effective and necessary. [ 175 ]  Some people with asthma use  pulse oximeters  to monitor their own blood oxygen levels during an asthma attack. However, there is no evidence regarding the use in these instances. [ 176 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1005", "contents": "Avoidance of triggers is a key component of improving control and preventing attacks. The most common triggers include  allergens , smoke (from tobacco or other sources), air pollution,  nonselective beta-blockers , and sulfite-containing foods. [ 177 ] [ 178 ]  Cigarette smoking and  second-hand smoke  (passive smoke) may reduce the effectiveness of medications such as corticosteroids. [ 179 ]   Laws that limit smoking  decrease the number of people hospitalized for asthma. [ 154 ]  Dust mite control measures, including air filtration, chemicals to kill mites, vacuuming, mattress covers and other methods had no effect on asthma symptoms. [ 63 ]  There is insufficient evidence to suggest that dehumidifiers are helpful for controlling asthma. [ 180 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1006", "contents": "Overall, exercise is beneficial in people with stable asthma. [ 181 ]  Yoga could provide small improvements in quality of life and symptoms in people with asthma. [ 182 ]  More research is necessary to determine how effective weight loss is in improving quality of life, the usage of health care services, and adverse effects for people of all ages with asthma. [ 183 ] [ 184 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1007", "contents": "Findings suggest that the  Wim Hof  Method may reduce inflammation in healthy and non-healthy participants as it increases epinephrine levels, causing an increase in interleukin-10 and a decrease in pro-inflammatory cytokines. [ 185 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1008", "contents": "Medications used to treat asthma are divided into two general classes: quick-relief medications used to treat acute symptoms; and long-term control medications used to prevent further exacerbation. [ 156 ]   Antibiotics  are generally not needed for sudden worsening of symptoms or for treating asthma at any time. [ 186 ] [ 187 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1009", "contents": "For children with asthma which is well-controlled on combination therapy of  inhaled corticosteroids  (ICS) and long-acting beta 2 -agonists (LABA), the benefits and harms of stopping LABA and stepping down to ICS-only therapy are uncertain. [ 225 ]  In adults who have stable asthma while they are taking a combination of LABA and inhaled corticosteroids (ICS), stopping LABA may increase the risk of asthma exacerbations that require treatment with corticosteroids by mouth. [ 226 ]  Stopping LABA probably makes little or no important difference to asthma control or asthma-related quality of life. [ 226 ]  Whether or not stopping LABA increases the risk of serious adverse events or exacerbations requiring an emergency department visit or hospitalization is uncertain. [ 226 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1010", "contents": "Medications are typically provided as  metered-dose inhalers  (MDIs) in combination with an  inhaler spacer  or as a  dry powder inhaler . The spacer is a plastic cylinder that mixes the medication with air, making it easier to receive a full dose of the drug. A  nebulizer  may also be used. Nebulizers and spacers are equally effective in those with mild to moderate symptoms. However, insufficient evidence is available to determine whether a difference exists in those with severe disease. [ 227 ]  For delivering short-acting beta-agonists in acute asthma in children, spacers may have advantages compared to nebulisers, but children with life-threatening asthma have not been studied. [ 228 ]  There is no strong evidence for the use of intravenous LABA for adults or children who have acute asthma. [ 229 ]  There is insufficient evidence to directly compare the effectiveness of a metered-dose inhaler attached to a homemade spacer compared to commercially available spacer for treating children with asthma. [ 230 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1011", "contents": "Long-term use of inhaled corticosteroids at conventional doses carries a minor risk of adverse effects. [ 231 ]  Risks include  thrush , the development of  cataracts , and a slightly slowed rate of growth. [ 231 ] [ 232 ] [ 233 ]  Rinsing the mouth after the use of inhaled steroids can decrease the risk of thrush. [ 234 ]  Higher doses of inhaled steroids may result in lower  bone mineral density . [ 235 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1012", "contents": "Inflammation in the lungs can be estimated by the level of exhaled  nitric oxide . [ 236 ] [ 237 ]  The use of exhaled nitric oxide levels (FeNO) to guide asthma medication dosing may have small benefits for preventing asthma attacks but the potential benefits are not strong enough for this approach to be universally recommended as a method to guide asthma therapy in adults or children. [ 236 ] [ 237 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1013", "contents": "When asthma is unresponsive to usual medications, other options are available for both emergency management and prevention of flareups. Additional options include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1014", "contents": "Staying with a treatment approach for preventing asthma exacerbations can be challenging, especially if the person is required to take medicine or treatments daily. [ 258 ]  Reasons for low  adherence  range from a conscious decision to not follow the suggested medical treatment regime for various reasons including avoiding potential  side effects ,  misinformation , or other beliefs about the medication. [ 258 ]  Problems accessing the treatment and problems administering the treatment effectively can also result in lower adherence. Various approaches have been undertaken to try and improve adherence to treatments to help people prevent serious asthma exacerbations including digital interventions. [ 258 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1015", "contents": "Many people with asthma, like those with other chronic disorders, use  alternative treatments ; surveys show that roughly 50% use some form of unconventional therapy. [ 259 ] [ 260 ]  There is little data to support the effectiveness of most of these therapies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1016", "contents": "Evidence is insufficient to support the usage of  vitamin C  or  vitamin E  for controlling asthma. [ 261 ] [ 262 ]  There is tentative support for use of vitamin C in exercise induced bronchospasm. [ 263 ]   Fish oil  dietary supplements (marine n-3 fatty acids) [ 264 ]  and reducing dietary sodium [ 265 ]  do not appear to help improve asthma control. In people with mild to moderate asthma, treatment with  vitamin D  supplementation or its hydroxylated metabolites does not reduce acute exacerbations or improve control. [ 266 ]  There is no strong evidence to suggest that vitamin D supplements improve day-to-day asthma symptoms or a person's lung function. [ 266 ]  There is no strong evidence to suggest that adults with asthma should avoid foods that contain  monosodium glutamate  (MSG). [ 267 ]  There have not been enough high-quality studies performed to determine if children with asthma should avoid eating food that contains MSG. [ 267 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1017", "contents": "Acupuncture  is not recommended for the treatment as there is insufficient evidence to support its use. [ 268 ] [ 269 ]   Air ionizers  show no evidence that they improve asthma symptoms or benefit lung function; this applied equally to positive and negative ion generators. [ 270 ]  Manual therapies, including  osteopathic ,  chiropractic ,  physiotherapeutic  and  respiratory therapeutic  manoeuvres, have insufficient evidence to support their use in treating asthma. [ 271 ]   Pulmonary rehabilitation, however, may improve quality of life and functional exercise capacity when compared to usual care for adults with asthma. [ 272 ]  The  Buteyko breathing technique  for controlling hyperventilation may result in a reduction in medication use; however, the technique does not have any effect on lung function. [ 157 ]   Thus an expert panel felt that evidence was insufficient to support its use. [ 268 ]  There is no clear evidence that breathing exercises are effective for treating children with asthma. [ 273 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1018", "contents": "The prognosis for asthma is generally good, especially for children with mild disease. [ 274 ]  Mortality has decreased over the last few decades due to better recognition and improvement in care. [ 275 ]  In 2010 the death rate was 170 per million for males and 90 per million for females. [ 276 ]  Rates vary between countries by 100-fold. [ 276 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1019", "contents": "Globally it causes moderate or severe disability in 19.4\u00a0million people as of 2004 [update]  (16\u00a0million of which are in low and middle income countries). [ 277 ]  Of asthma diagnosed during childhood, half of cases will no longer carry the diagnosis after a decade. [ 76 ]  Airway remodelling is observed, but it is unknown whether these represent harmful or beneficial changes. [ 278 ]  More recent data find that severe asthma can result in airway remodelling and the \"asthma with chronic obstructive pulmonary disease syndrome (ACOS)\" that has a poor prognosis. [ 279 ]   Early treatment with corticosteroids seems to prevent or ameliorates a decline in lung function. [ 280 ]  Asthma in children also has negative effects on quality of life of their parents. [ 281 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1020", "contents": "In 2019, approximately 262 million people worldwide were affected by asthma and approximately 461,000 people died from the disease. [ 8 ]  Rates vary between countries with prevalences between 1 and 18%. [ 21 ]  It is more common in  developed  than  developing countries . [ 21 ]  One thus sees lower rates in Asia, Eastern Europe and Africa. [ 20 ]  Within developed countries it is more common in those who are economically disadvantaged while in contrast in developing countries it is more common in the affluent. [ 21 ]  The reason for these differences is not well known. [ 21 ]  Low- and middle-income countries make up more than 80% of the mortality. [ 284 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1021", "contents": "While asthma is twice as common in boys as girls, [ 21 ]  severe asthma occurs at equal rates. [ 285 ]  In contrast adult women have a higher rate of asthma than men [ 21 ]  and it is more common in the young than the old. [ 20 ]  In 2010, children with asthma experienced over 900,000 emergency department visits, making it the most common reason for admission to the hospital following an emergency department visit in the US in 2011. [ 286 ] [ 287 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1022", "contents": "Global rates of asthma have increased significantly between the 1960s and 2008 [ 18 ] [ 288 ]  with it being recognized as a major public health problem since the 1970s. [ 20 ]  Rates of asthma have plateaued in the developed world since the mid-1990s with recent increases primarily in the developing world. [ 289 ]  Asthma affects approximately 7% of the population of the United States [ 203 ]  and 5% of people in the United Kingdom. [ 290 ]  Canada, Australia and New Zealand have rates of about 14\u201315%. [ 291 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1023", "contents": "The average death rate from 2011 to 2015 from asthma in the UK was about 50% higher than the average for the European Union and had increased by about 5% in that time. [ 292 ]  Children are more likely see a physician due to asthma symptoms after school starts in September. [ 293 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1024", "contents": "Population-based epidemiological studies describe temporal associations between acute respiratory illnesses, asthma, and development of severe asthma with irreversible airflow limitation (known as the asthma-chronic obstructive pulmonary disease \"overlap\" syndrome, or ACOS). [ 294 ] [ 295 ] [ 31 ]  Additional prospective population-based data indicate that ACOS seems to represent a form of severe asthma, characterized by more frequent hospitalizations, and to be the result of early-onset asthma that has progressed to fixed airflow obstruction. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1025", "contents": "From 2000 to 2010, the average cost per asthma-related hospital stay in the United States for children remained relatively stable at about $3,600, whereas the average cost per asthma-related hospital stay for adults increased from $5,200 to $6,600. [ 296 ]  In 2010, Medicaid was the most frequent primary payer among children and adults aged 18\u201344 years in the United States; private insurance was the second most frequent payer. [ 296 ]  Among both children and adults in the lowest income communities in the United States there is a higher rate of hospital stays for asthma in 2010 than those in the highest income communities. [ 296 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1026", "contents": "Asthma was recognized in  ancient Egypt  and was treated by drinking an  incense  mixture known as  kyphi . [ 19 ]  It was officially named as a specific respiratory problem by  Hippocrates  circa 450 BC, with the Greek word for \"panting\" forming the basis of our modern name. [ 20 ]  In 200 BC it was believed to be at least partly related to the emotions. [ 28 ]  In the 12th century the Jewish physician-philosopher  Maimonides  wrote a treatise on asthma in Arabic, based partly on Arabic sources, in which he discussed the symptoms, proposed various dietary and other means of treatment, and emphasized the importance of climate and clean air. [ 297 ]   Traditional Chinese medicine  also offered medication for asthma, as indicated by a surviving 14th-century manuscript curated by the Wellcome Foundation. [ 298 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1027", "contents": "In 1873, one of the first papers in modern medicine on the subject tried to explain the  pathophysiology  of the disease while one in 1872, concluded that asthma can be cured by rubbing the chest with  chloroform liniment . [ 299 ] [ 300 ]   Medical treatment  in 1880 included the use of  intravenous  doses of a drug called  pilocarpine . [ 301 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1028", "contents": "In 1886, F. H. Bosworth theorized a connection between asthma and  hay fever . [ 302 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1029", "contents": "At the beginning of the 20th century, the focus was the avoidance of allergens as well as selective beta-2 adrenoceptor agonists were used as treatment strategies. [ 303 ] [ 304 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1030", "contents": "Epinephrine  was first referred to in the treatment of asthma in 1905. [ 305 ]  Oral corticosteroids began to be used for the condition in 1950. The use of a pressurized metered-dose inhaler was developed in the mid-1950s for the administration of adrenaline and  isoproterenol  and was later used as a beta 2 -adrenergic agonist."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1031", "contents": "Inhaled corticosteroids and selective short-acting beta agonists came into wide use in the 1960s. [ 306 ] [ 307 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1032", "contents": "A well-documented case in the 19th century was that of  young Theodore Roosevelt  (1858\u20131919). At that time there was no effective treatment. Roosevelt's youth was in large part shaped by his poor health, partly related to his asthma. He experienced recurring nighttime asthma attacks that felt as if he was being smothered to death, terrifying the boy and his parents. [ 308 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1033", "contents": "During the 1930s to 1950s, asthma was known as one of the \"holy seven\"  psychosomatic illnesses . Its cause was considered to be psychological, with treatment often based on psychoanalysis and other  talking cures . [ 309 ]  As these psychoanalysts interpreted the asthmatic wheeze as the suppressed cry of the child for its mother, they considered the treatment of depression to be especially important for individuals with asthma. [ 309 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1034", "contents": "In January 2021, an appeal court in  France  overturned a deportation order against a 40-year-old Bangladeshi man, who was a patient of asthma. His lawyers had argued that the dangerous levels of  pollution  in  Bangladesh  could possibly lead to worsening of his health condition, or even premature death. [ 310 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1035", "contents": "Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap  (ACO), also known as  Asthma-COPD Overlap Syndrome (ACOS) , is a chronic inflammatory,  obstructive airway disease  in which features of both  asthma  and  COPD  predominate. Asthma and COPD were once thought of as distinct entities; however, in some, there are clinical features of both asthma and COPD with significant overlap in  pathophysiology  and symptom profile. It is unclear whether ACO is a separate disease entity or a clinical subtype of asthma and COPD. The  pathogenesis  of ACO is poorly understood, but it is thought to involve both  type 2 inflammation  (usually seen in asthma) as well as type 1 inflammation (seen in COPD). The incidence and prevalence of ACO are not well known. The risk factors for ACO are also incompletely understood, but  tobacco  smoke is known to be a major risk factor."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1036", "contents": "ACO presents with symptoms of both  asthma  and  COPD . [ 1 ]  ACO presents in adulthood, usually after the age of 40 (after there has been significant tobacco smoke or other toxic fumes exposure), with symptoms of  dyspnea  (shortness of breath),  exercise intolerance ,  sputum production ,  cough  and episodes of symptomatic worsening known as exacerbations."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1037", "contents": "A history of significant and persistent noxious fumes exposure is required for the diagnosis of COPD; therefore, it is also required for the diagnosis of ACO. [ 2 ]  This can be due to tobacco smoking, indoor air pollution, or outdoor  air pollution ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1038", "contents": "ACOS presents with features of both asthma and COPD. Both asthma and COPD (as well as ACO) present with exacerbations, periods where symptoms deteriorate, with marked reductions in airflow. However,  in asthma, the airflow limitation usually completely resolves after exacerbations, whereas in COPD it may not. [ 1 ]  ACO presents with a chronic airflow limitation or obstruction (due to  inflammation ), with characteristics of both asthma and COPD. Inflammation of the large and medium airways (classically seen with asthma) is seen in ACO. [ 1 ]  This consists of  bronchoconstriction  due to  smooth muscle  spasm as well as smooth muscle hyperresponsiveness (due to allergens or irritants) causing  obstruction of airflow . [ 1 ]   Mucus  production and inflammation in the airways can also cause airflow obstruction in asthma. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1039", "contents": "Features of COPD (which includes the subtypes of chronic  bronchitis  and COPD) are also seen in ACO. These include the features of chronic bronchitis such as inflammation of the small airways and mucus production or hypersecretion. [ 1 ]   Peribronchial  inflammation may lead to  fibrosis  ( obliterative bronchiolitis ) [ 1 ]  as well as features of  emphysema , including inflammation leading to  alveolar  destruction resulting in lung hyperinflation and air trapping. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1040", "contents": "There are no widely accepted diagnostic criteria for ACO. However, the diagnosis requires clinical features of both asthma and COPD. [ 3 ]  One diagnostic criteria, based on expert consensus, first described in 2016, requires the presence of three major and at least one minor criteria for the diagnosis of ACO. The major criteria are: a persistent airflow limitation (a ratio of forced expiratory volume in 1 second divided by forced vital capacity ( FEV1/FVC ) of less than 0.7 or below the lower limit of normal), a significant exposure history to tobacco smoke (defined as a greater than 10-pack/year history), or significant exposure to other indoor or outdoor air pollution, and a documented history of asthma or a significant improvement in FEV1 (of greater than 400mL) to an inhaled  bronchodilator . [ 4 ]  The minor criteria include a history of  atopy  or  allergic rhinitis , a more limited response to an inhaled bronchodilator (greater than 200 mL improvement in the FEV1 or a 12% improvement from baseline), and peripheral blood  eosinophils  greater than 300 cells/\u03bcL.  Spirometry  (documenting obstruction) is required for the diagnosis of ACO. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1041", "contents": "In those with asthma, some features often seen in COPD that may aid in the diagnosis of ACO include emphysema seen on imaging or a decreased diffusion capacity ( DLCO ) indicating significant lung tissue damage. In those with COPD, other features often seen in asthma that may aid in the diagnosis of ACO include an increase in the fraction of exhaled nitric oxide ( FENO ), a marker that is specific to the degree of airway inflammation in those with asthma, or increased levels of  IgE  (either total IgE or specific to inhaled antigens). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1042", "contents": "Treatment of ACO is based on expert opinion, as there are no universally accepted clinical guidelines. Treatment is usually based on whether clinical features of asthma or COPD predominate. [ 4 ]   Inhaled corticosteroids  are the primary treatment in those with ACOS. [ 2 ] [ 1 ] [ 4 ]   Inhaled corticosteroids  (ICS) should be continued in those with asthma who develop decreased airway responsiveness to bronchodilators consistent with ACO. [ 1 ]  Therapy can be escalated to include a  long-acting beta-agonist  (LABA) and inhaled steroid combination (ICS-LABA) or by adding on a long-acting  anti-muscarinic  inhaler (LAMA), known as triple therapy, in those with more severe or resistant disease. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1043", "contents": "Monoclonal antibodies  targeting  type 2 inflammation  (which is predominant in asthma) have been used to treat severe asthma, and may also be used in severe cases of ACO. [ 4 ]  These monoclonal antibodies include  omalizumab  (an Anti-IgE antibody),  mepolizumab  (an anti-IL-5 antibody) and  benralizumab  (an anti-IL-5 receptor \u03b1 antibody). [ 4 ]  People with ACOS and  eosinophilia  have a better response to ICS, with fewer exacerbations and hospitalizations seen in ACOS treated with long-term ICS. [ 1 ]  Systemic corticosteroids ( intravenous  or oral steroids) may be used during exacerbations of ACOS. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1044", "contents": "The progression of permanent airflow obstruction (as measured by the rate of FEV1 decline) is slower in ACO as compared to COPD, but ACO with late-onset asthma is associated with a more rapid FEV1 decline (a more rapid progression of obstruction) and a worse  prognosis . [ 4 ]  ACO  with late-onset asthma is associated with a higher mortality as compared to COPD, asthma or healthy controls. [ 4 ]  Excluding ACO with late-onset asthma, ACO has better survival (lower mortality) than COPD, but higher mortality compared to asthma. [ 4 ]  In other studies, ACO was associated with worse  dyspnea  symptoms, more coughing,  wheezing , and  sputum  production, as well as more frequent and more severe exacerbations as compared to COPD or asthma. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1045", "contents": "Due to heterogeneity of  diagnostic criteria  and a paucity of clinical trials, the prevalence of ACO is not well known. Based on a meta analysis, the prevalence of ACO in the general population is estimated to be 2%, whereas the prevalence of ACO in those with asthma is 26.5% and in those with COPD it is 29.6%. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1046", "contents": "Atelectasis  is the partial collapse or closure of a lung resulting in reduced or absence in gas exchange.  It is usually unilateral, affecting part or all of one lung. [ 2 ]  It is a condition where the  alveoli  are deflated down to little or no volume, as distinct from  pulmonary consolidation , in which they are filled with liquid. It is often referred to  informally  as a  collapsed lung , although more accurately it usually involves only a partial collapse, and that ambiguous term is also informally used for a fully collapsed lung caused by a  pneumothorax . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1047", "contents": "It is a very common finding in  chest X-rays  and other radiological studies, and may be caused by normal  exhalation  or by various medical conditions. Although frequently described as a  collapse of lung tissue , atelectasis is not synonymous with a pneumothorax, which is a more specific condition that can cause atelectasis.  Acute atelectasis may occur as a post-operative complication or as a result of  surfactant  deficiency.  In  premature babies , this leads to  infant respiratory distress syndrome ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1048", "contents": "The term uses combining forms of  atel-  +  ectasis , from  Greek :  \u1f00\u03c4\u03b5\u03bb\u03ae\u03c2 , \"incomplete\" + \u1f14\u03ba\u03c4\u03b1\u03c3\u03b9\u03c2, \"extension\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1049", "contents": "May have no signs and symptoms or they may include: [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1050", "contents": "It is a common misconception and pure speculation that atelectasis causes fever. This claim has been perpetuated in medical textbooks as recently as 2010. [ 4 ]  A review article published in 2011 summarizing the available evidence on the association between atelectasis and post-operative fever concluded that there is no clinical evidence supporting this speculation. [ 5 ]  A recent article outlined the history of this myth and the true causes of post-operative fever. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1051", "contents": "The most common cause is post-surgical atelectasis, characterized by splinting, i.e. restricted breathing after abdominal surgery. Atelectasis develops in 75\u201390% of people undergoing general anesthesia for a surgical procedure. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1052", "contents": "Another common cause is pulmonary  tuberculosis .  Smokers  and the elderly are also at an increased risk. Outside of this context, atelectasis implies some blockage of a  bronchiole  or  bronchus , which can be within the airway (foreign body,  mucus  plug), from the wall (tumor, usually  squamous cell carcinoma ) or compressing from the outside ( tumor ,  lymph node ,  tubercle ). Another cause is poor  surfactant  spreading during  inspiration , causing the  surface tension  to be at its highest which tends to collapse smaller  alveoli . Atelectasis may also occur during suction, as along with  sputum , air is withdrawn from the lungs. There are several types of atelectasis according to their underlying mechanisms or the distribution of alveolar collapse; resorption, compression, microatelectasis and contraction atelectasis. Relaxation atelectasis (also called passive atelectasis) is when a  pleural effusion  or a  pneumothorax  disrupts the contact between the parietal and visceral  pleurae . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1053", "contents": "Risk factors associated with increased likelihood of the development of atelectasis include: type of surgery (thoracic, cardiopulmonary surgeries), use of muscle relaxation, obesity, high oxygen, the lower lung segments."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1054", "contents": "Factors also associated with the development of atelectasis include: age, presence of  chronic obstructive pulmonary disease  or  asthma , and type of  anesthetic ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1055", "contents": "In the early 1950s, in UK  aviation medicine , the condition acceleration atelectasis was given the name \"Hunter lung\" due to its prevalence in pilots of the transonic fighter jet, the  Hawker Hunter , which used a 100%  oxygen supply . [ 9 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1056", "contents": "Clinically significant atelectasis is generally visible on chest X-ray; findings can include lung opacification and/or loss of lung volume. Post-surgical atelectasis will be bibasal in pattern. Chest  CT  or  bronchoscopy  may be necessary if the cause of atelectasis is not clinically apparent. Direct signs of atelectasis include displacement of interlobar fissures and mobile structures within the thorax, overinflation of the unaffected ipsilateral lobe or contralateral lung, and opacification of the collapsed lobe. In addition to clinically significant findings on chest X-rays, patients may present with indirect signs and symptoms such as elevation of the diaphragm, shifting of the trachea, heart and mediastinum; displacement of the hilus and shifting granulomas. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1057", "contents": "Atelectasis is broadly categorized into obstructive (resorptive) and nonobstructive types. It may be further classified as an acute or chronic condition. In acute atelectasis, the lung has recently collapsed and is primarily notable only for airlessness. In chronic atelectasis, the affected area is often characterized by a complex mixture of airlessness, infection, widening of the bronchi ( bronchiectasis ), destruction, and scarring ( fibrosis )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1058", "contents": "This type is defined by blockage of the airway with air trapping and subsequent absorption of air distal to the obstruction. [ 12 ]  The resulting absorption of air distal to the obstruction results in collapse of the  alveoli . It is most commonly due to intrathoracic tumors, aspiration of a foreign body, or mucus plugs. [ 13 ]  Children are notably more susceptible to atelectasis due to poorly developed collateral airways, which protect against alveolar collapse by maintaining inflation. [ 12 ]  The  Earth's atmosphere  is mainly composed of 78%  nitrogen  and 21%  oxygen  (+ 1%  argon  and traces of other gases). Since oxygen is exchanged at the alveoli-capillary membrane, nitrogen is a major component for the alveoli's state of inflation. If a large volume of nitrogen in the lungs is replaced with oxygen, the oxygen may subsequently be absorbed into the blood, reducing the volume of the alveoli, resulting in a form of alveolar collapse known as absorption atelectasis. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1059", "contents": "There are four types of acute atelectasis: absorption atelectasis, compressive atelectasis, contraction atelectasis, and patchy atelectasis. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1060", "contents": "It is usually associated with accumulation of blood, fluid, or air within the  pleural cavity , which mechanically collapses the lung. This is a frequent occurrence with pleural effusion, caused by congestive  heart failure  (CHF). Leakage of air into the pleural cavity ( pneumothorax ) also leads to compression atelectasis. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1061", "contents": "This type occurs when either local or generalized fibrotic changes in the lung or  pleura  hamper expansion and increase elastic recoil during expiration. [ 15 ]  Causes include granulomatous disease, necrotising pneumonia and radiation fibrosis. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1062", "contents": "This type of atelectasis is due to lack of surfactant, as occurs in hyaline membrane disease of newborn or acute (adult) respiratory distress syndrome (ARDS). [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1063", "contents": "Chronic atelectasis may take one of two forms: right middle lobe syndrome, or rounded atelectasis. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1064", "contents": "In right middle lobe syndrome, the middle lobe of the right lung contracts, usually because of pressure on the bronchus from enlarged  lymph  glands and occasionally a  tumor . The blocked, contracted  lung  may develop  pneumonia  that fails to resolve completely and leads to  chronic inflammation , scarring, and  bronchiectasis . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1065", "contents": "In rounded atelectasis (folded lung or Blesovsky syndrome [ 18 ] ), an outer portion of the lung slowly collapses as a result of scarring and shrinkage of the membrane layers covering the lungs (pleura), which would show as visceral pleural thickening and entrapment of lung tissue. This produces a rounded appearance on X-ray that doctors may mistake for a tumor. Rounded atelectasis is usually a complication of  asbestos -induced disease of the pleura, but it may also result from other types of chronic scarring and thickening of the pleura. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1066", "contents": "Treatment is directed at correcting the underlying cause. In atelectasis manifestations that result from the mucus plugging of the airways as seen in patients with cystic fibrosis and pneumonia, mucolytic agents such as acetylcysteine (NAC) is used. This nebulized treatment works by reducing mucous viscosity and elasticity by breaking disulfide bonds in mucoproteins within the mucus complex, thus facilitating mucus clearance. [ 19 ]  Post-surgical atelectasis is treated by  physiotherapy , focusing on deep breathing and encouraging coughing. An  incentive spirometer  is often used as part of the breathing exercises.   Walking  is also highly encouraged to improve lung inflation.  People with chest deformities or  neurologic  conditions that cause shallow breathing for long periods may benefit from mechanical devices that assist their breathing. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1067", "contents": "The primary treatment for acute massive atelectasis is correction of the underlying cause. A blockage that cannot be removed by coughing or by suctioning the airways often can be removed by bronchoscopy.  Antibiotics  are given for an infection. Chronic atelectasis is often treated with antibiotics because infection is almost inevitable. In certain cases, the affected part of the lung may be surgically removed when recurring or chronic infections become disabling or bleeding is significant. If a tumor is blocking the airway, relieving the obstruction by surgery, radiation therapy, chemotherapy, or laser therapy may prevent atelectasis from progressing and recurrent obstructive pneumonia from developing. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1068", "contents": "Atypical canine infectious respiratory disease complex  ( aCIRDC ) is a proposed novel respiratory disease in dogs [ 1 ]  of unknown cause. It has been recorded in 19 US states, with more cases on the West Coast. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1069", "contents": "It has also been referred to as respiratory syndrome of unknown aetiology in dogs and as canine respiratory disease of unknown origin. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1070", "contents": "It was first described in summer 2023 as a cluster of 200 cases around Portland, Oregon. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1071", "contents": "Symptoms include a cough, fever, lethargy, sneezing and watery eyes. In some cases, the illness proceeds to death. [ 1 ]  Cases tend to fit three clinical syndromes: chronic mild/moderate  tracheobronchitis  of prolonged duration (6+ weeks), [ 4 ]  with coughing, sneezing, and watery eyes; chronic pneumonia that is minimally responsive to antimicrobials, possibly including dyspnea; and, rarely, acute pneumonia that rapidly becomes severe and can lead to death. [ 5 ] [ 6 ]  Most cases are self-limiting and respond well to supportive care. [ 7 ]  Antibiotics may be indicated. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1072", "contents": "Diagnosis should rule out known forms of  canine infectious respiratory disease complex  (CIRDC; also known as kennel cough). aCIRDC does not respond to regular treatment protocols for CIRCD and the course of the disease is longer and more severe. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1073", "contents": "There is no evidence that it can spread to humans. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1074", "contents": "The cause is currently unknown. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1075", "contents": "The Veterinary Diagnostic Laboratory at the University of New Hampshire have put forth a possible bacterium as the cause. [ 5 ]  They have tentatively identified this as  IOLA KY405 , [ 9 ]  which was previously identified in humans in 2021. [ 10 ]  This is similar to  Mycoplasma  in lacking a  cell wall  and having a small genome. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1076", "contents": "However, other vets have suggested that this might just represent a peak in CIRDC cases and not involve any new pathogens. This could be due to changes in human behaviour following the end of COVID-19 lockdowns and other COVID-19-related disruption to veterinary care ( e.g.  frequency of vaccination), as well as to the general increase in dog numbers in the US. [ 11 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1077", "contents": "Sir Peter John Barnes ,  FRCP ,  FCCP ,  FMedSci ,  FRS  (born 29 October 1946) is a British  respiratory scientist  and  clinician , a specialist in the mechanisms and treatment of  asthma  and  chronic obstructive pulmonary disease  (COPD). [ 1 ]  He was Margaret Turner-Warwick Professor of Thoracic Medicine at the National Heart & Lung Institute, [ 2 ]  previous head of respiratory medicine at  Imperial College  and honorary consultant physician at the  Royal Brompton Hospital  London. [ 3 ]  He is one of the most highly cited scientists in the world. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1078", "contents": "Barnes was born in  Birmingham  and went to school at  Leamington College . He won an open scholarship to  St Catharine's College , Cambridge, where he graduated with a Bachelor of Arts in natural sciences (first-class honours) in 1969. He moved to the Clinical School  University of Oxford , where he was a scholar and graduated  BM, BCh  in 1972."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1079", "contents": "After qualifying in medicine, he undertook clinical training at the  Radcliffe Infirmary  Oxford, followed by posts in London at  Brompton Hospital ,  Queen Square  and  UCH . In 1978 he moved to the  Royal Postgraduate Medical School  to undertake research in  respiratory pharmacology  and was awarded the degree of  Doctor of Medicine (DM) from the  University of Oxford . In 1981 he spent a year at the Cardiovascular Research Institute  UCSF  Medical Center. Returning to London, he worked as a senior registrar at  Hammersmith Hospital  and in 1982 was appointed consultant physician and clinical senior lecturer at  RPMS . He then took up the newly created chair of clinical pharmacology at the NHLI in 1985, which was subsequently incorporated as a postgraduate institute into  Imperial College  and became an honorary consultant physician at  Royal Brompton Hospital  where he directed the  National Heart and Lung Institute . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1080", "contents": "In 1987 he was appointed to the established chair of thoracic medicine at NHLI and was head of respiratory medicine at  Imperial College  until 2017. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1081", "contents": "Barnes was  knighted  in the  2023 Birthday Honours  for services to respiratory science. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1082", "contents": "His research initially focussed on adrenergic regulation of the airways, the role of endogenous  catecholamines  (particularly  epinephrine ),  adrenergic receptors  and the role of  cholinergic  neural mechanisms in  asthma . He was the first to map the distribution of receptors in the lung using  radioligand   autoradiography . [ 8 ]  His group investigated the role of  neuropeptides  in  asthma  and he proposed the  axon reflex  mechanism of  asthma [ 9 ]  Their investigation into the role of inflammatory mechanisms in asthma and the role of  inflammatory mediators , lead to an understanding of how  transcription factors , such as  NF-\u03baB , regulate the expression of multiple inflammatory genes in the airways and how  glucocorticosteroids  suppress inflammation by switching off these transcriptional mechanisms. [ 10 ]  His research explored mechanisms of severe asthma and in particular steroid-resistance in asthma, identifying several molecular mechanisms. He also investigated how \u03b2 2 -agonists and corticosteroids interact as these are the most commonly used drug therapies for asthma. His research group has also investigated inflammatory mechanisms in  COPD , using the same approaches that had been used in asthma. [ 11 ]  An important achievement was to elucidate the molecular mechanism for the anti-inflammatory effects of glucocorticosteroids in asthma through the recruitment of  histone deacetylase 2 (HDAC2) to activated inflammatory genes, thereby reversing the histone acetylation that is involved in inflammatory gene activation. [ 12 ]  His research also investigated why glucocorticosteroids are ineffective in suppressing inflammation in COPD, demonstrating that this is due to decreased activity and expression of  HDAC2 [ 13 ]  as a result of  oxidative stress  through tyrosine nitration and  phosphorylation  via  PI3K -\u03b4. He also showed that  theophylline  was able to restore HDAC2 and reverse steroid resistance in COPD by selectively inhibiting oxidant-activated PI3K\u03b4. [ 14 ]  He also pioneered the use of non-invasive markers to monitor inflammation in the airways and particularly exhaled nitric oxide, which is increased in asthma and reduced by steroid therapy. [ 15 ]  His research has had a major impact on current understanding of asthma and COPD mechanisms and how current therapies for these diseases work. This has identified several novel targets for therapy."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1083", "contents": "As a result of his research on steroid-resistance he co-founded (together with Garth Rapeport and Kazuhiro Ito) a  spin-out  company within  Imperial College  called RespiVert in 2007, [ 16 ]  which has discovered novel inhaled therapies that are now in clinical development for treatment of severe asthma and COPD since the company was acquired by  Johnson & Johnson  in 2010. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1084", "contents": "Barnes is the author of over 1,500 publications in peer-reviewed journals [ 18 ]  and is one of the most highly cited scientists in the world. [ 19 ]  He has edited or co-edited over 50 books on asthma, COPD and respiratory pharmacology. His Web of Science  h-index  is over 200 with over 150,000 citations."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1085", "contents": "He married Olivia Harvard-Watts, a  psychotherapist , in 1976 and they have three sons: Adam (born 1978), Toby (born 1983) and Julian (born 1988). [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1086", "contents": "Central hypoventilation syndrome  ( CHS ) is a  sleep-related breathing disorder  that causes ineffective breathing,  apnea , or  respiratory arrest  during sleep (and during wakefulness in severe cases). CHS can either be congenital (CCHS) or acquired (ACHS) later in life. The condition can be fatal if untreated. CCHS was once known as  Ondine's curse."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1087", "contents": "ACHS can develop as a result of severe injury or trauma to the  brain  or  brainstem . [ 1 ]  Congenital cases are very rare and involve a failure of  autonomic control  of breathing. In 2006, there were only about 200 known cases worldwide. As of 2008, only 1000 total cases were known. [ 2 ]  The diagnosis may be delayed because of variations in the severity of the manifestations or lack of awareness in the medical community, particularly in milder cases. [ 3 ]   However, as there have been cases where asymptomatic family members also were found to have CCHS, it may be that these figures only reflect those found to require mechanical ventilation. In all cases, episodes of  apnea  occur in sleep, but in a few patients, at the most severe end of the spectrum, apnea also occurs while awake."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1088", "contents": "Although rare, cases of long-term untreated CCHS have been reported and are termed late onset CCHS (LO-CCHS). [ 4 ]   There have, however, even been cases of LO-CCHS where family members found to have it have been asymptomatic. [ 5 ]  Again, lack of awareness in the medical community may cause such a delay. [ 6 ]  CCHS susceptibility is not known to be affected by sex or race. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1089", "contents": "CHS is associated with respiratory arrests during sleep and, in some cases, to  neuroblastoma  (tumors of the  sympathetic ganglia ),  Hirschsprung disease  (partial agenesis of the  enteric nervous system ), [ 7 ]   dysphagia  (difficulty swallowing) and anomalies of the pupilla.  Other symptoms include darkening of skin color from inadequate amounts of oxygen, drowsiness, fatigue, headaches, and an inability to sleep at night.  Patients with CHS also have a sensitivity to sedatives and narcotics, which makes respiration even more difficult. A low concentration of oxygen in the  red blood cells  also may cause hypoxia-induced pulmonary vasoconstriction and pulmonary hypertension, culminating in  cor pulmonale  or a failure of the right side of the heart. [ 8 ]   Associated complications may also include gastro-esophageal reflux, ophthalmologic issues, seizures, recurrent pneumonia, developmental delays, learning disabilities, episodes of fainting, and temperature disregulation. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1090", "contents": "CHS is exhibited typically as a  congenital  disorder, but in rare circumstances, can also result from severe brain or spinal trauma or injury (such as after an  automobile accident ,  stroke ,  asphyxiation ,  brain tumor ,  encephalitis ,  poisoning , as a complication of  neurosurgery ) or due to particular  neurodegenerative  conditions such as  Parkinson's disease ,  multiple system atrophy , or  multiple sclerosis .  Long and Allen (1984) were the first to report the abnormal brainstem auditory-evoked responses in an  alcoholic  woman who recovered from Ondine's curse. These investigators hypothesized that their patient's  brainstem  was poisoned\u2014not destroyed\u2014by her chronic alcoholism. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1091", "contents": "Medical investigation of patients with this syndrome has led to a deeper understanding of how the body and brain regulate breathing on a molecular level.  PHOX2B , a transcription factor involved in the development of neurons, [ 11 ]  can be associated with this condition. [ 12 ] [ 13 ] [ 14 ] [ 15 ]  This  homeobox gene  is important for the normal development of the  autonomic nervous system . [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1092", "contents": "The disease used to be classified as a \" neurocristopathy \", [ 17 ] [ 18 ]  or disease of the  neural crest  because part of the autonomic nervous system (such as sympathetic ganglia) derives from the neural crest. However, this denomination is no longer favored because essential neurons of the autonomic nervous system, including those that underlie the defining symptom of the disease (respiratory arrests), are derived from the  neural tube  (the  medulla ), not from the neural crest, which may be the case in other mixed embryological origins and neurocristopathies. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1093", "contents": "Children with CCHS develop life-threatening episodes of apnea with  cyanosis , usually in the first months of life. Medical evaluation excludes lesions of the brain, heart, and lungs but demonstrates impaired responses to build-up of carbon dioxide ( hypercapnia ) and decreases of oxygen in the circulation ( hypoxia ), the two strongest stimuli to increase breathing rate. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1094", "contents": "Polysomnography  shows that hypoventilation is most marked during  slow-wave sleep . Specifically, infants with CCHS usually display lower tidal volumes during sleep, meaning they inhale less air during a normal breath. [ 20 ]  In the most severe cases,  hypoventilation  is present during other nonrapid eye movement sleep stages and even wakefulness. A subset of CCHS patients are at very high risk for developing malignant neural crest-derived  tumors , such as  neuroblastoma ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1095", "contents": "Sequencing of the gene  PHOX2B  revealed mutations in 91% of the cases within a French cohort. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1096", "contents": "Physicians unable to recognize the disorder should seek help from a neurologist and a pulmonologist. In some locations, such as France, optimal management of patients, once identified, has been aided by the creation of a national registry and the formation of a network of centers. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1097", "contents": "People generally require tracheostomy and lifetime mechanical ventilation on a ventilator in order to survive. However, it has now been shown that  biphasic cuirass ventilation  can effectively be used without the need for a tracheotomy. Other potential treatments for CCHS include oxygen therapy and medicine for stimulating the respiratory system.  Currently, problems arise with the extended use of ventilators, including fatal infections and pneumonia. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1098", "contents": "There are two primary organisations focused on delivering new treatments for CCHS. These are  Keep Me Breathing , a UK based research charity which focuses solely on CCHS and  The CCHS Network , a US based research charity which focuses the vast majority of its funding on CCHS scientific research."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1099", "contents": "Most people with CCHS (unless they have the Late Onset form) do not survive infancy, unless they receive ventilatory assistance during sleep. An alternative to a mechanical ventilator is  diaphragm pacing . [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1100", "contents": "CCHS was first described in 1962 by Severinghaus and Mitchell in three patients following surgery to the upper cervical  spinal cord  and  brainstem . [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1101", "contents": "Its name is a reference to the story of Ondine and Hans, characters in  Ondine , a 1938 play  by  Jean Giraudoux  based on traditions tracing back through  Undine  (a novella of 1811)  to earlier European folk tales. The water-spirit Ondine tells her future husband Hans, whom she had just met, that \"I shall be the shoes of your feet ... I shall be the breath of your lungs\". Ondine reluctantly makes a pact with her uncle the King of the Ondines that if Hans ever deceives her he will die. After their honeymoon, Hans is reunited with his first love Princess Bertha. Ondine leaves Hans in an attempt to protect him, but she is recaptured by a fisherman and Hans is stricken by the King's curse. On meeting Ondine again, Hans tells her that \"all the things my body once did by itself, it does now only by special order ... A single moment of inattention and I forget to breathe\". Hans and Ondine kiss, after which he dies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1102", "contents": "Since being coined in 1962 the name has become controversial in medical literature, as later summaries frequently misunderstood the plot of  Ondine  and its connection to the diagnosis. Most frequently, Ondine was inaccurately blamed for cursing Hans, but other mistakes sometimes changed the nature of the curse itself. Such errors led to confusion in defining the medical condition. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1103", "contents": "Chemical pneumonitis  is inflammation of the lung caused by aspirating or inhaling irritants. [ 1 ]  It is sometimes called a \"chemical  pneumonia \", though it is not infectious. There are two general types of chemical pneumonitis: acute and chronic."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1104", "contents": "Irritants capable of causing chemical pneumonitis include  vomitus , [ 2 ]   barium  used in gastro-intestinal imaging,  chlorine  gas (among other  pulmonary agents ), [ 2 ]  ingested  gasoline [ 2 ]  or other  petroleum distillates , ingested or skin absorbed  pesticides , [ 2 ]  gases from  electroplating , [ 2 ]  smoke [ 2 ]  and others. It may also be caused by the use of  inhalants .\n Mendelson's syndrome  is a type of chemical pneumonitis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1105", "contents": "Mineral oil should not be given internally to young children, pets, or anyone with a cough,  hiatal hernia , or nocturnal reflux, because it can cause complications such as  lipoid pneumonia . [ 3 ]   Due to its low density, it is easily aspirated into the lungs, where it cannot be removed by the body. In children, if aspirated, the oil can work to prevent normal breathing, resulting in death of brain cells and permanent paralysis and/or  brain damage ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1106", "contents": "Acute:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1107", "contents": "Chronic:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1108", "contents": "Symptoms of chronic chemical pneumonitis may or may not be present, and can take months or years to develop to the point of noticeability. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1109", "contents": "The pragmatic challenge is to distinguish from aspiration pneumonia with an infectious component because the former does not require antibiotics while the latter does.  While some issues, such as a recent history of exposure to substantive toxins, can foretell the diagnosis, for a patient with dysphagia the diagnosis may be less obvious, as the dysphagic patient may have caustic gastric contents damaging the lungs which may or may not have progressed to bacterial infection. \n [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1110", "contents": "The following tests help determine how severely the lungs are affected:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1111", "contents": "Treatment is focused on reversing the cause of inflammation and reducing symptoms. Corticosteroids may be given to reduce inflammation, often before long-term scarring occurs.  Antibiotics are usually not helpful or needed, unless there is a secondary infection. Oxygen therapy may be helpful."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1112", "contents": "The  COVID-19 pandemic in Guinea-Bissau  is part of the  worldwide pandemic  of  coronavirus disease 2019  ( COVID-19 ) caused by  severe acute respiratory syndrome coronavirus\u00a02  ( SARS-CoV-2 ). The virus was confirmed to have reached  Guinea-Bissau  in March 2020. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1113", "contents": "Guinea-Bissau reported their first two cases of COVID-19 on March 24, 2020. Restrictions were officially placed on March 18 to retain the spread of the virus. [ 3 ]  Authorities in Guinea-Bissau declared that land borders were to close and a ban to all flights arriving and leaving  Osvaldo Vieira International Airport  on March 17, 2020. The government has closed or restricted access to public services, markets, restaurants and forbid religious or traditional ceremonies, to reduce the spread of COVID-19, yet essential services for basic needs remained open as of March 31, 2020. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1114", "contents": "On 12 January 2020, the  World Health Organization  (WHO) confirmed that a  novel coronavirus  was the cause of a respiratory illness in a cluster of people in Wuhan City, Hubei Province, China, which was reported to the WHO on 31 December 2019. [ 5 ] [ 6 ]  COVID-19 is an infectious disease that can be transmitted through  saliva  droplets or discharge from an infected person by  sneezing ,  coughing  or contracted from surfaces. Most people infected by the COVID-19 virus will show mild to moderate illnesses related to their respiratory system and will not require special treatment for recovery. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1115", "contents": "The  case fatality ratio  for COVID-19 has been much lower than  SARS of 2003 , [ 8 ] [ 9 ]  but the  transmission  has been significantly greater, with a significant total death toll. [ 10 ] [ 8 ]  Model-based simulations for Guinea-Bissau suggest that the 95%  confidence interval  for the  time-varying reproduction number   R  t  has been lower than 1.0 since August 2021. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1116", "contents": "On 25 March, Guinea-Bissau confirmed its first two COVID-19 cases, a  Congolese  U.N. employee and an  Indian citizen . [ 12 ]  A month-long state of emergency with night-time curfew was introduced on 28 March. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1117", "contents": "During the month nine persons tested positive. All nine cases remained active at the end of the month. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1118", "contents": "Guinea-Bissau recorded its first death on 26 April. [ 15 ]  The existing state of emergency was prolonged until 11 May. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1119", "contents": "On 29 April, the Prime Minister  Nuno Gomes Nabiam , Interior Minister  Botche Cand\u00e9 , Secretary of State for Public Order Mario Famb\u00e9, and Secretary of State for Regional Integration Monica Buaro da Costa had tested positive for the coronavirus. [ 16 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1120", "contents": "In April, 192 new cases were reported, bringing the total number of confirmed cases to 201. The death toll was 1. Fifteen patients recovered, leaving 185 active cases at the end of the month. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1121", "contents": "On 1 May, the Minister of Public Health  Antonio Deuna  tested positive for the coronavirus. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1122", "contents": "There were 1,121 new cases in May, raising the total number of confirmed cases to 1,322. The death toll rose to 8. The number of the active cases at the end of the month was 1,206. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1123", "contents": "On 16 June, Reuters reported that 9% of health care workers have been infected with COVID-19. According to Joana Cortez, a WHO expert in Guinea-Bissau, the three main  Bissau  hospitals are currently facing rooms filled with COVID-19 patients and a breakdown in essential medical services. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1124", "contents": "On 26 June, president  Umaro Sissoco Embal\u00f3  announced a one-month extension of the state of emergency, but lifted the curfew. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1125", "contents": "In June, the number of confirmed cases grew by 332 to 1654. The death toll rose to 24. There were 1313 active cases at the end of the month. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1126", "contents": "There were 327 new cases in July, [ 24 ]  224 in August, [ 25 ]  119 in September, [ 26 ]  89 in October, [ 27 ]  28 in November, [ 28 ]  and 11 in December. [ 29 ]  The total number of cases stood at 1981 in July, [ 24 ]  2205 in August, [ 25 ]  2324 in September, [ 26 ]  2413 in October, [ 27 ]  2441 in November, [ 28 ]  and 2452 in December. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1127", "contents": "The number of recovered patients reached 802 in July, [ 24 ]  1549 in September, [ 26 ]  1818 in October, [ 27 ]  2327 in November, [ 28 ]  and 2397 in December, [ 29 ]  leaving 1152 active cases at the end of July, [ 24 ]  1044 at the end of August, [ 25 ]  736 at the end of September, [ 26 ]  554 at the end of October, [ 27 ]  70 at the end of November, [ 28 ]  and 10 at the end of December. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1128", "contents": "The death toll rose to 27 in July, [ 24 ]  34 in August, [ 25 ]  39 in September, [ 26 ]  41 in October, [ 27 ]  44 in November, [ 28 ]  and 45 in December. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1129", "contents": "Vaccinations started on 2 April."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1130", "contents": "There were 182 new cases in January, [ 30 ]  628 in February, [ 31 ]  388 in March, [ 32 ]  83 in April, [ 33 ]  33 in May, [ 34 ]  87 in June, [ 35 ]  645 in July, [ 36 ]  1301 in August, [ 37 ]  308 in September, 27 in October, [ 38 ]  306 in November, [ 39 ]  and 44 in December. [ 40 ]  The total number of cases stood at 2634 in January, [ 30 ]  3262 in February, [ 31 ]  3650 in March, [ 32 ]  3733 in April, [ 33 ]  3766 in May, [ 34 ]  3853 in June, [ 35 ]  4498 in July, [ 36 ]  5799 in August, [ 37 ]  6107 in September, 6134 in October, [ 38 ]  6440 in November, [ 39 ]  and 6484 in December. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1131", "contents": "The number of recovered patients stood at 2427 in January, [ 30 ]  2613 in February, [ 31 ]  2972 in March, [ 32 ]  3300 in April, [ 33 ]  3518 in May, [ 34 ]  3579 in June, [ 35 ]  3968 in July, [ 36 ]  4810 in August, [ 37 ]  5312 in September, 5588 in October, [ 38 ]  6271 in November, [ 39 ]  6302 in December, [ 40 ]  leaving 162 active cases at the end of January, [ 30 ]  601 at the end of February, [ 31 ]  615 at the end of March, [ 32 ]  366 at the end of April, [ 33 ]  180 at the end of May, [ 34 ]  205 at the end of June, [ 35 ]  454 at the end of July, [ 36 ]  870 at the end of August, [ 37 ]  655 at the end of September, 405 at the end of October, [ 38 ]  21 at the end of November, [ 39 ]  and 33 at the end of December. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1132", "contents": "The death toll rose to 48 in February, [ 31 ]  63 in March, [ 32 ]  67 in April, [ 33 ]  68 in May, [ 34 ]  69 in June, [ 35 ]  76 in July, [ 36 ]  119 in August, [ 37 ]  140 in September, 141 in October, [ 38 ]  148 in November, [ 39 ]  and 149 in December. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1133", "contents": "Modeling carried out by the WHO's Regional Office for Africa suggests that due to under-reporting, the true cumulative number of infections by the end of 2021 was around 880,000 while the true number of COVID-19 deaths was around 940. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1134", "contents": "There were 1102 new cases in January, [ 42 ]  436 in February, [ 43 ]  129 in March, [ 44 ]  51 in April, [ 45 ]  78 in May, [ 46 ]  89 in June, [ 47 ]  43 in July, [ 48 ]  384 in August, [ 49 ]  52 in September, [ 50 ]  and 99 in December. [ 51 ]  The total number of cases stood at 7586 in January, [ 42 ]  8022 in February, [ 43 ]  8151 in March, [ 44 ]  8202 in April, [ 45 ]  8280 in May, [ 46 ]  8369 in June, [ 47 ]  8412 in July, [ 48 ]  8796 in August, [ 49 ]  8848 in September, [ 50 ]  and 8947 in December. [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1135", "contents": "The number of recovered patients stood at 6642 in January, [ 42 ]  7002 in February, [ 43 ]  7146 in March, [ 44 ]  7528 in April, [ 45 ]  8042 in May, [ 46 ]  8124 in June, [ 47 ]  8301 in August, [ 49 ]  8642 in September, [ 50 ]  and 8656 in December, [ 51 ]  leaving 788 active cases at the end of January, [ 42 ]  853 at the end of February, [ 43 ]  835 at the end of March, [ 44 ]  503 at the end of April, [ 45 ]  61 at the end of May, [ 46 ]  68 at the end of June, [ 47 ]  320 at the end of August, [ 49 ]  30 at the end of September, [ 50 ]  and 115 at the end of December. [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1136", "contents": "The death toll rose to 156 in January, [ 42 ]  167 in February, [ 43 ]  170 in March, [ 44 ]  171 in April, [ 45 ]  175 in August, [ 49 ]  and 176 in September. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1137", "contents": "There were 667 confirmed cases in 2023, bringing the total number of cases to 9614. One person died in 2023, bringing the total death toll to 177. [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1138", "contents": "Guinea-Bissau's health system is highly fragile, they have been exposed to various infectious diseases such as  Cholera ,  Malaria  and  Meningitis  and the country has the highest prevalence of  HIV  and  Tuberculosis  infections. With the current diseases, poor infrastructure and public sector implications makes the outbreak of COVID-19 highly severe. There is one doctor for every 5,964 people and one nurse for every 1,223 people. Guinea-Bissau possesses no  intensive care unit  specialist or fully practical beds and does not have the ascertain supply of oxygen in the Simao Mendes Hospital, which is the principal public hospital in Guinea-Bissau. There are two missionary hospitals in  Bissau  which lack equipment and coordination and provide some responses to COVID-19. With the rapid transmission of COVID-19 the National Public Health Laboratory is lacking to provide daily testing as a result of limited staff availability and restrains of COVID-19 diagnostic extent. Financial and geographical barriers to testing increase due to quarantine measures, closure of economy activity and the incoming rainy season. [ 53 ]  Health services are limited due to underfunding. This has caused 35-40% of Guinea-Bissau's population to have to travel greater than 5\u00a0km to reach the closest Health Centre (DENARPII) to seek medical attention. Guinea-Bissau has been subjected to financial hardship, lack of technical knowledge to diagnosis and treatment, as well as imposed restrictions by the government which has limited personal  freedom  for the population and has intensified  social inequalities  further. [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1139", "contents": "Guinea-Bissau's main source of  investment  comes from  international trade . Closure of international borders and trade movement restrictions have prevented the trade of cashew nuts between Guinea-Bissau and international partners. Limited export of cashews has greatly impacted the  economy  and thus a reduction of daily and seasonal labor force of the country, such as the harvesting of cashew nuts for farmers. [ 53 ]  The COVID-19 pandemic has greatly reduced international trade for cashews in Guinea-Bissau. Guinea-Bissau's economy is dependent on the export of raw  cashew nuts . [ 3 ]  The yearly cashew campaign has been delayed due to lockdowns affecting 80% of the populations' income. [ 53 ]  The Finance Minister, Jo\u00e3o Fadi\u00e1 of Guinea-Bissau's said that COVID-19 has caused a \"very negative\" impact on the economy as it has impacted the cashew nut market. [ 55 ]  A report by De Barros et al. (2020) revealed that many Guinean individuals ask the question: \"how to ensure social confinement at home in the absence of public policies to assist families?\", due to the lack of safety measure communication to the public. The main city for all urban transport and attraction is the capital of  Guinea , Bandim, which would highly affect the entire capital's economy if borders were to close. [ 54 ]  Transportation between regions have greatly reduced international trade, leading to massive losses for the economy. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1140", "contents": "Since Guinea-Bissau confirmed their positive cases of COVID-19 in the country, the community have changed meaning in simple greetings such as \"Kuma di kurpu (how is your body)?\"  [ 54 ]  People in the community express  worry , mistrust and  anxiety  during  communication . Social distancing measures and practices have disturbed Bissau-Guinean  religions  and cultural codes, as grouping together is essential for traditional rituals. [ 54 ]  However,  stimulation  studies have shown that social distancing has minimised the spread of COVID-19, by reducing physical contact, which involves staying at home, closing of businesses and schools and banning travel. [ 56 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1141", "contents": "With imposed restriction measures due to the  outbreak  of COVID-19 many Bissau-Guinean citizens lost jobs and income opportunities. Two in three Bissau-Guinean citizens are affected by  poverty , with a majority living on less than U$1.90 a day. Citizens struggle to sell produce and earn a daily  income  in  rural  and  urban  areas. Income inequality is prominent in rural areas, as many people lacks in decent living standards and access to basic needs such as clean water. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1142", "contents": "With imposed restriction measures to limit the spread of COVID-19,  schools  nationwide were temporarily closed leading to high internet and  technology  cost which makes home schooling a less practical choice generally. The closure of schools for children may lead to higher risks of dropping out. Due to the temporary closure of schools and loss of jobs during the outbreak children are likely to engage in activities such as  child labour ,  teenage pregnancy  or wedlock. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1143", "contents": "As a result of lockdown practices and restrictions in place, basic supplies were restricted around 2800 tons of chicken and 280,000 tons of rice are imported yearly to sustain the country's demands. With these imposed measures, prices of supplies have increased. [ 3 ]  Mobility measures have restricted access to food especially in urban areas. Lockdown measures mostly affect jobs such as  construction ,  transportation ,  small business  and informal traders, resulting to major barriers in accessing food and basic services. Nutritional status is highly affected due to food access restrains, leading to  malnutrition , with the decrease in import of goods due to economic lockdowns, households are more likely to prioritise  calorie  intake over nutritional values. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1144", "contents": "Women in the  workforce  are substantially affected, gender-based  violence  may be increased due to confinement measures as a result of the COVID-19 pandemic. Women are greatly employed in informal wage activities such as preparing food in restaurants, trading or selling fish, fruit or other foods. These implemented lockdowns and restrictions could potentially lead to the increase risk of  domestic violence  due to an increase in  stress  levels. Women are the most vulnerable to the pandemic, such as early  marriages , trafficking and female health workers and are largely subjected to COVID-19 than men. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1145", "contents": "A reduction of  tourism  has affected the Guinea-Bissau economy, as profit made by tourism activities are limited  [ 3 ]  and for people to enter and exit Guinea-Bissau's borders a negative COVID-19 test result must be presented. [ 4 ]  Travelers travelling to Guinea-Bissau have a reduced dependence on medical facilities and some  prescription medication  needs to be legalised in the country, which further impacts Guinea-Bissau's economy. [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1146", "contents": "A  state of emergency  was declared to reduce the spread of the COVID-19 virus by the  government  and announced for the closing of sea and air transportation and borders by land. The government also implemented guidelines and  laws  to prevent the spread of the COVID-19 virus within the community. These laws limited social gatherings and screenings were made available to detect the COVID-19 virus. [ 58 ]  The prevention of COVID-19 was led by religious leaders and  public figures , as well as traditional power entities and social collectives during communication and social mobilisation. Guinean families were supported through awareness and prevention information against COVID-19 which were provided through networks, associations and most importantly radio stations, which reduces socio-cultural barriers such as attitudes, cultural differences, ethnicity and status to access information about COVID-19. [ 54 ]  Both Guinea-Bissau's government and the  United Nations Children's Emergency Fund  ( UNICEF ) have helped in preparing Guinea-Bissau for the pandemic. The UNICEF and the Secretary of State for Social Communication embedded preventative measures and techniques to the Bissau-Guinean public through social media and on national television to prevent the spread of COVID-19. Public  sanitations  across 960 communities were provided by the UNICEF ( WASH  program) around the country to avoid spreading the virus. [ 58 ]  The  World Health Organization  recommends practicing hand hygiene and physical distancing which could allow for the best protection of oneself and others. [ 59 ]  Health workers in Guinea-Bissau have also received training in preventative practices and in identifying cases by the  U.N . [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1147", "contents": "Guinea-Bissau was supported by many  organisations  including  Global Partnership for Education  (GPE), MPTF and  GAVI , as well as the government of Guinea-Bissau who has provided $200, 000 for the country to help detain the COVID-19 virus. [ 58 ]  The Ministries of  Finance  and  Health  financially supported  hospitals  in Guinea- Bissau on March 27, 2020. The  Fiscal policy  supported and improved hospitals, doctors and nurses received pay benefits of $55,000 monthly, $50,000 for medicine and $100,000 for meals for patients and staff. [ 3 ]  An official of the WHO in Guinea-Bissau has reported that  Cuba  has sent a medical team consisting doctors and nurses to assist in fighting the pandemic during the outbreak. [ 60 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1148", "contents": "Reports on the COVID-19 pandemic in Guinea-Bissau revealed that the UNICEF supported the National Contingency Plan in response to COVID-19 through strategies and interventions focusing on:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1149", "contents": "The UNICEF have adjusted development programmes to the COVID-19 context to improve  interventions  and prevention of COVID-19 shown in the reports \"GUINEA-BISSAU: COVID-19 Situation Report - #05, 2\u20138 May 2020\" and \"GUINEA-BISSAU: COVID-19 Situation Report - #07, 16\u201322 May 2020\", which reveals adaptations to ongoing UNICEF development programmes in Guinea-Bissau to enhance the current COVID-19 interventions and prevention programmes. These UNICEF development programmes adapted to the COVID-19 context include: [ 62 ] [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1150", "contents": "A study in Guinea-Bissau showed that the  BCG vaccine  could decrease respiratory tract infections in children. Bacillus Calmette-Guerin (BCG) is a vaccination developed to fight against tuberculosis and has been widely used around the world. However, the BCG vaccine was reported to reduce 50% of  mortality rates  in infants. Recent studies have also shown a decrease of respiratory tract infections in  adolescents  by using BCG vaccination in  South Africa . [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1151", "contents": "Cystic fibrosis  ( CF ) is a  genetic disorder  inherited in an  autosomal recessive  manner that impairs the normal clearance of  mucus  from the  lungs , which facilitates the colonization and infection of the lungs by bacteria, notably  Staphylococcus aureus . [ 6 ]  CF is a rare [ 7 ] [ 8 ]  genetic disorder that affects mostly the lungs, but also the  pancreas ,  liver ,  kidneys , and  intestine . [ 1 ] [ 9 ]  The hallmark feature of CF is the accumulation of thick mucus in different organs. Long-term issues include  difficulty breathing  and coughing up mucus as a result of frequent  lung infections . [ 1 ]  Other signs and  symptoms  may include  sinus infections ,  poor growth ,  fatty stool ,  clubbing  of the fingers and toes, and  infertility  in most males. [ 1 ]  Different people may have different degrees of symptoms. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1152", "contents": "Cystic fibrosis is inherited in an  autosomal recessive  manner. [ 1 ]  It is caused by the presence of mutations in both copies (alleles) of the  gene  encoding the  cystic fibrosis transmembrane conductance regulator  (CFTR) protein. [ 1 ]  Those with a single working copy are carriers and otherwise mostly healthy. [ 3 ]  CFTR is involved in the production of sweat,  digestive  fluids, and mucus. [ 10 ]  When the CFTR is not functional, secretions that are usually thin instead become thick. [ 11 ]  The condition is diagnosed by a  sweat test  and  genetic testing . [ 1 ]  The sweat test measures sodium concentration, as people with cystic fibrosis have abnormally salty sweat, which can often be tasted by parents kissing their children. Screening of infants at birth takes place in some areas of the world. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1153", "contents": "There is no known cure for cystic fibrosis. [ 3 ]  Lung infections are treated with  antibiotics  which may be given intravenously, inhaled, or by mouth. [ 1 ]  Sometimes, the antibiotic  azithromycin  is used long-term. [ 1 ]  Inhaled  hypertonic saline  and  salbutamol  may also be useful. [ 1 ]   Lung transplantation  may be an option if lung function continues to worsen. [ 1 ]   Pancreatic enzyme replacement  and  fat-soluble vitamin  supplementation are important, especially in the young. [ 1 ]   Airway clearance techniques  such as  chest physiotherapy  may have some short-term benefit, but long-term effects are unclear. [ 12 ]  The average life expectancy is between 42 and 50 years in the  developed world , [ 5 ] [ 13 ]  with a median of 40.7 years. [ 14 ]  Lung problems are responsible for death in 70% of people with cystic fibrosis. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1154", "contents": "CF is most common among people of  Northern European  ancestry, for whom it affects about 1 out of 3,000 newborns, [ 1 ]  and among which around 1 out of 25 people is a carrier. [ 3 ]  It is least common in Africans and Asians, though it does occur in all  races . [ 1 ]  It was first recognized as a specific disease by  Dorothy Andersen  in 1938, with descriptions that fit the condition occurring at least as far back as 1595. [ 9 ]  The name \"cystic fibrosis\" refers to the characteristic  fibrosis  and  cysts  that form within the  pancreas . [ 9 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1155", "contents": "Cystic fibrosis typically manifests early in life. Newborns and infants with cystic fibrosis tend to have frequent, large, greasy  stools  (a result of  malabsorption ) and are  underweight for their age . [ 16 ] :\u200aClinical Manifestations\u200a  15\u201320% of newborns have their  small intestine  blocked by  meconium , often requiring surgery to correct. [ 16 ] :\u200aClinical Manifestations\u200a  Newborns occasionally have  neonatal jaundice  due to blockage of the  bile ducts . [ 16 ] :\u200aClinical Manifestations\u200a  Children with cystic fibrosis lose excessive salt in their sweat, and parents often notice salt crystallizing on the skin, or a salty taste when they kiss their child. [ 16 ] :\u200aClinical Manifestations"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1156", "contents": "The primary cause of  morbidity  and death in people with cystic fibrosis is progressive lung disease, which eventually leads to  respiratory failure . [ 16 ] :\u200aRespiratory Tract\u200a  This typically begins as a prolonged respiratory infection that continues until treated with  antibiotics . [ 16 ] :\u200aRespiratory Tract\u200a  Chronic infection of the respiratory tract is nearly universal in people with cystic fibrosis, with  Pseudomonas aeruginosa , fungi, and  mycobacteria  all increasingly common over time. [ 17 ]  Inflammation of the upper airway results in frequent  runny nose  and  nasal obstruction .  Nasal polyps  are common, particularly in children and teenagers. [ 16 ] :\u200aRespiratory Tract\u200a  As the disease progresses, people tend to have  shortness of breath , and a chronic cough that produces  sputum . [ 16 ] :\u200aBiliary Tract\u200a  Breathing problems make it increasingly challenging to exercise, and prolonged illness causes those affected to be underweight for their age. [ 16 ] :\u200aBiliary Tract\u200a  In late adolescence or adulthood, people begin to develop severe signs of lung disease: wheezing,  digital clubbing ,  cyanosis ,  coughing up blood ,  pulmonary heart disease , and collapsed lung ( atelectasis  or  pneumothorax ). [ 16 ] :\u200aRespiratory Tract"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1157", "contents": "In rare cases, cystic fibrosis can manifest itself as a  coagulation disorder .  Vitamin K  is normally absorbed from  breast milk , formula, and later, solid foods. This absorption is impaired in some CF patients. Young children are especially sensitive to vitamin K malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin K from dietary sources after birth. Because clotting factors II, VII, IX, and X are vitamin K\u2013dependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether an underlying disease is present. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1158", "contents": "Lung disease results from clogging of the airways due to mucus build-up, decreased  mucociliary clearance , and resulting  inflammation . [ 19 ] [ 20 ]  In later stages, changes in the architecture of the lung, such as pathology in the major airways ( bronchiectasis ), further exacerbate difficulties in breathing. Other signs include high  blood pressure  in the lung ( pulmonary hypertension ),  heart failure , difficulties getting enough  oxygen  to the body ( hypoxia ), and respiratory failure requiring support with breathing masks, such as  bilevel positive airway pressure  machines or  ventilators . [ 21 ]   Staphylococcus aureus ,  Haemophilus influenzae , and  Pseudomonas aeruginosa  are the three most common organisms causing lung infections in CF patients. [ 20 ] :\u200a1254\u200a  In addition, opportunistic infection due to  Burkholderia cepacia  complex  can occur, especially through transmission from patient to patient. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1159", "contents": "In addition to typical bacterial infections, people with CF more commonly develop other types of lung diseases. Among these is  allergic bronchopulmonary aspergillosis , in which the body's response to the common  fungus   Aspergillus fumigatus  causes worsening of breathing problems. Another is infection with  Mycobacterium avium  complex, a group of bacteria related to  tuberculosis , which can cause lung damage and do not respond to common antibiotics. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1160", "contents": "Mucus in the  paranasal sinuses  is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and  headaches . Individuals with CF may develop overgrowth of the nasal tissue ( nasal polyps ) due to inflammation from chronic sinus infections. [ 24 ]  Recurrent sinonasal polyps can occur in 10% to 25% of CF patients. [ 20 ] :\u200a1254\u200a  These polyps can block the nasal passages and increase breathing difficulties. [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1161", "contents": "Cardiorespiratory complications are the most common causes of death (about 80%) in patients at most CF centers in the United States. [ 20 ] :\u200a1254"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1162", "contents": "Digestive problems are also prevalent in individuals with CF. Approximately 15%-20% of newborns diagnosed with CF experience intestinal blockage ( meconium ileus ), and other digestive issues may arise due to mucus accumulation in the pancreas. [ 27 ]  Consequently, there is impaired insulin production, leading to cystic fibrosis-related diabetes mellitus. Moreover, enzyme transport disruption from the pancreas to the intestines results in digestive problems such as recurrent diarrhea or weight loss. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1163", "contents": "In cystic fibrosis there is impaired chloride secretion due to mutation of CFTR. This disrupts the ionic balance, causes impaired bicarbonate secretion, and alters the pH. The pancreatic enzymes that work in a specific pH range cannot act as the chyme is not neutralized by bicarbonate ions. This causes impairment of the digestion process. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1164", "contents": "The thick mucus seen in the lungs has a counterpart in thickened secretions from the  pancreas , an organ responsible for providing  digestive juices  that help break down food. These secretions block the  exocrine  movement of the digestive enzymes into the  duodenum  and result in irreversible damage to the pancreas, often with painful inflammation ( pancreatitis ). [ 30 ]  The  pancreatic ducts  are totally plugged in more advanced cases, usually seen in older children or adolescents. [ 20 ]  This causes atrophy of the exocrine glands and progressive fibrosis. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1165", "contents": "In addition, protrusion of internal  rectal  membranes ( rectal prolapse ) is more common, occurring in as many as 10% of children with CF, [ 20 ]  and it is caused by increased fecal volume,  malnutrition , and  increased intra\u2013abdominal pressure  due to coughing. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1166", "contents": "Individuals with CF also have difficulties absorbing the fat-soluble vitamins  A ,  D ,  E , and  K . [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1167", "contents": "In addition to the pancreas problems, people with CF experience more  heartburn , [ 32 ]  intestinal blockage by  intussusception , and  constipation . [ 33 ]  Older individuals with CF may develop  distal intestinal obstruction syndrome , which occurs when feces becomes thick with mucus ( inspissated ) and can cause bloating, pain, and incomplete or complete bowel obstruction. [ 34 ] [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1168", "contents": "Exocrine pancreatic insufficiency  occurs in the majority (85\u201390%) of patients with CF. [ 20 ] :\u200a1253\u200a  It is mainly associated with \"severe\" CFTR mutations, where both alleles are completely nonfunctional (e.g.  \u0394F508 /\u0394F508). [ 20 ] :\u200a1253\u200a  It occurs in 10\u201315% of patients with one \"severe\" and one \"mild\" CFTR mutation where little CFTR activity still occurs, or where two \"mild\" CFTR mutations exist. [ 20 ] :\u200a1253\u200a  In these milder cases, sufficient pancreatic exocrine function is still present so that enzyme supplementation is not required. [ 20 ] :\u200a1253\u200a  Usually, no other GI complications occur in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development. [ 20 ] :\u200a1254\u200a  Despite this, idiopathic  chronic pancreatitis  can occur in a subset of pancreas-sufficient individuals with CF, and is associated with recurrent abdominal pain and life-threatening complications. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1169", "contents": "Liver diseases are another common complication in CF patients. The prevalence observed in studies ranged from 18% at age two to 41% at age 12, with no significant increase thereafter. [ 35 ]  Another study found that males with CF are more prone to liver diseases compared to females, and those with meconium ileus have an increased risk of liver diseases. [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1170", "contents": "Thickened secretions also may cause liver problems in patients with CF.  Bile  secreted by the liver to aid in digestion may block the  bile ducts , leading to liver damage. Impaired digestion or absorption of lipids can result in  steatorrhea . Over time, this can lead to scarring and nodularity ( cirrhosis ). The liver fails to rid the blood of toxins and does not make important proteins, such as those responsible for  blood clotting . [ 37 ] [ 38 ]  Liver disease is the third-most common cause of death associated with CF. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1171", "contents": "Around 5\u20137% of people experience  liver damage  severe enough to cause symptoms: typically  gallstones  causing  biliary colic . [ 16 ] :\u200aBiliary Tract"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1172", "contents": "The pancreas contains the  islets of Langerhans , which are responsible for making  insulin , a hormone that helps regulate blood  glucose . Damage to the pancreas can lead to loss of the islet cells, leading to a type of diabetes unique to those with the disease. [ 39 ]  This  cystic fibrosis-related diabetes  shares characteristics of  type 1  and  type 2  diabetes, and is one of the principal nonpulmonary complications of CF. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1173", "contents": "Vitamin D is involved in  calcium  and  phosphate  regulation. Poor uptake of vitamin D from the diet because of malabsorption can lead to the bone disease  osteoporosis  in which weakened bones are more susceptible to  fractures . [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1174", "contents": "Infertility affects both men and women. At least 97% of men with cystic fibrosis are infertile, but not sterile, and can have children with assisted reproductive techniques. [ 42 ]  The main cause of infertility in men with cystic fibrosis is  congenital absence of the vas deferens  (which normally connects the  testes  to the  ejaculatory ducts  of the  penis ), but potentially also by other mechanisms causing  no sperm ,  abnormally shaped sperm , and  few sperm with poor motility . [ 43 ]  Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF. [ 44 ]  While females with CF are generally fertile, around 20% of women with CF have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts  ovulation  and causes  a lack of menstruation . [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1175", "contents": "CF is caused by having no functional copies (alleles) of the  gene   cystic fibrosis transmembrane conductance regulator  ( CFTR ). As of 2018, over 1,900 mutations leading to CF have been described, but only 5 of them have a frequency greater than 1% among patients. The most common mutant allele,  \u0394F508  (also termed F508del), is a deletion ( \u0394  signifying deletion) of three nucleotides that results in a loss of the amino-acid residue  phenylalanine  (F) at the 508th position of the protein. [ 46 ] [ 47 ]  This mutant allele is already present in 1 in 20 to 25 people of Northern European ancestry; it accounts for 70% of CF cases worldwide and 90% of cases in the  United States ; however, over 700 other mutant alleles, some of which represent new mutations, can produce CF. [ 48 ]  Although most people have two working copies (alleles) of the  CFTR  gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is considered an  autosomal recessive disease . [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1176", "contents": "The  CFTR  gene, found at the q31.2  locus  of  chromosome 7 , is 230,000  base pairs  long, and encodes a protein that is 1,480  amino acids  long. More specifically, the location is between base pair 117,120,016 and 117,308,718 on the long arm of chromosome 7, region 3, band 1, subband 2, represented as 7q31.2. Structurally, the  CFTR  is a type of gene known as an  ABC gene . The product of this gene (the CFTR protein) is a chloride ion channel important in creating sweat, digestive juices, and mucus. This protein possesses two  ATP-hydrolyzing   domains , which allows the protein to use energy in the form of  ATP . It also contains two domains comprising six  alpha helices  apiece, which allow the protein to cross the cell membrane. A regulatory  binding site  on the protein allows activation by  phosphorylation , mainly by  cAMP-dependent protein kinase . [ 21 ]  The  carboxyl terminal  of the protein is anchored to the  cytoskeleton  by a  PDZ  domain interaction. [ 50 ]  The majority of CFTR in lung passages is produced by rare ion-transporting cells that regulate mucus properties. [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1177", "contents": "In addition, the evidence is increasing that genetic modifiers besides  CFTR  modulate the frequency and severity of the disease. One example is  mannan-binding lectin , which is involved in  innate immunity  by facilitating  phagocytosis  of microorganisms.  Polymorphisms  in one or both mannan-binding lectin alleles that result in lower circulating levels of the protein are associated with a threefold higher risk of end-stage lung disease, as well as an increased burden of chronic bacterial infections. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1178", "contents": "Up to one in 25 individuals of Northern European ancestry is considered a  genetic carrier . [ 52 ]  The disease appears only when two of these carriers have children, as each pregnancy between them has a 25% chance of producing a child with the disease. Although only about one of every 3,000 newborns of the affected ancestry has CF, since the CFTR gene's discovery in 1989, over 2,000 variants have been identified, but only about 700 of these have been recognized as responsible for causing CF. [ 53 ]  Current tests look for the most common mutations. [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1179", "contents": "The mutant alleles screened by the test vary according to a person's ethnic group or by the occurrence of CF already in the family. More than 10 million Americans, including one in 25 white Americans, are carriers of one mutant allele of the CF gene.  CF is present in other races , though not as frequently as in white individuals. About one in 46 Hispanic Americans, one in 65 African Americans, and one in 90 Asian Americans carry a mutation of the CF gene. [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1180", "contents": "The  CFTR  gene regulates the transport of salts and water through cell membranes, providing instructions for creating a pathway that allows the passage of chloride ions. [ 54 ]  A mutation in the CFTR gene can impair the normal function of chloride channels, leading to abnormal transport of chloride ions and water, resulting in the formation of thick and abnormal mucus. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1181", "contents": "In the pancreatic duct chloride transport occurs through the voltage gated chloride channels which are influenced by CFTR (Cystic Fibrosis transmembrane conductance regulator). These channel are localised in apical membrane of epitheal cell in pancreatic duct. [ 56 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1182", "contents": "Several mutations in the  CFTR  gene can occur, and different mutations cause different defects in the CFTR protein, sometimes causing a milder or more severe disease. These protein defects are also targets for drugs which can sometimes restore their function.  \u0394F508-CFTR  gene mutation, which occurs in >90% of patients in the U.S., creates a protein that does not  fold  normally and is not appropriately transported to the cell membrane, resulting in its degradation. [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1183", "contents": "Other mutations result in proteins that are too short (truncated) because  production  is ended prematurely. Other mutations produce proteins that do not use energy (in the form of ATP) normally, do not allow chloride, iodide, and thiocyanate to cross the membrane appropriately, [ 58 ]  and degrade at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1184", "contents": "The protein created by this gene is anchored to the  outer membrane  of cells in the  sweat glands , lungs, pancreas, and all other remaining exocrine glands in the body.\nThe protein spans this membrane and acts as a  channel  connecting the inner part of the cell ( cytoplasm ) to the  surrounding fluid . This channel is primarily responsible for controlling the movement of halide anions from inside to outside of the cell; however, in the sweat ducts, it facilitates the movement of chloride from the sweat duct into the cytoplasm. When the CFTR protein does not resorb ions in sweat ducts, chloride, and thiocyanate [ 59 ]  released from sweat glands are trapped inside the ducts and pumped to the skin."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1185", "contents": "Additionally  hypothiocyanite , OSCN, cannot be produced by the immune defense system. [ 60 ] [ 61 ]  Because chloride is  negatively charged , this modifies the electrical potential inside and outside the cell that normally causes  cations  to cross into the cell. Sodium is the most common cation in the extracellular space. The excess chloride within sweat ducts prevents sodium resorption by epithelial sodium channels and the combination of sodium and chloride creates the salt, which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1186", "contents": "Most of the damage in CF is due to blockage of the narrow passages of affected organs with thickened secretions. These blockages lead to remodeling and infection in the lung, damage by accumulated digestive enzymes in the pancreas, blockage of the intestines by thick feces, etc. Several theories have been posited on how the defects in the protein and cellular function cause the clinical effects. The most current theory suggests that defective ion transport leads to dehydration in the airway epithelia, thickening mucus. [ 62 ]  In airway epithelial cells, the cilia exist in between the cell's apical surface and mucus in a layer known as airway surface liquid (ASL). The flow of ions from the cell and into this layer is determined by ion channels such as CFTR. CFTR not only allows chloride ions to be drawn from the cell and into the ASL, but it also regulates another channel called ENac, which allows sodium ions to leave the ASL and enter the respiratory epithelium. CFTR normally inhibits this channel, but if the CFTR is defective, then sodium flows freely from the ASL and into the cell. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1187", "contents": "As water follows sodium, the depth of ASL will be depleted and the cilia will be left in the mucous layer. [ 63 ]  As cilia cannot effectively move in a thick, viscous environment, mucociliary clearance is deficient and a buildup of mucus occurs, clogging small airways. [ 64 ]  The accumulation of more viscous, nutrient-rich mucus in the lungs allows bacteria to hide from the body's immune system, causing repeated respiratory infections. The presence of the same CFTR proteins in the pancreatic duct and sweat glands in the skin also cause symptoms in these systems. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1188", "contents": "The lungs of individuals with cystic fibrosis are colonized and infected by bacteria from an early age. These bacteria, which often spread among individuals with CF, thrive in the altered mucus, which collects in the small airways of the lungs. This mucus leads to the formation of bacterial microenvironments known as  biofilms  that are difficult for immune cells and antibiotics to penetrate. Viscous secretions and persistent respiratory infections repeatedly damage the lung by gradually remodeling the airways, which makes infection even more difficult to eradicate. [ 65 ]  The natural history of CF lung infections and airway remodeling is poorly understood, largely due to the immense spatial and temporal heterogeneity both within and between the microbiomes of CF patients. [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1189", "contents": "Over time, both the types of bacteria and their individual characteristics change in individuals with CF. In the initial stage, common bacteria such as  S.\u00a0aureus  and  H.\u00a0influenzae  colonize and infect the lungs. [ 20 ]  Eventually,  Pseudomonas aeruginosa  (and sometimes  Burkholderia cepacia ) dominates. By 18 years of age, 80% of patients with classic CF harbor  P.\u00a0aeruginosa , and 3.5% harbor  B.\u00a0cepacia . [ 20 ]  Once within the lungs, these bacteria adapt to the environment and develop  resistance  to commonly used antibiotics.  Pseudomonas  can develop special characteristics that allow the formation of large colonies, known as \"mucoid\"  Pseudomonas , which are rarely seen in people who do not have CF. [ 65 ]  Scientific evidence suggests the  interleukin 17  pathway plays a key role in resistance and modulation of the inflammatory response during  P.\u00a0aeruginosa  infection in CF. [ 67 ]  In particular, interleukin 17-mediated immunity plays a double-edged activity during chronic airways infection; on one side, it contributes to the control of  P.\u00a0aeruginosa  burden, while on the other, it propagates exacerbated pulmonary neutrophilia and tissue remodeling. [ 67 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1190", "contents": "Infection can spread by passing between different individuals with CF. [ 68 ]  In the past, people with CF often participated in summer \"CF camps\" and other recreational gatherings. [ 69 ] [ 70 ]  Hospitals grouped patients with CF into common areas and routine equipment (such as  nebulizers ) [ 71 ]  was not sterilized between individual patients. [ 72 ]  This led to transmission of more dangerous strains of bacteria among groups of patients. As a result, individuals with CF are now routinely isolated from one another in the healthcare setting, and healthcare providers are encouraged to wear gowns and gloves when examining patients with CF to limit the spread of virulent bacterial strains. [ 73 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1191", "contents": "CF patients may also have their airways chronically colonized by filamentous fungi (such as  Aspergillus fumigatus ,  Scedosporium apiospermum ,  Aspergillus terreus ) and/or yeasts (such as  Candida albicans ); other filamentous fungi less commonly isolated include  Aspergillus flavus  and  Aspergillus nidulans  (occur transiently in CF respiratory secretions) and  Exophiala dermatitidis  and  Scedosporium prolificans  (chronic airway-colonizers); some filamentous fungi such as  Penicillium emersonii  and  Acrophialophora fusispora  are encountered in patients almost exclusively in the context of CF. [ 74 ]  Defective mucociliary clearance characterizing CF is associated with local immunological disorders. In addition, the prolonged therapy with antibiotics and the use of corticosteroid treatments may also facilitate fungal growth. Although the clinical relevance of the fungal airway colonization is still a matter of debate, filamentous fungi may contribute to the local inflammatory response and therefore to the progressive deterioration of the lung function, as often happens with allergic bronchopulmonary aspergillosis \u00a0 \u2013 the most common fungal disease in the context of CF, involving a Th2-driven immune response to  Aspergillus  species. [ 74 ] [ 75 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1192", "contents": "Diagnosis of CF is initially based on clinical findings indicative of respiratory diseases, various digestive problems, meconium ileus, and more. Definitive diagnosis may involve genetic testing based on family history or chloride concentration testing in sweat, which is relatively high (>60mEq/L) in individuals with CF."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1193", "contents": "In many localities all newborns are screened for cystic fibrosis within the first few days of life, typically by  blood test  for high levels of  immunoreactive trypsinogen . [ 76 ]  Newborns with positive tests or those who are otherwise suspected of having cystic fibrosis based on symptoms or family history, then undergo a  sweat test . An  electric current  is used to drive  pilocarpine  into the skin, stimulating sweating. The sweat is collected and analyzed for salt levels. Having unusually high levels of chloride in the sweat suggests  CFTR  is dysfunctional; the person is then diagnosed with cystic fibrosis. [ 16 ] :\u200aDiagnosis and Assessment\u200a [ note 1 ]  Genetic testing is also available to identify the CFTR mutations typically associated with cystic fibrosis. Many laboratories can test for the 30\u201396 most common CFTR mutations, which can identify over 90% of people with cystic fibrosis. [ 16 ] :\u200aDiagnosis and Assessment"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1194", "contents": "People with CF have less thiocyanate and  hypothiocyanite  in their saliva [ 78 ]  and mucus (Banfi et al.). In the case of milder forms of CF,  transepithelial potential difference  measurements can be helpful. CF can also be diagnosed by identification of mutations in the CFTR gene. [ 79 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1195", "contents": "In many cases, a parent makes the diagnosis because the infant tastes salty. [ 20 ]  Immunoreactive trypsinogen levels can be increased in individuals who have a single mutated copy of the  CFTR  gene (carriers) or, in rare instances, in individuals with two normal copies of the  CFTR  gene. Due to these  false positives , CF screening in newborns can be controversial. [ 80 ] [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1196", "contents": "By 2010 every US state had instituted newborn screening programs [ 82 ]  and as of 2016 [update]  21 European countries had programs in at least some regions. [ 83 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1197", "contents": "Women who are  pregnant  or couples planning a pregnancy can have themselves tested for the  CFTR  gene mutations to determine the risk that their child will be born with CF. Testing is typically performed first on one or both parents and, if the risk of CF is high, testing on the fetus is performed. The  American College of Obstetricians and Gynecologists  recommends all people thinking of becoming pregnant be tested to see if they are a carrier. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1198", "contents": "Because development of CF in the fetus requires each parent to pass on a mutated copy of the  CFTR  gene and because CF testing is expensive, testing is often performed initially on one parent. If testing shows that parent is a  CFTR  gene mutation carrier, the other parent is tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations. [ 49 ]  As of 2016 [update] , typically only the most common mutations are tested for, such as \u0394F508. [ 49 ]  Most commercially available tests look for 32 or fewer different mutations. If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF. [ 85 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1199", "contents": "During pregnancy, testing can be performed on the placenta ( chorionic villus sampling ) or the fluid around the fetus ( amniocentesis ). However, chorionic villus sampling has a risk of fetal death of one in 100 and amniocentesis of one in 200; [ 86 ]  a recent study has indicated this may be much lower, about one in 1,600. [ 87 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1200", "contents": "Economically, for carrier couples of cystic fibrosis, when comparing  preimplantation genetic diagnosis  (PGD) with natural conception (NC) followed by prenatal testing and abortion of affected pregnancies, PGD provides net economic benefits up to a maternal age around 40 years, after which NC, prenatal testing, and abortion have higher economic benefit. [ 88 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1201", "contents": "Treatment for CF is diverse, tailored to different symptoms, and includes various devices, inhalation medications to alleviate respiratory difficulties, oral enzyme supplements to address exocrine pancreatic insufficiency, and, in some cases, surgical interventions for conditions such as meconium ileus. [ 89 ]  While treatment alleviates symptoms and prevents potential complications, there is currently no cure for the disease."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1202", "contents": "The management of CF has improved significantly over the past 70 years. While infants born with it 70 years ago would have been unlikely to live beyond their first year, infants today are likely to live well into adulthood. Advances in the treatment of cystic fibrosis have meant that people with cystic fibrosis can live a fuller life less encumbered by their condition. The cornerstones of management are the proactive treatment of  airway infection , encouragement of good nutrition, and an active lifestyle.  Pulmonary rehabilitation  as a management of CF continues throughout a person's life, and is aimed at maximizing organ function, and therefore the quality of life. [ 90 ]  Occupational therapists use energy conservation techniques in the rehabilitation process for patients with cystic fibrosis. [ 91 ]  Examples of energy conservation techniques are ergonomic principles, pursed lip breathing, and diaphragmatic breathing. [ 92 ]  People with CF tend to have fatigue and dyspnoea due to chronic pulmonary infections, so reducing the amount of energy spent during activities can help people feel better and gain more independence. [ 91 ]  At best, current treatments delay the decline in organ function. [ citation needed ]  Because of the wide variation in disease symptoms, treatment typically occurs at specialist multidisciplinary centers and is tailored to the individual. Targets for therapy are the lungs, gastrointestinal tract (including pancreatic enzyme supplements), the  reproductive organs  (including  assisted reproductive technology ), and psychological support. [ 93 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1203", "contents": "The most consistent aspect of therapy in CF is limiting and treating the lung damage caused by thick mucus and infection, with the goal of maintaining  quality of life .  Intravenous ,  inhaled , and oral antibiotics are used to treat chronic and acute infections. Mechanical devices and inhalation medications are used to alter and clear the thickened mucus. These therapies, while effective, can be extremely time-consuming.  Oxygen therapy  at home is recommended in those with significant low oxygen levels. [ 94 ]  Many people with CF use  probiotics , which are thought to be able to correct intestinal dysbiosis and inflammation, but the clinical trial evidence regarding the effectiveness of probiotics for reducing pulmonary exacerbations in people with CF is uncertain. [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1204", "contents": "Many people with CF are on one or more antibiotics at all times, even when healthy, to  prophylactically  suppress infection. The choice of antibiotics for cystic fibrosis depends on the specific bacteria that are causing the infection, as well as the patient's age, weight, and other medical conditions. [ citation needed ]  Antibiotics are absolutely necessary whenever pneumonia is suspected or a noticeable decline in lung function is seen, and are usually chosen based on the results of a sputum analysis and the person's past response. [ citation needed ]  This prolonged therapy often necessitates hospitalization and insertion of a more permanent  IV  such as a  peripherally inserted central catheter  or  Port-a-Cath . Inhaled therapy with antibiotics such as  tobramycin ,  colistin , and  aztreonam  is often given for months at a time to improve lung function by impeding the growth of colonized bacteria. [ 96 ] [ 97 ] [ 98 ]  Inhaled antibiotic therapy helps lung function by fighting infection, but also has significant drawbacks such as development of antibiotic resistance, tinnitus, and changes in the voice. [ 99 ]  Inhaled  levofloxacin  may be used to treat  Pseudomonas aeruginosa  in people with cystic fibrosis who are infected. [ 100 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1205", "contents": "Antibiotics by mouth such as ciprofloxacin or  azithromycin  are given to help prevent infection or to control ongoing infection. [ 101 ]  The  aminoglycoside  antibiotics (e.g. tobramycin) used can cause  hearing loss , damage to the  balance system  in the  inner ear  or kidney failure with long-term use. [ 102 ]  To prevent these  side-effects , the amount of antibiotics in the blood is routinely measured and adjusted accordingly. [ 103 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1206", "contents": "Currently, no reliable clinical trial evidence shows the effectiveness of antibiotics for pulmonary exacerbations in people with cystic fibrosis and  Burkholderia cepacia  complex [ 104 ]  or for the use of antibiotics to treat  nontuberculous mycobacteria  in people with CF. [ 105 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1207", "contents": "The early management of  Pseudomonas aeruginosa  infection is usually suggested using nebulised antibiotics with or without oral antibiotics to remove the bacteria from the person's airways for a period of time. [ 106 ]  When choosing antibiotics to treat lung infections caused by  Pseudomonas aeruginosa  in people with cystic fibrosis, it is still unclear whether the choice of antibiotics should be based on the results of testing antibiotics separately (one at a time) or in combination with each other. [ 107 ]  It is also not clear if these treatment approaches for the  Pseudomonas aeruginosa  infection improve the person's quality of life or lifespan. [ 106 ]  The negative side effects of antibiotics for this infection are also not well studied. [ 106 ]  Intravenous antibiotic therapy to treat  Pseudomonas aeruginosa  infections has been shown not to be any better than antibiotics taken orally. [ 106 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1208", "contents": "Methicillin-resistant  Staphylococcus aureus  (MRSA) infections can be dangerous for people with cystic fibrosis and can worsen lung damage leading to more rapid decline. Early treatment with antibiotics is standard; however, further research is needed to determine longer term effects and benefits (3\u20136 months after the treatment or longer) and survival rates associated with different treatment options. [ 108 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1209", "contents": "Factors related to the antibiotics use, the chronicity of the disease, and the emergence of resistant bacteria demand more exploration for different strategies such as antibiotic  adjuvant  therapy. [ 109 ]  Antibiotic adjuvant therapy refers to therapeutic approaches that aim to improve the action of antibiotics such a pharmaceutical agents or supplements that impact the virulence of the bacterium or that change the susceptibility of the organism to the antibiotic so that the antibiotics are more effective. [ 109 ]  There is no strong evidence to recommend specific antibiotic adjuvant therapies such as  \u03b2-carotene ,  nitric oxide ,  zinc supplements , or KB001-A. [ 109 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1210", "contents": "Aerosolized medications that help loosen secretions include  dornase alfa  and  hypertonic   saline . [ 110 ]  Dornase is a  recombinant  human  deoxyribonuclease , which breaks down DNA in the sputum, thus decreasing its viscosity. [ 111 ]  Dornase alpha improves lung function and probably decreases the risk of exacerbations but there is insufficient evidence to know if it is more or less effective than other similar medications. [ 112 ]  Dornase alpha may improve lung function; however, there is no strong evidence that it is better than other hyperosmolar therapies. [ 112 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1211", "contents": "Denufosol , an investigational drug, opens an alternative chloride channel, helping to liquefy mucus. [ 113 ]  Whether  inhaled corticosteroids  are useful is unclear, but stopping inhaled corticosteroid therapy is safe. [ 114 ]  There is weak evidence that corticosteroid treatment may cause harm by interfering with growth. [ 114 ]   Pneumococcal vaccination  has not been studied as of 2014 [update] . [ 115 ]  As of 2014 [update] , there is no clear evidence from randomized controlled trials that the  influenza vaccine  is beneficial for people with cystic fibrosis. [ 116 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1212", "contents": "Ivacaftor  is a medication taken by mouth for the treatment of CF due to a number of specific mutations responsive to ivacaftor-induced CFTR protein enhancement. [ 117 ] [ 118 ]  It improves lung function by about 10%; however, as of 2014 [update]  it is expensive. [ 117 ]  The first year it was on the market, the list price was over $300,000 per year in the United States. [ 117 ]  In July 2015, the U.S. Food and Drug Administration approved  lumacaftor/ivacaftor . [ 119 ]  In 2018, the FDA approved the combination  ivacaftor/tezacaftor ; the manufacturer announced a list price of $292,000 per year. [ 120 ]   Tezacaftor  helps move the CFTR protein to the correct position on the cell surface, and is designed to treat people with the  F508del  mutation. [ 121 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1213", "contents": "In 2019, the  combination drug   elexacaftor/ivacaftor/tezacaftor , marketed as Trikafta,was approved for CF patients over the age of 12 in the United States. [ 122 ] [ 123 ]  In 2021, this was extended to include patients over the age of 6. [ 124 ]  In Europe this drug was approved in 2020 and marketed as Kaftrio. [ 125 ]   It is used in those that have a f508del mutation, which occurs in about 90% of patients with cystic fibrosis. [ 122 ] [ 126 ]  According to the  Cystic Fibrosis Foundation , \"this medicine represents the single greatest therapeutic advancement in the history of CF, offering a treatment for the underlying cause of the disease that could eventually bring modulator therapy to 90 percent of people with CF.\" [ 127 ]  In a clinical trial, participants who were administered the combination drug experienced a subsequent 63% decrease in pulmonary exacerbations and a 41.8\u00a0mmol/L decrease in sweat chloride concentration. [ 128 ]  By mitigating a repertoire of symptoms associated with cystic fibrosis, the combination drug significantly improved quality-of-life metrics among patients with the disease as well. [ 128 ] [ 127 ]  The combination drug is also known to interact with CYP3A inducers, [ 129 ]  such as carbamazepine used in the treatment of bipolar disorder, causing elexafaftor/ivacaftor/tezacaftor to circulate in the body at decreased concentrations. As such, concurrent use is not recommended. [ 130 ]  The list price in the US is going to be $311,000 per year; [ 131 ]  however, insurance may cover much of the cost of the drug. [ 132 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1214", "contents": "Ursodeoxycholic acid , a  bile salt , has been used; however, there is insufficient data to show if it is effective. [ 133 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1215", "contents": "The combination  vanzacaftor/tezacaftor/deutivacaftor  (Alyftrek) was approved for medical use in the United States in December 2024. [ 134 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1216", "contents": "It is uncertain whether  vitamin A  or  beta-carotene  supplementation have any effect on eye and skin problems caused by vitamin A deficiency. [ 135 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1217", "contents": "There is no strong evidence that people with cystic fibrosis can prevent  osteoporosis  by increasing their intake of  vitamin D . [ 136 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1218", "contents": "For people with  vitamin E  deficiency and cystic fibrosis, there is evidence that vitamin E supplementation may improve vitamin E levels, although it is still uncertain what effect supplementation has on vitamin E-specific deficiency disorders or on lung function. [ 137 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1219", "contents": "Robust evidence regarding the effects of  vitamin K  supplementation in people with cystic fibrosis is lacking as of 2020. [ 138 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1220", "contents": "Various studies have examined the effects of omega-3 fatty acid supplementation for people with cystic fibrosis but the evidence is uncertain whether it has any benefits or adverse effects. [ 139 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1221", "contents": "Several mechanical techniques are used to dislodge sputum and encourage its expectoration. One technique good for short-term airway clearance is  chest physiotherapy  where a respiratory therapist percusses an individual's chest by hand several times a day, to loosen up secretions. This \"percussive effect\" can be administered also through specific devices that use  chest wall oscillation  or  intrapulmonary percussive ventilator . Other methods such as  biphasic cuirass ventilation , and associated clearance mode available in such devices, integrate a cough assistance phase, as well as a vibration phase for dislodging secretions. These are portable and adapted for home use. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1222", "contents": "Another technique is positive expiratory pressure physiotherapy that consists of providing a back pressure to the airways during expiration. This effect is provided by devices that consists of a mask or a mouthpiece in which a resistance is applied only on the expiration phase. [ 140 ]  Operating principles of this technique seems to be the increase of gas pressure behind mucus through  collateral ventilation  along with a temporary increase in functional residual capacity preventing the early collapse of small airways during exhalation. [ 141 ] [ 142 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1223", "contents": "As lung disease worsens, mechanical breathing support may become necessary. Individuals with CF may need to wear special masks at night to help push air into their lungs. These machines, known as  bilevel positive airway pressure  (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. Non-invasive ventilators may be used during physical therapy to improve sputum clearance. [ 143 ]  It is not known if this type of therapy has an impact on pulmonary exacerbations or disease progression. [ 143 ]  It is not known what role non-invasive ventilation therapy has for improving exercise capacity in people with cystic fibrosis. [ 143 ]  However, the authors noted that \"non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum\". [ 144 ]  During severe illness, a tube may be placed in the throat (a procedure known as a  tracheostomy ) to enable breathing supported by a ventilator. [ 145 ] [ 146 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1224", "contents": "For children, preliminary studies show  massage therapy  may help people and their families' quality of life. [ 147 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1225", "contents": "Some lung infections require surgical removal of the infected part of the lung. If this is necessary many times, lung function is severely reduced. [ 148 ]  The most effective treatment options for people with CF who have spontaneous or recurrent  pneumothoraces  is not clear. [ 149 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1226", "contents": "Lung transplantation  may become necessary for individuals with CF as lung function and  exercise tolerance  decline. Although single lung transplantation is possible in other diseases, individuals with CF must have both lungs replaced because the remaining lung might contain bacteria that could infect the transplanted lung. A pancreatic or liver transplant may be performed at the same time to alleviate liver disease and/or diabetes. [ 150 ]  Lung transplantation is considered when lung function declines to the point where assistance from mechanical devices is required or someone's survival is threatened. [ 151 ]  According to  Merck Manual , \"bilateral lung transplantation for severe lung disease is becoming more routine and more successful with experience and improved techniques. Among adults with CF, median survival posttransplant is about 9 years.\" [ 152 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1227", "contents": "Newborns with intestinal obstruction typically require surgery, whereas adults with distal intestinal obstruction syndrome typically do not. Treatment of pancreatic insufficiency by replacement of missing digestive enzymes allows the duodenum to properly absorb nutrients and vitamins that would otherwise be lost in the feces. However, the best dosage and form of pancreatic enzyme replacement is unclear, as are the risks and long-term effectiveness of this treatment. [ 153 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1228", "contents": "So far, no large-scale research involving the incidence of  atherosclerosis  and  coronary heart disease  in adults with cystic fibrosis has been conducted. This is likely because the vast majority of people with cystic fibrosis do not live long enough to develop clinically significant atherosclerosis or coronary heart disease. [ 154 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1229", "contents": "Diabetes  is the most common nonpulmonary complication of CF. It mixes features of type 1 and type 2 diabetes, and is recognized as a distinct entity,  cystic fibrosis-related diabetes . [ 40 ] [ 155 ]  While oral  antidiabetic drugs  are sometimes used, the recommended treatment is the use of  insulin  injections or an  insulin pump , [ 156 ]  and, unlike in type 1 and 2 diabetes, dietary restrictions are not recommended. [ 40 ]  While  Stenotrophomonas maltophilia  is relatively common in people with cystic fibrosis, the evidence about the effectiveness of antibiotics for  S. maltophilia  is uncertain. [ 157 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1230", "contents": "Bisphosphonates  taken by mouth or  intravenously  can be used to improve the bone mineral density in people with cystic fibrosis, but there are no proof that this reduces fractures or increases survival rates. [ 158 ]  When taking bisphosphates intravenously,  adverse effects  such as pain and flu-like symptoms can be an issue. [ 158 ]  The adverse effects of bisphosphates taken by mouth on the gastrointestinal tract are not known. [ 158 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1231", "contents": "Poor growth may be avoided by insertion of a  feeding tube  for increasing food energy through supplemental feeds or by administration of injected  growth hormone . [ 159 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1232", "contents": "Sinus infections are treated by prolonged courses of antibiotics. The development of nasal polyps or other chronic changes within the nasal passages may severely limit airflow through the nose, and over time reduce the person's sense of smell. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such as  fluticasone propionate  are used to decrease nasal inflammation. [ 160 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1233", "contents": "Female infertility may be overcome by  assisted reproduction  technology, particularly  embryo transfer  techniques. Male infertility caused by absence of the vas deferens may be overcome with  testicular sperm extraction , collecting sperm cells directly from the testicles. If the collected sample contains too few sperm cells to likely have a spontaneous fertilization,  intracytoplasmic sperm injection  can be performed. [ 161 ]   Third party reproduction  is also a possibility for women with CF. Whether taking  antioxidants  affects outcomes is unclear. [ 162 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1234", "contents": "Physical exercise is usually part of outpatient care for people with cystic fibrosis. [ 163 ]  Aerobic exercise seems to be beneficial for aerobic exercise capacity, lung function and health-related quality of life; however, the quality of the evidence was poor. [ 163 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1235", "contents": "Due to the use of aminoglycoside antibiotics, ototoxicity is common. Symptoms may include \"tinnitus, hearing loss, hyperacusis, aural fullness, dizziness, and vertigo\". [ 164 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1236", "contents": "Problems with the gastrointestinal system including constipation and obstruction of the gastrointestinal tract including distal intestinal obstruction syndrome are frequent complications for people with cystic fibrosis. [ 34 ]  Treatment of gastrointestinal problems is required in order to prevent a complete obstruction, reduce other CF symptoms, and improve the quality of life. [ 34 ]  While stool softeners, laxatives, and prokinetics (GI-focused treatments) are often suggested, there is no clear consensus from experts at to which approach is the best and comes with the least risks. [ 34 ]  Mucolytics or systemic treatments aimed at dysfunctional CFTR are also sometimes suggested to improve symptoms. [ 165 ]  The evidence supporting these recommendations are very weak and more research is needed to understand how to prevent and treat GI problems in people with CF. [ 165 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1237", "contents": "The prognosis for cystic fibrosis has improved due to earlier diagnosis through screening and better treatment and access to health care. In 1959, the median age of survival of children with CF in the United States was six months. [ 166 ] \nIn 2010, survival is estimated to be 37 years for women and 40 for men. [ 167 ]  In Canada, median survival increased from 24 years in 1982 to 47.7 in 2007. [ 168 ]  In the United States those born with CF in 2016 have a predicted life expectancy of 47.7 when cared for in specialty clinics. [ 169 ]  Due to the recent development of new treatments, such as CFTR modulators, life expectancy has increased rapidly during recent years. In 2020 the median predicted life expectancy was around 59 years, although there are uncertainties in the estimates due to the low number of annual deaths for persons with cystic fibrosis. [ 170 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1238", "contents": "In the US, of those with CF who are more than 18 years old as of 2009, 92% had graduated from high school, 67% had at least some college education, 15% were disabled, 9% were unemployed, 56% were single, and 39% were married or living with a partner. [ 171 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1239", "contents": "Chronic illnesses can be difficult to manage. CF is a chronic illness that affects the \"digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections\". [ 172 ]  The thick secretions clog the airways in the lungs, which often cause inflammation and severe lung infections. [ 173 ] [ 174 ]  If it is compromised, it affects the quality of life of someone with CF and their ability to complete such tasks as everyday chores. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1240", "contents": "According to Schmitz and Goldbeck (2006), CF significantly increases emotional stress on both the individual and the family, \"and the necessary time-consuming daily treatment routine may have further negative effects on quality of life\". [ 175 ]  However, Havermans and colleagues (2006) have established that young outpatients with CF who have participated in the Cystic Fibrosis Questionnaire-Revised \"rated some quality of life domains higher than did their parents\". [ 176 ]  Consequently, outpatients with CF have a more positive outlook for themselves. As  Merck Manual  notes, \"with appropriate support, most patients can make an age-appropriate adjustment at home and school. Despite myriad problems, the educational, occupational, and marital successes of patients are impressive.\" [ 152 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1241", "contents": "Furthermore, there are many ways to enhance the quality of life in CF patients. Exercise is promoted to increase lung function. Integrating an exercise regimen into the CF patient's daily routine can significantly improve quality of life. [ 177 ]  No definitive cure for CF is known, but diverse medications are used, such as mucolytics, bronchodilators, steroids, and antibiotics, that have the purpose of loosening mucus, expanding airways, decreasing inflammation, and fighting lung infections, respectively. [ 178 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1242", "contents": "Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage. [ 180 ]  In the United States, about 30,000 individuals have CF; most are diagnosed by six months of age. In Canada, about 4,000 people have CF. [ 181 ]  Around 1 in 25 people of European descent, and one in 30 of white Americans, [ 182 ]  is a carrier of a CF mutation. Although CF is less common in these groups, roughly one in 46  Hispanics , one in 65  Africans , and one in 90  Asians  carry at least one abnormal  CFTR  gene. [ 183 ] [ 184 ]  Ireland has the world's highest prevalence of CF, at one in 1353; [ 185 ]  Japan's prevalence of CF is among the lowest in the world, at one in 350,000. [ 186 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1243", "contents": "Although technically a rare disease, CF is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world. An exception is  Finland , where only one in 80 people carries a CF mutation. [ 187 ]  The  World Health Organization  states, \"In the European Union, one in 2000\u20133000 newborns is found to be affected by CF\". [ 188 ]  In the United States, one in 3,500 children is born with CF. [ 189 ]  In 1997, about one in 3,300 white children in the United States was born with CF. In contrast, only one in 15,000 African American children have it, and in Asian Americans, the rate was even lower at one in 32,000. [ 190 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1244", "contents": "Cystic fibrosis is diagnosed equally in males and females. For reasons that remain unclear, data have shown that males tend to have a longer life expectancy than females, [ 191 ] [ 192 ]  though recent studies suggest this gender gap may no longer exist, perhaps due to improvements in health care facilities. [ 193 ] [ 194 ]  A recent study from Ireland identified a link between the female hormone estrogen and worse outcomes in CF. [ 195 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1245", "contents": "The distribution of CF alleles varies among populations. The frequency of \u0394F508 carriers has been estimated at one in 200 in northern Sweden, one in 143 in Lithuanians, and one in 38 in Denmark. No \u0394F508 carriers were found among 171 Finns and 151  Saami people . [ 196 ]  \u0394F508 does occur in Finland, but it is a minority allele there. CF is known to occur in only 20 families (pedigrees) in Finland. [ 197 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1246", "contents": "The \u0394F508 mutation is estimated to have occurred up to 52,000 years ago. [ 198 ]  Numerous hypotheses have been advanced as to why such a lethal allele has persisted and spread in the human population. Other common autosomal recessive diseases such as  sickle-cell anemia  have been found to protect carriers from other diseases, an  evolutionary trade-off  known as  heterozygote advantage . Resistance to the following have all been proposed as possible sources of heterozygote advantage:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1247", "contents": "CF is supposed to have appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment. [ 208 ]  Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier. Indeed, literature from Germany and Switzerland in the 18th century warned  \"Wehe dem Kind, das beim Ku\u00df auf die Stirn salzig schmeckt, es ist verhext und muss bald sterben\"  (\"Woe to the child who tastes salty from a kiss on the forehead, for he is bewitched and soon must die\"), recognizing the association between the salt loss in CF and illness. [ 208 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1248", "contents": "In the 19th century,  Carl von Rokitansky  described a case of fetal death with  meconium peritonitis , a complication of meconium ileus associated with CF. Meconium ileus was first described in 1905 by  Karl Landsteiner . [ 208 ]  In 1936,  Guido Fanconi  described a connection between  celiac disease , cystic fibrosis of the pancreas, and  bronchiectasis . [ 209 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1249", "contents": "In 1938,  Dorothy Hansine Andersen  published an article, \"Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study\", in the  American Journal of Diseases of Children . She was the first to describe the characteristic cystic fibrosis of the pancreas and to correlate it with the lung and intestinal disease prominent in CF. [ 15 ]  She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952,  Paul di Sant'Agnese  discovered abnormalities in sweat electrolytes; a sweat test was developed and improved over the next decade. [ 210 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1250", "contents": "The first linkage between CF and another marker ( paraoxonase ) was found in 1985 by  Hans Eiberg , indicating that only one locus exists for CF. [ 211 ]  In 1988, the first mutation for CF,  \u0394F508 , was discovered by  Francis Collins ,  Lap-Chee Tsui , and  John R. Riordan  on the seventh chromosome. [ 212 ]  Subsequent research has found over 1,000 different mutations that cause CF. [ 213 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1251", "contents": "Because mutations in the  CFTR  gene are typically small,  classical genetics  techniques had been unable to accurately pinpoint the mutated gene. [ 214 ]  Using protein markers,  gene-linkage  studies were able to map the mutation to chromosome 7.  Chromosome walking  and  chromosome jumping  techniques were then used to identify and  sequence  the gene. [ 214 ]  In 1989, Lap-Chee Tsui led a team of researchers at the  Hospital for Sick Children  in  Toronto  that discovered the gene responsible for CF. [ 215 ]  CF represents a classic example of how a human genetic disorder was elucidated strictly by the process of  forward genetics . [ 214 ] [ 216 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1252", "contents": "People with CF may be listed in a  disease registry  that allows researchers and doctors to track health results and identify candidates for clinical trials. [ 217 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1253", "contents": "Gene therapy  has been explored as a potential cure for CF. Results from clinical trials have shown limited success as of 2016 [update] , and using gene therapy as routine therapy is not suggested. [ 218 ]  A small study published in 2015 found a small benefit. [ 219 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1254", "contents": "The focus of much CF gene therapy research is aimed at trying to place a normal copy of the  CFTR  gene into affected cells. Transferring the normal  CFTR  gene into the affected epithelial cells would result in the production of functional CFTR protein in all target cells, without adverse reactions or an inflammation response; this is known as the somatic cell therapy. To prevent the lung manifestations of CF, only 5\u201310% the normal amount of CFTR gene expression is needed. [ 220 ]  Multiple approaches have been tested for gene transfer, such as liposomes and viral vectors in animal models and clinical trials. However, both methods were found to be relatively inefficient treatment options, [ 221 ]  mainly because very few cells take up the vector and express the gene, so the treatment has little effect. Additionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable. [ 222 ]  There has been a functional repair in culture of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. [ 223 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1255", "contents": "Bacteriophage therapy ( phage therapy ) is being studied for multidrug resistant bacteria in people with CF. [ 224 ] [ 225 ]  Bacteriophage therapy is a treatment method that uses viruses, known as  bacteriophages , to target and destroy harmful bacteria in the body. Unlike antibiotics, which can kill a wide range of bacteria and potentially disrupt the body's normal flora, phage therapy is highly specific, targeting only the harmful bacteria while leaving the beneficial ones unharmed. As such, the bacteriophage therapy makes is a promising alternative for treating infections caused by multidrug-resistant bacteria, such as Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa in CF patients, which are often protected by biofilms and thus resistant to conventional antibiotics. [ 226 ] [ 227 ] [ 228 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1256", "contents": "Bacteriophage therapy uses viruses as antimicrobial agents to overcome the antibiotic resistance in bacteria with biofilms [ 229 ]  Phage therapy is used to treat the  Pseudomonas aeruginosa  infection in the lungs, which is frequently seen in cystic fibrosis patients, as these bacteria produce biofilms which give them multi-drug resistance. [ 230 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1257", "contents": "A number of small molecules that aim at compensating various mutations of the  CFTR  gene are under development. CFTR  modulator therapies  have been used in place of other types of genetic therapies. These therapies focus on the expression of a genetic mutation instead of the mutated gene itself. Modulators are split into two classes: potentiators and correctors. Potentiators act on the CFTR ion channels that are embedded in the cell membrane, and these types of drugs help open up the channel to allow transmembrane flow. Correctors are meant to assist in the transportation of nascent proteins, a protein that is formed by ribosomes before it is morphed into a specific shape, to the cell surface to be implemented into the cell membrane. [ 231 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1258", "contents": "Most target the transcription stage of genetic expression. One approach has been to try and develop medication that get the ribosome to overcome the  stop codon  and produce a full-length CFTR protein. About 10% of CF results from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. These drugs target  nonsense mutations  such as G542X, which consists of the amino acid  glycine  in position 542 being replaced by a stop codon. Aminoglycoside antibiotics interfere with protein synthesis and error-correction. In some cases, they can cause the cell to overcome a premature stop codon by inserting a random amino acid, thereby allowing expression of a full-length protein. Future research for these modulators is focused on the cellular targets that can be effected by a change in a gene's expression. Otherwise, genetic therapy will be used as a treatment when modulator therapies do not work given that 10% of people with cystic fibrosis are not affected by these drugs. [ 232 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1259", "contents": "Elexacaftor/ivacaftor/tezacaftor  was approved in the United States in 2019 for cystic fibrosis. [ 233 ]  This combination of previously developed medicines is able to treat up to 90% of people with cystic fibrosis. [ 231 ] [ 233 ]  This medications restores some effectiveness of the CFTR protein so that it can work as an ion channel on the cell's surface. [ 234 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1260", "contents": "It has previously been shown that inter-species interactions are an important contributor to the pathology of CF lung infections. Examples include the production of antibiotic degrading enzymes such as \u03b2-lactamases and the production of metabolic by-products such as short-chain fatty acids (SCFAs) by anaerobic species, which can enhance the pathogenicity of traditional pathogens such as  Pseudomonas aeruginosa . [ 235 ]  Due to this, it has been suggested that the direct alteration of CF microbial community composition and metabolic function would provide an alternative to traditional antibiotic therapies. [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1261", "contents": "Antisense therapy  is being researched to treat a subset of mutations which have limited or no response to CFTR modulators. [ 236 ]  Such mutations fall into two classes: splicing (e.g., c.3718-2477C>T) and nonsense (e.g., G542X, W1282X), both of which result in very low expression of CFTR protein, although the protein itself is usually unaffected. This is contrary to the more common mutations such as \u0394F508 which have normal CFTR expression but in a non-functional form. Modulators serve only to correct these aberrant proteins and are of little to no benefit in the case of insufficient expression. Antisense oligonucleotides (ASOs) can solve this problem through the promotion of mRNA degradation or by changing pre-mRNA splicing, nonsense-mediated mRNA decay, or translation, thus increasing CFTR expression."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1262", "contents": "Diffuse panbronchiolitis  ( DPB ) is an  inflammatory   lung disease  of unknown cause. It is a severe, progressive form of  bronchiolitis , an inflammatory condition of the  bronchioles  (small air passages in the lungs). The term  diffuse  signifies that  lesions  appear throughout both lungs, while  panbronchiolitis  refers to inflammation found in all layers of the  respiratory bronchioles  (those involved in  gas exchange ). DPB causes severe inflammation and  nodule -like lesions of  terminal bronchioles , chronic  sinusitis , and intense coughing with large amounts of  sputum  production."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1263", "contents": "The disease is believed to occur when there is susceptibility, or a lack of  immune system  resistance, to DPB-causing  bacteria  or  viruses , caused by several genes that are found predominantly in individuals of  East Asian  descent. The highest  incidence  occurs among  Japanese people , followed by  Koreans . DPB occurs more often in males and usually begins around age 40. It was recognized as a distinct new disease in the early 1960s and was formally named  diffuse panbronchiolitis  in 1969."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1264", "contents": "If left untreated, DPB progresses to  bronchiectasis , an irreversible lung condition that involves enlargement of the bronchioles, and pooling of  mucus  in the bronchiolar passages. Daily treatment of DPB with  macrolide   antibiotics  such as  erythromycin  eases symptoms and increases survival time, but the disease currently has no known cure. The eventual result of DPB can be  respiratory failure  and heart problems."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1265", "contents": "The term \"bronchiolitis\" generally refers to inflammation of the bronchioles. [ 1 ]  DPB is classified as a form of \"primary bronchiolitis\", which means that the underlying cause of bronchiolitis is originating from or is confined to the bronchioles. [ 2 ] [ 3 ]  Along with DPB, additional forms of primary bronchiolitis include  bronchiolitis obliterans , follicular bronchiolitis,  respiratory bronchiolitis ,  mineral dust airway disease , and a number of others. [ 2 ]  Unlike DPB, bronchiolitis that is not considered \"primary\" would be associated with diseases of the larger airways, such as  chronic bronchitis . [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1266", "contents": "Symptoms of DPB include  chronic sinusitis  (inflamed  paranasal sinuses ), wheezing,  crackles  ( respiratory sounds  made by obstructions such as phlegm and  secretions  in the lungs),  dyspnea  (shortness of breath), and a severe cough that yields large amounts of sputum (coughed-up phlegm). There may be  pus  in the sputum, and affected individuals may have fever. Typical signs of DPB progression include  dilation  (enlargement) of the bronchiolar passages and  hypoxemia  (low levels of oxygen in the blood). If DPB is left untreated, bronchiectasis will occur; it is characterized by dilation and thickening of the walls of the bronchioles, inflammatory damage to respiratory and  terminal bronchioles , and pooling of mucus in the lungs. [ 4 ] [ 5 ]  DPB is associated with progressive  respiratory failure ,  hypercapnia  (increased levels of carbon dioxide in the blood), and can eventually lead to  pulmonary hypertension  (high blood pressure in the  pulmonary vein  and  artery ) and  cor pulmonale  (dilation of the  right ventricle  of the heart, or \"right heart failure\"). [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1267", "contents": "DPB is  idiopathic , which means an exact  physiological ,  environmental , or  pathogenic  cause of the disease is unknown. However, several factors are suspected to be involved with its  pathogenesis  (the way in which the disease works). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1268", "contents": "The  major histocompatibility complex  (MHC) is a large  genomic  region found in most  vertebrates  that is associated with the immune system. It is located on  chromosome 6  in humans. A subset of MHC in humans is  human leukocyte antigen  (HLA), which controls the  antigen-presenting system , as part of  adaptive immunity  against pathogens such as  bacteria  and  viruses . When human cells are infected by a pathogen, some of them can present parts of the pathogen's proteins on their surfaces; this is called \"antigen presentation\". The infected cells then become targets for types of  cytotoxic T-cells , which kill the infected cells so they can be removed from the body. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1269", "contents": "Genetic predisposition for DPB susceptibility has been localized to two HLA  haplotypes  (a  nucleotide  or gene sequence difference between  paired chromosomes , that is more likely to occur among a common ethnicity or trait) common to people of East Asian descent.  HLA-B54  is associated with DPB in the Japanese, while  HLA-A11  is associated with the disease in Koreans. [ 9 ]  Several genes within this region of  class I HLA  are believed to be responsible for DPB, by allowing increased susceptibility to the disease. [ 7 ] [ 10 ]  The common genetic background and similarities in the HLA profile of affected Japanese and Korean individuals were considered in the search for a DPB gene. [ 10 ]  It was suggested that a mutation of a suspected disease-susceptibility gene located somewhere between  HLA-B [ 11 ]  and  HLA-A [ 12 ]  had occurred on an ancestral chromosome carrying both HLA-B54 and HLA-A11. Further, it is possible that a number of  genetic recombination  events around the disease  locus  (location on a chromosome) could have resulted in the disease being associated with HLA-B54 in the Japanese and HLA-A11 in Koreans. After further study, it was concluded that a DPB susceptibility gene is located near the HLA-B locus at chromosome 6p21.3. Within this area, the search for a genetic cause of the disease has continued. [ 9 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1270", "contents": "Because many genes belonging to HLA remain unidentified,  positional cloning  (a method used to identify a specific gene, when only its location on a chromosome is known) has been used to determine that a  mucin-like  gene is associated with DPB. In addition, diseases caused by identified HLA genes in the DPB-susceptibility region have been investigated. One of these,  bare lymphocyte syndrome I  (BLS I), exhibits a number of similarities with DPB in those affected, including chronic sinusitis, bronchiolar inflammation and nodules, and the presence of  H.\u00a0influenzae . Also like DPB, BLS I responds favorably to erythromycin therapy by showing a resolution of symptoms. The similarities between these two diseases, the corresponding success with the same mode of treatment, and the fact that the gene responsible for BLS I is located within the DPB-causing area of HLA narrows the establishment of a gene responsible for DPB. [ 9 ]  Environmental factors such as inhaling toxic fumes and cigarette smoking are not believed to play a role in DPB, and unknown environmental and other non-genetic causes\u2014such as unidentified bacteria or viruses\u2014have not been ruled out. [ 4 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1271", "contents": "Cystic fibrosis  (CF), a progressive multi-system lung disease, has been considered in the search for a genetic cause of DPB. This is for a number of reasons. CF, like DPB, causes severe lung inflammation, abundant mucus production, infection, and shows a genetic predominance among Caucasians of one geographic group to the rarity of others; whereas DPB dominates among East Asians, CF mainly affects individuals of European descent. While no gene has been implicated as the cause of DPB, mutation in a specific gene\u2014much more likely to occur in Europeans\u2014causes CF. This mutation in the  CF-causing gene  is not a factor in DPB, but a unique  polymorphism  (variation) in this gene is known to occur in many Asians not necessarily affected by either disease. It is being investigated whether this gene in any state of mutation could contribute to DPB. [ 4 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1272", "contents": "Inflammation is a normal part of the human immune response, whereby  leukocytes  (white blood cells), including  neutrophils  (white blood cells that specialize in causing inflammation), gather, and  chemokines  (proteins released from certain cells, which activate or elicit a response from other cells) accumulate at any location in the body where bacterial or viral infections occur. Inflammation interferes with the activity of bacteria and viruses, and serves to clear them from the body. In DPB, bacteria such as  Haemophilus influenzae  and  Pseudomonas aeruginosa  can cause the proliferation of inflammatory cells into the bronchiolar tissues. However, when neither bacteria are present with DPB, the inflammation continues for an as yet unknown reason. [ 4 ] [ 5 ]  In either circumstance, inflammation in DPB can be so severe that nodules containing inflammatory cells form in the walls of the bronchioles. [ 4 ] [ 13 ]  The presence of inflammation and infection in the airways also results in the production of excess mucus, which must be coughed up as sputum. [ 4 ] [ 6 ]  The combination of inflammation, nodule development, infection, mucus, and frequent cough contributes to the breathing difficulties in DPB. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1273", "contents": "The fact that inflammation in DPB persists with or without the presence of  P.\u00a0aeruginosa  and  H.\u00a0influenzae  provides a means to determine several mechanisms of DPB pathogenesis. [ 5 ]   Leukotrienes  are  eicosanoids ,  signaling molecules  made from  essential fatty acids , which play a role in many lung diseases by causing the proliferation of inflammatory cells and excess mucus production in the airways. [ 14 ]  In DPB and other lung diseases, the predominant mediator of neutrophil-related inflammation is  leukotriene B4 , which specializes in neutrophil proliferation via  chemotaxis  (the movement of some types of cells toward or away from certain molecules). [ 4 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1274", "contents": "Inflammation in DPB is also caused by the chemokine  MIP-1alpha  and its involvement with  CD8 +   T cells .  Beta defensins , a family of  antimicrobial   peptides  found in the respiratory tract, are responsible for further inflammation in DPB when a pathogen such as  P.\u00a0aeruginosa  is present. If present with DPB, the  human T-lymphotropic virus, type I , a  retrovirus , modifies DPB pathogenesis by infecting  T helper cells  and altering their effectiveness in recognizing the presence of known or unknown pathogens involved with DPB. [ 4 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1275", "contents": "The diagnosis of DPB requires  analysis  of the lungs and bronchiolar tissues, which can require a lung  biopsy , or the more preferred  high resolution computed tomography  (HRCT) scan of the lungs. [ 7 ]  The diagnostic criteria include severe inflammation in all layers of the respiratory bronchioles and lung tissue lesions that appear as nodules within the  terminal  and respiratory bronchioles in both lungs. [ 4 ]  The nodules in DPB appear as  opaque  lumps when viewed on  X-rays  of the lung, and can cause  airway obstruction , which is evaluated by a  pulmonary function test , or PFT. [ 6 ]    Lung X-rays can also reveal dilation of the bronchiolar passages, another sign of DPB. HRCT scans often show blockages of some bronchiolar passages with mucus, which is referred to as the  \"tree-in-bud\"  pattern. [ 7 ]   Hypoxemia, another sign of breathing difficulty, is revealed by measuring the oxygen and carbon dioxide content of the blood, using a blood test called  arterial blood gas . Other findings observed with DPB include the proliferation of  lymphocytes  ( white blood cells  that fight infection), neutrophils, and  foamy histiocytes  (tissue  macrophages ) in the lung  lining . Bacteria such as  H.\u00a0influenzae  and  P.\u00a0aeruginosa  are also detectable, with the latter becoming more prominent as the disease progresses. [ 4 ] [ 5 ]  The white blood, bacterial and other cellular content of the blood can be measured by taking a  complete blood count  (CBC). Elevated levels of  IgG  and  IgA  (classes of  immunoglobulins ) may be seen, as well as the presence of  rheumatoid factor  (an indicator of  autoimmunity ).  Hemagglutination , a clumping of red blood cells in response to the presence of  antibodies  in the blood, may also occur. Neutrophils, beta-defensins, leukotrienes, and chemokines can also be detected in  bronchoalveolar lavage  fluid injected then removed from the bronchiolar airways of individuals with DPB, for evaluation. [ 4 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1276", "contents": "In the  differential diagnosis  (finding the correct diagnosis between diseases that have overlapping features) of some obstructive lung diseases, DPB is often considered. A number of DPB symptoms resemble those found with other obstructive lung diseases such as  asthma ,  chronic bronchitis , and  emphysema .  Wheezing , coughing with  sputum  production, and shortness of breath are common symptoms in such diseases, and obstructive respiratory functional impairment is found on  pulmonary function testing . [ 6 ]  Cystic fibrosis, like DPB, causes severe lung inflammation, excess mucus production, and infection; but DPB does not cause disturbances of the pancreas nor the  electrolytes , as does CF, so the two diseases are different and probably unrelated. [ 4 ] [ 9 ]   DPB is distinguished by the presence of lesions that appear on X-rays as nodules in the bronchioles of both lungs; inflammation in all  tissue  layers of the respiratory bronchioles; and its higher prevalence among individuals with East Asian lineage. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1277", "contents": "DPB and  bronchiolitis obliterans  are two forms of primary bronchiolitis. [ 2 ]  Specific overlapping features of both diseases include strong cough with large amounts of often pus-filled sputum; nodules viewable on lung X-rays in the lower bronchi and bronchiolar area; and chronic sinusitis. In DPB, the nodules are more restricted to the respiratory bronchioles, while in OB they are often found in the membranous bronchioles (the initial non-cartilaginous section of the bronchiole, that divides from the  tertiary bronchus ) up to the  secondary bronchus . OB is a bronchiolar disease with worldwide prevalence, while DPB has more localized prevalence, predominantly in Japan. [ 2 ] [ 6 ]  Prior to clinical recognition of DPB in recent years, it was often misdiagnosed as  bronchiectasia ,  COPD ,  IPF ,  phthisis miliaris ,  sarcoidosis  or  alveolar cell carcinoma . [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1278", "contents": "Macrolide  antibiotics, such as  erythromycin , are an effective treatment for DPB when taken regularly over an extended period of time. [ 16 ] [ 17 ] [ 18 ]   Clarithromycin  or  roxithromycin  are also commonly used. [ 19 ]  The successful results of macrolides in DPB and similar lung diseases stems from managing certain symptoms through  immunomodulation  (adjusting the immune response), [ 17 ]  which can be achieved by taking the antibiotics in low  doses . Treatment consists of daily oral administration of erythromycin [ 7 ]  for two to three years, an extended period that has been shown to dramatically improve the effects of DPB. This is apparent when an individual undergoing treatment for DPB, among a number of disease-related remission criteria, has a normal neutrophil count detected in BAL fluid, and  blood gas  (an  arterial   blood test  that measures the amount of oxygen and carbon dioxide in the blood) readings show that free oxygen in the blood is within the normal range. [ 16 ] [ 17 ] [ 20 ]  Allowing a temporary break from erythromycin therapy in these instances has been suggested, to reduce the formation of macrolide-resistant  P.\u00a0aeruginosa . [ 16 ]  However, DPB symptoms usually return, and treatment would need to be resumed. Although highly effective, erythromycin may not prove successful in all individuals with the disease, particularly if macrolide-resistant  P.\u00a0aeruginosa  is present or previously untreated DPB has progressed to the point where respiratory failure is occurring. [ 17 ] [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1279", "contents": "With erythromycin therapy in DPB, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only  neutrophil  proliferation, but also lymphocyte activity and obstructive mucus and water  secretions  in airways. [ 16 ]  The antibiotic effects of macrolides are not involved in their beneficial effects toward reducing inflammation in DPB. [ 20 ]  This is evident because the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of macrolide-resistant  P.\u00a0aeruginosa , erythromycin therapy still reduces inflammation. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1280", "contents": "A number of factors are involved in suppression of inflammation by erythromycin and other macrolides. They are especially effective at inhibiting the proliferation of neutrophils, by diminishing the ability of  interleukin 8  and  leukotriene B4  to attract them. [ 21 ]  Macrolides also reduce the efficiency of  adhesion molecules  that allow neutrophils to stick to bronchiolar tissue linings. Mucus production in the airways is a major culprit in the morbidity and mortality of DPB and other respiratory diseases. The significant reduction of inflammation in DPB attributed to erythromycin therapy also helps to inhibit the production of excess mucus. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1281", "contents": "Untreated DPB leads to bronchiectasis, respiratory failure, and death. A journal report from 1983 indicated that untreated DPB had a five-year survival rate of 62.1%, while the 10-year survival rate was 33.2%. [ 6 ]  With erythromycin treatment, individuals with DPB now have a much longer life expectancy due to better management of symptoms, delay of progression, and prevention of associated infections like  P.\u00a0aeruginosa . [ 20 ]  The 10-year survival rate for treated DPB is about 90%. [ 4 ]  In DPB cases where treatment has resulted in significant improvement, which sometimes happens after about two years, treatment has been allowed to end for a while. However, individuals allowed to stop treatment during this time are closely monitored. As DPB has been proven to recur, erythromycin therapy must be promptly resumed once disease symptoms begin to reappear. In spite of the improved prognosis when treated, DPB currently has no known cure. [ 4 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1282", "contents": "DPB has its highest  prevalence  among the Japanese, at 11 per 100,000 population. [ 4 ]  Korean, [ 22 ]  Chinese, [ 23 ]  and Thai [ 24 ]  individuals with the disease have been reported as well. A genetic predisposition among East Asians is suggested. [ 9 ]  The disease is more common in males, [ 25 ]  with the male to female ratio at 1.4\u20132:1 (or about 5 men to 3 women). [ 4 ]  The average onset of the disease is around age 40, and two-thirds of those affected are non-smokers, although smoking is not believed to be a cause. [ 7 ]  The presence of HLA-Bw54 increases the risk of diffuse panbronchiolitis 13.3-fold. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1283", "contents": "In Europe and the Americas, a relatively small number of DPB cases have been reported in Asian immigrants and residents, as well as in individuals of non-Asian ancestry. [ 27 ] [ 28 ] [ 29 ]  Misdiagnosis has occurred in the West owing to less recognition of the disease than in Asian countries. Relative to the large number of Asians living in the west, the small number of them thought to be affected by DPB suggests non-genetic factors may play some role in its cause. This rarity seen in Western Asians may also be partly associated with misdiagnosis. [ 7 ] [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1284", "contents": "In the early 1960s, a relatively new chronic lung disease was being observed and described by physicians in Japan. In 1969, [ 31 ]  the name \"diffuse panbronchiolitis\" was introduced to distinguish it from chronic bronchitis, emphysema,  alveolitis , and other obstructive lung disease with inflammation. Between 1978 and 1980, the results of a nationwide survey initiated by the Ministry of Health and Welfare of Japan revealed more than 1,000 probable cases of DPB, with 82 histologically confirmed. By the 1980s, it was internationally recognized as a distinct disease of the lungs. [ 4 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1285", "contents": "Before the 1980s, the prognosis or expected outcome of DPB was poor, especially in cases with  superinfection  (the emergence of a new viral or bacterial infection, in addition to the currently occurring infection) by  P.\u00a0aeruginosa . [ 13 ]  DPB continued to have a very high mortality rate before generalized antibiotic treatment and  oxygen therapy  were beginning to be used routinely in the effort to manage symptoms. Around 1985, when long-term treatment with the antibiotic erythromycin became the standard for managing DPB, the prognosis significantly improved. [ 20 ]  In 1990, the association of DPB with HLA was initially asserted. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1286", "contents": "Diplophonia,  also known as diphthongia, is a phenomenon in which a voice is perceived as being produced with two concurrent pitches. [ 1 ]  Diplophonia is a result of vocal fold vibrations that are quasi-periodic in nature. [ 2 ]  It has been reported from old days, but there is no uniform interpretation of established mechanisms. [ 3 ]  It has been established that diplophonia can be caused by various vocal fold pathologies, such as  vocal folds   polyp ,  vocal fold nodule ,  recurrent laryngeal nerve  paralysis [ 3 ]  or  vestibular fold  hypertrophy. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1287", "contents": "The  Voice Quality Symbol  for diplophonia is V\u032c\u203c."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1288", "contents": "The  epithelial\u2013mesenchymal transition  ( EMT ) is a process by which  epithelial  cells lose their  cell polarity  and cell\u2013cell adhesion, and gain migratory and invasive properties to become  mesenchymal stem cells ; these are  multipotent   stromal cells  that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including  mesoderm  formation and  neural tube  formation. EMT has also been shown to occur in  wound healing , in organ  fibrosis  and in the initiation of  metastasis  in cancer progression."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1289", "contents": "Epithelial\u2013mesenchymal transition was first recognized as a feature of embryogenesis by  Betty Hay  in the 1980s. [ 1 ] [ 2 ]  EMT, and its reverse process, MET ( mesenchymal-epithelial transition ) are critical for development of many tissues and organs in the developing embryo, and numerous embryonic events such as  gastrulation ,  neural crest  formation,  heart valve  formation,  secondary palate development , and  myogenesis . [ 3 ]  Epithelial and mesenchymal cells differ in phenotype as well as function, though both share inherent plasticity. [ 2 ]  Epithelial cells are closely connected to each other by  tight junctions ,  gap junctions  and  adherens junctions , have an apico-basal  polarity , polarization of the  actin cytoskeleton  and are bound by a  basal lamina  at their basal surface. Mesenchymal cells, on the other hand, lack this polarization, have a spindle-shaped morphology and interact with each other only through focal points. [ 4 ]  Epithelial cells express high levels of  E-cadherin , whereas mesenchymal cells express those of  N-cadherin ,  fibronectin  and  vimentin . Thus, EMT entails profound morphological and phenotypic changes to a cell. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1290", "contents": "Based on the biological context, EMT has been categorized into 3 types: developmental (Type I),  fibrosis [ 6 ]  and  wound healing  (Type II), and  cancer  (Type III). [ 7 ] [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1291", "contents": "Loss of  E-cadherin  is considered to be a fundamental event in EMT. Many  transcription factors  (TFs) that can repress E-cadherin directly or indirectly can be considered as EMT-TF (EMT inducing TFs).  SNAI1 /Snail 1,  SNAI2 /Snail 2 (also known as Slug),  ZEB1 ,  ZEB2 ,  TCF3  and  KLF8  (Kruppel-like factor 8) can bind to the E-cadherin promoter and repress its transcription, whereas factors such as  Twist ,  Goosecoid ,  TCF4  (also known as E2.2), homeobox protein  SIX1  and  FOXC2  (fork-head box protein C2) repress E-cadherin indirectly. [ 10 ] [ 11 ]  SNAIL and ZEB factors bind to E-box consensus sequences on the promoter region, while KLF8 binds to promoter through GT boxes. These EMT-TFs not only directly repress E-cadherin, but also repress transcriptionally other junctional proteins, including  claudins  and  desmosomes , thus facilitating EMT. On the other hand, transcription factors such as grainyhead-like protein 2 homologue (GRHL2), and ETS-related transcription factors ELF3 and  ELF5  are downregulated during EMT and are found to actively drive MET when overexpressed in mesenchymal cells. [ 12 ] [ 13 ]  Since EMT in cancer progression recaptures EMT in developmental programs, many of the EMT-TFs are involved in promoting metastatic events. [ 14 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1292", "contents": "Several signaling pathways ( TGF-\u03b2 ,  FGF ,  EGF ,  HGF ,  Wnt / beta-catenin  and  Notch ) and  hypoxia  may induce EMT. [ 7 ] [ 16 ] [ 17 ]  In particular, Ras- MAPK  has been shown to activate Snail and Slug. [ 18 ] [ 19 ] [ 20 ]  Slug triggers the steps of  desmosomal  disruption, cell spreading, and partial separation at cell\u2013cell borders, which comprise the first and necessary phase of the EMT process. On the other hand, Slug cannot trigger the second phase, [ 21 ]  which includes the induction of cell motility, repression of the  cytokeratin  expression, and activation of  vimentin  expression. [ 22 ]  Snail and Slug are known to regulate the expression of  p63  isoforms, another transcription factor that is required for proper development of epithelial structures. [ 23 ]  The altered expression of  p63  isoforms reduced cell\u2013cell adhesion and increased the migratory properties of cancer cells. The  p63  factor is involved in inhibiting EMT and reduction of certain p63 isoforms may be important in the development of epithelial cancers. [ 24 ]  Some of them are known to regulate the expression of  cytokeratins . [ 25 ]  The  phosphatidylinositol 3' kinase  (PI3K)/AKT axis,  Hedgehog signaling pathway ,  nuclear factor-kappaB  and Activating Transcription Factor 2 have also been implicated to be involved in EMT. [ 26 ] [ 27 ] [ 28 ] [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1293", "contents": "Wnt signaling pathway regulates EMT in gastrulation, cardiac valve formation and cancer. [ 30 ]  Activation of Wnt pathway in breast cancer cells induces the EMT regulator  SNAIL  and upregulates the mesenchymal marker,  vimentin . Also, active Wnt/beta-catenin pathway correlates with poor prognosis in breast cancer patients in the clinic. Similarly, TGF-\u03b2 activates the expression of SNAIL and ZEB to regulate EMT in heart development, palatogenesis, and cancer. The breast cancer bone metastasis has activated TGF-\u03b2 signaling, which contributes to the formation of these lesions. [ 31 ]  However, on the other hand,  p53 , a well-known tumor suppressor, represses EMT by activating the expression of various  microRNAs  \u2013 miR-200 and miR-34 that inhibit the production of protein ZEB and SNAIL, and thus maintain the epithelial phenotype. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1294", "contents": "After the initial stage of embryogenesis, the implantation of the embryo and the initiation of  placenta  formation are associated with EMT. The trophoectoderm cells undergo EMT to facilitate the invasion of  endometrium  and appropriate placenta placement, thus enabling nutrient and gas exchange to the embryo. Later in embryogenesis, during gastrulation, EMT allows the cells to ingress in a specific area of the embryo \u2013 the  primitive streak  in  amniotes , and the ventral furrow in  Drosophila . The cells in this tissue express E-cadherin and apical-basal polarity. [ 33 ]  Since gastrulation is a very rapid process, E-cadherin is repressed transcriptionally by  Twist  and  SNAI1  (commonly called  Snail ), and at the protein level by P38 interacting protein. The primitive streak, through invagination, further generates mesoendoderm, which separates to form a mesoderm and an endoderm, again through EMT. Mesenchymal cells from the primitive streak participate also in the formation of many epithelial mesodermal organs, such as notochord as well as somites, through the reverse of EMT, i.e.  mesenchymal\u2013epithelial transition .  Amphioxus  forms an epithelial neural tube and dorsal notochord but does not have the EMT potential of the  primitive streak . In higher chordates, the mesenchyme originates out of the primitive streak migrates anteriorly to form the somites and participate with neural crest mesenchyme in formation of the heart mesoderm."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1295", "contents": "In vertebrates,  epithelium  and  mesenchyme  are the basic tissue phenotypes. During embryonic development, migratory  neural crest  cells are generated by EMT involving the epithelial cells of the neuroectoderm. As a result, these cells dissociate from neural folds, gain motility, and disseminate to various parts of the embryo, where they differentiate to many other cell types. Also, craniofacial crest mesenchyme that forms the connective tissue forming the head and face, is formed by  neural tube  epithelium by EMT. [ 34 ]  EMT takes place during the construction of the vertebral column out of the  extracellular matrix , which is to be synthesized by  fibroblasts  and  osteoblasts  that encircle the neural tube. The major source of these cells are  sclerotome  and  somite  mesenchyme as well as  primitive streak . Mesenchymal morphology allows the cells to travel to specific targets in the embryo, where they differentiate and/or induce differentiation of other cells. [ 34 ] [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1296", "contents": "During wound healing, keratinocytes at the border of the wound undergo EMT and undergo re-epithelialization or MET when the wound is closed. Snail2 expression at the migratory front influences this state, as its overexpression accelerates wound healing. Similarly, in each menstrual cycle, the ovarian surface epithelium undergoes EMT during post-ovulatory wound healing. [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1297", "contents": "Initiation of  metastasis  requires invasion, which is enabled by EMT. [ 37 ] [ 38 ]  Carcinoma cells in a primary tumor lose cell-cell adhesion mediated by E-cadherin repression and break through the basement membrane with increased invasive properties, and enter the bloodstream through  intravasation . Later, when these  circulating tumor cells  (CTCs) exit the bloodstream to form  micro-metastases , they undergo MET for clonal outgrowth at these metastatic sites. Thus, EMT and MET form the initiation and completion of the invasion-metastasis cascade. [ 39 ]  At this new metastatic site, the tumor may undergo other processes to optimize growth. For example, EMT has been associated with  PD-L1  expression, particularly in lung cancer. Increased levels of PD-L1 suppresses the immune system which allows the cancer to spread more easily.\u00a0 [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1298", "contents": "EMT confers resistance to  oncogene -induced premature  senescence . Twist1 and Twist2, as well as  ZEB1  protects human cells and mouse embryonic fibroblasts from senescence. Similarly, TGF-\u03b2 can promote tumor invasion and evasion of immune surveillance at advanced stages. When TGF-\u03b2 acts on activated Ras-expressing mammary epithelial cells, EMT is favored and apoptosis is inhibited. [ 41 ]  This effect can be reversed by inducers of epithelial differentiation, such as GATA-3. [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1299", "contents": "EMT has been shown to be induced by  androgen deprivation therapy  in metastatic  prostate cancer . [ 14 ]  Activation of EMT programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression.  Brachyury ,  Axl ,  MEK , and  Aurora kinase A  are molecular drivers of these programs, and inhibitors are currently in clinical trials to determine therapeutic applications. [ 14 ]  Oncogenic  PKC-iota  can promote melanoma cell invasion by activating Vimentin during EMT. PKC-iota inhibition or knockdown resulted an increase E-cadherin and RhoA levels while decreasing total Vimentin, phosphorylated Vimentin (S39) and Par6 in metastatic melanoma cells. These results suggested that PKC-\u03b9 is involved in signaling pathways which upregulate EMT in melanoma. [ 43 ] [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1300", "contents": "EMT has been indicated to be involved in acquiring drug resistance. Gain of EMT markers was found to be associated with the resistance of ovarian carcinoma epithelial cell lines to paclitaxel. Similarly, SNAIL also confers resistance to paclitaxel, adriamycin and radiotherapy by inhibiting p53-mediated apoptosis. [ 45 ]  Furthermore, inflammation, that has been associated with the progression of cancer and fibrosis, was recently shown to be related to cancer through inflammation-induced EMT. [ 46 ]  Consequently, EMT enables cells to gain a migratory phenotype, as well as induce multiple immunosuppression, drug resistance, evasion of apoptosis mechanisms."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1301", "contents": "Some evidence suggests that cells that undergo EMT gain stem cell-like properties, thus giving rise to  Cancer Stem Cells  (CSCs). Upon transfection by activated Ras, a subpopulation of cells exhibiting the putative stem cell markers CD44high/CD24low increases with the concomitant induction of EMT. [ 47 ]  Also, ZEB1 is capable of conferring stem cell-like properties, thus strengthening the relationship between EMT and stemness. Thus, EMT may present increased danger to cancer patients, as EMT not only enables the carcinoma cells to enter the bloodstream, but also endows them with properties of stemness which increases tumorigenic and proliferative potential. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1302", "contents": "However, recent studies have further shifted the primary effects of EMT away from invasion and metastasis, toward resistance to chemotherapeutic agents. Research on breast cancer and pancreatic cancer both demonstrated no difference in cells' metastatic potential upon acquisition of EMT. [ 49 ] [ 50 ]  These are in agreement with another study showing that the EMT transcription factor TWIST actually requires intact  adherens junctions  in order to mediate local invasion in breast cancer. [ 51 ]  The effects of EMT and its relationship to invasion and metastasis may therefore be highly context specific."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1303", "contents": "In  urothelial  carcinoma cell lines overexpression of  HDAC5  inhibits long-term proliferation but can promote epithelial-to-mesenchymal transition (EMT). [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1304", "contents": "Platelets  in the blood have the ability to initiate the induction of EMT in cancer cells. When platelets are recruited to a site in the blood vessel they can release a variety of growth factors ( PDGF , [ 53 ]   VEGF , [ 54 ]   Angiopoietin-1 [ 55 ] ) and cytokines including the EMT inducer TGF-\u03b2. [ 56 ]  The release of TGF-\u03b2 by platelets in blood vessels near primary tumors enhances invasiveness and promotes metastasis of cancer cells in the tumor. [ 57 ]  Studies looking at defective platelets and reduced platelet counts in mouse models have shown that impaired platelet function is associated with decreased metastatic formation. [ 58 ] [ 59 ]  In humans, platelet counts and  thrombocytosis  within the upper end of the normal range have been associated with advanced, often metastatic, stage cancer in cervical cancer, [ 60 ]  ovarian cancer, [ 61 ]  gastric cancer, [ 62 ]  and esophageal cancer. [ 63 ]  Although a great deal of research has been applied to studying interactions between tumor cells and platelets, a cancer therapy targeting this interaction has not yet been established. [ 64 ]  This may be in part due to the redundancy of prothrombotic pathways which would require the use of multiple therapeutic approaches in order to prevent pro-metastatic events via EMT induction in cancer cells by activated platelets."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1305", "contents": "To improve the chances for the development of a cancer metastasis, a cancer cell must avoid detection and targeting by the immune system once it enters the bloodstream. Activated platelets have the ability to bind glycoproteins and glycolipids ( P-selectin  ligands such as  PSGL-1 ) on the surface of cancer cells to form a physical barrier that protects the cancer cell from natural killer cell-mediated lysis in the bloodstream. [ 65 ]  Furthermore, activated platelets promote the adhesion of cancer cells to activated endothelial cells lining blood vessels using adhesion molecules present on platelets. [ 66 ] [ 64 ]  P-selectin ligands on the surface of cancer cells remain to be elucidated and may serve as potential biomarkers for disease progression in cancer. [ 64 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1306", "contents": "Many studies have proposed that induction of EMT is the primary mechanism by which epithelial cancer cells acquire malignant phenotypes that promote metastasis. [ 67 ]   Drug development  targeting the activation of EMT in cancer cells has thus become an aim of pharmaceutical companies. [ 68 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1307", "contents": "Small molecules that are able to inhibit TGF-\u03b2 induced EMT are under development. [ 68 ]   Silmitasertib  (CX-4945) is a small molecule inhibitor of protein kinase CK2, which has been supported to be linked with TGF-\u03b2 induced EMT, and is currently in clinical trials for  cholangiocarcinoma  (bile duct cancer), as well as in preclinical development for hematological and lymphoid malignancies. [ 69 ] [ 70 ]  In January 2017, Silmitasertib was granted  orphan drug  status by the U.S. Food and Drug Administration for cholangiocarcinoma and is currently in  phase II study . Silmitasertib is being developed by Senhwa Biosciences. [ 71 ]  Another small molecule inhibitor  Galunisertib  (LY2157299) is a potent TGF-\u03b2 type I receptor kinase inhibitor that was demonstrated to reduce the size, the growth rate of tumors, and the tumor forming potential in  triple negative breast cancer  cell lines using mouse  xenografts . [ 72 ]  Galunisertib is currently being developed by Lilly Oncology and is in  phase I/II  clinical trials for hepatocellular carcinoma, unresectable pancreatic cancer, and malignant glioma. [ 73 ]  Small molecule inhibitors of EMT are suggested to not act as a replacement for traditional chemotherapeutic agents but are likely to display the greatest efficacy in treating cancers when used in conjunction with them."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1308", "contents": "Antagomirs  and  microRNA  mimics have gained interest as a potential source of therapeutics to target EMT induced metastasis in cancer as well as treating many other diseases. [ 74 ]  Antagomirs were first developed to target  miR-122 , a microRNA that was abundant and specific to the liver, and this discovery has led to the development of other antagomirs that can pair with specific microRNAs present in the  tumor microenvironment  or in the cancer cells. [ 75 ] [ 73 ]  A microRNA mimic to miR-655 was found to suppress EMT through the targeting of EMT inducing transcription factor ZEB1 and TGF-\u03b2 receptor 2 in a pancreatic cancer cell line. Overexpression of the miR-655 mimic in the Panc1 cancer cell line upregulated the expression of E-cadherin and suppressed the migration and invasion of mesenchymal-like cancer cells. [ 76 ]  The use of microRNA mimics to suppress EMT has expanded to other cancer cell lines and holds potential for clinical  drug development . [ 74 ]  However, microRNA mimics and antagomirs suffer from a lack of stability  in vivo  and lack an accurate delivery system to target these molecules to the tumor cells or tissue for treatment. [ 77 ]  Improvements to antagomir and microRNA mimic stability through chemical modifications such as  locked nucleic acid  (LNA) oligonucleotides or  peptide nucleic acids  (PNA) can prevent the fast clearing of these small molecules by  RNases . [ 77 ] [ 74 ]  Delivery of antagomirs and microRNA mimics into cells by enclosing these molecules in liposome-nanoparticles has generated interest however liposome structures suffer from their own drawbacks that will need to be overcome for their effective use as a drug delivery mechanism. [ 77 ]  These drawbacks of liposome-nanoparticles include nonspecific uptake by cells and induction of immune responses. [ 78 ]  The role that microRNAs play in cancer development and metastasis is under much scientific investigation and it is yet to be demonstrated whether microRNA mimics or antagomirs may serve as standard clinical treatments to suppress EMT or oncogenic microRNAs in cancers. [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1309", "contents": "Similar to generation of Cancer Stem Cells, EMT was demonstrated to generate endocrine progenitor cells from human  pancreatic islets . [ 79 ]  Initially, the  human islet-derived progenitor cells  (hIPCs) were proposed to be better precursors since  \u03b2-cell  progeny in these hIPCs inherit  epigenetic  marks that define an active insulin promoter region. [ 80 ]  However, later, another set of experiments suggested that labelled \u03b2-cells de-differentiate to a mesenchymal-like phenotype  in vitro , but fail to proliferate; thus initiating a debate in 2007. [ 81 ] [ 82 ] [ 83 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1310", "contents": "Since these studies in human islets lacked lineage-tracing analysis, these findings from irreversibly tagged beta cells in mice were extrapolated to human islets. Thus, using a dual lentiviral and genetic lineage tracing system to label \u03b2-cells, it was convincingly demonstrated that adult human islet \u03b2-cells undergo EMT and proliferate  in vitro . [ 84 ] [ 85 ]  Also, these findings were confirmed in human fetal pancreatic insulin-producing cells, and the mesenchymal cells derived from pancreatic islets can undergo the reverse of EMT \u2013 MET \u2013 to generate islet-like cell aggregates. [ 86 ]  Thus, the concept of generating progenitors from insulin-producing cells by EMT or generation of Cancer Stem Cells during EMT in cancer may have potential for replacement therapy in diabetes, and call for drugs targeting inhibition of EMT in cancer. [ 86 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1311", "contents": "Not all cells undergo a complete EMT, i.e. losing their cell-cell adhesion and gaining solitary migration characteristics. Instead, most cells undergo partial EMT, a state in which they retain some epithelial traits such as cell-cell adhesion or apico-basal polarity, and gain migratory traits, thus cells in this hybrid epithelial/mesenchymal (E/M) phenotype are endowed with special properties such as collective cell migration. [ 51 ] [ 87 ] [ 88 ] [ 30 ] [ 89 ] [ 90 ] [ 91 ] [ 92 ]  Single-cell tracking contributes to enabling the visualization of morphological transitions during EMT, the discernment of cell migration phenotypes, and the correlation of the heritability of these traits among sister cells. [ 93 ]  Two mathematical models have been proposed, attempting to explain the emergence of this hybrid E/M phenotype, [ 89 ] [ 91 ]  and its highly likely that different cell lines adopt different hybrid state(s), as shown by experiments in MCF10A, HMLE and H1975 cell lines. [ 90 ] [ 94 ]  Although a hybrid E/M state has been referred to as 'metastable' or transient, recent experiments in H1975 cells suggest that this state can be stably maintained by cells. [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1312", "contents": "Extrapulmonary restriction  is a type of  restrictive lung disease , indicated by decreased  alveolar ventilation  with accompanying  hypercapnia . It is characterized as an inhibition to the drive to breathe, or an ineffective restoration of the drive to breathe. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1313", "contents": "Extrapulmonary restriction can be caused by  central  and  peripheral nervous system  dysfunctions, over-sedation, or trauma (such as a broken rib). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1314", "contents": "Generalized hypoxia  is a medical condition in which the tissues of the body are deprived of the necessary levels of oxygen due to an insufficient supply of oxygen, which may be due to the composition or pressure of the breathing gas, decreased lung ventilation, or respiratory disease, any of which may cause a lower than normal oxygen content in the arterial blood, and consequently a reduced supply of oxygen to all tissues perfused by the arterial blood. This usage is in contradistinction to  localized hypoxia , in which only an associated group of tissues, usually with a common blood supply, are affected, usually due to an insufficient or reduced blood supply to those tissues.  Generalized hypoxia  is also used as a synonym for  hypoxic hypoxia [ 1 ] [ 2 ]  This is not to be confused with  hypoxemia , which refers to low levels of  oxygen in the blood , although the two conditions often occur simultaneously, since a decrease in blood oxygen typically corresponds to a decrease in oxygen in the surrounding tissue. However, hypoxia may be present without hypoxemia, and vice versa, as in the case of  infarction . Several other classes of  medical hypoxia  exist. [ 2 ] [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1315", "contents": "Hypoxia can result from various causes which can be categorised as: anemic hypoxia, cellular hypoxia, generalised, or hypoxic hypoxia, pulmonary hypoxia, stagnant hypoxia, increased oxygen consumption due to a hypermetabolic state, or any combination of these. [ 2 ]  The three fundamental causes of hypoxia at the tissue level are low oxygen content in the blood (hypoxemia), low perfusion of the tissue, and inability of the tissue to extract and use the oxygen in the blood. [ 3 ]  Generalised, or hypoxic hypoxia may be caused by:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1316", "contents": "When breathing the ambient air at high altitudes (above 3048 metres/10,000 feet), the human body experiences  altitude sickness  and hypoxemia due to a low  partial pressure  of oxygen, decreasing the carriage of oxygen by hemoglobin."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1317", "contents": "While breathing pure oxygen at ambient pressure, from an oxygen cylinder or other source, the maximum altitude a human can tolerate [ clarification needed ]  while their body is at atmospheric pressure is 13,700 metres (45,000 feet), [ citation needed ]  , where atmospheric pressure is about 14.7kPa. This is a function of the partial pressure of oxygen in the breathing gas, and is also dependent on level of exertion which affects the oxygen requirements of metabolism, cardiovascular fitness, and acclimatization to altitude which affects the available hemoglobin and can vary significantly between individuals.  [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1318", "contents": "Generalized hypoxia is an effect of a lack of oxygen, and in many cases of a one-time event can be reversed simply by eliminating the lack. Where there is no underlying pathology, provision of oxygen at normobaric partial pressure (about 0.21 bar) is usually sufficient to reverse minor symptoms. Where there is a pathology causing the hypoxia, treatment of the underlying pathology is often effective. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1319", "contents": "Hajj cough  is the informal name for a  respiratory tract infection  that tends to spread among  pilgrims  in the crowded conditions of the  Islamic pilgrimage  to  Mecca , known as  Hajj . There is much  research  that on the health of the pilgrims before, during, and after their trip, as well as on the causes and remedies of the  ailments ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1320", "contents": "A 2020 study on  Australian  Hajj pilgrims deduced that of 421 pilgrims surveilled before their trip, 28% reported having already existing  health problems , 26 of them were of age 65 or greater, and 103 of them had other chronic problems such as  diabetes . 329 obtained recommended  vaccines , of which 180 simply got  influenza , 139 received that and other  vaccines , whereas 10 got a vaccine that was not  influenza . [ 1 ]  Now, when it comes to health during the  pilgrimage , 248 of 391 individuals indicated that hey had some type of  respiratory  issues, which included a  runny nose ,  cough , and  fever . Finally, after the Hajj pilgrimage, 157 out of 300 pilgrims reported health issues, many of them the similar respiratory issues mentioned above, but also others like  diarrhea  and  influenza-like illness (ILI) . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1321", "contents": "Oversaturation of pilgrims in a confined space greatly increases the likelihood of  transmission . A variation of  viruses  and  bacteria  cause the cough, one such being the  meningococcal  strains of 2000/2001, whose associated  statistics  showed it could easily be transmitted at places where people came together from all over the world. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1322", "contents": "In terms of the  prevalent  symptoms, a  Malaysian  study of 2010 concluded that of a 387-person sample, 91.5% of respondents reported having a cough, 79.3% a runny nose, 59.2% a fever, and 57.1% a  sore throat . About 40.1% had all three symptoms. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1323", "contents": "During the pilgrimage, symptoms of  upper respiratory tract infections  (URTIs) were prevalent amongst the pilgrims. Many  physicians  assigned to handle the pilgrimage would prescribe  antibiotics , and their decisions would be motivated by factors such as clinical assessment, or regulations that they consult. However, a study reports that 45.5% of  prescriptions  associated with URTIs were  unnecessitated , but when a decision was made by a physician to not prescribe, that decision was found to be 95% warranted. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1324", "contents": "Another remediation is to regularly  wash hands  and use  sanitization , as it helped with reducing influenza-like illness (ILI) symptoms. It is also said that the wearing of protective face masks (in men) lead to only 15% of pilgrims suffering from acute  respiratory tract infections  (ARI), compared to 31.4% of pilgrims who sometimes wore it, and 61.2% of those that refrained from wearing a face mask at all. [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1325", "contents": "Hamman's syndrome , also known as  Macklin's syndrome , is a  syndrome  of spontaneous  subcutaneous emphysema [ 1 ]  (air in the  subcutaneous tissues  of the skin) and  pneumomediastinum  (air in the  mediastinum , the center of the  chest cavity ), sometimes associated with pain and, less commonly,  dyspnea  (difficulty breathing),  dysphonia , and a low-grade  fever ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1326", "contents": "Hamman's syndrome can cause  Hamman's sign , an unusual combination of sounds that can be heard with a  stethoscope ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1327", "contents": "The cause of Hamman's syndrome is most commonly unknown (idiopathic)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1328", "contents": "Excessive duration and/or intensity of activities that mimic  valsalva manoeuvres ,  i.e.  that increase intrathoracic pressure, can cause barotrauma, and hence pregnancy (and constipation and other causes of excessive straining) can be a precipitating cause of Hamman's syndrome. Indeed, it is estimated to occur in approximately 1 in 100,000 live births and is associated with prolonged labour times. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1329", "contents": "Additionally, vomiting and coughing have also been noted as occasional precipitating factors. Hamman's is thus unsurprisingly occasionally known to be associated with asthma ( i.e.  frequent coughing), excessive alcohol use ( i.e.  frequent vomiting) and inhalational illicit substance use (such as cocaine use). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1330", "contents": "Despite these associations, often, no precipitating cause is found."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1331", "contents": "Macklin described the pathophysiology of Hamman's syndrome to be  barotrauma , whereby rupture of alveolar membranes causes a positive pressure gradient of air from the lungs into the mediastinum (the Macklin effect). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1332", "contents": "Treatment is  supportive . Hamman's syndrome tends to be benign and self-limiting. It is important to differentiate it from far more serious conditions that have similar symptoms, such as  Boerhaave's syndrome . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1333", "contents": "It was named after clinician  Louis Hamman , M.D. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1334", "contents": "Hemoptysis  or  haemoptysis  is the discharge of  blood  or blood-stained  mucus  through the mouth coming from the  bronchi ,  larynx ,  trachea , or  lungs . It does not necessarily involve coughing. In other words, it is the airway bleeding. This can occur with  lung cancer , infections such as  tuberculosis ,  bronchitis , or  pneumonia , and certain cardiovascular conditions. Hemoptysis is considered massive at 300\u00a0mL (11\u00a0imp\u00a0fl\u00a0oz; 10\u00a0US\u00a0fl\u00a0oz).  In such cases, there are always severe injuries. The primary danger comes from  choking , rather than  blood loss . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1335", "contents": "The most common causes for hemoptysis in adults are chest infections such as  bronchitis  or  pneumonia . [ 1 ]   In children, hemoptysis is commonly caused by the presence of a  foreign body  in the  airway . Other common causes include  lung cancers  and  tuberculosis . Less common causes include  aspergilloma ,  bronchiectasis ,  coccidioidomycosis ,  pulmonary embolism ,  pneumonic plague , and  cystic fibrosis . Rarer causes include  hereditary hemorrhagic telangiectasia  (HHT or Rendu-Osler-Weber syndrome),  Goodpasture's syndrome , and  granulomatosis with polyangiitis . A rare cause of hemoptysis in women is  endometriosis , which leads to intermittent hemoptysis coinciding with menstrual periods in 7% of women with thoracic endometriosis syndrome. [ 4 ]  Hemoptysis may be exacerbated or even caused by overtreatment with  anticoagulant  drugs such as  warfarin . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1336", "contents": "Blood-laced mucus from the sinus or nose area can sometimes be misidentified as symptomatic of hemoptysis (such secretions can be a sign of nasal or  sinus cancer , but also a  sinus infection ). Extensive non-respiratory injury can also cause one to cough up blood.  Cardiac causes like  congestive heart failure  and  mitral stenosis  should be ruled out. The origin of blood can be identified by observing its color. Bright-red, foamy blood comes from the respiratory tract, whereas dark-red, coffee-colored blood comes from the  gastrointestinal tract . Sometimes hemoptysis may be rust-colored. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1337", "contents": "Although there are reports that the fatality rate is as high as 80%, the mortality rate for hospitalized hemoptysis patients is 9.4% (with  n =28539), calculated from the data in the article by Kinoshita et al. [ 27 ]  This is probably the most reasonable figure considering the overwhelming number of cases. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1338", "contents": "The general definition of massive hemoptysis is more than 200 ml within 24 hours, but there is a wide range in the literature (100\u2013600 ml). Considering that the total volume of the tracheal and bronchial lumen is about 150 cc, [ 28 ] [ 29 ]  it may be reasonable to define massive hemoptysis as 200 ml, which is a little more than 150 ml, in terms of setting the threshold for fatal hemoptysis. More than 400ml/day is not adequate for screening purposes. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1339", "contents": "Treatment depends on the underlying cause. Treatments include iced  saline , and topical  vasoconstrictors  such as  adrenaline  or  vasopressin .  Tranexamic acid  was proved to improve in-hospital mortality. [ 27 ]  Selective  bronchial intubation  can be used to collapse the lung that is bleeding. Also, endobronchial tamponade can be used. [ 30 ]   Laser photocoagulation  can be used to stop bleeding during  bronchoscopy .  Angiography  of  bronchial arteries  can be performed to locate the bleeding, and it can often be  embolized . [ 31 ]   Bronchial artery embolization  (BAE) is the first line treatment nowadays. [ 32 ] [ 33 ] [ 34 ] [ 35 ] [ 36 ]  Surgical option is usually the last resort and can involve  removal of a lung lobe  or  removal of the entire lung . Cough suppressants can increase the risk of choking. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1340", "contents": "Hereditary hemorrhagic telangiectasia  ( HHT ), also known as  Osler\u2013Weber\u2013Rendu disease  and  Osler\u2013Weber\u2013Rendu syndrome , is a rare autosomal dominant  genetic disorder  that leads to abnormal blood vessel formation in the  skin ,  mucous membranes , and often in organs such as the  lungs ,  liver , and  brain . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1341", "contents": "It may lead to  nosebleeds ,  acute and chronic digestive tract bleeding , and various problems due to the involvement of other organs. Treatment focuses on reducing bleeding from talangecstacias, and sometimes  surgery  or other targeted interventions to remove  arteriovenous malformations  in organs. Chronic bleeding often requires  iron supplements , iron infusions and sometimes  blood transfusions . HHT is transmitted in an  autosomal dominant  fashion, and occurs in one in 5,000\u20138,000 people in North America. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1342", "contents": "The disease carries the names of Sir  William Osler ,  Henri Jules Louis Marie Rendu , and  Frederick Parkes Weber , who described it in the late 19th and early 20th centuries. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1343", "contents": "Telangiectasia  (small vascular malformations) may occur in the skin and mucosal linings of the nose and gastrointestinal tract. The most common problem is  nosebleeds  (epistaxis), which happen frequently from childhood and affect about 90\u201395% of people with HHT. Lesions on the skin and in the mouth bleed less often but may be considered cosmetically displeasing; they affect about 80%. [ 1 ] [ 2 ]  The skin lesions characteristically occur on the  lips , the  nose  and the  fingers , and on the skin of the face in sun-exposed areas. They appear suddenly, with the number increasing over time. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1344", "contents": "About 20% are affected by symptomatic digestive tract lesions, although a higher percentage have lesions that do not cause symptoms. These lesions may bleed intermittently, which is rarely significant enough to be noticed (in the form of  bloody vomiting  or  black stool ), but can eventually lead to depletion of  iron  in the body, resulting in  iron-deficiency anemia . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1345", "contents": "Arteriovenous malformations  (AVMs, larger vascular malformations) occur in larger organs, predominantly the lungs ( pulmonary AVMs ) (50%), liver (30\u201370%) and the  brain  ( cerebral AVMs , 10%), with a very small proportion (<1%) of AVMs in the  spinal cord . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1346", "contents": "Vascular malformations in the lungs may cause a number of problems. The lungs normally \"filter out\"  bacteria  and  blood clots  from the bloodstream; AVMs bypass the capillary network of the lungs and allow these to  migrate  to the brain, where bacteria may cause a  brain abscess  and blood clots may lead to  stroke . [ 1 ]  HHT is the most common cause of lung AVMs: out of all people found to have lung AVMs, 70\u201380% are due to HHT. [ 4 ] [ 5 ]  Bleeding from lung AVMs is relatively unusual, but may cause  hemoptysis  (coughing up blood) or  hemothorax  (blood accumulating in the chest cavity). [ 1 ] [ 2 ] [ 4 ]  Large vascular malformations in the lung allow oxygen-depleted blood from the  right ventricle  to bypass the  alveoli , meaning that this blood does not have an opportunity to absorb fresh oxygen. This may lead to  breathlessness . [ 4 ] [ 5 ]  Large AVMs may lead to  platypnea , difficulty in breathing that is more marked when sitting up compared to lying down; this probably reflects changes in blood flow associated with positioning. [ 4 ]  Very large AVMs cause a marked inability to absorb oxygen, which may be noted by  cyanosis  (bluish discoloration of the lips and skin),  clubbing of the fingernails  (often encountered in chronically low oxygen levels), and a  humming noise  over the affected part of the lung detectable by  stethoscope . [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1347", "contents": "The symptoms produced by AVMs in the liver depend on the type of abnormal connection that they form between blood vessels. If the connection is between  arteries  and  veins , a large amount of blood bypasses the body's organs, for which the heart compensates by increasing the  cardiac output . Eventually  congestive cardiac failure  develops (\"high-output cardiac failure\"), with breathlessness and leg swelling among other problems. [ 1 ] [ 6 ]  If the AVM creates a connection between the  portal vein  and the blood vessels of the liver, the result may be  portal hypertension  (increased portal vein pressure), in which collateral blood vessels form in the  esophagus  ( esophageal varices ), which may bleed violently; furthermore, the increased pressure may give rise to fluid accumulation in the abdominal cavity ( ascites ). If the flow in the AVM is in the other direction, portal venous blood flows directly into the veins rather than running through the liver; this may lead to  hepatic encephalopathy  (confusion due to portal waste products irritating the brain). Rarely, the bile ducts are deprived of blood, leading to severe  cholangitis  (inflammation of the bile ducts). [ 1 ] [ 6 ]  Liver AVMs are detectable in over 70% of people with HHT, but only 10% experience problems as a result. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1348", "contents": "In the brain, AVMs occasionally exert pressure, leading to  headaches . They may also increase the risk of  seizures , as would any abnormal tissue in the brain. Finally, hemorrhage from an AVM may lead to  intracerebral hemorrhage  (bleeding into the brain), which causes any of the symptoms of stroke such as weakness in part of the body or difficulty speaking. If the bleeding occurs into the  subarachnoid space  ( subarachnoid hemorrhage ), there is usually a  severe, sudden headache  and decreased level of consciousness and often weakness in part of the body. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1349", "contents": "A very small proportion (those affected by  SMAD4  (MADH4) mutations, see below) have  multiple benign polyps  in the  large intestine , which may bleed or transform into  colorectal cancer . A similarly small proportion experiences  pulmonary hypertension , a state in which the  pressure in the lung arteries  is increased, exerting pressure on the  right side of the heart  and causing  peripheral edema  (swelling of the legs),  fainting  and attacks of  chest pain . It has been observed that the risk of  thrombosis  (particularly  venous thrombosis , in the form of  deep vein thrombosis  or  pulmonary embolism ) may be increased. There is a suspicion that those with HHT may have a mild  immunodeficiency  and are therefore at a slightly increased risk from infections. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1350", "contents": "HHT is a  genetic disorder  with an  autosomal dominant  inheritance pattern. Those with HHT symptoms that have no relatives with the disease may have a new mutation. [ 7 ]  Homozygosity appears to be fatal in utero. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1351", "contents": "Five genetic types of HHT are recognized. Of these, three have been  linked  to particular  genes , while the two remaining have currently only been associated with a particular  locus . More than 80% of all cases of HHT are due to mutations in either  ENG  or  ACVRL1 . [ 8 ]  A total of over 600 different mutations are known. There is likely to be a predominance of either type in particular populations, but the data are conflicting.  MADH4  mutations, which cause colonic polyposis in addition to HHT, comprise about 2% of disease-causing mutations. Apart from  MADH4 , it is not clear whether mutations in  ENG  and  ACVRL1  lead to particular symptoms, [ 1 ]  although some reports suggest that  ENG  mutations are more likely to cause lung problems while  ACVRL1  mutations may cause more liver problems, [ 2 ] [ 5 ]  and pulmonary hypertension may be a particular problem in people with  ACVRL1  mutations. [ 8 ]  People with exactly the same mutations may have different nature and severity of symptoms, suggesting that additional genes or other risk factors may determine the rate at which lesions develop; these have not yet been identified. [ 2 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1352", "contents": "Telangiectasias and arteriovenous malformations in HHT are thought to arise because of changes in  angiogenesis , the development of blood vessels out of existing ones. The development of a new blood vessel requires the activation and migration of various types of cells, chiefly  endothelium ,  smooth muscle  and  pericytes . The exact mechanism by which the HHT mutations influence this process is not yet clear, and it is likely that they disrupt a balance between pro- and antiangiogenic signals in blood vessels. The wall of telangiectasias is unusually  friable , which explains the tendency of these lesions to bleed. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1353", "contents": "All genes known so far to be linked to HHT code for proteins in the  TGF-\u03b2 signaling pathway . This is a group of proteins that participates in  signal transduction  of hormones of the  transforming growth factor beta superfamily  (the  transforming growth factor beta ,  bone morphogenetic protein  and  growth differentiation factor  classes), specifically  BMP9/GDF2  and  BMP10 . The hormones do not enter the cell but link to receptors on the cell membrane; these then activate other proteins, eventually influencing cellular behavior in a number of ways such as cellular survival, proliferation (increasing in number) and differentiation (becoming more specialized). [ 1 ]  For the hormone signal to be adequately transduced, a combination of proteins is needed: two each of two types of  serine/threonine-specific kinase type   membrane receptors  and endoglin. When bound to the hormone, the type II receptor proteins  phosphorylate  (transfer  phosphate ) onto type I receptor proteins (of which Alk-1 is one), which in turn phosphorylate a complex of  SMAD proteins  (chiefly  SMAD1 ,  SMAD5  and  SMAD8 ). These bind to SMAD4 and migrate to the  cell nucleus  where they act as  transcription factors  and participate in the  transcription  of particular genes. In addition to the SMAD pathway, the membrane receptors also act on the  MAPK pathway , which has additional actions on the behavior of cells. [ 2 ]  Both Alk-1 and endoglin are  expressed  predominantly in endothelium, perhaps explaining why HHT-causing mutations in these proteins lead predominantly to blood vessel problems. [ 2 ] [ 8 ]  Both  ENG  and  ACVRL1  mutations lead predominantly to underproduction of the related proteins, rather than misfunctioning of the proteins. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1354", "contents": "Diagnostic tests may be conducted for various reasons. Firstly, some tests are needed to confirm or refute the diagnosis. Secondly, some are needed to identify any potential complications. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1355", "contents": "The skin and oral cavity telangiectasias are visually identifiable on  physical examination , and similarly the lesions in the nose may be seen on  endoscopy  of the  nasopharynx  or on  laryngoscopy . The severity of nosebleeds may be quantified objectively using a grid-like questionnaire in which the number of nosebleed episodes and their duration is recorded. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1356", "contents": "Digestive tract telangiectasias may be identified on  esophagogastroduodenoscopy  (endoscopy of the esophagus, stomach and first part of the small intestine). This procedure will typically only be undertaken if there is anemia that is more marked than expected by the severity of nosebleeds, or if there is evidence of severe bleeding (vomiting blood, black stools). If the number of lesions seen on endoscopy is unexpectedly low, the remainder of the small intestine may be examined with  capsule endoscopy , in which the patient swallows a capsule-shaped device containing a miniature camera which transmits images of the digestive tract to a portable digital recorder. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1357", "contents": "Identification of AVMs requires detailed  medical imaging  of the organs most commonly affected by these lesions. Not all AVMs cause symptoms or are at risk of doing so, and hence there is a degree of variation between specialists as to whether such investigations would be performed, and by which modality; often, decisions on this issue are reached together with the patient. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1358", "contents": "Lung AVMs may be suspected because of the abnormal appearance of the lungs on a  chest X-ray , or  hypoxia  (low oxygen levels) on  pulse oximetry  or  arterial blood gas  determination.  Bubble contrast echocardiography  (bubble echo) may be used as a screening tool to identify abnormal connections between the  lung arteries  and  veins . This involves the injection of agitated  saline  into a vein, followed by ultrasound-based imaging of the heart. Normally, the lungs remove small air bubbles from the circulation, and they are therefore only seen in the  right atrium  and the  right ventricle . If an AVM is present, bubbles appear in the  left atrium  and  left ventricle , usually 3\u201310  cardiac cycles  after the right side; this is slower than in  heart defects , in which there are direct connections between the right and left side of the heart. A larger number of bubbles is more likely to indicate the presence of an AVM. Bubble echo is not a perfect screening tool as it can miss smaller AVMs and does not identify the site of AVMs.  Often  contrast -enhanced  computed tomography  (CT angiography) is used to identify lung lesions; this modality has a  sensitivity  of over 90%. [ 1 ] [ 2 ]  It may be possible to omit contrast administration on modern CT scanners. [ 5 ]  Echocardiography is also used if there is a suspicion of pulmonary hypertension or high-output cardiac failure due to large liver lesions, sometimes followed by  cardiac catheterization  to measure the pressures inside the various chambers of the heart. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1359", "contents": "Liver AVMs may be suspected because of abnormal  liver function tests  in the blood, because the symptoms of heart failure develop, or because of  jaundice  or other symptoms of liver dysfunction. The most reliable initial screening test is  Doppler ultrasonography  of the liver; this has a very high sensitivity for identifying vascular lesions in the liver. If necessary, contrast-enhanced CT may be used to further characterize AVMs. [ 1 ] [ 2 ] [ 6 ]  It is extremely common to find incidental nodules on liver scans, most commonly due to  focal nodular hyperplasia  (FNH), as these are a hundredfold times more common in HHT compared to the general population. FNH is regarded as harmless. Generally,  tumor markers  and additional imaging modalities are used to differentiate between FNH and malignant tumors of the liver.  Liver biopsy  is discouraged in people with HHT as the risk of hemorrhage from liver AVMs may be significant. [ 6 ] [ 7 ]  Liver scans may be useful if someone is suspected of HHT, but does not meet the criteria (see below) unless liver lesions can be demonstrated. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1360", "contents": "Brain AVMs may be detected on  computed tomography angiography  (CTA or CT angio) or  magnetic resonance angiography  (MRA); CTA is better in showing the vessels themselves, and MRA provides more detail about the relationship between an AVM and surrounding brain tissue. [ 14 ]  In general, MRI is recommended. [ 2 ] [ 7 ]  Various types of vascular malformations may be encountered: AVMs, micro-AVMs, telangiectasias and arteriovenous  fistulas . [ 7 ]  If surgery, embolization, or other treatment is contemplated (see below),  cerebral angiography  may be required to get sufficient detail of the vessels. This procedure carries a small risk of stroke (0.5%) and is therefore limited to specific circumstances. [ 7 ] [ 14 ]  Recent professional guidelines recommend that all children with suspected or definite HHT undergo a brain MRI early in life to identify AVMs that can cause major complications. [ 7 ]  Others suggest that screening for cerebral AVMs is probably unnecessary in those who are not experiencing any neurological symptoms, because most lesions discovered on screening scans would not require treatment, creating undesirable conundrums. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1361", "contents": "Genetic tests are available for the  ENG ,  ACVRL1  and  MADH4  mutations. Testing is not always needed for diagnosis, because the symptoms are sufficient to distinguish the disease from other diagnoses. There are situations in which testing can be particularly useful. Firstly, children and young adults with a parent with definite HHT may have limited symptoms, yet be at risk from some of the complications mentioned above; if the mutation is known in the affected parent, absence of this mutation in the child would prevent the need for screening tests. Furthermore,  genetic testing  may confirm the diagnosis in those with limited symptoms who otherwise would have been labeled \"possible HHT\" (see below). [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1362", "contents": "Genetic diagnosis in HHT is difficult, as mutations occur in numerous different locations in the linked genes, without particular mutations being highly frequent (as opposed to, for instance, the  \u0394F508  mutation in  cystic fibrosis ).  Sequence analysis  of the involved genes is therefore the most useful approach (sensitivity 75%), followed by additional testing to detect large deletions and duplications (additional 10%). Not all mutations in these genes have been linked with disease. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1363", "contents": "Mutations in the  MADH4  gene is usually associated with juvenile polyposis, and detection of such a mutation would indicate a need to screen the patient and affected relatives for polyps and tumors of the large intestine. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1364", "contents": "The diagnosis can be made depending on the presence of four criteria, known as the \" Cura\u00e7ao  criteria\". [ 15 ]  If three or four are met, a patient has \"definite HHT\", while two gives \"possible HHT\":"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1365", "contents": "Despite the designation \"possible\", someone with a visceral AVM and a family history but no nosebleeds or telangiectasias is still extremely likely to have HHT, because these AVMs are very uncommon in the general population. At the same time, the same cannot be said of nosebleeds and sparse telangiectasias, both of which occur in people without HHT, in the absence of AVMs. Someone's diagnostic status may change in the course of life, as young children may not yet exhibit all the symptoms; at age 16, thirteen percent are still indeterminate, while at age 60 the vast majority (99%) have a definite diagnostic classification. The children of established HHT patients may therefore be labeled as \"possible HHT\", as 50% may turn out to have HHT in the course of their life. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1366", "contents": "Treatment of HHT is  symptomatic  (it deals with the symptoms rather than the disease itself), as there is no therapy that stops the development of telangiectasias and AVMs directly. Furthermore, some treatments are applied to prevent the development of common complications. [ 7 ]  Chronic nosebleeds and digestive tract bleeding can both lead to anemia; if the bleeding itself cannot be completely stopped, the anemia requires treatment with  iron supplements . Those who cannot tolerate iron tablets or solutions may require administration of  intravenous  iron, and  blood transfusion  if the anemia is causing severe symptoms that warrant rapid improvement of the blood count. [ 2 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1367", "contents": "Most treatments used in HHT have been described in adults, and the experience in treating children is more limited. [ 7 ]  Women with HHT who get  pregnant  are at an increased risk of complications, and are observed closely, although the absolute risk is still low (1%). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1368", "contents": "An acute nosebleed may be managed with a variety of measures, such as packing of the nasal cavity with absorbent swabs or gels. Removal of the packs after the bleeding may lead to reopening of the fragile vessels, and therefore lubricated or atraumatic packing is recommended. [ 7 ]  Some patients may wish to learn packing themselves to deal with nosebleeds without having to resort to medical help. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1369", "contents": "Frequent nosebleeds can be prevented in part by keeping the nostrils moist, and by applying  saline solution ,  estrogen -containing creams or  tranexamic acid ; these have few side effects and may have a small degree of benefit. [ 7 ]  A number of additional modalities has been used to prevent recurrent bleeding if simple measures are unsuccessful. Medical therapies include oral tranexamic acid and estrogen; the  evidence  for these is relatively limited, and estrogen is poorly tolerated by men and possibly carries risks of cancer and heart disease in women past the menopause. [ 2 ] [ 7 ]  Nasal coagulation and  cauterization  may reduce the bleeding from telangiectasias, and is recommended before surgery is considered. However, it is highly recommended to use the least heat and time to prevent septal perforations and excessive trauma to the nasal mucosa that are already susceptible to bleeding. [ citation needed ]  Sclerotherapy is another option to manage the bleeding. This process involves injecting a small amount of an aerated irritant (detergent such as sodium tetradecyl sulfate) directly into the telangiectasias. The detergent causes the vessel to collapse and harden, resulting in scar tissue residue. This is the same procedure used to treat varicose veins and similar disorders. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1370", "contents": "It may be possible to  embolize  vascular lesions through  interventional radiology ; this requires passing a catheter through a large artery and locating the  maxillary artery  under  X-ray guidance , followed by the injection into the vessel of particles that occlude the blood vessels. The benefit from the procedure tends to be short-lived, [ 7 ]  and it may be most appropriate in episodes of severe bleeding. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1371", "contents": "To more effectively minimize recurrence and severity of epistaxis, other options may be used in conjunction with therapies listed above. Intravenously administered anti-VEGF substances such as bevacizumab (brand name Avastin), pazopinab, and thalidomide or its derivatives (lenolidomide, pomalidomide) interfere with the production of new blood vessels that are weak and therefore prone to bleeding. Because thalidomide is a teratogen, thalidomide is considered by many to be a last resort therapy, and additionally can cause neuropathy, which can be mitigated by titrating dosages or prescribing thalidomide derivatives such as lenolidomide and pomalidomide. Pomalidomide causes a significant, clinically relevant reduction in epistaxis severity and improvement in quality of life. [ 17 ]  Nevertheless, many doctors prefer alternative VEGF inhibitors; eg bevacizumab nasal spray also significantly reduces epistaxis severity without side effects. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1372", "contents": "If other interventions have failed, several operations have been reported to provide benefit. One is septal dermoplasty or Saunders' procedure, [ 19 ]  in which skin is transplanted into the nostrils, and the other is Young's procedure, [ 20 ]  in which the nostrils are sealed off completely. [ 7 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1373", "contents": "The skin lesions of HHT can be disfiguring, and may respond to treatment with long-pulsed  Nd:YAG laser . [ 2 ]  Skin lesions in the fingertips may sometimes bleed and cause pain.  Skin grafting  is occasionally needed to treat this problem. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1374", "contents": "With regards to digestive tract lesions, mild bleeding and mild resultant anemia is treated with iron supplementation, and no specific treatment is administered. There is limited data on hormone treatment and tranexamic acid to reduce bleeding and anemia. Severe anemia or episodes of severe bleeding are treated with endoscopic  argon plasma coagulation  (APC) or laser treatment of any lesions identified; this may reduce the need for supportive treatment. The expected benefits are not such that repeated attempts at treating lesions are advocated. [ 7 ]  Sudden, very severe bleeding is unusual\u2014if encountered, alternative causes (such as a  peptic ulcer ) need to be considered [ 7 ] \u2014but embolization may be used in such instances. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1375", "contents": "Lung lesions, once identified, are usually treated to prevent episodes of bleeding and more importantly embolism to the brain. This is particularly done in lesions with a feeding blood vessel of 3\u00a0mm or larger, as these are the most likely to cause long-term complications unless treated. The most effective current therapy is embolization with detachable metal coils or plugs. [ 21 ]  The procedure involves puncture of a large vein (usually under a  general anesthetic ), followed by  advancing of a catheter through the right ventricle  and into the  pulmonary artery , after which  radiocontrast  is injected to visualize the AVMs ( pulmonary angiography ). Once the lesion has been identified, coils are deployed that obstruct the blood flow and allow the lesion to regress. In experienced hands, the procedure tends to be very effective and with limited side effects, but lesions may recur and further attempts may be required. CTA scans are repeated to monitor for recurrence. [ 2 ] [ 4 ] [ 5 ] [ 7 ]  Surgical excision has now essentially been abandoned due to the success of embolotherapy. [ 5 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1376", "contents": "Those with either definite pulmonary AVMs or an abnormal contrast echocardiogram with no clearly visible lesions are deemed to be at risk from brain emboli. They are therefore counselled to avoid  scuba diving , during which small air bubbles may form in the bloodstream that may migrate to the brain and cause stroke. Similarly,  antimicrobial prophylaxis  is advised during procedures in which bacteria may enter the bloodstream, such as  dental work , and avoidance of air bubbles during  intravenous therapy . [ 2 ] [ 5 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1377", "contents": "Given that liver AVMs generally cause high-output cardiac failure, the emphasis is on treating this with  diuretics  to reduce the circulating blood volume, restriction of salt and fluid intake, and  antiarrhythmic agents  in case of  irregular heart beat . This may be sufficient in treating the symptoms of swelling and breathlessness. If this treatment is not effective or leads to side effects or complications, the only remaining option is  liver transplantation . This is reserved for those with severe symptoms, as it carries a  mortality  of about 10%, but leads to good results if successful. [ 6 ] [ 7 ]  The exact point at which liver transplantion is to be offered is not yet completely established. [ 6 ]  Embolization treatment has been attempted, but leads to severe complications in a proportion of patients and is discouraged. [ 5 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1378", "contents": "Other liver-related complications (portal hypertension, esophageal varices, ascites, hepatic encephalopathy) are treated with the same modalities as used in  cirrhosis , although the use of  transjugular intrahepatic portosystemic shunt  treatment is discouraged due to the lack of documented benefit. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1379", "contents": "The decision to treat brain  arteriovenous malformations  depends on the symptoms that they cause (such as seizures or headaches). The bleeding risk is predicted by previous episodes of hemorrhage, and whether on the  CTA  or  MRA  scan the AVM appears to be deep-seated or have deep venous drainage. Size of the AVM and the presence of  aneurysms  appears to matter less. [ 14 ]  In HHT, some lesions (high-flow arteriovenous fistulae) tend to cause more problems, and treatment is warranted.  Other AVMs may regress over time without intervention. [ 7 ]  Various modalities are available, depending on the location of the AVM and its size: surgery, radiation-based treatment and embolization. Sometimes, multiple modalities are used on the same lesion. [ 2 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1380", "contents": "Surgery (by  craniotomy , open brain surgery) may be offered based on the risks of treatment as determined by the Spetzler\u2013Martin scale (grade I-V); this score is higher in larger lesions that are close to important brain structures and have deep venous drainage. High grade lesions (IV and V) have an unacceptably high risk and surgery is not typically offered in those cases.  Radiosurgery  (using targeted  radiation therapy  such as by a  gamma knife ) may be used if the lesion is small but close to vital structures. Finally, embolization may be used on small lesions that have only a single feeding vessel. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1381", "contents": "Several anti- angiogenesis  drugs approved for other conditions, such as cancer, have been investigated in small clinical trials. [ 22 ]  The anti- VEGF  antibody  bevacizumab , for instance, has been used  off-label  in several studies. In a large clinical trial, bevacizumab infusion was associated with a decrease in cardiac output and reduced duration and number of episodes of epistaxis in treated HHT patients. [ 23 ]   Thalidomide , another anti- angiogenesis  drug, was also reported to have beneficial effects in HHT patients. [ 24 ]  Thalidomide treatment was found to induce vessel maturation in an experimental mouse model of HHT and to reduce the severity and frequency of nosebleeds in the majority of a small group of HHT patients. The blood hemoglobin levels of these treated patients rose as a result of reduced hemorrhage and enhanced blood vessel stabilization. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1382", "contents": "Population studies from numerous areas in the world have shown that HHT occurs at roughly the same rate in almost all populations: somewhere around 1 in 5000. In some areas, it is much more common; for instance, in the  French  region of  Haut Jura  the rate is 1:2351 - twice as common as in other populations. This has been attributed to a  founder effect , in which a population descending from a small number of ancestors has a high rate of a particular genetic trait because one of these ancestors harbored this trait. [ 8 ]  In Haut Jura, this has been shown to be the result of a particular  ACVRL1  mutation (named c.1112dupG or c.1112_1113insG). [ 2 ]  The highest rate of HHT is 1:1331, reported in  Bonaire  and  Cura\u00e7ao , two islands in the  Caribbean  belonging to the  Netherlands Antilles . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1383", "contents": "Most people with HHT have a normal lifespan. [ 1 ]  The skin lesions and nosebleeds tend to develop during childhood. AVMs are probably present from birth, but don't necessarily cause any symptoms. Frequent nosebleeds are the most common symptom and can significantly affect  quality of life . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1384", "contents": "Several 19th century English physicians, starting with  Henry Gawen Sutton  (1836\u20131891) [ 26 ]  and followed by  Benjamin Guy Babington  (1794\u20131866) [ 27 ]  and  John Wickham Legg  (1843\u20131921), [ 28 ]  described the most common features of HHT, particularly the recurrent nosebleeds and the hereditary nature of the disease. The French physician Henri Jules Louis Marie Rendu (1844\u20131902) observed the skin and mucosal lesions, and distinguished the condition from  hemophilia . [ 29 ]  The Canadian-born  Sir William Osler  (1849\u20131919), then at  Johns Hopkins Hospital  and later at  Oxford University , made further contributions with a 1901 report in which he described characteristic lesions in the  digestive tract . [ 30 ]  The English physician Frederick Parkes Weber (1863\u20131962) reported further on the condition in 1907 with a series of cases. [ 31 ]  The term \"hereditary hemorrhagic telangiectasia\" was first used by the American physician Frederic M. Hanes (1883\u20131946) in a 1909 article on the condition. [ 3 ] [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1385", "contents": "The diagnosis of HHT remained a clinical one until the genetic defects that cause HHT were identified by a research group at  Duke University Medical Center , in 1994 and 1996 respectively. [ 9 ] [ 10 ]  In 2000, the international scientific advisory committee of cureHHT formerly called the HHT Foundation International published the now widely used Cura\u00e7ao criteria. [ 7 ] [ 15 ]  In 2006, a group of international experts met in  Canada  and formulated an  evidence-based   guideline , sponsored by cureHHT. [ 7 ]  This guideline has since been updated in 2020 and can be found  here ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1386", "contents": "EDAR  ( EDAR hypohidrotic ectodermal dysplasia )"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1387", "contents": "Human parainfluenza viruses  ( HPIVs ) are the viruses that cause  human parainfluenza . HPIVs are a  paraphyletic  group of four distinct  single-stranded   RNA   viruses  belonging to the  Paramyxoviridae  family. These viruses are closely associated with both human and veterinary disease. [ 2 ]  Virions are approximately 150\u2013250\u00a0nm in size and contain negative sense  RNA  with a  genome  encompassing about 15,000  nucleotides . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1388", "contents": "The viruses can be detected via  cell culture ,  immunofluorescent   microscopy , and  PCR . [ 4 ]  HPIVs remain the second main cause of hospitalisation in children under 5 years of age for a  respiratory illness  (only  respiratory syncytial virus (RSV)  causes more respiratory hospitalisations for this age group). [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1389", "contents": "The first HPIV was discovered in the late 1950s. The taxonomic division is broadly based on  antigenic  and  genetic  characteristics, forming four major  serotypes  or  clades , which today are considered distinct viruses. [ 6 ]  These include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1390", "contents": "HPIVs belong to two genera:  Respirovirus  (HPIV-1 & HPIV-3) and  Rubulavirus  (HPIV-2 & HPIV-4). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1391", "contents": "HPIVs are characterised by producing enveloped virions and containing single stranded negative sense  RNA . [ 3 ]  Non-infectious virions have also been reported to contain  RNA  with positive polarity. [ 3 ]  HPIV genomes are about 15,000  nucleotides  in length and encode six key structural  proteins . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1392", "contents": "The  structural gene  sequence of HPIVs is as follows:  3\u2032-NP-P-M-F-HN-L-5\u2032  (the protein prefixes and further details are outlined in the table below). [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1393", "contents": "With the advent of  reverse genetics , it has been found that the most efficient human parainfluenza viruses (in terms of replication and transcription) have a genome  nucleotide  total that is divisible by the number 6. This has led to the \" rule of six \" being coined. Exceptions to the rule have been found, and its exact advantages are not fully understood. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1394", "contents": "Electrophoresis  has shown that the  molecular weight  of the proteins for the four HPIVs are similar (with the exception of the  phosphoprotein , which shows significant variation). [ 3 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1395", "contents": "Viral replication is initiated only after successful entry into a cell by attachment and fusion between the virus and the host cell  lipid membrane . Viral RNA ( vRNA ) is initially associated with nucleoprotein (NP), phosphoprotein (P) and the large protein (L). The  hemagglutinin \u2013 neuraminidase  (HN) is involved with viral attachment and thus hemadsorption and  hemagglutination . Furthermore, the fusion (F) protein is important in aiding the fusion of the host and viral cellular membranes, eventually forming  syncytia . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1396", "contents": "Initially the F protein is in an inactive form (F 0 ) but can be cleaved by  proteolysis  to form its active form, F 1  and F 2 , linked by di-sulphide bonds. Once complete, this is followed by the HPIV nucleocapsid entering the  cytoplasm  of the cell. Subsequently, genomic transcription occurs using the viruses own 'viral RNA-dependent  RNA polymerase ' (L protein). The cell's own  ribosomes  are then tasked with  translation , forming the viral proteins from the viral  mRNA . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1397", "contents": "Towards the end of the process, (after the formation of the viral proteins) the replication of the viral genome occurs. Initially, this occurs with the formation of a  positive-sense RNA  (intermediate step, necessary for producing progeny), and finally,  negative-sense RNA  is formed which is then associated with the  nucleoprotein . This may then be either packaged and released from the cell by budding or used for subsequent rounds of  transcription  and replication. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1398", "contents": "The observable and morphological changes that can be seen in infected cells include the enlargement of the  cytoplasm , decreased  mitotic  activity and 'focal rounding', with the potential formation of multi-nucleate cells (syncytia). [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1399", "contents": "The  pathogenicity  of HPIVs is mutually dependent on the viruses having the correct accessory proteins that are able to elicit anti- interferon  properties. This is a major factor in the  clinical significance  of disease. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1400", "contents": "The main host remains the human. However, infections have been induced in other animals (both under natural and experimental situations), although these were always  asymptomatic . [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1401", "contents": "It is estimated that there are 5 million children with  lower respiratory infections  (LRI) each year in the United States alone. [ 14 ]   HPIV-1, HPIV-2 and HPIV-3 have been linked with up to a third of these infections. [ 15 ]   Upper respiratory infections  (URI) are also important in the context of HPIV, however, they are caused to a lesser extent by the virus. [ 16 ]  The highest rates of serious HPIV illnesses occur among young children, and surveys have shown that about 75% of children aged 5 or older have antibodies to HPIV-1. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1402", "contents": "For infants and young children, it has been estimated that about 25% will develop \"clinically significant disease\". [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1403", "contents": "Repeated infection throughout the life of the host is not uncommon and symptoms of later breakouts include  upper respiratory tract  illness, such as  cold  and a sore throat. [ 3 ]  The  incubation period  for all four serotypes is 1 to 7 days. [ 18 ]  In  immunosuppressed  people, parainfluenza virus infections can cause severe  pneumonia , which can be fatal. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1404", "contents": "HPIV-1 and HPIV-2 have been demonstrated to be the principal causative agent behind  croup  ( laryngotracheobronchitis ), which is a viral disease of the upper airway and is mainly problematic in children aged 6\u201348 months of age. [ 20 ] [ 21 ]  Biennial epidemics starting in autumn are associated with both HPIV-1 and -2; however, HPIV-2 can also have yearly outbreaks. [ 14 ]  Additionally, HPIV-1 tends to cause biennial outbreaks of croup in the fall. In the United States, large peaks have presently been occurring during odd-numbered years. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1405", "contents": "HPIV-3 has been closely associated with  bronchiolitis  and  pneumonia , and principally targets those aged <1 year. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1406", "contents": "HPIV-4 remains infrequently detected. It is now believed to be more common than previously thought but less likely to cause severe disease. By the age of 10, the majority of children are seropositive for HPIV-4 infection\u2014this may be indicative of a large proportion of  asymptomatic  or mild infections. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1407", "contents": "Those with compromised immunity have a higher risk of infection and mortality and may fall ill with more extreme forms of LRI. [ 13 ]  Associations between HPIVs and  neurologic disease  are known. For example, hospitalisation with certain HPIVs has a strong association with  febrile seizures . [ 23 ]  HPIV-4b has the strongest association (up to 62%) [ vague ]  followed by HPIV-3 and -1. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1408", "contents": "HPIVs have also been linked with rare cases of viral  meningitis [ 24 ]  and  Guillain\u2013Barr\u00e9 syndrome . [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1409", "contents": "HPIVs are spread from person to person (i.e.,  horizontal transmission ) by contact with infected secretions in  respiratory droplets  or contaminated  surfaces or objects . Infection can occur when infectious material contacts the mucous membranes of the eyes, mouth, or nose, and possibly through the inhalation of droplets generated by a sneeze or cough. HPIVs can remain infectious in airborne droplets for over an hour. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1410", "contents": "The inflammation of the airway is a common attribute of HPIV infection. It is believed to occur due to the large scale upregulation of  inflammatory cytokines . Common  cytokines  observed to be upregulated include  IFN\u2013\u03b1 , various  interleukins  (i.e.,  IL\u20132 ,  IL-6 ), and  TNF\u2013\u03b1 . Various  chemokines  and inflammatory proteins are also believed to be associated with the common symptoms of HPIV infection. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1411", "contents": "Recent evidence suggests that the virus-specific antibody  immunoglobulin E  may be responsible for mediating the large-scale releases of  histamine  in the  trachea  that are believed to cause  croup . [ 12 ] [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1412", "contents": "The body's primary defense against HPIV infection is  adaptive immunity  involving both  humoral  and  cellular immunity . With humoral immunity, antibodies that bind to the surface viral proteins HN and F protect against later infection. [ 26 ]  Patients with defective cell-mediated immunity also experience more severe infection, suggesting that  T cells  are important in clearing infection. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1413", "contents": "Diagnosis can be made in several ways, encompassing a range of multi-faceted techniques: [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1414", "contents": "Because of the similarity in terms of the antigenic profile between the viruses,  hemagglutination assay  (HA) or hemadsorption inhibition (HAdI) processes are often used. Both  complement fixation ,  neutralisation , and  enzyme linked immunosorbent assays  \u2013 ELISA, can also be used to aid in the process of distinguishing between viral  serotypes . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1415", "contents": "Mortality caused by HPIVs in developed regions of the world remains rare. Where mortality has occurred, it is principally in the three core risk groups (very young, elderly and  immuno-compromised ). Long-term changes can however be associated with airway remodeling and are believed to be a significant cause of morbidity. [ 27 ]  The exact associations between HPIVs and diseases such as  chronic obstructive pulmonary disease  (COPD) are still being investigated. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1416", "contents": "In developing regions of the world, preschool children remain the highest mortality risk group. Mortality may be a consequence of primary viral infection or secondary problems, such as bacterial infection. Predispositions, such as  malnutrition  and other deficiencies, may further elevate the chances of mortality associated with infection. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1417", "contents": "Overall, LRIs cause approximately 25\u201330% of total deaths in preschool children in the developing world. HPIVs are believed to be associated with 10% of all LRI cases, thus remaining a significant cause of mortality. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1418", "contents": "Numerous factors have been suggested and linked to a higher risk of acquiring the infection, inclusive of  malnutrition ,  vitamin A deficiency , absence of breastfeeding during the early stages of life,  environmental pollution  and overcrowding. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1419", "contents": "Despite decades of research, no  vaccines  currently exist. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1420", "contents": "Recombinant technology  has however been used to target the formation of vaccines for HPIV-1, -2 and -3 and has taken the form of several live-attenuated intranasal vaccines. Two vaccines in particular were found to be  immunogenic  and well tolerated against HPIV-3 in  phase I trials . HPIV-1 and -2 vaccine candidates remain less advanced. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1421", "contents": "Vaccine techniques which have been used against HPIVs are not limited to intranasal forms, but also viruses  attenuated  by cold passage, host range attenuation, chimeric construct vaccines and also introducing mutations with the help of  reverse genetics  to achieve attenuation. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1422", "contents": "Maternal  antibodies  may offer some degree of protection against HPIVs during the early stages of life via the  colostrum  in breast milk. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1423", "contents": "Ribavirin  is one medication which has shown good potential for the treatment of HPIV-3 given recent  in-vitro  tests ( in-vivo  tests show mixed results). [ 12 ]  Ribavirin is a broad-spectrum  antiviral , and as of 2012, was being administered to those who are severely  immuno-compromised , despite the lack of conclusive evidence for its benefit. [ 12 ]  Protein inhibitors and novel forms of medication have also been proposed to relieve the symptoms of infection. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1424", "contents": "Furthermore,  antibiotics  may be used if a secondary bacterial infection develops.  Corticosteroid  treatment and  nebulizers  are also a first line choice against  croup  if breathing difficulties ensue. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1425", "contents": "Parainfluenza viruses last only a few hours in the environment and are inactivated by soap and water. Furthermore, the virus can also be easily destroyed using common hygiene techniques and detergents, disinfectants and antiseptics. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1426", "contents": "Environmental factors which are important for HPIV survival are  pH ,  humidity ,  temperature  and the  medium  within which the virus is found. The optimal pH is around the physiologic pH values (7.4 to 8.0), whilst at high temperatures (above 37\u00a0\u00b0C) and low humidity, infectivity reduces. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1427", "contents": "The majority of transmission has been linked to close contact, especially in  nosocomial infections . Chronic care facilities and doctors' surgeries are also known to be transmission 'hotspots' with transmission occurring via  aerosols , large droplets and also  fomites  (contaminated surfaces). [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1428", "contents": "The exact infectious dose remains unknown. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1429", "contents": "In economically disadvantaged regions of the world, HPIV infection can be measured in terms of mortality. In the developed world where mortality remains rare, the economic costs of the infection can be estimated. Estimates from the US are suggestive of a cost (based on  extrapolation ) in the region of $200 million per annum. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1430", "contents": "Influenza viruses belong to the  Orthomyxoviridae  family; Parainfluenza viruses (HPIVs) belong to the  Paramyxoviridae  family. Influenza typically causes more severe illness than parainfluenza. While both can cause upper respiratory symptoms, influenza is more likely to result in high fever, body aches, and fatigue. Parainfluenza often produces milder, cold-like symptoms such as runny nose, cough, and low-grade fever. [ 35 ]  Influenza has a distinct seasonal pattern, with outbreaks occurring mainly in winter months. Parainfluenza viruses circulate year-round, with each type having its own seasonal patterns. The viruses have a tendency towards different complications: influenza is more likely to cause severe pneumonia in high-risk groups; parainfluenza is more likely to cause croup in children. Influenza has effective vaccines available and can be treated with antiviral medications like neuraminidase inhibitors. There are currently no vaccines or specific antiviral treatments for parainfluenza viruses. Parainfluenza tends to infect young children, with most children being infected by age 5. Influenza can affect all ages. [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1431", "contents": "Hypercapnia  (from the  Greek   hyper , \"above\" or \"too much\" and  kapnos , \" smoke \"), also known as  hypercarbia  and  CO 2  retention , is a condition of abnormally elevated  carbon dioxide  (CO 2 ) levels in the blood. Carbon dioxide is a  gaseous  product of the  body's   metabolism  and is normally expelled through the  lungs . Carbon dioxide may accumulate in any condition that causes  hypoventilation , a reduction of  alveolar ventilation  (the clearance of air from the small sacs of the lung where  gas exchange  takes place) as well as resulting from inhalation of CO 2 . Inability of the lungs to clear carbon dioxide, or inhalation of elevated levels of CO 2 , leads to  respiratory acidosis . Eventually the body compensates for the raised acidity by retaining alkali in the kidneys, a process known as \"metabolic compensation\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1432", "contents": "Acute hypercapnia is called  acute hypercapnic respiratory failure  ( AHRF ) and is a medical emergency as it generally occurs in the context of acute illness. Chronic hypercapnia, where metabolic compensation is usually present, may cause symptoms but is not generally an emergency. Depending on the scenario both forms of hypercapnia may be treated with medication, with mask-based  non-invasive ventilation  or with  mechanical ventilation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1433", "contents": "Hypercapnia is a hazard of underwater diving associated with breath-hold diving, scuba diving, particularly on rebreathers, and deep diving where it is associated with increased breathing gas density due to the high ambient pressure. [ 3 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1434", "contents": "Hypercapnia may happen in the context of an underlying health condition, and symptoms may relate to this condition or directly to the hypercapnia. Specific symptoms attributable to early hypercapnia are  dyspnea  (breathlessness), headache, confusion and lethargy. Clinical signs include flushed skin, full  pulse  (bounding pulse),  rapid breathing ,  premature heart beats , muscle twitches, and hand flaps ( asterixis ). The risk of dangerous  irregularities of the heart beat  is increased. [ 6 ] [ 7 ]  Hypercapnia also occurs when the breathing gas is contaminated with carbon dioxide, or respiratory gas exchange cannot keep up with the metabolic production of carbon dioxide, which can occur when gas density limits ventilation at high ambient pressures. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1435", "contents": "In severe hypercapnia (generally  \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}}}}} \n \n  greater than 10  kPa  or 75  mmHg ), symptomatology progresses to disorientation,  panic ,  hyperventilation ,  convulsions ,  unconsciousness , and eventually  death . [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1436", "contents": "Carbon dioxide is a normal metabolic product but it accumulates in the body if it is produced faster than it is cleared. During strenuous exercise the production rate of carbon dioxide can increase more than tenfold over the production rate during rest. Carbon dioxide is dissolved in the blood and elimination is by gas exchange in the lungs during breathing. [ 10 ]  Hypercapnia is generally caused by  hypoventilation ,  lung disease , or diminished  consciousness . It may also be caused by exposure to environments containing abnormally high concentrations of carbon dioxide, such as from volcanic or geothermal activity, or by  rebreathing  exhaled  carbon dioxide . In this situation the hypercapnia can also be accompanied by  respiratory acidosis . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1437", "contents": "Acute hypercapnic respiratory failure may occur in acute illness caused by  chronic obstructive pulmonary disease  (COPD), chest wall deformity, some forms of  neuromuscular disease  (such as  myasthenia gravis ), and  obesity hypoventilation syndrome . [ 12 ]  AHRF may also develop in any form of respiratory failure where the breathing muscles become exhausted, such as severe  pneumonia  and  acute severe asthma . It can also be a consequence of profound suppression of consciousness such as  opioid overdose . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1438", "contents": "Normal respiration in divers results in  alveolar   hypoventilation  resulting in inadequate CO 2  elimination or hypercapnia. Lanphier's work at the  US Navy Experimental Diving Unit  answered the question, \"Why don't divers breathe enough?\": [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1439", "contents": "A variety of reasons exist for carbon dioxide not being expelled completely when the diver exhales:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1440", "contents": "Skip breathing is a controversial technique to conserve  breathing gas  when using  open-circuit scuba , which consists of briefly holding one's breath between inhalation and exhalation (i.e., \"skipping\" a breath). It can lead to CO 2  not being exhaled efficiently. [ 19 ]  The risk of burst lung ( pulmonary barotrauma  of ascent) is increased if the breath is held while ascending.  It is particularly counterproductive with a  rebreather , where the act of breathing pumps the gas around the \"loop\", pushing carbon dioxide through the scrubber and mixing freshly injected oxygen. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1441", "contents": "In closed-circuit  rebreather diving , exhaled carbon dioxide must be removed from the breathing system, usually by a  scrubber  containing a solid chemical compound with a high affinity for CO 2 , such as  soda lime . If not removed from the system, it may be reinhaled, causing an increase in the inhaled concentration. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1442", "contents": "Under hyperbaric conditions, hypercapnia contributes to  nitrogen narcosis  and  oxygen toxicity  by causing cerebral vasodilation which increases the dosage of oxygen to the brain. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1443", "contents": "Hypercapnia normally triggers a reflex which increases breathing and access to  oxygen  (O 2 ), such as arousal and turning the head during sleep. A failure of this reflex can be fatal, for example as a contributory factor in  sudden infant death syndrome . [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1444", "contents": "Hypercapnia can induce increased cardiac output, an elevation in arterial blood pressure (higher levels of carbon dioxide stimulate aortic and carotid  chemoreceptors  with afferents -CN IX and X- to medulla oblongata with following  chrono-  and  ino-tropic  effects), [ clarification needed ]  and a propensity toward  cardiac arrhythmias . Hypercapnia may increase pulmonary capillary resistance. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1445", "contents": "A high arterial partial pressure of carbon dioxide ( \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}}}}} \n \n ) causes changes in brain activity that adversely affect both fine muscular control and reasoning.  EEG  changes denoting minor narcotic effects can be detected for expired gas  end tidal  partial pressure of carbon dioxide ( \n \n \n \n \n \n P \n \n E \n \n T \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{ET_{CO_{2}}}}} \n \n ) increase from 40 torrs (0.053\u00a0atm) to approximately 50 torrs (0.066\u00a0atm). The diver does not necessarily notice these effects. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1446", "contents": "Higher levels of  \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}}}}} \n \n  have a stronger narcotic effect: Confusion and irrational behaviour may occur around 72 torrs (0.095\u00a0atm), and loss of consciousness around 90 torrs (0.12\u00a0atm). High  \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}}}}} \n \n triggers the fight or flight response, affects hormone levels and can cause anxiety, irritability and inappropriate or panic responses, which can be beyond the control of the subject, sometimes with little or no warning. Vasodilation is another effect, notably in the skin, where feelings of unpleasant heat are reported, and in the brain, where blood flow can increase by 50% at a  \n \n \n \n \n \n P \n \n E \n \n T \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{ET_{CO_{2}}}}} \n \n  of 50 torrs (0.066\u00a0atm), Intracranial pressure may rise, with a throbbing headache. If associated with a high  \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}}}}} \n \n  the high delivery of oxygen to the brain may increase the risk of CNS oxygen toxicity at partial pressures usually considered acceptable. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1447", "contents": "In many people a high  \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}}}}} \n \n  causes a feeling of shortness of breath, but the lack of this symptom is no guarantee that the other effects are not occurring. A significant percentage of rebreather deaths have been associated with CO 2  retention. The effects of high  \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}}}}} \n \n  can take several minutes to hours to resolve once the cause has been removed. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1448", "contents": "Blood gas tests  may be performed, typically by  radial artery puncture , in the setting of acute breathing problems or other acute medical illness. Hypercapnia is generally defined as an arterial blood carbon dioxide level over 45 mmHg (6 kPa). Since carbon dioxide is in equilibrium with  carbonic acid  in the blood, hypercapnia drives serum pH down, resulting in respiratory acidosis. Clinically, the effect of hypercapnia on pH is estimated using the ratio of the arterial pressure of carbon dioxide to the concentration of bicarbonate ion,  \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n / \n \n H \n C \n \n O \n \n 3 \n \n \n \u2212 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}/HCO_{3}^{-}}}}} \n \n . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1449", "contents": "Tests performed on  mongrel  dogs showed the physiological effect of carbon dioxide on the body of the animal: after inhalation of a 50% CO 2  and 50% air mixture, respiratory movement increased for about 2 minutes, and then, it decreased for 30 to 90 minutes. Hill and Flack showed that CO 2  concentrations up to 35% have an exciting effect upon both circulation and respiration, but those beyond 35% are depressant upon them. [ citation needed ]  The blood pressure (BP) decreased transiently during the increased respiratory movement and then rose again and maintained the original level for a while. The heart rate slowed slightly just after the gas mixture inhalation. It is believed that the initial BP depression with the decreased heart rate is due to the direct depressant effect of CO 2  upon the heart and that the return of blood pressure to its original level was due to the rapid rise of  \n \n \n \n \n \n P \n \n \n a \n \n C \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle {P_{a_{CO_{2}}}}} \n \n . After 30\u201390 min, the respiratory center was depressed, and hypotension occurred gradually or suddenly from reduced cardiac output, leading to an apnea and eventually to circulatory arrest."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1450", "contents": "At higher concentrations of CO 2 , unconsciousness occurred almost instantaneously and respiratory movement ceased in 1 minute. After a few minutes of apnea, circulatory arrest was seen. These findings imply that the cause of death in breathing high concentrations of CO 2  is not the hypoxia but the intoxication of carbon dioxide. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1451", "contents": "The treatment for acute hypercapnic respiratory failure depends on the underlying cause, but may include medications and mechanical respiratory support. In those without contraindications,  non-invasive ventilation  (NIV) is often used in preference to  invasive mechanical ventilation . [ 12 ]  In the past, the drug  doxapram  (a respiratory stimulant), was used for hypercapnia in  acute exacerbation of chronic obstructive pulmonary disease  but there is little evidence to support its use compared to NIV, [ 24 ]  and it does not feature in recent professional guidelines. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1452", "contents": "Very severe respiratory failure, in which hypercapnia may also be present, is often treated with  extracorporeal membrane oxygenation  (ECMO), in which oxygen is added to and carbon dioxide removed directly from the blood. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1453", "contents": "A relatively novel modality is  extracorporeal carbon dioxide removal  (ECCO 2 R). This technique removes CO 2  from the bloodstream and may reduce the time mechanical ventilation is required for those with AHRF; it requires smaller volumes of blood flow compared to ECMO. [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1454", "contents": "Hypercapnia is the opposite of  hypocapnia , the state of having abnormally reduced levels of carbon dioxide in the blood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1455", "contents": "Hyperoxia  is the state of being exposed to high levels of  oxygen ; it may refer to organisms, cells and tissues that are experiencing excessive oxygenation, [ 1 ]  or to an abnormally high oxygen concentration in an environment (e.g. a body of water)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1456", "contents": "In  medicine , it refers to excessive oxygen in the  lungs  or other body  tissues , and results from raised  alveolar  oxygen  partial pressure  \u2015 that is, alveolar oxygen partial pressure greater than that due to breathing air at normal (sea level)  atmospheric pressure .  This can be caused by breathing air at a pressure above normal or by breathing other gas mixtures with a high oxygen  fraction , high ambient pressure or both."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1457", "contents": "The body is tolerant of some deviation from normal inspired oxygen partial pressure, but a sufficiently elevated level of hyperoxia can lead to  oxygen toxicity  over time, with the mechanism related to the partial pressure, and the severity related to the dose. Hyperoxia is the opposite of  hypoxia ; hyperoxia refers to a state in which oxygen supply to the tissues is excessive, while hypoxia refers to a state in which oxygen supply is insufficient. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1458", "contents": "Supplementary oxygen administration is widely used in emergency and intensive care medicine and can be life-saving in critical conditions, but too much can be harmful and affects a variety of  pathophysiological  processes.  Reactive oxygen species  are known problematic  by-products  of hyperoxia which have an important role in  cell signaling  pathways. There are a wide range of effects, but when the  homeostatic  balance is disturbed, reactive oxygen species tend to cause a cycle of tissue injury, with  inflammation , cell damage, and cell death. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1459", "contents": "Associated with hyperoxia is an increased level of  reactive oxygen species  (ROS), which are chemically reactive  molecules  containing oxygen. These oxygen containing molecules can damage  lipids ,  proteins , and  nucleic acids , and react with surrounding biological tissues. The human body has naturally occurring  antioxidants  to combat reactive molecules, but the protective antioxidant defenses can become depleted by abundant reactive oxygen species, resulting in  oxidation  of the tissues and organs. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1460", "contents": "The symptoms produced from breathing high concentrations of oxygen for extended periods have been studied in a variety of animals, such as frogs, turtles, pigeons, mice, rats, guinea pigs, cats, dogs and monkeys. The majority of these studies reported the occurrence of  irritation , congestion and  edema  of the lungs, and even death following prolonged exposures. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1461", "contents": "Excessive exposure to oxygen can lead to  oxygen toxicity , also known as oxygen toxicity syndrome, oxygen intoxication, and oxygen poisoning. There are two main ways in which oxygen toxicity can occur: exposure to significantly elevated partial pressures of oxygen for a short period of time (acute oxygen toxicity), or exposure to more modest elevations in oxygen partial pressures but for a longer duration (chronic oxygen toxicity). Acute toxicity often presents with central nervous system (CNS) effects, while chronic toxicity often manifests with pulmonary (lung) effects. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1462", "contents": "Early CNS signs of acute oxygen toxicity may vary, though perioral twitching and spasm of small muscles of the hand are common. As exposure is prolonged, additional symptoms may develop such as nausea, tinnitus (\"ringing in the ears\"), dysphoria (feeling of unease), and seizure. [ 5 ]  A  grand-mal seizure , also known as a  generalized tonic-clonic seizure  may occur. This type of  seizure  consists of a loss of consciousness and violent muscle contractions. Signs and symptoms of oxygen toxicity are usually prevalent, but there are no standard warning signs that suggest a seizure is about to ensue. The  convulsion  caused by oxygen toxicity does not lead to hypoxia, a side effect common to most seizures, because the body has an excess amount of oxygen when the convulsion begins. If oxygen toxicity is experienced while in a body of water, such as in underwater diving, a seizure may lead to drowning. [ 6 ]  If the inciting agent is removed, there are typically no long-term neurological impacts of oxygen toxicity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1463", "contents": "Pulmonary damage results from reactive oxygen species altering structures within the lungs, such as damaging the pulmonary epithelium and inactivating the surfactant. Pulmonary symptoms may begin with slight irritation in the  trachea . A mild cough usually ensues, followed by greater irritation and a worse cough, until breathing becomes quite painful and the cough becomes uncontrollable. If supplementation of oxygen is continued, the individual will notice tightness in the chest, difficulty breathing, and shortness of breath. If exposure is continued, a fatality may result due to the lack of oxygen. [ 6 ]  Hemoptysis (coughing up blood) may also be seen. Pulmonary damage is often reversible over time after inciting agent is removed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1464", "contents": "Ocular (eye) damage may also occur. In premature infants this may be seen as retinopathy of prematurity and retrolental fibroplasia. Swelling of the retina may also occur, and with prolonged exposure there is increased likelihood of cataract development. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1465", "contents": "The supplementation of oxygen has been a common procedure of pre-hospital treatment for many years. Hyperoxia often occurs in controlled medical environments where high concentrations of oxygen are administered, such as during  mechanical ventilation  or oxygen therapy in intensive care units. The highest risk of hyperoxia is in  hyperbaric oxygen therapy , where it is a high probability side effect of the treatment for more serious conditions, and is considered an acceptable risk as it can be managed effectively without apparent long term effects. [ 8 ]  In such settings, it is crucial to regularly monitor PaO2 levels to prevent hyperoxia and its associated complications. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1466", "contents": "An additional cause of hyperoxia is related to  underwater diving  with breathing apparatus. Divers breath a mixture of gases which must include oxygen, and the partial pressure of oxygen in any given gas mixture will increase with depth. Atmospheric air becomes hyperoxic during the dive, and a hyperoxic gas mixture known as  nitrox  is used to reduce the risk of decompression sickness by substituting oxygen for part of the nitrogen content. Breathing nitrox can lead to  oxygen toxicity  due to the high partial pressure of oxygen if used  too deep  or for too long. Protocols for the safe use of raised oxygen partial pressure in diving are well established and used routinely by recreational scuba divers, military combat divers and professional saturation divers alike. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1467", "contents": "Oxygen  rebreathers  are also used for normobaric routine work and emergency response in non-breatheable atmospheres, or in circumstances where the suitability of the ambient gas for breathing is unknown or may change without warning, such as firefighting, underground rescue, and work in confined spaces. Supplemental oxygen is also used for high altitude exposures in aviation and mountaineering. In all these cases, the maximum concentration is naturally limited by the ambient pressure, but the lower limit is usually more difficult to control, and the immediate consequences of hypoxia are generally more serious that the immediate consequences of hyperoxia, so there is a tendency to provide a larger margin for error for hypoxia, and the user is exposed to hyperoxic conditions for much of the time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1468", "contents": "Supplementary oxygen is an effective and widely available treatment for hypoxemia and hypoxia associated with many pathological processes, but other pathophysiological processes are associated with increased levels of ROS caused by hyperoxia. These ROS react with biological tissues and may damage  proteins ,  lipids , and  nucleic acids .  Antioxidants  that normally protect tissues can be overwhelmed by higher levels of ROS, thereby causing  oxidative stress . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1469", "contents": "Alveolar and alveolar capillary  epithelial cells  are vulnerable to injuries caused by oxygen  free radicals  due to hyperoxia. In acute lung injuries of this type, hyperpermeability of the pulmonary microvasculature allows plasma leakage, causing pulmonary edema and abnormalities in coagulation and  fibrin  deposition.  Surfactant  production can be impaired. The maximum benefit of oxygen availability is a balance between necessity and toxicity along a continuum. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1470", "contents": "Cumulative oxygen dose is determined by a combination of exposure time, ambient pressure, and the oxygen fraction of the inhaled gas. The latter two factors can be combined as the partial pressure of inhaled oxygen in the alveoli. Partial pressures of inhaled oxygen exceeding 0.6  bar  ( FIO2  >0.6 at normal atmospheric pressure), administered for extended periods in the order of days, are toxic to the lungs. This is known as low-pressure oxygen poisoning, pulmonary toxicity, or the  Lorrain Smith effect . This form of exposure leads to lung airway congestion, pulmonary edema, and  atelectasis  caused by damage to the linings of the  bronchi  and alveoli. Fluid accumulation in the lungs causes a feeling of shortness of breath, a burning sensation is felt in the throat and chest, and breathing becomes painful. At normal atmospheric pressures, the effect is mainly confined to the lungs as they are directly exposed to the high concentration of oxygen, which is not distributed throughout the body due to the hemoglobin-oxygen buffer system, with relatively little oxygen carried in solution in the plasma. At higher ambient pressures and higher oxygen partial pressures, where a larger amount of oxygen is carried in solution, toxic effects on the central nervous system manifest over a much shorter exposure time. This is known as high-pressure oxygen poisoning, or the Paul Bert effect. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1471", "contents": "Hyperoxia has also been linked to cellular damage through the induction of apoptosis and necrosis. The overproduction of ROS can disrupt cellular signaling pathways, lead to mitochondrial dysfunction, and trigger inflammatory responses. These effects contribute to the pathogenesis of diseases such as  acute respiratory distress syndrome  (ARDS) and  chronic obstructive pulmonary disease  (COPD). In the central nervous system, high levels of oxygen can cause seizures, which are a significant risk in hyperbaric oxygen therapy if not carefully monitored. [ 2 ]  Besides, hyperoxia can result in  vasoconstriction , particularly affecting cerebral and coronary circulation, potentially leading to adverse outcomes, including increased mortality in critically ill patients. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1472", "contents": "Further research is ongoing to better understand the long-term impacts of hyperoxia on various organs and systems, as well as to optimize oxygen therapy protocols to minimize these risks while ensuring effective treatment for hypoxic conditions. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1473", "contents": "Hyperoxia is primarily diagnosed by measuring the partial pressure of oxygen (PaO2) in  arterial blood . This method is more accurate than non-invasive measures like the Oxygen Reserve Index (ORI) and  oxygen saturation  (SpO2), which have shown limited diagnostic accuracy for detecting hyperoxia, particularly in critically ill patients. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1474", "contents": "The primary diagnostic method for hyperoxia involves measuring the partial pressure of oxygen in arterial blood through  arterial blood gas  (ABG) analysis. This approach is considered the gold standard for diagnosing hyperoxia, as it accurately assesses PaO2 levels. Normally, PaO2 ranges from 75 to 100  mmHg , with hyperoxia generally being recognized when PaO2 exceeds 100 mmHg."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1475", "contents": "In addition to PaO2 measurement, non-invasive methods such as the Oxygen Reserve Index (ORI) and oxygen saturation (SpO2) are also used, though their effectiveness is limited. The ORI, despite being non-invasive, has a low correlation with PaO2 and is therefore unreliable for diagnosing hyperoxia. Studies have shown that ORI's ability to detect PaO2 levels greater than 100 mmHg is limited, as indicated by an  area under the receiver operating characteristic curve  (AUROC) of only 0.567. [ 12 ]  Similarly, SpO2 measured via  pulse oximetry  is useful for monitoring oxygen levels, but its diagnostic utility for hyperoxia is constrained because SpO2 readings are capped at 100%. This makes SpO2 more effective for detecting hypoxia rather than hyperoxia."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1476", "contents": "The management of hyperoxia primarily involves titrating oxygen therapy to avoid excessive oxygen levels while ensuring adequate tissue oxygenation. Clinical guidelines recommend maintaining arterial oxygen saturation (SpO2) within a target range of 88-95% to prevent both  hypoxemia  and hyperoxemia."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1477", "contents": "Emerging evidence suggests that prolonged exposure to high oxygen levels, even when clinically indicated, can lead to cellular injury due to oxidative stress. Hyperoxia-induced lung injury,  neurological  effects, and disruptions in  systemic circulation  have been observed in certain cases, particularly in patients with preexisting conditions. These risks highlight the importance of constant vigilance in managing oxygen levels, especially in  critical care ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1478", "contents": "Antioxidant therapy may be employed to mitigate the harmful effects of ROS generated during hyperoxia. Additionally, careful monitoring and adjustment of mechanical ventilation settings are crucial in critical care settings to balance oxygen delivery and minimize the risk of oxygen toxicity. Recent studies emphasize the importance of individualized oxygen therapy, considering the patient\u2019s specific clinical condition and response to treatment. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1479", "contents": "Divers can be at risk from both central nervous system and pulmonary oxygen toxicity, and the risks have been well researched. Protocols have been developed which impose limits on oxygen partial pressure in the breathing gas which expose the diver to acceptable overall risks, bearing in mind that convulsions and loss of consciousness underwater on scuba equipment often lead to death by drowning. Diving with surface supplied gas using a  helmet  or  full-face mask  protects the  airway  much more than a  demand valve  held by the teeth, and in some circumstances, slightly higher partial pressures and a slightly higher risk of oxygen toxicity may be acceptable. There is a trade-off between risk from longer decompression obligations which keep the diver in the water longer, versus oxygen toxicity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1480", "contents": "In  surface orientated diving  the exposure time is usually insufficient to develop symptoms of pulmonary toxicity, and the intervals between dives are usually long enough for recovery, so oxygen partial pressure is commonly selected to maximise no-stop time or minimise decompression time as in-water decompression in cold water tends to be stressful to the diver. In  saturation diving , where the diver will be breathing the gas mixture under pressure for periods in the order of weeks to a month, the P O 2  must be kept low enough to avoid pulmonary toxicity, and allow downward excursions from storage pressure, while being high enough to allow for possible contingencies involving temporary reduction of pressure, during which it is highly desirable that the affected divers remain conscious and are able to perform necessary tasks to minimise the consequences, and to allow for upwards excursions without requiring a gas switch. A partial pressure of around 0.4 bar has been found to satisfy these conditions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1481", "contents": "Hyperbaric medicine is the medical use of oxygen at a higher pressure level than our atmosphere. [ 15 ]  Hyperbaric medicine is also known as hyperbaric oxygen therapy. The air we normally breathe is composed of 21 percent oxygen. Hyperbaric treatments utilise 100 percent oxygenated air to treat many conditions.  [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1482", "contents": "Supplemental oxygen is one of the most commonly used treatments for critical illness and is routinely used in treatment in acute shock and other emergency medicine, but the optimum dosage is seldom obvious, and during mechanical ventilation,  anesthesia , and  resuscitation  supply usually exceeds physiological requirements, to avoid a deficit. The resulting excess to requirements can be detrimental, but usually less so than an overall hypoxic state. Careful titration of the oxygen supply while monitoring oxygenation can allow sufficient tissue oxygenation without hyperoxic harm. [ 2 ]  While adhering to regulations and recommended levels, oxygen levels can be individualised and tailored to the patient's conditions to reduce the risk of hyperoxia. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1483", "contents": "At  atmospheric pressure , there is no risk of acute  oxygen toxicity , but the possibility of  pulmonary toxicity  exists, and hyperoxia can exacerbate some of the conditions for which supplementary oxygen provision is otherwise beneficial.  Long-term oxygen therapy  (LTOT) is the treatment proven to improve survival in chronic  obstructive pulmonary disease  (COPD) patients with  chronic respiratory failure . It also appears to reduce the number of hospitalizations, increase effort capacity, and improve health-related quality of life. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1484", "contents": "Epidemiologically, hyperoxia primarily centers on its prevalence in clinical settings where patients receive supplemental oxygen, such as intensive care units, neonatal wards, and while receiving anesthesia. It is frequently observed in populations with conditions like COPD, ARDS, and cardiac arrest, where oxygen therapy is routine. Though it is essential for treatment, prolonged exposure to high oxygen levels can lead to harmful oxidative stress, which could potentially lead to complications such as lung damage,  retinopathy  in neonates, and poor, or worsened neurological outcomes. The occurrence of hyperoxia varies across healthcare systems depending on the rigor of oxygen monitoring and management practices."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1485", "contents": "Infant respiratory distress syndrome  ( IRDS ), also known as  surfactant deficiency disorder  ( SDD ), [ 2 ]  and previously called  hyaline membrane disease  ( HMD ), is a  syndrome  in  premature infants  caused by developmental insufficiency of  pulmonary surfactant  production and structural immaturity in the  lungs . It can also be a consequence of  neonatal infection  and can result from a genetic problem with the production of surfactant-associated proteins. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1486", "contents": "IRDS affects about 1% of newborns and is the leading cause of morbidity and mortality in  preterm  infants. [ 5 ]  Data have shown the choice of elective  caesarean sections  to strikingly increase the incidence of respiratory distress in term infants; dating back to 1995, the UK first documented 2,000 annual caesarean section births requiring neonatal admission for respiratory distress. [ 6 ]  The incidence decreases with advancing  gestational age , from about 50% in babies born at 26\u201328 weeks to about 25% at 30\u201331 weeks. The syndrome is more frequent in males, Caucasians, infants of diabetic mothers and the second-born of premature twins. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1487", "contents": "IRDS is distinct from  pulmonary hypoplasia , another leading cause of neonatal death that involves respiratory distress. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1488", "contents": "The  European Consensus Guidelines on the Management of Respiratory Distress Syndrome  highlight new possibilities for early detection, and therefore treatment of IRDS. [ 8 ]  The guidelines mention an easy to use rapid point-of-care predictive test that is now available [ 9 ]  and how lung ultrasound, with appropriate training, expertise and equipment, may offer an alternative way of diagnosing IRDS early. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1489", "contents": "IRDS begins shortly after birth and is manifested by  fast breathing  (more than 60 breaths per minute), a  fast heart rate , chest wall retractions (recession), expiratory grunting, nasal flaring, and  blue discoloration of the skin  during breathing efforts. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1490", "contents": "As the disease progresses, the baby may develop ventilatory failure (rising carbon dioxide concentrations in the blood) and prolonged cessations of breathing (\" apnea \"). Whether treated or not, the clinical course for the acute disease lasts about two to three days. During the first day, the child worsens and requires more support. During the second day, the baby may be remarkably stable on adequate support and resolution is noted during the third day, heralded by a prompt  diuresis . Despite huge advances in care, IRDS remains the most common single cause of death in the first month of life in the developed world. Complications include metabolic disorders (acidosis,  low blood sugar ),  patent ductus arteriosus ,  low blood pressure , chronic lung changes and  bleeding in the brain . The syndrome is frequently complicated by prematurity and its additional effect on other organ functions. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1491", "contents": "The characteristic  histopathology  seen in babies who die from RDS was the source of the name \"hyaline membrane disease\". Waxlike layers of  hyaline  membrane line the collapsed  alveoli  of the lung. In addition, the lungs show bleeding, overdistention of airways, and damage to the lining cells. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1492", "contents": "The lungs of infants with respiratory distress syndrome are developmentally deficient in a material called  surfactant , which helps prevent the collapse of the terminal air spaces (the future site of  alveolar  development) throughout the normal cycle of inhalation and exhalation. This deficiency of surfactant is related to inhibition from the insulin that is produced in the newborn, especially those of diabetic mothers. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1493", "contents": "Pulmonary surfactant is a complex system of  lipids ,  proteins  and  glycoproteins  that is produced in specialized lung cells called Type II cells or  Type II pneumocytes . The surfactant is packaged by the cell in structures called  lamellar bodies , and extruded into the air spaces. The lamellar bodies then unfold into a complex lining of the air space. This layer reduces the  surface tension  of the fluid that lines the alveolar air space. Surface tension is responsible for approximately 2/3 of the  inward elastic recoil  forces. In the same way that a bubble will contract to give the smallest surface area for a given volume, so the air/water interface means that the liquid surface will tend toward being as small as possible, thereby causing the air space to contract. By reducing surface tension, surfactant prevents the air spaces from completely collapsing on exhalation. In addition, the decreased surface tension allows reopening of the air space with a lower amount of force. Therefore, without adequate amounts of surfactant, the air spaces collapse and are very difficult to expand. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1494", "contents": "Microscopically, a pulmonary surfactant-deficient lung is characterized by collapsed air spaces alternating with hyperexpanded areas, vascular congestion, and, in time,  hyaline  membranes. Hyaline membranes are composed of  fibrin , cellular debris,  red blood cells , rare  neutrophils  and  macrophages . They appear as an eosinophilic, amorphous material, lining or filling the air spaces and blocking gas exchange. As a result, blood passing through the lungs is unable to pick up oxygen and unload carbon dioxide. Blood oxygen levels fall and carbon dioxide rises, resulting in rising blood acid levels and  hypoxia . Structural immaturity, as manifested by a decreased number of gas exchange units and thicker walls, also contributes to the disease process. Therapeutic oxygen and positive-pressure ventilation, while potentially life-saving, can damage the lung. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1495", "contents": "The diagnosis is made by the clinical picture and the chest  X-ray , which demonstrates decreased  lung volumes  (bell-shaped chest), absence of the thymus (after about six hours), a small (0.5\u20131\u00a0mm), discrete, uniform infiltrate (sometimes described as a \"ground glass\" appearance or \"diffuse airspace and interstitial opacities\") that involves all lobes of the lung and air-bronchograms (i.e. the infiltrate will outline the larger airways passages, which remain air-filled). In severe cases, this becomes exaggerated until the cardiac borders become indiscernible (a 'white-out' appearance). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1496", "contents": "To improve clinical outcomes very early treatment with surfactant is necessary. [ 13 ]  However, only about half of infants with a gestational age (GA) below 30 weeks need surfactant treatment [ 14 ] [ 15 ]  and prophylactic surfactant treatment increases the combined mortality and incidence of  Bronchopulmonary Dysplasia  (BPD) contrary to selective rescue surfactant treatment. [ 16 ]  Therefore, there is a need for a rapid diagnostic test to guide early targeted surfactant treatment. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1497", "contents": "Professor Henrik Verder  has worked with lung-maturity diagnostics on gastric aspirates obtained at birth for over 15 years. With the introduction of surfactant treatment for IRDS,  Henrik Verder  developed additional lung maturity tests based on gastric aspirates (GAS); for example, the microbubble stability test [ 18 ]  and  lamellar body  counts (LBC) [ 19 ]  as well as a large randomised trial using lamellar body counts to guide surfactant treatment. [ 20 ]  However, a common problem with all these methods is dilution with foetal urine. Additionally, the methods are time\u2010consuming laboratory tests and are too slow to be used as a point\u2010of\u2010care test (POC) to guide surfactant treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1498", "contents": "Professor Henrik Verder , in collaboration with  chemometric  scientist  Agnar Hoskuldsson , developed a rapid point-of-care method for predicting IRDS by measuring the lecithin-sphingomyelin ratio (L/S) in gastric aspirate (GA). [ 9 ]  The new method, which is based on mid\u2010red Fourier Transform  Infrared spectroscopy  (FTIR), [ 21 ]   was shown to measure the L/S ratio at birth with a high sensitivity. [ 9 ]  This rapid bedside test for surfactant components in gastric aspirate is also now available, and clinical trials of this new point-of-care test to determine surfactant need at birth are underway. [ 22 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1499", "contents": "Lung ultrasound, with appropriate expertise, equipment, and training, may offer an alternative way to diagnose the severity of IRDS. [ 10 ]  A semi-quantitative lung ultrasound score performed during bedside lung echography was first described by Brat et al. and found to correlate with the oxygenation status of infants with RDS. [ 23 ]  Since then, several studies have supported the use of lung ultrasound scores to earlier predict an initial dose of surfactant when compared to current oxygenation-guided recommendations. [ 24 ] [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1500", "contents": "Oxygen is given with a small amount of  continuous positive airway pressure  (CPAP), and intravenous fluids are administered to stabilize the blood sugar, blood salts and blood pressure. CPAP application to preterm neonates with respiratory distress is associated with a reduction in respiratory failure, mechanical ventilation and mortality. [ 27 ]  However, CPAP is associated with an increased rate of pneumothorax compared to spontaneous breathing with or without supplemental oxygen. [ 27 ]  If the baby's condition worsens, an  endotracheal tube  (breathing tube) is inserted into the trachea and intermittent breaths are given by a mechanical device. An exogenous preparation of  pulmonary surfactant , either synthetic or extracted from animal lungs, is given through the breathing tube into the lungs.  Surfactant medications  can decrease the risk of death for very low- birth-weight  infants who are hospitalized by 30%. [ 28 ]  Such small premature infants may remain ventilated for months. A study shows that an aerosol of a  perfluorocarbon  such as  perfluoromethyldecalin  can reduce inflammation in swine model of IRDS. [ 29 ]  Chronic lung disease, including  bronchopulmonary dysplasia , is common in severe RDS. The etiology of BPD is problematic and may be the result of oxygen, overventilation or underventilation. The mortality rate for babies greater than 27 weeks of gestation is less than 20%. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1501", "contents": "Henrik Verder  is the inventor and pioneer of the INSURE (Intubation Surfactant Extubation) and LISA (Less Invasive Surfactant Administration) methods combined with nasal CPAP ( Continuous Positive Airway Pressure ), very effective approaches to managing preterm neonates with respiratory distress. In 1989 he used this pioneering method to successfully treat the first premature infant with severe RDS. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1502", "contents": "The INSURE method has been shown, through meta-analysis, to successfully decrease the use of  mechanical ventilation  and lower the incidence of  bronchopulmonary dysplasia  (BPD). [ 31 ]  Since its conception in 1989, the INSURE method has been academically cited in more than 500 papers. [ 32 ]  The first randomised study involving the INSURE method was published in 1994 [ 33 ]  and a second randomised study in infants less than 30 weeks gestation was published by the group in 1999. [ 34 ]  Based on the INSURE method,  Henrik Verder  has since developed a rapid bedside test that predicts IRDS at birth. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1503", "contents": "Extracorporeal membrane oxygenation  (ECMO) is a potential treatment, providing oxygenation through an apparatus that imitates the  gas exchange  process of the lungs. However, newborns cannot be placed on ECMO if they are under 4.5 pounds (2\u00a0kg), because they have extremely small vessels for  cannulation , thus hindering adequate flow because of limitations from cannula size and subsequent higher resistance to blood flow (compare with  vascular resistance ). Furthermore, in infants aged less than 34  weeks of gestation , several physiologic systems are not well-developed, especially the  cerebral vasculature  and  germinal matrix , resulting in high sensitivity to slight changes in  pH ,  PaO 2  and intracranial pressure. Subsequently, preterm infants are at unacceptably high risk for  intraventricular hemorrhage  (IVH) if administered ECMO at a gestational age of less than 32 weeks. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1504", "contents": "Giving the baby's mother  glucocorticoids  speeds the production of surfactant. For very premature deliveries, a glucocorticoid is given without testing the fetal lung maturity. The  American College of Obstetricians and Gynecologists  (ACOG), Royal College of Medicine and other major organizations have recommended antenatal glucocorticoid treatment for women at risk for preterm delivery prior to 34  weeks of gestation . [ 36 ]  Multiple courses of glucocorticoid administration, compared with a single course, do not seem to increase or decrease the risk of death or  neurodevelopmental disorders  of the child. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1505", "contents": "In pregnancies of longer than 30 weeks, the fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid by  amniocentesis , wherein a needle is inserted through the mother's abdomen and uterus. Several tests are available that correlate with the production of surfactant. These include the  lecithin-sphingomyelin ratio  (\" L/S ratio \"), the presence of  phosphatidylglycerol  (PG), and, more recently, the  surfactant/albumin (S/A) ratio . For the  L/S ratio , if the result is less than 2:1, the fetal lungs may be deficient in surfactant. The presence of PG usually indicates fetal lung maturity. For the S/A ratio, the result is given as milligrams of surfactant per gram of protein. A S/A ratio less than 35 indicates immature lungs, between 35 and 55 is indeterminate, and greater than 55 indicates mature surfactant production (correlating with an L/S ratio of 2.2 or greater). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1506", "contents": "Infant respiratory distress syndrome (IRDS) is the leading cause of death in premature infants. [ 38 ] \u00a0Despite only 1% of all birth complications being attributed to respiratory distress syndrome, there is a significantly higher prevalence in prematurely born babies. [ 39 ]  Incidence rates of IRDS in premature infants born at 30 weeks of gestational age (GA) are at 50%, and rise even higher to 93% for infants born prematurely at 28 weeks of gestational age or younger. [ 39 ]  IRDS is diagnosed within hours of delivery and usually leads to morbidity and mortality in preterm infants. There are many risk factors that can potentially cause IRDS. The most common risks factors that can potentially cause IRDS include male gender, white race, late preterm delivery, maternal diabetes, perinatal hypoxia (exposure to low oxygen) and ischemia (decreased blood flow), and low birth weight. [ 40 ]  Seventy percent of babies diagnosed with respiratory distress syndrome are born between 29 and 34 weeks of gestational age and are 55% more likely to be male. [ 39 ]  A study conducted at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network studied premature infants born between 22 and 37 weeks and the outcomes leading to IRDS. This study was conducted from 2002 to 2008. The incidence rate of IRDS for 24 weeks was 98%, for 34 weeks the incidence is 5%, and for 37 weeks the incidence rate was less than 1%. The results demonstrate that the incidence of IRDS increases with decreasing age at birth. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1507", "contents": "According to a study from the University of Miami's Department of Pediatrics and Division of Neonatology, from the time range of 2003 to 2014, respiratory distress syndrome prevalence jumped from 170 per 1000 preterm live births to 360 per 1000 preterm live births nationwide in the United States. [ 42 ]  This study population's duration under hospital care averaged 32 days in 2003, increasing by nearly a week to 38 days in 2014. [ 42 ]  Additionally, this study yielded average prevalence rates of 260 cases per 1000 livebirths from the years of 2003 to 2014, [ 42 ]  which coincided with the results yielded by a report from the Vermont Oxford Network in 2008 of 300 per 1000 livebirths. [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1508", "contents": "Infectious  coryza  is a serious  bacterial disease  of  chickens  that affects the  respiratory system , and it is manifested by  inflammation  of the area below the  eye ,  nasal discharge , and  sneezing . [ 1 ] [ 2 ]   The disease is found all over the world, causing high economic losses, which are due to stumping off and reduction of  egg production  in case of laying chickens. The disease was discovered early 1930s by considering  clinical signs . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1509", "contents": "Clinical appearance of the disease includes depression, a serous nasal discharge, and sporadically minor facial inflammation in the mild form of the disease. In severe form,  severe inflammation of one or both infraorbital sinuses with  edema  of the surrounding tissue occurs. The swelling can cause closure of one or both eyes. Intermandibular space and  wattles  of cocks do swell in the course of the disease. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1510", "contents": "The disease is caused by the bacterium  Avibacterium  paragallinarum , which is  Gram-negative . The bacterium is  microaerophilic , rod-shaped, and non motile . Its growth requires the presence of  nicotinamide adenine dinucleotide . The three  serovars   of  A. paragallinarum  are A, B, and C, related by immunotype specificity. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1511", "contents": "The  reservoirs  of the disease are carrier chickens that could be healthy, but harboring the disease, or chronically sick. The disease affects all ages of chickens. The disease can persist in the flock for 2-3 weeks and signs of the disease are seen 1\u20133 days after infection. Transmission of the disease is through direct interaction, airborne droplets, and drinking  contaminated water . Chickens having infection and those carriers contribute highly to the disease transmission. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1512", "contents": "Diagnosis is by isolation of bacteria from chickens suspected to have a history of coryza and clinical findings from infected chickens. [ 1 ] [ 4 ]   Polymerase chain reaction  testing is a reliable means of diagnosis of the disease. [ 5 ] [ 6 ] [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1513", "contents": "Prevention is through use of stock coryza-free  birds . In other cases,  culling  of the whole flock is a good means of disease control.  Bacterin  also is used to reduce the severity of the disease. Precise exposure has also has been used, but it should be done with care. [ citation needed ]   Vaccination  of chicks is done in areas with high disease occurrence.  Treatment consists of using  antibiotics  such as  erythromycin ,  dihydrostreptomycin ,  streptomycin ,  sulfonamides ,  tylosin , and  fluoroquinolones . [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1514", "contents": "Intrauterine hypoxia  (also known as  fetal hypoxia ) occurs when the fetus is  deprived  of an adequate supply of  oxygen .  It may be due to a variety of reasons such as  prolapse  or  occlusion  of the  umbilical cord ,  placental infarction , maternal diabetes (prepregnancy or  gestational diabetes ) [ 1 ]  and  maternal smoking .  Intrauterine growth restriction  may cause or be the result of hypoxia.  Intrauterine hypoxia can cause cellular damage that occurs within the  central nervous system  (the brain and spinal cord). This results in an increased mortality rate, including an increased risk of  sudden infant death syndrome  (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as  epilepsy ,  attention deficit hyperactivity disorder ,  eating disorders  and  cerebral palsy . [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1515", "contents": "Complications arising from intrauterine hypoxia are some of most common causes of preeclampsia. [ 8 ]  Preeclampsia is a hypertensive disorder that occurs during the second trimester (after the 20th week of pregnancy) resulting from a poorly perfused placenta. [ 9 ]  The World Health Organization estimates that preeclampsia and eclampsia are responsible for about 14% of maternal deaths globally (around 50,000 to 75,000 deaths annually). [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1516", "contents": "During pregnancy, women with preeclampsia faces serious risk of damage to vital organs such as the kidneys, liver, brain, and the blood system. This hypertensive disorder may also cause damage to the placenta leading to issues such as  premature births , miscarriages, placental abruption, or even stillbirths. In some cases, preeclampsia can eventually lead to stroke and organ failure.\u00a0 Untreated, preeclampsia can progress and turn into eclampsia which is much more severe with the addition of seizures. Eclampsia seizures could lead to uncontrollable twitching and a loss of consciousness, which could potentially lead to the death of the mother and or the baby. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1517", "contents": "Intrauterine hypoxia can be attributed to maternal, placental, or fetal conditions. [ 12 ]  Kingdom and Kaufmann classifies three categories for the origin of fetal hypoxia: 1) pre-placental (both mother and fetus are hypoxic), 2) utero-placental (mother is normal but placenta and fetus is hypoxic), 3) post-placental (only fetus is hypoxic). [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1518", "contents": "Pre-placental hypoxia is most commonly caused by external hypoxic environments (such as high altitude). It can also be caused by maternal respiratory conditions (such as asthma), cardiovascular conditions (such as  heart failure ,  pulmonary hypertension , and  cyanotic heart disease ), and hematological conditions (such as  anemia ). [ 14 ]  Conditions such as obesity, nutritional deficiencies, infections, chronic inflammations, and stress can also affect the maternal oxygen supply and fetal uptake. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1519", "contents": "The most preventable cause is maternal smoking.  Cigarette smoking  by expectant mothers has been shown to have a wide variety of deleterious effects on the developing fetus. [ 15 ]  Among the negative effects are  carbon monoxide  induced tissue hypoxia and  placental insufficiency  which causes a reduction in blood flow from the  uterus  to the  placenta  thereby reducing the availability of oxygenated blood to the fetus. Placental insufficiency as a result of smoking has been shown to have a  causal  effect in the development of  pre-eclampsia . While some previous studies have suggested that carbon monoxide from cigarette smoke may have a protective effect against preeclampsia, a recent study conducted by the Genetics of Pre-Eclampsia Consortium in the United Kingdom found that smokers were five times more likely to develop pre-eclampsia. [ 16 ] \n Nicotine  alone has been shown to be a  teratogen  which affects the  autonomic nervous system , leading to increased susceptibility to hypoxia-induced brain damage. [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ 21 ] \nMaternal anemia in which smoking has also been implicated is another factor associated with IH/BA. [ clarification needed ]  Smoking by expectant mothers causes a decrease in maternal nucleated red blood cells, thereby reducing the amount of red blood cells available for oxygen  transport . [ 22 ] [ 23 ] [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1520", "contents": "Utero-placental hypoxia is associated with abnormal placental implantation, impaired vascular remodeling and vascular diseases. [ 14 ]  It is also associated with pregnancies complicated by  gestational hypertension ,  intrauterine growth restriction , and  pre-eclampsia . [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1521", "contents": "Post-placental hypoxia is associated with mechanical obstructions of the umbilical cords, reduced uterine artery flow, progressive fetal cardiac failure, and genetic anomalies. [ 12 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1522", "contents": "The perinatal brain injury occurring as a result of birth asphyxia, manifesting within 48 hours of birth, is a form of  hypoxic ischemic encephalopathy . [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1523", "contents": "Treatment of infants with birth asphyxia by lowering the core body temperature is now known to be an effective therapy to reduce mortality and improve neurological outcome in survivors, and  hypothermia therapy for neonatal encephalopathy  begun within 6 hours of birth significantly increases the chance of normal survival in affected infants. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1524", "contents": "There has long been a debate over whether newborn infants with birth asphyxia should be resuscitated with 100% oxygen or normal air. [ 29 ]  It has been demonstrated that high concentrations of oxygen lead to generation of oxygen  free radicals , which have a role in  reperfusion injury  after asphyxia. [ 30 ]  Research by  Ola Didrik Saugstad  and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen. [ 31 ] [ 32 ]  Increasing the oxygen concentration to the mother has shown little effect on the fetus as hyperoxygenated blood does not perfuse the placental exchange site well. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1525", "contents": "Underlying etiology of intrauterine hypoxia serves as a potential therapeutic target. If maternal preeclampsia [ 34 ]  is the underlying cause of fetal growth restriction (FGR) antihypertensive therapy and magnesium sulfate are potential therapies. [ 12 ]  Antihypertensive treatment is used to reduce blood pressure and prevent pulmonary edema and cerebral hemorrhages. An effective course of antihypertensive treatments should reduce blood pressure to below 160/110 mmHg. Magnesium sulfate acts as a vasodilator, reducing vascular resistance and protect the blood-brain barrier (BBB). The goal of these treatments is to prolong pregnancy and increase fetal survival. Each day gained by treatment in utero increases fetal survival and intact survival by 1%\u20132% up to 28 weeks gestation. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1526", "contents": "Medical testing and care can be performed in order to prevent intrauterine hypoxia, though can be difficult. These tests don't directly detect hypoxia, but instead detects the general well-being of the baby and ensures that the baby is healthy since hypoxia causes a wide range of responses. These tests can include prenatal testing, such as fetal movement and amniotic fluid levels,  Doppler examination , or fetal heart rate. [ 36 ]  Another risk factor is premature birth in which medical intervention, such as premature birth prevention or C-section delivery, can be used as prevention for intrauterine hypoxia. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1527", "contents": "Studies have shown a connection between  tetrahydrobiopterin (BH 4 ) deficiency  and hypoxia-ischemia brain injury, though further studies need to be done. [ 38 ]  Measuring fetal BH 4  levels can be another way to look out for intrauterine hypoxia. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1528", "contents": "During birth, birth asphyxia can occur in which  cardiotocograph  can be used to monitor the baby's health during labor. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1529", "contents": "In the United States, intrauterine hypoxia and birth asphyxia were listed together as the tenth leading cause of neonatal death. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1530", "contents": "IH/BA is also a causative factor in cardiac and circulatory birth defects the sixth most expensive condition, as well as premature birth and low birth weight the second most expensive and it is one of the contributing factors to infant respiratory distress syndrome (RDS) also known as hyaline membrane disease, the most expensive medical condition to treat and the number one cause of infant mortality. [ 41 ] [ 42 ] [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1531", "contents": "In the United States the National Practitioner Data Bank 2006 Annual Report obstetrics-related cases accounted for 8.7 percent of all 2006 physician Malpractice Payment Reports and had the highest median payment amounts ($333,334). [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1532", "contents": "Kennel cough  (also \"canine infectious respiratory disease\" (CIRD), \"canine infectious respiratory disease complex\" (CIRDC) or \"canine infectious  tracheobronchitis \" (CIT)) is an  upper respiratory infection  affecting  dogs . [ 1 ]  There are multiple causative agents, the most common being the bacterium  Bordetella bronchiseptica  (found in 78.7% of cases in Southern Germany), followed by  canine parainfluenza virus  (CPIV; 37.7% of cases), and to a lesser extent  canine coronavirus  (9.8% of cases). [ 2 ]  It is highly contagious; [ 3 ]  however, adult dogs may display immunity to reinfection even under constant exposure. [ 4 ]  Kennel cough is so named because the infection can spread quickly among dogs in the close quarters of a  kennel  or  animal shelter ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1533", "contents": "Viral and bacterial causes of canine cough are  spread through airborne droplets  produced by sneezing and coughing. These agents also spread through contact with contaminated surfaces.  Symptoms begin after a several-day incubation period post-exposure, [ 3 ]  and in most cases will clear up on their own. However, in young puppies or immunocompromised animals, mixed or secondary infections can progress to lower respiratory infections such as  pneumonia . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1534", "contents": "The  incubation period  is 5\u20137 days (with a range of 3\u201310). [ 5 ]  Symptoms can include a harsh, dry cough, retching, sneezing, snorting, gagging or vomiting in response to light pressing of the  trachea  or after excitement or exercise. The presence of a  fever  varies from case to case. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1535", "contents": "Although kennel cough is considered to be a multifactorial infection, there are two main forms. The first is more mild and is caused by  B. bronchiseptica  and canine parainfluenza infections, without complications from  canine distemper  virus (CDV) or  canine mastadenovirus A  (formerly canine adenovirus-1). This form occurs most regularly in autumn, and can be distinguished by symptoms such as a retching cough and vomiting. The second form has a more complex combination of causative organisms, including CDV and CAV. It typically occurs in dogs that have not been vaccinated and it is not seasonal. Symptoms are more severe than the first form, and may include  rhinitis ,  conjunctivitis , and fever, in addition to a hacking cough. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1536", "contents": "Viral infections such as canine  parainfluenza  or  Canine respiratory coronavirus  are only spread for roughly one week following recovery; [ 5 ]  however, respiratory infections involving  B. bronchiseptica  can be transmissible for several weeks longer. [ 4 ]  While there was early evidence to suggest that  B. bronchiseptica  could be shed for many months post-infection, [ 4 ]  a more recent report places detectable nasal and  pharyngeal  levels of  B. bronchiseptica  in 45.6% of all clinically healthy dogs. [ 2 ]  This has potentially expanded the vector from currently or recently infected dogs to half the dog population as carriers.  To put the relative levels of shedding bacteria into perspective, a study analyzing the shedding kinetics of  B. bronchiseptica  presents the highest levels of bacterial shedding one week post-exposure, with an order of magnitude decrease in shedding observed every week. [ 7 ]   This projection places negligible levels of shedding to be expected six weeks post-exposure (or approximately five weeks post-onset of symptoms). Dogs which had been administered intranasal vaccine four weeks prior to virulent  B. bronchiseptica  challenge displayed little to no bacterial shedding within three weeks of exposure to the virulent strain. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1537", "contents": "Antibiotics  are given to treat any  bacterial  infection present.  Cough suppressants  are used if the cough is not productive.  NSAIDs  are often given to reduce fever and upper respiratory inflammation. Prevention is by  vaccinating  for canine  adenovirus ,  distemper , parainfluenza, and  Bordetella .  In kennels, the best prevention is to keep all the cages disinfected. In some cases, such as \"doggie daycares\" or nontraditional playcare-type boarding environments, it is usually not a cleaning or disinfecting issue, but rather an airborne issue, as the dogs are in contact with each other's saliva and breath. Although most kennels require proof of vaccination, the vaccination is not a fail-safe preventative. Just like human  influenza , even after receiving the vaccination, a dog can still contract mutated strains or less severe cases. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1538", "contents": "To increase their effectiveness, vaccines should be administered as soon as possible after a dog enters a high-risk area, such as a shelter. 10 to 14 days are required for partial immunity to develop. [ 8 ]  Administration of  B. bronchiseptica  and canine parainfluenza vaccines may then be continued routinely, especially during outbreaks of kennel cough. There are several methods of administration, including  parenteral  and  intranasal . [ 9 ]  However, the intranasal method has been recommended when exposure is imminent, due to a more rapid and localized protection. Several intranasal vaccines have been developed that contain canine  adenovirus  in addition to  B. bronchiseptica  and canine parainfluenza virus antigens. Studies have thus far not been able to determine which formula of vaccination is the most efficient. Adverse effects of vaccinations are mild, but the most common effect observed up to 30 days after administration is nasal discharge. [ 8 ]  Vaccinations are not always effective. In one study it was found that 43.3% of all dogs in the study population with respiratory disease had in fact been vaccinated. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1539", "contents": "Dogs will typically recover from kennel cough within a few weeks. However, secondary infections could lead to complications that could do more harm than the disease itself. [ 2 ]  Several opportunistic invaders have been recovered from the respiratory tracts of dogs with kennel cough, including  Streptococcus ,  Pasteurella ,  Pseudomonas , and various  coliform  bacteria. These bacteria have the potential to cause  pneumonia  or  sepsis , which drastically increase the severity of the disease. These complications are evident in  thoracic   radiographic  examinations. Findings will be mild in animals affected only by kennel cough, while those with complications may have evidence of segmental  atelectasis  (collapsed lung) and other severe side effects. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1540", "contents": "Laryngotracheal stenosis  refers to abnormal narrowing of the central air passageways. [ 1 ]   This can occur at the level of the   larynx ,  trachea ,  carina  or  main bronchi . [ 2 ] \nIn a small number of patients narrowing may be present in more than one anatomical location."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1541", "contents": "The most common symptom of laryngotracheal stenosis is gradually-worsening breathlessness ( dyspnea ) particularly when undertaking physical activities (exertional dyspnea).  The patient may also experience added respiratory sounds which in the more severe cases can be identified as  stridor  but in many cases can be readily mistaken for  wheeze .   This creates a diagnostic pitfall in which many patients with laryngotracheal stenosis are incorrectly diagnosed as having  asthma  and are treated for presumed lower airway disease. [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]   This increases the likelihood of the patient eventually requiring major open surgery for benign disease [ 9 ]  and can lead to tracheal cancer presenting too late for curative surgery to be performed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1542", "contents": "Laryngotracheal stenosis is an umbrella term for a wide and heterogeneous group of very rare conditions.  The population incidence of adult post-intubation laryngotracheal stenosis which is the commonest benign sub-type of this condition is approximately 1 in 200,000 adults per year. [ 10 ]  The main causes of adult laryngotracheal stenosis are:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1543", "contents": "Patient history, CT scan of neck and chest, fiberoptic bronchoscopy, and spirometry are all several ways to assess for laryngotracheal stenosis and effectively develop preoperational approaches to treating the disease. In addition, a methodology called the Cotton-Myer system is commonly used to evaluate the degree of severity of the laryngotracheal stenosis based on the percentage of obstruction; other systems have also been proposed to fill potential shortcomings of the Cotton-Myer classification and help capture the full complexity of the illness. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1544", "contents": "The optimal management of laryngotracheal stenosis is not well defined, depending  mainly on the type of the stenosis. [ 24 ] \nGeneral treatment options include"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1545", "contents": "Tracheal  dilation  is used to temporarily enlarge the airway. The effect of dilation typically lasts from a few days to 6 months. Several studies have shown that as a result of mechanical dilation (used alone) may occur a high mortality rate and a rate of recurrence of stenosis higher than 90%. [ 24 ] \nThus, many authors treat the stenosis by endoscopic excision with laser (commonly either the carbon dioxide or the neodymium: yttrium aluminum garnet laser) and then by using bronchoscopic dilatation and prolonged stenting with a T-tube (generally in silicone). [ 27 ] [ 28 ] [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1546", "contents": "There are differing opinions on treating with  laser surgery ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1547", "contents": "In very experienced surgery centers, tracheal resection and reconstruction (anastomosis complete end-to-end with or without laryngotracheal temporary stent to prevent airway collapse) is currently the best alternative to completely cure the stenosis and allows to obtain good results. Therefore, it can be considered the gold standard treatment and is suitable for almost all patients. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1548", "contents": "The narrowed part of the trachea will be cut off and the cut ends of the trachea sewn together with sutures. For stenosis of length greater than 5\u00a0cm a  stent  may be required to join the sections."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1549", "contents": "Late June or early July 2010, a new potential treatment was trialed at Great Ormond Street Hospital in London, where Ciaran Finn-Lynch (aged 11) received a transplanted trachea which had been injected with stem cells harvested from his own bone marrow.  The use of Ciaran's stem cells was hoped to prevent his immune system from rejecting the transplant, [ 31 ]  but there remain doubts about the operation's success, and  several later attempts at similar surgery have been unsuccessful ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1550", "contents": "Laryngotracheal stenosis ( Laryngo- : Glottic Stenosis; Subglottic Stenosis;  Tracheal : narrowings at different levels of the windpipe) is a more accurate description for this condition when compared, for example to  subglottic stenosis  which technically only refers to narrowing just below vocal folds or  tracheal stenosis .  In babies and young children however, the  subglottis  is the narrowest part of the airway and most stenoses do in fact occur at this level.  Subglottic stenosis  is often therefore used to describe central airway narrowing in children, and laryngotracheal stenosis is more often used in adults."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1551", "contents": "Lipid-laden alveolar macrophages , also known as  pulmonary foam cells , [ 2 ]  are cells found in  bronchoalveolar lavage  (BAL) specimens that consist of  macrophages  containing deposits of  lipids  (fats). [ 3 ]  The lipid content of the macrophages can be demonstrated using a lipid targeting stain like  Oil Red O  or  Nile red . [ 2 ] [ 4 ] [ 5 ] [ 6 ]  Increased levels of lipid-laden alveolar macrophages are associated with various respiratory conditions, including chronic smoking, [ 3 ]   gastroesophageal reflux ,  lipoid pneumonia ,  fat embolism , [ 7 ]   pulmonary alveolar proteinosis [ 3 ] [ 8 ]  and  pulmonary aspiration . [ 2 ] [ 9 ]  Lipid-laden alveolar macrophages have been reported in cases of  vaping-associated pulmonary injury . [ 10 ] [ 1 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1552", "contents": "The  lipid-laden macrophage index  (LLMI) can be calculated by counting 100 macrophages in a BAL specimen treated with a lipid stain and scoring each macrophage from 0 to 4 based on the amount of lipids present in the cell. [ 7 ] [ 12 ]  A LLMI score greater than 100 is considered positive for pulmonary aspiration. However, the test is limited by poor reproducibility [ 7 ]  and low  specificity  for pulmonary aspiration, as lipid-laden macrophages occur in many respiratory conditions. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1553", "contents": "This article related to  pathology  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1554", "contents": "Ludwig's angina  ( Latin :  Angina ludovici ) is a type of severe  cellulitis  involving the floor of the mouth [ 2 ]  and is often caused by bacterial sources. [ 1 ]  Early in the infection, the floor of the mouth raises due to swelling, leading to difficulty swallowing saliva. As a result, patients may present with drooling and difficulty speaking. [ 3 ]  As the condition worsens, the airway may be compromised and hardening of the spaces on both sides of the tongue may develop. [ 4 ]  Overall, this condition has a rapid onset over a few hours."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1555", "contents": "The majority of cases follow a  dental infection . [ 3 ]  Other causes include a  parapharyngeal abscess ,  mandibular fracture , cut or piercing inside the mouth, or  submandibular   salivary stones . [ 5 ]  The infection spreads through the connective tissue of the floor of the mouth and is normally caused by infectious and invasive organisms such as  Streptococcus ,  Staphylococcus , and  Bacteroides . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1556", "contents": "Prevention is by appropriate dental care including management of dental infections. Initial treatment is generally with  broad-spectrum antibiotics  and  corticosteroids . [ 1 ]  In more advanced cases  endotracheal intubation  or  tracheostomy  may be required. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1557", "contents": "With the advent of antibiotics in 1940s, improved oral and dental hygiene, and more aggressive surgical approaches for treatment, the risk of death due to Ludwig's angina has significantly reduced.  It is named after a German physician,  Wilhelm Frederick von Ludwig , who first described this condition in 1836. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1558", "contents": "Ludwig's angina is a form of severe, widespread  cellulitis  of the floor of the mouth, usually with bilateral involvement. Infection is usually primarily within the submandibular space, and the sublingual and submental spaces can also be involved. It presents with an acute onset and spreads very rapidly, therefore early diagnosis and immediate treatment planning is vital and lifesaving. [ 8 ]  The external signs may include bilateral lower facial  swelling  around the jaw and upper neck. Signs inside the mouth may include elevation of the floor of mouth due to sublingual space involvement and posterior displacement of the tongue, creating the potential for a compromised airway. [ 8 ]  Additional symptoms may include painful neck swelling, drooling, tooth pain,  dysphagia , shortness of breath, fever, and general malaise. [ 9 ]  Stridor,  trismus , and  cyanosis  may also be seen when an impending airway crisis is nearing. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1559", "contents": "The most prevalent cause of Ludwig's angina is dental related, [ 10 ]  accounting for approximately 75\u201390% of cases. [ 10 ] [ 11 ] [ 12 ] [ 13 ]  Infections of the lower second and third molars are usually implicated due to their roots extending below the mylohyoid muscle. [ 10 ] [ 14 ]  Periapical abscesses of these teeth also result in lingual cortical penetration, leading to submandibular infection. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1560", "contents": "Other causes such as oral ulcerations, infections secondary to oral malignancy, mandible fractures, sialolithiasis-related submandibular gland infections, [ 10 ]  and penetrating injuries of the mouth floor [ 15 ]  have also been documented as potential causes of Ludwig's angina. Patients with systemic illness, such as diabetes mellitus, malnutrition, compromised immune system, and organ transplantation are also commonly predisposed to Ludwig's angina. [ 13 ]  A review reporting the incidence of illnesses associated with Ludwig angina found that 18% of cases involved diabetes mellitus, 9% involved acquired immune deficiency syndrome, and another 5% were human immunodeficiency virus (HIV) positive. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1561", "contents": "Infections originating in the roots of teeth can be identified with a  dental X-ray . [ 17 ] [ 18 ]   A CT scan of the neck with contrast material is used to identify deep neck space infections. [ 19 ]  If there is suspicion of the  infection of the chest cavity , a  chest scan  is sometimes done. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1562", "contents": "Angioneurotic oedema, [ 20 ]   lingual carcinoma  and  sublingual hematoma  formation following anticoagulation should be ruled out as possible diagnoses. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1563", "contents": "There are a few methods that can be used for determining the microbiology of Ludwig's angina. Traditionally, a  culture sample  is collected although it has some limitations, primarily being the time-consuming and sometimes unreliable results if the culture is not processed correctly. [ 21 ]   Ludwig's angina is most often found to be polymicrobial and  anaerobic . [ 2 ] [ 22 ]  Some of the commonly found microbes are  Viridans streptococci ,  Staphylococci ,  Peptostreptococci ,  Prevotella ,  Porphyromonas  and  Fusobacterium . [ 2 ] [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1564", "contents": "For each patient, the treatment plan should be consider the patient's stage of infection, airway control, and comorbidities. Other things to consider include physician experience, available resources, and personnel are critical factors in formulation of a treatment plan. [ 23 ]  There are four principles that guide the treatment of Ludwig's angina: [ 24 ]  sufficient airway management, early and aggressive antibiotic therapy, incision and drainage for any who fail medical management or form localized abscesses, and adequate nutrition and hydration support."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1565", "contents": "Airway management has been found to be the most important factor in treating patients with Ludwig's angina, [ 25 ]  i.e. it is the \"primary therapeutic concern\". [ 26 ]  Airway compromise is known to be the leading cause of death from Ludwig's angina. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1566", "contents": "Adequate nutrition and hydration support is essential in any patient following surgery, particularly young children. [ 24 ]  In this case, pain and swelling in the neck region would usually cause difficulties in eating or swallowing, hence reducing patient's food and fluid intake. Patients must therefore be well-nourished and hydrated to promote wound healing and to fight off infection. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1567", "contents": "Extubation , which is the removal of endotracheal tube to liberate the patient from mechanical ventilation, should only be done when the patient's airway is proved to be patent, allowing adequate breathing. This is indicated by a decrease in swelling and patient's capability of breathing adequately around an uncuffed  endotracheal tube  with the lumen blocked. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1568", "contents": "During the hospital stay, patient's condition will be closely monitored by:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1569", "contents": "[ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1570", "contents": "The term \"angina\", is derived from the Latin word  angere , which means \"choke\"; and the Greek word  ankhone , which means \"strangle\". Placing it into context, Ludwig's angina refers to the feeling of strangling and choking, secondary to obstruction of the airway, which is the most serious potential complication of this condition. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1571", "contents": "Lung hernia  ( Sibson hernia ) is a protrusion of lung outside of thoracic wall. In 20% patients with lung hernia, the incidence is congenital. In 80% of the cases, the hernia is noted after chest trauma, thoracic surgery or certain pulmonary diseases. [ 1 ]  Congenital hernia occurs because of the weakness of the  suprapleural membrane  or neck muscles. In pulmonary diseases such as  asthma , frequent coughing can lead to high intra thoracic pressure, causing the lung to herniate out. Lung hernia may occur near the neck (cervical), between the ribs (intercostal), near the vertebrae (paravertebral) or near the sternum (parasternal). [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1572", "contents": "The patient presents with a protrusion near the neck or between the ribs. The mass becomes prominent when the patient is straining or coughing. In asymptomatic individuals, lung hernia is incidentally detected in a chest X-ray taken for another reason. [ 3 ]  On physical examination, a prominence or mass is seen during  Valsalva maneuver . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1573", "contents": "Asymptomatic lung hernias may be managed by close observation. In symptomatic cases, immediate reduction and closure of the defect is indicated to prevent incarceration and strangulation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1574", "contents": "Although lung hernias are rare and usually benign in nature, it is important for physicians to be aware that these entities do exist so that they are not alarmed when they are encountered. Knowledge of the benign nature of lung hernias will prevent the use of unnecessary invasive procedures and surgery."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1575", "contents": "Mediastinal fibrosis  is characterized by invasive, calcified fibrosis centered on  lymph nodes  that block major vessels and airways. In Europe, this disease is exceptionally rare. More cases are seen in USA where the disease may often be associated with  histoplasmosis . [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1576", "contents": "Mediastinitis  is  inflammation  of the tissues in the mid-chest, or  mediastinum .  It can be either  acute  or  chronic . It is thought to be due to four different etiologies: [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1577", "contents": "Acute mediastinitis is usually caused by bacteria and is most often due to perforation of the esophagus. As the infection can progress rapidly, this is considered a serious condition."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1578", "contents": "Chronic  sclerosing  (or  fibrosing ) mediastinitis, while potentially serious, is caused by a long-standing inflammation of the mediastinum, leading to growth of acellular collagen and fibrous tissue within the chest and around the central vessels and airways.  It has a different cause, treatment, and prognosis than acute infectious mediastinitis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1579", "contents": "Space infections: Pretracheal space \u2013 lies anterior to trachea. Pretracheal space infection leads to mediastinitis. Here, the fascia fuses with the pericardium and the parietal pleura, which explains the occurrence of  empyema  and  pericardial effusion  in mediastinitis. However, infectious of other spaces can also lead to mediastinitis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1580", "contents": "Acute mediastinitis is an  infectious  process and can cause fever, chills,  tachycardia . Pain can occur with mediastinitis but the location of the pain depends on which part of the mediastinum is involved. When the upper mediastinum is involved, the pain is typically  retro-sternal  pain. When the lower mediastinum is involved, pain can be located between in the  scapulae  and radiate around to the chest. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1581", "contents": "Symptoms depend on what organs of the mediastinum the disease is affecting. They might be caused by a constricted airway, constricted esophagus, or constricted blood vessels. Symptoms also depend on how much fibrosis has occurred. There may be cough, shortness of breath, coughing up blood, pain in the chest, and  difficulty in swallowing . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1582", "contents": "Esophageal perforation, a form of direct contamination, accounts for 90% of acute mediastinal infections. [ 1 ]   Esophageal perforation can arise from vomiting, incidental trauma from a procedure or operation, external trauma, ingestion of corrosive substances, malignancy, or other esophageal disease. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1583", "contents": "Other causes of acute mediastinitis include infection secondary to cervical disease which arises from dental procedures, skin infections of the neck, neck trauma, or neck procedures. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1584", "contents": "Descending necrotizing mediastinitis (DNM) was first described by Herman E. Pearse Jr., M.D. in 1938 and he stated, \"the term 'mediastinitis' means little unless qualified by a description of its type and kind.\" [ 4 ]  Although Descending Necrotizing Mediastinitis is an acute mediastinitis, it is distinct because it does not originate from structures within the mediastinum. Therefore, the term Descending Necrotizing Mediastinitis implies that the infection of the mediastinum originated from a primary site in the head or neck and descended through fascial spaces into the mediastinum. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1585", "contents": "Though rare in developed countries, acute mediastinitis can be caused by inhalation of bacterial spores such as  Anthrax . Historically, this infection was referred to as  Wool-sorter's Disease . In the lungs, spores can spread via lymphatics to mediastinal lymph nodes, where the mature rods can release exotoxins promoting edema and tissue necrosis. [ 5 ]  Clinically, persons infected with anthrax can develop a hemorrhagic mediastinitis, which manifests as acute pulmonary hemorrhage and meningitis. [ 5 ]  Hallmark finding of disease is a widened mediastinum visualized on chest x-ray. Once clinical symptoms of anthrax induced mediastinitis appear, disease is nearly 100% fatal. Individuals with known exposure to spores may be treated prophylactically with antibiotics (fluoroquinolones or tetracycline) to prevent disease progression."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1586", "contents": "There are two types of fibrosing mediastinitis: granulomatous and non-granulomatous.  Granulomatous  mediastinitis is due to a granulomatous process of the mediastinal lymph nodes leading to fibrosis and chronic abscesses in the mediastinum. The most common causes are  histoplasmosis  and  tuberculosis  infections. Non-granulomatous fibrosing mediastinitis is caused by an idiopathic reaction to drugs and  radiation  therapy. [ 6 ]  Autoimmune disease and  Behcet's disease  are also causes. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1587", "contents": "An observational retrospective study of 17 patients diagnosed with DNM found that the infections most often originated from neck infections including  tonsillar abscess ,  pharyngitis , and  epiglottitis . The study also found that most infections are poly-microbial. [ 7 ]  Often the culprits are usually  Gram-positive  bacteria and  anaerobes , though rarely,  Gram-negative  bacteria are also present. This severe form represents 20% of acute mediastinitis cases. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1588", "contents": "Acute mediastinitis can be confirmed by contrast  x-rays  since most cases of acute mediastinitis are due to esophageal perforation. Other studies that can be used include endoscopic visualization, Chest  CT  scan with oral and intravenous contrast. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1589", "contents": "With regards to  CT  Imaging, the extent of involvement of the mediastinum can be evaluated. Therefore, acute mediastinitis can be classified into three categories: [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1590", "contents": "Most cases of granulomatous mediastinitis (75%) are incidentally found on chest x-rays which show a mediastinal mass, or widening of the mediastinum. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1591", "contents": "Treatment for acute mediastinitis usually involves aggressive intravenous antibiotic therapy and hydration.  If discrete fluid collections or grossly infected tissue have formed (such as abscesses), they may have to be surgically drained or debrided. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1592", "contents": "Treatment for DNM usually requires an operation to remove and drain infected necrotic tissue. Broad spectrum intravenous antibiotics are also given to treat the infection. Patients are typically managed in the intensive care unit due to the severity of the disease. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1593", "contents": "Treatment for chronic fibrosing mediastinitis is somewhat controversial, and may include steroids or surgical decompression of affected vessels. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1594", "contents": "Fibrosing mediastinitis can lead to entrapment of mediastinal structures. The mortality of DNM ranges from 10 to 40% due to  sepsis  and multi-organ failure if not recognized and intervened upon early. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1595", "contents": "Mineral dust airway disease  is a general term used to describe complications due to inhaled mineral dust causing  fibrosis  and narrowing of primarily the  respiratory bronchioles . [ 1 ]  It is a part of a group of disorders known as  pneumoconioses  which is characterized by inhaled mineral dust and the effects on the lungs. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1596", "contents": "The three main types of  pneumoconioses  are  Asbestosis  (caused by inhaling asbestos),  Silicosis  (caused by inhaling silica), and  Coal Workers  pneumoconioses  A.K.A  Black Lung  (caused by inhaling coal dust). [ 3 ]  There are other forms called  Mixed Dust  pneumoconioses  (caused by inhaling more than one mineral) and  Byssinosis  (caused by inhaling cotton dust). [ 3 ]  These two forms are less common and doctors do not often encounter them. Other forms can develop from inhaling a number of different minerals including but not limited to; aluminum, antimony, barium, graphite, iron, kaolin, mica, and talc. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1597", "contents": "Shortness of breath, Wheezing, Coughing. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1598", "contents": "Breathing in or inhaling inorganic dust. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1599", "contents": "Chest X-ray, CT scan of the chest, Pulmonary function tests. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1600", "contents": "Neonatal resuscitation,  also known as  newborn resuscitation,  is an  emergency procedure  focused on supporting approximately 10% of  newborn children  who do not readily begin  breathing , putting them at risk of irreversible organ injury and  death . [ 1 ]  Many of the infants who require this support to start breathing well on their own after assistance. Through  positive airway pressure , and in severe cases chest compressions, medical personnel certified in neonatal resuscitation can often stimulate neonates to begin breathing on their own, with attendant normalization of  heart rate . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1601", "contents": "Face masks that cover the infant's mouth and nose are often used in the resuscitation procedures. Nasal prongs/tubes/masks and laryngeal mask airway devices are also sometimes used. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1602", "contents": "Up to 10% of infants are born requiring assistance to begin breathing. After assistance, many of these infants begin to breath on their own and are healthy. Breathing problems at birth is a high priority emergency and interventions such as breathing support and resuscitation is sometimes required. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1603", "contents": "All infants who are ' gasping ', show signs of being  apnoeic  (suspension of breathing), or have  bradycardia  with a heart rate lower than 100 beats per minute after birth are recommended to be administered  positive pressure ventilation  with a 'manual ventilation device' to provide breathing support. [ 4 ]  Examples of manual ventilation devices include a self-inflating bag or a T-piece. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1604", "contents": "About a quarter of all neonatal deaths globally are caused by birth asphyxia. [ 5 ]  This dangerous condition of  oxygen deprivation  may begin before birth. For example, if the  umbilical cord , which supplies oxygen throughout  fetal development , is compressed or tears during  delivery . Depending on how quickly and successfully the infant is resuscitated, hypoxic damage can occur to most of the infant's organs ( heart ,  lungs ,  liver ,  gut ,  kidneys ). One serious complication is a brain injury known as  neonatal hypoxic-ischemic encephalopathy . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1605", "contents": "The most widely known training/certification for neonatal resuscitation is the  Neonatal Resuscitation Program  (NRP)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1606", "contents": "The  International Liaison Committee on Resuscitation  (ILCOR) has published  Consensus on science and treatment recommendations for neonatal resuscitation . [ 4 ]  Traditionally, newborn children have been resuscitated using  mechanical ventilation  with 100% oxygen, but there has since the 1980s increasingly been debated whether newborn infants with asphyxia should be resuscitated with 100% oxygen or normal air, and notably  Ola Didrik Saugstad  has been a major advocate of using normal air. [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1607", "contents": "In 2020, the  International Liaison Committee on Resuscitation  (ILCOR) published its 4th and most recent recommendations for newborn life support. The committee reviewed 8 major topics, including anticipation and preparation, initial assessment and intervention,  physiologic  monitoring and feedback devices,  ventilation  and  oxygenation ,  circulatory  support, drug and fluid administration,  prognostication  during  CPR , and post-resuscitation care. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1608", "contents": "Initial evaluation of a newborn is done by obtaining an  Apgar score , which gives the clinician an approximation of the infant's cardiovascular and neurologic condition at birth. A score of 7\u201310 at 5 minutes is normal, a score of 4 to 6 at 5 minutes is intermediate, and a score of 0-3 is considered low. It is important to understand that an Apgar score is not a diagnosis, it is merely a clinical finding. [ 9 ]  If a newborns score is 0\u20133, then resuscitation efforts are initiated."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1609", "contents": "Neonatal resuscitation guidelines closely resemble those of the  pediatric basic and advanced life support.  The main differences in training include an emphasis on  positive pressure ventilation  (PPV), updated timings on ventilation assistance rates, and some differences in the  cardiac arrest  chain of survival."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1610", "contents": "Guidelines for neonatal resuscitation are assessed annually and are developed in collaboration with multiple organizations of numerous experts, including the  American Academy of Pediatrics  (AAP)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1611", "contents": "In 2020, the ILCOR recommended the following changes to current resuscitation guidelines: [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1612", "contents": "While some guidelines do tend to change, certain elements of neonatal resuscitation have persisted. These include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1613", "contents": "Most neonatal deaths (roughly 75%) after resuscitation occur within the first week, but the vast majority occur within 24 hours. [ citation needed ]  This statistic is based on a  mean  Apgar score of 5.9, which is considered intermediate. More data is needed to understand outcomes for more severe patients. Outcomes after resuscitation for neonates vary widely based on many factors. One study in  Norway  analyzed 15  peer-reviewed  published articles and found that high-income countries have a mortality rate as high as 10% while low-income countries have a mortality rate as high as 28%. [ 10 ]  One major factor that improved survival was how quickly medical responders were able to intervene, noting that the first minutes are critical. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1614", "contents": "It has been demonstrated that high concentrations of oxygen lead to generation of oxygen  free radicals , which have a role in  reperfusion injury  after asphyxia. [ 12 ]  Clinical trial evidence suggests that resuscitation using air probably reduces the risk of death [ 13 ]  and the 2010 ILCOR guidelines recommend the use of normal air rather than 100% oxygen. [ 14 ]  Another study showed that  preterm  infants have little or no difference in risk of death or neurodevelopment disability when higher concentrations of oxygen are used compared to lower concentrations but the evidence from clinical trials is still relatively uncertain. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1615", "contents": "Currently, it is the  gold standard  to place neonates on a cooling blanket for 72 hours to achieve  total body cooling . This is done in order to minimize brain swelling. After cooling is achieved, an MRI is obtained roughly 1 week after  hypoxic brain injury  in order to classify the severity of brain damage. However, one study found that there was no significant correlation between MRI findings and developmental delay up to 2 years of life. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1616", "contents": "Obesity hypoventilation syndrome  ( OHS ) is a condition in which  severely overweight  people  fail to breathe rapidly or deeply enough , resulting in low  oxygen  levels and high blood  carbon dioxide  (CO 2 ) levels. The syndrome is often associated with  obstructive sleep apnea  (OSA), which causes periods of absent or reduced breathing in sleep, resulting in many partial awakenings during the night and sleepiness during the day. [ 1 ]  The disease puts strain on the heart, which may lead to  heart failure  and  leg swelling ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1617", "contents": "Obesity hypoventilation syndrome is defined as the combination of  obesity  and an  increased blood carbon dioxide  level during the day that is not attributable to another cause of  excessively slow or shallow breathing . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1618", "contents": "The most effective treatment is  weight loss , but this may require  bariatric surgery  to achieve. [ 3 ]  Weight loss of 25 to 30% is usually required to resolve the disorder. [ 3 ]  The other first-line treatment is non-invasive positive airway pressure (PAP), usually in the form of  continuous positive airway pressure  (CPAP) at night. [ 4 ] [ 5 ]  The disease was known initially in the 1950s, as \"Pickwickian syndrome\" in reference to a  Dickensian  character. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1619", "contents": "Most people with obesity hypoventilation syndrome have concurrent  obstructive sleep apnea , a condition characterized by  snoring , brief episodes of  apnea  (cessation of breathing) during the night, interrupted sleep and  excessive daytime sleepiness . In OHS, sleepiness may be worsened by elevated blood levels of  carbon dioxide , which causes drowsiness (\"CO 2  narcosis\"). Other symptoms present in both conditions are  depression , and  hypertension  (high blood pressure) which is difficult to  control with medication . [ 4 ]  The high carbon dioxide can also cause  headaches , which tend to be worsening in the morning. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1620", "contents": "The low oxygen level leads to physiologic constriction of the pulmonary arteries to correct ventilation-perfusion mismatching, which puts excessive strain on the right side of the heart. When this leads to right sided heart failure, it is known as  cor pulmonale . [ 4 ]  Symptoms of this disorder occur because the heart has difficulty pumping blood from the body through the lungs. Fluid may, therefore, accumulate in the skin of the legs in the form of  edema  (swelling), and in the abdominal cavity in the form of  ascites ; decreased exercise tolerance and exertional  chest pain  may occur. On  physical examination , characteristic findings are the presence of a raised  jugular venous pressure , a palpable parasternal heave, a  heart murmur  due to  blood leaking through the tricuspid valve ,  hepatomegaly  (an enlarged liver),  ascites  and leg edema. [ 7 ]  Cor pulmonale occurs in about a third of all people with OHS. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1621", "contents": "It is not fully understood why some obese people develop obesity hypoventilation syndrome while others do not. It is likely that it is the result of an interplay of various processes. Firstly, work of breathing is increased as  adipose tissue  restricts the normal movement of the chest muscles and makes the chest wall less  compliant , the  diaphragm  moves less effectively, respiratory muscles are fatigued more easily, and airflow in and out of the lung is impaired by excessive tissue in the head and neck area. Hence, people with obesity need to expend more energy to breathe effectively. [ 8 ] [ 9 ]  These factors together lead to sleep-disordered breathing and inadequate removal of carbon dioxide from the circulation and hence hypercapnia; given that carbon dioxide in aqueous solution combines with water to form an acid (CO 2 [g] + H 2 O[l] + excess H 2 O[l] --> H 2 CO 3 [aq]), this causes  acidosis  (increased acidity of the blood). Under normal circumstances,  central chemoreceptors  in the  brain stem  detect the acidity, and respond by increasing the  respiratory rate ; in OHS, this \"ventilatory response\" is blunted. [ 5 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1622", "contents": "The blunted ventilatory response is attributed to several factors. Obese people tend to have raised levels of the hormone  leptin , which is secreted by adipose tissue and under normal circumstances increases ventilation. In OHS, this effect is reduced. [ 5 ] [ 10 ]  Furthermore, episodes of nighttime acidosis (e.g. due to sleep apnea) lead to  compensation by the kidneys  with retention of the  alkali   bicarbonate . This normalizes the acidity of the blood. However, bicarbonate stays around in the bloodstream for longer, and further episodes of hypercapnia lead to relatively mild acidosis and reduced ventilatory response in a  vicious circle . [ 5 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1623", "contents": "Low oxygen levels lead to  hypoxic pulmonary vasoconstriction , the tightening of small blood vessels in the lung to create an optimal distribution of blood through the lung. Persistently low oxygen levels causing chronic vasoconstriction leads to increased pressure on the  pulmonary artery  ( pulmonary hypertension ), which in turn puts strain on the  right ventricle , the part of the heart that pumps blood to the lungs. The right ventricle undergoes  remodeling , becomes distended and is less able to remove blood from the veins. When this is the case, raised  hydrostatic pressure  leads to accumulation of fluid in the skin (edema), and in more severe cases the liver and the abdominal cavity. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1624", "contents": "The chronically low oxygen levels in the blood also lead to increased release of  erythropoietin  and the activation of  erythropoeisis , the production of  red blood cells . This results in  polycythemia , abnormally increased numbers of circulating red blood cells and an elevated  hematocrit . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1625", "contents": "Formal criteria for diagnosis of OHS are: [ 4 ] [ 5 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1626", "contents": "If OHS is suspected, various tests are required for its confirmation. The most important initial test is the demonstration of elevated carbon dioxide in the blood. This requires an  arterial blood gas  determination, which involves taking a blood sample from an  artery , usually the  radial artery . Given that it would be complicated to perform this test on every patient with sleep-related breathing problems, some suggest that measuring bicarbonate levels in normal (venous) blood would be a reasonable screening test. If this is elevated (27\u00a0mmol/L or higher), blood gasses should be measured. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1627", "contents": "To distinguish various subtypes,  polysomnography  is required. This usually requires brief admission to a hospital with a specialized sleep medicine department where a number of different measurements are conducted while the subject is asleep; this includes  electroencephalography  (electronic registration of electrical activity in the brain),  electrocardiography  (same for electrical activity in the heart),  pulse oximetry  (measurement of oxygen levels) and often other modalities. [ 4 ]  Blood tests are also recommended for the identification of  hypothyroidism  and  polycythemia . [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1628", "contents": "To distinguish between OHS and various other lung diseases that can cause similar symptoms,  medical imaging  of the lungs (such as a  chest X-ray  or  CT/CAT scan ),  spirometry , electrocardiography and  echocardiography  may be performed. Echo- and electrocardiography may also show strain on the right side of the heart caused by OHS, and spirometry may show a  restrictive  pattern related to obesity. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1629", "contents": "Obesity hypoventilation syndrome is a form of  sleep disordered breathing . Two subtypes are recognized, depending on the nature of disordered breathing detected on further investigations. The first is OHS in the context of obstructive sleep apnea; this is confirmed by the occurrence of 5 or more episodes of apnea, hypopnea or respiratory-related arousals per hour (high  apnea-hypopnea index ) during sleep. The second is OHS primarily due to \"sleep hypoventilation syndrome\"; this requires a rise of CO 2  levels by 10 mmHg (1.3 kPa) after sleep compared to awake measurements and overnight drops in oxygen levels without simultaneous apnea or hypopnea. [ 4 ] [ 11 ]  Overall, 90% of all people with OHS fall into the first category, and 10% in the second. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1630", "contents": "In people with stable OHS, the most important treatment is  weight loss \u2014by diet, through  exercise , with medication, or sometimes  weight loss surgery  (bariatric surgery). This has been shown to improve the symptoms of OHS and resolution of the high carbon dioxide levels. Weight loss may take a long time and is not always successful. [ 4 ]  If the symptoms are significant, nighttime  positive airway pressure  (PAP) treatment is tried; this involves the use of a machine to assist with breathing. PAP exists in various forms, and the ideal strategy is uncertain. Some medications have been tried to stimulate breathing or correct underlying abnormalities; their benefit is again uncertain. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1631", "contents": "While many people with obesity hypoventilation syndrome are cared for on an outpatient basis, some deteriorate suddenly and when admitted to the hospital may show severe abnormalities such as markedly deranged blood acidity (pH<7.25) or depressed  level of consciousness  due to very high carbon dioxide levels. On occasions, admission to an  intensive care unit  with  intubation  and  mechanical ventilation  is necessary. Otherwise, \"bi-level\" positive airway pressure (see the next section) is commonly used to stabilize the patient, followed by conventional treatment. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1632", "contents": "Positive airway pressure , initially in the form of continuous positive airway pressure (CPAP), is a useful treatment for obesity hypoventilation syndrome, particularly when obstructive sleep apnea coexists. CPAP requires the use during sleep of a machine that delivers a continuous positive pressure to the airways and preventing the collapse of soft tissues in the throat during breathing; it is administered through a mask on either the mouth and nose together or if that is not tolerated on the nose only (nasal CPAP). This relieves the features of obstructive sleep apnea and is often sufficient to remove the resultant accumulation of carbon dioxide. The pressure is increased until the obstructive symptoms (snoring and periods of apnea) have disappeared. CPAP alone is effective in more than 50% of people with OHS. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1633", "contents": "In some occasions, the oxygen levels are persistently too low ( oxygen saturations  below 90%). In that case, the hypoventilation itself may be improved by switching from CPAP treatment to an alternate device that delivers \"bi-level\" positive pressure: higher pressure during inspiration (breathing in) and a lower pressure during expiration (breathing out). If this too is ineffective in increasing oxygen levels, the addition of  oxygen therapy  may be necessary. As a last resort,  tracheostomy  may be necessary; this involves making a surgical opening in the trachea to bypass obesity-related airway obstruction in the neck. This may be combined with mechanical ventilation with an assisted breathing device through the opening. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1634", "contents": "People who fail first-line treatments or have very severe, life-threatening disease may sometimes be treated with  tracheotomy , which is a reversible procedure. [ 13 ]  Treatments without proven benefit, and concern for harm, include oxygen alone or respiratory stimulant medications.  Medroxyprogesterone acetate , a  progestin , and  acetazolamide  are both associated with an increased risk of  thrombosis  and are not recommended. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1635", "contents": "Obesity hypoventilation syndrome is associated with a reduced  quality of life , and people with the condition incur increased healthcare costs, largely due to hospital admissions including observation and treatment on  intensive care units . OHS often occurs together with several other disabling medical conditions, such as  asthma  (in 18\u201324%) and  type 2 diabetes  (in 30\u201332%). Its main complication of heart failure affects 21\u201332% of patients. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1636", "contents": "Those with abnormalities severe enough to warrant treatment have an increased risk of death reported to be 23% over 18 months and 46% over 50 months. This risk is reduced to less than 10% in those receiving treatment with PAP. Treatment also reduces the need for hospital admissions and reduces healthcare costs. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1637", "contents": "The exact prevalence of obesity hypoventilation syndrome is unknown, and it is thought that many people with symptoms of OHS have not been diagnosed. [ 4 ]  About a third of all people with morbid obesity (a  body mass index  exceeding 40\u00a0kg/m 2 ) have elevated  carbon dioxide  levels in the blood. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1638", "contents": "When examining groups of people with obstructive sleep apnea, researchers have found that 10\u201320% of them meet the criteria for OHS as well. The risk of OHS is much higher in those with more severe obesity, i.e. a body mass index (BMI) of 40\u00a0kg/m 2  or higher. It is twice as common in men compared to women. The average age at diagnosis is 52. American  Black people  are more likely to be obese than American whites, and are therefore more likely to develop OHS, but obese Asians are more likely than people of other ethnicities to have OHS at a lower BMI as a result of physical characteristics. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1639", "contents": "It is anticipated that rates of OHS will rise as the prevalence of obesity rises. This may also explain why OHS is more commonly reported in the  United States , where obesity is more common than in other countries. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1640", "contents": "The discovery of obesity hypoventilation syndrome is generally attributed to the authors of a 1956 report of a professional  poker  player who, after gaining weight, became somnolent and fatigued and prone to fall asleep during the day, as well as developing  edema  of the legs suggesting  heart failure . The authors coined the condition \"Pickwickian syndrome\" after the character Joe from  Dickens'   The Posthumous Papers of the Pickwick Club  (1837), who was markedly obese and tended to fall asleep uncontrollably during the day. [ 14 ]  This report, however, was preceded by other descriptions of hypoventilation in obesity. [ 5 ] [ 15 ]  In the 1960s, various further discoveries were made that led to the distinction between obstructive sleep apnea and sleep hypoventilation. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1641", "contents": "The term \"Pickwickian syndrome\" has fallen out of favor because it does not distinguish obesity hypoventilation syndrome and sleep apnea as separate disorders (which may coexist). [ 16 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1642", "contents": "Organic dust toxic syndrome  is a potentially severe  flu-like  syndrome originally described in farmers, mushroom workers, bird breeders and other persons occupationally exposed to dusty conditions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1643", "contents": "Symptoms arise 4 to 12 hours after exposure to an organic dust, and generally last from one to five days. Common generalised symptoms include  fever  over 38\u00a0\u00b0C, chills,  myalgia  and  malaise . The most frequent respiratory symptoms are  dyspnea  and a  dry cough , while a wheeze may be present less commonly.  Headache ,  rhinitis ,  conjunctivitis  and  keratitis  can also be present, and skin  irritation  may occur in those handling grain. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1644", "contents": "Respiratory function may worsen to the point where  hypoxia  occurs, and damage to the airways may lead to non-cardiogenic  pulmonary edema  one to three days post exposure. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1645", "contents": "Laboratory investigations may show a raised  white cell  (and specifically  neutrophil ) count, while a chest X-ray is often normal or shows minimal  interstitial infiltration . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1646", "contents": "An  inflammatory  reaction of the airways and  alveoli , the mechanism of organic dust toxic syndrome is thought to be toxic rather than  autoimmune  in origin. [ 2 ]  The airways are exposed to high concentrations of organic dust created by some form of disturbance or mechanical process. They can be such materials such as grain kernel fragments, bits of insects, bacteria, fungal spores, molds or chemical residues, the individual particles 0.1 to 50\u00a0 \u03bcm  in size. [ 1 ]  A common scenario is exposure to moldy grain, hay or woodchips, with farmers and pig workers the most common occupations affected. Those who work with grain, poultry and mushrooms also frequently report symptoms. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1647", "contents": "Pulmonary reactions occur due to the exposure to grain dust. The amount of organic dust include hay, grain, wood and compost. [ 3 ]  Exposure to high amounts of dust particles cause syndromes of grain fever, organic dust toxic syndrome, toxic  pneumonitis , inhalation fever, silo unloaders' disease, hypersensitivity pneumonitis,  farmers' lung , mushroom workers' lung, and bark strippers' disease. [ 3 ]  Recent studies have conducted that organic dust syndrome has acute like symptoms of grain fever, silo unloaders' disease and toxic pneumonitis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1648", "contents": "Diagnosis is first done through the inspection of the swollen mucosa in the mouth and visible airways. Any inspection of the lung stays nonetheless unapparent. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1649", "contents": "The illness is generally  self-limiting . Management on the whole is preventive, by limiting exposure to mouldy environments with ventilation, or by wearing respiratory protection such as facemasks. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1650", "contents": "It was recognised as a distinct clinical syndrome in the 1980s. Previously, cases had been reported and given various names such as pulmonary mycotoxicosis, silo unloader's syndrome, grain fever, malt fever, toxin fever, humidifier fever, mill fever, toxic alveolitis or allergic alveolitis. In 1994, the  National Institute for Occupational Safety and Health  published case reports and highlighted the urgency for study of the syndrome."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1651", "contents": "There are two primary types of dust exposure in agriculture: inorganic and organic. Often the cause of allergy illnesses like  asthma , organic dusts come from both plant and animal sources. Inorganic dust illnesses are non-allergic lung reactions that originate in the  soil . [ 4 ]  Asthma-like symptoms are linked to inorganic dust syndrome."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1652", "contents": "Droughts"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1653", "contents": "In the  Sierra Nevada , where the dust cycle has responded significantly to climate change, droughts have been a competing element. The primary factors are the increased greenhouse gas emissions that have contributed to global warming, which has had a significant impact on moisture levels and the possibility of  evapotranspiration  (the amount of water that evaporates from the ground to the amount of water that is accessible). Crop water intake is also calculated using potential evapotranspiration. Dust emissions have increased as a result of land use, industrial development, and animal grazing, particularly in the western United States. Furthermore,\"Dust emissions in some regions have increased by up to 400% in the past several decades\". [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1654", "contents": "Inorganic dust (minerals)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1655", "contents": "The Central Valley is known about its agricultural aspects, including the dry farming, resulting in increase of airborne dust from field procedures (harvesting, crop cleanup, etc). Soil is a combination of small amounts of organic compound and large amounts of  inorganic compounds, yet it is part of external factors that often cause nonallergic lung symptoms. Exposure to mineral dust presents the hazards for farmers in the development of lung disease. [ 6 ]  In one analysis, 112 male Hispanic individuals in the Fresno county were part of a study conducted in the findings of the comparison between farm workers and non-farm workers. Out of 32 individuals, 22 farmers were diagnosed with mineral dust small airways disease, Thirty-one out of Sixty-one were diagnosed with smoking-related small airways disease and17 out 23 farmers were diagnosed with Pneumoconiosis. [ 7 ]  Furthermore, residents were as well found to be diagnosed with Interstitial fibrosis, Lymph node fibrosis,  Chronic bronchitis , Asthma-like airway disease and  Emphysema . The study resulted in Farm-workers having an higher risk of the diseases mentioned."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1656", "contents": "Oxygen toxicity  is a condition resulting from the harmful effects of breathing molecular  oxygen  ( O 2 ) at increased  partial pressures . Severe cases can result in  cell damage  and death, with effects most often seen in the central nervous system,  lungs , and eyes. Historically, the  central nervous system  condition was called the  Paul Bert  effect, and the pulmonary condition the  Lorrain Smith  effect, after the researchers who pioneered the discoveries and descriptions in the late 19th century. Oxygen toxicity is a concern for  underwater divers , those on high concentrations of supplemental oxygen, and those undergoing  hyperbaric oxygen therapy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1657", "contents": "The result of breathing increased partial pressures of oxygen is  hyperoxia , an excess of oxygen in body tissues. The body is affected in different ways depending on the type of exposure. Central nervous system toxicity is caused by short exposure to high partial pressures of oxygen at greater than atmospheric pressure. Pulmonary and ocular toxicity result from longer exposure to increased oxygen levels at normal pressure. Symptoms may include disorientation, breathing problems, and vision changes such as  myopia . Prolonged exposure to above-normal oxygen partial pressures, or shorter exposures to very high partial pressures, can cause  oxidative damage  to  cell membranes , collapse of the  alveoli  in the lungs,  retinal detachment , and  seizures . Oxygen toxicity is managed by reducing the exposure to increased oxygen levels. Studies show that, in the long term, a robust recovery from most types of oxygen toxicity is possible."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1658", "contents": "Protocols  for avoidance of the effects of hyperoxia exist in fields where oxygen is breathed at higher-than-normal partial pressures, including  underwater diving  using compressed  breathing gases , hyperbaric medicine,  neonatal care  and  human spaceflight . These protocols have resulted in the increasing rarity of seizures due to oxygen toxicity, with pulmonary and ocular damage being largely confined to the problems of managing premature infants."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1659", "contents": "In recent years, oxygen has become available for recreational use in  oxygen bars . The  US Food and Drug Administration  has warned those who have conditions such as heart or lung disease not to use oxygen bars. Scuba divers use breathing gases containing up to 100% oxygen, and should have specific training in using such gases."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1660", "contents": "The effects of oxygen toxicity may be classified by the organs affected, producing three principal forms: [ 2 ] [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1661", "contents": "Central nervous system oxygen toxicity can cause seizures, brief periods of rigidity followed by convulsions and unconsciousness, and is of concern to divers who encounter greater than atmospheric pressures. Pulmonary oxygen toxicity results in damage to the lungs, causing pain and difficulty in breathing. [ 2 ]  Oxidative damage to the eye may lead to myopia or partial detachment of the  retina . Pulmonary and ocular damage are most likely to occur when supplemental oxygen is administered as part of a treatment, particularly to newborn infants, but are also a concern during hyperbaric oxygen therapy. [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1662", "contents": "Oxidative damage may occur in any cell in the body but the effects on the three most susceptible organs will be the primary concern. It may also be implicated in damage to red blood cells ( haemolysis ), [ 7 ] [ 8 ]   the  liver , [ 9 ]   heart , [ 10 ]   endocrine glands  ( adrenal glands ,  gonads , and  thyroid ), [ 11 ] [ 12 ] [ 13 ]  or  kidneys , [ 14 ]  and general damage to  cells . [ 2 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1663", "contents": "In unusual circumstances, effects on other tissues may be observed: it is suspected that during spaceflight, high oxygen concentrations may contribute to bone damage. [ 16 ]  Hyperoxia can also indirectly cause  carbon dioxide narcosis  in patients with lung ailments such as  chronic obstructive pulmonary disease  or with central respiratory depression. [ 16 ]   Hyperventilation  of atmospheric air at atmospheric pressures does not cause oxygen toxicity, because sea-level air has a partial pressure of oxygen of 0.21\u00a0bar (21\u00a0kPa) whereas toxicity does not occur below 0.3\u00a0bar (30\u00a0kPa). [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1664", "contents": "Central nervous system  oxygen toxicity manifests as symptoms such as visual changes (especially  tunnel vision ), ringing in the ears ( tinnitus ),  nausea , twitching (especially of the face), behavioural changes (irritability,  anxiety , confusion), and  dizziness . This may be followed by a  tonic\u2013clonic seizure  consisting of two phases: intense muscle contraction occurs for several seconds (tonic phase); followed by rapid spasms of alternate muscle relaxation and contraction producing convulsive jerking ( clonic  phase). The seizure ends with a period of unconsciousness (the  postictal state ). [ 18 ] [ 19 ]  The onset of seizure depends upon the partial pressure of oxygen in the  breathing gas  and exposure duration. However, exposure time before onset is unpredictable, as tests have shown a wide variation, both amongst individuals, and in the same individual from day to day. [ 18 ] [ 20 ] [ 21 ]  In addition, many external factors, such as underwater immersion, exposure to cold, and exercise will decrease the time to onset of central nervous system symptoms. [ 1 ]  Decrease of tolerance is closely linked to retention of  carbon dioxide . [ 22 ] [ 23 ] [ 24 ]  Other factors, such as darkness and  caffeine , increase tolerance in test animals, but these effects have not been proven in humans. [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1665", "contents": "Exposure to oxygen pressures greater than 0.5 bar, such as during diving, oxygen prebreathing prior to flight, or hyperbaric therapy is associated with the onset of pulmonary toxicity symptoms, [ 27 ]   also referred to as chronic oxygen toxicity. [ 28 ]  Pulmonary toxicity symptoms result from an inflammation that starts in the airways leading to the lungs and then spreads into the lungs ( tracheobronchial tree ). The symptoms appear in the upper chest region ( substernal  and  carinal  regions). [ 29 ] [ 30 ] [ 31 ]  This begins as a mild tickle on inhalation and progresses to frequent coughing. [ 29 ]  If breathing increased partial pressures of oxygen continues, subjects experience a mild burning on inhalation along with uncontrollable coughing and occasional shortness of breath ( dyspnea ). [ 29 ]  Physical findings related to pulmonary toxicity have included bubbling sounds heard through a  stethoscope  (bubbling  rales ), fever, and increased blood flow to the lining of the nose ( hyperaemia  of the nasal  mucosa ). [ 31 ]  Initially, there is an exudative phase that results in  Pulmonary edema . An increase in the width of the interstitial space may be seen in histological examination. [ 27 ]  X-rays of the lungs show little change in the short term, but extended exposure leads to increasing diffuse shadowing throughout both lungs. [ 29 ]   Pulmonary function measurements  are reduced, as indicated by a reduction in the amount of air that the lungs can hold ( vital capacity ) and changes in expiratory function and lung elasticity. [ 31 ] [ 32 ]  Lung diffusing capacity decreases leading eventually to hypoxaemia. [ 27 ]  Tests in animals have indicated a variation in tolerance similar to that found in central nervous system toxicity, as well as significant variations between species. When the exposure to oxygen above 0.5\u00a0bar (50\u00a0kPa) is intermittent, it permits the lungs to recover and delays the onset of toxicity. [ 33 ]   A similar progression is common to all mammalian species. [ 27 ]  If death from hypoxaemia has not occurred after exposure for several days a proliferative phase occurs, developing a chronic thickening of the alveolar membrane and a decrement in lung diffusing capacity. These changes are mostly reversible on return to normoxia, but the time required for complete recovery is not known. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1666", "contents": "In premature babies, signs of damage to the eye ( retinopathy of prematurity , or ROP) are observed via an  ophthalmoscope  as a demarcation between the  vascularised  and non-vascularised regions of an infant's retina. The degree of this demarcation is used to designate four stages: (I) the demarcation is a line; (II) the demarcation becomes a ridge; (III) growth of new blood vessels occurs around the ridge; (IV) the retina begins to detach from the inner wall of the eye ( choroid ). [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1667", "contents": "Oxygen toxicity is caused by hyperoxia, exposure to oxygen at partial pressures greater than those to which the body is normally exposed. This occurs in three principal settings: underwater diving, [ 34 ]  hyperbaric oxygen therapy, [ 35 ]  and the provision of supplemental oxygen, in critical care, [ 36 ]  and for long-term treatment of chronic disorders, and particularly to premature infants. [ 37 ]  In each case, the  risk factors  are markedly different. [ 34 ] [ 35 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1668", "contents": "Under normal or reduced ambient pressures, the effects of hyperoxia are initially restricted to the lungs, which are directly exposed, but after prolonged exposure or at hyperbaric pressures, other organs can be at risk. At normal partial pressures of inhaled oxygen, most of the oxygen transported in the blood is carried by haemoglobin, but the amount of dissolved oxygen will increase at partial pressures of arterial oxygen exceeding 100 millimetres of mercury (0.13\u00a0bar), when oxyhemoglobin saturation is nearly complete. At higher concentrations the effects of hyperoxia are more widespread in the body tissues beyond the lungs. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1669", "contents": "Exposures, from minutes to a few hours, to partial pressures of oxygen above about 1.6  bars  (160\u00a0 kPa )\u2014about eight times normal atmospheric partial pressure\u2014are usually associated with central nervous system oxygen toxicity, also known as acute oxygen toxicity, [ 28 ]  and are most likely to occur among patients undergoing hyperbaric oxygen therapy and divers. Since sea level atmospheric pressure is about 1\u00a0bar (100\u00a0kPa), central nervous system toxicity can only occur under  hyperbaric  conditions, where  ambient pressure  is above normal. [ 35 ] [ 39 ]  Divers breathing air at depths beyond 60\u00a0m (200\u00a0ft) face an increasing risk of an oxygen toxicity \"hit\" (seizure). Divers breathing a gas mixture enriched with oxygen, such as  nitrox , similarly increase the risk of a seizure at shallower depths, should they descend below the  maximum operating depth  accepted for the mixture. [ 40 ] \nCNS toxicity is aggravated by a high partial pressure of carbon dioxide, stress, fatigue, and cold, all of which are much more likely in diving than in hyperbaric therapy. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1670", "contents": "The lungs and the remainder of the  respiratory tract  are exposed to the highest concentration of oxygen in the human body and are therefore the first organs to show chronic toxicity. [ 28 ]  Pulmonary toxicity occurs only with exposure to partial pressures of oxygen greater than 0.5\u00a0bar (50\u00a0kPa), corresponding to an oxygen fraction of 50% at normal atmospheric pressure. The earliest signs of pulmonary toxicity begin with evidence of tracheobronchitis, or inflammation of the upper airways, after an asymptomatic period between 4 and 22 hours at greater than 95% oxygen, [ 41 ]  with some studies suggesting symptoms usually begin after approximately 14 hours at this level of oxygen. [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1671", "contents": "At partial pressures of oxygen of 2 to 3\u00a0bar (200 to 300\u00a0kPa)\u2014100% oxygen at 2 to 3 times atmospheric pressure\u2014these symptoms may begin as early as 3 hours into exposure to oxygen. [ 41 ]  Experiments on rats breathing oxygen at pressures between 1 and 3 bars (100 and 300\u00a0kPa) suggest that pulmonary manifestations of oxygen toxicity may not be the same for  normobaric  conditions as they are for  hyperbaric  conditions. [ 43 ]  Evidence of decline in lung function as measured by pulmonary function testing can occur as quickly as 24 hours of continuous exposure to 100% oxygen, [ 42 ]  with evidence of  diffuse alveolar damage  and the onset of  acute respiratory distress syndrome  usually occurring after 48 hours on 100% oxygen. [ 41 ]  Breathing 100% oxygen also eventually leads to collapse of the  alveoli  ( atelectasis ), while\u2014at the same partial pressure of oxygen\u2014the presence of significant partial pressures of inert gases, typically nitrogen, will prevent this effect. [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1672", "contents": "Preterm newborns are known to be at higher risk for  bronchopulmonary dysplasia  with extended exposure to high concentrations of oxygen. [ 45 ]  Other groups at higher risk for oxygen toxicity are patients on  mechanical ventilation  with exposure to levels of oxygen greater than 50%, and patients exposed to chemicals that increase risk for oxygen toxicity such the chemotherapeutic agent  bleomycin . [ 42 ]  Therefore, current guidelines for patients on mechanical ventilation in  intensive care  recommend keeping oxygen concentration less than 60%. [ 41 ]  Likewise, divers who undergo treatment of  decompression sickness  are at increased risk of oxygen toxicity as treatment entails exposure to long periods of oxygen breathing under hyperbaric conditions, in addition to any oxygen exposure during the dive. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1673", "contents": "Prolonged exposure to high inspired fractions of oxygen causes damage to the  retina . [ 46 ] [ 47 ] [ 48 ]  Damage to the developing eye of infants exposed to high oxygen fraction at normal pressure has a different mechanism and effect from the eye damage experienced by adult divers under hyperbaric conditions. [ 49 ] [ 50 ]  Hyperoxia may be a contributing factor for the disorder called retrolental fibroplasia or retinopathy of prematurity (ROP) in infants. [ 49 ] [ 51 ]  In preterm infants, the retina is often not fully vascularised. Retinopathy of prematurity occurs when the development of the retinal vasculature is arrested and then proceeds abnormally. Associated with the growth of these new vessels is  fibrous tissue  (scar tissue) that may contract to cause retinal detachment. Supplemental oxygen exposure, while a  risk factor , is not the main risk factor for development of this disease. Restricting supplemental oxygen use does not necessarily reduce the rate of retinopathy of prematurity, and may raise the risk of hypoxia-related systemic complications. [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1674", "contents": "Hyperoxic myopia  has occurred in closed circuit oxygen rebreather divers with prolonged exposures. [ 50 ] [ 52 ] [ 53 ]  It also occurs frequently in those undergoing repeated hyperbaric oxygen therapy. [ 47 ] [ 54 ]  This is due to an increase in the refractive power of the  lens , since axial length and  keratometry  readings do not reveal a  corneal  or length basis for a myopic shift. [ 54 ] [ 55 ]  It is usually reversible with time. [ 47 ] [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1675", "contents": "A possible side effect of hyperbaric oxygen therapy is the initial or further development of  cataracts , which are an increase in opacity of the lens of the eye which reduces visual acuity, and can eventually result in blindness. This is a rare event, associated with lifetime exposure to raised oxygen concentration, and may be under-reported as it develops very slowly, and cataracts are a common disorder of advanced age. The cause is not fully understood, but evidence suggests that raised oxygen levels at the lens may be caused by deterioration of the  vitreous humour  due to age, and this causes degradation of lens crystallins by cross-linking, forming aggregates capable of scattering light. This may be an end-state development of the more commonly observed myopic shift associated with hyperbaric treatment. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1676", "contents": "The biochemical basis for the toxicity of oxygen is the partial reduction of oxygen by one or two electrons to form reactive oxygen species, [ 56 ]  which are natural by-products of the normal  metabolism  of oxygen and have important roles in  cell signalling . [ 57 ]  One species produced by the body, the  superoxide  anion ( O \u2212 2 ), [ 58 ]  is possibly involved in iron acquisition. [ 59 ]  Higher than normal concentrations of oxygen lead to increased levels of reactive oxygen species. [ 60 ]  Oxygen is necessary for cell metabolism, and the blood supplies it to all parts of the body. When oxygen is breathed at high partial pressures, a hyperoxic condition will rapidly spread, with the most vascularised tissues being most vulnerable. During times of environmental stress, levels of reactive oxygen species can increase dramatically, which can damage cell structures and produce  oxidative stress . [ 21 ] [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1677", "contents": "While all the reaction mechanisms of these species within the body are not yet fully understood, [ 62 ]  one of the most reactive products of oxidative stress is the  hydroxyl radical  ( \u00b7OH ), which can initiate a damaging chain reaction of  lipid peroxidation  in the unsaturated  lipids  within  cell membranes . [ 63 ]  High concentrations of oxygen also increase the formation of other  free radicals , such as  nitric oxide ,  peroxynitrite , and  trioxidane , which harm  DNA  and other biomolecules. [ 21 ] [ 64 ]  Although the body has many  antioxidant  systems such as  glutathione  that guard against oxidative stress, these systems are eventually overwhelmed at very high concentrations of free oxygen, and the rate of cell damage exceeds the capacity of the systems that prevent or repair it. [ 65 ] [ 66 ] [ 67 ]  Cell damage and cell death then result. [ 68 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1678", "contents": "Diagnosis of central nervous system oxygen toxicity in divers prior to seizure is difficult as the symptoms of visual disturbance, ear problems, dizziness, confusion and nausea can be due to many factors common to the underwater environment such as  narcosis , congestion and coldness. However, these symptoms may be helpful in diagnosing the first stages of oxygen toxicity in patients undergoing hyperbaric oxygen therapy. In either case, unless there is a prior history of  epilepsy  or tests indicate  hypoglycaemia , a seizure occurring in the setting of breathing oxygen at partial pressures greater than 1.4\u00a0bar (140\u00a0kPa) suggests a diagnosis of oxygen toxicity. [ 69 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1679", "contents": "Diagnosis of bronchopulmonary dysplasia in newborn infants with breathing difficulties is difficult in the first few weeks. However, if the infant's breathing does not improve during this time,  blood tests  and  x-rays  may be used to confirm bronchopulmonary dysplasia. In addition, an  echocardiogram  can help to eliminate other possible causes such as  congenital heart defects  or  pulmonary arterial hypertension . [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1680", "contents": "The diagnosis of retinopathy of prematurity in infants is typically suggested by the clinical setting. Prematurity, low birth weight, and a history of oxygen exposure are the principal indicators, while no hereditary factors have been shown to yield a pattern. [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1681", "contents": "Clinical diagnosis can be confirmed with arterial oxygen levels. [ 28 ] \nA number of other conditions can be confused with oxygen toxicity, these include: [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1682", "contents": "The prevention of oxygen toxicity depends entirely on the setting. Both underwater and in space, proper precautions can eliminate the most pernicious effects. Premature infants commonly require supplemental oxygen to treat complications of preterm birth. In this case prevention of bronchopulmonary dysplasia and retinopathy of prematurity must be carried out without compromising a supply of oxygen adequate to preserve the infant's life. [ 72 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1683", "contents": "Oxygen toxicity is a catastrophic hazard in  scuba diving , because a seizure results in high risk of death by drowning. [ 40 ] [ 73 ]  The seizure may occur suddenly and with no warning symptoms. [ 19 ]  The effects are sudden convulsions and unconsciousness, during which victims can lose their  regulator  and drown. [ 74 ] [ 75 ]  One of the advantages of a  full-face diving mask  is prevention of regulator loss in the event of a seizure. Mouthpiece retaining straps are a relatively inexpensive alternative with a similar but less effective function. [ 73 ]  As there is an increased risk of central nervous system oxygen toxicity on deep dives, long dives and dives where oxygen-rich breathing gases are used, divers are taught to calculate a  maximum operating depth  for oxygen-rich  breathing gases , and cylinders containing such mixtures should be clearly marked with that depth. [ 24 ] [ 76 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1684", "contents": "The risk of seizure appears to be a function of dose \u2013 a cumulative combination of partial pressure and duration. The threshold for oxygen partial pressure below which seizures never occur has not been established, and may depend on many variables, some of them personal. The risk to a specific person can vary considerably depending on individual sensitivity, level of exercise, and carbon dioxide retention, which is influenced by work of breathing. [ 73 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1685", "contents": "In some  diver training  courses for modes of diving in which exposure may reach levels with significant risk, divers are taught to plan and monitor what is called the 'oxygen clock' of their dives. [ 76 ]  This is a notional alarm clock, which ticks more quickly at increased oxygen pressure and is set to activate at the maximum single exposure limit recommended in the  National Oceanic and Atmospheric Administration  Diving Manual. [ 24 ] [ 76 ]  For the following partial pressures of oxygen the limits are: 45 minutes at 1.6\u00a0bar (160\u00a0kPa), 120 minutes at 1.5\u00a0bar (150\u00a0kPa), 150 minutes at 1.4\u00a0bar (140\u00a0kPa), 180 minutes at 1.3\u00a0bar (130\u00a0kPa) and 210 minutes at 1.2\u00a0bar (120\u00a0kPa), but it is impossible to predict with any reliability whether or when toxicity symptoms will occur. [ 77 ] [ 78 ]  Many  nitrox -capable  dive computers  calculate an oxygen loading and can track it across multiple dives. The aim is to avoid activating the alarm by reducing the partial pressure of oxygen in the breathing gas or by reducing the time spent breathing gas of greater oxygen partial pressure. As the partial pressure of oxygen increases with the fraction of oxygen in the breathing gas and the depth of the dive, the diver obtains more time on the oxygen clock by diving at a shallower depth, by breathing a less oxygen-rich gas, or by shortening the duration of exposure to oxygen-rich gases. [ 79 ] [ 80 ]  This function is provided by some technical diving decompression computers and rebreather control and monitoring hardware. [ 81 ] [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1686", "contents": "Diving below 56\u00a0m (184\u00a0ft) on air would expose a diver to increasing danger of oxygen toxicity as the partial pressure of oxygen exceeds 1.4\u00a0bar (140\u00a0kPa), so a gas mixture should be used which contains less than 21% oxygen (termed a hypoxic mixture). Increasing the proportion of  nitrogen  is not viable, since it would produce a strongly  narcotic  mixture. However,  helium  is not narcotic, and a usable mixture may be  blended  either by completely replacing nitrogen with helium (the resulting mix is called  heliox ), or by replacing part of the nitrogen with helium, producing a  trimix . [ 83 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1687", "contents": "Pulmonary oxygen toxicity is an entirely avoidable event while diving. The limited duration and naturally intermittent nature of most diving makes this a relatively rare (and even then, reversible) complication for divers. [ 84 ]  Established guidelines enable divers to calculate when they are at risk of pulmonary toxicity. [ 85 ] [ 86 ] [ 87 ]  In  saturation diving  it can be avoided by limiting the oxygen content of gas in living areas to below 0.4 bar. [ 88 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1688", "contents": "The intention of screening using an  oxygen tolerance test  is to identify divers with low tolerance to high partial pressures of hyperbaric oxygen who may be more prone to oxygen convulsions during diving operations or during hyperbaric treatment for decompression sickness. The value of this test has been questioned, and statistical studies have shown low incidence of seizures during standard hyperbaric treatment schedules, so some navies have discontinued its use, though an others continue to require the test for all candidate divers. [ 89 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1689", "contents": "The variability in tolerance and other variable factors such as workload have resulted in the U.S. Navy abandoning screening for oxygen tolerance. Of the 6,250 oxygen-tolerance tests performed between 1976 and 1997, only 6 episodes of oxygen toxicity were observed (0.1%). [ 90 ] [ 91 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1690", "contents": "The oxygen tolerance test used by the  Indian Navy , which follows recommendations of the  US Navy  and US National Oceanic and Atmospheric Administration, is to breathe 100% oxygen delivered by  BIBS  mask at an ambient pressure of 2.8 bar absolute (18 msw) for 30 minutes, at rest in a dry hyperbaric chamber. No symptoms of CNS oxygen toxicity may be observed by the attendant. [ 89 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1691", "contents": "The presence of a fever or a history of seizure is a relative contraindication to hyperbaric oxygen treatment. [ 92 ]  The schedules used for treatment of  decompression illness  allow for periods of breathing air rather than 100% oxygen (air breaks) to reduce the chance of seizure or lung damage. The U.S. Navy uses treatment tables based on periods alternating between 100% oxygen and air. For example,  USN table 6  requires 75\u00a0minutes (three periods of 20\u00a0minutes oxygen/5\u00a0minutes air) at an ambient pressure of 2.8  standard atmospheres  (280\u00a0kPa), equivalent to a depth of 18 metres (60\u00a0ft). This is followed by a slow reduction in pressure to 1.9\u00a0atm (190\u00a0kPa) over 30\u00a0minutes on oxygen. The patient then remains at that pressure for a further 150\u00a0minutes, consisting of two periods of 15\u00a0minutes air/60\u00a0minutes oxygen, before the pressure is reduced to atmospheric over 30\u00a0minutes on oxygen. [ 93 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1692", "contents": "Vitamin E  and  selenium  were proposed and later rejected as a potential method of protection against pulmonary oxygen toxicity. [ 94 ] [ 95 ] [ 96 ]  There is however some experimental evidence in rats that vitamin E and selenium aid in preventing  in vivo   lipid peroxidation  and free radical damage, and therefore prevent retinal changes following repetitive hyperbaric oxygen exposures. [ 97 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1693", "contents": "Bronchopulmonary dysplasia  is reversible in the early stages by use of break periods on lower pressures of oxygen, but it may eventually result in irreversible lung injury if allowed to progress to severe damage. One or two days of exposure without oxygen breaks are needed to cause such damage. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1694", "contents": "Retinopathy of prematurity  is largely preventable by screening. Current guidelines require that all babies of less than 32\u00a0weeks  gestational age  or having a birth weight less than 1.5\u00a0kg (3.3\u00a0lb) should be screened for retinopathy of prematurity at least every two weeks. [ 98 ]  The  National Cooperative Study  in 1954 showed a causal link between supplemental oxygen and retinopathy of prematurity, but subsequent curtailment of supplemental oxygen caused an increase in infant mortality. To balance the risks of  hypoxia  and retinopathy of prematurity, modern protocols now require monitoring of blood oxygen levels in premature infants receiving oxygen. [ 99 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1695", "contents": "Careful titration of dosage to minimise delivered concentration while achieving the desired level of oxygenation will both minimise the risk of oxygen toxicity damage and the amount of oxygen used for long term therapy. [ 38 ]  A typical target for oxygen saturation when receiving oxygen therapy, would be in the range of 91-95%, in both term and preterm infants. [ 72 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1696", "contents": "In low-pressure environments oxygen toxicity may be avoided since the toxicity is caused by high partial pressure of oxygen, not by high oxygen fraction. This is illustrated by the use of pure oxygen in spacesuits, which must operate at low pressure, and a high \noxygen fraction and cabin pressure lower than normal atmospheric pressure in early spacecraft, for example, the  Gemini  and  Apollo spacecraft . [ 100 ]  In such applications as  extra-vehicular activity , high-fraction oxygen is non-toxic, even at breathing mixture fractions approaching 100%, because the oxygen partial pressure is not allowed to  chronically  exceed 0.3\u00a0bar (4.4\u00a0psi). [ 100 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1697", "contents": "During hyperbaric oxygen therapy, the patient will usually breathe 100% oxygen from a mask while inside a hyperbaric chamber pressurised with air to about 2.8\u00a0bar (280\u00a0kPa). Seizures during the therapy are managed by removing the mask from the patient, thereby dropping the partial pressure of oxygen inspired below 0.6\u00a0bar (60\u00a0kPa). [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1698", "contents": "A seizure underwater requires that the diver be brought to the surface as soon as practicable. Although for many years the recommendation has been not to raise the diver during the seizure itself, owing to the danger of  arterial gas embolism  (AGE), [ 101 ]  there is some evidence that the glottis does not fully obstruct the airway. [ 102 ]  This has led to the current recommendation by the Diving Committee of the Undersea and Hyperbaric Medical Society that a diver should be raised during the seizure's clonic (convulsive) phase if the regulator is not in the diver's mouth\u2014as the danger of drowning is then greater than that of AGE\u2014but the ascent should be delayed until the end of the clonic phase otherwise. [ 74 ]  Rescuers ensure that their own safety is not compromised during the convulsive phase. They then ensure that where the victim's air supply is established it is maintained, and carry out a  controlled buoyant lift . Lifting an unconscious body is taught by most recreational  diver training  agencies as an advanced skill, and for professional divers it is a basic skill, as it is one of the primary functions of the  standby diver . Upon reaching the surface, emergency services are always contacted as there is a possibility of further complications requiring medical attention. [ 103 ]  If symptoms develop other than a seizure underwater the diver should immediately switch to a gas with a lower oxygen fraction or ascend to a shallower depth if decompression obligations allow. If a chamber is available at the surface, surface decompression is a recommended option. The U.S. Navy has published procedures for completing decompression stops where a recompression chamber is not immediately available. [ 104 ]  Some dive computers will recalculate decompression requirements for alternative mixtures provided the actual gas setting is activated. [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1699", "contents": "The occurrence of symptoms of bronchopulmonary dysplasia or acute respiratory distress syndrome is treated by lowering the fraction of oxygen administered, along with a reduction in the periods of exposure and an increase in the break periods where normal air is supplied. Where supplemental oxygen is required for treatment of another disease (particularly in infants), a  ventilator  may be needed to ensure that the lung tissue remains inflated. Reductions in pressure and exposure will be made progressively, and medications such as  bronchodilators  and  pulmonary surfactants  may be used. [ 105 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1700", "contents": "Divers manage the risk of pulmonary damage by limiting exposure to levels shown to be generally acceptable by experimental evidence, using a system of accumulated  oxygen toxicity unit s which are based on exposure time at specified partial pressures. In the event of emergency treatment for decompression illness, it may be necessary to exceed normal exposure limits to manage more critical symptoms. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1701", "contents": "Retinopathy of prematurity may  regress  spontaneously, but should the disease progress beyond a threshold (defined as five contiguous or eight cumulative hours of  stage 3 retinopathy of prematurity ), both  cryosurgery  and  laser surgery  have been shown to reduce the risk of blindness as an outcome. Where the disease has progressed further, techniques such as  scleral buckling  and  vitrectomy  surgery may assist in re-attaching the retina. [ 106 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1702", "contents": "Repeated exposure to potentially toxic oxygen concentrations in breathing gas is fairly common in hyperbaric activity, particularly in  hyperbaric medicine ,  saturation diving ,  underwater habitats , and repetitive  decompression diving . Research at the  National Oceanic and Atmospheric Administration  (NOAA) by  R.W. Hamilton  and others determined acceptable levels of exposure for single and repeated exposures. A distinction is made between acceptable exposure for acute and chronic toxicity, but these are really the extremes of a possible continuous range of exposures. A further distinction can be made between routine exposure and exposure required for emergency treatment, where a higher risk of oxygen toxicity may be justified to achieve a reduction of a more critical injury, particularly when in a relatively safe controlled and monitored environment. [ 34 ] [ 93 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1703", "contents": "The Repex (repetitive exposure) method, developed in 1988, allows oxygen toxicity dosage to be calculated using a single dose value equivalent to 1 minute of 100% oxygen at atmospheric pressure called an Oxygen Tolerance Unit (OTU), and is used to avoid toxic effects over several days of operational exposure. Some dive computers will automatically track the dosage based on measured depth and selected gas mixture. The limits allow a greater exposure when the person has not been exposed recently, and daily allowable dose decreases with an increase in consecutive days with exposure. [ 34 ]  These values may not be fully supported by current data. [ 107 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1704", "contents": "A more recent proposal uses a simple power equation, Toxicity Index (TI) = t 2  \u00d7 P O 2 c , where t is time and c is the power term. This was derived from the chemical reactions producing reactive oxygen or nitrogen species, and has been shown to give good predictions for CNS toxicity with c = 6.8 and for pulmonary toxicity for c = 4.57. [ 107 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1705", "contents": "For pulmonary toxicity, time is in hours, and P O 2  in atmospheres absolute, TI should be limited to 250."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1706", "contents": "For CNS toxicity, time is in minutes, P O 2  in atmospheres absolute, and a TI of 26,108 indicates a 1% risk."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1707", "contents": "Although the convulsions caused by central nervous system oxygen toxicity may lead to incidental injury to the victim, it remained uncertain for many years whether damage to the nervous system following the seizure could occur and several studies searched for evidence of such damage. An overview of these studies by Bitterman in 2004 concluded that following removal of breathing gas containing high fractions of oxygen, no long-term neurological damage from the seizure remains. [ 21 ] [ 108 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1708", "contents": "The majority of infants who have survived following an incidence of bronchopulmonary dysplasia will eventually recover near-normal lung function, since lungs continue to grow during the first 5\u20137 years and the damage caused by bronchopulmonary dysplasia is to some extent reversible (even in adults). However, they are likely to be more susceptible to respiratory infections for the rest of their lives and the severity of later infections is often greater than that in their peers. [ 109 ] [ 110 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1709", "contents": "Retinopathy of prematurity (ROP) in infants frequently regresses without intervention and eyesight may be normal in later years. Where the disease has progressed to the stages requiring surgery, the outcomes are generally good for the treatment of stage 3 ROP, but are much worse for the later stages. Although surgery is usually successful in restoring the anatomy of the eye, damage to the nervous system by the progression of the disease leads to comparatively poorer results in restoring vision. The presence of other complicating diseases also reduces the likelihood of a favourable outcome. [ 111 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1710", "contents": "Provision of supplementary oxygen remains of life-saving importance in critical care, and can increase survival in some chronic conditions, but hyperoxia and the formation of reactive oxygen species is involved in the pathogenesis of several life-threatening diseases. The toxic effects of hyperoxia are particularly prevalent in the pulmonary compartment, and cerebral and coronary circulations are at risk when vascular changes occur. Long-term hyperoxia harms the immune responses and susceptibility to infectious complications and tissue injury are increased. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1711", "contents": "The incidence of central nervous system toxicity among divers has decreased since the Second World War, as protocols have developed to limit exposure and partial pressure of oxygen inspired. In 1947, Donald recommended limiting the depth allowed for breathing pure oxygen to 7.6\u00a0m (25\u00a0ft), which equates to an oxygen partial pressure of 1.8\u00a0bar (180\u00a0kPa). [ 112 ]  Over time this limit has been reduced, until today a limit of 1.4\u00a0bar (140\u00a0kPa) during a recreational dive and 1.6\u00a0bar (160\u00a0kPa) during shallow decompression stops is generally recommended, [ 113 ]  though military divers using oxygen rebreathers may operate to greater depths for limited periods, at greater risk. [ 114 ]  Oxygen toxicity has now become a rare occurrence other than when caused by equipment malfunction and human error. Historically, the U.S. Navy has refined its Navy Diving Manual air and mixed gas tables to reduce oxygen toxicity incidents. Between 1995 and 1999, reports showed 405 surface-supported dives using the helium\u2013oxygen tables; of these, oxygen toxicity symptoms were observed on 6 dives (1.5%). As a result, the U.S. Navy in 2000 modified the schedules and conducted field tests of 150 dives, none of which produced symptoms of oxygen toxicity. Revised tables were published in 2001. [ 115 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1712", "contents": "Central nervous system oxygen toxicity among patients undergoing hyperbaric oxygen therapy is rare, and is influenced by a number of a factors: individual sensitivity and treatment protocol; and probably  therapy indication  and equipment used. A study by Welslau in 1996 reported 16 incidents out of a population of 107,264 patients (0.015%), while Hampson and Atik in 2003 found a rate of 0.03%. [ 116 ] [ 117 ]  Yildiz, Ay and Qyrdedi, in a summary of 36,500 patient treatments between 1996 and 2003, reported only 3 oxygen toxicity incidents, giving a rate of 0.008%. [ 116 ]  A later review of over 80,000 patient treatments revealed an even lower rate: 0.0024%. The reduction in incidence may be partly due to use of a mask rather than a hood to deliver oxygen as there is less  dead space  in a mask. [ 118 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1713", "contents": "The overall risk of CNS toxicity may be as high as 1 in 2000 to 3000 treatments. but it varies with the pressure and may be as high as 1 in 200 at higher pressure treatment schedules of 2.8 to 3.0 ATA, or as low as 1 in 10,000 for schedules at 2 ATA or less. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1714", "contents": "Bronchopulmonary dysplasia is among the most common complications of  prematurely born  infants and its incidence has grown as the survival of extremely premature infants has increased. Nevertheless, the severity has decreased as better management of supplemental oxygen has resulted in the disease now being related mainly to factors other than hyperoxia. [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1715", "contents": "In 1997 a summary of studies of neonatal intensive care units in industrialised countries showed that up to 60% of  low birth weight  babies developed retinopathy of prematurity, which rose to 72% in extremely low birth weight babies, defined as less than 1\u00a0kg (2.2\u00a0lb) at birth. However, severe outcomes are much less frequent: for very low birth weight babies\u2014those less than 1.5\u00a0kg (3.3\u00a0lb) at birth\u2014the incidence of blindness was found to be no more than 8%. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1716", "contents": "Administration of supplemental oxygen is extensively and effectively used in emergency and intensive care medicine, but the reactive oxygen species caused by excessive oxygenation tend to cause a vicious cycle of tissue injury, characterized by cell damage, cell death, and inflammation, mostly in the lungs, which can exacerbate problems of tissue oxygenation for which the supplemental oxygen was intended as  a treatment. Similar problems can occur in oxygen therapy for chronic conditions which involve hypoxia. Careful titration of oxygen supply to minimise the excess to physiological need also reduces pulmonary hyperoxic exposure to the reasonably practicable minimum. [ 38 ]  The incidence of pulmonary symptoms of oxygen toxicity is about 5%, and some drugs can increase the risk, such as the chemotherapeutic agent\u00a0bleomycin. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1717", "contents": "Central nervous system toxicity was first described by  Paul Bert  in 1878. [ 119 ] [ 120 ]  He showed that oxygen was toxic to insects,  arachnids ,  myriapods , molluscs, earthworms, fungi, germinating seeds, birds, and other animals. Central nervous system toxicity may be referred to as the \"Paul Bert effect\". [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1718", "contents": "Pulmonary oxygen toxicity was first described by J. Lorrain Smith in 1899 when he noted central nervous system toxicity and discovered in experiments in mice and birds that 0.43\u00a0bar (43\u00a0kPa) had no effect but 0.75\u00a0bar (75\u00a0kPa) of oxygen was a pulmonary irritant. [ 33 ]  Pulmonary toxicity may be referred to as the \"Lorrain Smith effect\". [ 16 ]  The first recorded human exposure was undertaken in 1910 by Bornstein when two men breathed oxygen at 2.8\u00a0bar (280\u00a0kPa) for 30\u00a0minutes, while he went on to 48\u00a0minutes with no symptoms. In 1912, Bornstein developed cramps in his hands and legs while breathing oxygen at 2.8\u00a0bar (280\u00a0kPa) for 51\u00a0minutes. [ 3 ]  Smith then went on to show that intermittent exposure to a breathing gas with less oxygen permitted the lungs to recover and delayed the onset of pulmonary toxicity. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1719", "contents": "Albert R. Behnke   et al.  in 1935 were the first to observe  visual field  contraction ( tunnel vision ) on dives between 1.0\u00a0bar (100\u00a0kPa) and 4.1\u00a0bar (410\u00a0kPa). [ 121 ] [ 122 ]  During World War II, Donald and Yarbrough  et al.  performed over 2,000 experiments on oxygen toxicity to support the initial use of closed circuit oxygen  rebreathers . [ 46 ] [ 123 ]  Naval divers in the early years of  oxygen rebreather  diving developed a mythology about a monster called \"Oxygen Pete\", who lurked in the bottom of the Admiralty Experimental Diving Unit \"wet pot\" (a water-filled  hyperbaric chamber ) to catch unwary divers. They called having an oxygen toxicity attack \"getting a Pete\". [ 124 ] [ 125 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1720", "contents": "In the decade following World War II,  Lambertsen   et al.  made further discoveries on the effects of breathing oxygen under pressure and methods of prevention. [ 126 ] [ 127 ]  Their work on intermittent exposures for extension of oxygen tolerance and on a model for prediction of pulmonary oxygen toxicity based on pulmonary function are key documents in the development of  standard operating procedures  when breathing increased pressures of oxygen. [ 128 ]  Lambertsen's work showing the effect of carbon dioxide in decreasing time to onset of central nervous system symptoms has influenced work from current exposure  guidelines  to future  breathing apparatus  design. [ 23 ] [ 24 ] [ 129 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1721", "contents": "Retinopathy of prematurity was not observed before World War II, but with the availability of supplemental oxygen in the decade following, it rapidly became one of the principal causes of infant blindness in developed countries. By 1960 the use of oxygen had become identified as a risk factor and its administration restricted. The resulting fall in retinopathy of prematurity was accompanied by a rise in infant mortality and  hypoxia -related complications. Since then, more sophisticated monitoring and diagnosis have established protocols for oxygen use which aim to balance between hypoxic conditions and problems of retinopathy of prematurity. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1722", "contents": "Bronchopulmonary dysplasia was first described by Northway in 1967, who outlined the conditions that would lead to the diagnosis. [ 130 ]  This was later expanded by Bancalari and in 1988 by Shennan, who suggested the need for supplemental oxygen at 36\u00a0weeks could predict long-term outcomes. [ 131 ]  Nevertheless, Palta  et al.  in 1998 concluded that  radiographic  evidence was the most accurate predictor of long-term effects. [ 132 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1723", "contents": "Bitterman  et al.  in 1986 and 1995 showed that  darkness  and  caffeine  would delay the onset of changes to  brain electrical activity  in rats. [ 25 ] [ 26 ]  In the years since, research on central nervous system toxicity has centred on methods of prevention and safe extension of tolerance. [ 133 ]  Sensitivity to central nervous system oxygen toxicity has been shown to be affected by factors such as  circadian rhythm , drugs, age, and gender. [ 134 ] [ 135 ] [ 136 ] [ 137 ]  In 1988, Hamilton  et al.  wrote procedures for the National Oceanic and Atmospheric Administration to establish oxygen exposure limits for  habitat  operations. [ 85 ] [ 86 ] [ 87 ]  Even today, models for the prediction of pulmonary oxygen toxicity do not explain all the results of exposure to high partial pressures of oxygen. [ 138 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1724", "contents": "Recreational scuba divers  commonly breathe  nitrox  containing up to 40% oxygen, while  technical divers  use pure oxygen or nitrox containing up to 80% oxygen to accelerate decompression. Divers who breathe oxygen fractions greater than of air (21%) need to be educated on the dangers of oxygen toxicity and how to manage the risk. [ 76 ]  To buy nitrox, a diver may be required to show evidence of relevant qualification. [ 139 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1725", "contents": "Since the late 1990s the recreational use of oxygen has been promoted by oxygen bars, where customers breathe oxygen through a  nasal cannula . Claims have been made that this reduces stress, increases energy, and lessens the effects of hangovers and headaches, despite the lack of any scientific evidence to support them. [ 140 ]  There are also devices on sale that offer \"oxygen massage\" and \"oxygen detoxification\" with claims of removing body toxins and reducing body fat. [ 141 ]  The  American Lung Association  has stated \"there is no evidence that oxygen at the low flow levels used in bars can be dangerous to a normal person's health\", but the U.S.  Center for Drug Evaluation and Research  cautions that people with heart or lung disease need their supplementary oxygen carefully regulated and should not use oxygen bars. [ 140 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1726", "contents": "Victorian society had a fascination for the rapidly expanding field of science. In \" Dr. Ox's Experiment \", a short story written by  Jules Verne  in 1872, the eponymous doctor uses  electrolysis of water  to separate oxygen and hydrogen. He then pumps the pure oxygen throughout the town of Quiquendone, causing the normally tranquil inhabitants and their animals to become aggressive and plants to grow rapidly. An explosion of the hydrogen and oxygen in Dr Ox's factory brings his experiment to an end. Verne summarised his story by explaining that the effects of oxygen described in the tale were his own invention (they are not in any way supported by empirical evidence). [ 142 ]   There is also a brief episode of oxygen intoxication in his \" From the Earth to the Moon \". [ 143 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1727", "contents": "The following external sites contain resources specific to particular topics:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1728", "contents": "Paroxysmal nocturnal dyspnea  or  paroxysmal nocturnal dyspnoea  ( PND ) is an attack of severe  shortness of breath  and coughing that generally occurs at night. [ 1 ]  It usually awakens the person from sleep, and may be quite frightening. [ 2 ]  PND, as well as simple  orthopnea , may be relieved by sitting upright at the side of the bed with legs dangling, as symptoms typically occur when the person is recumbent, or lying down. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1729", "contents": "Since paroxysmal nocturnal dyspnea occurs mainly because of heart or lung problems, common risk factors include those that affect the function of the heart and lungs. Risk factors for cardiac diseases include high blood pressure, high cholesterol, diabetes, obesity, and a lifestyle lacking exercise and a healthy diet. Risk factors for lung diseases include tobacco use, including second hand smoke, pollution, exposure to hazardous fumes, and allergens. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1730", "contents": "PND can be explained by mechanisms similar to those of  orthopnea  and typical dyspnea. When a person is recumbent, or is lying down, blood is redistributed from the lower extremities and abdominal cavity ( splanchnic circulation ) to the lungs. [ 5 ]  Failure to accommodate this redistribution results in decreased  vital capacity  and  pulmonary compliance , further causing the shortness of breath experienced in PND.  In addition to the redistribution of blood in the body, most cases of dyspnea are accompanied by an increase in the overall work of breathing, often caused by abnormal pulmonary mechanisms.  [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1731", "contents": "The perception of dyspnea is theorized to be a complicated connection between peripheral receptors,  neural pathways , and the  central nervous system .  [ 5 ]  Receptors in the chest wall and central airways, as well receptors in the respiratory center of the central nervous system, produce an increased requirement for ventilation which is not matched by respiratory output, resulting in the conscious recognition of dyspnea.  [ 5 ]  Respiratory muscles and vagal afferent neural pathways relay information from the chest wall/airways to the central nervous system, facilitating the presentation of dyspnea.  [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1732", "contents": "In people with underlying  congestive heart failure , this redistribution may overload the pulmonary circulation, causing increased  pulmonary congestion . In congestive heart failure, left ventricular dysfunction will also increase pulmonary congestion, so further congestion caused by the redistribution of blood volume upon laying down will worsen any dyspnea. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1733", "contents": "Other theories exist for why PND occurs, especially in those where PND only occurs while sleeping. Theories include decreased responsiveness of the  respiratory center  in the brain and decreased adrenergic activity in the  myocardium  during sleep. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1734", "contents": "Paroxysmal nocturnal dyspnea is a serious medical symptom that can develop into worsening conditions. Many tests can be done in order to evaluate the cause of paroxysmal nocturnal dyspnea. Because it is commonly associated with  heart failure , tests that may be run mainly focus on measuring the function and capability of the heart. Common tests may include an echocardiography, cardiac magnetic resonance imaging (MRI), coronary artery angiogram,  chest x-ray  or chest CT scan, blood tests, physical exams, or a myocardial biopsy. The diagnostic workup will vary depending on the suspected cause. [ 6 ]  For example, for people who enter the emergency room with shortness of breath, a diagnosis is achieved through a physical examination, electrocardiography, chest radiograph, and if necessary, a serum BNP level. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1735", "contents": "As a subjective symptom self-reported by people,  dyspnea  is difficult to characterize since its severity cannot be measured. Dyspnea can come in many forms, but it is commonly known as shortness of breath or having difficulty breathing. People presenting with dyspnea usually show signs of rapid and shallow breathing, use of their respiratory accessory muscles, and may have underlying conditions causing the dyspnea, such as cardiac or pulmonary diseases. [ 5 ]  With paroxysmal nocturnal dyspnea specifically, it is felt while sleeping and causes a person to wake up after about 1 to 2 hours of sleep. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1736", "contents": "More serious forms of dyspnea can be identified through accompanying findings, such as low blood pressure, decreased respiratory rate, altered mental status, hypoxia, cyanosis, stridor, or unstable arrhythmias.  [ 4 ]  When these symptoms accompany PND, it is typically a red flag that something more serious is causing the dyspnea presentation and should be evaluated further.  [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1737", "contents": "Paroxysmal nocturnal dyspnea is a common symptom of several heart conditions such as heart failure with preserved ejection fraction, in addition to  asthma ,  chronic obstructive pulmonary disease , and  sleep apnea . [ 8 ]  Other symptoms that may be seen alongside paroxysmal nocturnal dyspnea are weakness, orthopnea, edema, fatigue, and dyspnea. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1738", "contents": "Dyspnea affects about 25% of people in the ambulatory care setting and is a common symptom of many underlying conditions. [ 9 ]  Dyspnea is a subjective symptom, meaning it can only be expressed by the person experiencing it, and it is imperative in diagnosis to distinguish it from other breathing problems. [ 5 ]  Dyspnea is typically the sensation of feeling short of breath and should not be confused with rapid breathing ( tachypnea ), excessive breathing ( hyperpnea ) or  hyperventilation . [ 5 ]  Once dyspnea is properly identified, it is important to differentiate between acute and chronic dyspnea, typically through a detailed physical exam and observation of the person's breathing patterns. [ 9 ]  The most common causes of dyspnea are cardiac (cardiac asthma) [ 10 ]  and pulmonary conditions, like congestive heart failure with preserved  ejection fraction ,  COPD , or  pneumonia . [ 9 ]  Less commonly, some cases of dyspnea can be attributed to neuromuscular diseases of the chest wall or anxiety.  [ 5 ]  When distinguishing PND from typical dyspnea, it is important to identify common characteristics of PND. Some important criteria to identify are temporal characteristics (i.e., acute or chronic onset, intermittent or persistent symptoms), situational characteristics (i.e., symptoms at rest, upon exertion, upon different body positions, or upon special exposures), and pathogenic characteristics (i.e., physiologic or mental conditions). [ 9 ]  PND typically presents at night during sleep, especially while the person is laying down, distinguishing PND from typical dyspnea. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1739", "contents": "Treatment for paroxysmal nocturnal dyspnea depends on the underlying cause. If the underlying cause is  heart failure  with preserved ejection fraction ( HFpEF , when part of the heart does not fill properly with blood), treatments can include diuretics, beta blockers, and ACE inhibitors.  [ 9 ]  Another potential underlying cause of PND is  central sleep apnea  (CSA) with  Cheyne-Stokes Breathing  (CSB), for which the treatment recommended by the  American Academy of Sleep Medicine  is continuous positive airway pressure ( CPAP ) and nocturnal home oxygen therapy (HOT). [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1740", "contents": "The shortness of breath sensation felt from PND can typically be relieved by maintaining an upright position while sleeping. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1741", "contents": "While a small source of data exists on the prevalence of PND, a large pool of data exists on the epidemiology of dyspnea in general. Reports show that 7.4% of people reporting to the emergency room identify dyspnea as one of their symptoms, with 1-4% of people identifying dyspnea as their primary concern.  [ 9 ]  Dyspnea is often the cause of situational changes in a person's environment or activity. For example, 10% of people complain of dyspnea while walking on flat ground to their primary care provider (PCP),  [ 9 ]  while 25% of people complain of dyspnea upon more intense exertion (i.e. climbing stairs or a hill) to their PCP.  [ 9 ]  Of these people seeing a PCP, 1-4% see their provider for dyspnea specifically.  [ 9 ]  After identifying the cause of dyspnea, most people continue on to see a specialist to manage dyspnea presentation and address underlying conditions. Roughly 15-50% of people who are regularly seen by a  cardiologist  are seen in regard to dyspnea symptoms,  [ 9 ]  while just under 60% of people regularly see a pneumonologist in regard to their dyspnea.  [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1742", "contents": "Additionally, there have been epidemiological studies performed on central sleep apnea in heart failure. Central sleep apnea in heart failure's epidemiology is relevant, as sleep apnea and heart failure have both been associated in people with paroxysmal nocturnal dyspnea. [ 12 ]  According to the study, researchers were able to conclude that ~70% of people with heart failure had breathing disorders while they slept, while half of that ~70% also experienced central sleep apnea with Cheyne Stokes respiration (CSA-CSR). [ 12 ]   Atrial fibrillation , the male gender, an age greater than 60, and awake  PaCO 2  being less than or equal to 38\u00a0mm Hg were all risk factors associated with CSA-CSR."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1743", "contents": "Pregnancy"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1744", "contents": "In people who are pregnant, the presence of paroxysmal nocturnal dyspnea is abnormal. Further investigation and diagnostic tests should be done in order to prevent harm to the fetus and to the mother. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1745", "contents": "Hypereosinophilic Syndrome (HES)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1746", "contents": "Hypereosinophilic syndrome  is a combination of rare complications that are explained by an increased amount of serum and persistent tissue eosinophilia. [ 14 ]  An uncommon disorder that is known to be associated with Hypereosinophilic Syndrome is  L\u00f6ffler endocarditis . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1747", "contents": "The  pathophysiology of acute respiratory distress syndrome  involves  fluid accumulation in the lungs  not explained by heart failure (noncardiogenic pulmonary edema). It is typically provoked by an acute injury to the lungs that results in flooding of the  lungs' microscopic air sacs  responsible for the exchange of gases such as oxygen and carbon dioxide with  capillaries  in the lungs. [ 1 ]  Additional common findings in ARDS include partial collapse of the lungs ( atelectasis ) and low levels of oxygen in the blood ( hypoxemia ). The clinical syndrome is associated with pathological findings including pneumonia,  eosinophilic pneumonia ,  cryptogenic organizing pneumonia , acute fibrinous organizing pneumonia, and  diffuse alveolar damage (DAD) . Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung tissue. The triggering insult to the tissue usually results in an initial release of  chemical signals  and other inflammatory mediators secreted by local  epithelial  and  endothelial  cells."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1748", "contents": "Neutrophils  and some  T-lymphocytes  quickly migrate into the inflamed lung tissue and contribute in the amplification of the phenomenon. Typical histological presentation involves diffuse  alveolar  damage and  hyaline  membrane formation in alveolar walls. Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1749", "contents": "Inflammation, such as that caused by sepsis, causes  endothelial cell  dysfunction, fluid leakage from capillaries and impairs drainage of fluid from the lungs. Elevated inspired oxygen concentration often becomes necessary at this stage, and may facilitate a ' respiratory burst ' in immune cells. In a secondary phase, endothelial cell dysfunction causes cells and inflammatory exudate to enter the alveoli. This  pulmonary edema  increases the thickness of the layer separating the blood in the capillary from the space in the air sacs, which increases the distance the oxygen must diffuse to reach the blood. This impairs gas exchange and leads to hypoxia, increased work of breathing, and eventually induces  scarring  of the air sacs of the lungs. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1750", "contents": "Fluid accumulation in the lungs and decreased surfactant production by  type II pneumocytes  may cause whole  air sacs  to collapse or to completely fill with fluid. This  loss of aeration  contributes further to the  right-to-left shunt  in ARDS. A traditional right-to-left shunt refers to blood passing from the right side of the heart to the left side without traveling to the capillaries of the lung for more oxygen (e.g., as seen in a  patent foramen ovale ). In ARDS, a lung right-to-left shunting occurs within the lungs since some blood from the right side of the heart will enter capillaries which cannot exchange gas with damaged air sacs that are full of fluid and debris from ARDS. As the alveoli contain progressively less gas, the blood flowing through the alveolar capillaries is progressively less oxygenated, resulting in massive shunting within the lung. The collapse of the air sacs and small  airways  interferes with the process of normal gas exchange. It is common to see patients with a Pa O 2  of 60  mmHg  (8.0  kPa ) despite mechanical ventilation with 100% inspired oxygen. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1751", "contents": "The loss of aeration may follow different patterns depending upon the nature of the underlying disease and other factors. These are usually distributed to the lower  lobes  of the lungs, in their posterior segments, and they roughly correspond to the initial infected area. In sepsis or trauma-induced ARDS, infiltrates are usually more patchy and diffuse. The posterior and basal segments are always more affected, but the distribution is even less homogeneous. Loss of aeration also causes important changes [ vague ]  in lung mechanical properties that are fundamental in the process of inflammation amplification and progression to ARDS in mechanically ventilated patients."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1752", "contents": "As the loss of aeration and the underlying disease progress, the end  tidal volume  grows to a level incompatible with life. Thus, mechanical ventilation is initiated to relieve muscles responsible for supporting breathing (respiratory muscles) of their work and to protect the affected person's  airway . However, mechanical ventilation may constitute a risk factor for the development\u2014or the worsening\u2014of ARDS. [ 2 ]  Aside from the infectious complications arising from invasive ventilation with  endotracheal intubation , positive-pressure ventilation directly alters lung mechanics during ARDS. When these techniques are used the result is higher mortality through  barotrauma . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1753", "contents": "In 1998, Amato  et al.  published a paper showing substantial improvement in the outcome of patients ventilated with lower tidal volumes ( V t ) (6 mL\u00b7kg \u22121 ). [ 2 ] [ 3 ]  This result was confirmed in a 2000 study sponsored by the  NIH . [ 4 ]  Both studies were widely criticized for several reasons, and the authors were not the first to experiment with lower-volume ventilation, but they increased the understanding of the relationship between mechanical ventilation and ARDS. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1754", "contents": "This form of stress is thought to be applied by the  transpulmonary pressure  ( gradient ) ( P l ) generated by the ventilator or, better, its cyclical variations. The better outcome obtained in individuals ventilated with a lower  V t  may be interpreted as a beneficial effect of the lower  P l ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1755", "contents": "The way  P l  is applied on the alveolar surface determines the  shear stress  to which alveoli are exposed. ARDS is characterized by a usually heterogeneous reduction of the airspace, and thus by a tendency towards higher  P l  at the same  V t , and towards  higher  stress on  less  diseased units. The heterogeneity of alveoli at different stages of disease is further increased by the gravitational gradient to which they are exposed and the different  perfusion pressures  at which blood flows through them."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1756", "contents": "The different mechanical properties of alveoli in ARDS may be interpreted as having varying  time constants \u2014the product of alveolar  compliance  \u00d7  resistance . Slow alveoli are said to be \"kept open\" using  PEEP , a feature of modern ventilators which maintains a positive airway pressure throughout the whole respiratory cycle. A higher mean pressure cycle-wide slows the collapse of diseased alveoli, but it has to be weighed against the corresponding elevation in  P l /plateau pressure. Newer ventilatory approaches attempt to maximize mean airway pressure for its ability to \"recruit\" collapsed alveoli while minimizing the shear stress caused by frequent openings and closings of aerated units. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1757", "contents": "Mechanical ventilation can worsen the inflammatory response in people with ARDS by inducing hyperinflation of the alveoli and/or increased shear stress with frequent opening and closing of collapsible alveoli. [ 5 ]  The stress index is measured during constant-flow volume assist-control mechanical ventilation without changing the baseline ventilatory pattern. Identifying the steadiest portion of the inspiratory flow (F) waveform fit the corresponding portion of the airway pressure (Paw) waveform in the following power equation: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1758", "contents": "Paw = a \u00d7 t b  + c\nwhere the coefficient b\u2014the Stress Index\u2014describes the shape of the curve. The Stress Index depicts a constant compliance if the value is around 1, an increasing compliance during the inspiration if the value is below 1, and a decreasing compliance if the value is above 1. Ranieri, Grasso, et al. set a strategy guided by the stress index with the following rules:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1759", "contents": "Alveolar hyperinflation in patients with focal ARDS ventilated with the ARDSnet protocol is attenuated by a physiologic approach to PEEP setting based on the stress index measurement. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1760", "contents": "If the underlying disease or injurious factor is not removed, the quantity of inflammatory mediators released by the lungs in ARDS may result in a  systemic inflammatory response syndrome  (SIRS) or sepsis if there is lung infection. [ 2 ]  The evolution towards  shock  or  multiple organ dysfunction syndrome  follows paths analogous to the pathophysiology of sepsis. This leads to the impaired oxygenation, which is the central problem of ARDS, as well as to  respiratory acidosis . Respiratory acidosis in ARDS is often caused by ventilation techniques such as  permissive hypercapnia , which attempt to limit  ventilator-induced lung injury  in ARDS. The result is a critical illness in which the 'endothelial disease' of severe sepsis or SIRS is worsened by the lung dysfunction, which further impairs oxygen delivery to cells. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1761", "contents": "Pea soup fog  (also known as a  pea souper ,  black fog  or  killer fog ) is a very thick and often yellowish, greenish or blackish fog caused by  air pollution  that contains  soot   particulates  and the poisonous gas  sulphur dioxide . This very thick  smog  occurs in cities and is derived from the smoke given off by the burning of  soft coal  for home heating and in industrial processes. Smog of this intensity is often lethal to vulnerable people such as the elderly, the very young (infants) and those with  respiratory problems . The result of these phenomena was commonly known as a  London particular  or  London fog ; in a reversal of the idiom, \"London particular\" became the name for a thick  pea and ham soup . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1762", "contents": "From as early as the 13th century, [ 2 ] [ 3 ]  air pollution became increasingly prevalent, and a predominant perception in the 13th century was that  sea-coal [ 4 ]  smoke would affect one's health. [ 5 ] [ 6 ]  From the mid-17th century, in British cities, especially  London , the incidence of ill-health was attributed to coal smoke from both domestic and industrial  chimneys  combining with the mists and fogs of the  Thames Valley . [ 7 ]   Luke Howard , a pioneer in  urban climate  studies, published  The Climate of London  in 1818\u20131820, in which he uses the term \"city fog\" and describes the  heat island  effect which concentrated the accumulation of smog over the city. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1763", "contents": "In 1880,  Francis Albert Rollo Russell , son of former  prime minister   John Russell, 1st Earl Russell , published a leaflet that blamed home hearth smoke, rather than factories' smoke, for damaging the city's important buildings, depriving vegetation of sunlight, and increasing the expense and effort of laundering clothes. Furthermore, he charged the \"perpetually present\" sulphurous smoke with increasing bronchitis and other respiratory diseases. More than 2,000 Londoners had \"literally choked to death\", he wrote, on account of \"a want of carefulness in preventing smoke in our domestic fires\" which emitted coal smoke from \"more than a million chimneys\" that, when combined with the prolonged fogs of late January and early February 1880, fatally aggravated pre-existing lung conditions and was \"more fatal than the slaughter of many a great battle\". [ 9 ] [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1764", "contents": "The difficulties of driving through the fog were vividly described in the  Autocar  magazine, with an otherwise straightforward 45 mile car journey on the night of 12 December 1946 taking over eight hours to complete. At times, the passenger had to get out and walk alongside the car to see the kerb and operate the steering through the side window while the driver operated the pedals. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1765", "contents": "The most lethal incidence of this smog in London  occurred in 1952  and resulted in the  Clean Air Act 1956  and  Clean Air Act 1968 , both now repealed and consolidated into the  Clean Air Act 1993 , which were effective in largely removing sulphur dioxide and coal smoke, the causes of pea soup fog, though these have been replaced by less visible pollutants that derive from vehicles in urban areas. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1766", "contents": "Reference to the sources of smog, along with the earliest extant use of \"pea-soup\" as a descriptor, is found in a report by  John Sartain  published in 1820 on life as a young artist, recounting what it was like to"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1767", "contents": "slink home through a fog as thick and as yellow as the pea-soup of the eating house; return to your painting room ... having opened your window at going out, to find the stink of the paint rendered worse, if possible, by the entrance of the fog, which, being a compound from the effusions of gas pipes, tan yards, chimneys, dyers, blanket scourers, breweries, sugar bakers, and soap boilers, may easily be imagined not to improve the smell of a painting room! [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1768", "contents": "An 1871  New York Times  article refers to \"London, particularly, where the population are periodically submerged in a fog of the consistency of pea soup\". The fogs caused large numbers of deaths from respiratory problems. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1769", "contents": "King Edward I  of England banned the burning of  sea-coal  by proclamation in  London  in 1272, after its smoke became a problem. [ 17 ] [ 18 ]  By the 17th century London's  pollution  had become a serious problem, still due, in particular, to the burning of cheap, readily available sea coal. [ 7 ]  John Evelyn, advisor to  Charles II of England , defined the problem in his pamphlet,  Fumifugium: Or, the Inconvenience of the Aer and Smoak of London Dissipated [ 19 ] [ 20 ] [ 21 ]  published in 1661, blaming coal, a \"subterrany fuel\" that had \"a kind of virulent or arsenical vapour arising from it\" for killing many. He proposed the relocation of industry out of the city and the planting of massive gardens of \" odiferous  flowers\" to \"tinge the air\" and thus mask the pollution."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1770", "contents": "The worst recorded instance was the  Great Smog of 1952 , when 4,000 deaths were reported in the city over a couple of days, and a subsequent 8,000 related deaths, leading to the passage of the  Clean Air Act 1956 , which banned the use of coal for domestic fires in some urban areas. [ 15 ]  The overall death toll from that incident is now believed to be around 12,000. [ 22 ] [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1771", "contents": "Perinatal asphyxia  (also known as  neonatal asphyxia  or  birth asphyxia ) is the medical condition resulting from  deprivation of oxygen  to a newborn infant that lasts long enough during the  birth process  to cause physical harm, usually to the brain. It remains a serious condition which causes significant mortality and  morbidity . It is also the inability to establish and sustain adequate or spontaneous  respiration  upon delivery of the newborn, an emergency condition that requires adequate and quick  resuscitation  measures. Perinatal asphyxia is also an oxygen deficit from the 28th week of  gestation  to the first seven days following delivery. It is also an  insult  to the  fetus  or newborn due to lack of oxygen or lack of  perfusion  to various organs and may be associated with a lack of  ventilation . In accordance with  WHO , perinatal asphyxia is characterised by: profound  metabolic acidosis , with a  pH  less than 7.20 on  umbilical cord  arterial  blood sample , persistence of an  Apgar score  of 3 at the 5th minute, clinical neurologic sequelae in the immediate neonatal period, or evidence of multiorgan system dysfunction in the immediate neonatal period. Hypoxic damage can occur to most of the infant's organs ( heart ,  lungs ,  liver ,  gut ,  kidneys ), but  brain damage  is of most concern and perhaps the least likely to quickly or completely heal. In more pronounced cases, an infant will survive, but with damage to the brain manifested as either mental, such as developmental delay or  intellectual disability , or physical, such as  spasticity ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1772", "contents": "It results most commonly from  antepartum  causes like a drop in maternal  blood pressure  or some other substantial interference with blood flow to the infant's brain during delivery. This can occur due to inadequate  circulation  or perfusion, impaired respiratory effort, or inadequate ventilation. Perinatal asphyxia happens in 2 to 10 per 1000 newborns that are born at term, and more for those that are born prematurely. [ 1 ]  WHO estimates that 4 million neonatal deaths occur yearly due to birth asphyxia, representing 38% of deaths of children under 5 years of age. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1773", "contents": "Perinatal asphyxia can be the cause of  hypoxic ischemic encephalopathy  or  intraventricular hemorrhage , especially in  preterm births . An infant with severe perinatal asphyxia usually has poor color ( cyanosis ), perfusion, responsiveness, muscle tone, and respiratory effort, as reflected in a low 5 minute  Apgar score . Extreme degrees of asphyxia can cause  cardiac arrest  and death. If resuscitation is successful, the infant is usually transferred to a  neonatal intensive care unit ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1774", "contents": "There has long been a scientific debate over whether newborn infants with asphyxia should be resuscitated with 100% oxygen or normal air. [ 3 ]  It has been demonstrated that high concentrations of oxygen lead to generation of oxygen  free radicals , which have a role in  reperfusion injury  after asphyxia. [ 4 ]  Research by  Ola Didrik Saugstad  and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen. [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1775", "contents": "There is considerable controversy over the diagnosis of birth asphyxia due to medicolegal reasons. [ 7 ] [ 8 ]  Because of its lack of precision, the term is eschewed in modern obstetrics. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1776", "contents": "Basically, understanding of the etiology of perinatal asphyxia provides the platform on which to build on its pathophysiology. The  general principles guiding the causes and the pathophysiology of perinatal asphyxia are grouped into antepartum causes and intra partum causes. As these are the various points to which insults can occur to the foetus.  [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1777", "contents": "A 2008 bulletin from the  World Health Organization  estimates that 900,000 total infants die each year from birth asphyxia, making it a leading cause of death for newborns. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1778", "contents": "In the United States,  intrauterine hypoxia  and birth asphyxia was listed as the tenth leading cause of neonatal death. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1779", "contents": "There is current controversy regarding the medicolegal definitions and impacts of birth asphyxia. Plaintiff's attorneys often take the position that birth asphyxia is often preventable, and is often due to substandard care and human error. [ 13 ]  They have utilized some studies in their favor that have demonstrated that, \"... although other potential causes exist, asphyxia and hypoxic-ihy affect a substantial number of babies, and they are preventable causes of cerebral palsy.\" [ 14 ] [ 15 ] [ 16 ]  The  American Congress of Obstetricians and Gynecologists  disputes that conditions such as cerebral palsy are usually attributable to preventable causes, instead associating them with circumstances arising prior to birth and delivery. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1780", "contents": "Pleural thickening  is an increase in the bulkiness of one or both of the  pulmonary pleurae ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1781", "contents": "Pleural plaques are patchy collections of hyalinized collagen in the parietal pleura. [ 2 ]  They have a  holly  leaf appearance on  X-ray . [ 1 ]  They are indicators of  asbestos  exposure, and the most common asbestos-induced lesion. [ 3 ]  They usually appear after 20 years or more of exposure and never degenerate into  mesothelioma . They appear as fibrous plaques on the parietal  pleura , usually on both sides, and at the posterior and inferior part of the chest wall as well as the diaphragm. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1782", "contents": "Pleuropneumonia  is inflammation of the  lungs  and  pleura ,  pleurisy  being the inflammation of the pleura alone. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1783", "contents": "Pneumomediastinum  (from  Greek   pneuma  \u2013 \"air\", also known as  mediastinal emphysema ) [ 1 ]  is  pneumatosis  (abnormal presence of air or other gas) in the  mediastinum , the central part of the  chest cavity . First described in 1819 by  Ren\u00e9 Laennec , [ 2 ] [ 3 ]  the condition can result from  physical trauma  or other situations that lead to air escaping from the  lungs , airways, or bowel into the chest cavity. In  underwater divers  it is usually the result of  pulmonary barotrauma . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1784", "contents": "The main symptom is usually severe central chest pain. Other symptoms include laboured breathing, voice distortion (as with helium) and  subcutaneous emphysema , specifically affecting the face, neck, and chest. [ 4 ]  Pneumomediastinum can also be characterized by the shortness of breath that is typical of a respiratory system problem. It is often recognized on  auscultation  by a \"crunching\" sound timed with the cardiac cycle ( Hamman's crunch ).\nPneumomediastinum may also present with symptoms mimicking cardiac tamponade as a result of the increased intrapulmonary pressure on venous flow to the heart. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1785", "contents": "It is most commonly caused by: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1786", "contents": "It has also been associated with:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1787", "contents": "It can be induced to assist thoracoscopic surgery. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1788", "contents": "It can be caused by a pulmonary  barotrauma  induced by a person moving from a higher to a lower pressure environment, such as when a  scuba or surface-supplied diver , [ 9 ] [ 10 ]  a  free-diver  after  lung-packing , [ 11 ]   or an  airplane  passenger [ 12 ]  ascends. In the case of scuba and surface supplied divers, the diver breathes gas at ambient pressure, and if this is not able to escape freely during ascent, the pressure difference will cause it to expand, and may rupture the lung tissues ( pulmonary barotrauma ), and escape to a variety of places, one of which can be the mediastinum. A diver with symptoms of mediastinal emphysema may also have any combination of  arterial gas embolism ,  pneumothorax  and  subcutaneous  or  pulmonary interstitial emphysema . Factors which may prevent free escape of the compressed breathing gas include holding the breath or respiratory obstructions such as cysts, mucus plugs, or scar tissue. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1789", "contents": "In rare cases, pneumomediastinum may also arise as a result of blunt chest trauma (e.g. car accidents, fights, over pressure of breathing apparatus), while still evolving in the same fashion as the spontaneous form. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1790", "contents": "Pneumomediastinum is most commonly seen in otherwise healthy young male patients and may not be prefaced by a relevant medical history of similar ailments. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1791", "contents": "Pneumomediastinum is uncommon and occurs when air leaks into the  mediastinum . The diagnosis can be confirmed via  chest X-ray  showing a radiolucent outline around the heart and mediastinum or via  CT scanning  of the  thorax . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1792", "contents": "The tissues in the mediastinum will slowly resorb the air in the cavity so most pneumomediastinums are treated conservatively.  Breathing high flow oxygen will increase the absorption of the air.\nIf the air is under pressure and compressing the heart, a needle may be inserted into the cavity, releasing the air.\nSurgery may be needed to repair the hole in the trachea, esophagus or bowel. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1793", "contents": "If there is lung collapse, it is imperative the affected individual lies on the side of the collapse. Although painful, this allows full inflation of the unaffected lung."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1794", "contents": "Polymer fume fever  or  fluoropolymer fever , also informally called  Teflon flu , is an inhalation fever caused by the fumes released when  polytetrafluoroethylene  (PTFE, known under the trade name  Teflon ) reaches temperatures of 300\u00a0\u00b0C (572\u00a0\u00b0F) to 450\u00a0\u00b0C (842\u00a0\u00b0F). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1795", "contents": "When PTFE is heated above 450\u00a0\u00b0C the  pyrolysis  products are different and inhalation may cause  acute lung injury . [ 2 ]  Symptoms are  flu-like  (chills, headaches and fevers) with chest tightness and mild cough. Onset occurs about 4 to 8 hours after exposure to the  pyrolysis  products of PTFE. [ 3 ]  A  high white blood cell count  may be seen and chest x-ray findings are usually minimal."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1796", "contents": "The polymer fumes are especially harmful to certain animals whose  breathing , optimized for rapidity, allows in toxins which are excluded by  human lungs . Fumes from Teflon in very high heat are fatal to  parrots , [ 4 ]  as well as some other birds (PTFE toxicosis). [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1797", "contents": "Primary ciliary dyskinesia  ( PCD ) is a rare,  autosomal   recessive   genetic   ciliopathy , that causes defects in the action of  cilia  lining the upper and lower  respiratory tract ,  sinuses ,  Eustachian tube ,  middle ear ,  fallopian tube , and  flagella  of  sperm  cells. The alternative name of \"immotile ciliary syndrome\" is no longer favored as the cilia do have movement, but are merely inefficient or unsynchronized. When accompanied by  situs inversus  the condition is known as  Kartagener syndrome . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1798", "contents": "Respiratory epithelial   motile cilia , which resemble microscopic \"hairs\" (although structurally and biologically unrelated to  hair ), are complex  organelles  that beat synchronously in the respiratory tract, moving mucus toward the throat. Normally, cilia beat 7 to 22 times per second, and any impairment can result in poor  mucociliary clearance , with subsequent upper and lower respiratory infection. Cilia also are involved in other biological processes (such as  nitric oxide  production), currently the subject of dozens of research efforts. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1799", "contents": "Around 80% of people with primary ciliary dyskinesia experience respiratory problems beginning within a day of birth. Many have a collapsed lobe of the lung and blood oxygen low enough to require treatment with supplemental oxygen. [ 1 ]  Within the first few months of life, most develop a chronic  mucus -producing cough and  runny nose . [ 1 ]  The main consequence of impaired ciliary function is reduced or absent  mucus  clearance from the  lungs , and susceptibility to chronic recurrent respiratory infections, including  sinusitis ,  bronchitis ,  pneumonia , and  otitis media .  Progressive damage to the respiratory system is common, including progressive bronchiectasis beginning in early childhood, and sinus disease (sometimes becoming severe in adults).  However, diagnosis is often missed early in life despite the characteristic signs and symptoms. [ 2 ]  In males, immotility of sperm can lead to  infertility , although conception remains possible through the use of  in vitro fertilization , there also are reported cases where sperm were able to move. [ 8 ]  Trials have also shown that there is a marked reduction in fertility in females with Kartagener's syndrome due to dysfunction of the oviductal cilia. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1800", "contents": "Many affected individuals experience  hearing loss  and show symptoms of otitis media which demonstrates variable responsiveness to the insertion of  myringotomy  tubes or  grommets . Some patients have a poor sense of smell, which is believed to accompany high  mucus  production in the sinuses (although others report normal\u00a0\u2013 or even acute\u00a0\u2013 sensitivity to smell and taste). Clinical progression of the disease is variable, with  lung transplantation  required in severe cases. Susceptibility to infections can be drastically reduced by an early diagnosis. Treatment with various chest physiotherapy techniques has been observed to reduce the incidence of lung infection and to slow the progression of bronchiectasis dramatically. Aggressive treatment of sinus disease beginning at an early age is believed to slow long-term sinus damage (although this has not yet been adequately documented). Aggressive measures to enhance clearance of mucus, prevent respiratory infections, and treat bacterial superinfections have been observed to slow lung-disease progression. The predicted incidence is 1 in approximately 7500. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1801", "contents": "PCD is a genetically  heterogeneous  disorder affecting  motile  cilia [ 4 ]  which are made up of approximately 250 proteins. [ 11 ]  Around 90% [ 12 ]  of individuals with PCD have ultrastructural defects affecting protein(s) in the outer and/or inner  dynein  arms, which give cilia their motility, with roughly 38% [ 12 ]  of these defects caused by mutations on two genes,  DNAI1  and  DNAH5 , both of which code for proteins found in the ciliary outer dynein arm. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1802", "contents": "There is an international effort to identify genes that code for inner dynein arm proteins or proteins from other ciliary structures (radial spokes, central apparatus, etc.) associated with PCD. [ 6 ]  The role of DNAH5 in  heterotaxy  syndromes and left-right asymmetry is also under investigation. At least 50 genes have been implicated in this condition. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1803", "contents": "Another gene associated with this condition is  GAS2L2 . [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1804", "contents": "This condition is genetically inherited. Structures that make up the cilia, including inner and/or outer  dynein  arms, central apparatus, radial spokes, etc. are missing or dysfunctional and thus the  axoneme  structure lacks the ability to move. Axonemes are the elongated structures that make up  cilia  and  flagella . Additionally, there may be chemical defects that interfere with ciliary function in the presence of adequate structure. Whatever the underlying cause, dysfunction of the cilia begins during and impacts the  embryologic phase  of development. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1805", "contents": "Specialised monocilia known as  nodal cilia  are at the heart of this problem. They lack the central-pair microtubules of ordinary motile cilia and so rotate clockwise rather than beat; in the  primitive node  at the anterior end of the  primitive streak  in the embryo, these are angled posteriorly [ 15 ] [ 16 ]  such that they describe a D-shape rather than a circle. [ 16 ]  This has been shown to generate a net leftward flow in mouse and chick embryos, and sweeps the  protein  to the left, triggering normal  asymmetrical development . [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1806", "contents": "However, in some individuals with PCD, mutations thought to be in the gene coding for the key structural protein left-right  dynein  ( lrd ) [ 4 ]  result in monocilia which do not rotate. There is therefore no flow generated in the node,  Shh  moves at random within it, and 50% of those affected develop  situs inversus , which can occur with or without  dextrocardia , where the laterality of the  internal organs  is the mirror-image of normal. Affected individuals therefore have Kartagener syndrome. This is not the case with some PCD-related genetic mutations: at least 6% of the PCD population have a condition called  situs ambiguus  or heterotaxy, where organ placement or development is neither typical ( situs solitus ) nor totally reversed ( situs inversus totalis ) but is a hybrid of the two. [ 6 ]  Splenic abnormalities such as  polysplenia ,  asplenia  and complex congenital heart defects are more common in individuals with situs ambiguus and PCD, as they are in all individuals with situs ambiguus. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1807", "contents": "The genetic forces linking failure of nodal cilia and situs issues and the relationship of those forces to PCD are the subject of intense research interest. However, knowledge in this area is constantly advancing. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1808", "contents": "Several diagnostic tests for this condition have been proposed. [ 5 ]  These include nasal  nitric oxide  levels as a screening test, light microscopy of biopsies for ciliary beat pattern and frequency and electron microscopic examination of  dynein  arms, as the definite diagnosis method.  Genetic testing  has also been proposed but this is difficult given that there are multiple genes involved. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1809", "contents": "When accompanied by the combination of  situs inversus  (reversal of the internal organs),  chronic sinusitis , and  bronchiectasis , it is known as  Kartagener syndrome [ 3 ]  (only 50% of primary ciliary dyskinesia cases include situs inversus). [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1810", "contents": "There are no standardized effective treatment strategies for the condition. Current therapies for PCD are extrapolated from Cystic Fibrosis and patients with non-CF bronchiectasis and lack validation for PCD-specific use. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1811", "contents": "Severe fatal respiratory failure can develop; long-term treatment with macrolides such as  clarithromycin ,  erythromycin  and  azithromycin  has been empirically applied for the treatment of primary ciliary dyskinesia in Japan, though controversial due to the effects of the medications. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1812", "contents": "There is no reliable estimate of life expectancy for people with PCD. [ 21 ]   However, there is evidence that PCD, is a life altering [ 22 ]  life shortening [ 23 ]  multi-system condition, with some people progressing to lung transplant. [ 24 ] [ 25 ] [ 26 ] [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1813", "contents": "Decline in lung function in people with PCD has been observed in most studies, [ 28 ] [ 25 ] [ 29 ] [ 30 ] [ 31 ]  with FEV1 decline causing deterioration in health, impacting on, and reducing quality of life. [ 32 ]  With such a genetically and phenotypically heterogenous group, observation of median/mean decline in lung function risks regression to the mean, missing those groups with significantly worse lung function, [ 10 ] [ 33 ] [ 34 ] [ 35 ] [ 36 ] [ 37 ] [ 38 ]  masked by those with milder phenotypes. [ 10 ] [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1814", "contents": "The recent body of published data from respected clinicians in (the United Kingdom, Europe, North America, Canada and Israel) indicate that PCD morbidity and mortality appear to have been under-estimated by the medical community. [ 28 ] [ 25 ] [ 39 ] [ 40 ] [ 41 ]  While prospective outcome data is limited due to the early-stage patient registries, there is a growing body of evidence [ 25 ] [ 39 ] [ 40 ] [ 41 ] [ 42 ]  that dispels any \"myth that PCD is a mild disease. [ 25 ] [ 39 ] [ 40 ] [ 41 ] [ 43 ] [ 44 ] [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1815", "contents": "The studies presented here demonstrate that children with PCD typically have worse lung function than those with cystic fibrosis. [ 28 ] [ 31 ] [ 29 ] [ 46 ] [ 30 ]  While previously it was thought that with early diagnosis, lung function could largely be prevented in children with PCD, [ 47 ]  it is key to note that poor lung function is repeatedly observed in children with PCD [ 46 ] [ 28 ] [ 31 ] [ 29 ]   1,30,32,33,36\u201338  and some develop bronchiectasis during [ 48 ] [ 33 ]  childhood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1816", "contents": "Research to further the understanding of cilia, with the future aims of functional restoration of motile cilia is advancing. However, charitable funding for medical research, particularly for rare disease is vital and in the UK contributes to more than 50% of grants. The UK registered charity PCD Research supports research into PCD worldwide, with the ultimate aim of funding potentially curative research. [ 7 ]  Future promising avenues for functional replacement of cilia involve antisense,  gene editing via CRISPR-Cas9  and mRNA therapies. At present there have only been a handful of interventional trials in PCD. [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1817", "contents": "The classic symptom combination associated with PCD was first described in 1904 by  A. K. Siewert , [ 50 ]  while  Manes Kartagener  published his first report on the subject in 1933. [ 51 ]  The disorder is rarely referred to as Siewert's syndrome or Siewert-Kartagener syndrome. [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1818", "contents": "Psittacosis \u2014also known as  parrot fever , and  ornithosis \u2014is a  zoonotic   infectious disease  in humans caused by a  bacterium  called  Chlamydia psittaci  and contracted from infected  parrots , such as  macaws ,  cockatiels , and  budgerigars , and from  pigeons ,  sparrows ,  ducks ,  hens ,  gulls  and many other species of birds. The incidence of infection in canaries and finches is believed to be lower than in  psittacine  birds."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1819", "contents": "In certain contexts, the word is used when the disease is carried by any species of birds belonging to the family  Psittacidae , whereas  ornithosis  is used when other birds carry the disease. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1820", "contents": "In humans, after an incubation period of 5\u201319 days, the disease course ranges from asymptomatic to systemic illness with severe  pneumonia . It presents chiefly as an atypical pneumonia. In the first week of psittacosis, the symptoms mimic  typhoid fever , causing high  fevers ,  joint pain ,  diarrhea ,  conjunctivitis ,  nose bleeds , and  low level of white blood cells . [ 2 ]   Rose spots  called  Horder's spots  sometimes appear during this stage. [ 3 ] [ 4 ]  These are pink, blanching maculopapular eruptions resembling the rose spots of  typhoid fever . [ 5 ]   Spleen enlargement  is common towards the end of the first week, after which psittacosis may develop into a serious lung infection. Diagnosis is indicated where respiratory infection occurs simultaneously with splenomegaly and/or epistaxis.  Headache  can be so severe that it suggests  meningitis  and some  nuchal rigidity  is not unusual.  Towards the end of the first week, stupor or even  coma  can result in severe cases. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1821", "contents": "The second week is more akin to acute bacteremic  pneumococcal  pneumonia with continuous high fevers, headaches, cough, and  dyspnea .  X-rays  at that stage show patchy infiltrates or a diffuse whiteout of lung fields. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1822", "contents": "Complications in the form of  endocarditis ,  liver inflammation ,  inflammation of the heart's muscle ,  joint inflammation ,  keratoconjunctivitis  (occasionally  extranodal marginal zone lymphoma  of the lacrimal gland/orbit) [ citation needed ] , and neurologic complications ( brain inflammation ) may occasionally occur. Severe pneumonia requiring intensive-care support may also occur. Fatal cases have been reported (less than 1% of cases). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1823", "contents": "The  Chlamydia psittaci  bacterium that causes psittacosis can be transmitted by mouth-to-beak contact, or through the airborne inhalation of feather dust, dried faeces, or the respiratory secretions of infected birds. [ 6 ]  Person-to-person transmission is possible, but rare. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1824", "contents": "Blood analysis usually shows a normal white cell count, but marked  leukocytosis  is occasionally apparent.  Liver  enzymes are abnormal in half of the patients, with mild elevation of  aspartate transaminase . The erythrocyte sedimentation rate and C-reactive protein can be markedly elevated. Differential diagnosis must be made with typhus, typhoid, and atypical pneumonia by  Mycoplasma ,  Legionella , or  Q fever . Exposure history is paramount to diagnosis.\nDiagnosis involves  microbiological cultures  from respiratory secretions of patients or  serologically  with a fourfold or greater increase in  antibody  titers against  C. psittaci  in blood samples combined with the probable course of the disease. Typical inclusions called \"Leventhal-Cole-Lillie bodies\" [ 7 ]  can be seen within macrophages in BAL (bronchoalveolar lavage) fluid. Culture of  C. psittaci  is hazardous and should only be carried out in biosafety laboratories. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1825", "contents": "The infection is treated with  antibiotics ;  tetracyclines  and  chloramphenicol  are the choice for treating patients. [ 8 ]  Most people respond to oral therapy  doxycycline ,  tetracycline  hydrochloride, or chloramphenicol palmitate. For initial treatment of severely ill patients, doxycycline hyclate may be administered  intravenously . Remission of symptoms is usually evident within 48\u201372 hours. However, relapse can occur, and treatment must continue for at least 10\u201314 days after fever subsides. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1826", "contents": "Psittacosis was first reported in Europe in 1879. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1827", "contents": "In 1929, a highly publicized  outbreak of psittacosis  hit the United States.  Although not the first report of psittacosis in the United States, it was the largest up to that time.  It led to greater controls on the import of pet parrots. [ 9 ]   The aftermath of the outbreak and how it was handled led to the establishment of the  National Institutes of Health . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1828", "contents": "From 2002 through 2009, 66 human cases of psittacosis were reported to the Centers for Disease Control and Prevention, [ citation needed ]  and most resulted from exposure to infected pet birds, usually cockatiels,  parakeets , and macaws. Many more cases may occur that are not correctly diagnosed or reported.\nBird owners, pet shop employees, zookeepers, and veterinarians are at risk of the infection. Some outbreaks of psittacosis in poultry-processing plants have been reported."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1829", "contents": "In birds,  Chlamydia psittaci  infection is referred to as avian chlamydiosis. Infected birds shed the bacteria through feces and nasal discharges, which can remain infectious for several months. Many strains remain quiescent in birds until activated under stress. Birds are excellent, highly mobile vectors for the distribution of chlamydial infection because they feed on, and have access to, the detritus of infected animals of all sorts."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1830", "contents": "C. psittaci  in birds is often systemic and infections can be inapparent, severe, acute, or chronic with intermittent shedding. Signs in birds include \"inflamed eyes, difficulty in breathing, watery droppings, and green urates.\" [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1831", "contents": "Initial diagnosis may be by symptoms, but is usually confirmed by an  antigen  and  antibody  test.  A  polymerase chain reaction -based test is also available.  Although any of these tests can confirm psittacosis, false negatives are possible, so a combination of clinical and laboratory tests is recommended before giving the bird a clean bill of health. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1832", "contents": "Infection is usually by the droppings of another infected bird, though it can also be transmitted by feathers and eggs, [ 12 ]  and is typically either inhaled or ingested. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1833", "contents": "C. psittaci  strains in birds infect mucosal epithelial cells and macrophages of the respiratory tract. Septicaemia eventually develops and the bacteria become localized in epithelial cells and macrophages of most organs, conjunctiva, and gastrointestinal tract. It can also be passed in the eggs. Stress commonly triggers onset of severe symptoms, resulting in rapid deterioration and death.  C. psittaci  strains are similar in virulence, grow readily in cell culture, have 16S-rRNA genes that differ by <0.8%, and belong to eight known  serovars . All should be considered to be readily transmissible to humans. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1834", "contents": "C. psittaci  serovar A is endemic among psittacine birds and has caused sporadic zoonotic disease in humans, other mammals, and tortoises.  Serovar B is endemic among pigeons, has been isolated from turkeys, and has also been identified as the cause of abortion in a dairy herd.  Serovars C and D are occupational hazards for slaughterhouse workers and for people in contact with birds.  Serovar E isolates (known as Cal-10, MP, or MN) have been obtained from a variety of avian hosts worldwide, and although they were associated with the 1920s\u20131930s outbreak in humans, a specific reservoir for serovar E has not been identified.  The M56 and WC serovars were isolated during outbreaks in mammals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1835", "contents": "Treatment is usually with antibiotics, such as doxycycline or tetracycline, and can be administered through drops in the water or injections. [ 12 ]   Many strains of  C. psittaci  are susceptible to  bacteriophages . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1836", "contents": "Psittacosis was one of more than a dozen agents that the United States researched as potential  biological weapons  before the nation suspended its  biological weapons program . [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1837", "contents": "In 1930, during the  1929\u20131930 psittacosis pandemic , Lena Rose Pepperdine died of parrot fever. She was the first wife of  George Pepperdine , the founder of  Pepperdine University . [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1838", "contents": "Reactive airway disease  ( RAD ) is an informal label that physicians apply to patients with symptoms similar to those of  asthma . [ 1 ]  An exact definition of the condition does not exist. [ 1 ] [ 2 ]  Individuals who are typically labeled as having RAD generally have a history of wheezing, coughing,  dyspnea , and production of sputum that may or may not be caused by asthma. Symptoms may also include, but are not limited to, coughing, shortness of breath, excess mucus in the bronchial tube, swollen mucous membrane in the bronchial tube, and/or hypersensitive bronchial tubes. [ medical citation needed ]  Physicians most commonly label patients with RAD when they are hesitant about formally diagnosing a patient with asthma, which is most prevalent in the pediatric setting. While some physicians may use  RAD  and  asthma  synonymously, there is controversy over this usage."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1839", "contents": "More generally, there is controversy over the use of RAD as a label in the healthcare setting, largely due to the ambiguous definition that the term has. [ 1 ] [ 3 ]  Since RAD is not recognized as a real clinical diagnosis, its meaning is highly inconsistent and may cause confusion and misdiagnosis within the medical community. [ 1 ]  There are also concerns with overtreatment and undertreatment with RAD amongst physicians, since there is little formality with the label. [ 1 ]  Other problems that healthcare workers have with the use of the RAD label include its exclusion in the  International Statistical Classification of Diseases and Related Health Problems , which can lead to billing issues in hospitals and other health care facilities, and the creation of a fabricated sense of security when using it as a diagnosis. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1840", "contents": "RAD can be confused with reactive airways dysfunction syndrome, an asthma-like disorder that results from high exposure to vapors, fumes, and/or smoke. Unlike RAD, reactive airways dysfunction syndrome is recognized by multiple societies as a real clinical syndrome, including the  American Thoracic Society  and the  American College of Chest Physicians . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1841", "contents": "The term  reactive airway disease  originally began to appear in medical literature in the 1980s in reference to asthmatic patients with hyperactive airways, which is a common feature of asthma. This feature is characterized by increased  bronchoconstriction  reactions in response to stimuli that should not elicit so strong of response. These stimuli can include  methacholine ,  histamine , and distilled water. However, while this was how the term initially was introduced,  RAD  soon began to be used interchangeably with the term  asthma  itself, which has led to the current controversy over its place in medical diagnoses. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1842", "contents": "More commonly, RAD is now mostly used by physicians when they are hesitant to diagnose a patient with asthma. This is most prominent in pediatric settings for a variety of reasons. While infants tend to wheeze more often than adults, only one-third of them eventually go on to actually have asthma. Asthma and viral bronchiolitis can also be nearly identical to each other when presented in very young children, since they both consist of wheezing, coughing, and nasal congestion. In addition, typical tests used to accurately diagnose children with asthma, such as the  bronchial challenge test , are not considered to be accurate for children under the age of five. This can be due to failure of very young children to cooperate. [ 3 ] [ 4 ]  Diagnosing a child with asthma also carries a certain negative connotation, causing hesitancy from some physicians to do so. All of these factors lead physicians to label young children with RAD instead of asthma, since the disease is often only suspected and unable to be confirmed with pediatric patients. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1843", "contents": "Physicians will generally label an adult with RAD if they have no prior diagnosis or history of asthma while exhibiting symptoms of wheezing, production of sputum, and/or the use of an inhaler. [ 2 ]  Symptoms may also include, but are not limited to, coughing, shortness of breath, excess mucus in the bronchial tube, swollen mucous membrane in the bronchial tube, and/or hypersensitive bronchial tubes. [ medical citation needed ]  In order to make a formal asthma diagnosis in adult patients, there is requirement to have documentation of either airway hyperreactivity or some sort of reversible airway obstruction. If none of these symptoms are present in an adult patients' medical history or documentation, the physician may label the patient with RAD instead of asthma in order to still indicate there is an airway issue without formal diagnosis. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1844", "contents": "While the acronyms are similar, reactive airway disease (RAD) and reactive airways dysfunction syndrome (RADS) are not the same. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1845", "contents": "Reactive airways dysfunction syndrome was first identified by  Stuart M. Brooks  and colleagues in 1985 as an asthma-like syndrome developing after a single exposure to high levels of an irritating vapor, fume, or smoke. [ 1 ] [ 5 ]  It can manifest in adults with exposure to high levels of  chlorine ,  ammonia ,  acetic acid , or  sulphur dioxide , creating symptoms like asthma. [ 6 ]  These symptoms can vary from mild to fatal and can even create long-term airway damage, depending on the amount of exposure and the concentration of chlorine. Patients that have been diagnosed with RADS will likely have methacholine airway hyperreactivity, yet other tests that also measure pulmonary functions may appear normal. [ 1 ]  Some experts classify RADS as occupational asthma. Those with exposure to highly irritating substances should receive treatment to mitigate harmful effects. [ 7 ]  Treatment for RADS is similar to treatment for other disorders that result from acute inhalation. Preexisting allergies can be a risk factor for developing RADS. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1846", "contents": "The main difference between RAD and RADS is that RADS can occur after just one exposure to the inhalants and without any prior sensitization. In addition, although the symptoms of RADS are very similar to those of asthma, they may be resolved. While some physicians argue that RADS is also not a real clinical syndrome, it is more commonly recognized in legitimate associations than RAD. These associations include the American Thoracic Society and the American College of Chest Physicians. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1847", "contents": "There remains controversy over the use of RAD as an unofficial diagnosis. With its use not only being limited to clinical lexicon, but also transitioning to clinical literature now, more physicians are now increasingly disapproving its use in the healthcare setting. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1848", "contents": "One of the largest problems with the using RAD as a diagnostic label lies in the ambiguity of its meaning, as RAD has no true clinical definition. [ 1 ]  It is either not listed or redirects to \"asthma\" in all major medical journals and websites. It is also not recognized by the  American Academy of Pediatrics ; the American Thoracic Society; or the  National Heart Lung and Blood Institute . [ 3 ]  Its use may result in undertreatment, as treatments for asthma, chronic bronchitis, emphysema, or pneumonia may not be prescribed under a label of reactive airway disease. [ 1 ]  Alternatively, overtreatment may occur, as patients can be prescribed inhaled  beta-agonists  or inhaled  corticosteroids , which are medications used for asthma. If an individual with RAD does not have asthma, there is no evidence these treatments are beneficial. [ 1 ]  As a result of its ambiguous place in the medical field, the symptoms used to characterize it are often inconsistent and can lead to confusion in a healthcare setting. This is a troubling issue for many physicians, as care can be made more complicated; many patients labeled with RAD do not ultimately have asthma, and most RAD patients have never formally had their airway reactivity measured. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1849", "contents": "In addition to the inconsistencies of its labeling, there is no billing designation for RAD in the International Statistical Classification of Diseases and Related Health Problems, or the ICD, which can lead to problems for healthcare facilities. Searches in the ICD point to content relating to asthma. [ 3 ]  Some medical professionals argue that using RAD as a diagnosis will only complicate research on asthma in the context of clinical research and epidemiology. The ability to label a patient with RAD may it give physicians a fabricated sense of security that they have made a diagnosis, when no real recognizable diagnosis has been made. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1850", "contents": "Respiratory compromise  describes a deterioration in respiratory function with a high likelihood of rapid progression to  respiratory failure  and  death . [ 1 ]  Respiratory failure occurs when inadequate  gas exchange  by the  respiratory system  occurs, with a low  oxygen  level or a high  carbon dioxide  level."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1851", "contents": "Patients in  acute care   hospitals , particularly those with  respiratory conditions , are at risk for developing respiratory compromise. Respiratory failure requiring emergency  mechanical ventilation  occurs in over 40,000 patients per year in the  United States . [ 2 ]  In  postoperative  patients in the United States, the  National Surgical Quality Improvement Program  reports that 1.03% of all surgical patients require an unplanned  intubation  postoperatively. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1852", "contents": "Although respiratory compromise may develop de novo during hospitalization in patients without preexisting lung disease, in other patients, it develops as a complication of  chronic  respiratory diseases, such as  chronic obstructive pulmonary disease  (COPD). Although respiratory failure is caused by a  heterogeneous  group of processes, there are subsets of patients who manifest similar  physiologic  patterns of deterioration [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1853", "contents": "The term respiratory compromise is used to describe various intensities of respiratory dysfunction that can range from a chronic state of respiratory insufficiency to conditions that require emergency  resuscitation  and a  breathing machine . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1854", "contents": "Risk factors include a variety of substances, conditions, and environments: [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1855", "contents": "In addition to the lung deterioration observed for the various  etiologies  and mechanisms of respiratory compromise, severe respiratory compromise can have a concomitant impact on non-pulmonary systems of the body. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1856", "contents": "Central to implementing therapies to reverse or mitigate a state of respiratory compromise is an accurate diagnosis of the condition. Correctly diagnosing respiratory compromise requires a  screening  to determine the amount of gas in the patient's bloodstream. Two different tests are available for clinical diagnosis. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1857", "contents": "Testing and monitoring blood gas levels requires one of the following diagnostic procedures:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1858", "contents": "For this test, a small sensor is attached to the patient's finger or ear. The sensor uses light to estimate how much oxygen is in the blood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1859", "contents": "A  pulse oximeter  works by beaming red and  infrared light  through  capillaries . The amount of red and infrared light transmitted provides an approximate measure of oxygen in the blood. The oximeter reading is based on the color of the blood:  oxygenated blood  is a brighter red than  deoxygenated blood , which appears as bluish purple."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1860", "contents": "This test measures the precise levels of oxygen and  carbon dioxide  in the blood. A blood sample is  drawn  from an artery, typically in the wrist. A laboratory then processes the blood sample to determine oxygen and carbon dioxide levels."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1861", "contents": "Assessing and monitoring blood gas levels is the most accurate means to identify a state of respiratory compromise in patients. ABG testing does however require an arterial blood sample, which is more invasive and uncomfortable for patients than a  pulse oximetry  reading that uses a reading based on light and color. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1862", "contents": "The importance of diagnosing respiratory compromise is that with earlier diagnosis and treatment progression to respiratory failure may be prevented. Enhanced monitoring techniques and specific therapies may prevent progression of respiratory compromise to respiratory failure and possible death."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1863", "contents": "Classifying acutely ill respiratory patients into one or more of these categories may help in determining appropriate screening and monitoring strategies that are most effective for the patient's particular  pathophysiology . Although specific diagnostic and therapeutic interventions must be individualized, standardized screening and monitoring practices for patients with similar mechanisms of deterioration may enhance the ability to predict respiratory failure early and prevent its occurrence. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1864", "contents": "Therapy interventions for respiratory compromise target secondary effects of the condition, which manifest as pulmonary  pathologies  or aggravate existing pulmonary conditions. Appropriately administered  antibiotic therapy  can reduce the  risk of mortality  in patients with moderate to severe  pneumonia , and timely ventilation therapy can reduce mortality in patients with a diagnosis of COPD. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1865", "contents": "Respiratory failure  results from inadequate  gas exchange  by the  respiratory system , meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as  hypoxemia ; a rise in arterial  carbon dioxide  levels is called  hypercapnia . Respiratory failure is classified as either Type 1 or Type 2, based on whether there is a high carbon dioxide level, and can be acute or chronic. In clinical trials, the definition of respiratory failure usually includes  increased respiratory rate , abnormal blood gases (hypoxemia, hypercapnia, or both), and evidence of increased work of breathing. Respiratory failure causes an  altered state of consciousness  due to  ischemia in the brain ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1866", "contents": "The typical  partial pressure  reference values are oxygen  Pa   O 2  more than 80 mmHg (11 kPa) and carbon dioxide  Pa   CO 2  less than 45 mmHg (6.0 kPa). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1867", "contents": "A variety of conditions that can potentially result in respiratory failure. [ 1 ]  The etiologies of each type of respiratory failure (see below) may differ, as well. Different types of conditions may cause respiratory failure:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1868", "contents": "Respiratory failure is generally organized into 4 types. [ citation needed ]  Below is a diagram that provides a general overview of the 4 types of respiratory failure, their distinguishing characteristics, and major causes of each."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1869", "contents": "Type 1 respiratory failure is characterized by a  low level of oxygen in the blood (hypoxemia)  (PaO2) < 60 mmHg with a normal (normocapnia) or low (hypocapnia) level of carbon dioxide (PaCO2) in the blood. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1870", "contents": "The fundamental defect in type 1 respiratory failure is a failure of oxygenation characterized by:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1871", "contents": "Type I respiratory failure is caused by conditions that affect  oxygenation  and therefore lead to lower-than-normal oxygen in the blood. These include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1872", "contents": "Hypoxemia  (PaO 2  <8kPa or normal) with hypercapnia (PaCO 2  >6.0kPa)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1873", "contents": "The basic defect in type 2 respiratory failure is characterized by:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1874", "contents": "Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected.  Defined as the buildup of carbon dioxide levels (P a CO 2 ) that has been generated by the body but cannot be eliminated. The underlying causes include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1875", "contents": "Type 3 respiratory failure is a type of Type 1 respiratory failure, with decreased PaO2 (hypoxemia) and either normal or decreased PaCO2. [ 1 ]  However, because of its prevalence, it has been given its own category. Type 3 respiratory failure is often referred to as peri-operative respiratory failure, because it is distinguished by being a Type 1 respiratory failure that is specifically associated with an operation, procedure, or surgery. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1876", "contents": "The pathophysiology of type 3 respiratory failure often includes lung atelectasis, which is a term used to describe a collapsing of the functional units of the lung that allow for gas exchange. Because atelectasis occurs so commonly in the perioperative period, this form is also called  perioperative respiratory failure.  After  general anesthesia , decreases in functional residual capacity  leads to  collapse  of  dependent lung units. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1877", "contents": "Type 4 respiratory failure occurs when metabolic (oxygen) demands exceed what the cardiopulmonary system can provide. [ 1 ]  It often results from  hypoperfusion  of respiratory muscles as in patients in  shock , such as  cardiogenic shock  or  hypovolemic shock . Patients in shock often experience respiratory distress due to pulmonary edema (e.g., in  cardiogenic shock ).  Lactic acidosis  and  anemia  can also result in type 4 respiratory failure. [ 1 ]  However, type 1 and 2 are the most widely accepted. [ 1 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1878", "contents": "Physical exam findings often found in patients with respiratory failure include findings indicative of impaired oxygenation (low blood oxygen level). These include, but are not limited to, the following:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1879", "contents": "People with respiratory failure often exhibit other signs or symptoms that are associated with the underlying cause of their respiratory failure. For instance, if respiratory failure is caused by cardiogenic shock (decreased perfusion due to heart dysfunction, symptoms of heart dysfunction (e.g.,  pitting edema ) are also expected."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1880", "contents": "Arterial blood gas  (ABG) assessment is considered the gold standard diagnostic test for establishing a diagnosis of respiratory failure. [ 1 ]   This is because ABG can be used to measure blood oxygen levels (PaO2), and respiratory failure (all types) is characterized by a low blood oxygen level. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1881", "contents": "Alternative or supporting diagnostic methods include the following:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1882", "contents": "Imaging (eg. ultrasonography, radiography) may be used to assist in the diagnostic workup. For example, it may be utilized to determine the etiology of a person's respiratory failure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1883", "contents": "Treatment of the underlying cause is required, if possible. The treatment of acute respiratory failure may involve medication such as  bronchodilators  (for airways disease), [ 7 ] [ 8 ]   antibiotics  (for infections),  glucocorticoids  (for numerous causes),  diuretics  (for pulmonary oedema), amongst others. [ 1 ] [ 9 ] [ 10 ]  Respiratory failure resulting from an  overdose  of  opioids  may be treated with the antidote  naloxone . In contrast, most  benzodiazepine overdose  does not benefit from its antidote,  flumazenil . [ 11 ]   Respiratory therapy /respiratory  physiotherapy  may be beneficial in some cases of respiratory failure. [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1884", "contents": "Type 1 respiratory failure may require oxygen therapy to achieve adequate oxygen saturation. [ 14 ]  Lack of oxygen response may indicate other modalities such as  heated humidified high-flow therapy ,  continuous positive airway pressure  or (if severe)  endotracheal intubation  and  mechanical ventilation . . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1885", "contents": "Type 2 respiratory failure often requires  non-invasive ventilation  (NIV) unless medical therapy can improve the situation. [ 15 ]  Mechanical ventilation is sometimes indicated immediately or otherwise if NIV fails. [ 15 ]   Respiratory stimulants  such as  doxapram  are now rarely used. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1886", "contents": "There is tentative evidence that in those with respiratory failure identified before arrival in hospital,  continuous positive airway pressure  can be helpful when started before conveying to hospital. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1887", "contents": "Prognosis is highly variable and dependent on etiology and availability of appropriate treatment and management. [ 18 ]  One of three hospitalized cases of acute respiratory failure is fatal. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1888", "contents": "Respiratory risks of indoor  swimming pools  can include coughing, wheezing, aggravated  asthma , [ 1 ]  and airway hyper-responsiveness (spasms of the bronchial tubes in the lungs causing coughing and chest tightness). The chemicals used for pool water disinfection can react with organic compounds in the water to create  disinfection by-products  or DBPs. Exposure to these DBPs are the potential cause for respiratory symptoms in swimmers. [ 2 ]  Multiple studies have shown the potential correlation between chronic exposure to DBPs and respiratory symptoms among competitive swimmers but more research is needed on the effects of these DBPs on recreational swimmers. The studies on recreational swimmers that have been done show a decreased risk for respiratory symptoms due to a decreased exposure to DBPs. [ 3 ]  Some studies have been done on the vulnerability of younger children and DBP exposure. [ 4 ]  Studies done on the vulnerability of younger children demonstrate that immature lungs are more likely to absorb more of these DBPs. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1889", "contents": "Respiratory tract infections  ( RTIs ) are  infectious diseases  involving the lower or upper  respiratory tract . [ 1 ]  An infection of this type usually is further classified as an  upper respiratory tract infection  (URI or URTI) or a  lower respiratory tract infection  (LRI or LRTI). Lower respiratory infections, such as  pneumonia , tend to be far more severe than upper respiratory infections, such as the  common cold ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1890", "contents": "The  upper respiratory tract  is considered the airway above the  glottis  or vocal cords; sometimes, it is taken as the tract above the  cricoid cartilage . This part of the tract includes the  nose ,  sinuses ,  pharynx , and  larynx . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1891", "contents": "Typical infections of the upper respiratory tract include  tonsillitis ,  pharyngitis ,  laryngitis ,  sinusitis ,  otitis media , certain  influenza  types, and the  common cold . [ 3 ]  Symptoms of URIs can include  cough ,  sore throat ,  runny nose ,  nasal congestion ,  headache , low-grade  fever , facial pressure, and  sneezing . [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1892", "contents": "The  lower respiratory tract  consists of the  trachea  (windpipe),  bronchial tubes ,  bronchioles , and the  lungs . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1893", "contents": "Lower respiratory tract infections (LRIs) are generally more severe than upper respiratory infections. LRIs are the leading cause of death among all  infectious diseases . [ 7 ]  The two most common LRIs are  bronchitis  and  pneumonia . [ 8 ]   Influenza  affects both the upper and lower respiratory tracts, but more dangerous strains such as the highly pernicious  H5N1  tend to bind to receptors deep in the lungs. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1894", "contents": "Pulmonary Function Testing  (PFT) allows for the evaluation and assessment of airways, lung function, as well as specific benchmarks to diagnose an array of respiratory tract infections. [ 10 ]  Methods such as gas dilution techniques and  plethysmography  help determine the functional residual capacity and total lung capacity. [ 10 ]  To discover whether or not to perform a set of advanced Pulmonary Function Testing will be based on abnormally high values in previous test results. [ 10 ]  A 2014 systematic review of clinical trials does not support routine rapid viral testing to decrease antibiotic use for children in emergency departments. [ 11 ]  It is unclear if rapid viral testing in the emergency department for children with acute  febrile  respiratory infections reduces the rates of antibiotic use,  blood testing , or  urine testing . [ 11 ]  The relative risk reduction of  chest x-ray  utilization in children screened with rapid viral testing is 77% compared with controls. [ 11 ]  In 2013 researchers developed a breath tester that can promptly diagnose lung infections. [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1895", "contents": "Bacteria  are  unicellular organisms  present on Earth can thrive in various environments, including the human body. [ 14 ]   Antibiotics  are a medicine designed to treat  bacterial infections  that need a more severe treatment course; antibiotic use is not recommended for common bacterial infections as the  immune system  will resolve such infections. [ 15 ]   This medicine does not effectively treat a viral infection like  sore throats ,  influenza ,  bronchitis ,  sinusitis  and common respiratory tract infections. [ 15 ] [ 16 ]  This is because antibiotics were developed to target features of bacteria that are not present in viruses, and so antibiotics are ineffective as  antiviral agents . [ 17 ] [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1896", "contents": "The CDC has reported that antibiotic prescription is high; 47 million prescriptions in the United States in 2018 were made for infections that do not need antibiotics to be treated with. [ 19 ]   It is recommended to avoid antibiotic use unless bacterial infections are severe, transmissible, or have a high risk of further complications if left untreated. [ 20 ]   Unnecessary use of antibiotics could increase  antibiotic-resistant  infections, affect the  digestive system , create  allergic reactions , and other intense side effects. [ 21 ]  A study published in  JAMA  found that narrow-spectrum antibiotics, such as amoxicillin, are just as effective as broad-spectrum alternatives for treating acute respiratory tract infections in children, but have a lower risk of side effects. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1897", "contents": "Despite the superior filtration capability of  N95 filtering facepiece respirators  measured in vitro, insufficient clinical evidence has been published to determine whether standard surgical masks and N95 filtering facepiece respirators are equivalent to preventing respiratory infections in healthcare workers. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1898", "contents": "Adults in  intensive care units  (ICU) have a higher risk of acquiring an RTI. [ 24 ]  A combination of topical and systematic antibiotics taken  prophylactically  can prevent infection and improve adults' overall mortality in the ICU for adult patients receiving  mechanical ventilation  for at least 48 hours, and topical  antibiotic prophylaxis  probably reduces respiratory infections but not mortality. [ 24 ]   However, the combination of treatments cannot rule out the relevant contribution in the systemic component of the observed reduction of mortality. [ 24 ]  There is no sufficient evidence to recommend that antibiotics be used to prevent complications from an RTI of unknown cause in children under the age of 5 years old. [ 25 ]   High-quality clinical research in the form of randomized controlled trials assessed the effectiveness of Vitamin D, [ 26 ]  another review of poorer quality RCTs addressed the effectiveness of  immunostimulants  for preventing respiratory tract infections. [ 27 ]   Despite some uncertainty due to small study sizes, there is some evidence that exercise may reduce severity of symptoms but had no impact on number of episodes or number of symptom days per episode. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1899", "contents": "Viruses that cause RTI are more transmissible at very high or low  relative humidity ; ideal humidity for indoor spaces is between 40 and 60%. Therefore, relative humidity in this range can help lessen the risk of aerosol transmission. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1900", "contents": "Respiratory infections often have strong seasonal patterns, with  temperate climates  more affected during the  winter . Several factors explain winter peaks in respiratory infections, including environmental conditions and changes in human behaviors. Viruses that cause respiratory infections are affected by environmental conditions like  relative humidity  and temperature. Temperate climate winters have lower relative humidity, which is known to increase the transmission of  influenza . [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1901", "contents": "Of the viruses that cause respiratory infections in humans, most have seasonal variation in prevalence. Influenza,  Human orthopneumovirus  (RSV), and  human coronaviruses  are more prevalent in the winter.  Human bocavirus   and  Human metapneumovirus  occur year-round,  rhinoviruses  (which cause the  common cold ) occur mostly in the spring and fall, and  human parainfluenza viruses  have variable peaks depending on the specific strain.  Enteroviruses , with the exception of rhinoviruses, tend to peak in the summer. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1902", "contents": "Rising of the lights  was an illness or obstructive condition of the larynx, trachea or lungs, possibly  croup . It was a common entry on  bills of mortality  in the 17th century. [ 1 ] [ 2 ]  Lights in this case referred to the  lungs . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1903", "contents": "In his  A New Booke of Mistakes  (1637),  Robert Chamberlain  gives a humorous epitaph:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1904", "contents": "Of one Parkins a boone Companion in Essex who dyed of the rising of the Lights."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1905", "contents": "Poore Parkins, now percust here lies, \nLight hearted, till his Lights did rise. \nLights of the Body, are the Bellowes, \nAnd hee, one of the best good fellowes \nThat Essex yeelded, (all we do know) \nAnd breath'd, till they did cease to blow. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1906", "contents": "A  saber-sheath trachea  also known as  scabbard trachea  is a  trachea  that has an abnormal shape. This manifests as a narrowing of the portion of the trachea located within the thorax, and a widening of the diameter of the posterior area of the trachea. The lateral measurement of tracheal diameter decreases. In saber-sheath trachea, the inner wall of the trachea is smooth, there are no nodules or areas of thickening. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1907", "contents": "The trachea is a cartilaginous and tubular structure which serves as the main airway, carrying air from the nose and mouth to the lungs. The total length is variable, and can range from 8-13 centimeters. The trachea's length spans both within the lung cavity, termed the intra-thoracic portion of the trachea, and outside the lung cavity, termed the extra-thoracic portion. [ 2 ]  The intra-thoracic portion is typically 6-9 centimeters in length, while the extra-thoracic portion is 2-4 centimeters in length. The trachea is supported by C-shaped rings of cartilage, which supports the trachea and prevents it from collapsing during exhalation. [ 2 ]  In men, a normal trachea will have a diameter measuring the distance from one side of the trachea to the other, termed the coronal diameter, of 13-25 millimeters, and in women the coronal diameter of a normal trachea will range from 10-21 millimeters. The diameter of the front side of the trachea to the back, termed the sagittal diameter, in men typically is from 13-27 millimeters and in women is 10-23 millimeters. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1908", "contents": "It can occur in  chronic obstructive pulmonary disease  (COPD) or prolonged bilateral compression on it as in  goitre . It is considered to be widely associated with COPD. During normal exhalation, the size of the trachea within the chest cavity becomes slightly smaller. This reduction is more noticeable for patients with COPD. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1909", "contents": "The underlying process leading to the formation of the saber-sheath shape of the trachea is not fully understood. There are many currently suggested theories however, which include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1910", "contents": "Diagnosing a patient with saber-sheath trachea is based on calculating a value called the tracheal index. The tracheal index is measured by taking the ratio of the width of the trachea and the depth of the trachea using cross-sectional imaging. [ 6 ]  A tracheal index of 1.0 indicates that the trachea has a typical, appropriate rounded cross-section. A patient is considered to have saber-sheath trachea when the calculated tracheal index is below 0.67. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1911", "contents": "On typical CT scans of the trachea, the normal appearance is oval, round, or horseshoe shaped. A saber-sheath trachea has distinct findings compared to normal tracheas on imaging, and may have additional features on CT besides intra-thoracic narrowing and widening diameter of the posterior portion. When cartilage becomes weak, as in saber-sheath trachea, CT scans can show the sides of the trachea curving inwards. This can be more apparent with forceful exhalation Moreover, the walls of the trachea within the thorax can also show slight thickening on CT. Another finding that can be seen is the hardening and becoming more bone-like of the cartilaginous rings in the trachea, a process called ossification. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1912", "contents": "Silent hypoxia  (also known as  happy hypoxia ) [ 1 ] [ 2 ]  is generalised  hypoxia  that does not coincide with  shortness of breath . [ 3 ] [ 4 ] [ 5 ]  This presentation is known to be a complication of  COVID-19 , [ 6 ] [ 7 ]  and is also known in  walking pneumonia , [ 8 ]   altitude sickness , [ 9 ] [ 10 ] [ 11 ]  and  rebreather diving . [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1913", "contents": "One theory relating to COVID-19 presentation suggests the impaired processing of severe hypoxia and resumption of normal breathing may be due to the neurological pathway by which the virus spreads from the oral cavity to the brain. [ 14 ]  It is speculated that this condition is caused by  SARS-CoV-2  affecting the blood flow of the lungs' airways, in addition to the blood vessels within the lungs, which must match in order to allow proper airflow, but not affecting them enough to cause shortness of breath. [ 15 ] [ 16 ]  It is also speculated that silent hypoxia may be caused by the formation of small  blood clots  within the lungs. [ 17 ] [ 18 ] [ 19 ] [ clarification needed ]  It has been shown that the breathing rates of patients with COVID-19 gradually increase, which in turn leads to silent hypoxia. [ 20 ]  It has also been shown that COVID-19 patients experience lesser levels of shortness of breath after exercise than non-COVID-19 patients. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1914", "contents": "In healthy people this presentation can occur when the person breathes a gas which has a low oxygen content, and also a low carbon dioxide content, so there is no  hypercapnic alarm response . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1915", "contents": "In  COVID-19 , the arterial and general tissue oxygen levels can drop without any initial warning. The  chest x-ray  may show diffuse  pneumonia . Cases of silent hypoxia with COVID-19 have been reported for patients who did not experience  shortness of breath  or coughing until their  oxygen levels  had depressed to such a degree that they were at risk of  acute respiratory distress  (ARDS) and  organ failure . [ 22 ] [ medical citation needed ]  In a  New York Times  opinion piece (April 20, 2020), emergency room doctor  Richard Levitan  reported: \"A vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at  triage \u2014seemingly incompatible with life\u2014but they were using their cellphones as we put them on monitors.\" [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1916", "contents": "A tool used to diagnose silent hypoxia is the six-minute walk test, (6MWT), wherein a patient walks at a normal pace for six minutes, in order to monitor their physiological response. [ 23 ]  It has been proven that, after performing the 6MWT, COVID-19 patients were more likely to develop exercise-induced hypoxia  without  symptoms than non-COVID-19 patients who had  idiopathic pulmonary fibrosis . [ 24 ] [ clarification needed ]  The condition can also be first detected by using prehospital  pulse oximetry . [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1917", "contents": "Treatment depends on the cause. In some cases supplementary oxygen is needed, in severe cases artificial ventilation may be necessary. In mild cases where the cause was hypoxic breathing gas, it may only be necessary to return to a normally oxygenated environment. Underlying medical problems may require assessment and treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1918", "contents": "The prognosis for silent hypoxia in COVID-19 is generally poor, [ 27 ] [ 28 ] [ clarification needed ]  as oxygen levels in the blood can drop below 50 percent without being noticed. [ 29 ]  In cases where a healthy person was exposed to a hypoxic environment, the outcome will usually depend on the extent of associated tissue damage incurred. In mild cases a quick return to normal follows reversion to normally oxygenated breathing gas."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1919", "contents": "Known to be associated with:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1920", "contents": "Source control  is a strategy for reducing disease transmission by blocking  respiratory secretions  produced through breathing, speaking, coughing, sneezing or singing. [ 1 ]  Multiple source control techniques can be used in hospitals, but for the general public wearing  personal protective equipment  during  epidemics  or  pandemics ,  respirators  provide the greatest source control, followed by  surgical masks , with  cloth face masks  recommended for use by the public only when there are shortages of both respirators and surgical masks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1921", "contents": "Infections in general may spread by direct contact (for example, shaking hands or kissing), by inhaling  infectious droplets  in the air (droplet transmission), by inhaling long-lasting aerosols with tiny particles ( airborne transmission ), and by touching objects with infectious material on their surfaces ( fomites ). Different diseases spread in different ways; some spread by only some of these routes. For instance, fomite transmission of COVID-19 is thought to be rare while aerosol, droplet and contact transmission appear to be the primary transmission modes, as of April 2021 [update] . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1922", "contents": "Coughs and sneezes can spread airborne droplets up to ~8 meters (26\u00a0ft). Speaking can spread droplets up to ~2 meters (6.6\u00a0ft). [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1923", "contents": "Masking any person who may be a source of infectious droplets (or aerosols) thus reduces the unsafe range of physical distances. If a person can be infectious before they are symptomatic and diagnosed, then people who do not yet know if they are infectious may also be a source of infection."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1924", "contents": "For pathogens transmitted through the air, strategies to block cough air jets and to capture aerosols, e.g. the \"Shield & Sink\" approach, can be highly effective in minimizing exposure to respiratory secretions. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1925", "contents": "Outside of respiratory source control, handwashing helps to protect people against contact transmission, and against indirect droplet transmission. Handwashing removes infectious droplets that their mask caught (from either side) and which transferred to their hands when they touched their mask. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1926", "contents": "In the past, suggestions have been made that covering the mouth and nose, like with an elbow, tissue, or hand, would be a viable measure towards reducing the transmissions of airborne diseases. This method of source control was suggested,  but not empirically tested , in the \"Control of Airborne Infection\" section of a 1974 publication of Riley's  Airborne Infection. [ 5 ]   NIOSH  also noted that the use of a tissue as source control, in their guidelines for  TB , had not been tested as of 1992. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1927", "contents": "In 2013, Gustavo et al. looked into the effectiveness of various methods of source control, including via the arm, via a tissue, via bare hands, and via a surgical mask. They concluded that simply covering a cough was not an effective method of stopping transmission, and a surgical mask was not effective at reducing the amount of displaced droplets detected compared to the other rudimentary forms of source control. [ 7 ]  Another paper noted that the fit of a face mask matters in its source control performance. [ 8 ]  (However, note that  OSHA  29  CFR  1910.134 does not cover the fit of face masks other than  NIOSH-approved respirators . [ 9 ] )"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1928", "contents": "While source control protects others from transmission arising from the wearer,  personal protective equipment  protects the wearer themselves. [ 11 ]   Cloth face masks  can be used for source control (as a last resort) but are not considered personal protective equipment [ 12 ] [ 11 ]  as they have low filter efficiency (generally varying between 2\u201360%), although they are easy to obtain and reusable after washing. [ 13 ]  There are no standards or regulation for self-made cloth face masks, [ 14 ]  and source control on a well-fitted cloth mask is worse than a surgical mask. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1929", "contents": "Surgical masks  are designed to protect against splashes and sprays, [ 16 ]  but do not provide complete respiratory protection from  germs  and other contaminants because of the loose fit between the surface of the face mask and the face. [ 17 ]   Surgical masks  are regulated by various national standards to have high  bacterial filtration efficiency  (BFE). [ 18 ] [ 19 ] [ 20 ]   N95/N99/N100 masks  and other  filtering facepiece respirators  can provide source control in addition to respiratory protection, but respirators with an unfiltered exhalation valve may not provide source control and require additional measures to filter exhalation air when source control is required. [ 16 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1930", "contents": "Some masks have exhalation valve that let the exhaled air go out unfiltered. The certification grade of the mask (such as  N95 ) is about the mask itself and it does not warrant any safety about the air that is expelled by the wearer through the valve. A mask with valve mainly increases the comfort of the wearer. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1931", "contents": "Unfiltered exhalation of air is found on both filtering facepiece and elastomeric respirators with exhalation valves. [ 21 ]  Unfiltered air is also found on  powered air-purifying respirators , which cannot ever filter exhaled air. [ 22 ]  During the  COVID-19 pandemic , masks with unfiltered-exhalation valves ran counter to the requirements of some mandatory mask orders. [ 23 ] [ 24 ]  Despite the aforementioned belief, a 2020 research by the NIOSH and CDC shows that an uncovered exhalation valve already provides source control on a level similar to, or even better than, surgical masks. [ 25 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1932", "contents": "It is possible to seal some unfiltered exhalation valves [ 26 ]  or to cover it with an additional surgical mask; this might be done where mask shortages make it necessary. [ 27 ] [ 28 ]  However, so long as there are no shortages, respirators  without  exhalation valves should still be preferred in situations where source control is necessary. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1933", "contents": "HIV  was a noted co-infection in around 35% of those affected by  TB  in some regions of the US, [ 31 ]  despite extended close contact being a requisite factor for infection. Respirable particles are noted to be created by handling TB-infected tissue, or by coughing by those actively infected. Once in the air, droplet nuclei can persist in unventilated spaces. Most people infected with TB are asymptomatic, unless the immune system is weakened by some other factor, like  HIV/AIDS , which can turn an infected person's latent TB into active TB source. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1934", "contents": "1994  CDC  guidelines brought three methods of source control for the prevention of TB:  administrative controls ,  engineering controls , and  personal protective equipment , particularly with the use of fit-checked  respirators . [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1935", "contents": "Administrative controls  mainly involve people and areas in hospital responsible for TB controls, including training, skin-testing, and regulatory compliance, as well as those responsible for quantifying the amount of TB present in the hospital's community and in-hospital, like staff. To assist with this,  OSHA  proposed TB guidelines in 1997, [ 33 ]  but withdrew them in 2003 following the decline of TB. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1936", "contents": "Engineering controls  mainly involve ventilation and planning isolation rooms, [ 33 ]  but can also involve environmental controls, like negative pressure, ultraviolet germicidal radiation, and the use of  HEPA  filters. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1937", "contents": "The use of  personal protective equipment , in this system of TB controls, requires the use of respirators whenever personnel are in contact with someone suspected of having TB, including during transport. This includes anyone near the infected person, all of whom  must  be provided with some sort of personal protective equipment, to avoid contracting TB. If PPE cannot be provided in time, the infected patient should be delayed from being moved through an area not controlled by PPE until the controls are in place, unless the care of the infected patient is compromised by an  administrative delay . [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1938", "contents": "During TB outbreaks in the 1990s, multiple hospitals upgraded their controls and policies to attenuate the spread of TB. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1939", "contents": "In 2007, the CDC HICPAC published a set of guidelines, called the  2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings , suggesting that use of \"barrier precautions\", defined as \"masks, gowns, [and] gloves\", would  not  be required, so long as it was limited to \"routine entry\", patients were not confirmed to be infected, and no aerosol-generating procedures were being done. \"Standard precautions\"  requiring  the use of masks, face shields, and/or eye protection, would be needed if there was potential for the spraying of bodily fluids, like during  intubation . [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1940", "contents": "The guidelines are the same regardless of the type of pathogen, but the guidelines also note that, based on the experience of  SARS-CoV  in Toronto, that \"N95 or higher respirators may offer additional protection to those exposed to aerosol-generating procedures and high risk activities\". [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1941", "contents": "Separate from \"barrier precautions\" and \"standard precautions\" are \" airborne precautions \", a protocol for \"infectious agents transmitted by the airborne route\", like with  SARS-CoV  and  tuberculosis , requiring 12  air changes per hour  for new facilities, and use of fitted  N95 respirators . These measures are used whenever someone is suspected of harboring an \"infectious agent\". [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1942", "contents": "During the  COVID-19 pandemic , cloth face masks for source control had been recommended by the U.S.  Centers for Disease Control and Prevention  (CDC) for members of the public who left their homes, and health care facilities were recommended to consider requiring face masks for all people who enter a facility.  Health care personnel and patients with COVID-19 symptoms were recommended to use surgical masks if available, as they are more protective. [ 38 ]   Masking patients reduces the personal protective equipment recommended by CDC for health care personnel under crisis shortage conditions. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1943", "contents": "By 2023,  The New York Times  noted that the CDC had dropped mandates for masks in hospitals during COVID, limiting the COVID policies to an advisory role. Use of masks for source control is still recommended in times of high viral activity, but the CDC did not provide numbers for benchmarks. The new policies are thought, according to the New York Times, based on various citations to medical literature, to increase mortality among vulnerable patients, especially those with  cancer . [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1944", "contents": "The New York Times  article cites a paper published in 2023, that suggests the high mortality of cancer patients following the  Omicron wave  may have been due to relaxing of policies preventing COVID-19 transmission [ 41 ]  (like source control policies). The 2023 paper also cites a research letter published in 2022, that suggests that the surge of COVID-19 cases in hospitals may have been due to the high contagiousness of Omicron, [ 42 ]  an article which suggested a high secondary attack rate relative to  Delta , [ 43 ]  and papers finding increased mortality of cancer patients due to higher rates of  breakthrough infections . [ 44 ] [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1945", "contents": "Also in 2023, new draft guidelines were proposed by the CDC HICPAC, to update the pre-COVID  2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings . [ a ]  The proposed updates were met with disapproval by the  National Nurses United  union, as they felt the changes did not go far enough. [ 40 ]  Changes included clarifying by adding \"source control\" as a qualification for the use of \"barrier precautions\". [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1946", "contents": "A paper in the  Journal of Hospital Infection , published in 2024, focusing on hospitals in the UK, found that the removal of mandates, based around  surgical masks , in hospitals was not associated with an increase in SARS-CoV-2 infections from weeks between December 4, 2021 to December 10, 2022. However, the authors noted that the end of mask mandates also coincided with an increase in Omicron infections, and that more data would be needed despite evidence for removal of mask mandates from 2022-2023. [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1947", "contents": "Subcutaneous emphysema  ( SCE ,  SE ) occurs when  gas  or  air  accumulates and seeps under the  skin , where normally no gas should be present.  Subcutaneous  refers to the  subcutaneous tissue , and  emphysema  refers to trapped air pockets.  Since the air generally comes from the  chest cavity , subcutaneous emphysema usually occurs around the upper  torso , such as on the  chest ,  neck ,  face ,  axillae  and  arms , where it is able to travel with little resistance along the  loose connective tissue  within the  superficial fascia . [ 1 ]  Subcutaneous emphysema has a characteristic crackling-feel to the touch, a sensation that has been described as similar to touching warm  Rice Krispies . [ 2 ]  This sensation of air under the skin is known as  subcutaneous crepitation,  a form of  crepitus ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1948", "contents": "Numerous etiologies of subcutaneous emphysema have been described.  Pneumomediastinum  was first recognized as a medical entity by  Laennec , who reported it as a consequence of trauma in 1819. Later, in 1939, at  Johns Hopkins Hospital , Dr.  Louis Hamman  described it in  postpartum  woman; indeed, subcutaneous emphysema is sometimes known as  Hamman's syndrome . However, in some medical circles, it can instead be more commonly known as  Macklin's Syndrome  after L. Macklin, in 1939, and C.C. and  M.T. Macklin , in 1944, who cumulatively went on to describe the pathophysiology in more detail. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1949", "contents": "Subcutaneous emphysema can result from puncture of parts of the  respiratory  or  gastrointestinal systems .  Particularly in the chest and neck, air may become trapped as a result of  penetrating trauma  (e.g.,  gunshot wounds  or  stab wounds ) or  blunt trauma .  Infection   (e.g.,  gas gangrene ) can cause gas to be trapped in the subcutaneous tissues. Subcutaneous emphysema can be caused by medical procedures and medical conditions that cause the pressure in the  alveoli  of the lung to be higher than that in the tissues outside of them. [ 4 ]   Its most common causes are  pneumothorax  or a  chest tube  that has become occluded by a  blood clot  or fibrinous material.  It can also occur spontaneously due to rupture of the alveoli, with dramatic presentation. [ 5 ]   When the condition is caused by surgery it is called  surgical emphysema . [ 6 ]  The term  spontaneous subcutaneous emphysema  is used when the cause is not clear. [ 5 ]  \nSubcutaneous emphysema is not typically dangerous in and of itself, however it can be a symptom of very dangerous underlying conditions, such as pneumothorax. [ 7 ]   Although the underlying conditions require treatment, subcutaneous emphysema usually does not; small amounts of air are reabsorbed by the body.  However, subcutaneous emphysema can be uncomfortable and may interfere with breathing, and is often treated by removing air from the tissues, for example by using large bore needles, skin incisions or subcutaneous catheterization."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1950", "contents": "Signs and symptoms of spontaneous subcutaneous emphysema vary based on the cause, but it is often associated with swelling of the neck and  chest pain , and may also involve  sore throat ,  neck pain ,  difficulty swallowing ,  wheezing  and  difficulty breathing . [ 5 ]   Chest X-rays  may show air in the  mediastinum , the middle of the chest cavity. [ 5 ]  A significant case of subcutaneous emphysema can be detected by  touching the overlying skin , which will feel like tissue paper or Rice Krispies. [ 8 ]   Touching the bubbles causes them to move and sometimes make a crackling noise. [ 9 ]   The air bubbles, which are painless and feel like small nodules to the touch, may burst when the skin above them is palpated. [ 9 ]   The tissues surrounding SCE are usually  swollen .  If large amounts of air leak into the tissues around the head, the face can swell considerably. [ 8 ]   In cases of subcutaneous emphysema around the neck, there may be a feeling of fullness in the neck, and the sound of the voice may change. [ 10 ]  If SCE is particularly extreme around the neck and chest, the swelling can interfere with breathing. The air can travel to many parts of the body, including the abdomen and limbs, because there are no separations in the  fatty tissue  in the skin to prevent the air from moving. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1951", "contents": "Conditions that cause subcutaneous emphysema may result from both  blunt  and  penetrating trauma ; [ 5 ]  SCE is often the result of a  stabbing  or  gunshot wound . [ 12 ]  \nSubcutaneous emphysema is often found in  car accident  victims because of the force of the crash."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1952", "contents": "Chest trauma , a major cause of subcutaneous emphysema, can cause air to enter the skin of the chest wall from the neck or lung. [ 9 ]  When the  pleural  membranes are punctured, as occurs in penetrating trauma of the chest, air may travel from the lung to the muscles and subcutaneous tissue of the chest wall. [ 9 ]   When the alveoli of the lung are ruptured, as occurs in  pulmonary laceration , air may travel beneath the  visceral pleura  (the membrane lining the lung), to the  hilum of the lung , up to the  trachea , to the neck and then to the chest wall. [ 9 ]  The condition may also occur when a  fractured rib  punctures a lung; [ 9 ]  in fact, 27% of patients who have rib fractures also have subcutaneous emphysema. [ 11 ]   Rib fractures may tear the  parietal pleura , the membrane lining the inside of chest wall, allowing air to escape into the subcutaneous tissues. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1953", "contents": "Subcutaneous emphysema is frequently found in pneumothorax (air outside of the lung in the chest cavity) [ 14 ] [ 15 ]  and may also result from  pneumomediastinum  (air in the mediastinum) or  pneumopericardium  (air in the  pericardial cavity  around the heart). [ 16 ]   A  tension pneumothorax , in which air builds up in the  pleural cavity  and exerts pressure on the organs within the chest, makes it more likely that air will enter the subcutaneous tissues through pleura torn by a broken rib. [ 13 ]   When subcutaneous emphysema results from pneumothorax, air may enter tissues including those of the face, neck, chest, armpits, or abdomen. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1954", "contents": "Pneumomediastinum can result from a number of events.  For example, foreign body  aspiration , in which someone inhales an object, can cause pneumomediastinum (and lead to subcutaneous emphysema) by puncturing the airways or by increasing the pressure in the affected lung(s) enough to cause them to burst. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1955", "contents": "Subcutaneous emphysema of the chest wall is commonly among the first indications that  barotrauma , damage caused by excessive pressure, has occurred; [ 1 ] [ 18 ]  it suggests that the lung was subjected to significant barotrauma. [ 19 ]  Thus the phenomenon may occur in diving injuries. [ 5 ] [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1956", "contents": "Trauma to parts of the respiratory system other than the lungs, such as rupture of a  bronchial tube , may also cause subcutaneous emphysema. [ 13 ]  Air may travel upward to the neck from a pneumomediastinum that results from a bronchial rupture, or downward from a torn trachea or  larynx  into the soft tissues of the chest. [ 13 ]  It may also occur with  fractures  of the  facial bones ,  neoplasms , during  asthma  attacks, as an adverse effect of the  Heimlich maneuver , and during   childbirth . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1957", "contents": "Injury with  pneumatic tools  is also known to cause subcutaneous emphysema, even in extremities (the arms and legs). [ 21 ]   It can also occur as a result of  rupture of the esophagus ; when it does, it is usually as a late sign. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1958", "contents": "Subcutaneous emphysema is a common result of certain types of surgery; for example it is not unusual in  chest surgery . [ 8 ]   It may also occur from surgery around the esophagus, and is particularly likely in prolonged surgery. [ 7 ]  Other potential causes are  positive pressure ventilation  for any reason and by any technique, in which its occurrence is frequently unexpected. It may also occur as a result of  oral surgery , [ 23 ]   laparoscopy , [ 7 ]  and  cricothyrotomy .  In a  pneumonectomy , in which an entire lung is removed, the remaining bronchial stump may leak air, a rare but very serious condition that leads to progressive subcutaneous emphysema. [ 8 ]  Air can leak out of the pleural space through an incision made for a  thoracotomy  to cause subcutaneous emphysema. [ 8 ]   On infrequent occasions, the condition can result from  dental  surgery, usually due to use of high-speed tools that are air driven. [ 24 ]   These cases result in immediate onset (usually) painless swelling of the face and neck;  crepitus  (crunching sound) typical of subcutaneous emphysema is often present and the subcutaneous air will be visible on X-ray. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1959", "contents": "One of the main causes of subcutaneous emphysema, along with pneumothorax, is an improperly functioning chest tube. [ 2 ]   Thus subcutaneous emphysema is often a sign that something is wrong with a chest tube; it may be clogged, clamped, or out of place. [ 2 ]  The tube may need to be replaced, or, if large amounts of air are leaking, a new tube may be added. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1960", "contents": "Since  mechanical ventilation  can worsen a pneumothorax, it can force air into the tissues; when subcutaneous emphysema occurs in a ventilated patient, it is an indication that the ventilation may have caused a pneumothorax. [ 2 ]  It is not unusual for subcutaneous emphysema to result from  positive pressure ventilation . [ 25 ]   Another possible cause is a ruptured trachea. [ 2 ]   The trachea may be injured by  tracheostomy  or  tracheal intubation ; in cases of tracheal injury, large amounts of air can enter the subcutaneous space. [ 2 ]  An  endotracheal tube  can puncture the trachea or bronchi and cause subcutaneous emphysema. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1961", "contents": "Air can be trapped under the skin in  necrotizing  infections such as  gangrene , occurring as a late sign in  gas gangrene , [ 2 ]  of which it is the hallmark sign. Subcutaneous emphysema is also considered a hallmark of  Fournier gangrene . [ 26 ]  Symptoms of subcutaneous emphysema can result when infectious organisms produce gas by  fermentation . When emphysema occurs due to infection, signs that the infection is systemic (i.e. that it has spread beyond the initial location) are also present. [ 9 ] [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1962", "contents": "Air is able to travel to the soft tissues of the neck from the mediastinum and the  retroperitoneum  (the space behind the  abdominal cavity ) because these areas are connected by fascial planes. [ 4 ]   From the punctured lungs or airways, the air travels up the  perivascular  sheaths and into the mediastinum, from which it can enter the subcutaneous tissues. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1963", "contents": "Spontaneous subcutaneous emphysema is thought to result from increased pressures in the lung that cause alveoli to rupture. [ 5 ]  In spontaneous subcutaneous emphysema, air travels from the ruptured alveoli into the  interstitium  and along the  blood vessels  of the lung, into the mediastinum and from there into the tissues of the neck or head. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1964", "contents": "Significant cases of subcutaneous emphysema are easy to diagnose because of the characteristic signs of the condition. [ 1 ]  In some cases, the signs are subtle, making diagnosis more difficult. [ 13 ]   Medical imaging  is used to diagnose the condition or confirm a diagnosis made using clinical signs. On a  chest radiograph , subcutaneous emphysema may be seen as  radiolucent  striations in the pattern expected from the  pectoralis major  muscle group. Air in the subcutaneous tissues may interfere with  radiography  of the chest, potentially obscuring serious conditions such as pneumothorax. [ 18 ]  It can also reduce the effectiveness of chest  ultrasound . [ 27 ]   On the other hand, since subcutaneous emphysema may become apparent in chest X-rays before a pneumothorax does, its presence may be used to infer that of the latter injury. [ 13 ]  Subcutaneous emphysema can also be seen in  CT scans , with the air pockets appearing as dark areas. CT scanning is so sensitive that it commonly makes it possible to find the exact spot from which air is entering the soft tissues. [ 13 ]   In 1944,  M.T. Macklin  and C.C. Macklin published further insights into the pathophysiology of spontaneous Macklin's Syndrome occurring as a result of a severe asthmatic attack."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1965", "contents": "The presence of subcutaneous emphysema in a person who appears quite ill and febrile after bouts of vomiting followed by left chest pain is very suggestive of the diagnosis of  Boerhaave's syndrome , which is a life-threatening emergency caused by rupture of the distal esophagus."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1966", "contents": "Subcutaneous emphysema can be a complication of CO 2   insufflation  with  laparoscopic surgery . \u00a0A sudden rise in  end-tidal CO 2  following the initial rise that occurs with insufflation (first 15-30 min) should raise suspicion of subcutaneous emphysema. [ 4 ]  Of note, there are no changes in the  pulse oximetry  or airway pressure in subcutaneous emphysema, unlike in endobronchial intubation, capnothorax, pneumothorax, or  CO 2  embolism ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1967", "contents": "Subcutaneous emphysema is usually  benign . [ 1 ]  Most of the time, SCE itself does not need treatment (though the conditions from which it results may); however, if the amount of air is large, it can interfere with breathing and be uncomfortable. [ 28 ]  It occasionally progresses to a state \"Massive Subcutaneous Emphysema\" which is quite uncomfortable and requires surgical drainage. When the amount of air pushed out of the airways or lung becomes massive, usually due to  positive pressure ventilation , the eyelids may swell so much that the patient cannot see. The pressure of the air may impede the blood flow to the areolae of the breast and skin of the scrotum or labia which can lead to necrosis. The latter are urgent situations requiring rapid, adequate  decompression . [ 29 ] [ 30 ] [ 31 ]  Severe cases can compress the trachea and do require treatment. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1968", "contents": "In severe cases of subcutaneous emphysema,  catheters  can be placed in the subcutaneous tissue to release the air. [ 1 ]  Small cuts, or \"blow holes\", may be made in the skin to release the gas. [ 16 ]   When subcutaneous emphysema occurs due to pneumothorax, a chest tube is frequently used to control the latter; this eliminates the source of the air entering the subcutaneous space. [ 2 ]   If the volume of subcutaneous air is increasing, it may be that the chest tube is not removing air rapidly enough, so it may be replaced with a larger one. [ 8 ]   Suction  may also be applied to the tube to remove air faster. [ 8 ]  The progression of the condition can be monitored by  marking the boundaries  of the emphysema on the patient's skin. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1969", "contents": "Since treatment usually involves dealing with the underlying condition, cases of spontaneous subcutaneous emphysema may require nothing more than bed rest, medication to control pain, and perhaps  supplemental oxygen . [ 5 ]  Breathing oxygen may help the body to absorb the subcutaneous air more quickly. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1970", "contents": "Air in subcutaneous tissue does not usually pose a lethal threat; [ 4 ]  small amounts of air are reabsorbed by the body. [ 8 ]   Once the pneumothorax or pneumomediastinum that causes the subcutaneous emphysema is resolved, with or without medical intervention, the subcutaneous emphysema will usually clear. [ 18 ]   However, spontaneous subcutaneous emphysema can, in rare cases, progress to a life-threatening condition, [ 5 ]  and subcutaneous emphysema due to mechanical ventilation may induce ventilatory failure. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1971", "contents": "The first report of subcutaneous emphysema resulting from air in the mediastinum was made in 1850 in a patient who had been coughing violently. [ 5 ]   In 1900, the first recorded case of spontaneous subcutaneous emphysema was reported in a  bugler  for the  Royal Marines  who had had a tooth extracted: playing the instrument had forced air through the hole where the tooth had been and into the tissues of his face. [ 5 ]   Since then, another case of spontaneous subcutaneous emphysema was reported in a submariner for the US Navy who had had a  root canal  in the past; the increased pressure in the submarine forced air through it and into his face. A case was reported at the  University Hospital of Wales  of a young man who had been coughing violently causing a rupture in the esophagus resulting in SE. [ 5 ]   The cause of spontaneous subcutaneous emphysema was clarified between 1939 and 1944 by Macklin, contributing to the current understanding of the  pathophysiology  of the condition. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1972", "contents": "Thoracic insufficiency syndrome  is the inability of the  thorax  to support normal  respiration . [ 1 ]   It is frequently associated with  chest  and/or  spinal  abnormalities.  Treatment options are limited, but include supportive  pulmonary  care and surgical options ( thoracoplasty  and/or implantation of  vertical expandable prosthetic titanium rib  (VEPTR) devices). [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1973", "contents": "Tracheobronchitis  is inflammation of the  trachea  and  bronchi . It is characterised by a cough, fever, and purulent (containing pus)  sputum  and is therefore suggestive of  pneumonia . It is classified as a respiratory tract infection. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1974", "contents": "Tracheobronchitis is often a  hospital-acquired infection , particularly in an  intensive care setting , associated with the use of  mechanical ventilators , and the need for inserting a  tracheal tube . In these cases it is known as ventilator-associated tracheobronchitis.\u00a0The infection begins in the trachea where it colonises and spreads to the bronchi."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1975", "contents": "The characteristic increased sputum produced can give problems in the removal of the tracheal tube (extubation). Tracheobronchial infections are responsible for up to 80% of\u00a0exacerbations in  chronic obstructive pulmonary disease . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1976", "contents": "Ventilator-associated tracheobronchitis  is a  hospital-acquired infection  usually contracted in an  intensive care unit  when a  mechanical ventilator  is used. [ 1 ]  The insertion of a tracheal tube can cause an infection in the trachea which then colonises and spreads to the  bronchi . If there is further spread and development into the lungs this will give rise to  ventilator-associated pneumonia .\u00a0Antibiotics are recommended to prevent this development but only as a short term measure as antibiotic resistance is already high in some of the pathogens involved.\u00a0This does not always progress to pneumonia. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1977", "contents": "Fungal tracheobronchitis  can be invasive into the lung tissue or pulmonary artery and cause a severe lung infection. The extra secreted mucus from tracheobronchitis\u00a0plugs the airways allowing the fungal pathogens to lodge and multiply. Local damage to the tracheal wall that can be caused by mechanical ventilation is a risk factor for this. Respiratory failure may develop from this infection. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1978", "contents": "Herpetic tracheobronchitis  is caused by  herpes simplex virus  and causes small ulcers covered in exudate to form on the mucous membranes. The exudate contains necrotic cells from the mucosal epithelium."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1979", "contents": "The characteristic increased sputum produced can give problems in the removal of the tracheal tube (extubation). In the course of  cystic fibrosis  the lungs are affected. Thickened mucus secretions block the airways making infection possible. The recurrence of tracheobronchitis presents a major problem. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1980", "contents": "In  chronic obstructive pulmonary disease  tracheobronchial infections are responsible for up to 80% of\u00a0 exacerbations . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1981", "contents": "Tracheobronchitis often affects dogs particularly those confined in kennels where their persistent barking worsens the inflammation. This  canine infectious\u00a0tracheobronchitis  is more usually known as  kennel cough ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1982", "contents": "Tracheobronchopathia osteochondroplastica (TO)  is a rare benign disease of unknown cause, in which multiple  cartilaginous  or bony submucosal  nodules  project into the  trachea  and proximal  bronchi . The nodules usually  spare the posterior wall of the airway because they are of cartilaginous origin, while the posterior wall of the airway is membranous (does not contain cartilage). This is as opposed to tracheobronchial  amyloidosis , which does not spare the posterior wall."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1983", "contents": "It usually occurs in men around their fifth decade of life, as opposed to tracheobronchial papillomatosis due to  HPV infection , which usually occurs in younger patients. TO can cause airway obstruction, bleeding and chronic cough. Treatment involves the use of  bronchodilators , and physical dilatation by  bronchoscopy . The patients are also more prone to post-obstructive  pneumonia  and chronic lung infection in severe cases. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1984", "contents": "The differential of TO includes amyloidosis, which is typically circumferential, papillomatosis, though this usually occurs in younger patients and can cause lung cavitation when disseminated,  granulomatosis with polyangiitis , though this is circumferential as well and often involves distal lung cavitation as well.  Relapsing polychondritis  can also spare the posterior wall, though it is not typically nodular in appearance. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1985", "contents": "Tram tracks  or  tram-track signs  are  medical signs  that bear some resemblance to  tramway tracks ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1986", "contents": "When found in the  lungs , tram tracks are  radiologic signs  that are usually accompanied by  pulmonary edema  in cases of  congestive heart failure  and  bronchiectasis . Tram tracks are caused by  bronchial wall thickening , and can be detected on a lateral  chest X-ray . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1987", "contents": "The term \"tram tracks\" is also used to describe the  basement membrane  duplication found on light microscopy that is characteristic of  membranoproliferative glomerulonephritis  (MPGN) type I. (It is less commonly associated with types II and III.) [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1988", "contents": "The term has also been used to describe findings associated with  optic nerve sheath meningioma . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1989", "contents": "Tram track-shaped calcifications in the  cerebral cortex  indicate  Sturge\u2013Weber syndrome . [ citation needed ]  where intracranial gyriform calcification (brain imaging) seen mostly in occipital and posterior parietal/temporal lobe ;this syndrome consists triad of port wine stain,seizure(usually focal but may become generalized),eye manifestation(e.g. glaucoma)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1990", "contents": "Tram track appearance in mammography/USG indicates Duct Ectasia. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1991", "contents": "This  medical sign  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_1992", "contents": "In  transfusion medicine ,  transfusion-associated circulatory overload  (aka  TACO ) is a  transfusion reaction  (an  adverse effect  of  blood transfusion ) resulting in signs or symptoms of excess fluid in the circulatory system ( hypervolemia ) within 12 hours after transfusion. [ 2 ]  The symptoms of TACO can include shortness of breath ( dyspnea ), low blood oxygen levels ( hypoxemia ), leg swelling ( peripheral edema ), high blood pressure ( hypertension ), and a high heart rate ( tachycardia ). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1993", "contents": "It can occur due to a rapid transfusion of a large volume of  blood  but can also occur during a single red blood cell transfusion (about 15% of cases). [ 2 ]  It is often confused with  transfusion-related acute lung injury  (TRALI), another transfusion reaction. The difference between TACO and TRALI is that TRALI only results in symptoms of respiratory distress while TACO can present with either signs of respiratory distress, peripheral leg swelling, or both. [ 4 ]  Risk factors for TACO are diseases that increase the amount of fluid a person has, including liver, heart, or kidney failure, as well as conditions that require many transfusions. High and low extremes of age are a risk factor as well. [ 5 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1994", "contents": "The management of TACO includes immediate discontinuation of the transfusion, supplemental oxygen if needed, and medication to remove excess fluid. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1995", "contents": "The primary symptoms of TACO are signs of respiratory distress (shortness of breath, low oxygen levels in the blood) along with signs of excess fluid within the circulatory system (leg swelling, high blood pressure, and an elevated heart rate). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1996", "contents": "On physical exam, patients may present with crackles when listening to the lungs, a  murmur  (S-3 murmur) when listening to the heart, leg swelling, and distended veins in the neck ( jugular venous distension ). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1997", "contents": "Risk factors that can promote the development of TACO include conditions that predispose individuals to excess fluid in the circulatory system ( liver failure  causing low levels of protein in the blood ( hypoalbuminemia ), [ 5 ]   heart failure , [ 6 ] [ 7 ]   renal insufficiency , [ 6 ] [ 7 ]  or  nephrotic syndrome [ 7 ] ), conditions that place increased stress on the respiratory system ( lung disease [ 6 ] ), and conditions necessitating large volume transfusions ( severe anemia [ 6 ] ). Age has also been found to be a risk factor where individuals less than 3 years old and over 60 years old are at increased risk. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1998", "contents": "In addition, the risk of TACO increases as the number of units of blood products transfused increases. [ 9 ]  Table 1 shows the volume transfused with each blood product. Multiple blood products and blood products with larger volumes increase the risk for TACO. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_1999", "contents": "The National Healthcare Safety Safety Network division of the  Centers for Disease Control and Prevention  (CDC) released an updated criteria table in 2021: [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2000", "contents": "Patients diagnosed with TACO should have at least 1 of the following two characteristics within 12 hours after the transfusion was ended:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2001", "contents": "Along with:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2002", "contents": "TACO can be categorized by severity: [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2003", "contents": "TACO and  transfusion-related acute lung injury  (TRALI) are both complications following a transfusion, and both can result in respiratory distress. [ 2 ]  TACO and TRALI are often difficult to distinguish in the acute situation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2004", "contents": "Assessing fluid status is key in differentiating between the two. In TACO, the patient will always have a positive  fluid balance  and will often present with hypertension, jugular venous distension, elevated BNP, peripheral edema, and will respond well to  diuretics . In contrast, TRALI is not associated with fluid overload and the patient may have a positive, even, or net fluid balance. Patients with TRALI often present with hypotension, no signs of right-heart fluid overload, normal BNP, and lack of clinical improvement in response to diuretics. [ 12 ] [ 13 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2005", "contents": "Other causes of edema that can promote a volume-overloaded state and predispose individuals to TACO include: heart failure, renal insufficiency, nephrotic syndrome, cirrhosis, and chronic venous insufficiency. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2006", "contents": "The development of TACO is thought to be due to a 2-hit mechanism. [ 15 ]  The first hit is the state of the patient and the second hit is the blood transfusion itself. A patient may be receiving blood due to any number of causes and may have heart or kidney dysfunction which can lead to excess fluid. Upon transfusion of the blood product, the patient is overwhelmed by the excess fluid and develops symptoms related to volume overload. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2007", "contents": "The clinical symptoms from TACO are due to an excess of fluid within the circulatory system. As a result, there is increased pressure within the circulatory system, resulting in fluid moving into the surrounding tissues. [ 4 ]  In the lungs, the extra fluid accumulates into the air sacs within the lung, causing difficulties in oxygen getting into the blood. This results in low blood oxygen levels and shortness of breath. In the arms and legs, the fluid accumulates in the tissues, causing swelling. This is most prominent in the legs due to the effects of gravity. Conditions that predispose to increased hydrostatic pressure (heart failure and renal insufficiency) or decreased oncotic pressure (liver failure, malnutrition, nephrotic syndrome) places individuals at increased risk for TACO. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2008", "contents": "Transfusion associated circulatory overload is prevented by avoiding unnecessary transfusions by following strict criteria necessitating blood transfusion, closely monitoring patients receiving transfusions, and transfusing smaller volumes of blood at a slower rate. Blood products are typically transfused at 2.0 to 2.5 ml/kg per hour but can be reduced to 1.0 ml/kg per hour for individuals at increased risk for TACO. [ 16 ]  Patients susceptible to volume overload (e.g., renal insufficiency or heart failure) may be pre-treated with a diuretic either during or immediately following transfusion to reduce the overall net fluid balance. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2009", "contents": "If TACO is suspected, the transfusion is stopped immediately and the patient is sat upright to prevent the fluid from backing up into the lungs. Treatment is two-fold: respiratory support and removal of excess fluid. [ 8 ]  Patients with respiratory distress and/or hypoxemia are given supplemental oxygen or ventilatory support (through non-invasive or mechanical ventilation, if needed). To remove the excess fluid, patients are given diuretic therapy and their urine output is closely monitored to quantitate the amount removed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2010", "contents": "The reported incidence of TACO is difficult to determine as many cases may be undetected but its incidence is estimated at 1% of all individuals receiving transfusion, with hospitalized patients being at increased risk. [ 17 ] [ 18 ]  TACO is the most commonly reported cause of transfusion-related death and major morbidity in the UK, [ 2 ]  and second most common cause in the USA. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2011", "contents": "Death from pulmonary edema as the result of circulatory overload following transfusion was reported as early as 1936. [ 20 ]  However, the term 'transfusion associated circulatory overload' was not coined until the 1990s when it was seen as a separate complication following blood transfusion. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2012", "contents": "Vaping-associated pulmonary injury  ( VAPI ), [ 4 ]  also known as  vaping-associated lung injury  ( VALI ) [ 1 ]  or  e-cigarette, or vaping, product use associated lung injury  ( E/VALI ), [ 2 ] [ a ]  is an  umbrella term , [ 15 ] [ 16 ]  used to describe  lung diseases  associated with the use of  vaping products  that can be severe and life-threatening. [ 3 ]  Symptoms can initially mimic common pulmonary diagnoses, such as  pneumonia , but sufferers typically do not respond to  antibiotic  therapy. [ 4 ]   Differential diagnoses  have overlapping features with VAPI, including  COVID-19 . [ 17 ] [ 18 ] [ 19 ]  According to a systematic review article, \"Initial case reports of vaping-related lung injury date back to 2012, but the ongoing outbreak of EVALI began in the summer of 2019.\" [ 20 ]  EVALI cases continue to be diagnosed. \"EVALI has by no means disappeared,\" Dr. Kligerman said. \"We continue to see numerous cases, even during the pandemic, many of which are initially misdiagnosed as COVID-19.\" [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2013", "contents": "Sufferers usually present for care within a few days to weeks of symptom onset. [ 4 ]  Starting, in September\u00a02019, the US  Centers for Disease Control and Prevention  (CDC) reported on a nation-wide  outbreak of severe lung disease linked to vaping , [ 22 ]  or the process of inhaling aerosolized substances with battery-operated  electronic cigarettes  (e-cigarettes), [ 23 ]   ciga-likes , or  vape mods . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2014", "contents": "All CDC-reported cases of VAPI involved a history of using e-cigarette, or vaping, products, with most samples having tested positive for  tetrahydrocannabinol  (THC) by the US FDA and most patients reporting a history of using a THC-containing product. [ 3 ]  CDC data show that the outbreak peaked in September 2019, and declined steadily to a low level through January 2020. [ 24 ]  In late February 2020, a CDC-authored article in the  NEJM  stated that the VAPI outbreak was \"driven by the use of THC-containing products from informal and illicit sources.\" [ 25 ] [ 24 ]  However, the CDC also stated, \"Evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC or non-THC products, in some of the reported EVALI cases.\" [ 26 ]  In 2021, researchers at Johns Hopkins University analyzed the vape aerosols of popular brands such as Juul and Vuse, and found \"nearly 2,000 chemicals, the vast majority of which are unidentified.\" [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2015", "contents": "Due to the  COVID-19 pandemic , that exceeded 1 million worldwide deaths in October 2020, it is now possible that shared vaping devices spread  COVID-19 . [ 28 ]  Several organizations, including  Purdue University  and  Public Health England  (PHE), strongly advise against sharing vapes. [ 29 ] [ 30 ]  The CDC has stated that the THC  cutting agent   vitamin E acetate  is very strongly implicated in VAPI, [ 31 ]  but evidence was not sufficient to rule out a contribution from other chemicals of concern to VAPI as of January 2020. [ 3 ] [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2016", "contents": "Commonly reported symptoms include shortness of breath, cough, fatigue, body aches, dizziness, fever, nausea, vomiting, and diarrhea. [ 4 ]  Additional symptoms may include chest pain, abdominal pain, chills, or weight loss. [ 33 ]  Symptoms can initially mimic common pulmonary diagnoses like  pneumonia , but individuals typically do not respond to  antibiotic  therapy. [ 4 ]   In some patients, gastrointestinal symptoms can precede respiratory symptoms. [ 2 ]  Individuals typically present for care within a few days to weeks of symptom onset. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2017", "contents": "At the time of hospital presentation, the individual is often  hypoxic  and meets  systemic inflammatory response syndrome  (SIRS) criteria, including fever. [ 4 ]  Physical exam can reveal  rapid heart rate  or  rapid breathing . [ 34 ]   Auscultation  of the lungs tends to be unremarkable, even in patients with severe lung disease. [ 2 ]  In some cases, the affected individuals have progressive respiratory failure, leading to intubation. [ 4 ]  Several affected individuals have needed to be placed in the  intensive care unit  (ICU) and on  mechanical ventilation . [ 22 ]  Time to recovery for hospital discharge has ranged from days to weeks. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2018", "contents": "No single cause of these illnesses has been established as of November 2019 [update] . [ 3 ]  Many different substances and product sources continued to be under investigation. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2019", "contents": "Products have been found to be contaminated with fungi and bacteria, [ 49 ]  which may cause  fungal pneumonia , and  bacterial pneumonia  respectively."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2020", "contents": "Nicotine-containing e-liquids are extracted from tobacco that may contain impurities. [ 50 ]  Tobacco-specific impurities such as  cotinine , nicotine-N'-oxides ( cis  and  trans  isomers), and beta-nornicotyrine are believed to be the result of bacterial action or oxidation during the extracting of nicotine from tobacco. [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2021", "contents": "Infectious diseases  by  pathogens  uncleaned vapes and/or vape sharing:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2022", "contents": "In addition to vaping, some individuals have also experienced VAPI through \" dabbing \". [ 4 ]  Dabbing uses a different type of device to heat and extract cannabinoids for inhalation. [ 4 ]  It is a process that entails superheating and inhaling particles into the lungs that contain THC and other types of cannabidiol plant materials. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2023", "contents": "Vaping  refers to the practice of inhaling an  aerosol  from an  electronic cigarette device , [ 4 ]  which works by heating a liquid that can contain various substances, including  nicotine ,  tetrahydrocannabinol  (THC), flavoring, and additives (e.g.  glycerin  (sold as vegetable glycerine (VG)),  propylene glycol  (PG)). [ 8 ]  The  long-term health impacts of vaping  are unknown. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2024", "contents": "Most individuals treated for VAPI [ a ]  report vaping the cannabis compounds THC and/or  cannabidiol  (CBD), and some also report vaping nicotine products. [ 4 ]  A small but consistent minority of EVALI patients have been found not to be users of THC products. [ 56 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2025", "contents": "VAPI appears to be a type of acute lung injury, similar to acute fibrinous  pneumonitis ,  organizing pneumonia , or  diffuse alveolar damage . [ 57 ]  VAPI appears to be a general term for various causes of acute lung damage due to vaping. [ 58 ]  There is no evidence of an infectious etiology causing VAPI. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2026", "contents": "High clinical suspicion is necessary to make the diagnosis of VAPI. [ 4 ]  As of October\u00a02019, VAPI [ a ]  was considered a  diagnosis of exclusion  because no specific tests or markers existed for its diagnosis. [ 2 ]  Healthcare providers were advised to evaluate for alternative diagnoses (e.g., cardiac, gastrointestinal, rheumatologic, neoplastic, environmental, or occupational exposures, or causes of  acute respiratory distress syndrome ) as suggested by clinical presentation and medical history, while also considering multiple etiologies, including the possibility of VAPI occurring with a concomitant infection. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2027", "contents": "All healthcare providers evaluating patients for VAPI were urged to consider obtaining a thorough patient history, including symptoms and recent use of e-cigarette, or vaping, products, along with substances used, duration and frequency of use, and method of use. [ 2 ]  Additionally a detailed physical examination was recommended, specifically including vital signs and pulse- oximetry . [ 2 ]  Laboratory testing guided by clinical findings, which might include a respiratory virus panel to rule out infectious diseases,  complete blood count  with differential, serum inflammatory markers ( C-reactive protein  [CRP],  erythrocyte sedimentation rate  [ESR]), liver  transaminases , and urine toxicology testing, including testing for THC were recommended. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2028", "contents": "Imaging, typically a chest  X-ray , with consideration for a chest CT if chest X-ray results did not correlate with the clinical picture or to evaluate severe or worsening disease were urged. [ 2 ]  It was pointed out that consulting with specialists (e.g. critical care, pulmonology, medical toxicology, or infectious disease) could help guide further evaluation. [ 2 ]  The diagnosis is commonly suspected when the person does not respond to antibiotic therapy, and testing does not reveal an alternative diagnosis. [ 4 ]  Many of the reported cases involved worsening respiratory failure within 48\u00a0hours of admission, following the administration of empiric antibiotic therapy. [ 59 ]  Lung biopsies are not necessary for the diagnosis but are performed as clinically indicated to rule out the likelihood of infection. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2029", "contents": "There are non-specific laboratory abnormalities that have been reported in association with the disease, including elevations in white blood cell count (with neutrophilic predominance and absence of eosinophilia), transaminases, procalcitonin, and inflammatory markers. [ 4 ] [ 59 ]  Infectious disease testing, including blood and sputum cultures and tests for influenza,  Mycoplasma,  and  Legionella  were all found to be negative in the majority of reported cases. [ 59 ]  Imaging abnormalities are typically bilateral and are usually described as \"pulmonary infiltrates or opacities\" on chest X-ray and \"ground-glass opacities\" on chest CT. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2030", "contents": "Bronchoalveolar lavage  specimens may exhibit an increased level of  neutrophils  in combination with lymphocytes and vacuole-laden macrophages. [ 22 ]  Lavage cytology with oil red O staining demonstrated extensive  lipid-laden alveolar macrophages . [ 59 ] [ 60 ]  In the few cases in which lung biopsies were performed, the results were consistent with acute lung injury and included a broad range of features, such as acute fibrinous pneumonitis, diffuse alveolar damage, lipid-laden macrophages, and organizing pneumonia. [ 34 ] [ 55 ]  Lung biopsies often showed neutrophil predominance as well, with rare eosinophils. [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2031", "contents": "Based on the clinical characteristics of VAPI [ a ]  cases from ongoing federal and state investigations, interim surveillance case definitions for confirmed and probable cases have been developed. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2032", "contents": "The CDC surveillance case definition for  confirmed  cases of severe pulmonary disease associated with e-cigarette use: [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2033", "contents": "The CDC surveillance case definition for  probable  cases of severe pulmonary disease associated with e-cigarette use: [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2034", "contents": "These surveillance case definitions are meant for public health data collection purposes and are not intended to be used as a clinical diagnostic tool or to guide clinical care; they are subject to change and will be updated as additional information becomes available. [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2035", "contents": "As VAPI was, as of October\u00a02019, a diagnosis of exclusion, a variety of respiratory diseases must be ruled out before a diagnosis of VAPI can be made. [ 2 ]  The differential diagnosis should include more common diagnostic possibilities, such as  community-acquired pneumonia , as well as do-not-miss diagnoses, such as  pulmonary embolism . [ 2 ]  Other commonly documented hospital diagnoses for cases of severe pulmonary disease associated with e-cigarette use have included  acute respiratory distress syndrome  (ARDS), sepsis, acute hypoxic respiratory failure, and pneumonitis. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2036", "contents": "As of September\u00a02019, distinctions were still being made between processes occurring in association with vaping or the use of nicotine-containing liquids and those considered as alternative diagnoses to VAPI. [ 34 ]  These processes include the following:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2037", "contents": "The use of imaging and other diagnostic modalities, including chest CT, bronchoscopy with bronchoalveolar lavage, and lung biopsy, may provide additional information to determine the presence of these processes and potentially establish a definitive diagnosis, but are generally not performed unless clinically indicated. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2038", "contents": "As of October\u00a018, 2019 [update] , the CDC has published updated interim guidance based on the most current data to provide a framework for healthcare providers in their management and follow-up of persons with symptoms of VAPI. [ 2 ]  Initial management involves deciding whether to admit a patient with possible VAPI [ a ]  to the hospital. Currently, [ when? ]  the CDC recommends that patients with suspected VAPI should be admitted if they have decreased O 2  saturation (<95%) on room air, are in respiratory distress, or have comorbidities that compromise pulmonary reserve. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2039", "contents": "Once admitted, initiation of  corticosteroids  should be considered, which have been found to be helpful in treating this injury. [ 2 ]  Several case reports describe improvement with corticosteroids, likely because of a blunting of the inflammatory response. [ 2 ]  In a group of patients in Illinois and Wisconsin, 92% of 50\u00a0patients received corticosteroids, and those that began glucocorticoid therapy continued on it for at least seven\u00a0days. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2040", "contents": "The medical team documented in 65% of 46\u00a0patient notes that \"respiratory improvement was due to the use of glucocorticoids\". [ 34 ]  Among 140\u00a0cases reported nationally to the CDC that received corticosteroids, 82% of patients improved. [ 2 ]  In patients with more severe illness, a more aggressive empiric therapy with corticosteroids as well as antimicrobial and antiviral therapy may be warranted. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2041", "contents": "As a large proportion of patients were admitted to an intensive care unit based on data submitted to the CDC, many patients require  supplemental oxygen  via  nasal cannula , high-flow oxygen, bilevel positive airway pressure (BiPAP), or mechanical ventilation. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2042", "contents": "During influenza season, health care providers should consider influenza in all patients with suspected VAPI. [ 66 ]  Decisions on initiation or discontinuation of treatment should be based on specific clinical features and, when appropriate, in consultation with specialists. [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2043", "contents": "Special consideration should be given to high-risk patients such as the elderly, those with a history of cardiac or lung disease, or pregnant individuals. [ 2 ]  Patients over 50\u00a0years old have an increased risk of intubation and might need longer hospitalizations. [ 2 ] \nCDC says patients should be advised to discontinue the use of vaping products upon hospital admission and during outpatient follow-up, to speed recovery and avoid potential recurrence of symptoms or lung injury. [ 2 ]  Evidence-based tobacco product quitting strategies include behavioral counseling and U.S.  Food and Drug Administration  (US FDA)-approved  cessation medications . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2044", "contents": "Due to reports of relapse during corticosteroid tapers after hospitalization, the CDC recommends scheduling a follow-up visit no later than one to two weeks after discharge from inpatient hospital treatment for VAPI, with considerations for performing pulse-oximetry testing and repeat CXR. [ 2 ]  In one to two months, healthcare providers should consider additional follow-up testing, including spirometry, diffusion capacity testing, and another repeat CXR. [ 2 ]  In patients with persistent hypoxemia (O 2  saturation <95%) requiring home oxygen at discharge, consider ongoing pulmonary follow-up. [ 2 ]  In patients treated with high-dose corticosteroids, consider endocrinology follow-up to monitor adrenal function. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2045", "contents": "As it is unknown whether patients with a history of VAPI are at increased risk for severe complications with influenza or other respiratory infections, follow-up care should also include annual vaccination against influenza for all persons over 6\u00a0months of age, including patients with a history of VAPI, as well as administration of the pneumococcal vaccine according to current guidelines. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2046", "contents": "An important part of both inpatient and follow-up care for VAPI involves advising patients to discontinue use of e-cigarette or vaping products. [ 67 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2047", "contents": "The  CDC  and the  FDA  recommend that people not use e-cigarettes or other vaping products that contain  THC , particularly products purchased off the street or obtained from informal sources like friends, family, or online sellers. [ 68 ]  In addition, CDC recommends that individuals not modify or add any substances to e-cigarettes or other vaping products that are not intended by the manufacturer. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2048", "contents": "Avoiding e-cigarettes entirely avoids the risk of VAPI as well as other negative health consequences of vaping, but some health advocates promote e-cigarettes for certain populations as a means to help smokers of conventional cigarettes to quit. Research into the effectiveness of this approach is still incomplete. [ 69 ] [ 70 ] [ 71 ] [ 72 ] [ 73 ] [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2049", "contents": "The outbreak of vaping-related lung injuries in 2019 and 2020 mainly affected young people, [ 75 ]  primarily in the United States. [ 76 ]  As of February\u00a04, 2020 [update] , there have been 2,758\u00a0cases of VAPI [ a ]  reported from all 50\u00a0states, the District of Columbia, Puerto Rico, and the US Virgin Islands. [ 3 ]  The CDC has received complete gender and age data on these cases with 70% of cases being male. [ 3 ]  The median age of cases is 24\u00a0years and ranges from 13 to 85\u00a0years. [ 3 ]  79% of cases are under 35\u00a0years old. [ 3 ]  There have been 64\u00a0confirmed deaths in 28\u00a0states and the District of Columbia from this outbreak ranging from ages 15\u201375\u00a0years old. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2050", "contents": "Of the 2,051\u00a0cases reported to the CDC, information on substance use is known for 867\u00a0cases in the three months prior to symptom onset as of October 15, 2019. [ 3 ]  About 86% reported using THC-containing products; 34% reported exclusive use of THC-containing products. [ 3 ]  About 64% reported using nicotine-containing products; 11% reported exclusive use of nicotine-containing products. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2051", "contents": "On September 28, 2019, the first case of vaping-associated pulmonary injury was identified in Canada. [ 77 ]  A number of other probable cases have been reported in British Columbia and New Brunswick as of October\u00a02019. [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2052", "contents": "In September\u00a02019, a US  Insurance Journal  article stated that at least 15\u00a0incidents of vaping related illnesses have been reported worldwide prior to 2019, occurring from Guam to Japan to the UK to the US. [ 79 ]  12\u00a0cases of health problems with nicotine-containing e-cigarettes were reported to the UK's Medicines and Healthcare products Regulatory Agency (MHRA), with at least one case bearing high similarities to the  lipid pneumonia  cases reported in the US. [ 79 ]  One lipoid pneumonia-related death in the UK was associated with e-cigarettes in 2010. [ 80 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2053", "contents": "Medical officials in continental Europe have reported two cases serious medical problems related to vaping products, one early case related to e-cigarettes documented in Northern Spain in 2015 and a second in Belgium in 2019. Since many of the cases in North America were traced to THC cartridges as well as the use of e-cigarette vape products, but THC remains illegal in European countries, the disease burden related to vaping has been significantly lower in Europe despite the prevalence of e-cigarette use. [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2054", "contents": "Before the outbreak, one lipoid pneumonia-related death in the UK was associated with e-cigarettes in 2010. [ 80 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2055", "contents": "18-year-old Rapha\u00ebl Pauwaert from  Brussels  died on November 6, 2019, [ 82 ]  after developing pneumonia [ 83 ]  and being placed in a  medically induced coma  because he was unable to breathe on his own. [ 84 ]  He received an e-cigarette as a gift for his 18th birthday. [ 83 ]  His doctor stated Pauwaert's fatal  lung infection  probably resulted from the CBD vapor. [ 85 ]  This was considered the first death tied to vaping in Belgium. [ 85 ]  Pauwaert's CBD oils were tested for vitamin\u00a0E at the Saint-Luc Hospital in November 2019. [ 84 ]  \"Vitamin E (alpha  tocopherol ) and vitamin E acetate were not detected in the vaping fluid by ultraperformance liquid chromatography coupled with UV detection.\" [ 86 ]  The death is under investigation by the Brussels Public Prosecutor's Office. [ 87 ]  A friend of Pauwaert's was also hospitalized with the identical symptoms after using the same type of e-cigarette, but he survived. [ 88 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2056", "contents": "The first case of a vaping-related lung illness in the  Philippines  was reported in November 2019. [ 89 ]  A 16-year-old girl from central Philippines was vaping e-cigarettes for half a year. [ 89 ]  She had difficulty breathing and was admitted to the hospital in October 2019. [ 89 ]  She was discharged after she received treatment from a pediatric  pulmonologist . [ 89 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2057", "contents": "Yellow nail syndrome , also known as \" primary lymphedema associated with yellow nails and pleural effusion \", [ 1 ] :\u200a849\u200a  is a very rare  medical   syndrome  that includes  pleural effusions ,  lymphedema  (due to under development of the  lymphatic vessels ) and yellow  dystrophic  nails. [ 2 ]  Approximately 40% will also have  bronchiectasis . It is also associated with chronic  sinusitis  and persistent coughing.  It usually affects adults. [ 3 ] [ 4 ] :\u200a665\u200a [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2058", "contents": "The nails are markedly thickened with yellow to yellow-green discoloration of the nails. [ 1 ] :\u200a792\u200a [ 6 ]  They grow slowly, at a rate of 0.25\u00a0mm/week or less. The nails may have ridges and increased side-to-side curvature, reduction of the  white crescent  and  detachment of the nail from the nailbed . [ 5 ]  These nail abnormalities may also change over time. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2059", "contents": "Most people with yellow nail syndrome (four fifths) have lymphedema; it is symmetrical and typically affects both legs. It is the first symptom of the condition in about a third. Involvement of the arms and face is more unusual, as is lymphedema of the abdomen with  ascites  (fluid collection in the abdominal cavity) and  fluid collection around the heart . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2060", "contents": "Various lung problems can occur in people with yellow nail syndrome. Many experience cough and  shortness of breath . Forty percent of cases develop  pleural effusions , which are collections of fluid in the  pleural cavity  (the space that contains the lungs and normally only has a minimal amount of fluid in it). [ 5 ]  About half of all people with yellow nail syndrome have either recurrent  chest infections  or a chronic lung condition known as  bronchiectasis  which causes chronic production of  sputum  with episodes of worsening. Forty percent of people with yellow nail syndrome have chronic  sinusitis . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2061", "contents": "Yellow nail syndrome has been associated with some drugs,  e.g.   penicillamine ,  bucillamine  and  gold sodium thiomalate . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2062", "contents": "It has also been associated with exposure to titanium from dental implants or consuming food containing titanium dioxide. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2063", "contents": "Although it has been described in families, it has been suggested that it might not have a genetic link. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2064", "contents": "The diagnosis is based on the combination of the symptoms. Generally, people are diagnosed with yellow nail syndrome if they have two or three of the three classical symptoms (yellow nails, lymphedema and pleural effusion). The nail changes are considered essential for the diagnosis, but they can be subtle. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2065", "contents": "Pulmonary function testing  can show obstruction of the airways. People with pleural effusions may show evidence of restriction in lung volumes due to the fluid. Analysis of the fluid in pleural effusions generally shows high levels of protein but low levels of cholesterol and  lactate dehydrogenase , but about 30% of effusions are  chylous  ( chylothorax ) in that they have the characteristics of  lymph . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2066", "contents": "A  lymphogram  may be performed in people with lymphedema. This can show both under developed (hypoplastic) lymphatic ducts and dilated ducts. Dye may be found in the skin months after the initial test.  Scintigraphy  of lymph flow (lymphoscintigraphy) shows delays in drainage of lymph (sometimes asymmetrically), although this test can also be normal. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2067", "contents": "Normal treatment for swelling and any respiratory problems is appropriate.  Nutritional supplementation with  Vitamin E  in some studies has been shown to be effective in controlling nail changes. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2068", "contents": "People with yellow nail syndrome have been found to have a moderately reduced lifespan compared to people without the condition. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2069", "contents": "The condition is thought to be rare, with approximately 150 cases described in the medical literature. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2070", "contents": "The condition was first reported by Heller in 1927 and the first case series was described in a publication in 1964 by London physicians  Peter Samman  and William White. [ 10 ] [ 11 ] [ 12 ]  Other cases may have been recorded in 1962. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2071", "contents": "This template's  initial visibility currently defaults to  autocollapse , meaning that if there is another collapsible item on the page (a  navbox, sidebar , or  table with the collapsible attribute ), it is hidden apart from its title bar; if not, it is fully visible."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2072", "contents": "To change this template's initial visibility, the  |state=   parameter  may be used:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2073", "contents": "Acute respiratory distress syndrome  ( ARDS ) is a type of  respiratory failure  characterized by rapid onset of widespread  inflammation  in the  lungs . [ 1 ]  Symptoms include  shortness of breath  (dyspnea),  rapid breathing  (tachypnea), and  bluish skin coloration  (cyanosis). [ 1 ]  For those who survive, a decreased  quality of life  is common. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2074", "contents": "Causes may include  sepsis ,  pancreatitis ,  trauma ,  pneumonia , and  aspiration . [ 1 ]  The underlying mechanism involves  diffuse injury to cells which form the barrier of the microscopic air sacs of the lungs ,  surfactant  dysfunction, activation of the  immune system , and dysfunction of the body's regulation of  blood clotting . [ 5 ]  In effect, ARDS impairs the lungs' ability to exchange  oxygen  and  carbon dioxide . [ 1 ]  Adult diagnosis is based on a  PaO 2 /FiO 2  ratio  (ratio of partial pressure arterial oxygen and fraction of inspired oxygen) of less than 300\u00a0mm\u00a0Hg despite a  positive end-expiratory pressure  (PEEP) of more than 5\u00a0cm H 2 O. [ 1 ]   Cardiogenic pulmonary edema , as the cause, must be excluded. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2075", "contents": "The primary treatment involves  mechanical ventilation  together with treatments directed at the underlying cause. [ 1 ]  Ventilation strategies include using low volumes and low pressures. [ 1 ]  If oxygenation remains insufficient,  lung recruitment maneuvers  and  neuromuscular blockers  may be used. [ 1 ]  If these are insufficient,  extracorporeal membrane oxygenation  (ECMO) may be an option. [ 1 ]  The syndrome is associated with a death rate between 35 and 50%. [ 1 ] [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2076", "contents": "Globally, ARDS affects more than 3\u00a0million people a year. [ 1 ]  The condition was first described in 1967. [ 1 ]  Although the terminology of \"adult respiratory distress syndrome\" has at times been used to differentiate ARDS from \" infant respiratory distress syndrome \" in newborns, the international consensus is that \"acute respiratory distress syndrome\" is the best term because ARDS can affect people of all ages. [ 6 ]  There are separate diagnostic criteria for children and those in areas of the world with fewer resources. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2077", "contents": "The signs and symptoms of ARDS often begin within two hours of an inciting event, but have been known to take as long as 1\u20133 days; diagnostic criteria require a known insult to have happened within 7 days of the syndrome. Signs and symptoms may include  shortness of breath ,  fast breathing , and a  low oxygen level in the blood  due to abnormal ventilation. [ 7 ] [ 8 ]  Other common symptoms include muscle fatigue and general weakness, low blood pressure, a dry, hacking cough, and fever. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2078", "contents": "Complications may include the following: [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2079", "contents": "Other complications that are typically associated with ARDS include: [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2080", "contents": "There are  direct  and  indirect  causes of ARDS depending whether the lungs are initially affected. Direct causes include  pneumonia  (including bacterial and viral), aspiration, inhalational lung injury, lung contusion, chest trauma, and near-drowning. Indirect causes include  sepsis ,  shock ,  pancreatitis ,  trauma  (e.g. fat embolism),  cardiopulmonary bypass ,  TRALI , burns, increased  intracranial pressure . [ 11 ]  Fewer cases of ARDS are linked to large volumes of fluid used during post-trauma resuscitation. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2081", "contents": "ARDS is a form of  fluid accumulation in the lungs  not explained by heart failure (noncardiogenic pulmonary edema). It is typically provoked by an acute injury to the lungs that results in flooding of the  lungs' microscopic air sacs  responsible for the exchange of gases such as oxygen and carbon dioxide with  capillaries  in the lungs. [ 13 ]  Additional common findings in ARDS include partial collapse of the alveoli ( atelectasis ) and low levels of oxygen in the blood ( hypoxemia ). The clinical syndrome is associated with pathological findings including pneumonia,  eosinophilic pneumonia ,  cryptogenic organizing pneumonia , acute fibrinous organizing pneumonia, and  diffuse alveolar damage (DAD) . Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung tissue. The triggering insult to the tissue usually results in an initial release of  chemical signals  and other inflammatory mediators secreted by local  epithelial  and  endothelial  cells. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2082", "contents": "Neutrophils  and some T- lymphocytes  quickly migrate into the inflamed lung tissue and contribute in the amplification of the phenomenon. The typical histological presentation involves diffuse  alveolar  damage and  hyaline  membrane formation in alveolar walls. Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2083", "contents": "One research group has reported that broncho-alveolar lavage fluid in later-stage ARDS often contains  trichomonads , [ 14 ]  in an amoeboid form (i.e. lacking their characteristic flagellum) which makes them difficult to identify under the microscope. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2084", "contents": "Diagnostic criteria for ARDS have changed over time as understanding of the  pathophysiology  has evolved. The international consensus criteria for ARDS were most recently updated in 2012 and are known as the \"Berlin definition\". [ 16 ] [ 17 ]   In addition to generally broadening the diagnostic thresholds, other notable changes from the prior 1994 consensus criteria [ 6 ]  include discouraging the term \"acute lung injury\", and defining grades of ARDS severity according to degree of  decrease in the oxygen content of the blood . [ 16 ] [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2085", "contents": "According to the 2012 Berlin definition, adult ARDS is characterized by the following:  [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2086", "contents": "The 2012 \"Berlin criteria\" are a modification of the prior 1994 consensus conference definitions (see  history ). [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2087", "contents": "Radiologic imaging has long been a criterion for diagnosis of ARDS. Original definitions of ARDS specified that correlative  chest X-ray  findings were required for diagnosis, the diagnostic criteria have been expanded over time to accept  CT  and  ultrasound  findings as equally contributory. Generally, radiographic findings of fluid accumulation (pulmonary edema) affecting both lungs and unrelated to increased cardiopulmonary vascular pressure (such as in heart failure) may be suggestive of ARDS. [ 20 ] \nUltrasound findings suggestive of ARDS include the following:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2088", "contents": "Acute respiratory distress syndrome is usually treated with  mechanical ventilation  in the  intensive care unit (ICU) . Mechanical ventilation is usually delivered through a rigid tube which enters the oral cavity and is secured in the  airway  (endotracheal intubation), or by  tracheostomy  when prolonged ventilation (\u22652 weeks) is necessary. The role of  non-invasive ventilation  is limited to the very early period of the disease or to prevent worsening respiratory distress in individuals with  atypical pneumonias ,  lung bruising , or major surgery patients, who are at risk of developing ARDS. Treatment of the underlying cause is crucial. Appropriate  antibiotic  therapy is started as soon as  culture  results are available, or if  infection  is suspected (whichever is earlier).  Empirical therapy  may be appropriate if local microbiological surveillance is efficient. Where possible the origin of the infection is removed. When  sepsis  is diagnosed, appropriate local  protocols  are followed. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2089", "contents": "The overall goal of mechanical ventilation is to maintain acceptable gas exchange to meet the body's metabolic demands and to minimize adverse effects in its application. The parameters PEEP (positive end-expiratory pressure, to keep alveoli open), mean airway pressure (to promote recruitment (opening) of easily collapsible alveoli and predictor of hemodynamic effects), and  plateau pressure  (best predictor of alveolar overdistention) are used. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2090", "contents": "Previously, mechanical ventilation aimed to achieve tidal volumes ( V t ) of 12\u201315\u00a0ml/kg (where the weight is  ideal body weight  rather than actual weight). Recent studies have shown that high tidal volumes can overstretch alveoli resulting in  volutrauma  (secondary lung injury). The ARDS Clinical Network, or ARDSNet, completed a clinical trial that showed improved mortality when people with ARDS were ventilated with a tidal volume of 6 ml/kg compared to the traditional 12\u00a0ml/kg. Low tidal volumes ( V t ) may cause a permitted  rise in blood carbon dioxide levels  and  collapse of alveoli [ 10 ]  because of their inherent tendency to increase shunting within the lung. Physiologic dead space cannot change as it is ventilation without perfusion. A shunt is a perfusion without ventilation within a lung region. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2091", "contents": "Low tidal volume ventilation was the primary independent variable associated with reduced mortality in the NIH-sponsored ARDSNet trial of tidal volume in ARDS. Plateau pressure less than 30\u00a0cm  H 2 O  was a secondary goal, and subsequent analyses of the data from the ARDSNet trial and other experimental data demonstrate that there appears to be no safe upper limit to plateau pressure; regardless of plateau pressure, individuals with ARDS fare better with low tidal volumes. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2092", "contents": "No particular ventilator mode is known to improve mortality in acute respiratory distress syndrome (ARDS). [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2093", "contents": "Some  practitioners  favor  airway pressure release ventilation  when treating ARDS.  Well documented advantages to APRV ventilation [ 25 ]  include decreased airway pressures, decreased  minute ventilation , decreased dead-space ventilation, promotion of spontaneous breathing, almost 24-hour-a-day alveolar recruitment, decreased use of sedation, near elimination of neuromuscular blockade, optimized arterial blood gas results, mechanical restoration of FRC (functional residual capacity), a positive effect on cardiac output [ 26 ]  (due to the negative inflection from the elevated baseline with each spontaneous breath), increased organ and tissue perfusion and potential for increased urine output secondary to increased kidney perfusion. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2094", "contents": "A patient with ARDS, on average, spends between 8 and 11 days on a mechanical ventilator; APRV may reduce this time significantly and thus may conserve valuable resources. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2095", "contents": "Positive end-expiratory pressure  (PEEP) is used in mechanically ventilated people with ARDS to improve oxygenation.  In ARDS, three populations of alveoli can be distinguished.  There are normal alveoli that are always inflated and engaging in gas exchange, flooded alveoli which can never, under any ventilatory regime, be used for gas exchange, and atelectatic or partially flooded alveoli that can be \"recruited\" to participate in gas exchange under certain ventilatory regimens.  The recruitable alveoli represent a continuous population, some of which can be recruited with minimal PEEP, and others can only be recruited with high levels of PEEP.  An additional complication is that some alveoli can only be opened with higher airway pressures than are needed to keep them open, hence the justification for maneuvers where PEEP is increased to very high levels for seconds to minutes before dropping the PEEP to a lower level. PEEP can be harmful; high PEEP necessarily increases mean airway pressure and alveolar pressure, which can damage normal alveoli by overdistension resulting in DAD. A compromise between the beneficial and adverse effects of PEEP is inevitable. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2096", "contents": "The 'best PEEP' used to be defined as 'some' cm H 2 O  above the lower inflection point (LIP) in the  sigmoidal  pressure-volume relationship curve of the lung. Recent research has shown that the LIP-point pressure is no better than any pressure above it, as recruitment of collapsed alveoli\u2014and, more importantly, the overdistension of aerated units\u2014occur throughout the whole inflation. Despite the awkwardness of most procedures used to trace the pressure-volume curve, it is still used by some [ who? ]  to define the  minimum  PEEP to be applied to their patients. Some new ventilators can automatically plot a pressure-volume curve. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2097", "contents": "PEEP may also be set empirically. Some authors [ who? ]  suggest performing a 'recruiting maneuver'\u2014a short time at a very high continuous positive airway pressure, such as 50\u00a0cm H 2 O  (4.9\u00a0kPa)\u2014to recruit or open collapsed units with a high distending pressure before restoring previous ventilation. The final PEEP level should be the one just before the drop in Pa O 2  or  peripheral blood oxygen saturation  during a step-down trial. A large randomized controlled trial of patients with ARDS found that lung recruitment maneuvers and PEEP titration was associated with high rates of barotrauma and pneumothorax and increased mortality. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2098", "contents": "Intrinsic PEEP  (iPEEP) or auto-PEEP\u2014first described by John Marini of St. Paul Regions Hospital\u2014is a potentially unrecognized contributor to PEEP in intubated individuals.  When ventilating at high frequencies, its contribution can be substantial, particularly in people with obstructive lung disease such as  asthma  or  chronic obstructive pulmonary disease  (COPD). iPEEP has been measured in very few formal studies on ventilation in ARDS, and its contribution is largely unknown. Its measurement is recommended in the treatment of people who have ARDS, especially when using  high-frequency (oscillatory/jet) ventilation . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2099", "contents": "The position of lung infiltrates in acute respiratory distress syndrome is non-uniform. Repositioning into the prone position (face down) might improve oxygenation by relieving  atelectasis  and improving perfusion. If this is done early in the treatment of severe ARDS, it confers a mortality benefit of 26% compared to supine ventilation. [ 29 ] [ 30 ]  However, attention should be paid to avoid the  SIDS  in the management of the respiratory distressed infants by continuous careful monitoring of their cardiovascular system. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2100", "contents": "Several studies have shown that pulmonary function and outcome are better in people with ARDS who lost weight or whose  pulmonary wedge pressure  was lowered by  diuresis  or fluid restriction. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2101", "contents": "As of 2019, it is uncertain whether or not treatment with  corticosteroids  improves overall survival. Corticosteroids may increase the number of ventilator-free days during the first 28 days of hospitalization. [ 31 ]  One study found that dexamethasone may help. [ 32 ]  The combination of hydrocortisone, ascorbic acid, and thiamine also requires further study as of 2018. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2102", "contents": "Inhaled  nitric oxide  (NO) selectively widens the lung's arteries which allows for more blood flow to open alveoli for  gas exchange . Despite evidence of increased oxygenation status, there is no evidence that inhaled nitric oxide decreases morbidity and mortality in people with ARDS. [ 34 ]  Furthermore, nitric oxide may cause kidney damage and is not recommended as therapy for ARDS regardless of severity. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2103", "contents": "Alvelestat  (AZD 9668) had been quoted according to one review article. [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2104", "contents": "Extracorporeal membrane oxygenation  (ECMO) is mechanically applied prolonged cardiopulmonary support. There are two types of ECMO: Venovenous which provides respiratory support and venoarterial which provides respiratory and hemodynamic support. People with ARDS who do not require cardiac support typically undergo venovenous ECMO. Multiple studies have shown the effectiveness of ECMO in acute respiratory failure. [ 37 ] [ 38 ] [ 39 ]  Specifically, the CESAR (Conventional ventilatory support versus Extracorporeal membrane oxygenation for Severe Acute Respiratory failure) trial [ 40 ]  demonstrated that a group referred to an ECMO center demonstrated significantly increased survival compared to conventional management (63% to 47%). [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2105", "contents": "As of 2019, there is no evidence showing that treatments with exogenous  surfactants ,  statins ,  beta-blockers  or  n-acetylcysteine  decreases early mortality, late all-cause mortality, duration of mechanical ventilation, or number of ventilator-free days. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2106", "contents": "The overall prognosis of ARDS is poor, with mortality rates of approximately 40%. [ 31 ]  Exercise limitation, physical and psychological sequelae, decreased physical quality of life, and increased costs and use of health care services are important sequelae of ARDS. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2107", "contents": "The annual rate of ARDS is generally  13\u201323 people per 100,000 in the general population. [ 42 ]  It is more common in people who are  mechanically ventilated  with acute lung injury (ALI) occurring in 16% of ventilated people. Rates increased in 2020 due to  COVID-19 , with some cases also appearing similar to  HAPE . [ 43 ] [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2108", "contents": "Worldwide, severe sepsis is the most common trigger causing ARDS. [ 45 ]   Other triggers include mechanical ventilation, sepsis, pneumonia, Gilchrist's disease, drowning, circulatory shock,  aspiration ,  trauma \u2014especially  pulmonary contusion \u2014major surgery, massive  blood transfusions , [ 46 ]   smoke inhalation , drug reaction or overdose,  fat emboli  and reperfusion pulmonary edema after  lung transplantation  or pulmonary embolectomy. However, the majority of patients with all these conditions mentioned do not develop ARDS. It is unclear why some people with the mentioned factors above do not develop ARDS and others do. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2109", "contents": "Pneumonia and sepsis are the most common triggers, and pneumonia is present in up to 60% of patients and may be either causes or complications of ARDS. Alcohol excess appears to increase the risk of ARDS. [ 47 ]  Diabetes was originally thought to decrease the risk of ARDS, but this has shown to be due to an increase in the risk of pulmonary edema. [ 48 ] [ 49 ]   Elevated abdominal pressure of any cause is also probably a risk factor for the development of ARDS, particularly during mechanical ventilation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2110", "contents": "Acute respiratory distress syndrome was first described in 1967 by Ashbaugh  et al. [ 10 ] [ 50 ]  Initially there was no clearly established definition, which resulted in controversy regarding the incidence and death of ARDS."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2111", "contents": "In 1988, an expanded definition was proposed, which quantified physiologic respiratory impairment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2112", "contents": "In 1994, a new definition was recommended by the American-European  Consensus Conference  Committee  [ 6 ] [ 10 ]   which recognized the variability in severity of pulmonary injury. [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2113", "contents": "The definition required the following criteria to be met:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2114", "contents": "If Pa O 2 :Fi O 2 \u00a0< 300\u00a0mmHg (40\u00a0kPa), then the definitions recommended a classification as \"acute lung injury\" (ALI).  Note that according to these criteria,  arterial blood gas  analysis and  chest X-ray  were required for formal diagnosis.  Limitations of these definitions include lack of precise definition of acuity, nonspecific imaging criteria, lack of precise definition of hypoxemia with regards to PEEP (affects arterial oxygen partial pressure), arbitrary Pa O 2  thresholds without systematic data. [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2115", "contents": "In 2012, the Berlin Definition of ARDS was devised by the European Society of Intensive Care Medicine, and was endorsed by the  American Thoracic Society  and the  Society of Critical Care Medicine .  These recommendations were an effort to both update classification criteria in order to improve clinical usefulness and to clarify terminology. Notably, the Berlin guidelines discourage the use of the term \"acute lung injury\" or ALI, as the term was commonly being misused to characterize a less severe degree of lung injury.  Instead, the committee proposes a classification of ARDS severity as mild, moderate, or severe according to arterial oxygen saturation. [ 16 ]  The Berlin definitions represent the current international consensus guidelines for both clinical and research classification of ARDS. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2116", "contents": "ARDS is the severe form of acute lung injury (ALI), and of  transfusion-related acute lung injury  (TRALI), though there are other causes. The Berlin definition included ALI as a mild form of ARDS. [ 53 ]  However, the criteria for the diagnosis of ARDS in the Berlin definition excludes many children, and a new definition for children was termed  pediatric  acute respiratory distress syndrome (PARDS); this is known as the PALICC definition (2015). [ 54 ] [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2117", "contents": "There is ongoing research on the treatment of ARDS by  interferon (IFN) beta-1a  to aid in preventing leakage of vascular beds. Traumakine (FP-1201-lyo) is a recombinant human IFN beta-1a drug, developed by the Finnish company  Faron Pharmaceuticals , which is undergoing international phase-III clinical trials after an open-label, early-phase trial showed an 81% reduction-in-odds of 28-day mortality in ICU patients with ARDS. [ 56 ]  The drug is known to function by enhancing lung  CD73  expression and increasing production of anti-inflammatory adenosine, such that vascular leaking and escalation of inflammation are reduced. [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2118", "contents": "Aspirin  has been studied in those who are at high risk and was not found to be useful. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2119", "contents": "An intravenous  ascorbic acid  treatment was tested in the 2019  RCT , in people with ARDS due to sepsis and there was no change in primary endpoints. [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2120", "contents": "In  respiratory physiology ,  airway resistance  is the resistance of the  respiratory tract  to airflow during  inhalation  and  exhalation . Airway resistance can be measured using  plethysmography ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2121", "contents": "Analogously to  Ohm's law :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2122", "contents": "Where:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2123", "contents": "So:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2124", "contents": "N.B. P A  and  \n \n \n \n \n \n \n V \n \u02d9 \n \n \n \n \n \n {\\displaystyle {\\dot {V}}} \n \n  change constantly during the respiratory cycle."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2125", "contents": "There are several important determinants of airway resistance including:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2126", "contents": "In  fluid dynamics , the  Hagen\u2013Poiseuille equation  is a  physical law  that gives the  pressure  drop in a fluid flowing through a long cylindrical pipe.  The assumptions of the equation are that the flow is laminar  viscous  and  incompressible  and the flow is through a constant circular cross-section that is substantially longer than its diameter.  The equation is also known as the  Hagen\u2013Poiseuille law ,  Poiseuille law  and  Poiseuille equation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2127", "contents": "Dividing both sides by  \n \n \n \n \n \n \n V \n \u02d9 \n \n \n \n \n \n {\\displaystyle {\\dot {V}}} \n \n  and given the above definition shows:-"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2128", "contents": "While the assumptions of the Hagen\u2013Poiseuille equation are not strictly true of the respiratory tract it serves to show that, because of the fourth power, relatively small changes in the radius of the airways causes large changes in airway resistance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2129", "contents": "An individual small airway has much greater resistance than a large airway, however there are many more small airways than large ones. Therefore, resistance is greatest at the  bronchi  of intermediate size, in between the fourth and eighth bifurcation. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2130", "contents": "Where air is flowing in a  laminar manner  it has less resistance than when it is flowing in a  turbulent manner . If flow becomes turbulent, and the pressure difference is increased to maintain flow, this response itself increases resistance. This means that a large increase in pressure difference is required to maintain flow if it becomes turbulent."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2131", "contents": "Whether flow is laminar or turbulent is complicated, however generally flow within a pipe will be laminar as long as the  Reynolds number  is less than 2300. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2132", "contents": "This shows that larger airways are more prone to turbulent flow than smaller airways. In cases of upper airway obstruction the development of turbulent flow is a very important mechanism of increased airway resistance, this can be treated by administering  Heliox , a  breathing gas  which is much less dense than air and consequently more conductive to laminar flow."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2133", "contents": "Airway resistance is not constant. As shown above airway resistance is markedly affected by changes in the diameter of the airways. Therefore, diseases affecting the respiratory tract can increase airway resistance. Airway resistance can also change over time. During an  asthma  attack the airways constrict causing an increase in airway resistance. Airway resistance can also vary between inspiration and expiration: In  emphysema  there is destruction of the elastic tissue of the lungs which help hold the small airways open. Therefore, during expiration, particularly forced expiration, these airways may collapse causing increased airway resistance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2134", "contents": "This is simply the mathematical inverse of airway resistance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2135", "contents": "Also called volumic airway resistance. Due to the elastic nature of the tissue that supports the small airways airway resistance changes with lung volume. It is not practically possible to measure airway resistance at a set absolute lung volume, therefore specific airway resistance attempts to correct for differences in lung volume at which different measurements of airway resistance were made."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2136", "contents": "Specific airway resistance is often measured at FRC, in which case:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2137", "contents": "[ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2138", "contents": "Also called volumic airway conductance. Similarly to specific airway resistance, specific airway conductance attempts to correct for differences in lung volume."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2139", "contents": "Specific airway conductance is often measured at FRC, in which case:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2140", "contents": "[ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2141", "contents": "The  alveolar gas equation  is the method for calculating  partial pressure  of  alveolar  oxygen ( p A O 2 ). The equation is used in assessing if the  lungs  are properly transferring  oxygen  into the  blood .  The alveolar air equation is not widely used in clinical medicine, probably because of the complicated appearance of its classic forms.\nThe partial pressure of oxygen ( p O 2 ) in the  pulmonary alveoli  is required to calculate both the  alveolar-arterial gradient  of oxygen and the amount of right-to-left  cardiac shunt , which are both clinically useful quantities. However, it is not practical to take a sample of gas from the alveoli in order to directly measure the partial pressure of oxygen. The alveolar gas equation allows the calculation of the alveolar partial pressure of oxygen from data that is practically measurable. It was first characterized in 1946. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2142", "contents": "The equation relies on the following assumptions:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2143", "contents": "p \n \n A \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n = \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n ( \n \n P \n \n \n ATM \n \n \n \n \u2212 \n p \n \n \n H \n \n 2 \n \n \n \n \n \n O \n \n ) \n \u2212 \n \n \n \n \n p \n \n a \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n ( \n 1 \n \u2212 \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n ( \n 1 \n \u2212 \n \n RER \n \n ) \n ) \n \n \n RER \n \n \n \n \n \n {\\displaystyle p_{A}{\\ce {O2}}=F_{I}{\\ce {O2}}(P_{{\\ce {ATM}}}-p{\\ce {H2O}})-{\\frac {p_{a}{\\ce {CO2}}(1-F_{I}{\\ce {O2}}(1-{\\ce {RER}}))}{{\\ce {RER}}}}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2144", "contents": "If  F i O 2  is small, or more specifically if  \n \n \n \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n ( \n 1 \n \u2212 \n \n RER \n \n ) \n \u226a \n 1 \n \n \n {\\displaystyle F_{I}{\\ce {O2}}(1-{\\ce {RER}})\\ll 1} \n \n  then the equation can be simplified to:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2145", "contents": "p \n \n A \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2248 \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n ( \n \n P \n \n \n ATM \n \n \n \n \u2212 \n p \n \n \n H \n \n 2 \n \n \n \n \n \n O \n \n ) \n \u2212 \n \n \n \n \n p \n \n a \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n \n \n RER \n \n \n \n \n \n {\\displaystyle p_{A}{\\ce {O2}}\\approx F_{I}{\\ce {O2}}(P_{{\\ce {ATM}}}-p{\\ce {H2O}})-{\\frac {p_{a}{\\ce {CO2}}}{{\\ce {RER}}}}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2146", "contents": "Sample Values given for air at sea level at 37\u00a0\u00b0C."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2147", "contents": "Doubling  F i O 2  will double  p i O 2 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2148", "contents": "Other possible equations exist to calculate the alveolar air. [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2149", "contents": "p \n \n A \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n = \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n ( \n \n P \n B \n \u2212 \n p \n \n \n H \n \n 2 \n \n \n \n \n \n O \n \n \n ) \n \n \u2212 \n \n p \n \n A \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n \n ( \n \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n + \n \n \n \n 1 \n \u2212 \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n R \n \n \n \n ) \n \n \n \n \n \n \n \n = \n \n p \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n p \n \n A \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n \n ( \n \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n + \n \n \n \n 1 \n \u2212 \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n R \n \n \n \n ) \n \n \n \n \n \n \n \n = \n \n p \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n \n \n V \n \n T \n \n \n \n \n V \n \n T \n \n \n \u2212 \n \n V \n \n D \n \n \n \n \n \n \n ( \n \n \n p \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n p \n \n E \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n ) \n \n \n \n \n \n \n \n = \n \n \n \n \n p \n \n E \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n p \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n ( \n \n \n \n V \n \n D \n \n \n \n V \n \n T \n \n \n \n \n ) \n \n \n \n 1 \n \u2212 \n \n \n \n V \n \n D \n \n \n \n V \n \n T \n \n \n \n \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{aligned}p_{A}{\\ce {O2}}&=F_{I}{\\ce {O2}}\\left(PB-p{\\ce {H2O}}\\right)-p_{A}{\\ce {CO2}}\\left(F_{I}{\\ce {O2}}+{\\frac {1-F_{I}{\\ce {O2}}}{R}}\\right)\\\\[4pt]&=p_{I}{\\ce {O2}}-p_{A}{\\ce {CO2}}\\left(F_{I}{\\ce {O2}}+{\\frac {1-F_{I}{\\ce {O2}}}{R}}\\right)\\\\[4pt]&=p_{I}{\\ce {O2}}-{\\frac {V_{T}}{V_{T}-V_{D}}}\\left(p_{I}{\\ce {O2}}-p_{E}{\\ce {O2}}\\right)\\\\[4pt]&={\\frac {p_{E}{\\ce {O2}}-p_{I}{\\ce {O2}}\\left({\\frac {V_{D}}{V_{T}}}\\right)}{1-{\\frac {V_{D}}{V_{T}}}}}\\end{aligned}}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2150", "contents": "p \n \n A \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n = \n \n \n \n \n p \n \n E \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n p \n \n i \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n \n V \n \n D \n \n \n \n V \n \n T \n \n \n \n \n \n \n 1 \n \u2212 \n \n \n \n V \n \n D \n \n \n \n V \n \n T \n \n \n \n \n \n \n \n \n \n {\\displaystyle p_{A}{\\ce {O2}}={\\frac {p_{E}{\\ce {O2}}-p_{i}{\\ce {O2}}{\\frac {V_{D}}{V_{T}}}}{1-{\\frac {V_{D}}{V_{T}}}}}} \n \n \n p A O 2 ,  p E O 2 , and  p i O 2  are the partial pressures of oxygen in alveolar, expired, and inspired gas, respectively, and VD/VT is the ratio of physiologic dead space over tidal volume. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2151", "contents": "R \n = \n \n \n \n \n p \n \n E \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n ( \n 1 \n \u2212 \n \n F \n \n I \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n ) \n \n \n \n p \n \n i \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n p \n \n E \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2212 \n ( \n \n p \n \n E \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n \u2217 \n \n F \n \n i \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n ) \n \n \n \n \n \n {\\displaystyle R={\\frac {p_{E}{\\ce {CO2}}(1-F_{I}{\\ce {O2}})}{p_{i}{\\ce {O2}}-p_{E}{\\ce {O2}}-(p_{E}{\\ce {CO2}}*F_{i}{\\ce {O2}})}}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2152", "contents": "V \n \n D \n \n \n \n V \n \n T \n \n \n \n \n = \n \n \n \n \n p \n \n A \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n p \n \n E \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n \n \n \n p \n \n A \n \n \n \n \n CO \n \n 2 \n \n \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\frac {V_{D}}{V_{T}}}={\\frac {p_{A}{\\ce {CO2}}-p_{E}{\\ce {CO2}}}{p_{A}{\\ce {CO2}}}}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2153", "contents": "An  alveolar macrophage ,  pulmonary macrophage , (or  dust cell ) is a type of  macrophage , a  professional phagocyte , found in the airways and at the level of the  alveoli  in the  lungs , but separated from their walls. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2154", "contents": "Activity of the alveolar macrophage is relatively high, because they are located at one of the major boundaries between the body and the outside world. They are responsible for removing particles such as dust or  microorganisms  from the respiratory surfaces."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2155", "contents": "Alveolar macrophages are frequently seen to contain granules of exogenous material such as particulate  carbon  that they have picked up from respiratory surfaces. Such  black granules  may be especially common in  smoker 's lungs or long-term city dwellers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2156", "contents": "The alveolar macrophage is the third cell type in the alveolus; the others are the  type I  and  type II pneumocytes ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2157", "contents": "Alveolar macrophages are phagocytes that play a critical role in  homeostasis , host defense, and tissue remodeling. [ 7 ]  Their population density is decisive for these many processes. They are highly adaptive and can release many secretions, to interact with other cells and molecules using several  surface receptors . Alveolar macrophages are also involved in the  phagocytosis  of apoptotic and necrotic cells. [ 8 ]  They need to be selective of the material that is phagocytized to safeguard the normal cells and structures. [ 8 ]  To combat infection, the phagocytes facilitate many  pattern recognition receptors  (PRRs) to help recognize pathogen-associated molecular patterns (PAMPs) on the surface of pathogenic microorganisms. [ 9 ]  PAMPs all have the common features of being unique to a group of  pathogens  but invariant in their basic structure; and are essential for pathogenicity (ability of an organism to produce an infectious disease in another organism). [ 9 ]  Proteins involved in microbial pattern recognition include mannose receptor, complement receptors, DC-SIGN, Toll-like receptors(TLRs), the scavenger receptor,  CD14 ,  and Mac-1. [ 9 ] [ 10 ]  PRRs can be divided into three classes:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2158", "contents": "The recognition and clearance of invading microorganisms occurs through both opsonin-dependent and opsonin\u2013independent pathways.  The molecular mechanisms facilitating opsonin-dependent phagocytosis are different for specific opsonin/receptor pairs. For example, phagocytosis of IgG-opsonized pathogens occurs through the  Fc\u03b3 receptors  (Fc\u03b3R), and involves phagocyte extensions around the microbe, resulting in the production of pro-inflammatory mediators. Conversely, complement receptor-mediated pathogen ingestion occurs without observable membrane extensions (particles just sink into the cell) and does not generally results in an inflammatory mediator response."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2159", "contents": "Following internalization, the microbe is enclosed in a vesicular phagosome which then undergoes fusion with primary or secondary  lysosomes , forming a phagolysosome. [ 9 ]  There are various mechanisms that lead to intracellular killing; there are oxidative processes, and others independent of the oxidative metabolism. The former involves the activation of membrane enzyme systems that lead to a stimulation of oxygen uptake (known as the respiratory burst), and its reduction to reactive oxygen intermediates (ROIs), molecular species that are highly toxic for microorganisms. [ 9 ]  The enzyme responsible for the elicitation of the respiratory burst is known as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is composed of five subunits. [ 9 ]  One component is a membrane cytochrome made up of two protein subunits, gp91phox and p22phox; the remaining three components are cytosolic-derived proteins: p40phox, p47phox, and p67phox. [ 9 ]   NADPH oxidase exists in the cytosol of the AM when in a quiescent state; but upon activation, two of its cytosolic components, p47phox and p67phox, have their tyrosine and serine residues phosphorylated, which are then able to mediate translocation of NADPHox to the cytochrome component, gp91phox/p22phox, on the plasma membrane via cytoskeletal elements. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2160", "contents": "Compared to other phagocytes, the respiratory burst in AM is of a greater magnitude. [ 9 ]  Oxygen-independent microbicidal mechanisms are based on the production of acid, on the secretion of lysozymes, on iron-binding proteins, and on the synthesis of toxic cationic polypeptides. [ 9 ]  Macrophages possess a repertoire of antimicrobial molecules packaged within their granules and lysosomes. [ 9 ]  These organelles contain a myriad of  degradative enzymes  and antimicrobial peptides that are released into the phagolysosome, such as proteases, nucleases, phosphatases, esterases, lipases, and highly basic peptides. [ 9 ]  Moreover, macrophages possess a number of nutrient deprivation mechanisms that are used to starve phagocytosed pathogens of essential micronutrients. [ 9 ]  Certain microorganisms have evolved countermeasures which enable them to evade being destroyed by phagocytes. Although lysosomal-mediated degradation is an efficient means by which to neutralize an infection and prevent colonization, several pathogens parasitize macrophages, exploiting them as a host cell for growth, maintenance and replication. [ 9 ]  Parasites like Toxoplasma gondii and mycobacteria are able to prevent fusion of phagosomes with lysosomes, thus escaping the harmful action of lysosomal hydrolases. Others avoid lysosomes by leaving the phagocytic vacuole, to reach the cytosolic matrix where their development is unhindered. In these instances, macrophages may be triggered to actively destroy phagocytosed microorganisms by producing a number of highly toxic molecules and inducing deprivational mechanism to starve it. [ 9 ]   Finally, some microbes have enzymes to detoxify oxygen metabolites formed during the respiratory burst. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2161", "contents": "When insufficient to ward off the threat, alveolar macrophages can release  proinflammatory cytokines  and chemokines to call forth a highly developed network of defensive phagocytic cells responsible for the adaptive immune response. During COVID-19 infection, alveolar macrophages play a dual role by acting as the first line of defense against SARS-CoV-2 in the alveolar space, while also contributing to the hyperinflammatory response through excessive cytokine production, which can exacerbate lung damage and acute respiratory distress syndrome (ARDS)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2162", "contents": "The lungs are especially sensitive and prone to damage, thus to avoid collateral damage to type I and type II pneumocytes, alveolar macrophages are kept in a quiescent state, producing little inflammatory cytokines and displaying little phagocytic activity, as evidenced by downregulated expression of the phagocytic receptor Macrophage 1 antigen (Mac-1). [ 7 ] [ 12 ]  AMs actively suppress the induction of two of the immunity systems of the body: the adaptive immunity and humoral immunity. The adaptive immunity is suppressed through AM's effects on interstitial dendritic cells, B-cells and T-cells, as these cells are less selective of what they destroy, and often cause unnecessary damage to normal cells. To prevent uncontrolled inflammation in the lower respiratory tract, alveolar macrophages secrete nitric oxide,  prostaglandins , interleukin-4 and -10(IL-4, IL-10), and  transforming growth factor -\u03b2 (TGF-\u03b2). [ 12 ] [ 13 ] [ 14 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2163", "contents": "Nitric oxide  (NO) is a major source of immunomodulation in rodents, and is produced by enzyme nitric oxide synthetase type 2 (NOS2) in the alveolar macrophage. [ 14 ]   NO inhibits tyrosine  phosphorylation  of the kinases involved in production of the interleukin-2 (IL-2) receptor, the expression of which is fundamental for T cell proliferation. [ 13 ]  In humans, however, NOS2 activity has been difficult to verify. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2164", "contents": "There are two explanations for the lack of responsiveness in the promoter of human inducible nitric oxide synthetase (iNOS) to NO activation by  lipopolysaccharides  (LPS) +  interferon gamma  (IFN\u03b3). [ 14 ]  The first is that there are various inactivating nucleotide variations in the human counterpart of the enhancer element that regulates LPS/IFN\u03b3 induced expression of the mouse NOS2 gene. The second is because of the absence of a nuclear factor in human macrophages that is required for optimum expression of gene NOS2 (LPS-inducible nuclear factor-kappa B/Rel complex). [ 14 ]   It is assumed that the difficulty in verifying NOS2 is due to a much more tightly controlled expression in human AMs as compared to that in the rodent AMs. [ 14 ]  NOS2 is part of an autoregulatory feedback loop, wherein an allergen or provoker stimulates inflammatory cytokine production, which in turn stimulates NO production, and NO down-regulates cytokine production. [ 14 ]  In rats, NO inhibits the granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated maturation of dendritic cells, and in humans it inhibits the TNF-alpha-mediated maturation of human dendritic cells, through cyclic GMP-dependent mechanisms. [ 14 ]  NO prolongs the ability of human dendritic cells to internalize antigens at sites of inflammation, therefore modulating the beginning steps leading to antigen-specific immune responses. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2165", "contents": "NO production has been implicated as relevant to the pathology of asthma. People with asthma show an increased expression of iNOS in airway epithelial cells and an increased level of nitric oxide in exhaled air. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2166", "contents": "Many other immunomodulating factors have been isolated, the most important of which are prostaglandins and cytokines.  PGE2  was the first immunomodulator to be derived from macrophages and described. [ 14 ]  PGE2 functions in amplifying peripheral blood lymphocyte IL-10 transcription and protein production; as well as in deactivating macrophages and T-cells. [ 14 ]  PGE2 is an immunomodulatory eicosanoid derived from the cell membrane component,  arachidonic acid , and is processed in the arachidonic acid cascade:  the successive oxygenation and isomerization of arachidonic acid by  cyclooxygenase  and PGE2 synthase enzymes. [ 16 ]   The regulation of target cells by PGE2 occurs via signaling through four cell membrane-associated G-protein-coupled E-prostanoid (EP) receptors, named EP1, EP2, EP3, and EP4. [ 16 ]  PGE2 inhibits bacterial killing and ROI production by AM by impairing Fc\u03b3-mediated phagocytosis through its ability to stimulate the production of intracellular cyclic adenosine monophosphate (cAMP) effectors via EP2 and EP4 receptors signaling. [ 11 ] [ 16 ]  EP2 and EP4 receptors signal primarily through stimulatory G protein (Gs), increasing adenylyl cyclase (AC) activity and subsequent cAMP formation. [ 11 ]  cAMP is a second messenger that influences multiple cellular functions via the activation of two downstream effector molecules, protein kinase A (PKA) and the exchange proteins directly activated by cAMP (Epac-1 and -2). [ 11 ]  Epac-1 and PKA are both important factors involved in the inhibition of AM bacterial killing. [ 11 ]  The effects of PKA results from its ability to phosphorylate serine and threonine residues on many cellular proteins, especially transcription factor cAMP response element binding protein (CREB). cAMP/PKA/CREB axis mediates the inhibition of TNF-alpha release. [ 11 ]   The killing of phagocytosed bacteria by AMs is dependent upon several distinct microbicidal mechanisms, like the reduced NADPH oxidase-mediated release of ROI. [ 9 ] [ 11 ]  ROI generation by NADPH oxidase is an important bactericidal mechanism after FcR-mediated phagocytosis. [ 11 ]  PGE2 activates both Gs-coupled EP2 and EP4 receptors by ligation, stimulating cAMP production and subsequent activation of downstream cAMP effectors, PKA and Epac-1; both which in turn impair the phosphorylation and phagosomal membrane translocation of NADPH oxidase component, p47phox, thereby inhibiting the respiratory burst. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2167", "contents": "IL-4 is a pleiotropic cytokine that plays a key role in the development of T helper type 2(Th2) cells. IL-4 is important for the differentiation of na\u00efve CD4-T cells into mature Th2 type cells; as well as for Immunoglobulin (Ig) class switching to IgE and IgG4 during the development of immune responses. [ 17 ] [ 18 ]  Ig is a class of antibody found only in mammals that plays an important role in allergy response and defense against many kinds of pathogens by protecting the body against them by complement activation, opsonization for phagocytosis, and neutralization of their toxins. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2168", "contents": "IL-4 and IL-10 have both been shown to reduce the production of metalloproteinases (endopeptidases which break down collagen and other extracellular proteins) by human AMs. [ 14 ] [ 15 ]  IL-4 has dual effects upon macrophage biological function, which may be either stimulatory or inhibitory. [ 15 ]  It enhances MHC class II antigen (extracellular protein complex that interacts exclusively with CD4-T cells as part of the exogenous pathway) and Mac-1(surface receptor as part of innate complement system) expression, thus promoting phagocytosis. [ 15 ]  IL-4 has also been shown to inhibit the production of PGE2 by reducing the expression of the enzyme, prostaglandin H synthase -2 (PGHS-2), which is critical in the production of PGE2. [ 14 ]  However, IL-4 inhibits production of TNF-alpha, IL-1 and -6, which are all important cytokines in the proinflammatory response). [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2169", "contents": "IL-10 inhibits the secretion of pro-inflammatory cytokines TNF-alpha and INF-gamma, thus suppressing the proliferation of T-cells, NK cells, and AM. [ 14 ]  IL-10 shares similar immunomodulating mechanisms to TGF-\u03b2. [ 14 ]  It is thought that both cytokines reduce the rate of apoptosis in human alveolar macrophages, thus indirectly enhancing alveolar macrophage-mediated inhibition of T-cell proliferation. [ 14 ]  There is a significant increase in the basal rate of apoptosis upon activation by bacterial products. Apoptosis is particularly regulated by the presence of cytokines: IFN\u03b3 increases the rate of apoptosis, whereas IL-10 and TGF-\u03b2 decrease it. [ 14 ]  However, IL-10 has counterproductive effects on the immune system, and has been shown to actually promote infection by foreign pathogens. The role of IL-10 in bacterial and parasitic infection has been discovered as a strategy to evade host immune systems. [ 19 ]   There are bacteria which parasitize AMs by invading through their membranes, and thrive by growing and replicating inside of them, exploiting AMs as host cells. Normally, this infection can be eliminated by T-cells, which activate enzymes in alveolar macrophages that destroy the bacteria; but these bacteria have been shown to alter the cytokine signaling network to their advantage. As an inhibitory cytokine, IL-10 facilitates the infection of human alveolar macrophages and monocytes by completely reversing the protective effect of IFN\u03b3 against intracellular Legionella pneumophila replication. [ 19 ]  Yersinia enterocolitica has also been shown to releases virulence antigen LcrV, which induces IL-10 through Toll-like receptor-2 and CD14 (an accessory surface protein of TLR4-mediated LPS-signaling), resulting in the suppression of IFN\u03b3 and TNF-alpha suppression. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2170", "contents": "In normal conditions, alveolar macrophages adhere closely to alveolar epithelial cells, thus inducing the expression of the \u03b1v\u03b26 integrin. Integrins are dimeric cell-surface receptors composed of alpha and beta subunits, which activates TGF-\u03b2.< [ 20 ] [ 21 ]  TGF-\u03b2 is a multifunctional cytokine that modulates a variety of biological processes such as cell growth, apoptosis, extracellular matrix synthesis, inflammation, and immune responses. [ 22 ]  TGF-\u03b2 tightly regulates anti-inflammatory activity by suppressing pro-inflammatory cytokine production, thereby inhibiting T-lymphocyte function. [ 23 ]  Integrins av\u03b26 and av\u03b28 sequester latent TGF-\u03b2 to the cell surface, where activation can be tightly coupled to cellular responses to environmental stress in the maintenance of homeostasis; integrins also localize activated TGF\u03b2 in the vicinity of the macrophages. [ 24 ]   Normally mature TGF\u03b2 is secreted as a latent complex with its N-terminal fragment, latency-associated peptide (LAP), which inhibits its activity. [ 22 ]  The latent complex is covalently linked to the extracellular matrix by binding to latent TGF-\u03b2-binding proteins. [ 20 ]   TGF-\u03b2 is activated by diverse mechanisms in the lung, ultimately involving either proteolysis or conformational alteration of the LAP. [ 24 ]  \u03b1v\u03b26 integrin is able to mediate activation of TGF-\u03b2 by binding to TGF-\u03b21 LAP, which serves as a ligand binding site for the integrin, and is an essential component of the TGF-\u03b2 activation apparatus. [ 22 ] [ 25 ]  \nOnce activated, TGF\u03b2 leads to the suppression of macrophage functionality (cytokine production and phagocytosis). [ 22 ]  Binding of activated TGF-\u03b2 to its receptors expressed on alveolar macrophages induces a downstream signaling cascade, including phosphorylation of receptor-regulated Small Mothers Against Decapentaplegic (R-SMAD)homologs 2 and 3. [ 7 ] [ 22 ] [ 23 ]  Phosphorylated SMAD-2 and -3 then form heteromeric complexes with common-mediator SMAD 4 (co-SMAD-4). Once assembled, the complexes translocates into the nucleus via the nuclear pore with the assistance of importins alpha/beta. Once in the nucleus, these complexes accumulate and eventually act as a transcription factors, regulating the expression of TGF-\u03b2 target genes. [ 23 ]  Thus TGF-\u03b2 signaling involves a direct pathway from the receptors on the surface of a cell to the nucleus."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2171", "contents": "Toll-like receptors  (TLRs) are signaling  PRRs , capable of recognizing various bacterial proteins. [ 10 ]  Although bacteria have evolved means of evading host defense mechanisms, they express PAMPs, such as lipoglycans and lipoproteins that are recognized by cells of the innate immune system through the TLRs. [ 10 ]  Upon binding of PAMPs to TLRs, the TLR triggers inflammatory and defensive responses in the host cell, inducing actin polymerization in alveolar macrophages (a crucial component in endocytosis and motility). [ 22 ]  Actin polymerization in alveolar macrophages causes the suppression of integrin expression, which in turn causes the deactivation of TGF-\u03b2 and the downregulation of the basal phosphorylation level of SMAD 2/3; subsequently leading to the activation and detachment of alveolar macrophages from the alveolar epithelial cells  [ 22 ] [15]. Upon activation, macrophages become primed for phagocytosis and begin to secrete proinflammatory cytokines (TNF-\u03b1 and IL-6). [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2172", "contents": "The priming of macrophages involves the enhancement of respiratory burst activity by IFN-\u03b3 and TNF-\u03b1. [ 9 ]  IFN\u03b3 induces both an increased affinity of the NADPH oxidase for NADPH in macrophages, as well as an increased rate of gene transcription and message expression for gp91phox protein. [ 9 ]  TNF-\u03b1 acts as an autocrine stimulus by increasing the expression of both p47phox and p67phox transcripts. The ROIs produced during the respiration burst response, in turn, enhance production of TNF-\u03b1 by macrophages. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2173", "contents": "Gas exchange must be restored as quickly as possible to avoid collateral damage, so activated lymphocytes secrete IFN\u03b3 to stimulate the production of matrix metalloproteinase MMP-9 by macrophages. [ 22 ]  AMs have been reported to produce MMP-9 partly via PGE2-dependent PKA signaling pathways, which are the pathways involved in the inhibition of phagocytosis. [ 26 ]  MMP-9 activates latent TGF-\u03b2, reinducing expression of \u03b1v\u03b26 integrins on alveolar epithelial cells, thereby returning the alveolar macrophage to a resting state. [ 7 ] [ 22 ] [ 26 ]  Activation of TGF-\u03b2 is also advantageous because its production stimulates collagen synthesis in interstitial fibroblasts, which is necessary for restoring alveolar wall architecture. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2174", "contents": "The   Alveolar\u2013arterial gradient  (A- aO 2 , [ 1 ]  or  A\u2013a gradient ), is a measure of the difference between the  alveolar   concentration  ( A ) of  oxygen  and the  arterial  ( a ) concentration of oxygen. It is a useful parameter for narrowing the differential diagnosis of  hypoxemia . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2175", "contents": "The A\u2013a gradient helps to assess the integrity of the alveolar capillary unit. For example, in high altitude, the arterial oxygen  PaO 2  is low but only because the alveolar oxygen ( PAO 2 ) is also low. However, in states of  ventilation perfusion mismatch , such as  pulmonary embolism  or  right-to-left shunt , oxygen is not effectively transferred from the  alveoli  to the blood which results in an elevated A-a gradient."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2176", "contents": "In a perfect system, no A-a gradient would exist: oxygen would diffuse and equalize across the capillary membrane, and the pressures in the arterial system and alveoli would be effectively equal (resulting in an A-a gradient of zero). [ 2 ]  However even though the partial pressure of oxygen is about equilibrated between the pulmonary capillaries and the alveolar gas, this equilibrium is not maintained as blood travels further through pulmonary circulation. As a rule,  PAO 2  is always higher than  P a O 2  by at least 5\u201310 mmHg, even in a healthy person with normal ventilation and perfusion. This gradient exists due to both physiological  right-to-left shunting  and a physiological  V/Q mismatch  caused by gravity-dependent differences in perfusion to various  zones of the lungs . The  bronchial vessels  deliver nutrients and oxygen to certain lung tissues, and some of this spent, deoxygenated venous blood drains into the highly oxygenated  pulmonary veins , causing a right-to-left shunt. Further, the effects of gravity alter the flow of both blood and air through various heights of the lung. In the upright lung, both perfusion and ventilation are greatest at the base, but the gradient of perfusion is steeper than that of ventilation so  V/Q ratio  is higher at the apex than at the base. This means that blood flowing through capillaries at the base of the lung is not fully oxygenated. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2177", "contents": "The equation for calculating  the A\u2013a gradient is:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2178", "contents": "In its expanded form, the A\u2013a gradient can be calculated by:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2179", "contents": "On room air (  F i O 2  = 0.21, or 21% ), at sea level ( P atm  = 760 mmHg ) assuming 100% humidity in the alveoli (P H 2 O  = 47 mmHg), a simplified version of the equation is:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2180", "contents": "The A\u2013a gradient is useful in determining the source of  hypoxemia . The measurement helps isolate the location of the problem as either intrapulmonary (within the lungs) or extrapulmonary (elsewhere in the body)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2181", "contents": "A normal A\u2013a gradient for a young adult non-smoker breathing air, is between 5\u201310 mmHg. Normally, the A\u2013a gradient increases with age. For every decade a person has lived, their A\u2013a gradient is expected to increase by 1 mmHg. A conservative estimate of normal A\u2013a gradient is  [age in years + 10]/ 4 . Thus, a 40-year-old should have an A\u2013a gradient around 12.5 mmHg. [ 2 ]  The value calculated for a patient's A-a gradient can assess if their hypoxia is due to the dysfunction of the alveolar-capillary unit, for which it will elevate, or due to another reason, in which the A-a gradient will be at or lower than the calculated value using the above equation.  [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2182", "contents": "An abnormally increased A\u2013a gradient suggests a defect in  diffusion ,  V/Q mismatch , or  right-to-left shunt . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2183", "contents": "The A-a gradient has clinical utility in patients with hypoxemia of undetermined etiology. The A-a gradient can be broken down categorically as either elevated or normal. Causes of hypoxemia will fall into either category. To better understand which etiologies of hypoxemia falls in either category, we can use a simple analogy. Think of the oxygen's journey through the body like a river. The respiratory system will serve as the first part of the river. Then imagine a waterfall from that point leading to the second part of the river. The waterfall represents the alveolar and capillary walls, and the second part of the river represents the arterial system. The river empties into a lake, which can represent end-organ perfusion. The A-a gradient helps to determine where there is flow obstruction.  [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2184", "contents": "For example, consider hypoventilation. Patients can exhibit hypoventilation for a variety of reasons; some include CNS depression, neuromuscular diseases such as myasthenia gravis, poor chest elasticity as seen in kyphoscoliosis or patients with vertebral fractures, and many others. Patients with poor ventilation lack oxygen tension throughout their arterial system in addition to the respiratory system. Thus, the river will have decreased flow throughout both parts. Since both the \"A\" and the \"a\" decrease in concert, the gradient between the two will remain in normal limits (even though both values will decrease). Thus patients with hypoxemia due to hypoventilation will have an A-a gradient within normal limits.  [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2185", "contents": "Now let us consider pneumonia. Patients with pneumonia have a physical barrier within the alveoli, which limits the diffusion of oxygen into the capillaries. However, these patients can ventilate (unlike the patient with hypoventilation), which will result in a well-oxygenated respiratory tract (A) with poor diffusion of oxygen across the alveolar-capillary unit and thus lower oxygen levels in the arterial blood (a). The obstruction, in this case, would occur at the waterfall in our example, limiting the flow of water only through the second part of the river.  Thus patients with hypoxemia due to pneumonia will have an inappropriately elevated A-a gradient (due to normal \"A\" and low \"a\").  [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2186", "contents": "Applying this analogy to different causes of hypoxemia should help reason out whether to expect an elevated or normal A-a gradient. As a general rule of thumb, any pathology of the alveolar-capillary unit will result in a high A-a gradient. The table below has the different disease states that cause hypoxemia.  [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2187", "contents": "Because A\u2013a gradient is approximated as:  (150 \u2212 5/4( PCO 2 )) \u2013  PaO 2  at sea level and on room air (0.21x(760-47) = 149.7 mmHg for the alveolar oxygen partial pressure, after accounting for the water vapor), the direct mathematical cause of a large value is that the blood has a low  PaO 2 , a low PaCO 2 , or both. CO 2  is very easily exchanged in the lungs and low PaCO 2  directly correlates with high  minute ventilation ; therefore a low arterial PaCO 2  indicates that extra respiratory effort is being used to oxygenate the blood. A low  PaO 2  indicates that the patient's current minute ventilation (whether high or normal) is not enough to allow adequate oxygen diffusion into the blood. Therefore, the A\u2013a gradient essentially demonstrates a high respiratory effort (low arterial PaCO 2 ) relative to the achieved level of oxygenation (arterial  PaO 2 ). A high A\u2013a gradient could indicate a patient breathing hard to achieve normal oxygenation, a patient breathing normally and attaining low oxygenation, or a patient breathing hard and still failing to achieve normal oxygenation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2188", "contents": "If lack of oxygenation is proportional to low respiratory effort, then the A\u2013a gradient is not increased; a healthy person who hypoventilates would have hypoxia, but a normal A\u2013a gradient.  At an extreme, high CO 2  levels from hypoventilation can mask an existing  high A\u2013a gradient.  This mathematical artifact makes A\u2013a gradient more clinically useful in the setting of hyperventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2189", "contents": "In the  medulla oblongata , the  arcuate nucleus  is a group of  neurons  located on the anterior surface of the  medullary pyramids . These nuclei are the extension of the  pontine nuclei . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2190", "contents": "They receive afferents from the  corticospinal tract . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2191", "contents": "They in turn project efferents into the  cerebellum  through the  inferior cerebellar peduncle  as: [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2192", "contents": "Arcuate nuclei are capable of  chemosensitivity  and have a proven role in the  respiratory center  controlling the  breathing rate . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2193", "contents": "This  neuroanatomy  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2194", "contents": "An  arterial blood gas  ( ABG )  test , or  arterial blood gas analysis  ( ABGA ) measures the amounts of arterial gases, such as  oxygen  and  carbon dioxide . An ABG test requires that a small volume of blood be drawn from the  radial artery  with a  syringe  and a thin  needle , [ 1 ]  but sometimes the  femoral artery  in the  groin  or another site is used. The blood can also be drawn from an  arterial catheter ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2195", "contents": "An ABG test measures the  blood gas tension  values of the  arterial partial pressure of oxygen  (PaO2), and the  arterial partial pressure of carbon dioxide  (PaCO2), and the  blood's pH . In addition, the arterial  oxygen saturation  (SaO2) can be determined. Such information is vital when caring for patients with critical illnesses or respiratory disease. Therefore, the ABG test is one of the most common tests performed on patients in  intensive-care units . In other  levels of care ,  pulse oximetry  plus transcutaneous carbon-dioxide measurement is a less invasive, alternative method of obtaining similar information. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2196", "contents": "An ABG test can indirectly measure the level of  bicarbonate  in the blood.  The bicarbonate level is calculated using the Henderson-Hasselbalch equation. Many blood-gas analyzers will also report concentrations of  lactate ,  hemoglobin , several  electrolytes ,  oxyhemoglobin ,  carboxyhemoglobin , and  methemoglobin . ABG testing is mainly used in  pulmonology  and critical-care medicine to determine  gas exchange  across the alveolar-capillary membrane.  ABG testing also has a variety of applications in other areas of medicine. Combinations of disorders can be complex and difficult to interpret, so calculators, [ 2 ]   nomograms , and rules of thumb [ 3 ]  are commonly used."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2197", "contents": "ABG  samples  originally were sent from the clinic to the  medical laboratory  for analysis. Newer equipment lets the analysis be done also as  point-of-care testing , depending on the equipment available in each clinic."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2198", "contents": "Arterial blood for  blood-gas analysis  is usually drawn by a  respiratory therapist  and sometimes a  phlebotomist , a  nurse , a  paramedic  or a doctor. [ 4 ]  Blood is most commonly drawn from the  radial artery  because it is easily accessible, can be compressed to control bleeding, and has less risk for  vascular occlusion . The selection of which radial artery to draw from is based on the outcome of an  Allen's test . The  brachial artery  (or less often, the  femoral artery ) is also used, especially during emergency situations or with children. Blood can also be taken from an arterial catheter already placed in one of these arteries. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2199", "contents": "There are plastic and glass syringes used for blood gas samples. [ 6 ]   Most syringes come pre-packaged and contain a small amount of  heparin , to prevent  coagulation . Other syringes may need to be heparinised, by drawing up a small amount of liquid heparin and squirting it out again to remove air bubbles. Once the sample is obtained, [ 7 ]  care is taken to eliminate visible gas bubbles, as these bubbles can dissolve into the sample and cause inaccurate results.  The sealed syringe is taken to a  blood gas analyzer . [ 8 ]   If a plastic blood gas syringe is used, the sample should be transported and kept at room temperature and analyzed within 30 min.  If prolonged time delays are expected (i.e., greater than 30 min) prior to analysis, the sample should be drawn in a glass syringe and immediately placed on ice. [ 9 ]   Standard blood tests can also be performed on arterial blood, such as measuring  glucose ,  lactate ,  hemoglobins , dyshemoglobins,  bilirubin  and   electrolytes . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2200", "contents": "Derived parameters include bicarbonate concentration, SaO2, and base excess.  Bicarbonate concentration is calculated from the measured pH and PCO2 using the Henderson-Hasselbalch equation.  SaO2 is derived from the measured PO2 and calculated based on the assumption that all measured hemoglobin is normal (oxy- or deoxy-) hemoglobin. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2201", "contents": "The machine used for analysis aspirates this blood from the syringe and measures the  pH  and the  partial pressures  of oxygen and carbon dioxide. The bicarbonate concentration is also calculated. These results are usually available for interpretation within five minutes. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2202", "contents": "Two methods have been used in medicine in the management of blood gases  of patients in  hypothermia : pH-stat method and alpha-stat method. Recent studies suggest that the \u03b1-stat method is superior. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2203", "contents": "Both the pH-stat and alpha-stat strategies have theoretical disadvantages. \u03b1-stat method is the method of choice for optimal myocardial function. The pH-stat method may result in loss of autoregulation in the brain (coupling of the cerebral blood flow with the metabolic rate in the brain). By increasing the cerebral blood flow beyond the metabolic requirements, the pH-stat method may lead to cerebral microembolisation and intracranial hypertension. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2204", "contents": "These are typical  reference ranges , although various analysers and laboratories may employ different ranges."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2205", "contents": "There are two calculations for base excess (extra cellular fluid - BE(ecf); blood - BE(b)).  The calculation used for the BE(ecf) = [ HCO \u2212 3 ]\u2212 24.8 + 16.2 \u00d7 (pH \u2212 7.4). The calculation used for BE(b) = (1 \u2212 0.014 \u00d7  Hgb ) \u00d7 ([ HCO \u2212 3 ]\u2212 24.8 + (1.43 \u00d7 Hgb + 7.7) \u00d7 (pH \u2212 7.4)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2206", "contents": "Contamination of the sample with room air will result in abnormally low carbon dioxide and possibly elevated oxygen levels, and a concurrent elevation in pH.  Delaying analysis (without chilling the sample) may result in inaccurately low oxygen and high carbon dioxide levels as a result of ongoing cellular respiration."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2207", "contents": "The normal range for pH is 7.35\u20137.45. As the pH decreases (< 7.35), it implies  acidosis , while if the pH increases (> 7.45) it implies  alkalosis . In the context of arterial blood gases, the most common occurrence will be that of  respiratory acidosis .  Carbon dioxide is dissolved in the blood as carbonic acid, a weak acid; however, in large concentrations, it can affect the pH drastically. Whenever there is poor pulmonary ventilation, the carbon dioxide levels in the blood are expected to rise. This leads to a rise of carbonic acid, leading to a decrease in pH. The first buffer of pH will be the plasma proteins, since these can accept some H +  ions to try to maintain  acid-base homeostasis . As carbon dioxide concentrations continue to increase ( Pa CO 2  > 45 mmHg), a condition known as respiratory acidosis occurs. The body tries to maintain homeostasis by increasing the respiratory rate, a condition known as tachypnea. This allows much more carbon dioxide to escape the body through the lungs, thus increasing the pH by having less carbonic acid. If a person is in a critical setting and intubated, one must increase the number of breaths mechanically. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2208", "contents": "Respiratory alkalosis  ( Pa  CO 2  < 35 mmHg) occurs when there is too little carbon dioxide in the blood. This may be due to hyperventilation or else excessive breaths given via a  mechanical ventilator  in a critical care setting. The action to be taken is to calm the person and try to reduce the number of breaths being taken to normalize the pH. The respiratory pathway tries to compensate for the change in pH in a matter of 2\u20134 hours. If this is not enough, the metabolic pathway takes place. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2209", "contents": "Under normal conditions, the  Henderson\u2013Hasselbalch equation  will give the blood pH"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2210", "contents": "The kidney and the liver are two main organs responsible for the metabolic homeostasis of pH. Bicarbonate is a base that helps to accept excess hydrogen ions whenever there is acidaemia. However, this mechanism is slower than the respiratory pathway and may take from a few hours to 3 days to take effect. In acidaemia, the bicarbonate levels rise, so that they can neutralize the excess acid, while the contrary happens when there is alkalaemia. Thus when an arterial blood gas test reveals, for example, an elevated bicarbonate, the problem has been present for a couple of days, and metabolic compensation took place over a blood acidaemia problem. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2211", "contents": "In general, it is much easier to correct acute pH derangement by adjusting respiration. Metabolic compensations take place at a much later stage. However, in a critical setting, a person with a normal pH, a high CO 2 , and a high bicarbonate means that, although there is a high carbon dioxide level, there is metabolic compensation. As a result, one must be careful as to not artificially adjust breaths to lower the carbon dioxide. In such case, lowering the carbon dioxide abruptly means that the bicarbonate will be in excess and will cause a metabolic alkalosis. In such a case, carbon dioxide levels should be slowly diminished. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2212", "contents": "Since the advent of  pulse oximetry  which measures oxygen saturation transcutaneously and is non-invasive, arterial blood is seldom used for the determination of oxygenation outside the ICU. Acid base status can be determined with  venous blood   precluding the pain and inconvenience of arterial blood sampling in most cases. When an indwelling arterial line  catheter  is present, arterial blood is easy to obtain and still used.  Venous blood  is generally used otherwise, usually from a   peripheral   vein, such as a forearm vein. \nThe values of pH and HCO3 of venous blood are close enough to arterial blood for direct comparison. The pCO2 of  venous blood  is less reliably compared to arterial blood but may be used in some cases. The PO2 level of venous blood is always significantly lower that arterial and should be reported, labeled and interpreted as venous PO2.\n [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2213", "contents": "2,3-Bisphosphoglyceric acid  ( conjugate base   2,3-bisphosphoglycerate ) ( 2,3-BPG ), also known as  2,3-diphosphoglyceric acid  (conjugate base  2,3-diphosphoglycerate ) ( 2,3-DPG ), is a three-carbon isomer of the glycolytic intermediate  1,3-bisphosphoglyceric acid  (1,3-BPG)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2214", "contents": "D -2,3-BPG is present in human red blood cells (RBC;  erythrocyte ) at approximately 5\u00a0mmol/L. It binds with greater affinity to deoxygenated  hemoglobin  (e.g., when the red blood cell is near respiring tissue) than it does to oxygenated hemoglobin (e.g., in the lungs) due to conformational differences: 2,3-BPG (with an estimated size of about 9  \u00c5 ) fits in the deoxygenated hemoglobin conformation (with an 11-Angstrom pocket), but not as well in the oxygenated conformation (5 Angstroms). It interacts with deoxygenated hemoglobin beta subunits and decreases the affinity for oxygen and  allosterically  promotes the release of the remaining oxygen molecules bound to the hemoglobin. Therefore, it enhances the ability of RBCs to release oxygen near tissues that need it most. 2,3-BPG is thus an  allosteric effector ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2215", "contents": "Its function was discovered in 1967 by  Reinhold Benesch  and  Ruth Benesch . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2216", "contents": "2,3-BPG is formed from  1,3-BPG  by the enzyme  BPG mutase . It can then be broken down by  2,3-BPG phosphatase  to form  3-phosphoglycerate . Its synthesis and breakdown are, therefore, a way around a step of  glycolysis , with the net expense of one ATP per molecule of 2,3-BPG generated as the high-energy carboxylic acid-phosphate mixed anhydride bond is cleaved by  2,3-BPG phosphatase ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2217", "contents": "The normal glycolytic pathway generates 1,3-BPG, which may be dephosphorylated by  phosphoglycerate kinase  (PGK), generating ATP, or it may be shunted into the  Luebering-Rapoport pathway , where  bisphosphoglycerate mutase  catalyzes the transfer of a phosphoryl group from C1 to C2 of 1,3-BPG, giving 2,3-BPG. 2,3-BPG, the most concentrated organophosphate in the erythrocyte, forms 3-PG by the action of  bisphosphoglycerate phosphatase . The concentration of 2,3-BPG varies proportionately to the [H+]."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2218", "contents": "There is a delicate balance between the need to generate  ATP  to support energy requirements for cell metabolism and the need to maintain appropriate oxygenation/deoxygenation status of hemoglobin. This balance is maintained by isomerisation of 1,3-BPG to 2,3-BPG, which enhances the deoxygenation of hemoglobin."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2219", "contents": "When 2,3-BPG binds to deoxyhemoglobin, it acts to stabilize the low oxygen affinity state (T state) of the oxygen carrier. It fits neatly into the cavity of the deoxy- conformation, exploiting the  molecular symmetry  and positive polarity by forming salt bridges with  lysine  and  histidine  residues in the \u03b2 subunits of  hemoglobin . The R state, with oxygen bound to a heme group, has a different conformation and does not allow this interaction. By itself, hemoglobin has sigmoid-like kinetics. In selectively binding to deoxyhemoglobin, 2,3-BPG stabilizes the T state conformation, making it harder for oxygen to bind hemoglobin and more likely to be released to adjacent tissues."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2220", "contents": "An increase in 2,3-BPG essentially facilitates the delivery of oxygen from hemoglobin in target tissues, at a cost of also making it somewhat more difficult for hemoglobin to take up oxygen in the lungs. This mechanisms makes maternal-fetal oxygenation more efficient, as fetal 2,3-BPG is lower than maternal levels, resulting in a higher uptake of oxygen by the fetal blood in the placenta."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2221", "contents": "2,3-BPG may also serve to physiologically counteract certain metabolic disturbances to the oxygen-hemoglobin dissociation curve. For example, at  high altitudes , low atmospheric oxygen content of oxygen can cause  hyperventilation  and resultant  metabolic alkalosis  which causes an abnormal left-shift of the oxygen-hemoglobin dissociation curve, and this can be counteracted by an increase in 2,3-BPG. [ 2 ]  Traditional teaching has claimed that the physiologic  increased 2,3-BPG seen at high altitudes is simply to make it easier for oxygen to be delivered in target tissues, but this mechanism by itself is refuted by the reasoning that the decreased oxygen affinity would also inhibit oxygen uptake in the lungs, and arguably result in a net decrease in total oxygen delivery to target tissues. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2222", "contents": "In pregnant women, there is a 30% increase in intracellular 2,3-BPG. This lowers the maternal hemoglobin affinity for oxygen, and therefore allows more oxygen to be offloaded to the fetus in the maternal uterine arteries. The fetus has a low sensitivity to 2,3-BPG, so its hemoglobin has a higher affinity for oxygen. Therefore, although the pO2 in the uterine arteries is low, the fetal  umbilical artery  (which carries deoxygenated blood) can still get oxygenated from them."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2223", "contents": "The increased maternal 2,3-BPG also causes a decreased affinity for oxygen takeup in the lungs, but this is usually compensated by a physiologic increased respiratory rate in pregnancy. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2224", "contents": "Fetal hemoglobin  (HbF), on the other hand, exhibits a low affinity for 2,3-BPG, resulting in a higher binding affinity for oxygen. This increased oxygen-binding affinity relative to that of  adult hemoglobin  (HbA) is due to HbF's having two \u03b1/\u03b3 dimers as opposed to the two \u03b1/\u03b2 dimers of HbA.  The positive  histidine  residues of HbA \u03b2-subunits that are essential for forming the 2,3-BPG binding pocket are replaced by  serine  residues in HbF \u03b3-subunits. Like that, histidine n\u00ba143 gets lost, so 2,3-BPG has difficulties in linking to the fetal hemoglobin, and it looks like the pure hemoglobin.\nIncreased binding affinity of fetal hemoglobin relative to HbA facilitates the passage of oxygen across the placental membrane from the mother to the fetus."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2225", "contents": "Differences between myoglobin (Mb), fetal hemoglobin (Hb F), adult hemoglobin (Hb A)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2226", "contents": "Hyperthyroidism"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2227", "contents": "A 2004 study checked the effects of thyroid hormone on 2,3-BPG levels. The result was that the hyperthyroidism modulates in vivo 2,3-BPG content in erythrocytes by changes in the expression of  phosphoglycerate mutase  (PGM) and 2,3-BPG synthase.\nThis result shows that the increase in the 2,3-BPG content of erythrocytes observed in hyperthyroidism doesn\u2019t depend on any variation in the rate of circulating hemoglobin, but seems to be a direct consequence of the stimulating effect of thyroid hormones on erythrocyte glycolytic activity. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2228", "contents": "Chronic anemia"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2229", "contents": "Red cells increase their intracellular 2,3-BPG concentration as much as five times within one to two hours in patients with chronic anemia, when the oxygen carrying capacity of the blood is diminished. This results in a rightward shift of the oxygen dissociation curve and more oxygen being released to the tissues."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2230", "contents": "Chronic respiratory disease with  hypoxia"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2231", "contents": "Recently, scientists have found similarities between low amounts of 2,3-BPG with the occurrence of  high altitude pulmonary edema  at high altitudes."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2232", "contents": "In a 1998 study, erythrocyte 2,3-BPG concentration was analyzed during the  hemodialysis  process. The 2,3-BPG concentration was expressed relative to the hemoglobin tetramer (Hb4) concentration as the 2,3-BPG/Hb4 ratio. Physiologically, an increase in 2,3-BPG levels would be expected to counteract the hypoxia that is frequently observed in this process. Nevertheless, the results show a 2,3-BPG/Hb4 ratio decreased. This is due to the procedure itself: mechanical stress on the erythrocytes is believed to cause the 2,3-BPG escape, which is then removed by hemodialysis. The concentrations of  calcium ,  phosphate ,  creatinine ,  urea  and  albumin  did not correlate significantly with the total change in 2,3-BPG/Hb4 ratio. However, the ratio sampled just before dialysis correlated significantly and positively with the total weekly dosage of  erythropoietin  (main hormone in  erythrocyte  formation) given to the patients. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2233", "contents": "The  Bohr effect  is a phenomenon first described in 1904 by the Danish physiologist  Christian Bohr .  Hemoglobin 's oxygen binding affinity (see  oxygen\u2013haemoglobin dissociation curve ) is inversely related both to acidity and to the concentration of carbon dioxide. [ 1 ]  That is, the Bohr effect refers to the shift in the oxygen dissociation curve caused by changes in the concentration of  carbon dioxide  or the  pH  of the environment. Since carbon dioxide reacts with water to form  carbonic acid , an increase in CO 2  results in a decrease in blood  pH , [ 2 ]  resulting in hemoglobin proteins releasing their load of oxygen. Conversely, a decrease in carbon dioxide provokes an increase in pH, which results in hemoglobin picking up more oxygen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2234", "contents": "In the early 1900s, Christian Bohr was a professor at the  University of Copenhagen  in Denmark, already well known for his work in the field of respiratory physiology. [ 3 ]  He had spent the last two decades studying the solubility of oxygen, carbon dioxide, and other gases in various liquids, [ 4 ]  and had conducted extensive research on haemoglobin and its affinity for oxygen. [ 3 ]  In 1903, he began working closely with  Karl Hasselbalch  and  August Krogh , two of his associates at the university, in an attempt to experimentally replicate the work of  Gustav von H\u00fcfner , using whole blood instead of haemoglobin solution. [ 1 ]  H\u00fcfner had suggested that the oxygen-haemoglobin binding curve was  hyperbolic  in shape, [ 5 ]  but after extensive experimentation, the Copenhagen group determined that the curve was in fact  sigmoidal . Furthermore, in the process of plotting out numerous dissociation curves, it soon became apparent that high partial pressures of carbon dioxide caused the curves to shift to the right. [ 4 ]  Further experimentation while varying the CO 2  concentration quickly provided conclusive evidence, confirming the existence of what would soon become known as the Bohr effect. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2235", "contents": "There is some more debate over whether Bohr was actually the first to discover the relationship between CO 2  and oxygen affinity, or whether the Russian physiologist  Bronislav Verigo \u00a0[ ru ]  beat him to it, allegedly discovering the effect in 1898, six years before Bohr. [ 6 ]  While this has never been proven, Verigo did in fact publish a paper on the haemoglobin-CO 2  relationship in 1892. [ 7 ]  His proposed model was flawed, and Bohr harshly criticized it in his own publications. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2236", "contents": "Another challenge to Bohr's discovery comes from within his lab. Though Bohr was quick to take full credit, his associate Krogh, who invented the apparatus used to measure gas concentrations in the experiments, [ 8 ]  maintained throughout his life that he himself had actually been the first to demonstrate the effect. Though there is some evidence to support this, retroactively changing the name of a well-known phenomenon would be extremely impractical, so it remains known as the Bohr effect. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2237", "contents": "The Bohr effect increases the efficiency of oxygen transportation through the blood. After hemoglobin binds to oxygen in the  lungs  due to the high oxygen concentrations, the Bohr effect facilitates its release in the tissues, particularly those tissues in most need of oxygen. When a tissue's metabolic rate increases, so does its carbon dioxide waste production. When released into the bloodstream, carbon dioxide forms  bicarbonate  and protons through the following reaction:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2238", "contents": "Although this reaction usually proceeds very slowly, the enzyme  carbonic anhydrase  (which is present in  red blood cells ) drastically speeds up the conversion to bicarbonate and protons. [ 2 ]  This causes the pH of the blood to decrease, which promotes the dissociation of oxygen from haemoglobin, and allows the surrounding tissues to obtain enough oxygen to meet their demands. In areas where oxygen concentration is high, such as the lungs, binding of oxygen causes haemoglobin to release protons, which recombine with bicarbonate to eliminate carbon dioxide during  exhalation . These opposing protonation and deprotonation reactions occur in equilibrium resulting in little overall change in blood pH."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2239", "contents": "The Bohr effect enables the body to adapt to changing conditions and makes it possible to supply extra oxygen to tissues that need it the most. For example, when  muscles  are undergoing strenuous activity, they require large amounts of oxygen to conduct  cellular respiration , which generates CO 2  (and therefore HCO 3 \u2212  and H + ) as byproducts. These waste products lower the pH of the blood, which increases oxygen delivery to the active muscles. Carbon dioxide is not the only molecule that can trigger the Bohr effect. If muscle cells aren't receiving enough oxygen for cellular respiration, they resort to  lactic acid fermentation , which releases  lactic acid  as a byproduct. This increases the acidity of the blood far more than CO 2  alone, which reflects the cells' even greater need for oxygen. In fact, under anaerobic conditions, muscles generate lactic acid so quickly that pH of the blood passing through the  muscles  will drop to around 7.2, which causes haemoglobin to begin releasing roughly 10% more oxygen. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2240", "contents": "The magnitude of the Bohr effect is usually given by the slope of the   \n \n \n \n log \n \u2061 \n ( \n \n P \n \n 50 \n \n \n ) \n \n \n {\\textstyle \\log(P_{50})} \n \n  vs   \n \n \n \n \n pH \n \n \n \n {\\textstyle {\\text{pH}}} \n \n  curve where,  P 50  refers to the partial pressure of oxygen when 50% of haemoglobin's binding sites are occupied. The slope is denoted:  \n \n \n \n \n \n \n \u0394 \n log \n \u2061 \n ( \n \n P \n \n 50 \n \n \n ) \n \n \n \u0394 \n \n pH \n \n \n \n \n \n \n {\\textstyle {\\scriptstyle \\Delta \\log(P_{50}) \\over \\Delta {\\text{pH}}}} \n \n  where  \n \n \n \n \u0394 \n \n \n {\\textstyle \\Delta } \n \n  denotes change. That is,  \n \n \n \n \u0394 \n log \n \u2061 \n ( \n \n P \n \n 50 \n \n \n ) \n \n \n {\\textstyle \\Delta \\log(P_{50})} \n \n   denotes the change in  \n \n \n \n log \n \u2061 \n ( \n \n P \n \n 50 \n \n \n ) \n \n \n {\\textstyle \\log(P_{50})} \n \n  and  \n \n \n \n \u0394 \n \n pH \n \n \n \n {\\textstyle \\Delta {\\text{pH}}} \n \n  the change in  \n \n \n \n \n pH \n \n \n \n {\\textstyle {\\text{pH}}} \n \n .\nBohr effect strength exhibits an inverse relationship with the size of an organism: the magnitude increases as size and weight decreases. For example,  mice  possess a very strong Bohr effect, with a  \n \n \n \n \n \n \n \u0394 \n log \n \u2061 \n ( \n \n P \n \n 50 \n \n \n ) \n \n \n \u0394 \n \n pH \n \n \n \n \n \n \n {\\textstyle {\\scriptstyle \\Delta \\log(P_{50}) \\over \\Delta {\\text{pH}}}} \n \n  value of -0.96, which requires relatively minor changes in H +  or CO 2  concentrations, while  elephants  require much larger changes in concentration to achieve a much weaker effect  \n \n \n \n \n ( \n \n \n \n \n \u0394 \n log \n \u2061 \n ( \n \n P \n \n 50 \n \n \n ) \n \n \n \u0394 \n \n pH \n \n \n \n \n = \n \u2212 \n 0.38 \n \n ) \n \n \n \n {\\textstyle \\left({\\scriptstyle \\Delta \\log(P_{50}) \\over \\Delta {\\text{pH}}}=-0.38\\right)} \n \n . [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2241", "contents": "The Bohr effect hinges around allosteric interactions between the  hemes  of the haemoglobin  tetramer , a mechanism first proposed by Max Perutz in 1970. [ 10 ]  Haemoglobin exists in two conformations: a high-affinity R state and a low-affinity T state. When oxygen concentration levels are high, as in the lungs, the R state is favored, enabling the maximum amount of oxygen to be bound to the hemes. In the capillaries, where oxygen concentration levels are lower, the T state is favored, in order to facilitate the delivery of oxygen to the tissues. The Bohr effect is dependent on this allostery, as increases in CO 2  and H +  help stabilize the T state and ensure greater oxygen delivery to muscles during periods of elevated cellular respiration. This is evidenced by the fact that  myoglobin , a  monomer  with no allostery, does not exhibit the Bohr effect. [ 2 ]  Haemoglobin mutants with weaker allostery may exhibit a reduced Bohr effect. For example, in Hiroshima variant  haemoglobinopathy , allostery in haemoglobin is reduced, and the Bohr effect is diminished. As a result, during periods of exercise, the mutant haemoglobin has a higher affinity for oxygen and tissue may suffer minor  oxygen starvation . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2242", "contents": "When hemoglobin is in its T state, the  N-terminal  amino groups of the \u03b1-subunits and the  C-terminal   histidine  of the \u03b2-subunits are protonated, giving them a positive charge and allowing these residues to participate in  ionic interactions  with carboxyl groups on nearby residues. These interactions help hold the haemoglobin in the T state. Decreases in pH (increases in acidity) stabilize this state even more, since a decrease in pH makes these residues even more likely to be protonated, strengthening the ionic interactions. In the R state, the ionic pairings are absent, meaning that the R state's stability increases when the pH increases, as these residues are less likely to stay protonated in a more basic environment. The Bohr effect works by simultaneously destabilizing the high-affinity R state and stabilizing the low-affinity T state, which leads to an overall decrease in oxygen affinity. [ 2 ]  This can be visualized on an  oxygen-haemoglobin dissociation curve  by shifting the whole curve to the right."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2243", "contents": "Carbon dioxide can also react directly with the N-terminal amino groups to form  carbamates , according to the following reaction:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2244", "contents": "CO 2  forms carbamates more frequently with the T state, which helps to stabilize this conformation. The process also creates protons, meaning that the formation of carbamates also contributes to the strengthening of ionic interactions, further stabilizing the T state. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2245", "contents": "An exception to the otherwise well-supported link between animal body size and the sensitivity of its haemoglobin to changes in pH was discovered in 1961. [ 12 ]  Based on their size and weight, many  marine mammals  were hypothesized to have a very low, almost negligible Bohr effect. [ 9 ]  However, when their blood was examined, this was not the case.  Humpback whales  weighing 41,000 kilograms had an observed  \n \n \n \n \n \n \n \u0394 \n log \n \u2061 \n ( \n \n P \n \n 50 \n \n \n ) \n \n \n \u0394 \n \n pH \n \n \n \n \n \n \n {\\textstyle {\\scriptstyle \\Delta \\log(P_{50}) \\over \\Delta {\\text{pH}}}} \n \n  value of 0.82, which is roughly equivalent to the Bohr effect magnitude in a 0.57\u00a0kg  guinea pig . [ 9 ]  This extremely strong Bohr effect is hypothesized to be one of marine mammals' many adaptations for deep, long dives, as it allows for virtually all of the bound oxygen on haemoglobin to dissociate and supply the whale's body while it is underwater. [ 12 ]  Examination of other marine mammal species supports this. In  pilot whales  and  porpoises , which are primarily surface feeders and seldom dive for more than a few minutes, the  \n \n \n \n \n \n \n \u0394 \n log \n \u2061 \n ( \n \n P \n \n 50 \n \n \n ) \n \n \n \u0394 \n \n pH \n \n \n \n \n \n \n {\\textstyle {\\scriptstyle \\Delta \\log(P_{50}) \\over \\Delta {\\text{pH}}}} \n \n was 0.52, comparable to a  cow , [ 9 ]  which is much closer to the expected Bohr effect magnitude for animals of their size. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2246", "contents": "Another special case of the Bohr effect occurs when  carbon monoxide  is present. This molecule serves as a  competitive inhibitor  for oxygen, and binds to haemoglobin to form  carboxyhaemoglobin . [ 13 ]  Haemoglobin's affinity for CO is about 210 times stronger than its affinity for O 2 , [ 14 ]  meaning that it is very unlikely to dissociate, and once bound, it blocks the binding of O 2  to that subunit. At the same time, CO is structurally similar enough to O 2  to cause carboxyhemoglobin to favor the R state, raising the oxygen affinity of the remaining unoccupied subunits. This combination significantly reduces the delivery of oxygen to the tissues of the body, which is what makes carbon monoxide so  toxic . This toxicity is reduced slightly by an increase in the strength of the Bohr effect in the presence of carboxyhemoglobin. This increase is ultimately due to differences in interactions between heme groups in carboxyhemoglobin relative to oxygenated hemoglobin. It is most pronounced when the oxygen concentration is extremely low, as a last-ditch effort when the need for oxygen delivery becomes critical. However, the physiological implications of this phenomenon remain unclear. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2247", "contents": "The  Bohr equation , named after  Danish  physician  Christian Bohr  (1855\u20131911), describes the amount of  physiological dead space  in a person's lungs.  This is given as a  ratio  of dead space to  tidal volume .  It differs from  anatomical dead space  as measured by  Fowler's method  as it includes  alveolar  dead space."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2248", "contents": "The Bohr equation is used to quantify the ratio of physiological dead space to the total tidal volume, and gives an indication of the extent of wasted ventilation. The original formulation by Bohr, [ 1 ]  required measurement of the alveolar partial pressure P A ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2249", "contents": "The modification by Enghoff [ 2 ]  replaced the mixed alveolar partial pressure of CO 2  with the arterial partial pressure of that gas. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2250", "contents": "The Bohr equation, with Enghoff's modification, is commonly stated as follows: [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2251", "contents": "Here  \n \n \n \n \n V \n \n d \n \n \n \n \n {\\displaystyle V_{d}} \n \n  is the volume of the exhale that arises from the physiological dead space of the lung and  \n \n \n \n \n V \n \n t \n \n \n \n \n {\\displaystyle V_{t}} \n \n  is the tidal volume;"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2252", "contents": "Its derivation is based on the fact that only the ventilated gases involved in gas exchange ( \n \n \n \n \n V \n \n A \n \n \n \n \n {\\displaystyle V_{A}} \n \n ) will produce  CO 2 .  Because the total tidal volume ( \n \n \n \n \n V \n \n T \n \n \n \n \n {\\displaystyle V_{T}} \n \n ) is made up of  \n \n \n \n \n V \n \n A \n \n \n + \n \n V \n \n d \n \n \n \n \n {\\displaystyle V_{A}+V_{d}} \n \n  (alveolar volume + dead space volume), we can substitute  \n \n \n \n \n V \n \n A \n \n \n \n \n {\\displaystyle V_{A}} \n \n  for  \n \n \n \n \n V \n \n T \n \n \n \u2212 \n \n V \n \n d \n \n \n \n \n {\\displaystyle V_{T}-V_{d}} \n \n ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2253", "contents": "Initially, Bohr tells us V T  = V d  + V A . The Bohr equation helps us find the amount of any expired gas, CO 2 , N 2 , O 2 , etc."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2254", "contents": "In this case we will focus on CO 2 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2255", "contents": "Defining F e  as the fraction of CO 2  in the average expired breath, F A  as the fraction of CO 2  in the perfused alveolar volume, and F d  as the CO 2  makeup of the unperfused (and thus 'dead') region of the lung;"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2256", "contents": "V T  x F e  = ( V d  x F d  ) + (V A  x F A  )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2257", "contents": "This states that all of the CO 2  expired comes from two regions, the dead space volume and the alveolar volume.  \nIf we suppose that F d  = 0 (since carbon dioxide's concentration in air is normally negligible), then we can say that: [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2258", "contents": "The only source of CO 2  is the alveolar space where gas exchange with blood takes place. Thus the alveolar fractional component of CO 2 , F A , will always be higher than the average CO 2  content of the expired air because of a non-zero dead space volume V d , thus the above equation will always yield a positive number."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2259", "contents": "Where P tot  is the total pressure, we obtain:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2260", "contents": "Therefore:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2261", "contents": "A common step is to then presume that the partial pressure of carbon dioxide in the end-tidal exhaled air is in equilibrium with that gas' tension in the blood that leaves the alveolar capillaries of the lung."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2262", "contents": "Bronchoconstriction  is the constriction of the airways in the  lungs  due to the tightening of surrounding  smooth muscle , with consequent  coughing ,  wheezing , and  shortness of breath ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2263", "contents": "The condition has a number of causes, the most common being  emphysema  as well as  asthma .  Exercise  and  allergies  can bring on the symptoms in an otherwise asymptomatic individual. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2264", "contents": "With emphysema the shortness of breath due to effective bronchoconstriction from excessive very thick mucus blockage (it is so thick that great difficulty is encountered in expelling it resulting in near exhaustion at times) can bring on panic attacks unless the individual expects this and has effectively learned  pursed lip breathing  to more quickly transfer oxygen to the blood via the damaged alveoli resulting from the disease.  The most common cause of emphysema is smoking and  smoking cessation  is mandatory if this incurable disease is to be treated.  Prevention of bronchoconstriction by this pathway is vital for people with emphysema and there are several  anticholinergic  medications that in combination with mucous thinning agents such as  Guaifenesin  cause significant improvement in breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2265", "contents": "More generally termed  exercise-induced asthma , the preferred and more accurate term  exercise-induced bronchoconstriction  better reflects underlying  pathophysiology . It is also preferred due to the former term giving the false impression that asthma is caused by exercise."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2266", "contents": "In a patient with EIB, exercise initially follows the normal patterns of bronchodilation. However, by three minutes, the constriction sets in, which peaks at around 10\u201315 minutes, and usually resolves itself by an hour. During an episode of this type of bronchoconstriction, the levels of inflammatory mediators, particularly  leukotrienes ,  histamine , and  interleukin , increase. TH2-type  lymphocytes  are activated, with an increase in  T cells  expressing CD25 (IL-2R), and  B cells  expressing CD 23, causing increased production of  IgE . After exercise, the conditions will fade within one to three minutes. In most people with EIB, this is followed by a  refractory period , of generally less than four hours, during which if exercise is repeated, the bronchoconstriction  is less emphasised. This is probably caused by the release of  prostaglandins ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2267", "contents": "The underlying cause of this type of bronchoconstriction appear to be the large volume of cool, dry air inhaled during strenuous exercise. The condition appears to improve when the air inhaled is more fully humidified and closer to  body temperature ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2268", "contents": "This specific condition, in the general population, can vary between 7 and 20 percent. This increases to around 80 percent in those with symptomatic asthma. In many cases, however, the constriction, even during or after strenuous exercise, is not clinically significant except in cases of severe to moderate emphysema."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2269", "contents": "In May 2013, the American Thoracic Society issued the first treatment guidelines for EIB. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2270", "contents": "While a different cause, this has very similar symptoms, namely the immunological reaction involving release of inflammatory mediators."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2271", "contents": "Inhalation of  allergens  in sensitized subjects develops into bronchoconstriction  within 10 minutes, reaches a maximum within 30 minutes, and usually resolves itself within one to three hours. In some subjects, the constriction does not return to normal, and recurs after three to four hours, which may last up to a day or more. The first is named the  early asthmatic response , and the latter the  late asthmatic response ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2272", "contents": "Bronchoconstriction can occur as a result of  anaphylaxis , even when the allergen is not inhaled."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2273", "contents": "Bronchoconstriction is defined as the narrowing of the airways in the lungs (bronchi and bronchioles). Air flow in air passages can get restricted in three ways: [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2274", "contents": "The bronchial spasm is due to the activation of  parasympathetic nervous system .  Postganglionic  parasympathetic fibers will release  acetylcholine  causing the constriction of the  smooth muscle  layer surrounding the bronchi. These smooth muscle cells have  muscarinic M 3  receptors  on their membrane. The activation of these receptors by acetylcholine will activate an intracellular  G protein , that in turn will activate the  phospholipase C  pathway, that will end in an increase of intracellular calcium concentrations and therefore contraction of the smooth muscle cell. The muscle contraction will cause the diameter of the bronchus to decrease, therefore increasing its resistance to airflow. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2275", "contents": "Bronchoconstriction is common in people with respiratory problems, such as asthma, COPD, and cystic fibrosis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2276", "contents": "Medical management of transient bronchoconstriction or  chronic bronchitis  depends on the severity and etiology of the underlying disease and can be treated with combinations of the following medications:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2277", "contents": "A  bronchodilator  or  broncholytic [ 1 ]  (although the latter occasionally includes  secretory  inhibition as well) is a substance that dilates the  bronchi  and  bronchioles , decreasing resistance in the  respiratory airway  and increasing airflow to the  lungs . Bronchodilators may be  originating naturally within the body , or they may be  medications  administered for the treatment of breathing difficulties, usually in the form of  inhalers . They are most useful in  obstructive lung diseases , of which  asthma  and  chronic obstructive pulmonary disease  are the most common conditions. They may be useful in  bronchiolitis  and  bronchiectasis , although this remains somewhat controversial. They are often prescribed but of unproven significance in  restrictive lung diseases . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2278", "contents": "Bronchodilators are either short-acting or long-acting. Short-acting medications provide quick or \"rescue\" relief from acute  bronchoconstriction . Long-acting bronchodilators help to control and prevent symptoms. The three types of prescription bronchodilating drugs are  beta-2 adrenergic agonists  (short- and long-acting),  anticholinergics  (short- and long-acting), and  theophylline  (long-acting)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2279", "contents": "These are quick-relief or \"rescue\" medications that provide quick, temporary relief from asthma symptoms or flare-ups. These medications usually take effect within 20 minutes or less, and can last from four to six hours. These inhaled medications are best for treating sudden and severe or new asthma symptoms. Taken 15 to 20 minutes ahead of time, these medications can also prevent asthma symptoms triggered by exercise or exposure to cold air. Some short-acting \u03b2-agonists, such as  salbutamol , are specific to the lungs; they are called \u03b2 2 -adrenergic agonists and can relieve bronchospasms without unwanted  cardiac  side effects of nonspecific \u03b2-agonists (for example,  ephedrine  or  epinephrine ). Patients who regularly or frequently need to take a short-acting \u03b2 2 -adrenergic agonist should consult their doctor, as such usage indicates uncontrolled asthma, and their routine medications may need adjustment. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2280", "contents": "These are long-term medications taken routinely in order to control and prevent bronchoconstriction. They are not intended for fast relief. These medications may take longer to begin working, but relieve airway constriction for up to 12 hours.\nCommonly taken twice a day with an anti-inflammatory medication, they maintain open airways and prevent asthma symptoms, particularly at night. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2281", "contents": "Salmeterol  and  formoterol  are examples of these."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2282", "contents": "Some examples of anticholinergics are  tiotropium  (Spiriva) and  ipratropium bromide . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2283", "contents": "Tiotropium is a long-acting, 24-hour, anticholinergic bronchodilator used in the management of  chronic obstructive pulmonary disease  (COPD)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2284", "contents": "Only available as an inhalant, ipratropium bromide is used in the treatment of asthma and COPD. As a short-acting anticholinergic, it improves lung function and reduces the risk of exacerbation in people with symptomatic asthma. [ 3 ]  However, it will not stop an asthma attack already in progress. Because it has no effect on asthma symptoms when used alone, it is most often paired with a short-acting \u03b2 2 -adrenergic agonist. While it is considered a relief or rescue medication, it can take a full hour to begin working. For this reason, it plays a secondary role in acute asthma treatment. Dry throat is the most common side effect. If the medication gets in contact with the eyes, it may cause blurred vision for a brief time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2285", "contents": "The use of anticholinergics in combination with short-acting \u03b2 2 -adrenergic agonists has been shown to reduce hospital admissions in children and adults with acute asthma exacerbations. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2286", "contents": "Available in oral and injectable form,  theophylline  is a long-acting bronchodilator that prevents asthma episodes. It belongs to the chemical class  methylxanthines  (along with caffeine). It is prescribed in severe cases of asthma or those that are difficult to control. It must be taken 1\u20134 times daily, and doses cannot be missed. Blood tests are required to monitor therapy and to indicate when dosage adjustment is necessary. Side effects can include nausea, vomiting, diarrhea, stomach or headache, rapid or irregular heart beat, muscle cramps, nervous or jittery feelings, and hyperactivity. These symptoms may signal the need for an adjustment in medication. It may promote  acid reflux , also known as GERD, by relaxing the lower esophageal sphincter muscle. Some medications, such as seizure and ulcer medications and antibiotics containing  erythromycin , can interfere with the way theophylline works. Coffee, tea, colas, cigarette-smoking, and viral illnesses can all affect the action of theophylline and change its effectiveness. A physician should monitor dosage levels to meet each patient's profile and needs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2287", "contents": "Additionally, some  psychostimulant  drugs that have an amphetamine like mode of action, such as  amphetamine , [ 6 ]   methamphetamine , and  cocaine , [ 7 ]  have bronchodilating effects and were used often for  asthma  due to the lack of effective \u03b2 2 -adrenergic agonists for use as bronchodilator, but are now rarely, if ever, used medically for their bronchodilatory effects."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2288", "contents": "Gaseous  carbon dioxide  also relaxes airway musculature:  hypocapnia  caused by deliberate  hyperventilation  increases respiratory resistance while  hypercapnia  induced by carbon dioxide inhalation reduces it; [ 8 ]  however, this bronchodilating effect of carbon dioxide inhalation only lasts 4 to 5 minutes. [ 9 ]  Nonetheless, this observation has inspired the development of  S-1226 , carbon dioxide-enriched air formulated with  nebulized   perflubron . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2289", "contents": "The bronchodilators are divided into short- and long-acting groups. Short-acting bronchodilators are used for relief of bronchoconstriction, while long-acting bronchodilators are predominantly used for prevention."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2290", "contents": "Short-acting bronchodilators include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2291", "contents": "Long-acting bronchodilators include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2292", "contents": "Carboxyhemoglobin  ( carboxyhaemoglobin   BrE ) (symbol  COHb  or  HbCO ) is a stable  complex  of  carbon monoxide  and  hemoglobin  (Hb) that forms in  red blood cells  upon contact with carbon monoxide. Carboxyhemoglobin is often mistaken for the compound formed by the combination of carbon dioxide ( carboxyl ) and hemoglobin, which is actually  carbaminohemoglobin . Carboxyhemoglobin terminology emerged when carbon monoxide was known by its historic name, \"carbonic oxide\", and evolved through Germanic and British English etymological influences; the preferred  IUPAC  nomenclature is  carbonylhemoglobin . [ 2 ] [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2293", "contents": "The average non-smoker maintains a systemic carboxyhemoglobin level under 3% COHb whereas smokers approach 10% COHb. [ 4 ]  The biological threshold for carboxyhemoglobin tolerance is 15% COHb, meaning toxicity is consistently observed at levels in excess of this concentration. [ 5 ]  The  FDA  has previously set a threshold of 14% COHb in certain  clinical trials  evaluating the therapeutic potential of carbon monoxide. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2294", "contents": "The average  red blood cell  contains 250 million  hemoglobin  molecules. [ 7 ]  Hemoglobin contains a  globin  protein unit with four  prosthetic   heme  groups (hence the name  heme   -o-   globin ); each heme is capable of reversibly binding with one gaseous molecule (oxygen, carbon monoxide, cyanide, etc.), [ 8 ]  therefore a typical red blood cell may carry up to one billion gas molecules. As the binding of carbon monoxide with hemoglobin is reversible, certain models have estimated that 20% of the carbon monoxide carried as carboxyhemoglobin may dissociate in remote tissues. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2295", "contents": "In biology, carbon monoxide is naturally produced through many enzymatic and non-enzymatic pathways. [ 7 ]  The most extensively studied pathway is the metabolism of  heme  by  heme oxygenase  which occurs throughout the body with significant activity in the spleen to facilitate  hemoglobin  breakdown during  erythrocyte  recycling. Therefore heme can both carry carbon monoxide in the case of carboxyhemoglobin, or, undergo enzymatic catabolism to generate carbon monoxide."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2296", "contents": "Carbon monoxide was characterized as a neurotransmitter in 1993 and has since been subcategorized as a  gasotransmitter . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2297", "contents": "Most endogenously produced carbon monoxide is stored as carboxyhemoglobin. The gas primarily undergoes  pulmonary  excretion, however trace amounts may be oxidized to  carbon dioxide  by certain  cytochromes , metabolized by resident  microbiota , or excreted by transdermal diffusion. [ 4 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2298", "contents": "Compared to oxygen, carbon monoxide binds with approximately 240 times greater affinity, [ 9 ] [ 4 ]  however the affinity of carbon monoxide for hemoglobin varies both across species and within a species. In the 1950s,  Esther Killick  was among the first to recognize a difference in carbon monoxide affinity between adult and  foetal  blood, and a difference between humans and sheep. [ 4 ] [ 10 ] [ 11 ]  In humans, the Hb-Kirklareli mutation has a relative 80,000 times greater affinity for carbon monoxide than oxygen resulting in systemic carboxyhemoglobin reaching a sustained level of 16% COHb. [ 5 ]  Other human mutations have been described (see also:  hemoglobin variants ). [ 12 ] [ 13 ]  Structural variations and mutations across other  hemoproteins  likewise affect carbon monoxide's interaction with the heme prosthetic group as exemplified by  Cytochrome P450  where certain forms of the  CYP3A   family  is relatively less affected by the inhibitory effects of carbon monoxide. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2299", "contents": "Murinae  species have a COHb half-life of 20 minutes compared to 300 minutes for a typical human (see  \u00a7\u00a0Toxicokinetics ). [ 4 ]  As a result, the metabolic kinetics, blood saturation point, and tolerance for carbon monoxide exposure vary across species, potentially leading to data inconsistencies pertaining to the  toxicology  of  carbon monoxide poisoning  and  pharmacology  of low-dose therapeutic protocols. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2300", "contents": "Some deep-diving marine mammal species are known to contain concentrations of carbon monoxide in their blood that resembles levels seen in chronic cigarette smokers, which may provide benefits against hypoxia. [ 14 ]  Similarly, the elevated levels in smokers has been suggested to be a basis for the  smoker's paradox . [ 4 ]  Prolonged exposure to carbon monoxide and elevated carboxyhemoglobin, such as in smoking, results in  erythremia . [ 4 ]  Furthermore, humans can  acclimate  to toxic levels of carbon monoxide based on findings reported by  Esther Killick . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2301", "contents": "A bright red skin complexion is commonly associated with elevated carboxyhemoglobin levels. Trace evidence for an endogenous presence of carbon monoxide dates back to  Marcellus Donato  circa 1570 who noted an unusually red complexion upon conducting an autopsy of victims who died from charcoal fumes in  Mantua . [ 4 ]  Similar findings pertaining to red complexion later emerged as documented by  Johann Jakob Wepfer  in the 1600s, and  M.   Antoine Portal  in the late 1700s. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2302", "contents": "Phlogiston theory  is a trace origin for the first chemical explanations of endogenous carboxyhemoglobin exemplified by the work of  Joseph Priestley  in the eighteenth century who suspected phlogiston to be a cellular waste product carried by the blood of animals which was subsequently exhaled. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2303", "contents": "Thomas Beddoes ,  James Watt ,  Humphry Davy ,  James Lind , and many others investigated the therapeutic potential of inhaling  factitious airs  in the late eighteenth century (see also:  Pneumatic Institution ). Among the gases experimented with,  hydrocarbonate  had received significant attention. Hydrocarbonate is  water gas  generated by passing steam over  coke , the process of which generates carbon monoxide and hydrogen, and some considered it contain  phlogiston . Beddoes and Watt recognized hydrocarbonate brightened venous blood in 1793. Watt suggested coal fumes could act as an  antidote  to the oxygen in blood, and Beddoes and Watt likewise speculated hydrocarbonate has a greater affinity for animal fiber than oxygen in 1796. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2304", "contents": "After the discovery of carbon monoxide by  William Cruickshank  in 1800,  Johann D\u00f6mling  (1803) and  John Bostock  (1804) developed hypotheses suggesting blood returned to the heart loaded with carbon monoxide to subsequently be oxidized to carbon dioxide in the lung prior to exhalation. [ 4 ]  Later in 1854,  Adrien Chenot  similarly suggested carbon monoxide could remove oxygen from blood and be oxidized within the body to carbon dioxide. [ 4 ]  The mechanism for carbon monoxide poisoning in the context of carboxyhemoglobin formation is widely credited to  Claude Bernard  whose memoirs beginning in 1846 and published in 1857 notably phrased, \"prevents arterials blood from becoming venous\". [ 4 ]   Felix Hoppe-Seyler  independently published similar conclusions in the following year."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2305", "contents": "The first analytical method to detect carboxyhemoglobin emerged in 1858 with a colorimetric method developed by  Felix Hoppe-Seyler , and the first quantitative analysis method emerged in 1880 with  Josef von Fodor . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2306", "contents": "Carbon  is derived from the Latin term  carbo , meaning coal, via the French  charbone , which first appeared in print in 1786. [ 15 ]  The  etymology of oxygen  is generally accepted mean 'acid' based on Lavoisier's system, which also recognized carbon as a nonmetallic element capable of oxidation, although the original degrees of oxides were based on diamond, graphite, coal and  carbonic acid (CO 2 )  as the most oxidized form; [ 15 ]  Lavoisier's system was superseded by other obsolete oxide nomenclature systems. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2307", "contents": "Upon discovering carbon monoxide through a series of experiments originating from  coke  (short for coal-cake [ 15 ] ),  Cruickshank  named the new molecule \"gaseous oxide of carbon\" which evolved to \"carbonic oxide\" and was translated into German as \"kohlenoxyd\". Kohlen is the German word for coal. [ 4 ] [ 17 ]  As carbonic acid (CO 2 ) was considered to be the most highly oxidized form in Lavoisier's system, the name carbonic oxide implied an intermediate oxidized species between coal and carbonic acid (i.e. use of the word acid indicated maximum oxidation)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2308", "contents": "Haem is derived from Greek  meaning blood, [ 18 ] [ 19 ]  and globin is Latin derived from  globus  typically accepted to mean glob/spherical/round object; the terms are conjoined with an  -o-  . Regarding haem,  the use of \"ae / \u00e6\" remains prevalent in British English  in modern day [ 20 ]  whereas the American English spelling evolved to heme from hema. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2309", "contents": "Felix Hoppe-Seyler  coined the name \"h\u00e4moglobin\" in 1864. [ 21 ]  In German, an  umlaut  such as  \u00e4  is synonymous with spelling as \"ae\", therefore h\u00e4moglobin is commonly spelled as haemoglobin throughout German literature, hence haemoglobin is the term adopted by English literature."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2310", "contents": "Hoppe-Seyler likewise coined the name Kohlenoxydh\u00e4moglobin [ 22 ]  which may have similarly been directly translated back into English as \"carbonic oxide h\u00e6moglobin\". [ 23 ]  The term carboxyh\u00e6moglobin appeared as early as 1895 in works by  John Haldane  while the name for CO was still widely regarded as carbonic oxide. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2311", "contents": "The term \"carbon monoxide\" was formally introduced in 1879, but the name would not become mainstream for several decades. [ 4 ]  Variations of COHb terminology, such as carbonmonoxyhemoglobin, [ 25 ] [ 11 ]  followed and eventually evolved and simplified back into \"carboxyhemoglobin\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2312", "contents": "As carboxy is now firmly associated with the CO 2   carboxyl  group, and carbon monoxide is generally regarded as a  carbonyl , IUPAC has recommended \"carbonylhemoglobin\" as the preferred COHb nomenclature. [ 4 ]  Despite the IUPAC guidance, carboxyhemoglobin remains the most widely used term (akin to the  survival  of  bicarbonate  nomenclature)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2313", "contents": "Historically, carboxyhemoglobin detection has been achieved by  colorimetric analysis , chemical reactivity,  spectrophotometry , gasometric and  thermoelectric  detection methods. [ 4 ]   Gas chromatography  analysis emerged in 1961 and remains a commonly used method. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2314", "contents": "Modern methods include  pulse oximetry  with a  CO-oximeter , and a variety of other analytical techniques. [ 26 ] [ 27 ]  Most methods require laboratory equipment, skilled technicians, or expensive electronics therefore rapid and economical detection technologies remain in development."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2315", "contents": "Breath carbon monoxide  is another detection method that may correlate with carboxyhemoglobin levels. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2316", "contents": "Carbon monoxide poisoning, also known as carboxyhemoglobinemia, [ 29 ] [ 30 ]  has plagued humankind since primitive ancestors first harnessed fire. In modern times, carboxyhemoglobin data assist physicians in making a poisoning diagnosis. However, carboxyhemoglobin levels do not necessarily correlate with the symptoms of carbon monoxide poisoning. [ 31 ]  In general, 30% COHb is considered severe carbon monoxide poisoning. [ 4 ]  The highest reported non-fatal carboxyhemoglobin level was 73% COHb. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2317", "contents": "Gas exchange  is an essential process for many organisms to maintain homeostasis. Oxygen accounts for about 20% of Earth's atmospheric  air . While inhaling air is critical to supply cells with oxygen for  aerobic respiration  via the  Bohr effect  and  Haldane effect  (and perhaps local low oxygen partial pressure e.g. active muscles), [ 32 ]  exhaling the cellular waste product  carbon dioxide  is arguably the more critical aspect of respiration. Whereas the body can tolerate brief periods of  hypoxia  (as commonly occurs in  anaerobic exercise , although the brain, heart, liver and kidney are significantly less tolerant than skeletal muscle), failure to expel carbon dioxide may cause  respiratory acidosis  (meaning bodily fluids and blood become too acidic thereby affecting homeostasis). [ 33 ]  In absence of oxygen, cells switch to  anaerobic respiration  which if prolonged may significantly increase  lactic acid  leading to  metabolic acidosis . [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2318", "contents": "To provide a simplified synopsis of the molecular mechanism of systemic gas exchange, upon inhalation of air it was widely thought oxygen binding to any of the heme sites triggers a  conformational change  in the protein unit of hemoglobin which then enables the binding of additional oxygen to each of the other heme sites. Upon arrival to the cellular region, oxygen is released at the tissue due to a conformational change in hemoglobin as caused by ionization of hemoglobin's surface due to the \"acidification\" of the tissue's local pH (meaning a relatively higher concentration of 'acidic' protons / hydrogen  ions  annotated as H + ; an acidic pH is commonly referenced to as either low pH based on the acidity of pH 1-7 having a  low  number, or, referred to as a high pH due to the  high  concentration of H +  ions as the scale approaches pH 1); the local acidity is caused by an increase in the biotransformation of carbon dioxide waste into  carbonic acid  via  carbonic anhydrase . In other words, oxygenated arterial blood arrives to cells in the \" hemoglobin R-state \" which has deprotonated/unionized amino acid  residues  (regarding hemoglobin's  amines  transitioning between the deprotonated/unionized Hb-NH2 to the protonated/ionized Hb-NH3 +  state) based on the less-acidic pH (arterial blood averages pH 7.407 whereas venous blood is slightly more acidic at pH 7.371 [ 35 ] ). The \"T-state\" of hemoglobin is deoxygenated in venous blood partially due to protonation/ionization as caused by the acidic environment hence causing a conformation unsuited for oxygen-binding [ 36 ]  (i.e. oxygen is 'ejected' upon arrival at the cell due to H +  ions bombarding the hemoglobin surface residues to convert Hb from \"R-state\" to \"T-state\"). Furthermore, the mechanism for formation of  carbaminohemoglobin  generates additional H +  ions that may further stabilize the protonated/ionized deoxygenated hemoglobin. Upon return of venous blood into the lung and subsequent exhalation of carbon dioxide, the blood is \"de-acidified\" (see also:  hyperventilation ) for the deprotonation/unionization of hemoglobin to re-enable oxygen binding as part of the transition to arterial blood (note this process is complex due to involvement of  chemoreceptors , pH buffers and other physiochemical functionalities). Carbon monoxide poisoning disturbs this physiological process hence the venous blood of poisoning patients is bright red akin to arterial blood since the carbonyl/carbon monoxide is retained, whereas deoxygenated hemoglobin is dark red and carbaminohemoglobin has a blue hue. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2319", "contents": "At toxic concentrations, carbon monoxide as carboxyhemoglobin significantly interferes with respiration and gas exchange by simultaneously inhibiting acquisition and delivery of oxygen to cells, and preventing formation of  carbaminohemoglobin  which accounts for approximately 30% of carbon dioxide exportation. [ 37 ]  Therefore a patient suffering from carbon monoxide poisoning may experience severe  hypoxia  and  acidosis  in addition to the toxicities of excess carbon monoxide binding to numerous hemoproteins, metallic and non-metallic targets which affect cellular machinery (such as inhibition of  cytochrome c oxidase ). [ 7 ] [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2320", "contents": "In common air under normal atmospheric conditions, a typical patient's carboxyhemoglobin has a half-life around 300 minutes. [ 4 ]  This time can be reduced to 90 minutes upon administration of high-flow pure oxygen, and the time is further reduced when oxygen is administered with 5% carbon dioxide as first identified by  Esther Killick . [ 4 ]  Additionally, treatment in a  hyperbaric chamber  is a more effective manner of reducing the half-life of carboxyhemoglobin to 30 minutes [ 4 ]  and allows oxygen to dissolve in biological fluids for delivery to tissues. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2321", "contents": "Supplemental oxygen takes advantage of  Le Chatelier's principle  to quicken the decomposition of carboxyhemoglobin back to hemoglobin: [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2322", "contents": "As carbon monoxide is now understood to have a therapeutic potential, pharmaceutical efforts have focused on development of  carbon monoxide-releasing molecules  and selective  heme oxygenase  inducers. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2323", "contents": "An alternative method for drug delivery consists of carbon monoxide immobilized on  polyethylene glycol  (PEG)-lyated  bovine  carboxyhemoglobin which is currently in late clinical development. Similarly,  maleimide  PEG conjugated human carboxyhemoglobin had previously been the subject of pharmaceutical development. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2324", "contents": "Cardiorespiratory fitness  ( CRF ) refers to the ability of the  circulatory  and  respiratory systems  to supply  oxygen  to  skeletal muscles  during sustained physical activity. Scientists and researchers use CRF to assess the functional capacity of the respiratory and cardiovascular systems. These functions include  ventilation ,  perfusion ,  gas exchange , vasodilation, and delivery of oxygen to the body's tissues. As these body's functions are vital to an individual's health, CRF allows observers to quantify an individual's morbidity and mortality risk as a function of cardiorespiratory health."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2325", "contents": "In 2016, the  American Heart Association  published an official scientific statement advocating that CRF, quantifiable as  V\u0307O 2  max/peak , be categorized as a clinical vital sign and should be routinely assessed as part of clinical practice. [ 1 ]  Low levels of CRF have been shown to increase the risk of  cardiovascular disease  (CVD) and all-cause mortality. [ 1 ] [ 2 ]  Some medical researchers claim that CRF is an even stronger predictor of mortality than smoking,  hypertension ,  high cholesterol ,  type 2 diabetes mellitus , or other common risk factors. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2326", "contents": "Regular physical activity and exercise can improve CRF, thus decreasing risk of CVD and other conditions while improving overall health. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2327", "contents": "The emergence of a method to quantify CRF began in the 1920s when  Archibald Hill , a British physiologist, proposed a multifactorial relationship between the maximum rate of oxygen uptake by body tissues and intensity of physical activity. [ 5 ]  This measure was found to be dependent upon functional capacities of an individual's cardiovascular and respiratory systems. [ 5 ]  He coined the term  VO 2  max , or maximal oxygen consumption, the numerical result of exercise testing that represents the maximum rate of oxygen consumed per kilogram of body mass per minute during exercise which now serves as the primary measure of CRF. This proposal ignited a multitude of studies demonstrating a relationship between VO 2  max and cardiovascular disease and all-cause mortality."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2328", "contents": "In 2016, the  American Heart Association  published an official scientific statement advocating that CRF be categorized as a clinical vital sign and should be routinely assessed as part of clinical practice. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2329", "contents": "The prefix \"cardio-\" refers to the  heart  while \"-respiratory\" links the heart and respiratory system, which includes organs that contribute to gas exchange in plants and animals, especially the  lungs  (animals).  Fitness  refers to an individual's state of health."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2330", "contents": "Cardiorespiratory fitness can be increased by means of regular physical activity and exercise. The medical community agrees that regular physical activity plays an important role in reducing risk of cardiovascular disease,  stroke , hypertension, diabetes, and a variety of other morbid conditions. [ 3 ] [ 4 ]  A 2005 Cochrane review demonstrated that physical activity interventions are effective for increasing CRF, [ 7 ]  while other studies have determined that improved CRF is associated with lower risk of CVD and all-cause mortality. [ 8 ] [ 9 ] [ 2 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2331", "contents": "Multiple forms of exercise exist and are all generally beneficial to an individual's health (endurance running, weightlifting, sports activity, etc.), but studies show that  high intensity interval training  (HIIT) is highly effective in increasing CRF and VO 2  max in people of all ages. [ 11 ] [ 12 ] [ 13 ]  A 2020 review of the literature by Wu et al. concluded that HIIT is effective in increasing CRF, physical fitness, muscle power, cardiac contractile function, and reducing blood triglycerides in older individuals. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2332", "contents": "A method of estimating CRF entails using formulas, derived from extrapolated regressive analyses, to predict a theoretical level of CRF. These formulas take into consideration an individual's age, sex, BMI, substance use, relative levels of physical activity, and pathologic co-morbidites. In 2016, Nauman and Nes et al. demonstrated the added and unique utility of estimated cardiorespiratory fitness (eCRF) in predicting risk of cardiovascular disease and all-cause mortality. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2333", "contents": "Various methods of measurement exist for determining an individual's cardiorespiratory fitness.  VO 2  max  is the most commonly accepted indicator of CRF and has been since the 1960s. [ 15 ]  Cardiopulmonary exercise testing (CPET) with  spirometry  is the gold standard for determining VO 2  max. It requires the individual to perform exercise with analysis of gas exchange usually until maximal exertion is achieved. The use of  electrocardiography  is often used to examine heart response to exercise and exertion. [ 16 ]  CPET is performed on a treadmill or a cycle ergometer. The method of test administration is based on the abilities of the test subject, as the cycle ergometer is generally less taxing on the body and often better suited for elderly populations, although is shown to sometimes produce results 10% - 20% lower in individuals not accustomed to cycling due to leg fatigue. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2334", "contents": "In many cases, children or the elderly are not subjected to the vigor of cardiopulmonary exercise testing. There are other methods used to mathematically estimate the VO 2  max of a test subject by having the subject walk or jog a certain distance in as little time as possible, complete the maximum number of repetitions of a short-distance run (commonly known as the PACER test in the United States), or walk on a treadmill at increasing incline until a sub-maximal goal is achieved, along with others. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2335", "contents": "The  cardiovascular system  responds to changing demands on the body by adjusting cardiac output,  blood flow , and  blood pressure .  Cardiac output  is defined as the product of  heart rate  and  stroke volume  which represents the volume of blood being pumped by the heart each minute. Cardiac output increases during physical activity due to an increase in both the heart rate and stroke volume. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2336", "contents": "A  central chemoreceptor  is a  chemoreceptor  sensitive to the  pH  of its environment. [ 1 ]  Central chemoreceptors are located on the ventrolateral  medullary  surface in vicinity of the exit of  CN IX  and  CN X  in the  central nervous system ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2337", "contents": "These act to detect the changes in pH of nearby  cerebrospinal fluid  (CSF) that are indicative of altered oxygen or carbon dioxide concentrations available to brain tissues. An increase in carbon dioxide causes tension of the arteries, often resulting from increased CO 2  output ( hypercapnia ), indirectly causes the blood to become more acidic; the cerebrospinal fluid pH is closely comparable to  plasma , as  carbon dioxide  easily diffuses across the  blood\u2013brain barrier ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2338", "contents": "However, a change in plasma pH alone will not stimulate central chemoreceptors as  H +  are not able to diffuse across the  blood\u2013brain barrier  into the CSF. Only CO 2  levels affect this as it can diffuse across, reacting with H 2 O to form  carbonic acid  and thus decrease pH. Central chemoreception remains, in this way, distinct from  peripheral chemoreceptors ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2339", "contents": "The central chemoreception system has also been shown experimentally to respond to hypercapnic hypoxia (elevated CO 2 , decreased O 2 ) and aqueous  sodium cyanide  injection into the whole animal [ 2 ]  and  in vitro  slice preparation. These methods can be used to mimic some forms of  hypoxic hypoxia  and they are currently being studied including the detection of variation in arterial CO 2  tension acting as a quick-response-system for short term (or emergency) regulation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2340", "contents": "This system utilizes a negative feedback system, therefore if the pH of the cerebral spinal fluid does not compare to an ideal \u201cset\u201d level, then the receptor will send an error signal to the effectors and appropriate action may be executed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2341", "contents": "Peripheral chemoreceptors  (carotid and aortic bodies) and central chemoreceptors (medullary neurons) primarily function to regulate respiratory activity.  This is an important mechanism for maintaining arterial blood pO2,  pCO2 , and pH within appropriate physiological ranges. For example, a fall in arterial pO2 ( hypoxemia ) or an increase in arterial pCO2 (hypercapnia) leads to an increase in the rate and depth of respiration through activation of the chemoreceptor reflex. Chemoreceptor activity, however, also affects cardiovascular function either directly (by interacting with medullary  vasomotor centers ) or indirectly (via altered  pulmonary stretch receptor  activity).  Respiratory arrest  and  circulatory shock  (these conditions decrease arterial pO2 and pH, and increase arterial pCO2) dramatically increase chemoreceptor activity leading to enhanced sympathetic outflow to the heart and vasculature via activation of the vasomotor center in the medulla."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2342", "contents": "A  chemoreceptor , also known as  chemosensor , is a specialized  sensory receptor  which  transduces  a  chemical substance  ( endogenous  or induced) to generate a biological signal. [ 1 ]  This signal may be in the form of an  action potential , if the chemoreceptor is a  neuron , [ 2 ]  or in the form of a  neurotransmitter  that can activate a  nerve fiber  if the chemoreceptor is a specialized cell, such as  taste receptors , [ 3 ]  or an internal  peripheral chemoreceptor , such as the  carotid bodies . [ 4 ]  In  physiology , a chemoreceptor detects changes in the normal environment, such as an increase in blood levels of  carbon dioxide  (hypercapnia) or a decrease in blood levels of  oxygen  (hypoxia), and transmits that information to the  central nervous system  which engages body responses to restore  homeostasis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2343", "contents": "In  bacteria , chemoreceptors are essential in the mediation of  chemotaxis . [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2344", "contents": "Bacteria utilize complex long helical proteins as chemoreceptors, permitting signals to travel long distances across the cell's membrane. Chemoreceptors allow bacteria to react to chemical stimuli in their environment and regulate their movement accordingly. [ 7 ]  In  archaea ,  transmembrane receptors  comprise only 57% of chemoreceptors, while in bacteria the percentage rises to 87%. This is an indicator that chemoreceptors play a heightened role in the sensing of  cytosolic  signals in archaea. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2345", "contents": "Primary cilia , present in many types of mammalian  cells , serve as  cellular antennae . [ 9 ]  The motile function of these cilia is lost in favour of their sensory specialization. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2346", "contents": "Plants have various mechanisms to perceive danger in their environment. Plants are able to detect pathogens and microbes through surface level receptor kinases (PRK). Additionally, receptor-like proteins (RLPs) containing  ligand binding receptor domains  capture  pathogen-associated molecular patterns  (PAMPS) and  damage-associated molecular patterns  (DAMPS) which consequently initiates the plant's innate immunity for a defense response. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2347", "contents": "Plant receptor kinases are also used for growth and hormone induction among other important biochemical processes. These reactions are triggered by a series of  signaling pathways  which are initiated by plant chemically sensitive receptors. [ 12 ]   Plant hormone  receptors can either be integrated in plant cells or situate outside the cell, in order to facilitate chemical structure and composition. There are 5 major categories of hormones that are unique to plants which once bound to the receptor, will trigger a response in target cells. These include  auxin ,  abscisic acid ,  gibberellin ,  cytokinin , and  ethylene . Once bound, hormones can induce, inhibit, or maintain function of the target response. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2348", "contents": "There are two main classes of chemoreceptor: direct and distance. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2349", "contents": "When inputs from the environment are significant to the survival of the organism, the input must be detected. As all life processes are ultimately based on  chemistry  it is natural that detection and passing on of the external input will involve chemical events. The chemistry of the environment is, of course, relevant to survival, and detection of chemical input from the outside may well articulate directly with cell chemicals. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2350", "contents": "Chemoreception is important for the detection of food, habitat, conspecifics including mates, and predators. For example, the emissions of a predator's food source, such as odors or pheromones, may be in the air or on a surface where the food source has been. Cells in the head, usually the air passages or mouth, have chemical receptors on their surface that change when in contact with the emissions. It passes in either chemical or electrochemical form to the central processor, the  brain  or  spinal cord . The resulting output from the CNS ( central nervous system ) makes body actions that will engage the food and enhance survival. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2351", "contents": "Particular chemoreceptors, called  ASICs , detect the levels of  carbon dioxide  in the blood. To do this, they monitor the concentration of  hydrogen ions  in the blood, which decrease the  pH  of the blood. This can be a direct consequence of an increase in carbon dioxide concentration, because aqueous carbon dioxide in the presence of  carbonic anhydrase  reacts to form a  proton  and a  bicarbonate  ion. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2352", "contents": "The response is that the respiratory centre (in the medulla), sends  nervous impulses  to the external  intercostal muscles  and the  diaphragm , via the  intercostal nerve  and the  phrenic nerve , respectively, to increase breathing rate and the volume of the lungs during inhalation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2353", "contents": "Chemoreceptors that regulate the depth and rhythm of breathing are broken down into two categories. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2354", "contents": "The response to stimulation of chemoreceptors on the heart rate is complicated. Chemoreceptors in the heart or nearby large arteries, as well as chemoreceptors in the lungs, can affect heart rate. Activation of these peripheral chemoreceptors from sensing decreased O 2 , increased CO 2  and a decreased pH is relayed to cardiac centers by the vagus and glossopharyngeal nerves to the medulla of the brainstem. This increases the sympathetic nervous stimulation on the heart and a corresponding increase in heart rate and contractility in most cases. [ 20 ]  These factors include activation of stretch receptors due to increased ventilation and the release of circulating catecholamines."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2355", "contents": "However, if respiratory activity is arrested (e.g. in a patient with a high cervical spinal cord injury), then the primary cardiac reflex to transient hypercapnia and hypoxia is a profound  bradycardia  and coronary vasodilation through vagal stimulation and systemic vasoconstriction by sympathetic stimulation. [ 21 ]  In normal cases, if there is reflexive increase in respiratory activity in response to chemoreceptor activation, the increased sympathetic activity on the cardiovascular system would act to increase heart rate and contractility."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2356", "contents": "List of distinct cell types in the adult human body"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2357", "contents": "Chloride shift  (also known as the  Hamburger phenomenon  or  lineas phenomenon , named after  Hartog Jakob Hamburger ) is a process which occurs in a  cardiovascular system  and refers to the exchange of  bicarbonate  (HCO 3 \u2212 ) and  chloride  (Cl \u2212 ) across the membrane of  red blood cells  (RBCs). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2358", "contents": "Carbon dioxide  (CO 2 ) is produced in tissues as a byproduct of normal aerobic metabolism. It dissolves in the solution of blood plasma and into red blood cells (RBC), where  carbonic anhydrase  catalyzes its hydration to  carbonic acid  (H 2 CO 3 ). Carbonic acid then spontaneously  dissociates  to form bicarbonate Ions (HCO 3 \u2212 ) and a  hydrogen ion  (H + ). In response to the decrease in intracellular  pCO 2 , more CO 2  passively diffuses into the cell."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2359", "contents": "Cell membranes are generally impermeable to charged ions (i.e. H + , HCO 3 \u2212  ) but RBCs are able to exchange bicarbonate for chloride using the anion exchanger protein  Band 3 . Thus, the rise in intracellular bicarbonate leads to bicarbonate export and chloride intake. The term \"chloride shift\" refers to this exchange. Consequently, chloride concentration is lower in systemic venous blood than in systemic arterial blood: high venous pCO 2  leads to bicarbonate production in RBCs, which then leaves the RBC in exchange for chloride coming in. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2360", "contents": "The opposite process occurs in the pulmonary capillaries of the lungs when the PO 2  rises and PCO 2  falls, and the  Haldane effect  occurs (release of CO 2  from hemoglobin during oxygenation). This releases hydrogen ions from hemoglobin, increases free H +  concentration within RBCs, and shifts the equilibrium towards CO 2  and water formation from bicarbonate. The subsequent decrease in intracellular bicarbonate concentration reverses chloride-bicarbonate exchange: bicarbonate moves into the cell in exchange for chloride moving out. Inward movement of bicarbonate via the Band 3 exchanger allows carbonic anhydrase to convert it to CO 2  for expiration. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2361", "contents": "The chloride shift may also regulate the affinity of  hemoglobin  for  oxygen  through the chloride ion acting as an  allosteric  effector. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2362", "contents": "Reaction  (as it occurs in the pulmonary capillaries)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2363", "contents": "Bicarbonate in the red blood cell (RBC) exchanging with chloride from plasma in the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2364", "contents": "The underlying properties creating the chloride shift are the presence of carbonic anhydrase within the RBCs but not the plasma, and the permeability of the RBC membrane to carbon dioxide and bicarbonate ion but not to hydrogen ion. Continuous process of carbonic acid dissociation and outflow of bicarbonate ions would eventually lead to a change of intracellular electric potential because of lasting H+ ions. Inflow of chloride ions maintains electrical neutrality of a cell. The net direction of bicarbonate-chloride exchange (bicarbonate out of RBCs in the systemic capillaries, bicarbonate into RBCs at pulmonary capillaries) proceeds in the direction that decreases the sum of the electrochemical potentials for the chloride and bicarbonate ions being transported."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2365", "contents": "The  closing capacity  ( CC ) is the volume in the  lungs  at which its smallest airways, the respiratory bronchioles, collapse. It is defined mathematically as the sum of the closing volume and the residual volume. The alveoli lack supporting  cartilage  and so depend on other factors to keep them open. The closing capacity is less than the  Functional Residual Capacity , the amount of gas that normally remains in the lungs during  respiration . This means that there is normally enough air within the lungs to keep these airways open throughout both  inhalation  and  exhalation . As the lungs age, there is a gradual increase in the closing capacity (i.e. The small airways begin to collapse at a higher volume/before expiration is complete). This also occurs with certain disease processes, such as  asthma ,  chronic obstructive pulmonary disease , and  pulmonary edema . Any process that increases the CC by increasing the closing volume (CV) can increase an individual's risk of  hypoxemia , as the small airways may collapse during exhalation, leading to  air trapping  and  atelectasis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2366", "contents": "A mnemonic for factors increasing closing capacity is ACLS-S:\u00a0 Age, Chronic bronchitis, LV failure, Smoking, Surgery. Alternatively, CLOSE: Cigarettes, LV failure, Old age, Surgery, Emphysema (& asthma). Often supine positioning will decrease functional residual capacity (FRC) but has no effect on closing capacity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2367", "contents": "Compliance  is the ability of a hollow organ (vessel) to distend and increase volume with increasing  transmural pressure  or the tendency of a hollow organ to resist recoil toward its original dimensions on application of a distending or compressing force. The  reciprocal  of compliance is  elastance , a measure of the tendency of a hollow organ to  recoil  toward its original dimensions upon removal of a distending or compressing force."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2368", "contents": "The terms elastance and compliance are of particular significance in  cardiovascular physiology  and  respiratory physiology . In compliance, an increase in volume occurs in a vessel when the pressure in that vessel is increased. The tendency of the  arteries  and  veins  to stretch in response to pressure has a large effect on perfusion and blood pressure. This physically means that blood vessels with a higher compliance deform easier than lower compliance blood vessels under the same pressure and volume conditions. [ 1 ]  \nVenous compliance is approximately 30 times larger than arterial compliance. [ 2 ]  \nCompliance is calculated using the following equation, where  \n \n \n \n \u0394 \n V \n \n \n {\\displaystyle \\Delta V} \n \n  is the change in volume (mL), and  \n \n \n \n \u0394 \n P \n \n \n {\\displaystyle \\Delta P} \n \n  is the change in pressure ( mmHg ): [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2369", "contents": "Physiologic compliance is generally in agreement with the above and adds  \n \n \n \n \n \n \n \n d \n P \n \n \n d \n t \n \n \n \n \n \n \n {\\textstyle {\\tfrac {dP}{dt}}} \n \n  as a common academic physiologic measurement of both pulmonary and cardiac tissues. Adaptation of equations initially applied to  rubber  and  latex  allow modeling of the dynamics of pulmonary and cardiac tissue compliance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2370", "contents": "Veins have a much higher compliance than arteries (largely due to their thinner walls.) Veins which are abnormally compliant can be associated with  edema .  Pressure stockings  are sometimes used to externally reduce compliance, and thus keep blood from pooling in the legs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2371", "contents": "Vasodilation  and  vasoconstriction  are complex phenomena; they are functions not merely of the  fluid mechanics  of pressure and tissue  elasticity  but also of active  homeostatic  regulation with  hormones  and  cell signaling , in which the body produces  endogenous  vasodilators and vasoconstrictors to modify its vessels' compliance. For example, the  muscle tone  of the  smooth muscle tissue  of the  tunica media  can be adjusted by the  renin\u2013angiotensin system . In patients whose endogenous homeostatic regulation is not working well, dozens of  pharmaceutical drugs  that are also  vasoactive  can be added. The response of vessels to such vasoactive substances is called vasoactivity (or sometimes vasoreactivity). Vasoactivity can vary between persons because of  genetic  and  epigenetic  differences, and it can be impaired by pathosis and by age. This makes the topic of  haemodynamic response  (including vascular compliance and  vascular resistance ) a matter of medical and  pharmacologic  complexity beyond mere  hydraulic  considerations (which are complex enough by themselves)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2372", "contents": "The relationship between vascular compliance, pressure, and flow rate is: \n \n \n \n Q \n = \n C \n \n \n \n \n d \n \n P \n \n \n \n d \n \n t \n \n \n \n = \n \n ( \n f \n l \n o \n w \n r \n a \n t \n e \n ) \n ( \n c \n \n m \n \n 3 \n \n \n \n / \n \n s \n e \n c \n ) \n \n \n \n {\\displaystyle Q=C{\\frac {\\mathrm {d} P}{\\mathrm {d} t}}=\\mathrm {(flowrate)(cm^{3}/sec)} }"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2373", "contents": "The classic definition by MP Spencer and AB Denison of compliance ( \n \n \n \n C \n \n \n {\\displaystyle C} \n \n ) is the change in arterial blood volume ( \n \n \n \n \u0394 \n V \n \n \n {\\displaystyle \\Delta V} \n \n ) due to a given change in  arterial blood pressure  ( \n \n \n \n \u0394 \n P \n \n \n {\\displaystyle \\Delta P} \n \n ). They wrote this in the \"Handbook of Physiology\" in 1963 in work entitled \"Pulsatile Flow in the Vascular System\". So,  \n \n \n \n C \n = \n \n \n \n \u0394 \n V \n \n \n \u0394 \n P \n \n \n \n \n \n {\\displaystyle C={\\frac {\\Delta V}{\\Delta P}}} \n \n . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2374", "contents": "Arterial compliance is an index of the  elasticity  of large arteries such as the  thoracic aorta . Arterial compliance is an important cardiovascular risk factor. Compliance diminishes with age and menopause. Arterial compliance is measured by  ultrasound  as a pressure ( carotid artery ) and volume (outflow into  aorta ) relationship. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2375", "contents": "Compliance, in simple terms, is the degree to which a container experiences pressure or force without disruption. It is used as an indication of  arterial stiffness . An increase in the age and also in the systolic  blood pressure  (SBP) is accompanied with decrease on arterial compliance. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2376", "contents": "Endothelial dysfunction results in reduced compliance (increased arterial stiffness), especially in the smaller arteries. This is characteristic of patients with  hypertension . However, it may be seen in normotensive patients (with normal blood pressure) before the appearance of clinical hypertension. Reduced arterial compliance is also seen in patients with  diabetes  and also in smokers. It is actually a part of a vicious cycle that further elevates blood pressure, aggravates  atherosclerosis  (hardening of the arteries), and leads to increased cardiovascular risk. Arterial compliance can be measured by several techniques. Most of them are invasive and are not clinically appropriate.  Pulse contour analysis  is a non-invasive method that allows easy measurement of arterial elasticity to identify patients at risk for cardiovascular events. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2377", "contents": "The  control of ventilation  is the  physiological  mechanisms involved in the control of  breathing , which is the movement of air into and out of the lungs. Ventilation facilitates respiration. Respiration refers to the utilization of  oxygen  and balancing of  carbon dioxide  by the body as a whole, or by individual cells in  cellular respiration . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2378", "contents": "The most important function of breathing is the supplying of oxygen to the body and balancing of the carbon dioxide levels. Under most conditions, the  partial pressure of carbon dioxide  (PCO 2 ), or concentration of carbon dioxide, controls the  respiratory rate ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2379", "contents": "The  peripheral chemoreceptors  that detect changes in the  levels of oxygen and carbon dioxide  are located in the  arterial   aortic bodies  and the  carotid bodies . [ 2 ]   Central chemoreceptors  are primarily sensitive to changes in the   pH  of the  blood , (resulting from changes in the levels of carbon dioxide) and they are located on the  medulla oblongata  near to the  medullar respiratory groups  of the  respiratory center . [ 3 ] \nInformation from the peripheral chemoreceptors is conveyed along nerves to the respiratory groups of the respiratory center.  There are four respiratory groups, two in the medulla and two in the  pons . [ 2 ]  The two groups in the pons are known as the  pontine respiratory group ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2380", "contents": "From the respiratory center, the  muscles of respiration , in particular the  diaphragm , [ 4 ]  are activated to cause air to move in and out of the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2381", "contents": "Breathing is normally an unconscious, involuntary, automatic process. The pattern of motor stimuli during breathing can be divided into an  inhalation  stage and an  exhalation  stage.  Inhalation  shows a sudden, ramped increase in motor discharge to the  respiratory muscles  (and the  pharyngeal constrictor muscles ). [ 5 ]  Before the end of inhalation, there is a decline in, and end of motor discharge.  Exhalation  is usually silent, except at high  respiratory rates ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2382", "contents": "The  respiratory centre  in the medulla and pons of the brainstem controls the rate and depth of respiration, (the  respiratory rhythm ), through various inputs. These include signals from the peripheral chemoreceptors and central chemoreceptors; from the vagus nerve and glossopharyngeal nerve carrying input from the  pulmonary stretch receptors , and other mechanoreceptors in the  lungs . [ 3 ] [ 6 ]  as well as signals from the  cerebral cortex  and  hypothalamus ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2383", "contents": "Ventilation is normally unconscious and automatic, but can be overridden by  conscious alternative patterns . [ 3 ]  Thus the emotions can cause yawning, laughing, sighing (etc.), social communication causes speech, song and whistling, while entirely voluntary overrides are used to blow out candles, and breath holding (for instance, to swim underwater).  Hyperventilation  may be entirely voluntary or in response to emotional agitation or anxiety, when it can cause the distressing  hyperventilation syndrome . The voluntary control can also influence other functions such as the  heart rate  as in  yoga  practices and  meditation . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2384", "contents": "The ventilatory pattern is also temporarily modified by complex reflexes such as sneezing, straining, burping, coughing and vomiting."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2385", "contents": "Ventilatory rate ( respiratory minute volume ) is tightly controlled and determined primarily by blood levels of  carbon dioxide  as determined by  metabolic rate . Blood levels of  oxygen  become important in  hypoxia . These levels are sensed by  central chemoreceptors  on the surface of the  medulla oblongata  for decreased pH (indirectly from the increase of carbon dioxide in  cerebrospinal fluid ), and the  peripheral chemoreceptors  in the arterial blood for oxygen and carbon dioxide.  Afferent neurons from the peripheral chemoreceptors are via the  glossopharyngeal nerve  (CN IX) and the  vagus nerve  (CN X)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2386", "contents": "The concentration of  carbon dioxide  (CO 2 ) rises in the blood when the metabolic use of oxygen (O 2 ), and the production of CO 2  is increased during, for example, exercise. The CO 2  in the blood is transported largely as bicarbonate (HCO 3 \u2212 ) ions, by conversion first to  carbonic acid  (H 2 CO 3 ), by the enzyme  carbonic anhydrase , and then by disassociation of this acid to H +  and HCO 3 \u2212 . Build-up of CO 2  therefore causes an equivalent build-up of the disassociated hydrogen ions, which, by definition, decreases the pH of  the blood. The pH sensors on the brain stem immediately respond to this fall in pH, causing the respiratory center to increase the rate and depth of  breathing . The consequence is that the  partial pressure  of CO 2  (P CO 2 ) does not change from rest going into exercise. During very short-term bouts of intense exercise the release of lactic acid into the blood by the exercising muscles causes a fall in the blood plasma pH, independently of the rise in the P CO 2 , and this will stimulate pulmonary ventilation sufficiently to keep the  blood pH constant  at the expense of a lowered P CO 2 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2387", "contents": "Mechanical stimulation of the lungs can trigger certain reflexes as discovered in animal studies. In humans, these seem to be more important in neonates and ventilated patients, but of little relevance in health. The tone of respiratory muscle is believed to be modulated by  muscle spindles  via a reflex arc involving the spinal cord."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2388", "contents": "Drugs can greatly influence the rate of respiration.  Opioids  and   anesthetics  tend to depress ventilation, by decreasing the normal response to raised  carbon dioxide  levels in the arterial blood. Stimulants such as  amphetamines  can cause  hyperventilation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2389", "contents": "Pregnancy  tends to increase ventilation (lowering plasma carbon dioxide tension below normal values). This is due to increased  progesterone  levels and results in enhanced gas exchange in the  placenta ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2390", "contents": "Receptors  play important roles in the regulation of respiration and include the  central  and  peripheral chemoreceptors , and  pulmonary stretch receptors , a type of  mechanoreceptor ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2391", "contents": "The  cough center  is a region of the  brain  which controls  coughing . The cough center is located in the  medulla oblongata  in the  brainstem .   Cough suppressants  focus their action on the cough center. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2392", "contents": "The exact location and functionality of the cough center has remained somewhat elusive: while  Johannes Peter M\u00fcller  observed in 1838 that the medulla coordinates the cough reflex, investigating it has been slow because the usual anaesthetics for experimental animals were morphine or opiates, drugs which strongly inhibit cough. In addition, the center likely overlaps with the  respiratory rhythm  generator networks. [ 2 ]  It is hence not so much a specific area, but a function within the respiration and reflex networks of the brainstem."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2393", "contents": "Cough receptors project to relay neurones in the  solitary nucleus , which project to other parts of the  respiratory networks . In particular, the  pre-B\u00f6tzinger complex  may act as a  pattern generator  for the cough response. Parts of the caudal medullary  raphe nucleus  ( nucleus raphe obscurus  and  nucleus raphe magnus ) are known to be essential for the cough response. Other systems that may be involved in pattern generation and regulation are the  pontine respiratory group , the  lateral tegmental field  and the deep  cerebellar nuclei . [ 3 ]  Successful joint models of medullary systems coordinating breathing, coughing and swallowing has been constructed based on this model. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2394", "contents": "Coughing can occur or be inhibited as a  voluntary action , suggesting control from higher systems in the brain. Functional brain imaging of voluntary, suppressed, and induced coughing show that a number of cortical areas can get involved and may be important even for non-voluntary coughing. In contrast, voluntary coughing does not seem to activate medullary systems. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2395", "contents": "Dead space  is the volume of air that is inhaled that does not take part in the gas exchange, because it either remains in the conducting airways or reaches alveoli that are  not perfused or poorly perfused . It means that not all the air in each  breath  is available for the exchange of  oxygen  and  carbon dioxide .  Mammals  breathe in and out of their lungs, wasting that part of the inhalation which remains in the conducting airways where no gas exchange can occur."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2396", "contents": "Total dead space  (also known as  physiological dead space ) is the sum of the anatomical dead space and the alveolar dead space."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2397", "contents": "Benefits do accrue to a seemingly wasteful design for ventilation that includes dead space. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2398", "contents": "In humans, about a third of every resting breath has no change in O 2  and CO 2  levels. In adults, it is usually in the range of 150 mL. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2399", "contents": "Dead space can be increased (and better envisioned) by breathing through a long tube, such as a  snorkel . Although one end of the snorkel is open to the air, when the wearer breathes in, they inhale a significant quantity of air that remained in the snorkel from the previous exhalation. Therefore, a snorkel increases the person's dead space by adding even more airway that does not participate in gas exchange."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2400", "contents": "Anatomical dead space is the volume of the conducting airways (from the  nose ,  mouth  and  trachea  to the terminal bronchioles). These conduct gas to the  alveoli  but no gas exchange occurs here. In healthy lungs where the alveolar dead space is small,  Fowler's method  accurately measures the anatomic dead space using a single breath  nitrogen  washout technique. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2401", "contents": "The normal value for dead space volume (in mL) is approximately the lean mass of the body (in pounds), and averages about a third of the resting  tidal volume  (450-500 mL). In Fowler's original study, the anatomic dead space was 156 \u00b1 28 mL (n=45 males) or 26% of their tidal volume. [ 4 ]  Despite the flexibility of the trachea and smaller conducting airways, their overall volume (i.e. the anatomic dead space) changes little with bronchoconstriction or when breathing hard during exercise. [ 4 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2402", "contents": "As birds have a longer and wider trachea than mammals the same size, they have a disproportionately large anatomic dead space, reducing the airway resistance. This adaptation does not impact gas exchange because birds flow air through their lungs - they do not breathe in and out like mammals. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2403", "contents": "Alveolar dead space is defined as the difference between the physiologic dead space and the anatomic dead space. It is contributed to by all the terminal respiratory units that are over-ventilated relative to their perfusion. Therefore it includes, firstly those units that are ventilated but not perfused, and secondly those units which have a ventilation-perfusion ratio greater than one."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2404", "contents": "Alveolar dead space is negligible in healthy individuals, but it can increase dramatically in some  lung diseases  due to  ventilation-perfusion mismatch ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2405", "contents": "Just as dead space wastes a fraction of the inhaled breath, dead space dilutes alveolar air during exhalation. By quantifying this dilution, it is possible to measure physiological dead space, employing the concept of  mass balance , as expressed by the  Bohr equation . [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2406", "contents": "The Bohr equation is used to measure physiological dead space. Unfortunately, the concentration of carbon dioxide (CO 2 ) in alveoli is required to use the equation but this is not a single value as the ventilation-perfusion ratio is different in different lung units both in health and in disease. In practice, the arterial partial pressure of CO 2  is used as an estimate of the average alveolar partial pressure of CO 2 , a modification introduced by Henrik Enghoff in 1938 (Enghoff H. Volumen inefficax. Bemerkungen zur Frage des schadlichen Raumes. Upsala L\u00e4karef\u00f6ren Forhandl., 44:191-218, 1938). In effect, the single arterial pCO 2  value averages out the different pCO 2  values in the different alveoli, and so makes the Bohr equation useable."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2407", "contents": "The quantity of CO 2  exhaled from the healthy alveoli is diluted by the air in the conducting airways (anatomic dead space) and by gas from alveoli that are over-ventilated in relation to their perfusion. This dilution factor can be calculated once the mixed expired pCO 2  in the exhaled breath is determined (either by electronically monitoring the exhaled breath or by collecting the exhaled breath in a gas impermeant bag (a Douglas bag) and then measuring the pCO 2  of the mixed expired gas in the collection bag). Algebraically, this dilution factor will give us the physiological dead space as calculated by the Bohr equation:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2408", "contents": "The alveolar dead space is determined as the difference between the physiological dead space (measured using the Enghoff modification of the Bohr equation) and the anatomic dead space (measured using Fowler's single breath technique)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2409", "contents": "A clinical index of the size of the alveolar dead space is the difference between the arterial partial pressure of CO 2  and the end-tidal partial pressure of CO 2 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2410", "contents": "A different maneuver is employed in measuring anatomic dead space: the test subject breathes all the way out, inhales deeply from a 0% nitrogen gas mixture (usually 100% oxygen) and then breathes out into equipment that measures nitrogen and gas volume. This final exhalation occurs in three phases. The first phase (phase 1) has no nitrogen as that is gas that is 100% oxygen in the anatomic dead space. The nitrogen concentration then rapidly increases during the brief second phase (phase 2) and finally reaches a plateau in the third phase (phase 3). The  anatomic dead space  is equal to the volume exhaled during the first phase plus the volume up to the mid-point of the transition from phase 1 to phase 3."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2411", "contents": "The depth and frequency of our breathing is determined by chemoreceptors and the brainstem, as modified by a number of subjective sensations. When mechanically  ventilated  using a mandatory mode, the patient breathes at a rate and tidal volume that is dictated by the machine.\nBecause of dead space, taking deep breaths more slowly (e.g. ten 500 ml breaths per minute) is more effective than taking shallow breaths quickly (e.g. twenty 250 ml breaths per minute). Although the amount of gas per minute is the same (5 L/min), a large proportion of the shallow breaths is dead space, which does not help oxygen to get into the blood. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2412", "contents": "Mechanical dead space  or  external dead space  is volume in the  passages of a  breathing apparatus  in which the  breathing gas  flows in both directions as the user breathes in and out, causing the last exhaled gas to be immediately inhaled on the next breath, increasing the necessary tidal volume and respiratory effort to get the same amount of usable air or breathing gas, and increasing the accumulation of  carbon dioxide  from shallow breaths. It is in effect an external extension of the physiological dead space. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2413", "contents": "It can be reduced by:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2414", "contents": "Dead space reduces the amount of fresh breathing gas which reaches the alveoli during each breath. This reduces the oxygen available for gas exchange, and the amount of carbon dioxide that can be removed. The buildup of carbon dioxide is usually the more noticeable effect unless the breathing gas is hypoxic as occurs at high altitude. The body can compensate to some extent by increasing the volume of inspired gas, but this also increases  work of breathing , and is only effective when the ratio of dead space to tidal volume is reduced sufficiently to compensate for the additional carbon dioxide load due to the increased work of breathing.\nContinued buildup of carbon dioxide will lead to  hypercapnia  and  respiratory distress ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2415", "contents": "In healthy people, V d  is about one-third of V t  at rest and decreases with exercise to about one-fifth mainly due to an increase in V t , as anatomic dead space does not change much and alveolar dead space should be negligible or very small. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2416", "contents": "External dead space for a given breathing apparatus is usually fixed, and this volume must be added to tidal volume to provide equivalent effective ventilation at any given level of exertion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2417", "contents": "Diaphragmatic excursion  is the movement of the  thoracic diaphragm  during breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2418", "contents": "Normal diaphragmatic excursion should be 3\u20135\u00a0cm, but can be increased in well-conditioned persons to 7\u20138\u00a0cm. This measures the contraction of the diaphragm."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2419", "contents": "It is performed by asking the patient to exhale and hold it. The doctor then  percusses  down their back in the  intercostal margins  (bone will be dull), starting below the  scapula , until sounds change from resonant to dull (lungs are resonant, solid organs should be dull). That is where the provider marks the spot. Then the patient takes a deep breath in and holds it as the provider percusses down again, marking the spot where the sound changes from resonant to dull again. Then the provider will measure the distance between the two spots. Repeat on the other side, is usually higher up on the right side. If it is less than 3\u20135\u00a0cm the patient may have a  pneumonia  or a  pneumothorax  in which a chest x-ray is diagnostic for either. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2420", "contents": "This  anatomy  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2421", "contents": "Diffusing capacity  of the lung (D L ) (also known as  transfer factor ) measures the transfer of gas from air in the lung, to the  red blood cells  in lung blood vessels.  It is part of a comprehensive series of  pulmonary function tests  to determine the overall ability of the  lung  to transport gas into and out of the blood.  D L , especially  D LCO , is reduced in certain diseases of the lung and heart. D LCO  measurement has been standardized according to a position paper [ 1 ]  by a task force of the  European Respiratory  and  American Thoracic  Societies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2422", "contents": "In  respiratory physiology , the diffusing capacity has a long history of great utility, representing  conductance  of gas across the alveolar-capillary membrane and also takes into account factors affecting the behaviour of a given gas with hemoglobin. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2423", "contents": "The term may be considered a misnomer as it represents neither  diffusion  nor a  capacity  (as it is typically measured under submaximal conditions) nor  capacitance . In addition, gas transport is only diffusion limited in extreme cases, such as for oxygen uptake at very low ambient oxygen or very high pulmonary blood flow. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2424", "contents": "The diffusing capacity does not directly measure the primary cause of  hypoxemia , or low blood oxygen, namely mismatch of  ventilation to perfusion : [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2425", "contents": "The  single-breath diffusing capacity test  is the most common way to determine  \n \n \n \n \n D \n \n L \n \n \n \n \n {\\displaystyle D_{L}} \n \n . [ 1 ]  The test is performed by having the subject blow out all of the air that they can, leaving only the  residual lung volume  of gas.  The person then inhales a test gas mixture rapidly and completely, reaching the  total lung capacity  as nearly as possible. This test gas mixture contains a small amount of carbon monoxide (usually 0.3%) and a  tracer gas  that is freely distributed throughout the alveolar space but which doesn't cross the alveolar-capillary membrane.   Helium  and  methane  are two such gasses.  The test gas is held in the lung for about 10\u00a0seconds during which time the CO (but  not  the tracer gas) continuously moves from the alveoli into the blood. Then the subject exhales."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2426", "contents": "The anatomy of the airways means inspired air must pass through the mouth, trachea, bronchi and bronchioles ( anatomical dead space ) before it gets to the alveoli where gas exchange will occur; on exhalation, alveolar gas must return along the same path, and so the exhaled sample will be purely alveolar only after a 500 to 1,000\u00a0ml of gas has been breathed out. [ citation needed ]   While it is algebraically possible to approximate the effects of anatomy (the  three-equation method [ 3 ] ), disease states introduce considerable uncertainty to this approach. Instead, the first 500 to 1,000 ml of the expired gas is disregarded and the next portion which contain gas that has been in the alveoli is analyzed. [ 1 ]  By analyzing the concentrations of carbon monoxide and inert gas in the inspired gas and in the exhaled gas, it is possible to calculate  \n \n \n \n ( \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n ) \n \n \n {\\displaystyle (D_{L_{CO}})} \n \n  according to Equation  2 . First, the  rate  at which CO is taken up by the lung is calculated according to:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2427", "contents": "Similarly,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2428", "contents": "where"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2429", "contents": "Other methods that are not so widely used at present can measure the diffusing capacity.  These include the steady state diffusing capacity that is performed during regular tidal breathing, or the rebreathing method that requires rebreathing from a reservoir of gas mixtures."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2430", "contents": "The diffusion capacity for oxygen  \n \n \n \n ( \n \n D \n \n \n L \n \n \n O \n \n 2 \n \n \n \n \n \n \n ) \n \n \n {\\displaystyle (D_{L_{O_{2}}})} \n \n  is the proportionality factor relating the rate of oxygen uptake into the lung to the oxygen gradient between the capillary blood and the alveoli (per  Fick's laws of diffusion ). In  respiratory physiology , it is convenient to express the transport of gas molecules as changes in volume, since  \n \n \n \n \n \n V \n \n \n O \n \n 2 \n \n \n \n \n \n \u221d \n \n \n n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n {\\displaystyle {V_{O_{2}}}\\propto {n_{O_{2}}}} \n \n  (i.e., in a gas, a volume is proportional to the number of molecules in it).  Further, the oxygen concentration ( partial pressure ) in the pulmonary artery is taken to be representative of capillary blood.  Thus,  \n \n \n \n ( \n \n D \n \n \n L \n \n \n O \n \n 2 \n \n \n \n \n \n \n ) \n \n \n {\\displaystyle (D_{L_{O_{2}}})} \n \n  can be calculated as the rate that oxygen is taken up by the lung  \n \n \n \n ( \n \n \n \n \n V \n \u02d9 \n \n \n \n \n \n O \n \n 2 \n \n \n \n \n ) \n \n \n {\\displaystyle ({\\dot {V}}_{O_{2}})} \n \n  divided by the oxygen gradient between the alveoli (\"A\") and the pulmonary artery (\"a\")."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2431", "contents": "Thus, the higher the diffusing capacity  \n \n \n \n \n D \n \n L \n \n \n \n \n {\\displaystyle D_{L}} \n \n , the more gas will be transferred into the lung per unit time for a given gradient in partial pressure (or concentration) of the gas.  Since it can be possible to know the alveolar oxygen concentration and the rate of oxygen uptake - but not the oxygen concentration in the pulmonary artery - it is the venous oxygen concentration that is generally employed as a useful approximation in a clinical setting."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2432", "contents": "Sampling the oxygen concentration in the pulmonary artery is a highly invasive procedure, but fortunately another similar gas can be used instead that obviates this need ( DLCO ).  Carbon monoxide  (CO) is tightly and rapidly bound to hemoglobin in the blood, so the partial pressure of CO in the capillaries is negligible and the second term in the denominator can be ignored.  For this reason, CO is generally the test gas used to measure the diffusing capacity and the  \n \n \n \n \n D \n \n L \n \n \n \n \n {\\displaystyle D_{L}} \n \n  equation simplifies to:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2433", "contents": "In general, a healthy individual has a value of  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n  between 75% and 125% of the average. [ 4 ]  However, individuals vary according to age, sex, height and a variety of other parameters.  For this reason, reference values have been published, based on populations of healthy subjects [ 5 ] [ 6 ] [ 7 ]  as well as measurements made at altitude, [ 8 ]  for children [ 9 ]  and some specific population groups. [ 10 ] [ 11 ] [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2434", "contents": "In heavy smokers, blood CO is great enough to influence the measurement of  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n , and requires an adjustment of the calculation when COHb is greater than 2% of the whole."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2435", "contents": "While  \n \n \n \n ( \n \n D \n \n L \n \n \n ) \n \n \n {\\displaystyle (D_{L})} \n \n  is of great practical importance, being the overall measure of gas transport, the interpretation of this measurement is complicated by the fact that it does not measure any one part of a multi-step process. So as a conceptual aid in interpreting the results of this test, the time needed to transfer CO from the air to the blood can be divided into two parts.  First CO crosses the alveolar capillary membrane (represented by  \n \n \n \n \n D \n \n M \n \n \n \n \n {\\displaystyle D_{M}} \n \n  ) and then CO combines with the hemoglobin in capillary red blood cells at a rate  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n  times the volume of capillary blood present ( \n \n \n \n \n V \n \n c \n \n \n \n \n {\\displaystyle V_{c}} \n \n ). [ 13 ]  Since the steps are in series, the conductances add as the sum of the reciprocals:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2436", "contents": "The volume of blood in the lung capillaries,  \n \n \n \n \n V \n \n c \n \n \n \n \n {\\displaystyle V_{c}} \n \n , changes appreciably during ordinary activities such as  exercise .  Simply breathing in brings some additional blood  into  the lung because of the negative intrathoracic pressure required for inspiration.  At the extreme, inspiring against a closed glottis, the  M\u00fcller's maneuver , pulls blood  into  the chest.  The opposite is also true, as exhaling increases the pressure within the thorax and so tends to push blood out; the  Valsalva maneuver  is an exhalation against a closed airway which can move blood  out  of the lung. So breathing hard during exercise will bring extra blood into the lung during inspiration and push blood out during expiration. But during exercise (or more rarely when there is a  structural defect  in the heart that allows blood to be shunted from the high pressure, systemic circulation to the low pressure, pulmonary circulation) there is also increased blood flow throughout the body, and the lung adapts by recruiting extra capillaries to carry the increased output of the heart, further increasing the quantity of blood in the lung.  Thus  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n  will appear to increase when the subject is not at rest, particularly during inspiration."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2437", "contents": "In disease,  hemorrhage  into the lung will increase the number of haemoglobin molecules in contact with air, and so measured  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n  will increase. In this case, the carbon monoxide used in the test will bind to haemoglobin that has bled into the lung. This does not reflect an increase in diffusing capacity of the lung to transfer oxygen to the systemic circulation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2438", "contents": "Finally,  \n \n \n \n \n V \n \n c \n \n \n \n \n {\\displaystyle V_{c}} \n \n  is increased in  obesity  and when the subject lies down, both of which increase the blood in the lung by compression and by gravity and thus both increase  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2439", "contents": "The rate of CO uptake into the blood,  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n , depends on the concentration of hemoglobin in that blood, abbreviated  Hb  in the CBC ( Complete Blood Count ).  More hemoglobin is present in  polycythemia , and so  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n  is elevated.  In  anemia , the opposite is true.  In environments with high levels of CO in the inhaled air (such as  smoking ), a fraction of the blood's hemoglobin is rendered ineffective by its tight binding to CO, and so is analogous to anemia.  It is recommended that  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n  be adjusted when blood CO is high. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2440", "contents": "The lung blood volume is also reduced when blood flow is interrupted by blood clots ( pulmonary emboli ) or reduced by bone deformities of the thorax, for instance  scoliosis  and  kyphosis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2441", "contents": "Varying the ambient concentration of oxygen also alters  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n .  At high altitude, inspired oxygen is low and more of the blood's hemoglobin is free to bind CO; thus  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n  is increased and  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n  appears to be increased.  Conversely, supplemental oxygen increases Hb saturation, decreasing  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n  and  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2442", "contents": "Diseases that alter lung tissue reduce both  \n \n \n \n \n D \n \n M \n \n \n \n \n {\\displaystyle D_{M}} \n \n  and  \n \n \n \n \u03b8 \n \u2217 \n \n V \n \n c \n \n \n \n \n {\\displaystyle \\theta *V_{c}} \n \n  to a variable extent, and so decrease  \n \n \n \n \n D \n \n \n L \n \n C \n O \n \n \n \n \n \n \n {\\displaystyle D_{L_{CO}}} \n \n ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2443", "contents": "In one sense, it is remarkable that DL CO  has retained such clinical utility.  The technique was invented to settle one of the great controversies of pulmonary physiology a century ago, namely the question of whether oxygen and the other gases were actively transported into and out of the blood by the lung, or whether gas molecules diffused passively. [ 18 ]  Remarkable too is the fact that both sides used the technique to gain evidence for their respective hypotheses. To begin with,  Christian Bohr  invented the technique, using a protocol analogous to the steady state diffusion capacity for carbon monoxide, and concluded that oxygen was actively transported into the lung.  His student,  August Krogh  developed the single breath diffusion capacity technique along with his wife  Marie , and convincingly demonstrated that gasses diffuse passively, [ 19 ] [ 20 ] [ 21 ] [ 22 ] [ 23 ] [ 24 ] [ 25 ]  a finding that led to the demonstration that capillaries in the blood were recruited into use as needed \u2013 a Nobel Prize\u2013winning idea. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2444", "contents": "D LCO  or  T LCO  ( d iffusing capacity  or  t ransfer factor of the  l ung  for  carbon monoxide  (CO), [ 1 ] ) is the extent to which oxygen passes from the  air sacs  of the  lungs  into the  blood . Commonly, it refers to the test used to determine this parameter. It was introduced in 1909. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2445", "contents": "This test involves measuring the  partial pressure  difference between inspired and expired carbon monoxide. It relies on the strong affinity and large absorption capacity of  red blood cells  for carbon monoxide and thus demonstrates gas uptake by the capillaries that are less dependent on  cardiac output . [ 3 ]  The measurement of D LCO  is affected by atmospheric pressure and/or altitude and correction factors can be calculated using the method recommended by the American Thoracic Society. [ 4 ]  Expected D LCO  is also affected by the amount of hemoglobin,  carboxyhemoglobin , age and sex. The correction for hemoglobin is based on the method of Cotes [ 5 ] [ 6 ]  as recommended by the American Thoracic Society."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2446", "contents": "Generally D LCO  is measured in \"ml/min/ kPa \" and T LCO  is measured in \"mmol/min/kPa\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2447", "contents": "D LCO  is decreased in any condition which affects the effective alveolar surface area:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2448", "contents": "However, many modern devices compensate for the  hemoglobin  value of the patient (taken by blood test), and excludes it as a factor in the DLCO interpretation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2449", "contents": "Factors that can increase the D LCO  include  polycythaemia , asthma (can also have normal D LCO ) and increased pulmonary blood volume as occurs in exercise. Other factors are left to right intracardiac shunting, mild left heart failure (increased blood volume) and alveolar hemorrhage (increased blood available for which CO does not have to cross a barrier to enter).  [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2450", "contents": "There is no universally recognized reference value range for DLCO as of 2017, [ 10 ]  but values in the 80%-120% of predicted range based on instrument manufacturer standards are generally considered normal. [ 11 ]  A D LCO  of less than 60% predicted portends a poor prognosis for lung cancer resection.  FEV 1  is of lesser prognostic value for lung resection survival. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2451", "contents": "Dynamic compression of the airways  results when  intrapleural pressure  equals or exceeds  alveolar pressure , which causes dynamic collapsing of the  lung  airways. It is termed  dynamic  given the  transpulmonary pressure  (alveolar pressure \u2212 intrapleural pressure) varies based on factors including  lung volume ,  compliance ,  resistance , existing pathologies, etc. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2452", "contents": "It occurs during forced  expiration  when intrapleural pressure is greater than  atmospheric pressure  (positive  barometric  values), and not during passive expiration when intrapleural pressure remains at subatmospheric pressures (negative barometric values). Clinically, dynamic compression is most commonly associated with the wheezing sound during forced expiration, such as in individuals with  chronic obstructive pulmonary disorder (COPD) . [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2453", "contents": "The  effects of high altitude on humans  are mostly the consequences of reduced partial pressure of oxygen in the atmosphere. The medical problems that are direct consequence of high altitude are caused by the low inspired partial pressure of oxygen, which is caused by the reduced atmospheric pressure, and the constant gas fraction of oxygen in atmospheric air over the range in which humans can survive. [ 1 ]  The other major effect of altitude is due to lower ambient temperature."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2454", "contents": "The  oxygen saturation  of  hemoglobin  determines the content of  oxygen  in blood. After the  human body  reaches around 2,100 metres (6,900\u00a0ft) above sea level, the saturation of oxyhemoglobin begins to decrease rapidly. [ 2 ]  However, the human body has both short-term and  long-term adaptations  to altitude that allow it to partially compensate for the lack of oxygen. There is a limit to the level of adaptation; mountaineers refer to the altitudes above 8,000 metres (26,000\u00a0ft) as the  death zone , where it is generally believed that no human body can  acclimatize . [ 3 ] [ 4 ] [ 5 ] [ 6 ]  At  extreme altitudes , the ambient pressure can drop below the vapor pressure of water at body temperature, but at such altitudes even pure oxygen at ambient pressure cannot support human life, and a pressure suit is necessary. A rapid depressurisation to the low pressures of high altitudes can trigger  altitude decompression sickness ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2455", "contents": "The physiological responses to high altitude include  hyperventilation ,  polycythemia , increased capillary density in muscle and hypoxic pulmonary vasoconstriction\u2013increased intracellular oxidative enzymes. There are a range of responses to hypoxia at the cellular level, shown by discovery of hypoxia-inducible factors (HIFs), which determine the general responses of the body to oxygen deprivation. Physiological functions at high altitude are not normal and evidence also shows impairment of neuropsychological function, which has been implicated in mountaineering and aviation accidents. [ 1 ]  Methods of mitigating the effects of the high altitude environment include oxygen enrichment of breathing air and/or an increase of pressure in an enclosed environment. [ 1 ]  Other effects of high altitude include  frostbite ,  hypothermia ,  sunburn , and  dehydration ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2456", "contents": "Tibetans and Andeans are two groups which are relatively well adapted to high altitude, but display noticeably different  phenotypes . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2457", "contents": "The human body can perform best at  sea level , [ 7 ]  where the  atmospheric pressure  is 101,325  Pa  or 1013.25  millibars  (or 1  atm , by definition). The  concentration of oxygen  (O 2 ) in sea-level air is 20.9%, so the  partial pressure  of O 2  (pO 2 ) is 21.136 kilopascals (158.53\u00a0mmHg). In healthy individuals, this saturates  hemoglobin , the oxygen-binding red pigment in  red blood cells . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2458", "contents": "Atmospheric pressure decreases following the  Barometric formula  with  altitude  while the O 2  fraction remains constant to about 100\u00a0km (62\u00a0mi), so pO 2  decreases with altitude as well. It is about half of its sea-level value at 5,000\u00a0m (16,000\u00a0ft), the altitude of the  Everest Base Camp , and only a third at 8,848\u00a0m (29,029\u00a0ft), the summit of  Mount Everest . [ 9 ]  When pO 2  drops, the body responds with  altitude acclimatization . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2459", "contents": "The International Society for Mountain Medicine recognizes three altitude regions which reflect the lowered amount of oxygen in the atmosphere: [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2460", "contents": "Travel to each of these altitude regions can lead to medical problems, from the mild symptoms of  acute mountain sickness  to the potentially fatal  high-altitude pulmonary edema  ( HAPE ) and  high-altitude cerebral edema  ( HACE ). The higher the altitude, the greater the risk. [ 12 ]  Expedition doctors commonly stock a supply of  dexamethasone , to treat these conditions on site. [ 13 ]  Research also indicates elevated risk of permanent brain damage in people climbing to above 5,500\u00a0m (18,045\u00a0ft). [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2461", "contents": "People who develop acute mountain sickness can sometimes be identified before the onset of symptoms by changes in fluid balance hormones regulating salt and water metabolism. People who are predisposed to develop high-altitude pulmonary edema may present a reduction in urine production before respiratory symptoms become apparent.\n [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2462", "contents": "Humans have survived for two years at 5,950\u00a0m (19,520\u00a0ft, 475 millibars of atmospheric pressure), which is the highest recorded permanently tolerable altitude; the highest permanent settlement known,  La Rinconada , is at 5,100\u00a0m (16,700\u00a0ft). [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2463", "contents": "At altitudes above 7,500\u00a0m (24,600\u00a0ft, 383 millibars of atmospheric pressure), sleeping becomes very difficult, digesting food is near-impossible, and the risk of HAPE or HACE increases greatly. [ 12 ] [ 17 ] [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2464", "contents": "The  death zone  in  mountaineering  (originally the  lethal zone ) was first conceived in 1953 by  Edouard Wyss-Dunant , a Swiss physician and alpinist. [ 19 ]  It refers to altitudes above a certain point where the amount of  oxygen  is insufficient to sustain  human  life for an extended time span. This point is generally tagged as 8,000\u00a0m (26,000\u00a0ft, less than 356 millibars of atmospheric pressure). [ 20 ]  All 14 summits in the death zone above 8000 m, called  eight-thousanders , are located in the  Himalaya  and  Karakoram  mountain ranges."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2465", "contents": "Many deaths in high-altitude mountaineering have been caused by the effects of the death zone, either directly by loss of vital functions or indirectly through wrong decisions made under stress or physical weakening leading to accidents. In the death zone, the human body cannot acclimatize. An extended stay in the death zone without  supplementary oxygen  will result in deterioration of bodily functions, loss of consciousness, and, ultimately, death. [ 3 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2466", "contents": "At an altitude of 19,000\u00a0m (63,000\u00a0ft), the  atmospheric pressure  is sufficiently low that water  boils  at the  normal temperature  of the  human body . This altitude is known as the  Armstrong limit . Exposure to pressure below this limit results in a rapid loss of consciousness, followed by a series of changes to  cardiovascular  and  neurological  functions, and eventually death, unless pressure is restored within 60\u201390 seconds. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2467", "contents": "Even below the Armstrong limit, an abrupt decrease in atmospheric pressure can cause venous gas bubbles and  decompression sickness . A sudden change from sea-level pressure to pressures as low as those at 5,500\u00a0m (18,000\u00a0ft) can cause altitude-induced decompression sickness. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2468", "contents": "The human body can adapt to high altitude through both immediate and long-term acclimatization. At high altitude, in the short term, the lack of oxygen is sensed by the  carotid bodies , which causes an increase in the breathing depth and rate ( hyperpnea ). However, hyperpnea also causes the adverse effect of  respiratory alkalosis , inhibiting the  respiratory center  from enhancing the respiratory rate as much as would be required. Inability to increase the breathing rate can be caused by inadequate carotid body response or pulmonary or renal disease. [ 2 ] [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2469", "contents": "In addition, at high altitude, the  heart beats faster ; the  stroke volume  is slightly decreased; [ 24 ]  and non-essential bodily functions are suppressed, resulting in a decline in food digestion efficiency (as the body suppresses the  digestive system  in favor of increasing its cardiopulmonary reserves). [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2470", "contents": "Full acclimatization requires days or even weeks. Gradually, the body compensates for the respiratory alkalosis by renal excretion of bicarbonate, allowing adequate respiration to provide oxygen without risking alkalosis. It takes about four days at any given altitude and can be enhanced by drugs such as  acetazolamide . [ 23 ]  Eventually, the body undergoes physiological changes such as lower  lactate  production (because reduced glucose breakdown decreases the amount of lactate formed), decreased  plasma  volume, increased  hematocrit  ( polycythemia ), increased  RBC  mass, a higher concentration of  capillaries  in  skeletal muscle  tissue, increased  myoglobin , increased  mitochondria , increased  aerobic  enzyme concentration, increase in  2,3-BPG ,  hypoxic pulmonary vasoconstriction , and  right ventricular hypertrophy . [ 2 ] [ 26 ]  Pulmonary artery pressure increases in an effort to oxygenate more blood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2471", "contents": "Full hematological adaptation to high altitude is achieved when the increase of red blood cells reaches a plateau and stops. The length of full hematological adaptation can be approximated by multiplying the altitude in kilometres by 11.4 days. For example, to adapt to 4,000 metres (13,000\u00a0ft) of altitude would require 45.6 days. [ 27 ]  The upper altitude limit of this linear relationship has not been fully established. [ 6 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2472", "contents": "Even when acclimatized, prolonged exposure to high altitude can interfere with  pregnancy  and cause  intrauterine growth restriction  or  pre-eclampsia . [ 28 ]  High altitude causes decreased blood flow to the  placenta , even in acclimatized women, which interferes with fetal growth. [ 28 ]  Consequently, children born at high-altitudes are found to be born shorter on average  than children born at sea level. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2473", "contents": "It is estimated that 81.6\u00a0million people live at elevations above 2,500 metres (8,200\u00a0ft). [ 30 ]  \nGenetic changes have been detected in high-altitude population groups in  Tibet  in Asia, the  Andes  of the Americas, and  Ethiopia  in Africa. [ 31 ]  This adaptation means irreversible,  long-term physiological responses  to high-altitude environments, associated with heritable  behavioural  and  genetic changes . The indigenous inhabitants of these regions thrive well in the highest parts of the world. These humans have undergone extensive physiological and genetic changes, particularly in the regulatory systems of oxygen  respiration  and blood  circulation , when compared to the general lowland population. [ 32 ] [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2474", "contents": "Compared with acclimatized newcomers, native Andean and Himalayan populations have better oxygenation at birth, enlarged lung volumes throughout life, and a higher capacity for exercise. [ 1 ]  Tibetans demonstrate a sustained increase in cerebral blood flow, elevated resting ventilation, lower hemoglobin concentration (at elevations below 4000 metres), [ 34 ]  and less susceptibility to  chronic mountain sickness  (CMS). [ 1 ] [ 35 ]  Andeans possess a similar suite of adaptations but exhibit elevated hemoglobin concentration and a normal resting ventilation. [ 36 ]  These adaptations may reflect the longer history of high altitude habitation in these regions. [ 37 ] [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2475", "contents": "A lower  mortality rate  from  cardiovascular disease  is observed for residents at higher altitudes. [ 39 ]  Similarly, a  dose\u2013response relationship  exists between increasing elevation and decreasing  obesity  prevalence in the United States. [ 40 ]  This is not explained by migration alone. [ 41 ]   On the other hand, people living at higher elevations also have a higher rate of  suicide  in the United States. [ 42 ]  The correlation between elevation and suicide risk was present even when the researchers control for known suicide risk factors, including age, gender, race, and income. Research has also indicated that oxygen levels are unlikely to be a factor, considering that there is no indication of increased  mood disturbances  at high altitude in those with  sleep apnea  or in heavy smokers at high altitude. The cause for the increased suicide risk is as yet unknown. [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2476", "contents": "Mitigation may be by supplementary oxygen, pressurisation of the habitat or environmental protection suit, or a combination of both. In all cases the critical effect is the raising of oxygen partial pressure in the breathing gas. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2477", "contents": "Room air at altitude can be enriched with oxygen without introducing an unacceptable fire hazard. At an altitude of 8000 m the equivalent altitude in terms of oxygen partial pressure can be reduced to below 4000 m without increasing the fire hazard beyond that of normal sea level atmospheric air. In practice this can be done using oxygen concentrators. [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2478", "contents": "The ambient air temperature is predictably affected by altitude, and this also has physiological effects on people exposed to high altitudes. The temperature effects and their mitigation are not inherently different from temperature effects from other causes, but the effects of temperature and pressure are cumulative."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2479", "contents": "The temperature of the atmosphere decreases by a  lapse rate , mostly caused by convection and the adiabatic expansion of air with decreasing pressure. [ 44 ]  At the peak of Mount Everest, the average summer temperature is \u221219\u00a0\u00b0C (\u22122\u00a0\u00b0F) and the average winter temperature is \u221236\u00a0\u00b0C (\u221233\u00a0\u00b0F). [ 45 ]  At such low temperatures,  frostbite  and  hypothermia  become risks to humans. Frostbite is a  skin   injury  that occurs when exposed to extreme low temperatures, causing the  freezing  of the skin or other tissues, [ 46 ]  commonly affecting the  fingers ,  toes ,  nose ,  ears ,  cheeks  and  chin  areas. [ 47 ]  Hypothermia is defined as a body  core temperature  below 35.0\u00a0\u00b0C (95.0\u00a0\u00b0F) in humans. [ 48 ]  Symptoms range from  shivering  and  mental confusion, [ 49 ]  to hallucinations and  cardiac arrest . [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2480", "contents": "In addition to cold injuries, breathing cold air can cause  dehydration , because the air is warmed to body temperature and humidified from body moisture. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2481", "contents": "There is also a higher risk of  sunburn  due to the reduced blocking of ultraviolet by the thinner atmosphere. [ 50 ] [ 51 ]  The amount of  UVA  increases approximately 9% with every increase of altitude by 1,000 metres (3,300\u00a0ft). [ 52 ]  Symptoms of sunburn include  red or reddish skin  that is hot to the touch or  painful , general  fatigue , and mild  dizziness . Other symptoms include  blistering ,  peeling skin , swelling, itching, and nausea."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2482", "contents": "For athletes, high altitude produces two contradictory effects on performance. For explosive events (sprints up to 400 metres, long jump, triple jump) the reduction in atmospheric pressure means there is less resistance from the atmosphere and the athlete's performance will generally be better at high altitude. [ 53 ]  For endurance events (races of 800 metres or more), the predominant effect is the reduction in oxygen, which generally reduces the athlete's performance at high altitude. [ 54 ]  One way to gauge this reduction is by monitoring VO 2 max, a measurement of the maximum capacity of an individual to utilize O 2  during strenuous exercise. For an unacclimated individual, VO 2 max begins to decrease significantly at moderate elevation, starting at 1,500 metres and dropping 8 to 11 percent for every additional 1000 metres. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2483", "contents": "Sports organizations acknowledge the effects of altitude on performance: for example, the governing body for the  sport of athletics ,  World Athletics , has ruled that performances achieved at an altitude greater than 1,000 metres will be approved for  world record  purposes, but carry the notation of \"A\" to denote they were set at altitude."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2484", "contents": "The 1968 Summer Olympics  were held at altitude in  Mexico City . The world records in most short sprint and jump records were broken there. Other records were also set at altitude in anticipation of those Olympics.  Bob Beamon 's record in the  long jump  held for almost 23 years and has only been beaten once without altitude or  wind assistance . Many of the other records set at Mexico City were later surpassed by marks set at altitude."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2485", "contents": "An elite athletics meeting was held annually in  Sestriere , Italy, from 1988 to 1996, and again in 2004. The advantage of its high altitude in sprinting and jumping events held out hope of world records, with sponsor  Ferrari  offering a car as a bonus. [ 56 ] [ 57 ]  One record was set, in the  men's pole vault  by  Sergey Bubka  in 1994; [ 57 ]  the  men's  and  women's  records in  long jump  were also beaten, but  wind assisted . [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2486", "contents": "Athletes can also take advantage of altitude acclimatization to increase their performance. [ 10 ]  The same changes that help the body cope with high altitude increase performance back at sea level. However, this may not always be the case. Any positive acclimatization effects may be negated by a de-training effect as the athletes are usually not able to exercise with as much intensity at high altitudes compared to sea level. [ 59 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2487", "contents": "This conundrum led to the development of the altitude training modality known as \"Live-High, Train-Low\", whereby the athlete spends many hours a day resting and sleeping at one (high) altitude, but performs a significant portion of their training, possibly all of it, at another (lower) altitude. A series of studies conducted in Utah in the late 1990s showed significant performance gains in athletes who followed such a protocol for several weeks. [ 59 ] [ 60 ]  Another study from 2006 has shown performance gains from merely performing some exercising sessions at high altitude, yet living at sea level. [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2488", "contents": "The performance-enhancing effect of altitude training could be due to increased red blood cell count, [ 62 ]  more efficient training, [ 63 ]  or changes in muscle physiology. [ 64 ] [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2489", "contents": "In 2007,  FIFA  issued  a short-lived moratorium  on international  football  matches held at more than 2,500 metres above sea level, effectively barring select stadiums in Bolivia, Colombia, and Ecuador from hosting  World Cup  qualifiers, including their capital cities. [ 66 ]  In their ruling, FIFA's executive committee specifically cited what they believed to be an unfair advantage possessed by home teams acclimated to the elevation. The ban was reversed in 2008. [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2490", "contents": "Elastic recoil  means the rebound of the  lungs  after having been stretched by  inhalation , [ 1 ]  or rather, the ease with which the lung rebounds. With inhalation, the  intrapleural pressure  (the pressure within the  pleural cavity ) of the lungs decreases. Relaxing the diaphragm during expiration allows the lungs to recoil and regain the intrapleural pressure experienced previously at rest. Elastic recoil is inversely related to  lung compliance ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2491", "contents": "This phenomenon occurs because of the  elastin  in the  elastic fibers  in the connective tissue of the lungs, and because of the surface tension of the film of fluid that lines the  alveoli .  As water molecules pull together, they also pull on the alveolar walls causing the alveoli to recoil and become smaller.  But two factors prevent the lungs from collapsing:  surfactant  and the intrapleural pressure. Surfactant is a surface-active lipoprotein complex formed by type II alveolar cells. The proteins and lipids that comprise surfactant have both a  hydrophilic  region and a  hydrophobic  region. By absorbing to the air-water interface of alveoli with the hydrophilic head groups in the water and the hydrophobic tails facing towards the air, the main lipid component of surfactant, dipalmitoylphosphatidylcholine, reduces surface tension. It also means the rate of shrinking is more regular because of the stability of surface area caused by surfactant.  Pleural pressure is the pressure in the pleural space.  When this pressure is lower than the pressure of alveoli they tend to expand.  This prevents the elastic fibers and outside pressure from crushing the lungs.  It is a  homeostatic  mechanism."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2492", "contents": "Exercise-induced laryngeal obstruction  ( EILO ) is a transient, reversible narrowing of the  larynx  that occurs during high intensity exercise. This acts to impair airflow and cause  shortness of breath ,  stridor  and often discomfort in the throat and upper chest. EILO is a very common cause of breathing difficulties in young athletic individuals but is often misdiagnosed as  asthma  or  exercise-induced bronchoconstriction . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2493", "contents": "EILO may arise because of a relative mechanical 'insufficiency' of the laryngeal structures that should act to maintain glottic patency.\nIt has been proposed that a narrowing at the laryngeal inlet during the state of high airflow (e.g. when running fast), can act to cause a pressure drop across the larynx which then acts to 'pull' the laryngeal structures together. The  Bernoulli  principle states that increasing airflow through a tube creates increasing negative pressures within that tube. [ 3 ] \nComplex neuromuscular functioning is required to maintain laryngeal opening and to allow the larynx to achieve a great number of tasks (i.e. speaking, airway protection, swallowing). [ 4 ]  It is thus also possible that EILO may arise as form a degree of neuromuscular failure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2494", "contents": "A small heredity study indicated that an autosomal dominant model of inheritance with variable expressivity and reduced penetrance in males may be relevant; because in ten families studied, there was at least one affected person in every generation in which both parents were examined. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2495", "contents": "Further work is needed to determine if structural deficiencies in the laryngeal tissue of individuals with EILO are present. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2496", "contents": "EILO is typically caused by a narrowing of the supra-glottic structures of the larynx. In severe cases, these structures, also called  arytenoids , can close over to almost completely close the laryngeal inlet. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2497", "contents": "In fewer cases, the glottic (i.e. vocal cord) structures close together and this is typically what happens during exercise-induced vocal-cord dysfunction. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2498", "contents": "EILO develops during intense exercise and closure develops as exercise becomes more intense. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2499", "contents": "Closure of the voice box during exercise causes increased 'loading' on the breathing system and the respiratory muscles have to work much harder. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2500", "contents": "The prevalence of EILO in adolescents and young adults appears to be in the range of 5\u20137% in northern Europe, with some indication that EILO may be more prevalent in highly trained athletes. [ 8 ] [ 9 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2501", "contents": "Some, but not all studies report a higher female prevalence. Thus, in a study of 94 patients diagnosed using the CLE test, average age was ~15 years, and 68% were female. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2502", "contents": "In athletic individuals EILO appears to be a highly prevalent cause of cough and wheeze and can co-exist with  EIB . In one study, of almost 90 athletes, with unexplained respiratory symptoms, EILO was found to be present in approximately 30% of athletes, whilst EILO and EIB co-existed in one in ten. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2503", "contents": "This condition can co-exist with other conditions, including severe asthma. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2504", "contents": "The current gold-standard means for diagnosing EILO is the continuous laryngoscopy during exercise test (CLE-test). This test involves the placement of a flexible laryngoscope via nostril, which is then secured in place and held with headgear. It allows continuous visualization of the laryngeal aperture during exercise. \nThe CLE test can be used during indoor treadmill or cycle-ergometer exercise but also whilst rowing or swimming [ 15 ]  or exercising outdoors. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2505", "contents": "The examiner visually evaluates the relative change of the laryngeal inlet in the patient throughout the CLE-test. One common grading system uses 4 steps (0-3) on glottic and supraglottic level respectively. Grades 0-1 are considered normal, whereas grades 2-3 on either or both levels are consistent with EILO. [ 17 ] \nThere is a need to identify other less-invasive means of making a secure diagnosis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2506", "contents": "The current mainstay of treatment is therapy-based. Specialist breathing techniques, most commonly termed biphasic breathing techniques or EILOBI are recommended to reduce turbulent inspiratory airflow and thus reduce chance of laryngeal closure. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2507", "contents": "Direct laryngeal visualisation during exercise to deliver biofeedback has been employed with success. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2508", "contents": "The place of inspiratory muscle training (IMT) is yet to be defined in EILO therapy. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2509", "contents": "Surgical treatment with supraglottopasty has also been utilised with success. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2510", "contents": "Avoiding unnecessary treatment with asthma inhalers is important. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2511", "contents": "Exhalation  (or  expiration ) is the flow of the  breath  out of an organism. In animals, it is the movement of  air  from the  lungs  out of the  airways , to the external environment during  breathing .\nThis happens due to elastic properties of the lungs, as well as the  internal intercostal muscles  which lower the rib cage and decrease thoracic volume.  As the  thoracic diaphragm  relaxes during exhalation it causes the tissue it has depressed to rise superiorly and put pressure on the lungs to expel the air.  During  forced exhalation , as when blowing out a candle, expiratory muscles including the abdominal muscles and internal intercostal muscles generate abdominal and thoracic pressure, which forces air out of the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2512", "contents": "Exhaled air is 4%  carbon dioxide , [ 1 ]  a waste product of  cellular respiration  during the production of energy, which is stored as  ATP .  Exhalation has a complementary relationship to  inhalation  which together make up the  respiratory  cycle of a breath."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2513", "contents": "When a person loses weight, the majority of the weight is exhaled as  carbon dioxide  and  water vapor ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2514", "contents": "The main reason for exhalation is to rid the body of carbon dioxide, which is the waste product of gas exchange in humans.  Air is brought into the lungs through inhalation. Diffusion in the alveoli allows for the exchange of O 2  into the pulmonary capillaries and the removal of CO 2  and other gases from the pulmonary capillaries to be exhaled.  In order for the lungs to expel air the diaphragm relaxes, which pushes up on the lungs.  The air then flows through the trachea then through the larynx and pharynx to the nasal cavity and oral cavity where it is expelled out of the body. [ 2 ]  Exhalation takes longer than inhalation and it is believed to facilitate better exchange of gases.  Parts of the nervous system help to regulate respiration in humans. The exhaled air is not just carbon dioxide; it contains a mixture of other gases.  Human breath contains  volatile organic compounds  (VOCs).  These compounds consist of methanol, isoprene, acetone, ethanol and other alcohols.  The exhaled mixture also contains ketones, water and other hydrocarbons. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2515", "contents": "It is during exhalation that the  olfaction  contribution to  flavor  occurs in contrast to that of ordinary smell which occurs during the inhalation phase. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2516", "contents": "Spirometry  is the measure of lung function.  The  total lung capacity  (TLC),  functional residual capacity  (FRC),  residual volume  (RV), and  vital capacity  (VC) are all values that can be tested using this method.  Spirometry is used to help detect, but not diagnose, respiratory issues like  COPD , and asthma.  It is a simple and cost effective screening method. [ 6 ]  Further evaluation of a person's respiratory function can be done by assessing the  minute ventilation ,  forced vital capacity  (FVC), and  forced expiratory volume  (FEV). These values differ in men and women because men tend to be larger than women."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2517", "contents": "TLC is the maximum amount of air in the lungs after maximum inhalation. In men the average TLC is 6000 ml, and in women it is 4200 ml. FRC is the amount of air left in the lungs after normal exhalation. Men leave about 2400 ml on average while women retain around 1800 ml.  RV is the amount of air left in the lungs after a  forced exhalation .  The average RV in men is 1200 ml and women 1100 ml.  VC is the maximum amount of air that can be exhaled after a maximum inhalation.  Men tend to average 4800 ml and women 3100 ml. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2518", "contents": "Smokers, and those with Asthma and COPD, have reduced airflow ability. People with asthma and COPD show decreases in exhaled air due to inflammation of the airways.  This inflammation causes narrowing of the airways which allows less air to be exhaled.  Numerous things cause inflammation; some examples are cigarette smoke and environmental interactions such as allergies, weather, and exercise.  In smokers the inability to exhale fully is due to the loss of elasticity in the lungs.  Smoke in the lungs causes them to harden and become less elastic, which prevents the lungs from expanding or shrinking as they normally would. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2519", "contents": "Dead space  can be determined by two types of factors which are anatomical and physiological.  Some physiological factors are having non-perfuse but ventilated alveoli, such as a pulmonary embolism or smoking, excessive ventilation of the alveoli, brought on in relation to perfusion, in people with chronic obstructive lung disease, and \" shunt  dead space,\" which is a mistake between the left to right lung that moves the higher CO 2  concentrations in the venous blood into the arterial side. [ 7 ]   The anatomical factors are the size of the airway, the valves, and tubing of the respiratory system. [ 7 ]   Physiological dead space of the lungs can affect the amount of dead space as well with factors including smoking, and diseases. Dead space is a key factor for the lungs to work because of the differences in pressures, but it can also hinder the person. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2520", "contents": "One of the reasons we can breathe is because of the  elasticity of the lungs .  The internal surface of the lungs on average in a non-emphysemic person is normally 63m2 and can hold about 5lts of air volume. [ 8 ]   Both lungs together have the same amount of surface area as half of a tennis court.  Disease such as, emphysema, tuberculosis, can reduce the amount of surface area and elasticity of the lungs. Another big factor in the elasticity of the lungs is smoking because of the residue left behind in the lungs from the smoking.  The elasticity of the lungs can be trained to expand further. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2521", "contents": "Brain control of exhalation can be broken down into voluntary control and involuntary control. During voluntary exhalation, air is held in the lungs and released at a fixed rate. Examples of voluntary expiration include: singing, speaking, exercising, playing an instrument, and voluntary  hyperpnea . Involuntary breathing includes metabolic and behavioral breathing. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2522", "contents": "The neurological pathway of voluntary exhalation is complex and not fully understood. However, a few basics are known. The  motor cortex  within the cerebral cortex of the brain is known to control voluntary respiration because the motor cortex controls voluntary muscle movement. [ 9 ]  This is referred to as the corticospinal pathway or ascending respiratory pathway. [ 9 ] [ 10 ]  The pathway of the electrical signal starts in the motor cortex, goes to the spinal cord, and then to the respiratory muscles. The spinal neurons connect directly to the respiratory muscles. Initiation of voluntary contraction and relaxation of the internal and external internal costals has been shown to take place in the superior portion of the primary motor cortex. [ 9 ]  Posterior to the location of thoracic control (within the superior portion of the primary motor cortex) is the center for diaphragm control. [ 9 ]  Studies indicate that there are numerous other sites within the brain that may be associated with voluntary expiration. The inferior portion of the  primary motor cortex  may be involved, specifically, in controlled exhalation. [ 9 ]  Activity has also been seen within the supplementary motor area and the premotor cortex during voluntary respiration. This is most likely due to the focus and mental preparation of the voluntary muscular movement. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2523", "contents": "Voluntary expiration is essential for many types of activities. Phonic respiration (speech generation) is a type of controlled expiration that is used every day. Speech generation is completely dependent on expiration, this can be seen by trying to talk while inhaling. [ 11 ]   Using airflow from the lungs, one can control the duration, amplitude, and pitch. [ 12 ]  While the air is expelled it flows through the glottis causing vibrations, which produces sound.  Depending on the glottis movement the pitch of the voice changes and the intensity of the air through the glottis change the volume of the sound produced by the glottis. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2524", "contents": "Involuntary respiration is controlled by respiratory centers within the medulla oblongata and pons. The medullary respiratory center can be subdivided into anterior and posterior portions. They are called the ventral and dorsal respiratory groups respectively. The  pontine respiratory group  consists of two parts: the  pneumotaxic center  and the  apneustic center . [ 10 ]   All four of these centers are located in the brainstem and work together to control involuntary respiration. In our case, the  ventral respiratory group  (VRG) controls involuntary exhalation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2525", "contents": "The neurological pathway for involuntary respiration is called the bulbospinal pathway. It is also referred to as the descending respiratory pathway. [ 10 ]   \"The pathway descends along the spinal ventralateral column. The descending tract for autonomic inspiration is located laterally, and the tract for autonomic expiration is located ventrally.\" [ 13 ]   Autonomic Inspiration is controlled by the pontine respiratory center and both medullary respiratory centers. In our case, the VRG controls autonomic exhalation. Signals from the VRG are sent along the spinal cord to several nerves. These nerves include the intercostals, phrenic, and abdominals. [ 10 ]   These nerves lead to the specific muscles they control.  The bulbospinal pathway descending from the VRG allows the respiratory centers to control muscle relaxation, which leads to exhalation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2526", "contents": "Yawning  is considered a non-respiratory gas movement.  A non-respiratory gas movement is another process that moves air in and out of the lungs that do not include breathing. Yawning is a reflex that tends to disrupt the normal breathing rhythm and is believed to be contagious as well. [ 14 ]   The reason why we yawn is unknown. A common belief is that yawns are a way to regulate the body's levels of O 2  and CO 2,  but studies done in a controlled environment with different levels of O 2  and CO 2  have disproved that hypothesis.  Although there is not a concrete explanation as to why we yawn, others think people exhale as a cooling mechanism for our brains.  Studies on animals have supported this idea and it is possible humans could be linked to it as well. [ 15 ]  What is known is that yawning does ventilate all the alveoli in the lungs. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2527", "contents": "Several receptor groups in the body regulate metabolic breathing. These receptors signal the  respiratory center  to initiate inhalation or exhalation.  Peripheral chemoreceptors  are located in the aorta and carotid arteries. They respond to changing blood levels of oxygen, carbon dioxide, and  H +  by signaling the pons and medulla. [ 10 ]   Irritant and stretch receptors in the lungs can directly cause exhalation. Both sense foreign particles and promote spontaneous coughing. They are also known as mechanoreceptors because they recognize physical changes not chemical changes. [ 10 ]   Central chemoreceptors  in the medulla also recognize chemical variations in H + . Specifically, they monitor pH change within the medullary interstitial fluid and cerebral spinal fluid. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2528", "contents": "Yogis such as  B. K. S. Iyengar  advocate both  inhaling and exhaling through the nose  in the practice of  yoga , rather than inhaling through the nose and  exhaling through the mouth . [ 16 ] [ 17 ] [ 18 ]  They tell their students that the \"nose is for breathing, the mouth is for eating.\" [ 17 ] [ 19 ] [ 20 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2529", "contents": "The  FEV1/FVC ratio , also called  modified Tiffeneau-Pinelli index , [ 1 ]   is a calculated ratio used in the diagnosis of  obstructive  and  restrictive lung disease . [ 2 ] [ 3 ]  It represents the proportion of a person's  vital capacity  that they are able to expire in the first second of forced expiration ( FEV1 ) to the full, forced vital capacity ( FVC ). [ 4 ]  FEV1/FVC ratio was first proposed by E.A. Haensler in 1950. [ 5 ]  The FEV1/FVC index should not be confused with the FEV1/VC index (Tiffeneau-Pinelli index) as they are different, although both are intended for diagnosing airway obstruction. Current recommendations for diagnosing pulmonary function recommend using the modified Tiffeneau-Pinelli index (also known as the Haensler index). [ 6 ]  This index is recommended to be represented as a decimal fraction with two digits after the decimal point (for example, 0.70)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2530", "contents": "Normal values are approximately 75%. [ 7 ]  Predicted normal values can be  calculated online  and depend on age, sex, height, and ethnicity as well as the research study that they are based upon."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2531", "contents": "A derived value of FEV1% is  FEV1% predicted , which is defined as FEV1% of the patient divided by the average FEV1% in the population for any person of similar age, sex, and body composition."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2532", "contents": "In obstructive lung disease, the FEV1 is reduced due to an obstruction of air escaping from the lungs. Thus, the FEV1/FVC ratio will be reduced. [ 4 ]   More specifically, according to the  National Institute for Clinical Excellence , the diagnosis of  COPD  is made when the FEV 1 /FVC ratio is less than 0.7 or [ 8 ]  the FEV 1  is less than 75% of predicted; [ 9 ]  however, other authoritative bodies have different diagnostic cutoff points. [ 10 ]  The  Global Initiative for Chronic Obstructive Lung Disease  criteria also require that values are after  bronchodilator  medication has been given to make the diagnosis. According to the  European Respiratory Society  (ERS) criteria, it is  FEV1% predicted  that defines when a patient has COPD\u2014that is, when the patient's FEV1% is less than 88% of the predicted value for men, or less than 89% for women. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2533", "contents": "In restrictive lung disease, the FEV1  and  FVC are equally reduced due to fibrosis or other lung pathology (not obstructive pathology). Thus, the FEV1/FVC ratio should be approximately normal, or even increased due to a decrease in magnitude of FVC as compared to FEV1 (because of the decreased compliance associated with the presence of fibrosis in some pathological conditions). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2534", "contents": "Freediving blackout ,  breath-hold blackout , [ 1 ]  or  apnea blackout  is a class of  hypoxic blackout , a  loss of consciousness  caused by  cerebral hypoxia  towards the end of a breath-hold ( freedive  or dynamic  apnea ) dive, when the swimmer does not necessarily experience an urgent need to breathe and has no other obvious medical condition that might have caused it. It can be provoked by  hyperventilating  just before a dive, or as a consequence of the pressure reduction on ascent, or a combination of these. Victims are often established practitioners of breath-hold diving, are fit, strong swimmers and have not experienced problems before. [ 2 ] [ 3 ] [ 4 ]  Blackout may also be referred to as a  syncope  or  fainting ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2535", "contents": "Divers and swimmers who black out or  grey out  underwater during a dive will usually  drown  unless rescued and resuscitated within a short time. [ 5 ]  Freediving blackout has a high fatality rate, and mostly involves males younger than 40 years, but is generally avoidable. Risk cannot be quantified, but is clearly increased by any level of hyperventilation. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2536", "contents": "Freediving  blackout can occur on any dive profile: at constant depth, on an ascent from depth, or at the surface following ascent from depth and may be described by a number of terms depending on the dive profile and depth at which consciousness is lost. Blackout during a shallow dive differs from blackout during ascent from a deep dive in that blackout during ascent is precipitated by depressurisation on ascent from depth while blackout in consistently shallow water is a consequence of  hypocapnia  following hyperventilation. [ 4 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2537", "contents": "Different types of freediving blackout have become known under a variety of names; these include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2538", "contents": "In this article  constant pressure blackout  and  shallow water blackout  refers to blackouts in shallow water following hyperventilation and  ascent blackout  and  deep water blackout  refers to blackout on ascent from depth. Some free divers consider blackout on ascent to be a special condition or subset of shallow water blackout but the primary underlying mechanisms differ. This confusion is exacerbated by the fact that in the case of blackout on ascent, hyperventilation induced  hypocapnia  also may be a contributory factor even if depressurisation on ascent is the actual precipitator. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2539", "contents": "Some scuba diving curricula may apply the terms  shallow-water blackout  and  deep-water blackout  differently; deep-water blackout being applied to the final stage of  nitrogen narcosis  while shallow water blackout may be applied to a blackout from a deep free dive. [ 9 ]   Nitrogen narcosis does not normally apply to freediving as free-divers start and finish the dive with only a single lungful of air and it has long been assumed that free divers are not exposed to the necessary pressure for long enough to absorb sufficient nitrogen. [ 3 ] [ 9 ] [ 13 ]   Where these terms are used in this manner there is usually little or no discussion of the phenomenon of blackouts not involving depressurisation and the cause may be variously attributed to either depressurisation or  hypocapnia  or both. [ 9 ]  This problem may stem from the origin of the term  latent hypoxia  in the context of a string of fatal, shallow water accidents with early military, closed-circuit  rebreather  apparatus prior to the development of effective  oxygen partial pressure measurement . [ 4 ]  In the very different context of dynamic  apnea  sports careful consideration of terms is needed to avoid potentially dangerous confusion between two phenomena that actually have different characteristics, mechanisms and prevention measures. The application of the term  shallow water blackout  to deep dives and its subsequent association with extreme sports has tended to mislead many practitioners of static apnea and dynamic apnea distance diving into thinking that it does not apply to them even though isobaric shallow water blackout kills swimmers every year, often in shallow swimming pools. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2540", "contents": "The  CDC  has identified a consistent set of voluntary behaviors associated with unintentional drowning, known as dangerous underwater breath-holding behaviors; these are intentional hyperventilation,  static apnea , and  hypoxic training . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2541", "contents": "Other terms generally associated with freediving blackout include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2542", "contents": "The minimum tissue and venous partial pressure of oxygen which will maintain consciousness is about 20 millimetres of mercury (27\u00a0mbar). [ 21 ]  This is equivalent to approximately 30 millimetres of mercury (40\u00a0mbar) in the lungs. [ 13 ]  Approximately 46\u00a0ml/min oxygen is required for brain function. This equates to a minimum arterial ppO 2  of 29 millimetres of mercury (39\u00a0mbar) at 868\u00a0ml/min cerebral flow. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2543", "contents": "Hyperventilation depletes the blood of carbon dioxide (hypocapnia), which causes respiratory alkylosis (increased pH), and causes a leftward shift in the  oxygen\u2013hemoglobin dissociation curve . This results in a lower venous partial pressure of oxygen, which worsens hypoxia. [ 21 ]  A normally ventilated breath-hold usually breaks (from CO 2 ) with over 90% saturation which is far from hypoxia.  Hypoxia produces a respiratory drive but not as strong as the hypercapnic respiratory drive. [ 12 ]  This has been studied in altitude medicine, where hypoxia occurs without hypercapnia due to the low ambient pressure. [ 13 ]  The balance between the hypercapnic and hypoxic respiratory drives has genetic variability and can be modified by hypoxic training. These variations imply that predictive risk cannot be reliably estimated, but pre-dive hyperventilation carries definite risks. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2544", "contents": "There are three different mechanisms behind blackouts in freediving: [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2545", "contents": "The mechanism for blackout on ascent differs from hyperventilation induced hypocapnia expedited blackouts and does not necessarily follow hyperventilation. [ 4 ] [ 7 ]  However, hyperventilation will exacerbate the risk and there is no clear line between them. Shallow water blackouts can happen in extremely shallow water, even on dry land following hyperventilation and  apnoea  but the effect becomes much more dangerous in the ascent stage of a deep freedive. There is considerable confusion surrounding the terms  shallow  and  deep  water blackout and they have been used to refer to different things, or be used interchangeably, in different water sports circles. For example, the term shallow water blackout has been used to describe blackout on ascent because the blackout usually occurs when the diver ascends to a shallow depth. [ 9 ] [ 10 ] [ 24 ]  For the purposes of this article there are two separate phenomena  Shallow water blackout  and  Blackout on ascent  as follows:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2546", "contents": "Otherwise unexplained blackouts underwater have been associated with the practice of  hyperventilation . [ 2 ] [ 3 ] [ 4 ] [ 25 ]  Survivors of shallow water blackouts often report using hyperventilation as a technique to increase the time they can spend underwater. Hyperventilation, or over-breathing, involves breathing faster and/or deeper than the body naturally demands and is often used by divers in the mistaken belief that this will increase  oxygen saturation . Although this appears true intuitively, under normal circumstances the breathing rate dictated by the body alone already leads to 98\u201399% oxygen saturation of the arterial  blood  and the effect of over-breathing on the oxygen intake is minor. What is really happening differs from divers' understanding; these divers are extending their dive by postponing the body's natural breathing mechanism, not by increasing oxygen load. [ 10 ]   The mechanism is as follows:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2547", "contents": "The primary urge to breathe is triggered by rising  carbon dioxide  (CO 2 ) levels in the bloodstream. [ 25 ]  Carbon dioxide builds up in the bloodstream when oxygen is metabolized and it needs to be expelled as a waste product. The body detects carbon dioxide levels very accurately and relies on this as the primary trigger to control breathing. [ 25 ]  Hyperventilation artificially depletes the resting concentration of carbon dioxide causing a low blood carbon dioxide condition called  hypocapnia . Hypocapnia reduces the reflexive respiratory drive, allowing the delay of breathing and leaving the diver susceptible to loss of consciousness from  hypoxia . For most healthy people, the first sign of low oxygen levels is a  greyout  or unconsciousness: there is no bodily sensation that warns a diver of an impending blackout. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2548", "contents": "Significantly, victims drown quietly underwater without alerting anyone to the fact that there is a problem and are typically found on the bottom as shown in the staged image above. Survivors of shallow water blackout are typically puzzled as to why they blacked out. Pool life guards are trained to scan the bottom for the situation shown. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2549", "contents": "Breath-hold divers who hyperventilate before a dive increase their risk of drowning.  Many drownings unattributed to any other cause result from shallow water blackout and could be avoided if this mechanism was properly understood and the practice eliminated. Shallow water blackout can be avoided by ensuring that carbon dioxide levels in the body are normally balanced prior to diving and that appropriate safety measures are in place. [ 1 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2550", "contents": "A high level of hypocapnia is readily identifiable as it causes dizziness and tingling of the fingers. These extreme symptoms are caused by the increase of blood pH ( alkalosis ) following the reduction of carbon dioxide, which acts to lower the pH of the blood. The absence of any symptoms of hypocapnia is not an indication that the diver's carbon dioxide is within safe limits and cannot be taken as an indication that it is therefore safe to dive. Conservative breath-hold divers who hyperventilate but stop doing so before the onset of these symptoms are likely to be already hypocapnic without knowing it. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2551", "contents": "Note that the urge to breathe is triggered by rising carbon dioxide levels in the blood and not by the reduction of oxygen.  The body can actually detect low levels of oxygen but this is not normally perceptible prior to blackout. [ 10 ]   Persistently elevated levels of carbon dioxide in the blood,  hypercapnia  (the opposite to  hypocapnia ), tend to desensitise the body to carbon dioxide, in which case the body may come to rely on the oxygen level in the blood to maintain respiratory drive. This is illustrated in the scenario of type II  respiratory failure . However, in a normal healthy person there is no subjective awareness of low oxygen levels. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2552", "contents": "An ascent blackout, or deep water blackout, is a loss of consciousness caused by  cerebral hypoxia  on ascending from a deep freedive or breath-hold dive, typically of ten metres or more when the swimmer does not necessarily experience an urgent need to breathe and has no other obvious medical condition that might have caused it. [ 2 ] [ 3 ] [ 7 ] [ 10 ]   Victims typically black out close to the surface, usually within the top three metres, sometimes even as they break surface and have often been seen to approach the surface without apparent distress only to sink away.  It is quite rare for blackouts to occur while at the bottom or in the early stages of ascent; divers who  drown  in these stages are usually found to have inhaled water, indicating that they were conscious and succumbed to an uncontrollable urge to breathe rather than blacking out.  Victims are usually established practitioners of deep breath-hold diving, are fit, strong swimmers and have not experienced problems before. Blackout by this mechanism may occur even after surfacing from depth and breathing has commenced if the inhaled oxygen has not yet reached the brain and may be referred to as a  surface blackout . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2553", "contents": "The partial pressure of oxygen in the air in the lungs controls the oxygen loading of blood. A critical pO 2  of 30 millimetres of mercury (40\u00a0mbar) in the lungs will sustain consciousness when breathing is resumed after a breath-hold dive. This is about 4% oxygen in the lungs and 45% oxygen saturation of the arterial blood. At 30\u00a0msw (4 bar), 2% by volume oxygen in the lung gas gives a pO 2  of 60 millimetres of mercury (80\u00a0mbar). At 10\u00a0msw (2 bar), for the same 2% oxygen, the pO 2  would be 30 millimetres of mercury (40\u00a0mbar), i.e. marginal. At the surface the same 2% oxygen drops to 15 millimetres of mercury (20\u00a0mbar), ignoring metabolic use. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2554", "contents": "Three factors are thought to be involved: Voluntary suppression of breathing and rapid depressurisation are necessarily present, and self-induced hypocapnia by hyperventilation is known to be present in many cases. Depressurisation on ascent is an explanation for the shallow depth of ascent blackouts but does not fully explain all cases unless accompanied by an underlying suppression of the urge to breathe through self-induced hypocapnia via hyperventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2555", "contents": "Surface blackout occurs just after the diver exhales on the surface, and may happen before, during or after inhalation of the first breath. When the diver exhales, there is usually a reduction of intrathoracic pressure, which is exacerbated by the effort of inhalation, which can further compromise the partial pressure of oxygen in the alveolar capillaries, and after a small time lag, the oxygen supply to the brain. The exhalation also reduces the buoyancy of the diver and increases the risk of sinking as a consequence of blackout. The drop in intrathoracic pressure may also reduce cardiac output for this period and thereby further compromise the cerebral oxygen supply. [ 28 ]  The delay between breathing and the oxygenated blood reaching the brain can exceed 15 seconds. Competitive freediving safety monitors watch the diver for at least 30 seconds after surfacing. Recovery breathing may reduce the risk of surface blackout during the critical period after surfacing. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2556", "contents": "The usual consequence of blackout, if the diver's airway is not protected, is drowning. A diver who has blacked out and has been promptly returned to the surface will usually regain consciousness within seconds. While the diver is still unconscious underwater, they are at high risk of drowning. The time between loss of consciousness and death varies considerably depending on a number of factors but can be as little as  2 + 1 \u2044 2  minutes. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2557", "contents": "An unconscious diver loses voluntary bodily control, but still has protective reflexes that protect the airway. One of these is  laryngospasm , which closes the  larynx  to prevent water from entering the lungs. After some time a laryngospasm will relax and the airway will open. If the diver has reached the surface and the diver's face is kept above water, when the laryngospasm relaxes spontaneous breathing will often resume. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2558", "contents": "If the diver is still underwater when the laryngospasm relaxes, then water will enter the airway and may reach the lungs, which will cause complications even if resuscitation is successful.  Secondary drowning  may occur as a result. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2559", "contents": "The sudden and unexpected death of a swimmer, with no involuntary drowning sequence, can be difficult to ascribe to a specific cause. The possibilities may include pre-existing organic cardiac disease, pre-existing cardiac electrical abnormalities, epilepsy, hypoxic blackout, homicide and suicide. The diagnosis may have significant legal consequences. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2560", "contents": "Careful recording of observed events can improve the chances of correct diagnosis. The victim of hypoxic blackout may have been seen to be hyperventilating before the dive, and typically the blackout will have occurred some time after immersion, often without surfacing, and usually close to the surface. The victim is subsequently found unconscious or dead at the bottom of the water. Accounts of witnesses may be useful in diagnosing the cause and in the resuscitation and treatment of survivors. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2561", "contents": "The risk of freediving blackout is not known as there are currently no rigorous data on freediving blackouts. However, the estimated, average, annual fatalities attributed to freediver blackout over a period of ten years in a population of approximately 135,000 divers in nine countries was 53 per year, or one in 2,547. [ 28 ]   The total number of fatalities appears to have remained unchanged in recent years, but it is not possible to calculate the fatality rate because variables such as the number of dives and the diver population are not known. [ 6 ] \nThe risk also differs across diving cultures and practices.  For example, approximately 70% of Italian divers who regularly compete in national and international spearfishing competitions have had at least one blackout whereas Japanese  Ama  divers have a low rate of blackout as they follow a conservative dive profile, limiting dive duration to one minute, resting between dives and making several short dives rather than fewer long ones. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2562", "contents": "Experienced free-divers are at particular risk because of their practiced ability to suppress the carbon dioxide induced urge to breathe. Some argue that the highest risk may be to intermediate skilled divers who are training hard and have not recognised their limits. [ 10 ] [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2563", "contents": "Where deep breath-hold divers are observed to use hyperventilation, timely and informed advice may save their lives but experience suggests that divers are reluctant to change their practice unless they have a very clear understanding of the mechanics of the process. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2564", "contents": "Breath-hold divers who hyperventilate before a dive increase their risk of drowning.  Many drownings unattributed to any other cause are assumed to result from shallow water blackout, and could be avoided if this mechanism was properly understood and the practice controlled or eliminated. Increased advocacy to improve public awareness of the risk is one of the few available ways to attempt to reduce the incidence of this problem. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2565", "contents": "Shallow water blackout can be avoided by ensuring that carbon dioxide levels in the body are normally balanced prior to diving and that appropriate safety measures are in place. The following precautions are recommended by several organizations: [ 10 ] [ 33 ] [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2566", "contents": "A high level of hypocapnia is readily recognized as it causes dizziness and tingling of the fingers. These extreme symptoms are caused by the increase of blood pH ( alkalosis ) following the reduction of CO 2 , which is required to maintain the acidity of the blood. The absence of any symptoms of hypocapnia is not an indication that the diver's carbon dioxide level is within safe limits and cannot be taken as an indication that it is therefore safe to dive. Conservative breath-hold divers who hyperventilate but stop doing so before the onset of these symptoms are likely to be hypocapnic already without knowing it. [ 12 ] [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2567", "contents": "Outright banning of hyperventilation and breath-hold training at swimming pools may reduce or prevent instances of blackout at those pools, but may result in the activity being done at other places where there may be less supervision and a higher risk of fatality. Supervision by a person not involved in the activity and familiar with the risks and management of blackouts is a preferred option. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2568", "contents": "An analysis of incidents suggests that lifeguards at swimming pools could prevent most accidents by watching out for young male swimmers who are practicing hyperventilation and underwater swimming. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2569", "contents": "Recognition of the problem in time to help is critical; the diver will not notice any symptoms and is dependent on a dive buddy or surface support team for recognition.  Indicators of blackout to look for in a diver include: [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2570", "contents": "Rescue requires a competent diver on site to recover the unconscious diver to the surface, or prevent them from sinking in the case of a surface blackout. This requires that the safety diver is aware of the status of the diver in time to react effectively. The unconscious freediver should be brought to the surface with minimum delay. There is no risk of lung over-pressure injury, and the  airway  should be secured if possible to prevent aspiration. The mask is adequate protection of the nasal passages if in place, and a hand can be used to cover the mouth and hold it closed. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2571", "contents": "Once surfaced, ensure an open airway. The mask may be removed at this point. The diver may spontaneously resume breathing. Typical response time after shallow dives is 3 to 10 seconds, increasing to 10 to 30 seconds for deep dives. If the diver starts breathing and regains consciousness spontaneously, they should be continuously monitored until out of the water. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2572", "contents": "If the diver does not spontaneously resume breathing,  rescue breathing  (artificial ventilation) is indicated. The casualty should be removed from the water expeditiously and  basic life support  provided until expert assistance is available. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2573", "contents": "When first aid and medical treatment are necessary, it is for  drowning ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2574", "contents": "Initial resuscitation follows the standard procedure for drowning. The checks for responsiveness and breathing are carried out with the person horizontally supine. If unconscious but breathing, the  recovery position  is appropriate. If not breathing,  rescue ventilation  is necessary. Drowning can produce a gasping pattern of apnea while the heart is still beating, and ventilation alone may be sufficient, as the heart may be basically healthy, but hypoxic. The airway-breathing-circulation sequence should be followed, not starting with compressions, as the basic problem is lack of oxygen. Five initial breaths are recommended, as the initial ventilation may be difficult because of water in the airways which can interfere with effective alveolar inflation. Thereafter a sequence of two breaths and 30  chest compressions  is recommended, repeated until vital signs are re-established, the rescuers are unable to continue, or  advanced life support  is available. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2575", "contents": "Attempts to actively expel water from the airway by abdominal thrusts or positioning head downwards should be avoided as they delay the start of ventilation and increase the risk of vomiting, with a significantly increased risk of death, as aspiration of stomach contents is a common complication of resuscitation efforts. Administration of oxygen at 15 litres per minute by face mask or  bag mask  is often sufficient, but  tracheal intubation  with  mechanical ventilation  may be necessary. Suctioning of pulmonary oedema fluid should be balanced against the need for oxygenisation. The target of ventilation is to achieve 92% to 96% arterial saturation and adequate chest rise.  Positive end-expiratory pressure  will generally improve oxygenation. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2576", "contents": "The  Haldane effect  is a property of  hemoglobin  first described by  John Scott Haldane , within which oxygenation of blood in the lungs displaces carbon dioxide from hemoglobin, increasing the removal of carbon dioxide. Consequently, oxygenated blood has a reduced affinity for carbon dioxide. Thus, the Haldane effect describes the ability of hemoglobin to carry increased amounts of carbon dioxide (CO 2 ) in the deoxygenated state as opposed to the oxygenated state. Vice versa, it is true that a high concentration of CO 2  facilitates dissociation of oxyhemoglobin, though this is the result of two distinct processes (Bohr effect and Margaria-Green effect) and should be distinguished from Haldane effect."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2577", "contents": "Carbon dioxide travels through the  blood  in three different ways. One of these ways is by binding to  amino  groups, creating  carbamino  compounds. Amino groups are available for binding at the N-terminals and at side-chains of  arginine  and  lysine  residues in hemoglobin. When carbon dioxide binds to these residues  carbaminohemoglobin  is formed. [ 1 ]  This amount of  carbaminohemoglobin  formed is inversely proportional to the amount of oxygen attached to hemoglobin. Thus, at lower oxygen saturation, more  carbaminohemoglobin  is formed. These dynamics explain the relative difference in hemoglobin's affinity for carbon dioxide depending on oxygen levels known as the Haldane effect. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2578", "contents": "Histidine  residues in hemoglobin can accept protons and act as  buffers . Deoxygenated hemoglobin is a better  proton acceptor  than the oxygenated form. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2579", "contents": "In red blood cells, the enzyme  carbonic anhydrase  catalyzes the conversion of dissolved carbon dioxide to  carbonic acid , which rapidly dissociates to  bicarbonate  and a free  proton :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2580", "contents": "By  Le Chatelier's principle , anything that stabilizes the proton produced will cause the reaction to shift to the right, thus the enhanced affinity of deoxyhemoglobin for protons enhances synthesis of bicarbonate and accordingly increases capacity of deoxygenated blood for carbon dioxide. The majority of carbon dioxide in the blood is in the form of bicarbonate. Only a very small amount is actually dissolved as carbon dioxide, and the remaining amount of carbon dioxide is bound to hemoglobin."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2581", "contents": "In addition to enhancing removal of carbon dioxide from oxygen-consuming tissues, the Haldane effect promotes dissociation of  carbon dioxide  from hemoglobin in the presence of  oxygen . In the oxygen-rich capillaries of the lung, this property causes the displacement of carbon dioxide to plasma as low-oxygen blood enters the  alveolus  and is vital for  alveolar gas exchange ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2582", "contents": "The general equation for the Haldane Effect is:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2583", "contents": "However, this equation is confusing as it reflects primarily the  Bohr effect . The significance of this equation lies in realizing that oxygenation of Hb promotes dissociation of H +  from Hb, which shifts the bicarbonate buffer equilibrium towards CO 2  formation; therefore, CO 2  is released from RBCs. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2584", "contents": "In patients with lung disease, lungs may not be able to increase  alveolar ventilation  in the face of increased amounts of dissolved CO 2 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2585", "contents": "This partially explains the observation that some patients with  emphysema  might have an increase in P a CO 2  (partial pressure of arterial dissolved carbon dioxide) following administration of supplemental oxygen even if content of CO 2  stays equal. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2586", "contents": "Hemoglobin  ( haemoglobin , [ a ]   Hb  or  Hgb ) is a  protein  containing  iron  that facilitates the transportation of  oxygen  in  red blood cells . Almost all  vertebrates  contain hemoglobin, [ 3 ]  with the sole exception of the fish family  Channichthyidae . [ 4 ]  Hemoglobin in the  blood  carries oxygen from the respiratory organs ( lungs  or  gills ) to the other tissues of the body, where it releases the oxygen to enable  aerobic respiration  which powers an animal's  metabolism . A healthy human has 12 \u00a0 to 20 \u00a0 grams of hemoglobin in every 100 \u00a0 mL of blood. Hemoglobin is a  metalloprotein , a  chromoprotein , and  globulin ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2587", "contents": "In  mammals , hemoglobin makes up about 96% of a red blood cell's  dry weight  (excluding water), and around 35% of the total weight (including water). [ 5 ]  Hemoglobin has an oxygen-binding capacity of 1.34 \u00a0 mL of O 2  per gram, [ 6 ]  which increases the total  blood oxygen capacity  seventy-fold compared to dissolved oxygen in blood plasma alone. [ 7 ]  The mammalian hemoglobin molecule can bind and transport up to four oxygen molecules. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2588", "contents": "Hemoglobin also transports other gases. It carries off some of the body's respiratory  carbon dioxide  (about 20\u201325% of the total) [ 9 ]  as  carbaminohemoglobin , in which CO 2  binds to the  heme protein . The molecule also carries the important regulatory molecule  nitric oxide  bound to a  thiol  group in the globin protein, releasing it at the same time as oxygen. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2589", "contents": "Hemoglobin is also found in other cells, including in the  A9 dopaminergic neurons  of the  substantia nigra ,  macrophages ,  alveolar cells , lungs, retinal pigment epithelium, hepatocytes,  mesangial cells  of the kidney, endometrial cells, cervical cells, and vaginal epithelial cells. [ 11 ]  In these tissues, hemoglobin absorbs unneeded oxygen as an  antioxidant , and regulates  iron metabolism . [ 12 ]  Excessive glucose in the blood can attach to hemoglobin and raise the level of hemoglobin A1c. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2590", "contents": "Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants. [ 14 ]  In these organisms, hemoglobins may carry oxygen, or they may transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant called  leghemoglobin  serves to scavenge oxygen away from  anaerobic  systems such as the nitrogen-fixing nodules of  leguminous  plants, preventing oxygen poisoning."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2591", "contents": "The medical condition  hemoglobinemia , a form of  anemia , is caused by  intravascular hemolysis , in which hemoglobin leaks from red blood cells into the  blood plasma ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2592", "contents": "In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species. [ 16 ] [ 17 ]  From the known atomic mass of iron, he calculated the molecular mass of hemoglobin to  n  \u00d7 16000 ( n =number of iron atoms per hemoglobin molecule, now known to be 4), the first determination of a protein's molecular mass. This \"hasty conclusion\" drew ridicule from colleagues who could not believe that any molecule could be so large. However,  Gilbert Smithson Adair  confirmed Engelhart's results in 1925 by measuring the osmotic pressure of hemoglobin solutions. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2593", "contents": "Although blood had been known to carry oxygen since at least 1794, [ 19 ] [ 20 ]  the oxygen-carrying property of hemoglobin was described by H\u00fcnefeld in 1840. [ 21 ]  In 1851, German physiologist  Otto Funke  published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. [ 22 ] [ 23 ]  Hemoglobin's reversible oxygenation was described a few years later by  Felix Hoppe-Seyler . [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2594", "contents": "With the development of  X-ray crystallography , it became possible to sequence protein structures. [ 25 ]  In 1959,  Max Perutz  determined the molecular structure of hemoglobin. [ 26 ] [ 27 ]  For this work he shared the 1962  Nobel Prize in Chemistry  with  John Kendrew , who sequenced the globular protein  myoglobin . [ 25 ] [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2595", "contents": "The role of hemoglobin in the blood was elucidated by French  physiologist   Claude Bernard ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2596", "contents": "The name  hemoglobin  (or  haemoglobin ) is derived from the words  heme  (or  haem ) and  globin , reflecting the fact that each  subunit  of hemoglobin is a  globular protein  with an embedded  heme  group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2597", "contents": "Hemoglobin consists of  protein subunits  ( globin  molecules), which are  polypeptides , long folded chains of specific  amino acids  which determine the protein's chemical properties and function. The amino acid sequence of any polypeptide is  translated  from a segment of DNA, the corresponding  gene ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2598", "contents": "There is more than one hemoglobin gene. In humans,  hemoglobin A  (the main form of hemoglobin in adults) is coded by genes  HBA1 ,  HBA2 , and  HBB . [ 30 ]  Alpha 1 and alpha 2 subunits are respectively coded by genes  HBA1  and  HBA2  close together on chromosome 16, while the beta subunit is coded by gene  HBB  on chromosome 11. The amino acid sequences of the globin subunits usually differ between species, with the difference growing with evolutionary distance. For example, the most common hemoglobin sequences in humans, bonobos and chimpanzees are completely identical, with exactly the same alpha and beta globin protein chains. [ 31 ] [ 32 ] [ 33 ]  Human and gorilla hemoglobin differ in one amino acid in both alpha and beta chains, and these differences grow larger between less closely related species. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2599", "contents": "Mutations  in the genes for hemoglobin can result in  variants of hemoglobin  within a single species, although one sequence is usually \"most common\" in each species. [ 34 ] [ 35 ]  Many of these mutations cause no disease, but some cause a group of  hereditary diseases  called  hemoglobinopathies . The best known hemoglobinopathy is  sickle-cell disease , which was the first human disease whose  mechanism  was understood at the molecular level. A mostly separate set of diseases called  thalassemias  involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin  gene regulation . All these diseases produce  anemia . [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2600", "contents": "Variations in hemoglobin sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to the thin air at high altitudes, where lower partial pressure of oxygen diminishes its binding to hemoglobin compared to the higher pressures at sea level. Recent studies of deer mice found mutations in four genes that can account for differences between high- and low-elevation populations. It was found that the genes of the two breeds are \"virtually identical\u2014except for those that govern the oxygen-carrying capacity of their hemoglobin. . . . The genetic difference enables highland mice to make more efficient use of their oxygen.\" [ 37 ]   Mammoth  hemoglobin featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during the  Pleistocene . [ 38 ]  This was also found in hummingbirds that inhabit the Andes. Hummingbirds already expend a lot of energy and thus have high oxygen demands and yet Andean hummingbirds have been found to thrive in high altitudes. Non-synonymous mutations in the hemoglobin gene of multiple species living at high elevations ( Oreotrochilus, A. castelnaudii, C. violifer, P. gigas,  and  A. viridicuada ) have caused the protein to have less of an affinity for  inositol hexaphosphate  (IHP), a molecule found in birds that has a similar role as 2,3-BPG in humans; this results in the ability to bind oxygen in lower partial pressures. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2601", "contents": "Birds' unique  circulatory lungs  also promote efficient use of oxygen at low partial pressures of O 2 . These two adaptations reinforce each other and account for birds' remarkable high-altitude performance. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2602", "contents": "Hemoglobin adaptation extends to humans, as well. There is a higher offspring survival rate among Tibetan women with high oxygen saturation genotypes residing at 4,000 m. [ 40 ]  Natural selection seems to be the main force working on this gene because the mortality rate of offspring is significantly lower for women with higher hemoglobin-oxygen affinity when compared to the mortality rate of offspring from women with low hemoglobin-oxygen affinity. While the exact genotype and mechanism by which this occurs is not yet clear, selection is acting on these women's ability to bind oxygen in low partial pressures, which overall allows them to better sustain crucial metabolic processes. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2603", "contents": "Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the  mitochondria  and the  cytosol  of immature red blood cells, while the  globin  protein parts are synthesized by  ribosomes  in the cytosol. [ 41 ]  Production of Hb continues in the cell throughout its early development from the  proerythroblast  to the  reticulocyte  in the  bone marrow . At this point, the  nucleus  is lost in mammalian red blood cells, but not in  birds  and many other species. Even after the loss of the nucleus in mammals, residual  ribosomal RNA  allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering the  vasculature  (this hemoglobin-synthetic RNA in fact gives the reticulocyte its reticulated appearance and name). [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2604", "contents": "Hemoglobin has a  quaternary structure  characteristic of many multi-subunit globular proteins. [ 43 ]  Most of the amino acids in hemoglobin form  alpha helices , and these helices are connected by short non-helical segments. Hydrogen bonds stabilize the helical sections inside this protein, causing attractions within the molecule, which then causes each polypeptide chain to fold into a specific shape. [ 44 ]  Hemoglobin's quaternary structure comes from its four subunits in roughly a tetrahedral arrangement. [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2605", "contents": "In most vertebrates, the hemoglobin  molecule  is an assembly of four  globular protein  subunits. Each subunit is composed of a protein chain tightly associated with a non-protein  prosthetic   heme  group. Each protein chain arranges into a set of  alpha-helix  structural segments connected together in a  globin fold  arrangement. Such a name is given because this arrangement is the same folding motif used in other heme/globin proteins such as  myoglobin . [ 45 ] [ 46 ]  This folding pattern contains a pocket that strongly binds the heme group. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2606", "contents": "A heme group consists of an iron (Fe)  ion  held in a  heterocyclic  ring, known as a  porphyrin . This porphyrin ring consists of four  pyrrole  molecules cyclically linked together (by  methine  bridges) with the iron ion bound in the center. [ 47 ]  The iron ion, which is the site of oxygen binding, coordinates with the four  nitrogen  atoms in the center of the ring, which all lie in one plane. The heme is bound strongly (covalently) to the globular protein via the N atoms of the  imidazole  ring of F8  histidine  residue (also known as the proximal histidine) below the porphyrin ring. A sixth position can reversibly bind oxygen by a  coordinate covalent bond , [ 48 ]  completing the octahedral group of six ligands. This reversible bonding with oxygen is why hemoglobin is so useful for transporting oxygen around the body. [ 49 ]  Oxygen binds in an \"end-on bent\" geometry where one oxygen atom binds to Fe and the other protrudes at an angle. When oxygen is not bound, a very weakly bonded water molecule fills the site, forming a distorted  octahedron ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2607", "contents": "Even though carbon dioxide is carried by hemoglobin, it does not compete with oxygen for the iron-binding positions but is bound to the amine groups of the protein chains attached to the heme groups."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2608", "contents": "The iron ion may be either in the  ferrous Fe 2+  or in the  ferric Fe 3+  state, but ferrihemoglobin ( methemoglobin ) (Fe 3+ ) cannot bind oxygen. [ 50 ]  In binding, oxygen temporarily and reversibly oxidizes (Fe 2+ ) to (Fe 3+ ) while oxygen temporarily turns into the  superoxide  ion, thus iron must exist in the +2 oxidation state to bind oxygen. If superoxide ion associated to Fe 3+  is protonated, the hemoglobin iron will remain oxidized and incapable of binding oxygen. In such cases, the enzyme  methemoglobin reductase  will be able to eventually reactivate methemoglobin by reducing the iron center."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2609", "contents": "In adult humans, the most common hemoglobin type is a  tetramer  (which contains four subunit proteins) called  hemoglobin A , consisting of two \u03b1 and two \u03b2 subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively. This is denoted as \u03b1 2 \u03b2 2 . The subunits are structurally similar and about the same size. Each subunit has a molecular weight of about 16,000\u00a0 daltons , [ 51 ]  for a total  molecular weight  of the tetramer of about 64,000\u00a0daltons (64,458 g/mol). [ 52 ]  Thus, 1 g/dL=0.1551\u00a0mmol/L. Hemoglobin A is the most intensively studied of the hemoglobin molecules. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2610", "contents": "In human infants, the  fetal hemoglobin  molecule is made up of 2 \u03b1 chains and 2 \u03b3 chains. The \u03b3 chains are gradually replaced by \u03b2 chains as the infant grows. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2611", "contents": "The four  polypeptide chains  are bound to each other by  salt bridges ,  hydrogen bonds , and the  hydrophobic effect ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2612", "contents": "In general, hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with oxygen molecules (deoxyhemoglobin). [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2613", "contents": "Oxyhemoglobin  is formed during  physiological respiration  when oxygen binds to the heme component of the protein hemoglobin in red blood cells. This process occurs in the  pulmonary capillaries  adjacent to the  alveoli  of the lungs. The oxygen then travels through the blood stream to be dropped off at cells where it is utilized as a terminal electron acceptor in the production of  ATP  by the process of  oxidative phosphorylation . It does not, however, help to counteract a decrease in blood pH.  Ventilation , or breathing, may reverse this condition by removal of  carbon dioxide , thus causing a shift up in pH. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2614", "contents": "Hemoglobin exists in two forms, a  taut (tense) form  (T) and a  relaxed form  (R). Various factors such as low pH, high CO 2  and high  2,3 BPG  at the level of the tissues favor the taut form, which has low oxygen affinity and releases oxygen in the tissues. Conversely, a high pH, low CO 2 , or low 2,3 BPG favors the relaxed form, which can better bind oxygen. [ 56 ]  The partial pressure of the system also affects O 2  affinity where, at high partial pressures of oxygen (such as those present in the alveoli), the relaxed (high affinity, R) state is favoured. Inversely, at low partial pressures (such as those present in respiring tissues), the (low affinity, T) tense state is favoured. [ 57 ]  Additionally, the binding of oxygen to the iron(II) heme pulls the iron into the plane of the porphyrin ring, causing a slight conformational shift. The shift encourages oxygen to bind to the three remaining heme units within hemoglobin (thus, oxygen binding is cooperative). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2615", "contents": "Classically, the iron in oxyhemoglobin is seen as existing in the iron(II) oxidation state. However, the complex of oxygen with heme iron is  diamagnetic , whereas both oxygen and high-spin iron(II) are  paramagnetic . Experimental evidence strongly suggests heme iron is in the iron(III) oxidation state in oxyhemoglobin, with the oxygen existing as  superoxide anion  (O 2 \u2022\u2212 ) or in a covalent charge-transfer complex. [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2616", "contents": "Deoxygenated hemoglobin (deoxyhemoglobin) is the form of hemoglobin without the bound oxygen. The  absorption spectra  of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of the 660\u00a0nm  wavelength  than deoxyhemoglobin, while at 940\u00a0nm its absorption is slightly higher. This difference is used for the measurement of the amount of oxygen in a patient's blood by an instrument called a  pulse oximeter . This difference also accounts for the presentation of  cyanosis , the blue to purplish color that tissues develop during  hypoxia . [ 59 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2617", "contents": "Deoxygenated hemoglobin is  paramagnetic ; it is weakly attracted to  magnetic fields . [ 60 ] [ 61 ]  In contrast, oxygenated hemoglobin exhibits  diamagnetism , a weak repulsion from a magnetic field. [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2618", "contents": "Scientists agree that the event that separated myoglobin from hemoglobin occurred after  lampreys  diverged from  jawed vertebrates . [ 62 ]  This separation of myoglobin and hemoglobin allowed for the different functions of the two molecules to arise and develop: myoglobin has more to do with oxygen storage while hemoglobin is tasked with oxygen transport. [ 63 ]  The \u03b1- and \u03b2-like globin genes encode the individual subunits of the protein. [ 30 ]  The predecessors of these genes arose through another duplication event also after the gnathosome common ancestor derived from jawless fish, approximately 450\u2013500\u00a0million years ago. [ 62 ]  Ancestral reconstruction studies suggest that the preduplication ancestor of the \u03b1 and \u03b2 genes was a dimer made up of identical globin subunits, which then evolved to assemble into a tetrameric architecture after the duplication. [ 64 ]  The development of \u03b1 and \u03b2 genes created the potential for hemoglobin to be composed of multiple distinct subunits, a physical composition central to hemoglobin's ability to transport oxygen. Having multiple subunits contributes to hemoglobin's ability to bind oxygen cooperatively as well as be regulated allosterically. [ 63 ] [ 64 ]  Subsequently, the \u03b1 gene also underwent a duplication event to form the  HBA1  and  HBA2  genes. [ 65 ]  These further duplications and divergences have created a diverse range of \u03b1- and \u03b2-like globin genes that are regulated so that certain forms occur at different stages of development. [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2619", "contents": "Most ice fish of the family  Channichthyidae  have lost their hemoglobin genes as an adaptation to cold water. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2620", "contents": "When oxygen binds to the iron complex, it causes the iron atom to move back toward the center of the plane of the  porphyrin  ring (see moving diagram). At the same time, the  imidazole  side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in the protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2621", "contents": "As oxygen binds to one monomer of hemoglobin, the tetramer's conformation shifts from the T (tense) state to the R (relaxed) state. This shift promotes the binding of oxygen to the remaining three monomers' heme groups, thus saturating the hemoglobin molecule with oxygen. [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2622", "contents": "In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a  cooperative process . The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first molecules of oxygen bound influencing the shape of the binding sites for the next ones, in a way favorable for binding. This positive cooperative binding is achieved through  steric  conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence, the oxygen binding curve of hemoglobin is  sigmoidal , or  S -shaped, as opposed to the normal  hyperbolic  curve associated with noncooperative binding."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2623", "contents": "The dynamic mechanism of the cooperativity in hemoglobin and its relation with low-frequency  resonance  has been discussed. [ 67 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2624", "contents": "Besides the oxygen  ligand , which binds to hemoglobin in a cooperative manner, hemoglobin ligands also include  competitive inhibitors  such as  carbon monoxide  (CO) and  allosteric ligands  such as carbon dioxide (CO 2 ) and  nitric oxide  (NO). The carbon dioxide is bound to amino groups of the globin proteins to form  carbaminohemoglobin ; this mechanism is thought to account for about 10% of carbon dioxide transport in mammals.  Nitric oxide  can also be transported by hemoglobin; it is bound to specific  thiol  groups in the globin protein to form an S-nitrosothiol, which dissociates into free nitric oxide and thiol again, as the hemoglobin releases oxygen from its heme site. This nitric oxide transport to peripheral tissues is hypothesized to assist oxygen transport in tissues, by releasing  vasodilatory  nitric oxide to tissues in which oxygen levels are low. [ 68 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2625", "contents": "The binding of oxygen is affected by molecules such as carbon monoxide (for example, from  tobacco smoking ,  exhaust gas , and incomplete combustion in furnaces). CO competes with oxygen at the heme binding site. Hemoglobin's binding affinity for CO is 250 times greater than its affinity for oxygen, [ 69 ] [ 70 ]  Since carbon monoxide is a colorless, odorless and tasteless gas, and poses a potentially fatal threat,  carbon monoxide detectors  have become commercially available to warn of dangerous levels in residences. When hemoglobin combines with CO, it forms a very bright red compound called  carboxyhemoglobin , which may cause the skin of  CO poisoning  victims to appear pink in death, instead of white or blue. When inspired air contains CO levels as low as 0.02%,  headache  and  nausea  occur; if the CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2626", "contents": "In similar fashion, hemoglobin also has competitive binding affinity for  cyanide  (CN \u2212 ),  sulfur monoxide  (SO), and  sulfide  (S 2\u2212 ), including  hydrogen sulfide  (H 2 S). All of these bind to iron in heme without changing its oxidation state, but they nevertheless inhibit oxygen-binding, causing grave toxicity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2627", "contents": "The iron atom in the heme group must initially be in the  ferrous  (Fe 2+ ) oxidation state to support oxygen and other gases' binding and transport (it temporarily switches to ferric during the time oxygen is bound, as explained above). Initial oxidation to the  ferric  (Fe 3+ ) state without oxygen converts hemoglobin into \"hem i globin\" or  methemoglobin , which cannot bind oxygen. Hemoglobin in normal red blood cells is protected by a reduction system to keep this from happening. Nitric oxide is capable of converting a small fraction of hemoglobin to methemoglobin in red blood cells. The latter reaction is a remnant activity of the more ancient  nitric oxide dioxygenase  function of globins."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2628", "contents": "Carbon  di oxide occupies a different binding site on the hemoglobin. At tissues, where carbon dioxide concentration is higher, carbon dioxide binds to allosteric site of hemoglobin, facilitating unloading of oxygen from hemoglobin and ultimately its removal from the body after the oxygen has been released to tissues undergoing metabolism. This increased affinity for carbon dioxide by the venous blood is known as the  Bohr effect . Through the enzyme  carbonic anhydrase , carbon dioxide reacts with water to give  carbonic acid , which decomposes into  bicarbonate  and  protons :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2629", "contents": "Hence, blood with high carbon dioxide levels is also lower in  pH  (more  acidic ). Hemoglobin can bind protons and carbon dioxide, which causes a conformational change in the protein and facilitates the release of oxygen. Protons bind at various places on the protein, while carbon dioxide binds at the \u03b1-amino group. [ 71 ]  Carbon dioxide binds to hemoglobin and forms  carbaminohemoglobin . [ 72 ]  This decrease in hemoglobin's affinity for oxygen by the binding of carbon dioxide and acid is known as the  Bohr effect . The Bohr effect favors the T state rather than the R state. (shifts the O 2 -saturation curve to the  right ). Conversely, when the carbon dioxide levels in the blood decrease (i.e., in the lung capillaries), carbon dioxide and protons are released from hemoglobin, increasing the oxygen affinity of the protein. A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH is called the  root effect . This is seen in bony fish."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2630", "contents": "It is necessary for hemoglobin to release the oxygen that it binds; if not, there is no point in binding it. The sigmoidal curve of hemoglobin makes it efficient in binding (taking up O 2  in lungs), and efficient in unloading (unloading O 2  in tissues). [ 73 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2631", "contents": "In people acclimated to high altitudes, the concentration of  2,3-Bisphosphoglycerate  (2,3-BPG) in the blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower  oxygen tension . This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a  heterotropic  allosteric effect. Hemoglobin in organisms at high altitudes has also adapted such that it has less of an affinity for 2,3-BPG and so the protein will be shifted more towards its R state. In its R state, hemoglobin will bind oxygen more readily, thus allowing organisms to perform the necessary metabolic processes when oxygen is present at low partial pressures. [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2632", "contents": "Animals other than humans use different molecules to bind to hemoglobin and change its O 2  affinity under unfavorable conditions. Fish use both  ATP  and  GTP . These bind to a phosphate \"pocket\" on the fish hemoglobin molecule, which stabilizes the tense state and therefore decreases oxygen affinity. [ 75 ]  GTP reduces hemoglobin oxygen affinity much more than ATP, which is thought to be due to an extra  hydrogen bond  formed that further stabilizes the tense state. [ 76 ]  Under hypoxic conditions, the concentration of both ATP and GTP is reduced in fish red blood cells to increase oxygen affinity. [ 77 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2633", "contents": "A variant hemoglobin, called  fetal hemoglobin  (HbF, \u03b1 2 \u03b3 2 ), is found in the developing  fetus , and binds oxygen with greater affinity than adult hemoglobin. This means that the oxygen binding curve for fetal hemoglobin is left-shifted (i.e., a higher percentage of hemoglobin has oxygen bound to it at lower oxygen tension), in comparison to that of adult hemoglobin. As a result, fetal blood in the  placenta  is able to take oxygen from maternal blood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2634", "contents": "Hemoglobin also carries  nitric oxide  (NO) in the globin part of the molecule. This improves oxygen delivery in the periphery and contributes to the control of respiration. NO binds reversibly to a specific cysteine residue in globin; the binding depends on the state (R or T) of the hemoglobin. The resulting S-nitrosylated hemoglobin influences various NO-related activities such as the control of vascular resistance, blood pressure and respiration. NO is not released in the cytoplasm of red blood cells but transported out of them by an anion exchanger called  AE1 . [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2635", "contents": "Hemoglobin variants  are a part of the normal  embryonic  and  fetal  development. They may also be pathologic mutant forms of hemoglobin in a  population , caused by variations in genetics. Some well-known hemoglobin variants, such as  sickle-cell anemia , are responsible for diseases and are considered  hemoglobinopathies . Other variants cause no detectable  pathology , and are thus considered non-pathological variants. [ 34 ] [ 79 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2636", "contents": "In  embryos :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2637", "contents": "In fetuses:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2638", "contents": "In  neonates  (newborns inmmediately after birth):"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2639", "contents": "Abnormal forms that occur in diseases:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2640", "contents": "When  red blood cells  reach the end of their life due to aging or defects, they are removed from the circulation by the phagocytic activity of macrophages in the spleen or the liver or hemolyze within the circulation.  Free hemoglobin  is then cleared from the circulation via the hemoglobin transporter  CD163 , which is exclusively expressed on monocytes or macrophages. Within these cells the hemoglobin molecule is broken up, and the iron gets recycled. This process also produces one molecule of carbon monoxide for every molecule of heme degraded. [ 80 ]  Heme degradation is the only natural source of carbon monoxide in the human body, and is responsible for the normal blood levels of carbon monoxide in people breathing normal air. [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2641", "contents": "The other major final product of heme degradation is  bilirubin . Increased levels of this chemical are detected in the blood if red blood cells are being destroyed more rapidly than usual. Improperly degraded hemoglobin protein or hemoglobin that has been released from the blood cells too rapidly can clog small blood vessels, especially the delicate blood filtering vessels of the  kidneys , causing kidney damage. Iron is removed from heme and salvaged for later use, it is stored as hemosiderin or  ferritin  in tissues and transported in plasma by beta globulins as  transferrins . When the porphyrin ring is broken up, the fragments are normally secreted as a yellow pigment called bilirubin, which is secreted into the intestines as bile. Intestines metabolize bilirubin into urobilinogen. Urobilinogen leaves the body in faeces, in a pigment called stercobilin. Globulin is metabolized into amino acids that are then released into circulation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2642", "contents": "Hemoglobin deficiency can be caused either by a decreased amount of hemoglobin molecules, as in  anemia , or by decreased ability of each molecule to bind oxygen at the same partial pressure of oxygen.  Hemoglobinopathies  (genetic defects resulting in abnormal structure of the hemoglobin molecule) [ 82 ]  may cause both. In any case, hemoglobin deficiency decreases  blood oxygen-carrying capacity . Hemoglobin deficiency is, in general, strictly distinguished from  hypoxemia , defined as decreased  partial pressure  of oxygen in blood, [ 83 ] [ 84 ] [ 85 ] [ 86 ]  although both are causes of  hypoxia  (insufficient oxygen supply to tissues)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2643", "contents": "Other common causes of low hemoglobin include loss of blood, nutritional deficiency, bone marrow problems, chemotherapy, kidney failure, or abnormal hemoglobin (such as that of sickle-cell disease)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2644", "contents": "The ability of each hemoglobin molecule to carry oxygen is normally modified by altered blood pH or CO 2 , causing an altered  oxygen\u2013hemoglobin dissociation curve . However, it can also be pathologically altered in, e.g.,  carbon monoxide poisoning ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2645", "contents": "Decrease of hemoglobin, with or without an absolute decrease of red blood cells, leads to symptoms of anemia. Anemia has many different causes, although  iron deficiency  and its resultant  iron deficiency anemia  are the most common causes in the Western world. As absence of iron decreases heme synthesis, red blood cells in iron deficiency anemia are  hypochromic  (lacking the red hemoglobin pigment) and  microcytic  (smaller than normal). Other anemias are rarer. In  hemolysis  (accelerated breakdown of red blood cells), associated  jaundice  is caused by the hemoglobin metabolite bilirubin, and the circulating hemoglobin can cause  kidney failure ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2646", "contents": "Some mutations in the globin chain are associated with the  hemoglobinopathies , such as sickle-cell disease and  thalassemia . Other mutations, as discussed at the beginning of the article, are benign and are referred to merely as  hemoglobin variants ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2647", "contents": "There is a group of genetic disorders, known as the  porphyrias  that are characterized by errors in metabolic pathways of heme synthesis. King  George III of the United Kingdom  was probably the most famous porphyria sufferer."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2648", "contents": "To a small extent, hemoglobin A slowly combines with  glucose  at the terminal valine (an alpha aminoacid) of each \u03b2 chain. The resulting molecule is often referred to as  Hb A 1c , a  glycated hemoglobin . The binding of glucose to amino acids in the hemoglobin takes place spontaneously (without the help of an enzyme) in many proteins, and is not known to serve a useful purpose. However, as the concentration of glucose in the blood increases, the percentage of Hb A that turns into Hb A 1c  increases. In  diabetics  whose glucose usually runs high, the percent Hb A 1c  also runs high. Because of the slow rate of Hb A combination with glucose, the Hb A 1c  percentage reflects a weighted average of blood glucose levels over the lifetime of red cells, which is approximately 120 days. [ 87 ]  The levels of glycated hemoglobin are therefore measured in order to monitor the long-term control of the chronic disease of type 2 diabetes mellitus (T2DM). Poor control of T2DM results in high levels of glycated hemoglobin in the red blood cells. The normal reference range is approximately 4.0\u20135.9%. Though difficult to obtain, values less than 7% are recommended for people with T2DM. Levels greater than 9% are associated with poor control of the glycated hemoglobin, and levels greater than 12% are associated with very poor control. Diabetics who keep their glycated hemoglobin levels close to 7% have a much better chance of avoiding the complications that may accompany diabetes (than those whose levels are 8% or higher). [ 88 ]  In addition, increased glycated of hemoglobin increases its affinity for oxygen, therefore preventing its release at the tissue and inducing a level of hypoxia in extreme cases. [ 89 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2649", "contents": "Elevated levels of hemoglobin are associated with increased numbers or sizes of red blood cells, called  polycythemia . This elevation may be caused by  congenital heart disease ,  cor pulmonale ,  pulmonary fibrosis , too much  erythropoietin , or  polycythemia vera . [ 90 ]  High hemoglobin levels may also be caused by exposure to high altitudes, smoking, dehydration (artificially by concentrating Hb), advanced lung disease and certain tumors. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2650", "contents": "Hemoglobin concentration measurement is among the most commonly performed  blood tests , usually as part of a  complete blood count . For example, it is typically tested before or after  blood donation . Results are reported in  g / L , g/ dL  or  mol /L. 1 g/dL equals about 0.6206\u00a0mmol/L, although the latter units are not used as often due to uncertainty regarding the polymeric state of the molecule. [ 91 ]  This conversion factor, using the single globin unit molecular weight of 16,000  Da , is more common for hemoglobin concentration in blood. For MCHC (mean corpuscular hemoglobin concentration) the conversion factor 0.155, which uses the tetramer weight of 64,500 Da, is more common. [ 92 ]  Normal levels are:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2651", "contents": "Normal values of hemoglobin in the 1st and 3rd trimesters of pregnant women must be at least 11 g/dL and at least 10.5 g/dL during the 2nd trimester. [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2652", "contents": "Dehydration or hyperhydration can greatly influence measured hemoglobin levels. Albumin can indicate hydration status."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2653", "contents": "If the concentration is below normal, this is called anemia. Anemias are classified by the size of red blood cells, the cells that contain hemoglobin in vertebrates. The anemia is called \"microcytic\" if red cells are small, \"macrocytic\" if they are large, and \"normocytic\" otherwise."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2654", "contents": "Hematocrit , the proportion of blood volume occupied by red blood cells, is typically about three times the hemoglobin concentration measured in g/dL. For example, if the hemoglobin is measured at 17 g/dL, that compares with a hematocrit of 51%. [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2655", "contents": "Laboratory hemoglobin test methods require a blood sample (arterial, venous, or capillary) and analysis on hematology analyzer and CO-oximeter. Additionally, a new noninvasive hemoglobin (SpHb) test method called Pulse CO-Oximetry is also available with comparable accuracy to invasive methods. [ 97 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2656", "contents": "Concentrations of oxy- and deoxyhemoglobin can be measured continuously, regionally and noninvasively using  NIRS . [ 98 ] [ 99 ] [ 100 ] [ 101 ] [ 102 ]  NIRS can be used both on the head and on muscles. This technique is often used for research in e.g. elite sports training, ergonomics, rehabilitation, patient monitoring, neonatal research, functional brain monitoring,  brain\u2013computer interface , urology (bladder contraction), neurology (Neurovascular coupling) and more."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2657", "contents": "Hemoglobin mass can be measured in humans using the non-radioactive, carbon monoxide (CO) rebreathing technique that has been used for more than 100 years. With this technique, a small volume of pure CO gas is inhaled and rebreathed for a few minutes. During rebreathing, CO binds to hemoglobin present in red blood cells. Based on the increase in blood CO after the rebreathing period, the hemoglobin mass can be determined through the dilution principle. [ 103 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2658", "contents": "Long-term control of  blood sugar  concentration can be measured by the concentration of Hb A 1c . Measuring it directly would require many samples because blood sugar levels vary widely through the day. Hb A 1c  is the product of the  irreversible reaction  of hemoglobin A with glucose. A higher glucose  concentration  results in more Hb A 1c . Because the reaction is slow, the Hb A 1c  proportion represents glucose level in blood averaged over the half-life of red blood cells, is typically ~120 days. An Hb A 1c  proportion of 6.0% or less show good long-term glucose control, while values above 7.0% are elevated. This test is especially useful for diabetics. [ c ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2659", "contents": "The  functional magnetic resonance imaging  (fMRI) machine uses the signal from deoxyhemoglobin, which is sensitive to magnetic fields since it is paramagnetic. Combined measurement with  NIRS  shows good correlation with both the oxy- and deoxyhemoglobin signal compared to the  BOLD signal . [ 104 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2660", "contents": "Hemoglobin can be tracked noninvasively, to build an individual data set tracking the hemoconcentration and hemodilution effects of daily activities for better understanding of sports performance and training. Athletes are often concerned about endurance and intensity of exercise. The sensor uses light-emitting diodes that emit red and infrared light through the tissue to a light detector, which then sends a signal to a processor to calculate the absorption of light by the hemoglobin protein. [ 105 ]  This sensor is similar to a  pulse oximeter , which consists of a small sensing device that clips to the finger."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2661", "contents": "A variety of oxygen-transport and -binding proteins exist in organisms throughout the animal and plant kingdoms. Organisms including  bacteria ,  protozoans , and  fungi  all have hemoglobin-like proteins whose known and predicted roles include the reversible binding of gaseous  ligands . Since many of these proteins contain  globins  and the heme  moiety  (iron in a flat porphyrin support), they are often called hemoglobins, even if their overall tertiary structure is very different from that of vertebrate hemoglobin. In particular, the distinction of \"myoglobin\" and hemoglobin in lower animals is often impossible, because some of these organisms do not contain  muscles . Or, they may have a recognizable separate  circulatory system  but not one that deals with oxygen transport (for example, many  insects  and other  arthropods ). In all these groups, heme/globin-containing molecules (even monomeric globin ones) that deal with gas-binding are referred to as oxyhemoglobins. In addition to dealing with transport and sensing of oxygen, they may also deal with NO, CO 2 , sulfide compounds, and even O 2  scavenging in environments that must be anaerobic. [ 106 ]  They may even deal with detoxification of chlorinated materials in a way analogous to heme-containing P450 enzymes and peroxidases."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2662", "contents": "The structure of hemoglobins varies across species. Hemoglobin occurs in all kingdoms of organisms, but not in all organisms. Primitive species such as bacteria, protozoa,  algae , and  plants  often have single-globin hemoglobins. Many  nematode  worms,  molluscs , and  crustaceans  contain very large multisubunit molecules, much larger than those in vertebrates. In particular, chimeric hemoglobins found in  fungi  and giant  annelids  may contain both globin and other types of proteins. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2663", "contents": "One of the most striking occurrences and uses of hemoglobin in organisms is in the  giant tube worm  ( Riftia pachyptila , also called Vestimentifera), which can reach 2.4 meters length and populates ocean  volcanic vents . Instead of a  digestive tract , these worms contain a population of bacteria constituting half the organism's weight. The bacteria oxidize H 2 S from the vent with O 2  from the water to produce energy to make food from H 2 O and CO 2 . The worms' upper end is a deep-red fan-like structure (\"plume\"), which extends into the water and absorbs H 2 S and O 2  for the bacteria, and CO 2  for use as synthetic raw material similar to photosynthetic plants. The structures are bright red due to their content of several extraordinarily complex hemoglobins that have up to 144 globin chains, each including associated heme structures. These hemoglobins are remarkable for being able to carry oxygen in the presence of sulfide, and even to carry sulfide, without being completely \"poisoned\" or inhibited by it as hemoglobins in most other species are. [ 107 ] [ 108 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2664", "contents": "Some nonerythroid cells (i.e., cells other than the red blood cell line) contain hemoglobin. In the brain, these include the A9  dopaminergic  neurons in the  substantia nigra ,  astrocytes  in the  cerebral cortex  and  hippocampus , and in all mature  oligodendrocytes . [ 12 ]  It has been suggested that brain hemoglobin in these cells may enable the \"storage of oxygen to provide a homeostatic mechanism in anoxic conditions, which is especially important for A9 DA neurons that have an elevated metabolism with a high requirement for energy production\". [ 12 ]  It has been noted further that \"A9  dopaminergic  neurons may be at particular risk of anoxic degeneration since in addition to their high mitochondrial activity they are under intense oxidative stress caused by the production of hydrogen peroxide via autoxidation and/or monoamine oxidase (MAO)-mediated deamination of dopamine and the subsequent reaction of accessible ferrous iron to generate highly toxic hydroxyl radicals\". [ 12 ]  This may explain the risk of degeneration of these cells in  Parkinson's disease . [ 12 ]  The hemoglobin-derived iron in these cells is not the cause of the post-mortem darkness of these cells (origin of the Latin name, substantia  nigra ), but rather is due to  neuromelanin ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2665", "contents": "Outside the brain, hemoglobin has non-oxygen-carrying functions as an  antioxidant  and a regulator of  iron metabolism  in  macrophages , [ 109 ]   alveolar cells , [ 110 ]  and  mesangial cells  in the kidney. [ 111 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2666", "contents": "Historically, an association between the color of blood and rust occurs in the association of the planet  Mars , with the Roman god of war, since the planet is an orange-red, which reminded the ancients of blood. Although the color of the planet is due to iron compounds in combination with oxygen in the Martian soil, it is a common misconception that the iron in hemoglobin and its oxides gives blood its red color. The color is actually due to the  porphyrin   moiety  of hemoglobin to which the iron is bound, not the iron itself, [ 112 ]  although the ligation and redox state of the iron can influence the pi to pi* or n to pi* electronic transitions of the porphyrin and hence its optical characteristics."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2667", "contents": "Artist  Julian Voss-Andreae  created a  sculpture  called  Heart of Steel (Hemoglobin)  in 2005, based on the protein's backbone. The sculpture was made from glass and  weathering steel . The intentional rusting of the initially shiny work of art mirrors hemoglobin's fundamental chemical reaction of oxygen binding to iron. [ 113 ] [ 114 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2668", "contents": "Montreal artist Nicolas Baier created  Lustre (H\u00e9moglobine) , a sculpture in stainless steel that shows the structure of the hemoglobin molecule. It is displayed in the atrium of  McGill University Health Centre 's research centre in Montreal. The sculpture measures about 10 metres \u00d7 10 metres \u00d7 10 metres. [ 115 ] [ 116 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2669", "contents": "Hemoglobin D  ( HbD ) is a  variant of hemoglobin , a protein complex that makes up  red blood cells . Based on the locations of the original identification, it has been known by several names such as  hemoglobin D-Los Angeles ,  hemoglobin D-Punjab , [ 1 ]   D-North Carolina ,  D-Portugal ,  D-Oak Ridge , and  D-Chicago. [ 2 ]  Hemoglobin D-Los Angeles was the first type identified by  Harvey Itano  in 1951, and was subsequently discovered that hemoglobin D-Punjab is the most abundant type that is common in the  Sikhs  of Punjab (of both Pakistan and India) and of Gujarat. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2670", "contents": "Unlike normal adult human hemoglobin ( HbA ) which has  glutamic acid  at its 121 amino acid position, it has  glutamine  instead. [ 4 ]  The single amino acid substitution can cause various  blood diseases , from fatal genetic anemia to mild  hemolytic anemia , an abnormal destruction of red blood cells. [ 5 ]  Depending on the type of genetic inheritance, it can produce four different conditions: [ 4 ]  heterozygous (inherited in only one of the chromosome 11) HbD trait, HbD- thalassemia , HbS-D ( sickle cell ) disease, and, very rarely, homozygous (inherited in both chromosome 11) HbD disease. [ 6 ]  It is the fourth hemoglobin type discovered after HbA, HbC and HbS; [ 1 ]  the third hemoglobin variant identified after HbC and HbS; [ 2 ]  and the fourth most common hemoglobin variant after HbC, HbS, and HbO. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2671", "contents": "Hemoglobin was discovered as some sort of crystal formed from earthworm body fluid and animal blood by German biochemist Friedrich Ludwig H\u00fcnefeld at  Leipzig University  in 1840. [ 7 ] [ 8 ]  When the protein nature was established another German  Felix Hoppe-Seyler  gave the name hemoglobin (literally \"blood protein\") in 1864. [ 9 ] [ 10 ]  Its role as an oxygen transporter was later established. [ 1 ]  While studying  sickle cell disease ,  Linus Pauling  and  Harvey Itano  at the  California Institute of Technology  discovered in 1949 that the disease was due to abnormal hemoglobin, later called hemoglobin S (HbS). [ 11 ] [ 12 ]  In 1950, Itano and  James V. Neel  discovered a slightly different case in which individuals had sickled red blood cells but not anemia. [ 13 ] [ 14 ]  The hemoglobin was named hemoglobin III, [ 15 ]  but later known as hemoglobin C (HbC). [ 16 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2672", "contents": "In 1934, Jean V. Cooke and J. Keller Mack, pediatricians at St. Louis, USA, reported a case of white American family which had some member suffering from sickle cell anemia. [ 18 ] [ 19 ]  Of six siblings, two children had anemia, while others, including their parents, were healthy. Blood tests indicated the two children had sickled red blood cells, but with uncharacteristically slow process of sickling. The father, who had no disease, was found to have sickled re blood cells. [ 18 ]  With the new techniques for identifying different hemoglobin, Itano investigated the family and found that like their father, three other children had abnormal hemoglobin but without the disease or sickled cells; their hemoglobin giving same mobility (in  electrophoresis ) and but different solubility as sickled cells. He recorded in 1951:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2673", "contents": "The resent report deals with the identification of still another form of human hemoglobin in five members of a family in which the genetic picture is not typical of sickle cell anemia, although two of the members have in the past been diagnosed as having sickle cell anemia. An earlier study of this family disclosed that the two anemic children and the father, who was not anemic, had sickling erythrocytes while the mother, two sisters and two brothers of the anemic children had non-sickling erythrocytes and were not anemic. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2674", "contents": "In the paper published in the  Proceedings of the National Academy of Sciences of the United States of America , Itano presented the need to have naming convention for the different types of hemoglobin, and introduced the alphabet-coding system such as hemoglobin  a  (for normal adult type),  b  (sickle cell type),  c  (sickle cell-associated type) and  d  (for the novel type); as he explained:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2675", "contents": "In order to facilitate the discussion in the present paper and to avoid confusion in future works, it seems desirable at this time to establish a system of symbols for identifying the various forms of adult human hemoglobin... normal hemoglobin, sickle cell hemoglobin, the abnormal hemoglobin reported by Itano and Neel, and the abnormal hemoglobin reported in the present paper will be designated adult human hemoglobins a, b, c and d, respectively, more briefly as hemoglobins a, b, c and d. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2676", "contents": "It was the discovery of hemoglobin D and creation of hemoglobin naming system. [ 3 ]  In 1953, Amoz Immanuel Chernoff at the Washington University School of Medicine, St. Louis, introduced the capitalised-letter designation such as A (for normal adult type), C (second abnormal type), D (third abnormal type), S (sickle cell type) and F (fetal form). [ 21 ]  Although the nomeclature system became a convention, hemoglobin D, in particular, became known by various names, generally based on their origin of identification; like hemoglobin D-Los Angeles for the first discovered, [ 19 ]  hemoglobin D-Punjab, [ 1 ]  D-North Carolina, D-Portugal, D-Oak Ridge, and D-Chicago. [ 2 ]  By 1961, it was known that the structural difference of HbD from HbA was in the \u03b2-chain. [ 22 ]  Around the same time, Corrado Baglioni of Massachusetts Institute of Technology identified the exact abnormality that substitution of glutamic acid with glutamine at position 121 in the \u03b2-chain was the basis of HbD, the findings which he reported in 1962. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2677", "contents": "Hemoglobin D has the basic structure and composition of normal adult hemoglobin. It is a globular protein containing  prosthetic  (non-protein) group called heme. There are four individual peptide chains, namely two \u03b1- and two \u03b2-subunits, each made of 141 and 146 amino acid residues, respectively. One heme is associated with each chain and responsible for binding free oxygen in the blood. A single HbD is therefore a  tetramer  (containing four molecules), denoted as \u03b1 2 \u03b2 2 . [ 24 ]  Each subunit has a molecular weight of about 16,000 Da ( daltons ), making the tetramer about 64,000 Da (64,458 g/mol) in size. [ 25 ]  HbD is different from HbA only on the \u03b2-subunit where the amino acid glutamic acid at 121 position is replaced with glutamine (\u03b1 2 \u03b2 2 121Glu\u2192Gln ). [ 4 ]  It has the same chemical characteristic as HbS (a hemoglobin of sickle cell trait), with one fewer negative charge at an alkaline pH than HbA. However, unlike HbS, it does not produce sickled RBC on its own under low level of oxygen. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2678", "contents": "Hemoglobin D is synthesised due to mutation in  HBB , the gene that produces \u03b2-subunits of hemoglobin and is present on human chromosome 11. A point mutation in the first base of the 121 codon that normally has GAA sequence for normal hemoglobin is changed to CAA. [ 26 ] [ 27 ]  GAA codes for glutamic acid, while CAA for glutamine. [ 28 ]  This gene mutation makes HbD, which can further give rise to several genetic and disease conditions. The specific mutations can occur at different sites of the gene. According to the Globin Gene Server database, there are other types of HbD such as HbD-Agri ( HBB :c.29C\u2192A;364G\u2192C), HbD-Bushman ( HBB :c.49G\u2192C), HbD-Ouled Rabah ( HBB :c.60C\u2192A or 60C\u2192G), HbD-Iran ( HBB :c.67G\u2192C), HbD-Granada ( HBB :c.68A\u2192T), HbD-Ibadan ( HBB :c.263C\u2192A) and HbD-Neath ( HBB :c.365A\u2192C). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2679", "contents": "Depending on the nature of inheritance of HbD mutation there are four conditions, some of which can be deadly diseases: [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2680", "contents": "Hemoglobin in combination with normal hemoglobin (heterozygous HBD/HbA) is asymptomatic, causing no effects. Individuals have normal hemoglobin level and their red blood cells are normal spherical structure. [ 29 ]  Homozygous HbD/HbD causes mild hemolytic anemia and chronic non-progressive  splenomegaly  (enlargement of  spleen ). [ 4 ]  Heterozygous HbD/HbS causes sickle cell anemia. However, most cases of the disease are milder than the usual HbS/HbS conditions. The most serious complication noted is stroke. HbD-thalassemia causes microcytic anemia which is generally milder that in typical thalassemia. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2681", "contents": "As hemoglobin can be inherited in several conditions, no single diagnostic test can confirm the specific protein completely. Electrophoresis is one of the most commonly used and requires sequential identification with other hemoglobins. All hemoglobins can be separated in cellulose acetate at pH 8.6 and in agarose gel at pH 6.2. In alkaline medium of cellulose acetate, HbD moves slower and can be identified at shorter distance than HbA, but it migrates exactly as HbS. It can be differentiated from HbS in acidic agarose gel in which it moves faster and farther than HbS, but at the same level with HbA. [ 30 ] [ 31 ]   High-performance liquid chromatography  (HPLC) can directly detect the protein, but its specific identification of HbD from other hemoglobins can be inconclusive. [ 32 ]  HPLC coupled with  mass spectrometry  (HPLC-ESI-MS/MS) can accurately detect the protein but the procedure is costly and time consuming. [ 33 ]  Genetic screening can be done with  polymerase chain reaction  that can identify HbS from other hemoglobin variants. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2682", "contents": "Hemoglobin D conditions such as homozygous and HbD/HbA heterozygous do not require medical intervention. HbD/HbS and HbD-thalassemia conditions are managed like the typical cases of sickle cell anemia and thalassemia. [ 29 ]  In case of sickle cell anemia, daily treatment with  penicillin  recommended up to five years of age. [ 35 ]  Dietary supplementation of  folic acid  is recommended by the  WHO . [ 36 ]  In 2019,  Crizanlizumab , a monoclonal antibody was approved by the United States FDA for reducing the frequency of blood vessel blockage in 16 years and older individuals. [ 37 ]  For thalassemia, regular lifelong  blood transfusions  is the usual treatment.  Bone marrow transplants  can be curative for some children. [ 38 ]  Medications like  deferoxamine ,  deferiprone  and  luspatercept . [ 39 ]   Gene therapy ,  exagamglogene autotemcel  is approved for medical use in the United Kingdom since November 2023. [ 40 ] [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2683", "contents": "Hemoglobin D is most abundant among Sikhs, with occurrence of 2% in Punjab and 1% in Gujarat. It is also found in small number of individuals among Africans, Americans and Europeans who usually had close ethnicity with Indians in the past. [ 5 ]  It is below 2% among the African-Americans. [ 4 ]  Combination with \u03b2-thalassemia and HbS are known in south and east India; the first resulting in thalassemia and the latter in sickle cell anemia. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2684", "contents": "There is also high occurrence in China, with prevalence rate of 12.5% in  Chongqing . [ 42 ]  It is sporadically recorded in some Turkish, Algerian, West African, Saudi Arabian, native American, English, and Irish population. [ 29 ]  Rare conditions like HbD/HbJ, [ 43 ]  HbD/ HbQ, [ 44 ]  and HbD/Hb Fontainebleau [ 45 ]  are also found in India. A rare case of HbS/HbD is reported from Pakistan in which individuals are diagnosed with bone infection ( osteomyelitis ). [ 31 ]  An isolated condition of HbD/HbC is recorded in US. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2685", "contents": "Hemoglobin  is a protein that transports oxygen in the blood. Genetic differences lead to structural variants in the hemoglobin protein structure. Some variants can cause disease while others have little to no effect."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2686", "contents": "The normal hemoglobin types are Hemoglobin A (HbA), which makes up 95\u201398% of total hemoglobin in adults, Hemoglobin A2 (HbA2), which constitutes 2\u20133% of total hemoglobin in adults, and Hemoglobin F (HbF), which is the predominant hemoglobin in the fetus during pregnancy, and may persist in small amounts in adults. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2687", "contents": "Hemoglobin variants occur when there are mutations in specific genes that code for the protein chains, known as globins, which make up the hemoglobin molecule. This leads to  amino acid   substitutions  in the hemoglobin molecule that could affect the structure, properties, and/or the stability of the hemoglobin molecule. There are over 1,000 naturally occurring structural variants of  hemoglobin  in humans. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2688", "contents": "The physiological effects of these variants can range from minor to severe. [ 3 ]  Mutations can caused impaired production of hemoglobin ( thalassemia ) or produce structurally altered hemoglobins. Some hemoglobin variants, such as HbS which causes  sickle-cell anemia , are responsible for severe diseases and are considered  hemoglobinopathies . Other variants cause no detectable  pathology , and are thus considered non-pathological variants. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2689", "contents": "Hemoglobin variants can be discovered through examination, routine laboratory testing, or evaluation of patients with severe anemia. [ 3 ]  In some countries, all newborns are tested for hemoglobinopathies, thalassemias, and HbS.  Isoelectric focusing  or  high-performance liquid chromatography  are used to identify structural abnormalities in hemoglobin."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2690", "contents": "There are in excess of 1,000 known hemoglobin variants. [ 2 ]  A research database of hemoglobin variants is maintained by  Penn State University . [ 6 ]  A few of these variants are listed below."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2691", "contents": "The  Hering\u2013Breuer inflation reflex , named for  Josef Breuer  and  Ewald Hering , [ 1 ] [ 2 ] [ 3 ]  is a  reflex  triggered to prevent the over-inflation of the  lung .  Pulmonary stretch receptors  present on the wall of bronchi and bronchioles of the airways respond to excessive stretching of the lung during large  inspirations . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2692", "contents": "Once activated, they send  action potentials  through large  myelinated  fibers [ 5 ]  of the  vagus nerve  to the inspiratory area in the medulla and  apneustic center  of the  pons .  In response, the inspiratory area is inhibited directly and the  apneustic center  is inhibited from activating the inspiratory area. This inhibits inspiration, allowing expiration to occur. [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2693", "contents": "The Hering\u2013Breuer inflation reflex should not be confused with the deflation reflex discovered by the same individuals, Hering and Breuer.  The majority of this page discusses the  inflation  reflex; the deflation reflex is considered separately at the end."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2694", "contents": "Josef Breuer and Ewald Hering reported in 1868 that a maintained distention of the lungs of anesthetized animals decreased the frequency of the inspiratory effort or caused a transient apnea. The stimulus was therefore pulmonary inflation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2695", "contents": "The Hering-Breuer reflex, put simply, is what keeps the lungs from over-inflating with inspired air. The neural circuit that controls the Hering\u2013Breuer inflation reflex involves several regions of the  central nervous system , and both sensory and motor components of the  vagus nerve ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2696", "contents": "Increased sensory activity of the pulmonary-stretch lung afferents (via the vagus nerve) results in inhibition of the central inspiratory drive and thus inhibition of inspiration and initiation of expiration. The lung afferents also send inhibitory projections to the cardiac vagal motor neurones (CVM) in the nucleus ambiguus (NA) and dorsal motor vagal nucleus (DMVN). The CVMs, which send motor fibers to the  heart  via the vagus nerve, are responsible for tonic inhibitory control of  heart rate . Thus, an increase in pulmonary stretch receptor activity leads to inhibition of the CVMs and an elevation of heart rate ( tachycardia ). This is a normal occurrence in healthy individuals and is known as  sinus arrhythmia ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2697", "contents": "Early physiologists believed the reflex plays a major role in establishing the rate and depth of breathing in humans. [ 5 ]  While this may be true for most animals, it is not the case for most adult humans at rest. [ 5 ]  However, the reflex may determine breathing rate and depth in newborns and in adult humans when  tidal volume  is more than 1 L, as when exercising. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2698", "contents": "The Hering\u2013Breuer deflation reflex serves to shorten exhalation when the lung is deflated. [ 8 ]   It is initiated either by stimulation of stretch receptors or stimulation of proprioceptors activated by lung deflation.  Like the inflation reflex, impulses from these receptors travel afferently via the vagus.  Unlike the inflation reflex, the afferents terminate on inspiratory centers rather than the pontine apneustic center.  These reflexes appear to play a more minor role in humans than in non-human mammals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2699", "contents": "The absence of this reflex contributes to the diagnosis of brain death."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2700", "contents": "High-altitude adaptation in humans  is an instance of  evolutionary modification  in certain human populations, including those of  Tibet  in Asia, the  Andes  of the Americas, and  Ethiopia  in Africa, who have acquired the ability to survive at  altitudes  above 2,500 meters (8,200 ft). [ 1 ]  This adaptation means irreversible,  long-term physiological responses  to high-altitude environments associated with heritable  behavioral  and  genetic changes . While the rest of the human population would suffer serious health consequences at high altitudes, the indigenous inhabitants of these regions thrive in the highest parts of the world. These humans have undergone extensive physiological and genetic changes, particularly in the regulatory systems of oxygen  respiration  and blood  circulation  when compared to the general lowland population. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2701", "contents": "Around 81.6 million humans (approximately 1.1% of the world's human population) live permanently at  altitudes  above 2,500 meters (8,200 ft), [ 4 ]  which would seem to put these populations at risk for  chronic mountain sickness (CMS) . [ 1 ]  However, the high-altitude populations in South America,  East Africa , and  South Asia  have lived there for  millennia  without apparent complications. [ 5 ]  This special  adaptation  is now recognized as an example of  natural selection  in action. [ 6 ]  The adaptation of the Tibetans is the fastest known example of  human evolution , as it is estimated to have occurred between 1,000 BCE [ 7 ] [ 8 ] [ 9 ]  to 7,000 BCE. [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2702", "contents": "Humans  are generally adapted to  lowland  environments where oxygen is abundant. [ 12 ]  At altitudes above 2,500 meters (8,200\u00a0ft), such humans experience  altitude sickness , which is a type of  hypoxia , a clinical syndrome of severe lack of oxygen. Some humans develop the illness beginning at above 1,500 meters (5,000 ft). [ 13 ]  Symptoms include  fatigue ,  dizziness ,  breathlessness ,  headaches ,  insomnia ,  malaise ,  nausea ,  vomiting ,  body pain ,  loss of appetite ,  ear-ringing ,  blistering  and  purpling of the hands and feet , and  dilated blood vessels . [ 14 ] [ 15 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2703", "contents": "The sickness is compounded by related symptoms such as  cerebral oedema (swelling of brain)   and  pulmonary oedema (fluid accumulation in lungs)  . [ 17 ] [ 18 ]  Over a span of multiple days, individuals experiencing the effects of high-altitude hypoxia demonstrate raised respiratory activity and elevated metabolic conditions which persist during periods of rest. Subsequently, afflicted people will experience slowly declining heart rate. Hypoxia is a primary contributor to fatalities within mountaineering groups, making it a significant risk factor within high-altitude related challenges. [ 19 ] [ 20 ]  In women, pregnancy can be severely affected, such as development of  preeclampsia , which causes  premature labor ,  low birth weight  of babies, and often  complicates  with  profuse bleeding ,  seizures , or  death of the mother . [ 2 ] [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2704", "contents": "An estimated 81.6 million humans live at an elevation higher than 2,500 meters (8,200\u00a0ft) above sea level, of which 21.7 million reside in  Ethiopia , 12.5 million in  China , 11.7 million in  Colombia , 7.8 million in  Peru , and 6.2 million in  Bolivia . [ 4 ]  Certain natives of Tibet, Ethiopia, and the Andes have been living at these high altitudes for generations and are resistant to hypoxia as a consequence of genetic adaptation. [ 5 ] [ 14 ]  It is estimated that at 4,000 meters (13,000\u00a0ft) altitude, every  lungful of air  has approximately 60% of the oxygen molecules found in a lungful of air at sea level. [ 22 ]  Highlanders are thus constantly exposed to a low oxygen environment, yet they live without any debilitating problems. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2705", "contents": "One of the best-documented effects of high altitude on non-adapted women is a progressive reduction in  birth weight . By contrast, the women of long-resident, high-altitude populations are known to give birth to heavier-weight infants than women of the lowland. This is particularly true among Tibetan babies, whose average birth weight is 294\u2013650g (~470) g heavier than the surrounding  Chinese population , and their  blood-oxygen level  is considerably higher. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2706", "contents": "Scientific investigation of high-altitude adaptation was initiated by  A. Roberto Frisancho  of the  University of Michigan  in the late 1960s among the  Quechua people  of Peru. [ 25 ] [ 26 ]   Paul T. Baker  of  Penn State University \u2019s  Department of Anthropology  also conducted a considerable amount of research into human adaptation to high altitudes, and mentored students who continued this research. [ 27 ]  One of these students, anthropologist  Cynthia Beall  of  Case Western Reserve University , began conducting decades-long research on high altitude adaptation among the Tibetans in the early 1980s. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2707", "contents": "Among the different native highlander populations, the underlying physiological responses to adaptation differ. For example, among four quantitative features, such as resting ventilation, hypoxic ventilatory response, oxygen saturation, and hemoglobin concentration, the levels of variations are significantly different between the Tibetans and the  Aymaras . [ 29 ]   Methylation  also influences oxygenation. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2708", "contents": "In the early 20th century, researchers observed the impressive physical abilities of Tibetans during Himalayan climbing expeditions. They considered the possibility that these abilities resulted from an evolutionary genetic adaptation to high-altitude conditions. [ 31 ]  The  Tibetan plateau  has an average elevation of 4,000 meters (13,000\u00a0ft) above sea level and covers more than 2.5 million km 2 ; it is the highest and largest  plateau  in the world. In 1990, it was estimated that 4,594,188 Tibetans live on the plateau, with 53% living at an altitude over 3,500 meters (11,500\u00a0ft). Fairly large numbers (approximately 600,000) live at an altitude exceeding 4,500 meters (14,800\u00a0ft) in the Chantong-Qingnan area. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2709", "contents": "Tibetans who have been living in the Chantong-Qingnan area for 3,000 years do not exhibit the same elevated hemoglobin concentrations to cope with oxygen deficiency that are observed in other populations who have moved temporarily or permanently to high altitudes. Instead, the Tibetans inhale more air with each breath and breathe more rapidly than either sea-level populations or Andeans. Tibetans have better  oxygenation  at birth, enlarged lung volumes throughout life, and a higher capacity for  exercise . They show a sustained increase in  cerebral  blood flow, lower hemoglobin concentration, and less susceptibility to  chronic mountain sickness  than other populations due to their longer history of high-altitude habitation. [ 33 ] [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2710", "contents": "With the proper physical preparation, individuals can develop short-term tolerance to high-altitude conditions. However, these biological changes are temporary and will reverse upon returning to lower elevations. [ 35 ]  Moreover, while lowland people typically experience increased breathing for only a few days after entering high altitudes, Tibetans maintain this rapid breathing and elevated lung capacity throughout their lifetime. [ 36 ]  This enables them to inhale large amounts of air per unit of time to compensate for low oxygen levels. Additionally, Tibetans typically have significantly higher levels of  nitric oxide  in their blood, often double that of lowlanders. This likely contributes to enhanced blood circulation by promoting  vasodilation . [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2711", "contents": "Furthermore, their hemoglobin level is not significantly different (average 15.6\u00a0g/dl in males and 14.2\u00a0g/dl in females) [ 38 ]  from those of humans living at low altitude.  This is evidenced by mountaineers experiencing an increase of over 2 g/dl in hemoglobin levels within two weeks at the Mt. Everest base camp. [ 39 ]  Consequently, Tibetans demonstrate the capacity to mitigate the effects of hypoxia and mountain sickness throughout their lives. Even when ascending extraordinarily high peaks such as Mount Everest, they exhibit consistent oxygen uptake, heightened ventilation, augmented hypoxic ventilatory responses, expanded lung volumes, increased diffusing capacities, stable body weight, and improved sleep quality compared to lowland populations. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2712", "contents": "In contrast to the Tibetans, Andean highlanders show different patterns of hemoglobin adaptation. Their hemoglobin concentration is higher than those of the lowlander population, which also happens to lowlanders who move to high altitudes. When they spend some weeks in the lowlands, their hemoglobin drops to the same levels as lowland humans. However, in contrast to lowland humans, they have increased oxygen levels in their hemoglobin; that is, more oxygen per blood volume. This confers an ability to carry more oxygen in each red blood cell, meaning a more effective transport of oxygen throughout their bodies. [ 36 ]  This enables Andeans to overcome hypoxia and normally reproduce without risk of death for the mother or baby. They have developmentally-acquired enlarged residual lung volume and an associated increase in  alveolar  area, which are supplemented with increased tissue thickness and moderate increase in  red blood cells . Though Andean highlander children show  delayed  body growth, change in lung volume is accelerated. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2713", "contents": "Among the Quechua people of the  Altiplano , there is a significant variation in  NOS3  (the gene encoding  endothelial nitric oxide synthase , eNOS), which is associated with higher levels of nitric oxide at high altitude. [ 42 ]  Nu\u00f1oa children of Quechua ancestry exhibit higher blood-oxygen content (91.3) and lower heart rate (84.8) than their peers of different ethnicities, who have an average of 89.9 blood-oxygen and 88\u201391 heart rate. [ 43 ]  Quechua women have comparatively enlarged lung volume for increased respiration. [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2714", "contents": "Blood profile  comparisons show that among the Andeans,  Aymaran highlanders  are better adapted to highlands than the Quechuas. [ 45 ] [ 46 ]  Among the  Bolivian  Aymara people, the resting ventilation and hypoxic ventilatory response were quite low (roughly 1.5 times lower) compared to those of the Tibetans. The intrapopulation genetic variation was relatively smaller among the Aymara people. [ 47 ] [ 48 ]  Moreover, when compared to Tibetans, blood hemoglobin levels at high altitudes among Aymaran is notably higher, with an average of 19.2\u00a0g/dl for males and 17.8\u00a0g/dl for females. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2715", "contents": "The people of the  Ethiopian highlands  also live at extremely high altitudes, around 3,000 meters (9,800\u00a0ft) to 3,500 meters (11,500\u00a0ft). Highland Ethiopians exhibit elevated hemoglobin levels, like Andeans and lowlander humans at high altitudes, but do not exhibit the Andeans\u2019 increase in oxygen content of hemoglobin. [ 49 ]  Among healthy individuals, the average hemoglobin concentrations are 15.9 and 15.0\u00a0g/dl for males and females, respectively (which is lower than normal, similar to the Tibetans), and an average oxygen saturation of hemoglobin is 95.3% (which is higher than average, like the Andeans). [ 50 ]   Additionally, Ethiopian highlanders do not exhibit any significant change in blood circulation of the brain, which has been observed among the Peruvian highlanders and attributed to their frequent altitude-related illnesses. [ 51 ]  Yet, similar to the Andeans and Tibetans, the Ethiopian highlanders are immune to the extreme dangers posed by high-altitude environment, and their pattern of adaptation is unique from that of other highland people. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2716", "contents": "The underlying  molecular evolution  of high-altitude adaptation has been explored in recent years. [ 23 ]  Depending on geographical and environmental pressures, high-altitude adaptation involves different genetic patterns, some of which have evolved not long ago. For example, Tibetan adaptations became prevalent in the past 3,000 years, an example of rapid  recent human evolution . At the turn of the 21st century, it was reported that the genetic makeup of the respiratory components of the Tibetan and the Ethiopian populations were significantly different. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2717", "contents": "Substantial evidence from Tibetan highlanders suggests that variation in hemoglobin and  blood-oxygen  levels are adaptive as  Darwinian fitness.  It has been documented that Tibetan women with a high likelihood of possessing one to two  alleles  for high blood-oxygen content (which is rare in other women) had more surviving children; the higher the oxygen capacity, the lower the infant mortality. [ 52 ]  In 2010, for the first time, the genes responsible for the unique adaptive traits were identified following genome sequencing of 50 Tibetans and 40  Han Chinese  from  Beijing . Initially, the strongest signal of natural selection was a transcription factor involved in response to hypoxia, called endothelial Per-Arnt-Sim (PAS) domain protein 1 ( EPAS1 ). It was found that one  single-nucleotide polymorphism  (SNP) at  EPAS1  shows a 78% frequency difference between Tibetan and mainland Chinese samples, representing the fastest genetic change observed in any human gene to date. Hence, Tibetan adaptation to high altitude is recognized as one of the fastest processes of  phenotypically observable  evolution in humans, [ 53 ]  which is estimated to have occurred a few thousand years ago, when the Tibetans split from the mainland Chinese population. The time of genetic divergence has been variously estimated as 2,750 (original estimate), [ 9 ]  4,725, [ 11 ]  8,000, [ 54 ]  or 9,000 [ 10 ]  years ago."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2718", "contents": "Mutations  in  EPAS1  occur at a higher frequency in Tibetans than their Han neighbors and correlates with decreased hemoglobin concentrations among the Tibetans. This is known as the hallmark of their adaptation to hypoxia. Simultaneously, two genes, egl nine homolog 1 ( EGLN1 ), which inhibits hemoglobin production under high oxygen concentration, and peroxisome proliferator-activated receptor alpha ( PPARA ), were also identified to be positively selected for decreased hemoglobin levels in the Tibetans. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2719", "contents": "Similarly, the  Sherpas , known for their Himalayan hardiness, exhibit similar patterns in the  EPAS1  gene, which is further evidence that the gene is under  selection  pressure for adaptation to the high-altitude life of Tibetans. [ 56 ]  A study in 2014 indicates that the mutant  EPAS1  gene could have been inherited from archaic  hominins , the  Denisovans . [ 57 ]   EPAS1  and  EGLN1  are believed to be important genes for unique adaptive traits when compared with those of the Chinese and Japanese. [ 58 ]  Comparative genome analysis in 2014 revealed that the Tibetans inherited an equal mixture of genomes from the Nepalese Sherpas and Hans, and that they acquired adaptive genes from the Sherpa lineage. Further, the population split was estimated to occur around 20,000 to 40,000 years ago, a range supported by archaeological, mitochondria DNA, and Y chromosome evidence for an initial colonization of the Tibetan plateau around 30,000 years ago. [ 59 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2720", "contents": "The genes  EPAS1 ,  EGLN1 , and  PPARA  function in concert with another gene named  hypoxia inducible factors  ( HIF ), which is in turn a principal regulator of red blood cell production ( erythropoiesis ) in response to oxygen metabolism. [ 60 ] [ 61 ] [ 62 ]  The genes are associated not only with decreased hemoglobin levels, but also with regulating metabolism.  EPAS1  is significantly associated with increased lactate concentration, a product of  anaerobic glycolysis , and  PPARA  is correlated with decrease in the activity of  fatty acid oxidation . [ 63 ]   EGLN1  codes for an enzyme, prolyl hydroxylase 2 (PHD2), involved in erythropoiesis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2721", "contents": "Among the Tibetans, a mutation in  EGLN1  (specifically at position 12, where cytosine is replaced with guanine; and at 380, where G is replaced with C) results in mutant PHD2 (aspartic acid at position 4 becomes glutamine, and cysteine at 127 becomes serine) and this mutation inhibits erythropoiesis. This mutation is estimated to have occurred approximately 8,000 years ago. [ 64 ]  Further, the Tibetans are enriched for genes in the disease class of human reproduction (such as genes from the  DAZ ,  BPY2 ,  CDY , and  HLA-DQ  and  HLA-DR  gene clusters) and biological process categories of response to  DNA damage  stimulus and  DNA repair  (such as  RAD51 ,  RAD52 , and  MRE11A ), which are related to the adaptive traits of high infant birth weight and  darker skin tone  and are most likely due to recent local adaptation. [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2722", "contents": "The patterns of genetic adaptation among the Andeans are largely distinct from those of the Tibetans, with both populations showing evidence of positive natural selection in different genes or gene regions. For genes in the HIF pathway,  EGLN1  is the only instance where evidence of positive selection is observed in both Tibetans and Andeans. [ 66 ]  Even then, the pattern of variation for this gene differs between the two populations. [ 6 ]  Furthermore, there are no significant associations between  EPAS1  or  EGLN1  SNP  genotypes  and hemoglobin concentration among the Andeans, which is characteristic of the Tibetans. [ 67 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2723", "contents": "The Andean pattern of adaptation is characterized by selection in a number of genes involved in cardiovascular development and function (such as  BRINP3 ,  EDNRA ,  NOS2A ). [ 68 ] [ 69 ]  This suggests that selection in Andeans, instead of targeting the HIF pathway like in the Tibetans, focused on adaptations of the cardiovascular system to combat chronic disease at high altitude. Analysis of ancient Andean genomes, some dating back 7,000 years, discovered selection in  DST , a gene involved in cardiovascular function. [ 70 ]  The whole genome sequences of 20 Andeans (half of them having chronic mountain sickness) revealed that two genes, SENP1 (an erythropoiesis regulator) and ANP32D (an oncogene) play vital roles in their weak adaptation to hypoxia. [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2724", "contents": "The adaptive mechanism of Ethiopian highlanders differs from those of the Tibetans and Andeans due to the fact that their migration to the highland was relatively early. For example, the  Amhara  have inhabited altitudes above 2,500 meters (8,200\u00a0ft) for at least 5,000 years and altitudes around 2,000 meters (6,600\u00a0ft) to 2,400 meters (7,900\u00a0ft) for more than 70,000 years. [ 72 ]  Genomic analysis of two ethnic groups, Amhara and  Oromo , has revealed that gene variations associated with hemoglobin difference among Tibetans or other variants at the exact  gene location  do not influence the adaptation in Ethiopians. [ 73 ]  Several candidate genes have been identified as possible explanations for the adaptation of Ethiopians, including  CBARA1 ,  VAV3 ,  ARNT2  and  THRB . Two of these genes ( THRB  and  ARNT2 ) are known to play a role in the  HIF-1 pathway , a pathway implicated in previous work reported in Tibetan and Andean studies. This supports the hypothesis that adaptation to high altitude arose independently among different highlander populations as a result of  convergent evolution . [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2725", "contents": "Hypoxic pulmonary vasoconstriction  ( HPV ), also known as the  Euler\u2013Liljestrand mechanism , is a  physiological  phenomenon in which small  pulmonary  arteries constrict in the presence of alveolar  hypoxia  (low oxygen levels). By redirecting blood flow from poorly-ventilated lung regions to well-ventilated lung regions, HPV is thought to be the primary mechanism underlying  ventilation/perfusion matching . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2726", "contents": "The process might initially seem counterintuitive, as  low  oxygen levels might theoretically stimulate  increased  blood flow to the lungs to increase gas exchange. However, the purpose of HPV is to distribute bloodflow  regionally  to increase the overall efficiency of gas exchange between air and blood. While the maintenance of  ventilation/perfusion ratio  during  regional  obstruction of airflow is beneficial, HPV can be detrimental during  global  alveolar hypoxia which occurs with exposure to  high altitude , where HPV causes a significant increase in total  pulmonary vascular resistance , and pulmonary arterial pressure, potentially leading to  pulmonary hypertension  and  pulmonary edema ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2727", "contents": "Several factors inhibit HPV including increased  cardiac output ,  hypocapnia ,  hypothermia ,  acidosis / alkalosis , increased pulmonary vascular resistance, inhaled  anesthetics , calcium channel blockers,  positive end-expiratory pressure  (PEEP),  high-frequency ventilation  (HFV),  isoproterenol ,  nitric oxide , and  vasodilators . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2728", "contents": "The classical explanation of HPV involves inhibition of hypoxia-sensitive  voltage-gated potassium channels  in pulmonary artery smooth muscle cells leading to depolarization. [ 3 ] [ 4 ]  This depolarization activates  voltage-dependent calcium channels , which increases intracellular calcium and activates smooth muscle contractile machinery which in turn causes vasoconstriction. However, later studies have reported additional ion channels and mechanisms that contribute to HPV, such as  transient receptor potential canonical 6  (TRPC6) channels, and transient receptor potential vanilloid 4 (TRPV4) channels. [ 5 ] [ 6 ]  Recently it was proposed that hypoxia is sensed at the alveolar/capillary level, generating an electrical signal that is transduced to pulmonary arterioles through  gap junctions  in the pulmonary  endothelium  to cause HPV. [ 7 ]  This contrasts with the classical explanation of HPV which presumes that hypoxia is sensed at the pulmonary artery smooth muscle cell itself. Specialized  epithelial cells  (neuroepithelial bodies) that release serotonin have been suggested to contribute to hypoxic pulmonary venoconstriction. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2729", "contents": "High-altitude mountaineering can induce pulmonary hypoxia due to decreased atmospheric pressure.  This hypoxia causes vasoconstriction that ultimately leads to  high altitude pulmonary edema  (HAPE).  For this reason, some climbers carry supplemental oxygen to prevent hypoxia, edema, and HAPE.  The standard drug treatment of  dexamethasone  does not alter the hypoxia or the consequent vasoconstriction, but stimulates fluid reabsorption in the lungs to reverse the edema. Additionally, several studies on native populations remaining at high altitudes have demonstrated to varying degrees the blunting of the HPV response. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2730", "contents": "Hysteresivity  derives from \u201c hysteresis \u201d, meaning \u201clag\u201d.  It is the tendency to react slowly to an outside force, or to not return completely to its original state.   Whereas the area within a hysteresis loop represents energy dissipated to heat and is an  extensive  quantity with units of energy, the hysteresivity represents the fraction of the elastic energy that is lost to heat, and is an intensive property that is dimensionless."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2731", "contents": "When a force deforms a material it generates  elastic stresses  and  internal frictional stresses .  Most often, frictional stress is described as being analogous to the stress that results from the flow of a  viscous fluid , but in many engineering materials, in soft  biological tissues , and in  living cells , the concept that friction arises only from a viscous stress is now known to be erroneous. [ 1 ] [ 2 ]   For example, Bayliss and Robertson  [ 3 ] \nand Hildebrandt  [ 4 ]  demonstrated that frictional stress in  lung tissue  is dependent upon the amount of lung expansion but not the  rate of expansion , findings that are fundamentally incompatible with the notion of friction being caused by a viscous stress.  If not by a viscous stress, how then does friction arise, and how is it properly described?"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2732", "contents": "In many inert and living materials, the relationship between elastic and frictional stresses turns out to be very nearly  invariant  (something unaltered by a transformation).  In lung tissues, for example, the frictional stress is almost invariably between 0.1 and 0.2 of the elastic stress, where this fraction is called the hysteresivity, h, or, equivalently, the structural damping coefficient. [ 2 ]   It is a simple phenomenological fact, therefore, that for each unit of peak elastic strain energy that is stored during a cyclic deformation, 10 to 20% of that elastic energy is taxed as friction and lost irreversibly to heat.  This fixed relationship holds at the level of the whole lung [ 5 ] \n, [ 6 ] [ 7 ]  isolated lung  parenchymal  tissue strips, [ 8 ]  isolated  smooth muscle  strips, [ 2 ] [ 9 ]  and even isolated living cells. [ 10 ] [ 11 ] [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2733", "contents": "This close relationship between frictional and elastic stresses is called the  structural damping law [ 1 ] [ 2 ] [ 4 ] [ 14 ]  or, sometimes, the  constant phase model . [ 5 ]   The structural damping law implies that frictional losses are coupled tightly to elastic stresses rather than to viscous stresses, but the precise  molecular mechanical origin  of this phenomenon remains unknown. [ 10 ] [ 15 ]  \n'\nIn  material science , the complex elastic modulus of a material,  G *( f'), at frequency of oscillatory deformation  f , is given by,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2734", "contents": "This relationship can be rewritten as,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2735", "contents": "In systems conforming to the structural damping law, the hysteresivity  h  is constant with or insensitive to changes in  oscillatory frequency , and the loss modulus  G \u2032\u2032 (=  hG \u2032) becomes a constant fraction of the elastic modulus."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2736", "contents": "Impulse oscillometry  ( IOS ), also known as  respiratory oscillometry ,  forced oscillatory technique  ( FOT ), or just  oscillometry , is a  non-invasive   lung function test  that measures the  mechanical properties  of the  respiratory system , particularly the  upper  and  intrathoracic airways ,  lung tissue  and  chest wall , usually during the patient's  tidal breathing  (the way someone breathes when they are  relaxed ). [ 1 ] [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2737", "contents": "Impulse oscillometry measures the  mechanical impedance  of the respiratory system ( Z rs ), which encompasses the  resistance  of the respiratory system to flow ( R rs ), the reactance or  stiffness  of the  lung parenchyma  in response to changes in volume ( X rs ) and the  inertance  of accelerating gas in the airways ( I rs ). [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2738", "contents": "The following relations hold between these parameters:  \n \n \n \n \n Z \n \n r \n s \n \n \n = \n \n R \n \n r \n s \n \n \n + \n i \n \n X \n \n r \n s \n \n \n \n \n {\\displaystyle Z_{rs}=R_{rs}+iX_{rs}} \n \n , where  \n \n \n \n i \n \n \n {\\displaystyle i} \n \n  is the  imaginary unit  ( \n \n \n \n \n \n \u2212 \n 1 \n \n \n \n \n {\\displaystyle {\\sqrt {-1}}} \n \n ), and  \n \n \n \n \n X \n \n r \n s \n \n \n = \n \u03c9 \n \n I \n \n r \n s \n \n \n \u2212 \n \n \n \n E \n \n r \n s \n \n \n \u03c9 \n \n \n \n \n {\\displaystyle X_{rs}=\\omega I_{rs}-{\\frac {E_{rs}}{\\omega }}} \n \n , where  \n \n \n \n \n E \n \n r \n s \n \n \n \n \n {\\displaystyle E_{rs}} \n \n  is the airway  elastance  and  \n \n \n \n \u03c9 \n \n \n {\\displaystyle \\omega } \n \n  is the  angular velocity  such that  \n \n \n \n \u03c9 \n = \n 2 \n \u03c0 \n f \n \n \n {\\displaystyle \\omega =2\\pi f} \n \n , where  \n \n \n \n f \n \n \n {\\displaystyle f} \n \n  is the  frequency  of the stimulus oscillation. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2739", "contents": "Z rs  is measured by comparing the magnitudes of mechanical stimuli, specifically oscillations of  pressure , i.e. pressure  waves , transmitted into the respiratory system with the magnitudes of the stimuli's effects on tidal airflow; this is done by superimposing these oscillations over spontaneous tidal breathing. [ 1 ] [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2740", "contents": "The stimulus is an oscillation of pressure of a particular frequency that is transmitted to the lungs of the patient. [ 1 ]  This is usually done by  mouth , though the direct stimulation of the chest wall is also possible. [ 2 ]  These pressure waves cause changes in the airflow during tidal breathing; the magnitudes of the pressure waves and the changes in airflow they cause are then used to determine the airways' mechanical impedance. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2741", "contents": "Frequencies ranging from 4-50  Hz  are commonly generated by a  loudspeaker , while frequencies between 0.5 and 4 Hz may alternatively also be generated by a  piston  or  pneumatic proportional solenoid valves . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2742", "contents": "Different frequencies measure the mechanical properties of different parts of the respiratory system; the resistance at 5 Hz ( R 5 ) represents total airway resistance, while the resistance at 20 Hz ( R 20 ) represents the resistance of the central airways. The reactance at 5 Hz ( X 5 ) reflects the elasticity of the peripheral airways. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2743", "contents": "Inhalation  (or  inspiration ) happens when air or other gases enter the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2744", "contents": "Inhalation of air, as part of the cycle of  breathing , is a vital process for all human life. The process is autonomic (though there are exceptions in some disease states) and does not need conscious  control  or effort. However, breathing can be consciously controlled or interrupted (within limits)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2745", "contents": "Breathing allows oxygen (which humans and a lot of other species need for survival) to enter the lungs, from where it can be absorbed into the bloodstream."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2746", "contents": "Examples of accidental inhalation includes inhalation of water (e.g. in drowning), smoke, food, vomitus and less common foreign substances [ 1 ]  (e.g. tooth fragments, coins, batteries, small toy parts, needles)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2747", "contents": "Nitrous oxide  (\"laughing gas\") has been   used recreationally since 1899  for its ability to induce  euphoria ,  hallucinogenic  states and  relaxation , and is legal in some countries."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2748", "contents": "Helium  can be inhaled to give the voice a reedy, duck-like quality, but this can be dangerous as the gas is an  asphyxiant  and displaces the oxygen needed for normal respiration. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2749", "contents": "Various illegal gaseous, vapourised  or aerosolized  recreational drugs  exist, and are classed as  inhalants ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2750", "contents": "Various specialized investigations use the inhalation of known substances for diagnostic purposes. Examples include  pulmonary function testing  (e.g.  nitrogen washout  test,  diffusion capacity  testing ( carbon monoxide ,  helium ,  methane )) and  diagnostic radiology  (e.g.  radioactive xenon isotopes )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2751", "contents": "Gases and other drugs used in anaesthesia include oxygen, nitrous oxide, helium, xenon,  volatile anaesthetic agents . Medication for  asthma , croup, cystic fibrosis and some other conditions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2752", "contents": "Inhalation begins with the contraction of the muscles attached to the rib cage; this causes an expansion in the chest cavity.  Then takes place the onset of contraction of the  thoracic diaphragm , which results in expansion of the  intrapleural space  and an increase in negative pressure according to  Boyle's law .  This negative pressure generates airflow because of the pressure difference between the atmosphere and alveolus."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2753", "contents": "The inflow of air into the lungs occurs via the  respiratory airways . In health, these airways  begin with the nose . [ 3 ] [ 4 ]  It is possible to begin with the mouth, which is the backup breathing system. However, chronic  mouth breathing  leads to, or is a sign of, illness, and it does not have mucus in the mouth to trap the unwanted substance unlike the nostrils [ 5 ] [ 6 ] [ 7 ]  They end in the microscopic dead-end sacs( alveoli ) always opened, though the diameters of the various sections can be changed by the  sympathetic  and  parasympathetic nervous systems . The alveolar air pressure is therefore always close to atmospheric air pressure (about 100\u00a0 kPa  at sea level) at rest, with the pressure gradients that cause air to move in and out of the lungs during breathing rarely exceeding 2\u20133\u00a0kPa. [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2754", "contents": "Other muscles that can be involved in inhalation include: [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2755", "contents": "Hyperinflation  or  hyperaeration  is where the lung volume is abnormally increased, with increased filling of the alveoli. This results in an increased  radiolucency  on X-ray, a reduction in lung markings and depression of the diaphragm. It may occur in partial obstruction of a large airway, as in e.g.  congenital lobar emphysema , bronchial  atresia  and mucus plugs in  asthma . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2756", "contents": "Yogis such as  B. K. S. Iyengar  advocate both  inhaling and exhaling through the nose  in the practice of  yoga , rather than inhaling through the nose and  exhaling through the mouth . [ 12 ] [ 13 ] [ 14 ]  They tell their students that the \"nose is for breathing, the mouth is for eating.\" [ 13 ] [ 15 ] [ 16 ] [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2757", "contents": "Juxtacapillary receptors ,  J-receptors , or  pulmonary C-fiber receptors  are sensory nerve endings located within the  alveolar walls  in juxtaposition to the pulmonary capillaries of the lung, and are innervated by fibers of the  vagus nerve . [ 1 ]  Although their functional role is unclear, J-receptors respond to events such as  pulmonary edema ,  pulmonary emboli ,  pneumonia ,  congestive heart failure  and  barotrauma , which cause a decrease in oxygenation and thus lead to an increase in respiration. [ 2 ]  They may be also stimulated by hyperinflation of the lung as well as intravenous or intracardiac administration of chemicals such as capsaicin. [ 3 ] \nThe stimulation of the J-receptors causes a  reflex   increase in breathing rate , and is also thought to be involved in the  sensation of  dyspnea , the subjective sensation of difficulty breathing. [ 4 ] [ 5 ]  The reflex response that is produced is apnea followed by rapid breathing,  bradycardia , and hypotension (pulmonary chemoreflex). The physiologic role of this reflex is uncertain, but it probably occurs in pathologic states such as pulmonary congestion or embolization. [ 3 ]  These receptors were discovered by  Autar Paintal . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2758", "contents": "Because these receptors have been found in the walls of bronchi, the larynx, and the nose, they appear to be part of a widespread population of nociceptors found in most tissue. For this reason, they are now usually referred to as  pulmonary C-fiber receptors . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2759", "contents": "The  lactate shuttle hypothesis  describes the movement of  lactate  intracellularly (within a cell) and intercellularly (between cells). The hypothesis is based on the observation that lactate is formed and utilized continuously in diverse cells under both  anaerobic  and  aerobic  conditions. [ 1 ]   Further, lactate produced at sites with high rates of  glycolysis  and  glycogenolysis  can be shuttled to adjacent or remote sites including heart or skeletal muscles where the lactate can be used as a  gluconeogenic  precursor or substrate for oxidation. [ 2 ] [ 3 ]  The hypothesis was proposed in 1985 by George Brooks of the  University of California at Berkeley . [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2760", "contents": "In addition to its role as a fuel source predominantly in the muscles, heart, brain, and liver, the lactate shuttle hypothesis also relates the role of lactate in  redox signalling ,  gene expression , and lipolytic control.  These additional roles of lactate have given rise to the term \"lactormone\", pertaining to the role of lactate as a signalling hormone. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2761", "contents": "Prior to the formation of the lactate shuttle hypothesis, lactate had long been considered a byproduct resulting from  glucose  breakdown through glycolysis in times of anaerobic metabolism. [ 6 ] [ 3 ]  As a means of regenerating oxidized NAD + ,  lactate dehydrogenase  catalyzes the conversion of  pyruvate  to lactate in the  cytosol , oxidizing NADH to NAD + , regenerating the necessary substrate needed to continue glycolysis.  Lactate is then transported from the peripheral tissues to the liver by means of the  Cori Cycle  where it is reformed into pyruvate through the reverse reaction using  lactate dehydrogenase .  By this logic, lactate was traditionally considered a toxic metabolic byproduct that could give rise to fatigue and muscle pain during times of anaerobic respiration. [ 7 ]   Lactate was essentially payment for \u2018 oxygen debt \u2019 defined by  Hill  and Lupton as the \u2018total amount of oxygen used, after cessation of exercise in recovery therefrom\u2019. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2762", "contents": "In addition to Cori Cycle, the lactate shuttle hypothesis proposes complementary functions of lactate in multiple tissues. Contrary to the long-held belief that lactate is formed as a result of oxygen-limited metabolism, substantial evidence exists that suggests lactate is formed under both aerobic and anaerobic conditions, as a result of substrate supply and equilibrium dynamics. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2763", "contents": "During physical exertion or moderate intensity exercise lactate released from working muscle and other tissue beds is the primary fuel source for the heart, exiting the muscles through  monocarboxylate transport protein  (MCT). [ 10 ]    This evidence is supported by an increased amount of MCT shuttle proteins in the heart and muscle in direct proportion to exertion as measured through muscular contraction. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2764", "contents": "Furthermore, both neurons and  astrocytes  have been shown to express MCT proteins, suggesting that the lactate shuttle may be involved in brain metabolism. Astrocytes express MCT4, a low affinity transporter for lactate (Km = 35mM), suggesting its function is to export lactate produced by glycolysis. Conversely, neurons express MCT2, a high affinity transporter for lactate (Km = 0.7mM) [ clarification needed ] . Thus, it is hypothesized that the astrocytes produce lactate which is then taken up by the adjacent neurons and oxidized for fuel."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2765", "contents": "The lactate shuttle hypothesis also explains the balance of lactate production in the cytosol, via  glycolysis  or  glycogenolysis , and lactate oxidation in the  mitochondria  (described below)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2766", "contents": "MCT2 transporters within the  peroxisome  function to transport pyruvate into the peroxisome where it is reduced by peroxisomal LDH (pLDH) to lactate.  In turn, NADH is converted to NAD + , regenerating this necessary component for subsequent  \u03b2-oxidation . Lactate is then shuttled out of the peroxisome via MCT2, where it is oxidized by cytoplasmic LDH (cLDH) to pyruvate, generating NADH for energy use and completing the cycle (see figure). [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2767", "contents": "While the cytosolic  fermentation pathway  of lactate is well established, a novel feature of the lactate shuttle hypothesis is the oxidation of lactate in the mitochondria. Baba and Sherma (1971) were the first to identify the enzyme lactate dehydrogenase (LDH) in the mitochondrial inner membrane and matrix of rat skeletal and cardiac muscle. [ 13 ]  Subsequently, LDH was found in the rat liver, kidney, and heart mitochondria. [ 14 ]   It was also found that lactate could be oxidized as quickly as pyruvate in rat liver mitochondria. Because lactate can either be oxidized in the mitochondria (back to pyruvate for entry into the  Krebs cycle , generating NADH in the process), or serve as a gluconeogenic precursor, the intracellular lactate shuttle has been proposed to account for the majority of lactate turnover in the human body (as evidenced by the slight increases in arterial lactate concentration). Brooks et al. confirmed this in 1999, when they found that lactate oxidation exceeded that of pyruvate by 10-40% in rat liver, skeletal, and cardiac muscle."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2768", "contents": "In 1990, Roth and Brooks found evidence for the facilitated transporter of lactate, monocarboxylate transport protein (MCT), in the  sarcolemma  vesicles of rat skeletal muscle. Later, MCT1 was the first of the MCT super family to be identified. [ 15 ]   The first four MCT isoforms are responsible for pyruvate/lactate transport. MCT1 was found to be the predominant isoform in many tissues including skeletal muscle, neurons,  erythrocytes , and sperm. [ 16 ]   In skeletal muscle, MCT1 is found in the membranes of the sarcolemma, [ 15 ]  peroxisome, [ 12 ]  and mitochondria. [ 6 ]   Because of the mitochondrial localization of MCT (to transport lactate into the mitochondria), LDH (to oxidize the lactate back to pyruvate), and COX ( cytochrome c oxidase , the terminal element of the  electron transport chain ), Brooks et al. proposed the possibility of a mitochondrial lactate oxidation complex in 2006. This is supported by the observation that the ability of muscle cells to oxidize lactate was related to the density of mitochondria. [ 17 ]   Furthermore, it was shown that training increases MCT1 protein levels in skeletal muscle mitochondria, and that corresponded with an increase in the ability of muscle to clear lactate from the body during exercise. [ 18 ]   The affinity of MCT for pyruvate is greater than lactate, however two reactions will ensure that lactate will be present in concentrations that are orders of magnitude greater than pyruvate: first, the  equilibrium constant  of LDH (3.6 \u00d7 10 4 ) greatly favors the formation of lactate. Secondly, the immediate removal of pyruvate from the mitochondria (either via the Krebs cycle or gluconeogenesis) ensures that pyruvate is not present in great concentrations within the cell."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2769", "contents": "LDH  isoenzyme  expression is tissue-dependent. It was found that in rats, LDH-1 was the predominant form in the mitochondria of  myocardium , but LDH-5 was predominant in the  liver  mitochondria. [ 6 ]   It is suspected that this difference in  isoenzyme  is due to the predominant pathway the lactate will take \u2013 in liver it is more likely to be gluconeogenesis, whereas in the myocardium it is more likely to be oxidation. Despite these differences, it is thought that the  redox  state of the mitochondria dictates the ability of the tissues to oxidize lactate, not the particular LDH isoform."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2770", "contents": "As illustrated by the  peroxisomal  intracellular lactate shuttle described above, the interconversion of lactate and pyruvate between cellular compartments plays a key role in the oxidative state of the cell. Specifically, the interconversion of NAD +  and NADH between compartments has been hypothesized to occur in the mitochondria. However, the evidence for this is lacking, as both lactate and pyruvate are quickly metabolized inside the mitochondria. However, the existence of the peroxisomal lactate shuttle suggests that this redox shuttle could exist for other  organelles . [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2771", "contents": "Increased intracellular levels of lactate can act as a signalling hormone, inducing changes in gene expression that will upregulate genes involved in lactate removal. [ 19 ]   These genes include MCT1,  cytochrome c oxidase  (COX), and other enzymes involved in the lactate oxidation complex. Additionally, lactate will increase levels of  peroxisome proliferator activated receptor gamma coactivator 1-alpha  (PGC1-\u03b1), suggesting that lactate stimulates mitochondrial biogenesis. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2772", "contents": "In addition to the role of the lactate shuttle in supplying NAD +  substrate for \u03b2-oxidation in the peroxisomes, the shuttle also regulates FFA mobilization by controlling plasma lactate levels.  Research has demonstrated that lactate functions to inhibit  lipolysis  in fat cells through activation of an orphan G-protein couple receptor ( GPR81 ) that acts as a lactate sensor, inhibiting lipolysis in response to lactate . [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2773", "contents": "As found by Brooks, et al., while lactate is disposed of mainly through oxidation and only a minor fraction supports  gluconeogenesis , lactate is the main gluconeogenic precursor during sustained exercise. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2774", "contents": "Brooks demonstrated in his earlier studies that little difference in lactate production rates were seen in trained and untrained subjects at equivalent power outputs.  What was seen, however, was more efficient clearance rates of lactate in the trained subjects suggesting an upregulation of MCT protein. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2775", "contents": "Local lactate use depends on exercise exertion.  During rest, approximately 50% of lactate disposal take place through lactate oxidation whereas in time of strenuous exercise (50-75%  VO 2  max ) approximately 75-80% of lactate is used by the active cell, indicating lactate's role as a major contributor to energy conversion during increased exercise exertion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2776", "contents": "Highly  malignant tumors  rely heavily on  anaerobic glycolysis  (metabolism of glucose to lactic acid even under ample tissue oxygen;  Warburg effect ) and thus need to efflux lactic acid via MCTs to the tumor micro-environment to maintain a robust glycolytic flux and to prevent the tumor from being \"pickled to death\". [ 21 ]  The MCTs have been successfully targeted in pre-clinical studies using RNAi  [ 22 ]  and a small-molecule inhibitor  alpha-cyano-4-hydroxycinnamic acid  (ACCA; CHC) to show that inhibiting lactic acid efflux is a very effective therapeutic strategy against highly glycolytic malignant tumors. [ 23 ] [ 24 ] [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2777", "contents": "In some tumor types, growth and metabolism relies on the exchange of lactate between glycolytic and rapidly respiring cells. This is of particular importance during tumor cell development when cells often undergo anaerobic metabolism, as described by the  Warburg effect . Other cells in the same tumor may have access to or recruit sources of oxygen (via  angiogenesis ), allowing it to undergo aerobic oxidation. The lactate shuttle could occur as the hypoxic cells anaerobically metabolize glucose and shuttle the lactate via MCT to the adjacent cells capable of using the lactate as a substrate for oxidation. Investigation into how MCT-mediated lactate exchange in targeted tumor cells can be inhibited, therefore depriving cells of key energy sources, could lead to promising new  chemotherapeutics . [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2778", "contents": "Additionally, lactate has been shown to be a key factor in tumor  angiogenesis . Lactate promotes angiogenesis by upregulating  HIF-1  in  endothelial cells . Thus a promising target of cancer therapy is the inhibition of lactate export, through MCT-1 blockers, depriving developing tumors of an oxygen source. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2779", "contents": "In biochemistry, the  Luebering\u2013Rapoport pathway  (also called the Luebering\u2013Rapoport shunt) is a  metabolic pathway  in mature  erythrocytes  involving the formation of  2,3-bisphosphoglycerate  (2,3-BPG), which regulates  oxygen  release from  hemoglobin  and delivery to tissues. 2,3-BPG, the reaction product of the Luebering\u2013Rapoport pathway was first described and isolated in 1925 by the Austrian biochemist  Samuel Mitja Rapoport  and his technical assistant Jane Luebering. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2780", "contents": "Through the Luebering\u2013Rapoport pathway  bisphosphoglycerate mutase  catalyzes the transfer of a phosphoryl group from C1 to C2 of 1,3-BPG, giving 2,3-BPG. 2,3-bisphosphoglycerate, the most concentrated organophosphate in the erythrocyte, forms 3-PG by the action of  bisphosphoglycerate phosphatase . The concentration of 2,3-BPG varies proportionately with the pH, since it is inhibitory to catalytic action of bisphosphoglyceromutase."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2781", "contents": "Lung compliance , or  pulmonary compliance , is a measure of the  lung 's  ability to stretch and expand  (distensibility of elastic tissue). In clinical practice it is separated into two different measurements, static compliance and dynamic compliance. Static lung compliance is the change in volume for any given applied pressure. [ 1 ]  Dynamic lung compliance is the compliance of the lung at any given time during actual movement of air."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2782", "contents": "Low compliance indicates a stiff lung (one with high  elastic recoil ) and can be thought of as a thick balloon \u2013 this is the case often seen in  fibrosis . High compliance indicates a pliable lung (one with low elastic recoil) and can be thought of as a grocery bag \u2013 this is the case often seen in  emphysema . Compliance is highest at moderate  lung volumes , and much lower at volumes which are very low or very high. The compliance of the lungs demonstrate  lung hysteresis ; that is, the compliance is different on inspiration and expiration for identical volume."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2783", "contents": "Pulmonary compliance is calculated using the following equation, where \u0394 V  is the change in volume,  and \u0394 P  is the change in pleural pressure:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2784", "contents": "For example, if a patient inhales 500 mL of air from a spirometer with an intrapleural pressure before inspiration of \u22125\u00a0cm H 2 O and \u221210\u00a0cm H 2 O at the end of inspiration. Then:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2785", "contents": "Static compliance represents pulmonary compliance during periods without gas flow, such as during an inspiratory pause. It can be calculated with the formula:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2786", "contents": "P plat  is measured at the end of inhalation and prior to exhalation by using an inspiratory hold maneuver. During this maneuver, airflow is transiently (~0.5 sec) discontinued, which eliminates the effects of airway resistance.  P plat  is never bigger than  PIP  and is typically <10 cm H 2 O lower than PIP when airway resistance is not elevated."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2787", "contents": "Dynamic compliance represents pulmonary compliance during periods of gas flow, such as during active inspiration. Dynamic compliance is always lesser than or equal to static lung compliance because PIP \u2212 PEEP is always greater than  P plat  \u2212 PEEP. It can be calculated using the following equation,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2788", "contents": "Alterations in airway resistance, lung compliance and chest wall compliance influence  C dyn ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2789", "contents": "The dimensions of compliance in respiratory physiology are inconsistent with the dimensions of compliance in physics-based applications. In physiology,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2790", "contents": "whereas in  newtonian physics , compliance is defined as the inverse of the elastic  stiffness  constant  k ,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2791", "contents": "Pulmonary compliance is analogous to  capacitance ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2792", "contents": "Lung compliance is an important measurement in  respiratory physiology . [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2793", "contents": "Pulmonary surfactant  increases compliance by decreasing the surface tension of water. The internal surface of the  alveolus  is covered with a thin coat of fluid. The water in this fluid has a high surface tension, and provides a force that could collapse the alveolus. The presence of surfactant in this fluid breaks up the surface tension of water, making it less likely that the alveolus can collapse inward. If the alveolus were to collapse, a great force would be required to open it, meaning that compliance would decrease drastically. Lung volume at any given pressure during inhalation is less than the lung volume at any given pressure during exhalation, which is called  hysteresis . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2794", "contents": "Low compliance indicates a stiff lung and means extra work is required to bring in a normal volume of air. This occurs as the lungs in this case become fibrotic, lose their distensibility and become stiffer."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2795", "contents": "In a highly compliant lung, as in  emphysema , the elastic tissue is damaged by  enzymes . These enzymes are secreted by leukocytes (white blood cells) in response to a variety of inhaled irritants, such as cigarette smoke. Patients with emphysema have a very high lung compliance due to the poor  elastic recoil . They have extreme difficulty exhaling air. In this condition extra work is required to get air out of the lungs. In addition, patients often have difficulties inhaling air as well. This is due to the fact that a highly compliant lung results in many  Atelectasis  which makes inflation difficult. [ further explanation needed ]  Compliance also increases with increasing age."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2796", "contents": "Both peak inspiratory and plateau pressure increase when elastic resistance increases or when pulmonary compliance decreases (e.g. during abdominal insufflation, ascites, intrinsic lung disease, obesity, pulmonary edema, tension pneumothorax). On the other hand, only peak inspiratory pressure increases (plateau pressure unchanged) when airway resistance increases (e.g. airway compression, bronchospasm, mucous plug, kinked tube, secretions, foreign body). [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2797", "contents": "Compliance decreases in the following cases:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2798", "contents": "Lung volumes  and  lung capacities  are measures of the  volume  of  air  in the  lungs  at different phases of the  respiratory cycle ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2799", "contents": "The average total lung capacity of an adult human male is about 6  litres  of air. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2800", "contents": "Tidal breathing is normal, resting breathing; the  tidal volume  is the volume of air that is inhaled or exhaled in only a single such breath."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2801", "contents": "The average human  respiratory rate  is 30\u201360 breaths per minute at birth, [ 2 ]  decreasing to 12\u201320 breaths per minute in adults. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2802", "contents": "Several factors affect lung volumes; some can be controlled, and some cannot be controlled. Lung volumes vary with different people as follows:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2803", "contents": "A person who is born and lives at  sea level  will develop a slightly smaller lung capacity than a person who spends their life at a high  altitude . This is because the partial pressure of oxygen is lower at higher altitude which, as a result means that oxygen less readily diffuses into the bloodstream. In response to higher altitude, the body's diffusing capacity increases in order to process more air. Also, due to the lower environmental air pressure at higher altitudes, the air pressure within the breathing system must be lower in order to inhale; in order to meet this requirement, the thoracic diaphragm has a tendency to lower to a greater extent during inhalation, which in turn causes an increase in lung volume."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2804", "contents": "When someone living at or near sea level travels to locations at high altitudes (e.g. the  Andes ;  Denver, Colorado ;  Tibet ; the  Himalayas ) that person can develop a condition called  altitude sickness  because their lungs remove adequate amounts of carbon dioxide but they do not take in enough oxygen. (In normal individuals, carbon dioxide is the primary determinant of respiratory drive.)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2805", "contents": "Lung function development is reduced in children who grow up near motorways [ 5 ] [ 6 ]  although this seems at least in part reversible. [ 7 ]  Air pollution exposure affects FEV 1  in asthmatics, but also affects FVC and FEV 1  in healthy adults even at low concentrations. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2806", "contents": "Specific changes  in lung volumes also occur during pregnancy.  Functional residual capacity  drops 18\u201320%, [ 9 ]  typically falling from 1.7 to 1.35 litres, [ citation needed ]  due to the compression of the  diaphragm  by the uterus. [ citation needed ]  The compression also causes a decreased  total lung capacity  (TLC) by 5% [ 9 ]  and decreased  expiratory reserve volume  by 20%. [ 9 ]   Tidal volume  increases by 30\u201340%, from 0.5 to 0.7 litres, [ 9 ]  and  minute ventilation  by 30\u201340% [ 9 ] [ 10 ]  giving an increase in pulmonary ventilation. This is necessary to meet the increased oxygen requirement of the body, which reaches 50\u00a0ml/min, 20 ml of which goes to reproductive tissues. Overall, the net change in maximum breathing capacity is zero. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2807", "contents": "The  tidal volume ,  vital capacity ,  inspiratory capacity  and  expiratory reserve volume  can be measured directly with a  spirometer . These are the basic elements of a ventilatory  pulmonary function test ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2808", "contents": "Determination of the  residual volume  is more difficult as it is impossible to \"completely\" breathe out. Therefore, measurement of the residual volume has to be done via indirect methods such as radiographic planimetry,  body plethysmography , closed circuit dilution (including the  helium dilution technique ) and  nitrogen washout ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2809", "contents": "In absence of such, estimates of  residual volume  have been prepared as a proportion of body mass for infants (18.1 ml/kg), [ 12 ]  or as a proportion of  vital capacity  (0.24 for men and 0.28 for women) [ 13 ]  or in relation to height and age ((0.0275* Age [Years]+0.0189*Height [cm]\u22122.6139) litres for normal-mass individuals and (0.0277*Age [Years]+0.0138*Height [cm]\u22122.3967) litres for overweight individuals). [ 14 ]   Standard errors in prediction equations for residual volume have been measured at 579 ml for men and 355 ml for women, while the use of 0.24*FVC gave a standard error of 318 ml. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2810", "contents": "Online calculators are available  that can compute predicted lung volumes, and other spirometric parameters based on a patient's age, height, weight, and ethnic origin for many reference sources."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2811", "contents": "British rower and three-time Olympic gold medalist  Pete Reed  is reported to hold the largest recorded lung capacity of 11.68 litres; [ 16 ] [ 17 ] [ 18 ]  US swimmer  Michael Phelps  is also said to have a lung capacity of around 12 litres. [ 17 ] [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2812", "contents": "The mass of one breath is approximately a gram (0.5-5 g). A litre of air weighs about 1.2 g (1.2\u00a0kg/m 3 ). [ 20 ]  A half litre ordinary tidal breath [ 11 ]  weighs 0.6 g; a maximal 4.8 litre breath (average vital capacity for males) [ 11 ]  weighs approximately 5.8 g."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2813", "contents": "The results (in particular  FEV 1 /FVC  and FRC) can be used to distinguish between restrictive and obstructive pulmonary diseases:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2814", "contents": "Methemoglobin  (British:  methaemoglobin , shortened  MetHb ) (pronounced \"met-hemoglobin\") is a  hemoglobin   in the form of  metalloprotein , in which the  iron  in the  heme  group is in the Fe 3+  ( ferric ) state, not the Fe 2+  ( ferrous ) of normal hemoglobin. Sometimes, it is also referred to as ferrihemoglobin. [ 2 ]  Methemoglobin cannot bind  oxygen , which means it cannot carry oxygen to tissues. It is bluish chocolate-brown in color. In human  blood  a trace amount of methemoglobin is normally produced spontaneously, but when present in excess the blood becomes abnormally dark bluish brown. The  NADH -dependent enzyme  methemoglobin reductase  ( a type of diaphorase ) is responsible for converting methemoglobin back to  hemoglobin ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2815", "contents": "Normally one to two percent of a person's hemoglobin is methemoglobin; a higher percentage than this can be genetic or caused by exposure to various chemicals and depending on the level can cause health problems known as  methemoglobinemia . A higher level of methemoglobin will tend to cause a  pulse oximeter  to read closer to 85% regardless of the true level of  oxygen saturation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2816", "contents": "The word methemoglobin derives from the  Ancient Greek  prefix  \u03bc\u03b5\u03c4\u03b1-  (meta-: behind, later, subsequent) and the word  hemoglobin ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2817", "contents": "The name  hemoglobin  is itself derived from the words  heme  and  globin , each  subunit  of hemoglobin being a  globular protein  with an embedded  heme  group."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2818", "contents": "Amyl nitrite  is administered to treat  cyanide poisoning . It works by converting  hemoglobin  to methemoglobin, which allows for the binding of  cyanide  (CN \u2013 )  anions  by  ferric  (Fe 3+ )  cations  and the formation of  cyanomethemoglobin . The immediate goal of forming this cyanide adduct is to prevent the binding of free cyanide to the  cytochrome  a 3  group in  cytochrome c oxidase . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2819", "contents": "Methemoglobin is expressed as a concentration or a percentage. Percentage of methemoglobin is calculated by dividing the concentration of methemoglobin by the concentration of total hemoglobin. Percentage of methemoglobin is likely a better indicator of illness severity than overall concentration, as underlying medical conditions play an important role. For example, a methemoglobin concentration of 1.5 g/dL may represent a percentage of 10% in an otherwise healthy patient with a baseline hemoglobin of 15\u00a0mg/dL, whereas the presence of the same concentration of 1.5 g/dL of methemoglobin in an anemic patient with a baseline hemoglobin of 8 g/dL would represent a percentage of 18.75%. The former patient will be left with a functional hemoglobin concentration of 13.5 g/dL and potentially remain asymptomatic while the latter patient with a functional hemoglobin concentration 6.5 g/dL may be severely symptomatic with a methemoglobin of less than 20%. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2820", "contents": "This may be further compounded by the \"functional hemoglobin's\" decreased ability to release oxygen in the presence of methemoglobin.  Anemia ,  congestive heart failure ,  chronic obstructive pulmonary disease , and essentially any pathology that impairs the ability to deliver oxygen may worsen the symptoms of methemoglobinemia. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2821", "contents": "Increased levels of methemoglobin are found in blood stains. Upon exiting the body,  bloodstains  transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO 2 ) to methemoglobin (met-Hb) and  hemichrome  (HC). [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2822", "contents": "Minute ventilation  (or  respiratory minute volume  or  minute volume ) is the  volume  of gas  inhaled  (inhaled minute volume) or  exhaled  (exhaled minute volume) from a person's  lungs  per minute. It is an important parameter in  respiratory medicine  due to its relationship with  blood carbon dioxide levels . It can be measured with devices such as a Wright respirometer or can be calculated from other known respiratory parameters. Although minute volume can be viewed as a unit of volume, it is usually treated in practice as a  flow rate  (given that it represents a volume change over time).  Typical units involved are (in metric) 0.5 L \u00d7 12 breaths/min = 6 L/min."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2823", "contents": "Several symbols can be used to represent minute volume. They include  \n \n \n \n \n \n \n V \n \u02d9 \n \n \n \n \n \n {\\displaystyle {\\dot {V}}} \n \n  (V\u0307 or V-dot) or Q (which are general symbols for flow rate),  MV, and V E ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2824", "contents": "Minute volume can either be measured directly or calculated from other known parameters."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2825", "contents": "Minute volume is the amount of gas inhaled or exhaled from a person's lungs in one minute. It can be measured by a  Wright respirometer  or other device capable of cumulatively measuring gas flow, such as  mechanical ventilators ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2826", "contents": "If both  tidal volume  (V T ) and  respiratory rate  (\u0192 or RR) are known, minute volume can be calculated by multiplying the two values. One must also take care to consider the effect of dead space on alveolar ventilation, as seen below in \"Relationship to other physiological rates\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2827", "contents": "Blood carbon dioxide (PaCO 2 ) levels generally vary inversely with minute volume. [ citation needed ]  For example, a person with increased minute volume (e.g. due to  hyperventilation ) should demonstrate a lower blood carbon dioxide level. The healthy human body will alter minute volume in an attempt to maintain physiologic homeostasis. A normal minute volume while resting is about 5\u20138  liters  per minute in humans. [ 1 ]  Minute volume generally decreases when at rest, and increases with exercise. For example, during light activities minute volume may be around 12 litres. Riding a bicycle increases minute ventilation by a factor of 2 to 4 depending on the level of exercise involved. Minute ventilation during moderate exercise may be between 40 and 60 litres per minute. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2828", "contents": "Hyperventilation  is the term for having a minute ventilation higher than physiologically appropriate.  Hypoventilation  describes a minute volume less than physiologically appropriate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2829", "contents": "Minute volume comprises the sum of  alveolar ventilation  and  dead space ventilation . That is:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2830", "contents": "where  \n \n \n \n \n \n \n \n V \n \u02d9 \n \n \n \n \n A \n \n \n \n \n {\\displaystyle {\\dot {V}}_{A}} \n \n  is alveolar ventilation, and  \n \n \n \n \n \n \n \n V \n \u02d9 \n \n \n \n \n D \n \n \n \n \n {\\displaystyle {\\dot {V}}_{D}} \n \n  represents dead space ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2831", "contents": "Obligate nasal breathing  describes a physiological  instinct  to  breathe  through the nose (or other forms of external nasal passages, depending on the species) as opposed to  breathing through the mouth ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2832", "contents": "The term may be misleading, as it implies that the organism has no choice but to breathe through its nose; however, it is also used to describe cases where effective breathing through the mouth is possible but not preferred. [ 1 ]  Alternatively, the term has been defined by some as the ability to breathe through the nose while swallowing. While this ability is a common trait of obligate nasal breathers, the definition does not require that nasal breathing is necessary for the animal. Even in obligate nasal breathers such as horses, rabbits, and rodents, there is a potential patent path for air to travel from the mouth to the lungs which can be used for endotracheal intubation. It has been suggested that obligate nasal breathing is an adaptation especially useful in prey species, as it allows an animal to feed while preserving their ability to detect predators by scent. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2833", "contents": "Horses are considered obligate nasal breathers. The  respiratory system of the horse  prevents horses from breathing orally. The  epiglottis  rests above the soft palate while the animal is not swallowing, forming an airtight seal. Oral breathing can only occur with significant anatomical abnormalities or pathological conditions. For example, denervation of the pharyngeal branch of the  vagus nerve  results in the dorsal displacement of the  soft palate  (DDSP), [ 3 ]  and it has been suggested that this leads to a clinical syndrome which may include oral breathing. [ 4 ]  However, significant respiratory dysfunction including airway obstruction is observed with DDSP, and the animal cannot function normally in this state."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2834", "contents": "Rabbits and rodents are also obligate nasal breathers. Like horses, the normal anatomical position of the epiglottis causes it to be engaged over the caudal rim of the soft palate, sealing the oral pharynx from the lower airways. [ 5 ]  Air entering the mouth will not fully make it to the lungs. [ 6 ]  Even so, rabbits with advanced upper airway disease will attempt to breathe through their mouths."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2835", "contents": "Many other mammals, such as adult dogs and humans, have the ability to breathe indefinitely through either the oral or nasal cavity.  Cats are preferential nasal breathers.  [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2836", "contents": "According to Jason Turowski, MD of the  Cleveland Clinic , \"We are designed to breathe through our noses from birth \u2014 it\u2019s the way humans have evolved.\" [ 9 ]  This is because it is the  job of the nose  to filter out all of the particles that enter the body, as well as to humidify the air we breathe and warm it to body temperature. [ 10 ] [ 11 ]  In addition, nasal breathing produces  nitric oxide  within the body while  mouth breathing  does not. [ 12 ] [ 10 ] [ 13 ] [ 14 ]  Mouth breathing also leads to dry mouth, throat infections, a reduced sense of taste, [ 11 ]  and other chronic conditions. [ 13 ] [ 15 ] [ 16 ] [ 17 ]  Nasal breathing is a research interest in  orthodontics  (and the related field of  myofunctional therapy) [ 18 ]  and for  biological anthropologists . [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2837", "contents": "Human infants are commonly described as obligate nasal breathers as they breathe through their nose rather  than the mouth . [ 20 ]  Most infants, however, are able to breathe through their mouth if their nose is blocked. [ 20 ]  There are however certain infants with conditions such as  choanal atresia  in which deaths have resulted from nasal obstruction. [ 20 ]  In these cases, there are cyclical periods of  cyanosis . The infant initially attempts to breathe through the nose, and is unable to;  hypercapnia  occurs, and many babies instinctively begin to cry. While crying, oral ventilation occurs and cyanosis subsides. There is variation in the length of time until a baby begins oral breathing, and some will never cease attempts at nasal breathing. It has also been suggested that infants may not be able to sustain oral breathing for significant lengths of time, because of the weakness of the muscles required to seal the nasal airway and open the oral airway. [ 20 ]  One study employing monitored anatomical occlusion concluded that human infants are not obligate nasal breathers: [ 21 ]   its  sample  of nineteen infants, ranging in age from 1 day to 7.5 months, reliably transitioned from nose to mouth breathing after nasal occlusion, providing evidence that infants possess the physiological capability to mouth breathe."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2838", "contents": "Some authors argue that nasal breathing offers a greater advantage over mouth breathing during exercise. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2839", "contents": "George Catlin  was a 19th-century American painter, author, and traveler, who specialized in portraits of Native Americans in the  Old West . Travelling to the  American West  five times during the 1830s, he wrote about the life of the  Plains Indians , and painted portraits that depicted them. [ 22 ]  He was also the author of several books, including  The Breath of Life [ 23 ]  (later retitled as  Shut Your Mouth and Save Your Life )\u00a0in 1862. [ 24 ] [ 25 ]  It was based on his experiences traveling through the West, where he observed a consistent lifestyle habit among the Native American communities he encountered: a preference for nose breathing over  mouth breathing . He also observed that they had perfectly straight teeth. [ 26 ]  He repeatedly heard that this was because they believed that mouth breathing made an individual weak and caused disease, while nasal breathing made the body strong and prevented disease. [ 26 ]  He also observed that mothers repeatedly closed the mouth of their infants while they were sleeping, to instill nasal breathing as a habit. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2840", "contents": "Yogis such as  B. K. S. Iyengar  advocate both inhaling and exhaling through the nose in the practice of  yoga , rather than inhaling through the nose and exhaling through the mouth. [ 28 ] [ 29 ] [ 30 ]  They tell their students that the \"nose is for breathing, the mouth is for eating.\" [ 29 ] [ 31 ] [ 32 ] [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2841", "contents": "Organisms can live at  high altitude , either on land, in water, or while flying.  Decreased oxygen availability and decreased temperature make life at such altitudes challenging, though many species have been successfully  adapted  via considerable  physiological  changes. As opposed to short-term  acclimatisation  (immediate physiological response to changing environment), high-altitude  adaptation  means irreversible,  evolved physiological responses  to high-altitude environments, associated with heritable  behavioural  and  genetic changes . Among vertebrates, only few mammals (such as  yaks ,  ibexes ,  Tibetan gazelles ,  vicunas ,  llamas ,  mountain goats , etc.) and certain  birds  are known to have completely adapted to high-altitude environments. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2842", "contents": "Human populations such as some  Tibetans ,  South Americans  and  Ethiopians  live in the otherwise uninhabitable high mountains of the  Himalayas ,  Andes  and  Ethiopian Highlands  respectively. The adaptation of humans to high altitude is an example of  natural selection  in action. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2843", "contents": "High-altitude adaptations provide examples of  convergent evolution , with adaptations occurring simultaneously on three continents. Tibetan humans and Tibetan domestic dogs share a genetic mutation in  EPAS1 , but it has not been seen in Andean humans. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2844", "contents": "Tardigrades  live over the entire world, including the high  Himalayas . [ 4 ]  Tardigrades are also able to survive temperatures of close to  absolute zero  (\u2212273\u00a0\u00b0C or \u2212459\u00a0\u00b0F), [ 5 ]  temperatures as high as 151\u00a0\u00b0C (304\u00a0\u00b0F), radiation that would kill other animals, [ 6 ]  and almost a decade without water. [ 7 ]  Since 2007, tardigrades have also returned alive from studies in which they have been exposed to the vacuum of outer space in low Earth orbit. [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2845", "contents": "Other invertebrates with high-altitude habitats are  Euophrys omnisuperstes , a spider that lives in the Himalaya range at altitudes of up to 6,700\u00a0m (22,000\u00a0ft); [ 10 ]  it feeds on stray insects that are blown up the mountain by the wind. [ 11 ]  The  springtail   Hypogastrura nivicola  (one of several insects called snow fleas) also lives in the Himalayas. It is active in the dead of winter, its blood containing a compound similar to  antifreeze . Some allow themselves to become dehydrated instead, preventing the formation of ice crystals within their body. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2846", "contents": "Insects can fly and kite at very high altitude.  Flies  are common in the Himalayas up to 6,300\u00a0m (20,700\u00a0ft). [ 13 ]   Bumble bees  were discovered on  Mount Everest  at more than 5,600\u00a0m (18,400\u00a0ft) above sea level. [ 14 ]  In subsequent tests, bumblebees were still able to fly in a flight chamber which recreated the thinner air of 9,000\u00a0m (30,000\u00a0ft). [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2847", "contents": "Ballooning  is a term used for the mechanical kiting [ 16 ] [ 17 ]  that many  spiders , especially small species such as  Erigone atra , [ 18 ]  as well as certain  mites  and some  caterpillars  use to disperse through the air. Some spiders have been detected in atmospheric data balloons collecting air samples at slightly less than 5\u00a0km (16,000\u00a0ft) above sea level. [ 19 ]  It is the most common way for spiders to pioneer isolated islands and mountaintops. [ 20 ] [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2848", "contents": "Fish at high altitudes have a lower metabolic rate, as has been shown in highland  westslope cutthroat trout  when compared to introduced lowland  rainbow trout  in the  Oldman River  basin. [ 22 ]  There is also a general trend of smaller body sizes and lower  species richness  at high altitudes observed in aquatic invertebrates, likely due to lower oxygen partial pressures. [ 23 ] [ 24 ] [ 25 ]  These factors may decrease  productivity  in high altitude habitats, meaning there will be less energy available for consumption, growth, and activity, which provides an advantage to fish with lower metabolic demands. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2849", "contents": "The  naked carp  from  Lake Qinghai , like other members of the  carp  family, can use  gill remodelling  to increase oxygen uptake in  hypoxic environments . [ 26 ]  The response of naked carp to cold and low-oxygen conditions seem to be at least partly mediated by  hypoxia-inducible factor 1 (HIF-1) . [ 27 ]  It is unclear whether this is a common characteristic in other high altitude dwelling fish or if gill remodelling and HIF-1 use for cold adaptation are limited to carp."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2850", "contents": "Mammals  are also known to reside at high altitude and exhibit a striking number of adaptations in terms of  morphology ,  physiology  and  behaviour . The  Tibetan Plateau  has very few mammalian species, ranging from  wolf ,  kiang  (Tibetan wild ass),  goas ,  chiru  (Tibetan antelope),  wild yak ,  snow leopard ,  Tibetan sand fox ,  ibex ,  gazelle ,  Himalayan brown bear  and  water buffalo . [ 29 ] [ 30 ] [ 31 ]   These mammals can be broadly categorised based on their adaptability in high altitude into two broad groups, namely  eurybarc  and  stenobarc . Those that can survive a wide range of high-altitude regions are  eurybarc  and include yak, ibex,  Tibetan gazelle  of the Himalayas and  vicu\u00f1as   llamas  of the Andes. Stenobarc animals are those with lesser ability to endure a range of differences in altitude, such as  rabbits ,  mountain goats ,  sheep , and  cats . Among  domesticated animals , yaks are perhaps the highest dwelling animals. The  wild   herbivores  of the Himalayas such as the  Himalayan tahr ,  markhor  and  chamois  are of particular interest because of their ecological versatility and tolerance. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2851", "contents": "A number of  rodents  live at high altitude, including  deer mice ,  guinea pigs , and  rats . Several mechanisms help them survive these harsh conditions, including altered  genetics  of the  hemoglobin  gene in guinea pigs and deer mice. [ 33 ] [ 34 ]  Deer mice use a high percentage of fats as metabolic fuel to retain  carbohydrates  for small bursts of energy. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2852", "contents": "Other physiological changes that occur in rodents at high altitude include increased  breathing rate [ 36 ]  and altered morphology of the lungs and heart, allowing more efficient  gas exchange  and delivery. Lungs of high-altitude mice are larger, with more capillaries, [ 37 ]  and their hearts have a heavier right ventricle (the latter applies to rats too), [ 38 ] [ 39 ]  which pumps blood to the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2853", "contents": "At high altitudes, some rodents even shift their  thermal neutral zone  so they may maintain normal  basal metabolic rate  at colder temperatures. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2854", "contents": "The deer mouse ( Peromyscus maniculatus ) is the best studied species, other than humans, in terms of high-altitude adaptation. [ 1 ]  The deer mice native to Andes highlands (up to 3,000\u00a0m (9,800\u00a0ft)) are found to have relatively low hemoglobin content. [ 41 ]  Measurement of food intake,  gut  mass, and  cardiopulmonary organ  mass indicated proportional increases in mice living at high altitudes, which in turn show that life at high altitudes demands higher levels of energy. [ 42 ]  Variations in the  globin  genes ( \u03b1  and  \u03b2-globin ) seem to be the basis for increased oxygen-affinity of the hemoglobin and faster transport of oxygen. [ 43 ] [ 44 ]  Structural comparisons show that in contrast to normal hemoglobin, the deer mouse hemoglobin lacks the  hydrogen bond  between  \u03b11Trp14  in the A  helix  and \u03b11Thr67 in the E helix owing to the  Thr 67 Ala  substitution, and there is a unique hydrogen bond at the \u03b11\u03b21 interface between residues  \u03b11Cys34  and  \u03b21Ser128 . [ 45 ]  The Peruvian native species of mice ( Phyllotis andium  and  Phyllotis xanthopygus ) have adapted to the high Andes by using proportionately more  carbohydrates  and have higher oxidative capacities of  cardiac muscles  compared to closely related native species residing at low-altitudes (100\u2013300\u00a0m (330\u2013980\u00a0ft)), ( Phyllotis amicus  and  Phyllotis limatus ). This shows that highland mice have evolved a metabolic process to economise oxygen usage for physical activities in the hypoxic conditions. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2855", "contents": "Among  domesticated animals , yaks ( Bos grunniens ) are the highest dwelling animals of the world, living at 3,000\u20135,000\u00a0m (9,800\u201316,400\u00a0ft). The yak is the most important domesticated animal for Tibet highlanders in  Qinghai Province  of  China , as the primary source of  milk ,  meat  and  fertilizer . Unlike other yak or  cattle  species, which suffer from hypoxia in the Tibetan Plateau, the Tibetan domestic yaks thrive only at high altitude, and not in lowlands. Their physiology is well-adapted to high altitudes, with proportionately larger lungs and heart than other cattle, as well as greater capacity for transporting oxygen through their blood. [ 47 ]  In yaks,  hypoxia-inducible factor  1 ( HIF-1 ) has high expression in the  brain ,  lung  and  kidney , showing that it plays an important role in the adaptation to low oxygen environment. [ 48 ]  On 1 July 2012 the complete genomic sequence and analyses of a female domestic yak was announced, providing important insights into understanding mammalian  divergence  and adaptation at high altitude. Distinct gene expansions related to  sensory perception  and energy metabolism were identified. [ 49 ]  In addition, researchers also found an enrichment of protein domains related to the extracellular environment and hypoxic stress that had undergone positive selection and rapid evolution. For example, they found three genes that may play important roles in regulating the body\u02bcs response to hypoxia, and five genes that were related to the optimisation of the energy from the food scarcity in the extreme plateau. One gene known to be involved in regulating response to low oxygen levels, ADAM17, is also found in human Tibetan highlanders. [ 50 ] [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2856", "contents": "Over 81 million people live permanently at high  altitudes  (>2,500\u00a0m or 8,200\u00a0ft) [ 52 ]  in  North ,  Central  and  South America ,  East Africa , and  Asia , and have flourished for  millennia  in the exceptionally high mountains, without any apparent complications. [ 53 ]  For average human populations, a brief stay at these places can risk  mountain sickness . [ 54 ]  For the native highlanders, there are no adverse effects to staying at high altitude."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2857", "contents": "The physiological and genetic  adaptations  in native highlanders involve modification in the  oxygen transport system of the blood , especially  molecular changes  in the structure and functions of  hemoglobin , a protein for carrying oxygen in the body. [ 53 ] [ 55 ]  This is to compensate for the  low oxygen environment . This adaptation is associated with developmental patterns such as high  birth weight , increased  lung volumes , increased  breathing , and higher  resting metabolism . [ 56 ] [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2858", "contents": "The  genome  of Tibetans provided the first clue to the  molecular evolution  of high-altitude adaptation in 2010. [ 58 ]  Genes such as  EPAS1 ,  PPARA  and  EGLN1  are found to have significant  molecular changes  among the Tibetans, and the genes are involved in  hemoglobin production . [ 59 ]  These genes function in concert with transcription factors,  hypoxia inducible factors  ( HIF ), which in turn are central mediators of  red blood cell production  in response to oxygen metabolism. [ 60 ]  Further, the Tibetans are enriched for genes in the disease class of human reproduction (such as genes from the  DAZ ,  BPY2 ,  CDY , and  HLA-DQ  and  HLA-DR  gene clusters) and biological process categories of response to  DNA damage  stimulus and  DNA repair  (such as  RAD51 ,  RAD52 , and  MRE11A ), which are related to the adaptive traits of high infant birth weight and  darker skin tone  and, are most likely due to recent local adaptation. [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2859", "contents": "Among the Andeans, there are no significant associations between  EPAS1  or  EGLN1  and hemoglobin concentration, indicating variation in the pattern of molecular adaptation. [ 62 ]  However,  EGLN1  appears to be the principal signature of evolution, as it shows evidence of positive selection in both Tibetans and Andeans. [ 63 ]  The adaptive mechanism is different among the Ethiopian highlanders. Genomic analysis of two ethnic groups,  Amhara  and  Oromo , revealed that gene variations associated with hemoglobin differences among Tibetans or other variants at the same  gene location  do not influence the adaptation in Ethiopians. [ 64 ]  Instead, several other genes appear to be involved in Ethiopians, including  CBARA1 ,  VAV3 ,  ARNT2  and  THRB , which are known to play a role in  HIF  genetic functions. [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2860", "contents": "The EPAS1 mutation in the Tibetan population has been linked to  Denisovan -related populations. [ 66 ]  The Tibetan  haplotype  is more similar to the Denisovan haplotype than any modern human haplotype. This mutation is seen at a high frequency in the Tibetan population, a low frequency in the Han population and is otherwise only seen in a sequenced Denisovan individual. This mutation must have been present before the Han and Tibetan populations diverged 2750 years ago. [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2861", "contents": "Birds have been especially successful at living at high altitudes. [ 67 ]   In general, birds have physiological features that are advantageous for high-altitude flight. The  respiratory system of birds  moves oxygen across the pulmonary surface during both inhalation and exhalation, making it more efficient than that of mammals. [ 68 ]  In addition, the air circulates in one direction through the  parabronchioles  in the lungs. Parabronchioles are oriented perpendicularly to the  pulmonary arteries , forming a  cross-current gas exchanger . This arrangement allows for more oxygen to be extracted compared to mammalian  concurrent gas exchange ; as oxygen diffuses down its concentration gradient and the air gradually becomes more deoxygenated, the pulmonary arteries are still able to extract oxygen. [ 69 ] [ page\u00a0needed ]  Birds also have a high capacity for oxygen delivery to the tissues because they have larger hearts and cardiac  stroke volume  compared to mammals of similar body size. [ 70 ]  Additionally, they have increased vascularization in their flight muscle due to increased branching of the  capillaries  and small muscle fibres (which increases  surface-area-to-volume  ratio). [ 71 ]  These two features facilitate oxygen diffusion from the blood to muscle, allowing flight to be sustained during environmental hypoxia. Birds' hearts and brains, which are very sensitive to arterial hypoxia, are more vascularized compared to those of mammals. [ 72 ]   The  bar-headed goose  ( Anser indicus ) is an iconic high-flyer that surmounts the Himalayas during migration, [ 73 ]  and serves as a model system for derived physiological adaptations for high-altitude flight.  R\u00fcppell's vultures ,  whooper swans ,  alpine chough , and  common cranes  all have flown more than 8\u00a0km (26,000\u00a0ft) above sea level."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2862", "contents": "Adaptation to high altitude has fascinated  ornithologists  for decades, but only a small proportion of high-altitude species have been studied. In Tibet, few birds are found (28  endemic species ), including  cranes ,  vultures ,  hawks ,  jays  and  geese . [ 29 ] [ 31 ] [ 74 ] \nThe Andes is quite rich in bird diversity. The  Andean condor , the largest bird of its kind in the  Western Hemisphere , occurs throughout much of the Andes but generally in very low densities; species of  tinamous  (notably members of the genus  Nothoprocta ),  Andean goose ,  giant coot ,  Andean flicker ,  diademed sandpiper-plover ,  mountain parakeet ,  miners ,  sierra-finches  and  diuca-finches  are also found in the highlands. [ 75 ] [ 76 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2863", "contents": "Evidence for adaptation is best investigated among the Andean birds. The  water fowls  and cinnamon teal ( Anas cyanoptera ) are found to have undergone significant  molecular modifications . It is now known that the \u03b1-hemoglobin subunit gene is highly structured between elevations among cinnamon teal populations, which involves almost entirely a single non-synonymous  amino acid   substitution  at position 9 of the  protein , with  asparagine  present almost exclusively within the low-elevation species, and  serine  in the high-elevation species. This implies important functional consequences for oxygen affinity. [ 77 ]  In addition, there is  strong divergence in body size in the Andes and adjacent lowlands. These changes have shaped distinct morphological and genetic divergence within South American cinnamon teal populations. [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2864", "contents": "In 2013, the molecular mechanism of high-altitude adaptation was elucidated in the Tibetan ground tit ( Pseudopodoces humilis ) using a draft genome sequence. Gene family expansion and positively selected gene analysis revealed genes that were related to cardiac function in the ground tit. Some of the genes identified to have positive selection include  ADRBK1  and  HSD17B7 , which are involved in the  adrenaline  response and  steroid hormone biosynthesis . Thus, the strengthened  hormonal system  is an adaptation strategy of this bird. [ 79 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2865", "contents": "Alpine  Tibet hosts a limited diversity of animal species, among which  snakes  are common. There are only two endemic  reptiles  and ten endemic  amphibians  in the Tibetan highlands. [ 74 ]   Gloydius himalayanus  is perhaps the geographically highest living snake in the world, living at as high as 4,900\u00a0m (16,100\u00a0ft) in the Himalayas. [ 80 ]  Another notable species is the  Himalayan jumping spider , which can live at over 6,500\u00a0m (21,300\u00a0ft) of elevation. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2866", "contents": "Many different plant species live in the high-altitude environment. These include  perennial grasses ,  sedges ,  forbs ,  cushion plants ,  mosses , and  lichens . [ 81 ]  High-altitude plants must adapt to the harsh conditions of their environment, which include low temperatures, dryness, ultraviolet radiation, and a short growing season. Trees cannot grow at high altitude, because of cold temperature or lack of available moisture. [ 82 ] :\u200a51\u200a  The lack of trees causes an  ecotone , or boundary, that is obvious to observers. This boundary is known as the  tree line ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2867", "contents": "The highest-altitude plant species is a  moss  that grows at 6,480\u00a0m (21,260\u00a0ft) on  Mount Everest . [ 83 ]  The sandwort  Arenaria bryophylla  is the highest flowering plant in the world, occurring as high as 6,180\u00a0m (20,280\u00a0ft). [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2868", "contents": "In  respiratory physiology , the  oxygen cascade  describes the flow of oxygen from air to  mitochondria , where it is consumed in  aerobic respiration  to release energy. [ 1 ]  Oxygen flows from areas with high  partial pressure  of oxygen (PO 2 , also known as  oxygen tension ) to areas of lower PO 2 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2869", "contents": "Air is typically around 21% oxygen, and at  sea level , the PO 2  of air is typically around 159  mmHg . [ 2 ]   Humidity  dilutes the concentration of oxygen in air. As air is inhaled into the lungs, it mixes with water and exhaust gasses including CO 2 , further diluting the oxygen concentration and lowering the PO 2 . As oxygen continues to flow down the  concentration gradient  from areas of higher concentration to areas of lower concentration, it must pass through barriers such as the  alveoli  walls,  capillary walls , capillary  blood plasma ,  red blood cell  membrane,  interstitial space , other  cell membranes , and cell  cytoplasm . The partial pressure of oxygen drops across each barrier. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2870", "contents": "Table 1 gives the example of a typical oxygen cascade for  skeletal muscle  of a healthy, adult male at rest who is breathing air at  atmospheric pressure  at  sea level . Actual values in a person may vary widely due to ambient conditions, health status, tissue type, and metabolic demands."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2871", "contents": "Oxygen equivalent  compares the relative amount of  oxygen  available for respiration at a variable pressure to that available at  SATP .  As  external respiration  depends on the exchange of gases due to partial pressures across a semipermeable membrane and normally occurs at SATP, an oxygen equivalent may aid in recognizing and managing variable oxygen availability during procedures such as hyperbaric oxygen therapy or  medical air transport ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2872", "contents": "It does so by expressing oxygen concentration as a ratio of the partial pressure of oxygen at a given altitude or pressure to Standard Atmospheric Pressure; rather than as a ratio of the PO 2  at a given pressure to the total pressure of the gas mixture.  The latter would generally be 0.2095, the atmospheric concentration by volume of O 2 , although FO 2  and P atm  vary for extraterrestrials. Calculations occur as follows:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2873", "contents": "Let O 2 E be oxygen equivalent, FO 2  be the fractional concentration of oxygen, P atm  (generally 760 mmHg, barring intergalactic travel), P b  be the barometric pressure, and dP be the change in pressure at a given altitude.  Then,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2874", "contents": "O 2 E = FO 2 (P b  + dP)/ P atm"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2875", "contents": "It is worthwhile to note that pressures may often be expressed in units of distance such as feet when diving.  For this, note that descending 33\u00a0ft in salt water or 33.9\u00a0ft in fresh water results in a change of 1 atm, so distance and pressure are used interchangeably in this context."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2876", "contents": "Oxygen pulse  is a  physiological  term for  oxygen  uptake per  heartbeat  at rest. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2877", "contents": "The  oxygen\u2013hemoglobin dissociation curve , also called the  oxyhemoglobin dissociation curve  or  oxygen dissociation curve  ( ODC ), is a  curve  that plots the proportion of  hemoglobin  in its saturated (oxygen-laden) form on the vertical axis against the prevailing  oxygen tension  on the horizontal axis. This curve is an important tool for understanding how our blood carries and releases oxygen. Specifically, the oxyhemoglobin dissociation curve relates  oxygen saturation  (S O 2 ) and  partial pressure  of oxygen in the blood (P O 2 ), and is determined by what is called \"hemoglobin affinity for oxygen\"; that is, how readily hemoglobin acquires and releases oxygen molecules into the fluid that surrounds it."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2878", "contents": "Hemoglobin  (Hb) is the primary vehicle for transporting  oxygen  in the  blood . Each hemoglobin molecule has the capacity to carry four oxygen molecules. These molecules of oxygen bind to the globin chain of the  heme   prosthetic group . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2879", "contents": "When hemoglobin has no bound oxygen, nor bound  carbon dioxide , it has the unbound conformation (shape). The binding of the first oxygen molecule induces change in the shape of the hemoglobin that increases its ability to bind to the other three oxygen molecules."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2880", "contents": "In the presence of dissolved carbon dioxide, the  pH  of the blood changes; this causes another change in the shape of hemoglobin, which increases its ability to bind carbon dioxide and decreases its ability to bind oxygen. With the loss of the first oxygen molecule, and the binding of the first carbon dioxide molecule, yet another change in shape occurs, which further decreases the ability to bind oxygen, and increases the ability to bind carbon dioxide. The oxygen bound to the hemoglobin is released into the blood's plasma and absorbed into the  tissues , and the carbon dioxide in the tissues is bound to the hemoglobin."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2881", "contents": "In the  lungs  the reverse of this process takes place. With the loss of the first carbon dioxide molecule the shape again changes and makes it easier to release the other three carbon dioxides."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2882", "contents": "Oxygen is also carried dissolved in the blood's  plasma , but to a much lesser degree. Hemoglobin is contained in  red blood cells . Hemoglobin releases the bound oxygen when  carbonic acid  is present, as it is in the tissues. In the  capillaries , where  carbon dioxide  is produced, oxygen bound to the hemoglobin is released into the blood's plasma and absorbed into the tissues."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2883", "contents": "How much of that capacity is filled by oxygen at any time is called the  oxygen saturation . Expressed as a percentage, the oxygen saturation is the ratio of the amount of oxygen bound to the hemoglobin, to the oxygen-carrying capacity of the hemoglobin. The oxygen-carrying capacity of hemoglobin is determined by the type of hemoglobin present in the blood. The amount of oxygen bound to the hemoglobin at any time is related, in large part, to the  partial pressure  of oxygen to which the hemoglobin is exposed. In the lungs, at the  alveolar\u2013capillary interface , the partial pressure of oxygen is typically high, and therefore the oxygen binds readily to hemoglobin that is present. As the blood circulates to other body tissue in which the partial pressure of oxygen is less, the hemoglobin releases the oxygen into the tissue because the hemoglobin cannot maintain its full bound capacity of oxygen in the presence of lower oxygen partial pressures."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2884", "contents": "The curve is usually best described by a  sigmoid  plot, using a formula of the kind:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2885", "contents": "A hemoglobin molecule can bind up to four oxygen molecules in a reversible method."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2886", "contents": "The shape of the curve results from the interaction of bound oxygen molecules with incoming molecules. The binding of the first molecule is difficult. However, this facilitates the binding of the second, third and fourth, this is due to the induced conformational change in the structure of the hemoglobin molecule induced by the binding of an oxygen molecule."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2887", "contents": "In its simplest form, the oxyhemoglobin dissociation curve describes the relation between the partial pressure of oxygen (x axis) and the oxygen saturation (y axis). Hemoglobin's affinity for oxygen increases as successive molecules of oxygen bind. More molecules bind as the oxygen partial pressure increases until the maximum amount that can be bound is reached. As this limit is approached, very little additional binding occurs and the curve levels out as the hemoglobin becomes saturated with oxygen. Hence the curve has a sigmoidal or S-shape. At pressures above about 60\u00a0mmHg, the standard dissociation curve is relatively flat, which means that the oxygen content of the blood does not change significantly even with large increases in the oxygen partial pressure. To get more oxygen to the tissue would require blood transfusions to increase the hemoglobin count (and hence the oxygen-carrying capacity), or supplemental oxygen that would increase the oxygen dissolved in plasma.\nAlthough binding of oxygen to hemoglobin continues to some extent for pressures about 50\u00a0mmHg, as oxygen partial pressures decrease in this steep area of the curve, the oxygen is unloaded to peripheral tissue readily as the hemoglobin's affinity diminishes.\nThe partial pressure of oxygen in the blood at which the hemoglobin is 50% saturated, typically about 26.6\u00a0mmHg (3.5\u00a0kPa) for a healthy person, is known as the  P 50 . The P 50  is a conventional measure of hemoglobin affinity for oxygen. In the presence of disease or other conditions that change the hemoglobin oxygen affinity and, consequently, shift the curve to the right or left, the P 50  changes accordingly. An increased P 50  indicates a rightward shift of the standard curve, which means that a larger partial pressure is necessary to maintain a 50% oxygen saturation. This indicates a decreased affinity. Conversely, a lower P 50  indicates a leftward shift and a higher affinity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2888", "contents": "The 'plateau' portion of the oxyhemoglobin dissociation curve is the range that exists at the pulmonary capillaries (minimal reduction of oxygen transported until the p(O 2 ) falls 50\u00a0mmHg)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2889", "contents": "The 'steep' portion of the oxyhemoglobin dissociation curve is the range that exists at the systemic capillaries (a small drop in systemic capillary p(O 2 ) can result in the release of large amounts of oxygen for the metabolically active cells)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2890", "contents": "To see the relative affinities of each successive oxygen as you remove/add oxygen from/to the hemoglobin from the curve compare the relative increase/decrease in p(O 2 ) needed for the corresponding increase/decrease in s(O 2 )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2891", "contents": "The strength with which oxygen binds to hemoglobin is affected by several factors. These factors shift or reshape the oxyhemoglobin dissociation curve. A  shift to right indicates that the hemoglobin under study has a decreased affinity for oxygen. This makes it more difficult for hemoglobin to bind to oxygen (requiring a higher partial pressure of oxygen to achieve the same oxygen saturation), but it makes it easier for the hemoglobin to release oxygen bound to it. \nThe effect of this shift of the curve increases the partial pressure of oxygen in the tissues when it is most needed, such as during exercise, or hemorrhagic shock."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2892", "contents": "In contrast, the curve is shifted to the left by the opposite of these conditions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2893", "contents": "This shift indicates that the hemoglobin under study has an increased affinity for oxygen so that hemoglobin binds oxygen more easily, but unloads it more reluctantly.\nLeft shift of the curve is a sign of hemoglobin's increased affinity for oxygen (e.g. at the lungs)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2894", "contents": "Similarly, right shift shows decreased affinity, as would appear with an increase in either body temperature, hydrogen ions,  2,3-bisphosphoglycerate  (2,3-BPG) concentration or carbon dioxide concentration."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2895", "contents": "Note:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2896", "contents": "The causes of shift to right can be remembered using the  mnemonic , \" CADET , face Right!\" for  C O 2 ,  A cid, 2,3- D PG, [ Note 1 ]   E xercise and  T emperature. [ 2 ]  Factors that move the oxygen dissociation curve to the right are those physiological states where tissues need more oxygen. For example, during exercise, muscles have a higher metabolic rate, and consequently need more oxygen, produce more carbon dioxide and lactic acid, and their temperature rises."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2897", "contents": "A decrease in pH (increase in  \u200a H +  ion concentration) shifts the standard curve to the right, while an increase shifts it to the left. This occurs because at greater  \u200a H +  ion concentration, various amino acid residues, such as Histidine 146 exist predominantly in their protonated form allowing them to form ion pairs that stabilize deoxyhemoglobin in the T state. [ 3 ]  The T state has a lower affinity for oxygen than the R state, so with increased acidity, the hemoglobin binds less O 2  for a given P O2  (and more H + ). This is known as the  Bohr effect . [ 4 ]  A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH is called the  root effect . This is seen in bony fish. The binding affinity of hemoglobin to O 2  is greatest under a relatively high pH."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2898", "contents": "Carbon dioxide  affects the curve in two ways. First, CO 2  accumulation causes  carbamino  compounds to be generated through chemical interactions, which bind to hemoglobin forming  carbaminohemoglobin . CO 2  is considered an  Allosteric regulation  as the inhibition happens not at the binding site of hemoglobin. [ 5 ]  Second, it influences  intracellular pH  due to formation of bicarbonate ion. Formation of carbaminohemoglobin stabilizes T state hemoglobin by formation of ion pairs. [ 3 ]  Only about 5\u201310% of the total CO 2  content of blood is transported as carbamino compounds, whereas (80\u201390%) is transported as bicarbonate ions and a small amount is dissolved in the plasma. The formation of a bicarbonate ion will release a proton into the plasma, decreasing pH (increased acidity), which also shifts the curve to the right as discussed above; low CO 2  levels in the blood stream results in a high pH, and thus provides more optimal binding conditions for hemoglobin and O 2 . This is a physiologically favored mechanism, since hemoglobin will drop off more oxygen as the concentration of carbon dioxide increases dramatically where tissue respiration is happening rapidly and oxygen is in need. [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2899", "contents": "2,3-Bisphosphoglycerate or 2,3-BPG (formerly named 2,3-diphosphoglycerate or 2,3-DPG) is an organophosphate formed in  red blood cells  during  glycolysis  and is the  conjugate base  of  2,3-bisphosphoglyceric acid . The production of 2,3-BPG is likely an important adaptive mechanism, because the production increases for several conditions in the presence of diminished peripheral tissue O 2  availability, such as  hypoxemia , chronic lung disease,  anemia , and  congestive heart failure , among others, which necessitate easier oxygen unloading in the peripheral tissue. High levels of 2,3-BPG shift the curve to the right (as in childhood), while low levels of 2,3-BPG cause a leftward shift, seen in states such as  septic shock , and  hypophosphataemia . [ 4 ]  In the absence of 2,3-BPG, hemoglobin's affinity for oxygen increases. 2,3-BPG acts as a  heteroallosteric effector  of hemoglobin, lowering hemoglobin's affinity for oxygen by binding preferentially to deoxyhemoglobin. An increased concentration of BPG in red blood cells favours formation of the T (taut or tense), low-affinity state of hemoglobin and so the oxygen-binding curve will shift to the right."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2900", "contents": "Increase in temperature shifts the oxygen dissociation curve to the right. When temperature is increased keeping the oxygen concentration constant, oxygen saturation decreases as the bond between oxygen and iron gets denatured. Additionally, with increased temperature, the partial pressure of oxygen increases as well. So, one will have a lesser amount of hemoglobin saturated for the same oxygen concentration but at a higher partial pressure of oxygen. Thus, any point in the curve will shift rightwards (due to increased partial pressure of oxygen) and downwards (due to weakened  \n \n \n \n \n Hb \n \n \u2212 \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n {\\displaystyle {\\ce {Hb-O2}}} \n \n bond), hence, the rightward shift of the curve. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2901", "contents": "Hemoglobin binds with  carbon monoxide  210 times more readily than with oxygen. [ 4 ]  Because of this higher affinity of hemoglobin for carbon monoxide than for oxygen, carbon monoxide is a highly successful competitor that will displace oxygen even at minuscule partial pressures. The reaction HbO 2  + CO \u2192 HbCO + O 2  almost irreversibly displaces the oxygen molecules forming  carboxyhemoglobin ; the binding of the carbon monoxide to the iron centre of hemoglobin is much stronger than that of oxygen, and the binding site remains blocked for the remainder of the life cycle of that affected red blood cell. [ 9 ]   With an increased level of carbon monoxide, a person can suffer from severe tissue  hypoxia  while maintaining a normal pO 2  because carboxyhemoglobin does not carry oxygen to the tissues."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2902", "contents": "Methemoglobinaemia  is a form of abnormal hemoglobin where the iron centre has been oxidised from the  ferrous +2   oxidation state  (the normal form, which on binding with oxygen changes to the ferric state) to the  ferric +3  state. This causes a leftward shift in the oxygen hemoglobin dissociation curve, as any residual heme with oxygenated ferrous iron (+2 state) is unable to unload its bound oxygen into tissues (because 3+ iron impairs hemoglobin's cooperativity), thereby increasing its affinity with oxygen. However, methemoglobin has increased affinity for  cyanide , and is therefore useful in the treatment of  cyanide poisoning . In cases of accidental ingestion, administration of a  nitrite  (such as  amyl nitrite ) can be used to deliberately oxidise hemoglobin and raise methemoglobin levels, restoring the functioning of  cytochrome oxidase . The nitrite also acts as a  vasodilator , promoting the cellular supply of oxygen, and the addition of an iron salt provides for competitive binding of the free cyanide as the biochemically inert  hexacyanoferrate(III)  ion, [Fe(CN) 6 ] 3\u2212 . An alternative approach involves administering  thiosulfate , thereby converting cyanide to  thiocyanate , SCN \u2212 , which is excreted  via  the kidneys.  Methemoglobin is also formed in small quantities when the dissociation of oxyhemoglobin results in the formation of methemoglobin and  superoxide , O 2 \u2212 , instead of the usual products. Superoxide is a  free radical  and causes biochemical damage, but is neutralised by the action of the enzyme  superoxide dismutase ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2903", "contents": "Myo-inositol trispyrophosphate  (ITPP), also known as OXY111A, is an  inositol phosphate  that causes a rightward shift in the oxygen hemoglobin dissociation curve through  allosteric modulation  of hemoglobin within red blood cells.  It is an experimental drug intended to reduce tissue  hypoxia .  The effects appear to last roughly as long as the affected red blood cells remain in circulation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2904", "contents": "Fetal hemoglobin  (HbF) is structurally different from normal  adult hemoglobin  (HbA), giving HbF a higher affinity for oxygen than HbA.  HbF is composed of two alpha and two gamma chains whereas HbA is composed of two alpha and two beta chains.  The fetal dissociation curve is shifted to the left relative to the curve for the normal adult because of these structural differences:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2905", "contents": "In adult hemoglobin, the binding of 2,3-bisphosphoglycerate (2,3-BPG) primarily occurs with the beta chains, preventing the binding of oxygen with haemoglobin. This binding is crucial for stabilizing the  deoxygenated state of hemoglobin, promoting the efficient release of oxygen to body tissues."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2906", "contents": "In fetal hemoglobin, which possesses a gamma chain instead of a beta chain, the interaction with 2,3-BPG differes because 2,3 - -BPG not binds with gamma chain as it has lower to no affinity with gamma chain.This distinction contributes to fetal hemoglobin having a higher affinity for oxygen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2907", "contents": "Typically, fetal arterial oxygen pressures are lower than adult arterial oxygen pressures.  Hence higher affinity to bind oxygen is required at lower levels of partial pressure in the fetus to allow diffusion of oxygen across the  placenta .  At the placenta, there is a higher concentration of  2,3-BPG  formed, and 2,3-BPG binds readily to beta chains rather than to alpha chains. As a result, 2,3-BPG binds more strongly to adult hemoglobin, causing HbA to release more oxygen for uptake by the fetus, whose HbF is unaffected by the 2,3-BPG. [ 10 ]  HbF then delivers that bound oxygen to tissues that have even lower partial pressures where it can be released."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2908", "contents": "Pendelluft (Derived from the German words for pendulum and air. [ 1 ] ) refers to the movement of gas between two regions of the lung, usually between regions of differing  compliance  or  airway resistance . Pendelluft is an important physiological concept to take into account during  mechanical ventilation , particularly in patients with an open thorax, severe  bronchospasm  (e.g. asthma or  COPD ), or with heterogeneous lung compliance (e.g.  ARDS ). It was first published as a physiological concept in 1956. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2909", "contents": "An extreme example of pendelluft is found in a spontaneously breathing patient with an  open hemithorax [ 3 ]  or large  flail segment . [ 4 ]  During the inspiratory phase, the contralateral lung (with a closed / intact chest wall) will expand with most of the tidal volume, with the open  plura  or paradoxical chest wall movement preventing expansion of the ipsilateral lung. However, during the expiratory phase, there will be gas flow (pendelluft) from the contralateral lung to the lung ipsilateral to the open thorax. Inspiration can also cause gas movement from the ipsilateral to the contralateral lung. [ 3 ]  This can significantly impair ventilation, and historically was one issue that limited thoracic surgery until more complex methods of mechanical ventilation were available."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2910", "contents": "Less profound bulk gas flow occurs in conditions where lung compliance and resistance is heterogenous. Lung units which have slow time constants may fill through gas flow from neighbouring lung units with fast time constants. This gas flow can help improve ventilation of  alveoli  in regions with increased airway resistance or poorer compliance, improving  V/Q matching . The consequence of this is that increased respiratory rates / reduced inspiratory times may prevent slow time unit alveoli from being recruited, worsening V/Q matching and thus worsening oxygenation. The presence of pendelluft between different lung units in a mechanically ventilated patient can be demonstrated by an inspiratory hold manoeuvre, allowing gas flow between lung units to equilibrate, reflected in a  plateau pressure . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2911", "contents": "Pendelluft is one mechanism by which ventilation occurs during  High-frequency oscillatory ventilation [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2912", "contents": "A final example of pendelluft is if two separate individuals are mechanically ventilated with one ventilator, as might be considered during a shortage of ventilators (such as during a  pandemic ). Even for two individuals well matched for weight and height (and thus appropriate tidal volume), differences in lung mechanics such as resistance and compliance (particularly due to underlying  ARDS ) may lead to pendelluft between the two patients in the circuit. Despite this and many other limitations, ventilation of two patients simultaneously was considered [ 7 ]  and trialled [ 8 ]  during the  COVID-19 pandemic , however was not used widely."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2913", "contents": "Perfusion  is the passage of fluid through the  circulatory system  or  lymphatic system  to an  organ  or a  tissue , [ 1 ]  usually referring to the delivery of  blood  to a  capillary  bed in tissue. Perfusion may also refer to fixation via perfusion, used in histological studies. Perfusion is measured as the rate at which blood is delivered to tissue, [ 2 ]  or volume of blood per unit time (blood  flow ) per unit tissue mass. The  SI unit  is m 3 /(s\u00b7kg) [ citation needed ] , although for human organs perfusion is typically reported in ml/min/g. [ 3 ]  The word is derived from the French verb  perfuser , meaning to \"pour over or through\". [ 4 ]  All animal tissues require an adequate blood supply for  health  and  life . Poor perfusion (malperfusion), that is,  ischemia , causes health problems, as seen in  cardiovascular disease , including  coronary artery disease ,  cerebrovascular disease ,  peripheral artery disease , and many other conditions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2914", "contents": "Tests verifying that adequate perfusion exists are a part of a patient's assessment process that are performed by  medical  or emergency personnel.  The most common methods include evaluating a body's  skin  color,  temperature , condition (dry/soft/firm/swollen/sunken/etc), and  capillary refill ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2915", "contents": "During major surgery, especially  cardiothoracic surgery , perfusion must be maintained and managed by the  health professionals  involved, rather than left to the body's  homeostasis  alone. As the lead surgeons are often too busy to handle all  hemodynamic  control by themselves, specialists called  perfusionists  manage this aspect. There are more than one hundred thousand perfusion procedures annually. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2916", "contents": "In 1920,  August Krogh  was awarded the  Nobel Prize in Physiology or Medicine  for his discovering the mechanism of regulation of  capillaries  in  skeletal muscle . [ 6 ] [ 7 ]  Krogh was the first to describe the adaptation of blood perfusion in muscle and other organs according to demands through the opening and closing of  arterioles  and  capillaries . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2917", "contents": "Malperfusion  can refer to any type of incorrect perfusion though it usually refers to hypoperfusion. The meaning of the terms \"overperfusion\" and \"underperfusion\" is relative to the average level of perfusion that exists across all the tissues in an individual body. Perfusion levels also differ from person to person depending on metabolic demand. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2918", "contents": "Examples follow: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2919", "contents": "Overperfusion and underperfusion should not be confused with  hypoperfusion  and  hyperperfusion , which relate to the perfusion level relative to a tissue's current need to meet its metabolic needs. For example, hypoperfusion can be caused when an  artery  or  arteriole  that supplies blood to a volume of tissue becomes blocked by an  embolus , causing either no blood or at least not enough blood to reach the tissue. Hyperperfusion can be caused by  inflammation , producing  hyperemia  of a body part. Malperfusion, also called poor perfusion, is any type of incorrect perfusion. There is no official or formal dividing line between hypoperfusion and  ischemia ; sometimes the latter term refers to zero perfusion, but often it refers to any hypoperfusion that is bad enough to cause  necrosis . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2920", "contents": "In equations, the symbol Q is sometimes used to represent perfusion when referring to  cardiac output . However, this terminology can be a source of confusion since both cardiac output and the symbol Q refer to  flow  (volume per unit time, for example, L/min), whereas perfusion is measured as flow per unit tissue mass (mL/(min\u00b7g)). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2921", "contents": "Microspheres that are labeled with  radioactive isotopes  have been widely used to measure perfusion since the 1960s. Radioactively labeled particles are injected into the test subject and a  radiation detector  measures radioactivity in tissues of interest. [ 8 ]  Microspheres are used in  radionuclide angiography , a method of diagnosing heart problems."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2922", "contents": "In the 1990s, methods for using  fluorescent  microspheres became a common substitute for radioactive particles. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2923", "contents": "Perfusion of various tissues can be readily measured  in vivo  with nuclear medicine methods which are mainly  positron emission tomography  (PET) and  single photon emission computed tomography  (SPECT). [ citation needed ]  Various radiopharmaceuticals targeted at specific organs are also available, some of the most common are: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2924", "contents": "Two main categories of magnetic resonance imaging (MRI) techniques can be used to measure tissue perfusion  in vivo ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2925", "contents": "Brain perfusion (more correctly transit times) can be estimated with contrast-enhanced computed tomography. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2926", "contents": "Perfusion can be determined by measuring the total  thermal diffusion  and then separating it into  thermal conductivity  and perfusion components. [ 13 ]   rCBF  is usually measured continuously in time.  It is necessary to stop the measurement periodically to cool down and reassess the  thermal conductivity . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2927", "contents": "Peripheral chemoreceptors  (of the  carotid  and  aortic bodies ) are so named because they are  sensory  extensions of the  peripheral nervous system  into  blood vessels  where they detect changes in chemical concentrations. [ 1 ]  As  transducers  of patterns of variability in the surrounding environment, carotid and aortic bodies count as chemosensors in a similar way as  taste buds  and  photoreceptors . [ 2 ]  However, because carotid and aortic bodies detect variation within the body's internal organs, they are considered  interoceptors . [ 3 ]   Taste buds ,  olfactory bulbs , photoreceptors, and other receptors associated with the five traditional  sensory modalities , by contrast, are exteroceptors in that they respond to stimuli outside the body. [ 3 ]  The body also contains  proprioceptors , which respond to the amount of stretch within the  organ , usually  muscle , that they occupy. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2928", "contents": "As for their particular function, peripheral chemoreceptors help maintain  homeostasis  in the cardiorespiratory system by monitoring concentrations of blood borne chemicals. [ 4 ]  These  polymodal  sensors respond to variations in a number of blood properties, including low oxygen ( hypoxia ), high carbon dioxide ( hypercapnia ), and low glucose ( hypoglycemia ). [ 4 ]  Hypoxia and  hypercapnia  are the most heavily studied and understood conditions detected by the peripheral chemoreceptors.  Glucose  is discussed in a later section.  Afferent nerves  carry signals back from the carotid and aortic bodies to the  brainstem , which responds accordingly (e.g. increasing  ventilation ). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2929", "contents": "Both  carotid bodies  and  aortic bodies  increase sensory discharge during hypoxia. [ 5 ]  Carotid bodies are considered the primary peripheral chemoreceptor and have been shown to contribute more to a  hypoxic  response. However, in the chronic absence of the carotid body, the aortic body is able to perform a similar respiratory regulatory role, suggesting that it possesses efficacious mechanisms of  signal transduction  as well. [ 5 ]  The differing locations of the two bodies ideally position them to take advantage of different information; the carotid bodies, located on one of the main  arteries  of the  neck , monitor  partial pressure  within arterial vessels while aortic body, located on the  aortic arch , monitors oxygen concentration closer to the  heart . [ 3 ]  Each of these bodies is composed of a similar collection of cells, and it is the post-transduction  signal processing  that differentiates their responses. However, little is known about the specifics of either of these signaling mechanisms. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2930", "contents": "Carotid and aortic bodies are clusters of cells located on the  common carotid artery  and the  aortic arch , respectively. [ 6 ]  Each of these peripheral chemoreceptors is composed of type I  glomus cells  and glia-like type II cells. [ 6 ]  The type-I cells  transduce  the signals from the bloodstream and are  innervated  by  afferent nerve  fibers leading back to (in the carotid body) the  carotid sinus nerve  and then on to the  glossopharyngeal nerve  and medulla of the  brainstem . The aortic body, by contrast, is connected to the medulla via the  vagus nerve . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2931", "contents": "They also receive input from  efferent nerve  fibers leading back to the same set of nerves. The entire cluster of cells is infiltrated with  capillaries  to provide access to the bloodstream; the high capillary density makes this one of the areas of the body with the greatest blood flow. [ 6 ]  Type I cells are densely packed with  vesicles  containing various neurotransmitters, including  dopamine ,  ATP ,  serotonin ,  catecholamine , released during  transduction . [ 1 ]  Type I cells are often connected via  gap junctions , which might allow for quick communication between cells when transducing signals. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2932", "contents": "Type II cells occur in a ratio of about 1 to 4 with type I cells. Their long bodies usually occur in close association with type I cells, though they do not entirely encase type I cells. [ 6 ]  They lack the vesicles of type I cells used in  neurotransmitter  communication, [ 1 ]  but studies indicate they function as chemoreceptor  stem cells  and can respond to prolonged exposure to hypoxia by proliferating into type I cells themselves. [ 7 ]  They may also bolster rapid communication among type I cells by amplifying release of one of the primary  neurotransmitters  in chemoreceptive signaling, ATP. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2933", "contents": "Sensitivity and  physiology  of the peripheral chemoreceptors changes throughout the lifespan. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2934", "contents": "Respiration in  neonates  is irregular, prone to  periodic breathing  and  apnea . [ 8 ]  In utero and at birth, the carotid body's response to hypoxia is not fully developed; it takes a few days to a few weeks to increase its sensitivity to that of an adult carotid body. During this period of development, it is proposed that  neonates  heavily rely on other oxygen-sensing chemoreceptors, such as the aortic body or  central chemoreceptors . [ 5 ]  However, non-carotid body chemoreceptors are sometimes not enough to ensure appropriate ventilatory response;  SIDS  deaths occur most frequently during the days or weeks in which the carotid body is still developing, and it is suggested that lack of appropriate carotid body activity is implicated in this condition. SIDS victims often are reported to have displayed some of the characteristic troubles in carotid body development, including  periodic breathing , much  sleep apnea , impaired  arousal  during sleep, and low sensitivity to hypoxia. The carotid bodies of SIDS victims also often display physiological abnormalities, such as hypo- and  hypertrophy . Many of the findings on to carotid body's relation to SIDS report that carotid body development is impaired by environmental factors that were already known to increase the risk of SIDS, such as  premature birth  and exposure to smoke, substances of abuse,  hyperoxia , and hypoxia, so it may seem initially as if carotid body studies are only extending what we know about SIDS into another domain. However, understanding the mechanisms that impair carotid body development could help elucidate how certain aspects of  neonatal , particularly  premature , care might be improved. For example,  oxygen therapy  may be an example of a technique that exposes premature infants to such high oxygen levels that it prevents them from acquiring appropriate sensitivity to normal oxygen levels. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2935", "contents": "Increased base rate of  ventilation  and  sensitivity  to both  hypoxia  and  hypercapnia  occur in pregnant women after  gestation  week 20, and studies suggest this is due at least in part to changes in peripheral chemoreceptor sensitivity. Similar changes in sensitivity have been found in women administered levels of  hormones  that mimic the stage of the pregnancy in which these effects being to appear, suggesting that carotid and aortic body sensitivity is modulated by  neuroendocrine  processes. [ 5 ]  However, findings tying peripheral chemoreceptors to pregnancy-induced variations in breathing could just be correlational, so further studies are needed to identify the cause behind this relation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2936", "contents": "Peripheral chemoreceptors were identified as necessary to  breathing  regulation much sooner than their mechanisms for acquiring information from the bloodstream were beginning to be understood. [ 4 ]  Both carotid and aortic bodies are composed of type I and type II cells and are believed to  transduce  signals from blood chemicals in the same way, though post-transduction signal communication may differ. [ 6 ]  Chemosensory transduction in these  receptors  is still an active area of research, and not all studies agree, but there is growing support for a transduction mechanism dependent upon  mitochondrial  consumption of oxygen affecting the  AMPK  enzyme. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2937", "contents": "Transferring the signal to the medulla requires that  neurotransmitter  be released from the vesicles in the type I cells, and as with many other neural cells, this is triggered by an influx of  calcium  into the cell after membrane  depolarization . [ 6 ]  The process of identifying  signal transduction  in  interoceptors  such as the peripheral chemoreceptors requires moving backward from membrane depolarization to discover the previous steps, often internal to the cell, that transduces blood chemicals to a neural signal. Up to this point, most research agrees that membrane depolarization is caused by  inhibition  of  potassium channels  that otherwise maintain the  resting potential . [ 4 ]   As to the step before potassium channel inhibition, many mechanisms are proposed, none of which receive unanimous support from the research community. [ 7 ]  Multiple types of potassium channels respond to  hypoxia , with significant differences between different species, and a number of different types for each species. [ 4 ]   Expression of potassium channels also changes throughout the lifetime. [ 8 ]  Some studies propose that heme-oxygenase 2 is the  transducer ; however, since its deletion in mice does not affect chemoreceptor oxygen sensitivity, [ 10 ]  this hypothesis is open to question. Another enzyme, AMP-activated protein kinase (AMPK), provides a mechanism that could apply not only to all types of potassium channels but also other oxygen-sensing  tissues  in the body, such as  pulmonary  vasculature and  neonatal   chromaffin cells . AMPK is an  enzyme  activated by an increase in the  AMP : ATP  ratio resulting from increasing  cellular respiration .  Once activated, the  enzyme  promotes production of ATP and suppresses reactions that consume it. AMPK activation is also a more appealing candidate because it can activate both of the two most common types of potassium channels. Another study identified that AMPK opens and closes potassium channels via  phosphorylation , further underlining the link between the two. The role of AMPK in oxygen sensing in type-1 cells has however also recently been called into question. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2938", "contents": "This enzyme's function positions type I cells to uniquely take advantage of their mitochondria.  However, AMPK is an enzyme found in many more types of cells than chemoreceptors because it helps regulate  metabolism . The difference may actually lie in the cell's metabolism, rather than the AMPK enzyme; peripheral chemoreceptors display very high background rates of oxygen consumption, supported by its dense network of  capillaries . Since its base rate of cellular respiration is so high, its AMPK would be more sensitive to reductions in blood borne oxygen, thus allowing it to respond to small variations in oxygen content before other cells begin to feel the effects of its absence. [ 4 ]   In this way, transduction in peripheral chemoreceptor cells is relatively unique. It does not require any specialized proteins that change shape in the presence of  light  or a specific receptor site for a particular tastant. Its necessary components include merely the mitochondria and an enzyme used to regulate its activity common to all aerobic cells, a suite of  potassium  and  calcium channels  and neurotransmitters common to many types of nerve cells, and a well-endowed version of the vasculature supporting all aerobic cells. [ 4 ]   Further research should identify why type I cells exhibit such a high metabolic rate compared to other cell types, as this may be the truly unique feature of the receptor. And thus, a receptor for an  aerobic  organism's most basic energy source is composed of collection of cell structures common throughout the body."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2939", "contents": "Peripheral chemoreceptors are put under stress in a number of situations involving low access to oxygen, including exercise and exposure to high altitude. [ 5 ]  Under sustained hypoxic stress, regardless of the cause, peripheral chemoreceptors show a great deal of  plasticity ; they will both swell the size of chemosensing cells and increase their number. [ 5 ]  Though researchers were previously unsure how carotid and aortic bodies came to increase their numbers so rapidly, recent findings point to the type II cells, which were previously thought to have only a supportive role and are now believed to retain properties of  stem cells  and can  differentiate  into type I transducer cells. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2940", "contents": "Several studies suggest peripheral chemoreceptors play a role in  ventilation  during exercise. However, there is disagreement about whether they perform an  excitatory  or  inhibitory  role. Several studies point to increased circulation of  catecholamine  or potassium during exercise as a potential effector on peripheral chemoreceptors; however, the specifics of this effect are not yet understood. All suggestions of peripheral chemoreceptor involvement conclude that they are not solely accountable for this response, emphasizing that these receptors are only one in a suite of oxygen-sensing cells that can respond in times of stress. Collecting information on carotid and aortic body activity in live, exercising humans is fraught with difficulty and often only indicates indirect evidence, so it is hard to draw expansive conclusions until more evidence has been amassed, and hopefully with more advanced techniques. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2941", "contents": "In addition to ventilatory effects, peripheral chemoreceptors may influence  neuroendocrine  responses to exercise that can influence activities other than ventilation. [ 5 ]  Circulation of the  glucose -promoting  hormone ,  glucagon  and a neurotransmitter,  norepinephrine , is increased in carotid- and aortic-body-enervated dogs, suggesting that peripheral chemoreceptors respond to low glucose levels in and may respond to other neuroendocrine signals in addition to what is traditionally considered to be their sole role of ventilatory regulation. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2942", "contents": "Peripheral chemoreceptors work in concert with  central chemoreceptors , which also monitor blood CO 2  but do it in the  cerebrospinal fluid  surrounding the  brain . A high concentration of central chemoreceptors is found in the  ventral   medulla , the  brainstem  area that receives input from peripheral chemoreceptors. [ 12 ]  Taken together, these blood oxygen monitors contribute nerve signals to the  vasomotor center  of the medulla which can modulate several processes, including breathing,  airway resistance ,  blood pressure , and  arousal . [ 3 ]  At an evolutionary level, this stabilization of oxygen levels, which also results in a more constant  carbon dioxide  concentration and  pH , was important to manage oxygen flow in air-vs.-water breathing,  sleep , and to maintain an ideal  pH  for  protein structure , since fluctuations in pH can  denature  a cell's enzymes. [ 3 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2943", "contents": "The  preB\u00f6tzinger complex , often abbreviated as  preB\u00f6tC , is a functionally and anatomically specialized site in the ventral-lateral region of the lower  medulla oblongata  (i.e., lower  brainstem ). The preB\u00f6tC is part of the  ventral respiratory group  of respiratory related  interneurons . Its foremost function is to generate the inspiratory breathing rhythm in mammals. In addition, the preB\u00f6tC is widely and paucisynaptically connected to higher brain centers that regulate arousal and excitability more generally such that respiratory brain function is intimately connected with many other rhythmic and cognitive functions of the brain and central nervous system. Further, the preB\u00f6tC receives mechanical sensory information from the airways that encode lung volume as well as pH, oxygen, and carbon dioxide content of circulating blood and the cerebrospinal fluid."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2944", "contents": "The preB\u00f6tC is approximately colocated with the hypoglossal (XII) cranial motor nucleus as well as the \u2018loop\u2019 portion of the inferior olive in the anterior-posterior axis. The caudal border of the preB\u00f6tC is slightly caudal to the  obex , where the brainstem merges with the cervical spinal cord."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2945", "contents": "The initial description of the preB\u00f6tC was widely disseminated in a 1991 paper in  Science , [ 1 ]  but its discovery predates that paper by one year. [ 2 ]  The team was led by Jack L. Feldman and Jeffrey C. Smith at the University of California, Los Angeles (UCLA), but the  Science  paper  [ 1 ]  also included UCLA coauthor Howard Ellenberger, as well as Klaus Ballanyi and Diethelm W. Richter from G\u00f6ttingen University in Germany. The region derives its name from a neighboring medullary region involved in expiratory breathing rhythm dubbed  B\u00f6tzinger complex , which was named after the  Silvaner  (B\u00f6tzinger) variety of wine, featured at the conference at which that region was named ( click here  to hear a BBC interview with Jack Feldman on the topic of B\u00f6tzinger / preB\u00f6tzinger nomenclature)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2946", "contents": "The first definition of the preB\u00f6tC was based largely on functional criteria. If the central  neuraxis  from pons to lumbar spinal cord is removed from a newborn rodent, then basic neural motor patterns can be generated and recorded using microelectrodes  in vitro . The breathing rhythm emerges spontaneously with robust and continuous motor activity measurable on any cranial or spinal motor nerve that innervates breathing related musculature. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2947", "contents": "By isolating a rhythmically active newborn rat brainstem-spinal cord in a microsectioning vibratome, Smith and colleagues performed a series of 75\u00a0\u03bcm-thick transverse sections while monitoring inspiratory-related motor rhythms. The preB\u00f6tC represented the portion of the ventral-lateral lower brainstem that was necessary and sufficient to generate inspiratory related rhythm and motor output  in vitro . Surprisingly, if microsections were applied from the anterior and posterior regions of the neuraxis simultaneously, a transverse section of thickness ~500\u00a0\u03bcm \u2013 which retained the preB\u00f6tC and XII motoneurons \u2013 generated a rhythm and motor pattern that was almost identical to the rhythm and pattern in the full brainstem-spinal cord preparation. Perturbations that elevated excitability in preB\u00f6tC sped up respiratory rhythm, whereas perturbations that depressed its excitability slowed the rhythm down. The authors concluded that these preB\u00f6tC-retaining slice preparations preserved the core network generating inspiratory rhythm as well as premotor and motor neurons that define a minimal breathing-related circuit suitable for studies under controlled conditions  in vitro .  Breathing slices  became a widely exploited preparation for such studies that continue to be used by laboratories worldwide to the present day. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2948", "contents": "Anatomical observations advanced understanding of the preB\u00f6tC by providing specific markers expressed by its constituent neurons, which helped understand its approximate borders. The superset of markers is based largely on neuropeptides and peptide receptors, whose expression patterns have come to define the borders of preB\u00f6tC and its constituent rhythm-generating and output pattern-related interneurons . preB\u00f6tC neurons selectively express neurokinin-1 receptors (NK1Rs), \u03bc-opioid receptors (\u03bcORs), as well as \u00a0somatostatin (SST) and SST2a-type receptors. [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ]  Of course,  selectively  does not mean exclusively or entirely. Each marker has limitations as a defining feature of the preB\u00f6tC core, but generally speaking, the neuropeptide-related markers below have proved to be both reliable and of great utility in the quest to define preB\u00f6tC structure and function."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2949", "contents": "Peptide markers have been used to probe preB\u00f6tC function. Substance P (SP) accelerated inspiratory rhythms  in vitro   [ 6 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ]  by depolarizing putatively rhythmogenic preB\u00f6tC neurons. SP also depolarized preB\u00f6tC neurons whose function is premotor-related, i.e., those neurons transmit the nascent inspiratory rhythm to motoneurons outside the preB\u00f6tC. [ 17 ] [ 18 ]  The net result was that SP sped up the rhythm and elevated the baseline level neural activity in XII nerve recordings  in vitro ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2950", "contents": "The expression of NK1Rs by preB\u00f6tC neurons was used to test its inspiratory rhythm-generating, role. SP, conjugated to the ribosomal toxin saporin, was injected into the preB\u00f6tC of adult rats. Over the course of a week, this intervention caused progressive breathing deficits that ultimately resulted in severely pathological (i.e., ataxic) breathing. [ 19 ] [ 20 ]  SP-saporin-injected rats also experienced sleep deficits and extraordinary sensitivity to anesthesia. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2951", "contents": "Expression of \u03bcORs appear to be less widespread than NK1Rs among constituent preB\u00f6tC neurons. Although expressed somewhat more sparsely, the application of \u03bcOR agonists like [D-Ala 2 , NMe-Phe 4 , Gly-ol 5 ]-enkephalin (i.e., DAMGO) potently slowed the inspiratory rhythm. Note, this observation  in vitro  presaged the 2010-2020's crisis of opioid-drug related deaths by respiratory failure, which are attributable in large part to depression of rhythm-generating function in the preB\u00f6tC (but also see: [ 22 ] [ 23 ] )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2952", "contents": "In the late 1980s and early 1990s, following discovery of the preB\u00f6tC,  in vitro  preparations from neonates were not yet widely accepted as experimental models of the respiratory neural control system in adults. Some groups argued that  in vitro  rhythms reflected gasping rather than breathing, [ 24 ]  despite the fact that  in vitro  preparations, show physiological levels of oxygen and pH even several hundred micrometers below the surface of the tissue. [ 25 ] [ 26 ]  Thus, the SP-saporin experiments  [ 21 ] [ 19 ] [ 20 ]  were critical for showing that the preB\u00f6tC was necessary for normal breathing in un-anesthetized adult animals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2953", "contents": "Nevertheless, one is confronted with a disparity of motor patterns. The pattern of phrenic or XII nerve activity  in vitro  shows an abrupt onset followed by a decremental pattern, whereas  in vivo  the inspiratory motor nerves typically show an incremental onset followed by a more precipitous offset. The differences in the motor patterns measured in adults  in vivo  and those of  in vitro  preparations can be explained age- and development-related differences, the loss of mechanical sensory feedback  in vitro  , and the temperature ( in vitro  preparations are typically maintained ~10\u00a0\u00b0C lower than physiological temperature). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2954", "contents": "SST and SST2a receptors are expressed by neurons in the preB\u00f6tC. Unlike NK1R expression, which remains rather strong in regions caudal to the preB\u00f6tC within the cervical spinal cord, [ 9 ]  SST expression appears to peak in the anterior-posterior axis at the region recognized as the preB\u00f6tC. [ 11 ]  Could SST-expressing preB\u00f6tC neurons be markers for the preB\u00f6tC core? Investigators installed in the preB\u00f6tC a peptide receptor from  fruit fly , adapted for expression in mammals, that activates potassium channels. Whether awake or anesthetized, activation of those potassium channel-linked receptors in SST-expressing neurons of the preB\u00f6tC reduced breathing movements, both their amplitude and frequency, and ultimately caused apnea, i.e., a lack of breathing. The exogenous peptide that activates the fly receptor was ultimately cleared from the central nervous system: injected rats nonetheless needed mechanical ventilation until they recovered from the experiment. [ 27 ]  Subsequent studies examined the underlying cellular mechanisms and have come to the conclusion that preB\u00f6tC neurons expressing SST are related to transmission of the rhythm from core rhythmogenic neurons to premotor neurons inspiratory neurons. The SST \u201coutput\u201d neurons are intermingled in the preB\u00f6tC with rhythm-generating neurons, and their function is to coactivate and pass on inspiratory rhythm to dedicated premotor populations outside of the preB\u00f6tC. [ 28 ] [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2955", "contents": "Other markers for the preB\u00f6tC include peptide hormone thyrotropin releasing hormone (TRH) and the glycoprotein reelin. [ 30 ] [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2956", "contents": "In summary, the preB\u00f6tC is the source of rhythmic activity that \u2013 once distributed to premotor and motoneurons of respiratory muscles \u2013 produces inspiratory breathing movements. The neurons that comprise the preB\u00f6tC express NK1Rs, \u03bcORs, SST2a receptors, and SST. Each of these markers holds functional significance for modulation of preB\u00f6tC rhythmicity, and their expression delineates the borders of the preB\u00f6tC. SP accelerated inspiratory rhythms measured  in vitro  and ablation of NK1R-expressing preB\u00f6tC neurons caused severe pathologies of breathing that were ultimately fatal. The \u03bcORs also map the preB\u00f6tC and opioid drugs depress breathing rhythms, which is further evidence of the preeminent rhythmogenic role of the preB\u00f6tC. SST is a peptide transmitter rather than a receptor, but its expression also maps the preB\u00f6tC. SST-expressing neurons are breathing essential, but their role is linked to the production of motor output rather than generation of rhythm  per se ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2957", "contents": "The rhythm-generating core of preB\u00f6tC incorporates glutamatergic interneurons that express the gene  Slc17a6  (i.e.,  Vglut2 ). preB\u00f6tC glutamatergic neurons also express NK1Rs and \u03bcORs, but probably not SST. Pharmacological studies showed that excitatory transmission, predominantly via AMPA- and kainate-type ionotropic glutamate receptors were essential for rhythm generation as well as transmission to premotor neurons and ultimately motor output. [ 32 ] [ 33 ]  Furthermore,  Vglut2 -knockout mice fail to breathe at birth. Transverse slices from late-stage embryos of  Vglut2 -knockout mice fail to generate rhythmic activity in the preB\u00f6tC. Nevertheless, the cellular composition of the preB\u00f6tC appears relatively unperturbed and constituent neurons express electrical properties associated with the preB\u00f6tC in early postnatal mice, which emphasizes the importance of excitatory synaptic interactions for rhythm generation. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2958", "contents": "A subset of preB\u00f6tC glutamatergic neurons are derived from progenitor cells that express transcription factor  Dbx1  (developing brain homeobox 1) during embryonic development. In slices from early postnatal  Dbx1  reporter mice,  Dbx1 -derived preB\u00f6tC neurons are rhythmically active  in vitro  in sync with inspiratory rhythm and motor output. Examined histologically,  Dbx1 -derived preB\u00f6tC neurons express NK1Rs, \u03bcORs, SST2a receptors, as well as SST. [ 35 ] [ 36 ]  Also in slices from postnatal  Dbx1  reporter mice, the selective photonic ablation of  Dbx1 -derived preB\u00f6tC neurons diminishes XII motor output magnitude and decelerates then irreversibly stops the XII rhythm. [ 37 ]  In adult mice that express light-sensitive cation channels (channelrhodopsin 2) in  Dbx1 -derived neurons, optogenetic photostimulation speeds up breathing and increases tidal volume of the breaths. Mice expressing proton pumps (archaerhodopsin) in  Dbx1 -derived preB\u00f6tC neurons slows or stops breathing movements. When the breathing is slowed via photoinhibition of  Dbx1 -derived preB\u00f6tC neurons, the tidal volume of the breaths is diminished. [ 28 ] [ 38 ] [ 39 ] [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2959", "contents": "Dbx1  is a useful marker for the core preB\u00f6tC neurons, but with caveats. First,  Dbx1  is expressed during embryonic development, [ 35 ] [ 36 ] [ 41 ]  which makes it more challenging (though far from impossible  [ 42 ] [ 43 ] ) to use as a marker or a tool to manipulate neuronal function compared to genes like  Vglut2  that are expressed throughout life. Second,  Dbx1 , like  Vglut2 , marks output-related preB\u00f6tC neurons as well as premotor neurons in the reticular formation that transmit to the hypoglossal motoneurons and phrenic premotor neurons upper cervical spinal cord. [ 44 ]  Third,  Dbx1  is an embryonic transcription factor that governs the development of many populations in the brain and central nervous system, notably the V0 interneuron class involved in locomotion. [ 45 ]  Nevertheless,  Dbx1  expression patterns can be mapped using Cre-Lox recombination in genetically modified mice to find and record preB\u00f6tC core rhythmogenic interneurons. [ 42 ] [ 43 ] [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2960", "contents": "Approximately half of preB\u00f6tC interneurons are inhibitory, glycinergic or GABAergic. [ 47 ] [ 48 ] [ 49 ] [ 50 ] [ 51 ]  Inhibitory preB\u00f6tC neurons modulate the amplitude as well as the frequency of the rhythmic inspiratory bursts. [ 52 ] [ 53 ]  These inhibitory populations receive sensorimotor information from the nucleus of the solitary tract (NTS), located in the dorsomedial medulla near the XII motor nucleus and the dorsal motor nucleus of vagus. Inhibitory neurons project to core rhythmogenic preB\u00f6tC neurons. [ 8 ] [ 10 ] [ 54 ]  During normal breathing, inhibitory neurons in the preB\u00f6tC are recruited periodically during each breath to hasten inspiratory termination. That role profoundly influences phase transition from inspiration to post-inspiration, then expiration, and that speeds up breathing cycles. [ 55 ] [ 40 ]  Without preB\u00f6tC inhibitory microcircuits, the breathing rhythm is slower overall and 'stiff' in the sense that its oscillation stabilizes even when faced with normally effective respiratory drive like CO 2  or SP. [ 55 ] [ 40 ]  Inhibitory preB\u00f6tC neurons also inhibit neurons involved in generating expiratory (exhale-related) rhythm to enforce an exclusively inspiratory phase when the preB\u00f6tC is active."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2961", "contents": "The preB\u00f6tC produces two types of breathing rhythm in the presence of physiological levels of oxygen and carbon dioxide. In eupnea, or normal resting breathing, the preB\u00f6tC generates a rhythm that is relatively fast (~2\u20134\u00a0Hz in rodents, ~0.1-0.2\u00a0Hz in humans) with each breath achieving a  tidal volume  of air movement. Sigh breaths, on the other hand, are much slower (cycle periods range from 1-4 min \u22121  in mammals) with breath amplitudes being two or three-fold larger than tidal volume. [ 56 ] [ 57 ] [ 58 ]  Both eupnea and sigh rhythms are generated within the pre-B\u00f6tzinger complex and both eupnea and sigh bursts can be recorded in rhythmically active brain-slices containing the pre-BotC. [ 59 ]  Robust sigh rhythmicity in slices requires that the slice retain some tissue immediately rostral to preB\u00f6tC, [ 60 ]  which contains the cut axons from a rostral site at the level of the Facial (VII) cranial nucleus that projects to preB\u00f6tC and delivers bombesin-like peptides, namely Gastrin-releasing peptide (GRP) and Neuromedin-B (NMB). [ 61 ]  Producing both inspiratory (eupnea-related) and sigh bursts appears to involve the majority of excitatory neurons in the preB\u00f6tC  [ 59 ] [ 60 ]  (although see  [ 62 ] ). However, each type of rhythmic activity appears to depend on different mechanisms. The sigh rhythm depends on synaptic mechanisms that involve P/Q type calcium channels, suggesting there is a subset of neurons with specialized synapses for this type of rhythm generation since only a very small number of respiratory neurons receive  glutamatergic  inputs that depend on P/Q type calcium currents, or emphasizing the need for calcium influx to produce sighs. [ 63 ] [ 64 ] [ 62 ]  The sigh burst rhythm also depends on mGluR8 receptor activation. [ 65 ] [ 66 ]  Further, whether the preB\u00f6tC network generates a predominantly eupneic rhythm or sigh rhythm appears to depend on acetylcholine modulation (muscarinic acetylcholine receptor activity (mAChR) PMID 18287547.  A subset of preBotC neurons active during sigh, but not eupnea, so-called 'sigh-only' neurons has been identified PMID 18287547. Additionally, a different subset of preBotC neurons has been identified that have rhythmogenic bursting properties that even after being synaptically isolated, appear to intrinsically generate both eupneic and sigh-like rhythms PMID 18287547; similar to network behavior, whether these neurons generate eupneic or sigh-like activity depends on mAChR activation.  The above studies suggest both intrinsic and synaptic mechanisms contribute to eupneic and sigh rhythmogenesis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2962", "contents": "Under low levels of oxygen, the preB\u00f6tC rearranges its activity, to generate a rhythmic gasping-related pattern. The gasping rhythm is proposed to play a critical role in autoresuscitation, failure of which may contribute to, or underlie, Sudden Infant Death Syndrome (SIDS). Gasping-related rhythmic bursts of neural activity generated by the preB\u00f6tC  are characterized by faster rise time and shorter duration than eupnea, and gasp-activity occurs a lower frequency than eupnea. [ 67 ]  When under a low oxygenated state (hypoxia) the respiratory network responds by transitioning into an  augmentation  followed by a depression phase, controlled in the pre-B\u00f6tC. [ 63 ]  During the depression phase, the inspiratory burst changes from an augmenting bell-shaped burst to a decrementing burst, a primary feature of gasping. Neuronal discharge patterns are altered during the depressed  synaptic inhibition , evidence of a rearrangement of the network, presumably attributable to changes in synaptic connectivity strengths as well as modifications in the intrinsic properties of rhythmogenic preB\u00f6tC neurons. [ 68 ]  Excitatory neuromodulators, including serotonin (a.k.a. 5-HT) acting via 5-HT type 2a receptors PMID: 16525041 and norepinephrine acting via alpha-2 receptors PMID: 21615559   likely play an important role in activating persistent sodium-dependent rhythmogenic mechanisms proposed to underlie gasping activity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2963", "contents": "In summary, the preB\u00f6tC gives rise to more than one breathing-related rhythm: inspiratory (eupnea), sigh, and gasping. This single neuronal network can create multiple respiratory rhythmic patterns and is by itself both necessary and sufficient to generate these respiratory rhythms."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2964", "contents": "Located within the ventrolateral  medulla , the pre-B\u00f6tzinger complex contains subnetworks that hold distinct  synapses  and intrinsic membrane properties. [ 69 ]  In mammals, the respiratory network system and the nuclei controlling breathing modulation are found along the neuronal axis. The  neuronal networks  involved in respiratory function are located in the ventral respiratory column (VRC). From  rostral  to  caudal , these networks include the retrotrapezoid nucleus/parafacial respiratory group complex (RTN/pFRG)  [ 70 ] [ 71 ]  the B\u00f6tzinger complex, [ 72 ] [ 73 ] [ 74 ]  the preB\u00f6tzinger complex (preB\u00f6tC), as well as the rostral and the caudal divisions of the ventral respiratory group (rVRG and cVRG). [ 75 ]  The dorsal pons, including the K\u00f6lliker-Fuse [ 76 ]  and the parabrachial nuclei, play an important role in respiratory control and rhythm generation. Other areas that aid in breathing control are the  cerebellum ,  neocortex , and the  periaqueductal gray  (speech and breathing), although the mechanisms are not yet well explained. Mononsynaptic projections to the preB\u00f6tC have been mapped. [ 77 ]  Efferent projections from the preB\u00f6tC to other respiratory and non-respiratory sites throughout the brain and central nervous system have been mapped too. [ 78 ] [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2965", "contents": "The exact mechanism of the rhythm generation and transmission to motor nuclei remains controversial and the topic of much research  [ 79 ] [ 80 ] [ 81 ] [ 82 ] [ 83 ] [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2966", "contents": "There are several inward  currents  that are proposed to help produce  action potentials  and  bursts  in pacemaker neurons. There are two main voltage dependent  sodium  currents that contribute to the depolarization and firing of action potentials in neurons. The fast and transient sodium current produces a large depolarization that fires the initial action potential in neurons, however this current is quickly inactivated and does not help maintain bursting activity in neurons. [ 83 ]  To achieve bursts, a persistent sodium current provides enough depolarization to facilitate the firing of action potentials during a burst. [ 84 ]  Unlike the fast and transient sodium current, the persistent sodium current (I NaP ) is activated at very low  membrane potentials  and has a much slower inactivation, which allows neurons to intrinsically fire action potentials at sub-threshold membrane potentials. [ 83 ]  Studies have shown that the inactivation of this persistent sodium current helps end bursts in pacemaker neurons. The amount of time it takes for I NaP  to become activated again establishes the timeframe between each burst. The neuron can receive synaptic inputs and different amounts of inward and outward currents to regulate the time between each burst, which ultimately helps generate a specific breathing pattern."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2967", "contents": "NALCN sodium leak channels have been hypothesized to give rise to an inward current that may play an important role in the modulation of bursting and spiking activity. [ 83 ]  These nonselective cation channels may provide a voltage-independent sodium current that also helps slightly depolarize neurons. The channels are regulated by  G protein\u2013coupled receptors  that can activate or inhibit the NALCN channels depending on the neurotransmitter that binds the receptor and the specific signaling pathway that is involved. Activation of M3  muscarinic  receptors by acetylcholine and NK1 by Substance P significantly increases NALCN currents, while activation of CaSR by calcium stops the flow of the currents. Since NALCN sodium leak channels may contribute to the depolarization of neurons, their regulation by G-protein coupled receptors may be vital for the alteration of bursting and breathing rhythms."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2968", "contents": "Other inward currents that help generate intrinsic spiking and bursting in pacemaker neurons are the calcium current and calcium-activated nonspecific currents (I CAN ). [ 83 ]  When a neuron becomes depolarized, voltage gated  calcium channels  become activated and calcium is able to flow into the cell which usually leads to the release of neurotransmitters. Calcium-sensitive dyes have shown that internal concentrations of calcium increase during bursts. The activation of different calcium channels has distinct effects on the activity of neurons in the pre-B\u00f6tzinger complex.  L-type calcium channels  are known to increase the frequency of action potentials in some neurons, which might be the reason calcium influx through these channels has been observed during the  augmentation  when tissues have low levels of oxygen. P/Q-type calcium channels are mainly responsible for the release of neurotransmitters that excite, or activate, postsynaptic neurons. Studies have shown that blockage of these channels leads to the inhibition of sighs, which indicates calcium flow through these channels is necessary for sighs. Other research has also suggested that calcium flow through  N-type calcium channels  is essential for normal breathing, and is responsible for the activation of calcium-dependent potassium channels. Calcium-activated nonselective cation currents are important for the intrinsic spiking and bursting activity in CS pacemaker neurons.  Metabotropic glutamate  1/5 receptors appear to be important for the increase in intracellular calcium that activate I CAN . The initial burst in a neuron usually leads to the activation of the transient sodium current and the several types of calcium currents. These currents depolarize the cell further enough to activate  NMDA receptors  and I CAN , which helps cell regenerate its bursts."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2969", "contents": "The ratio between inward and outward currents helps determine the activity of pacemaker neurons in the pre-B\u00f6tzinger complex. The major outward currents involved in the regulation of neuron activity are potassium currents. [ 83 ]  Although the exact role of potassium currents is still being investigated, it appears that potassium and sodium leak currents are crucial for the rhythmicity of the pre-B\u00f6tzinger complex. Transient A-type potassium currents are more common in neurons that are involved in the inspiration process. When A-type potassium currents were blocked with  4-AP  in slices of the pre-B\u00f6tzinger complex, synchronized bursts in inspiratory neurons was affected as well as communication with  hypoglossal   motor pools  that help regulate breathing. This suggests that transient A-type potassium currents are needed for the synchronized bursts in inspiratory neurons and for effective respiratory control. Other  potassium channels  like large conductance calcium-dependent potassium channels and sodium chloride dependent potassium channels appear to end burst potentials in neurons. Moreover, ATP-dependent potassium channels help neurons detect changes in energy or oxygen levels to modify breathing patterns. These channels are activated by decreases in ATP, which suggests they provide the needed hyperpolarization during  hypoxia ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2970", "contents": "Several synthetic compounds have been shown to act on neurons specific to the preB\u00f6tC, most being selective  agonists  or  antagonists  to receptor subtypes on neurons in the vicinity. Since many of these neurons express  GABA ,  glutamate ,  serotonin [ 85 ]  and  adenosine  receptors, chemicals custom tailored to bind at these sites are most effective at altering respiratory rhythm."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2971", "contents": "Adenosine modulates the preB\u00f6tC output via activation of the  A 1  and  A 2A  receptor  subtypes. [ 86 ] [ 87 ]  An adenosine A 1  receptor agonist has been shown to depress preB\u00f6tC rhythmogenesis independent of the neurotransmitters GABA and glycine in in vitro preparations from 0- to 7-day-old mice. [ 88 ]  Another synthetic drug specific to the adenosine  A 2A  receptor  subtype is  CGS-21680  that has been shown to cause apneas in 14- to 21-day-old rat pups  in vivo . For this reason, it has been used as a model to study pathological conditions such as  apnea of prematurity  and  sudden infant death syndrome ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2972", "contents": "The complex regulation of respiratory rhythm involves the integration of multiple signaling molecules and the activation of numerous diverse  metabotropic  and  ionotropic receptors . [ 83 ]  These include norepinephrine, serotonin,  acetylcholine , substance P,  ATP ,  TRH ,  somatostatin ,  dopamine ,  endorphins , and  adenosine , which in turn activate  g-protein coupled receptors  to produce the diverse responses mediated by the pre-B\u00f6tzinger complex."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2973", "contents": "Nonpacemaker and pacemaker neurons involved in inspiration are stimulated by NE. [ 63 ]  They are found within the pre-B\u00f6tC and act via  alpha-1 , alpha-2, and beta-noradrenergic mechanisms. NE induces I CAN -dependent bursting in active nonpacemakers and depolarizes CI pacemakers, increasing the frequency of their bursting. In CS pacemakers, NE increases only the amplitude of the depolarizing drive potential and the number of action potentials during the burst, [ 63 ]  but does not affect the burst frequency in CS pacemakers, unlike in CI pacemakers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2974", "contents": "Serotonergic neurons are also involved in breathing systems. [ 63 ]  Their actions are diverse and dependent upon the activity level and species of the animal. Serotonin plays a critical role in altering the pacemaker neurons involved in gasping and normal respiratory activity. [ 83 ]  Blocking of the  5-HT2 receptor  eliminates the bursts occurring in the pacemaker neurons and leads to the abolishing of gasps. The blocking of this receptor is therefore problematic, especially in SIDS, because gasping is an important mechanism involved in autoresuscitation. A lack of serotonin binding to the serotonin receptor 2 leads to the inability to autoresuscitation due to the lack of drive for gasping."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2975", "contents": "Substance P , a peptidergic modulator, also plays a role in  neuromodulation  of the pre-B\u00f6tC. [ 63 ]  It is often coreleased with other neurotransmitters. Substance P activates the inspiratory frequency at the level of the network and behavioral systems. Cellularly, substance P is involved in the  depolarization  of nonpacemaker neurons slowly, causing an increase in action potential firing rate. The  neuropeptide  can also activate CS pacemakers and less dramatically, CI pacemakers. This leads to an increase in burst amplitude, frequency, and duration. When Substance P is coreleased with serotonin, it plays a crucial role in hypoxic response. [ 83 ]  This occurs because substance P stabilizes the respiratory rhythm through depolarization of neurons and activation of Pacemaker neurons."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2976", "contents": "Acetylcholine plays an important modulatory role on the respiratory system by altering  nicotinic  and muscarinic receptors. [ 83 ]  The suppression of muscarinic receptors and the activation of nicotinic receptors due to prenatal exposure to nicotine have been linked to SIDS. This is due to the reduction of excitatory synaptic transmission in a nucleus and increased excitability in motor neurons caused by nicotinic activation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2977", "contents": "Many other  neuromodulators  have roles in respiration. The aforementioned are simply three examples."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2978", "contents": "Investigation of the respiratory response to Acute  intermittent hypoxia  (AIH), repeated episodes of  hypoxia , reveals connection to various breathing disorders, such as  Rett syndrome  and  obstructive sleep apnea . [ 63 ]  AIH leads to persistent increases in respiratory frequency and amplitude of integrated motor neuronal bursts in vivo. [ 63 ]  These changes lasting for 90 minutes or longer are termed long-term facilitation (LTF). AIH causes homeostatic changes in multiple sites of the respiratory system; the pre-B\u00f6tC is likely the site for the LTF, since intermittent hypoxia causes an increase in persistent frequency after ongoing hypoxia. The respiratory system is regulated by multiple forms of long-term synaptic plasticity. The role of  synaptic inhibition  has been proved widespread and critical within the expiratory  Botzinger complex  respiratory network, through  cross-correlation  and  antidromic  mapping techniques. The inhibitory connections discovered indicate their ability to connect different classes of neurons, their importance in regulating the interval of inspiration, and their ability to control driving potential of respiratory neurons. These characteristics show the interaction between the  parafacial  respiratory group and the pre-B\u00f6tzinger complex, which allows for active expiration to be produced by synaptic inhibition within the respiratory network. Synaptic inhibition is critical for allowing the pre-B\u00f6tzinger complex to communicate with other  respiratory centers  in order to generate respiratory activity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2979", "contents": "Glycinergic  and  GABAergic  inhibitory neurons make up half of all inspiratory neurons. Exposure of the pre-B\u00f6tzinger complex to these inhibitory neurotransmitters results in the rhythmic nature associated with respiration. Blocking this inhibition from Glycine or GABA causes its neurons to be incapable of switching from the active phase to the inspiration phase, demonstrated by shorter inspiratory activity (as seen  in vivo ). [ 83 ]  However, the absence of  inhibitory synapses  still resulted in rhythmic respiratory activity  in vitro  and  in situ . This is largely due to the fact that respiratory rhythm results from numerous aspects, with synaptic inhibition playing only a single part."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2980", "contents": "In addition to the inhibitory synaptic regulation of respiratory rhythm within the pre-B\u00f6tzinger complex, there is also an excitatory component utilizing mostly  AMPA receptors . [ 83 ]  The generation of inspirations is due to a signaling cascade involving transient Ca2+ influx as a result of glutamate activating a postsynaptic receptor. In addition to glutamates role in activating the synaptic drive of inspiration, it is also understood that pacemaker neurons, with  autonomous  voltage-dependent properties, are also responsible for the generation of respiratory rhythm. Evidence of this is seen when isolating neurons within the pre-B\u00f6tzinger complex, which results in rhythmic bursts due to synaptically coupled micronetworks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2981", "contents": "However, the generation of respiratory rhythm requires other excitatory components, such as glutamate, in order to produce a wide range of behavioral functions including eupneic and sigh activity. [ 83 ]  The pre-B\u00f6tzinger complex is responsible for generating the wide variety of components that make up the respiratory rhythm. The accomplishment of these precise activities requires distinct neuron populations that overlap to allow the generation of different respiratory actions. Eupneic activity is generated using the excitatory mechanism through the NMDA glutamate receptor. Sighs have a differential generation originating from pacemaker neurons. The pre-B\u00f6tzinger complex is capable of generating differential rhythmic activities due to the intricate integration of modulatory, synaptic, and intrinsic properties of the neurons involved."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2982", "contents": "In addition to its involvement in generating respiratory rhythm, the pre-B\u00f6tzinger complex is also capable of integrating sensory information from changes in the biochemical environment, particularly oxygen. The capability to detect focal hypoxia causes an excitatory response in the motor output responsible for respiration, which causes alterations in the firing pattern of neurons within the pre-B\u00f6tzinger complex. [ 83 ]  Among these changes are the transition of a fully integrated network involving complex networks and autonomous mechanisms, to a system dependent on the activity of pacemaker neurons through sodium current activation. Hypoxia results in gasping due to the increased dependence on the sodium current and the overlap in networks between the generation of respiratory rhythm and intrinsic oxygen sensitization."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2983", "contents": "Disturbances in neuromodulatory processes acting on  ion channels , receptors, and second messengers have been associated with numerous  pathophysiological  conditions, such as  Rett syndrome  and  sudden infant death syndrome ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2984", "contents": "Rhythmic breathing continuously adapts to posture, activity level, speech, and can reveal whether someone is calm, agitated, or scared. Plasticity of the mechanisms involved in respiratory behavior is modulated in part by the preB\u00f6tC. Disruption causes irreversible loss or major disruption of breathing  in vivo . The frequency and amplitude change according to the behavioral and metabolic demands of the organism it controls. Breathing is thus extremely sensitive to the internal state of the organism."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2985", "contents": "The  pulmonary circulation  is a division of the  circulatory system  in all vertebrates. The circuit begins with  deoxygenated blood  returned from the body to the  right atrium  of the  heart  where it is pumped out from the  right ventricle  to the  lungs . In the lungs the blood is  oxygenated  and returned to the  left atrium  to complete the circuit. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2986", "contents": "The other division of the circulatory system is the  systemic circulation  that begins with receiving the oxygenated blood from the pulmonary circulation into the left atrium. From the atrium the oxygenated blood enters the  left ventricle  where it is pumped out to the rest of the body, returning as deoxygenated blood back to the pulmonary circulation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2987", "contents": "The  blood vessels  of the pulmonary circulation are the  pulmonary arteries  and the  pulmonary veins ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2988", "contents": "A separate circulatory circuit known as the  bronchial circulation  supplies oxygenated blood to the tissue of the  larger airways  of the lung."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2989", "contents": "De-oxygenated blood leaves the heart, goes to the lungs, and then enters back into the heart. [ 2 ]  De-oxygenated blood leaves through the right ventricle through the  pulmonary artery . [ 2 ]  From the right atrium, the blood is pumped through the  tricuspid valve  (or right atrioventricular valve) into the  right ventricle . Blood is then pumped from the right ventricle through the  pulmonary valve  and into the  pulmonary artery . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2990", "contents": "The pulmonary arteries carry deoxygenated blood to the lungs, where  carbon dioxide  is released and oxygen is picked up during  respiration . [ 3 ]  Arteries are further divided into very fine  capillaries  which are extremely thin-walled. [ 4 ]  The pulmonary veins return oxygenated blood to the left atrium of the heart. [ 3 ]  The pulmonary arteries have both an internal and external elastic membrane, whereas pulmonary veins have a single (outer) elastic layer. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2991", "contents": "Oxygenated blood leaves the lungs through pulmonary veins, which return it to the left part of the heart, completing the pulmonary cycle. [ 3 ] [ 6 ]  This blood then enters the left atrium, which pumps it through the  mitral valve  into the  left ventricle . [ 3 ] [ 6 ]  From the left ventricle, the blood passes through the  aortic valve  to the aorta. [ 3 ] [ 6 ]  The blood is then distributed to the body through the systemic circulation before returning again to the pulmonary circulation. [ 3 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2992", "contents": "From the right ventricle, blood is pumped through the semilunar pulmonary valve into the left and right main pulmonary artery (one for each lung), which branch into smaller pulmonary arteries that spread throughout the lungs. [ 3 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2993", "contents": "The pulmonary circulation loop is virtually bypassed in  fetal circulation . [ 7 ]  The fetal lungs are collapsed, and blood passes from the right atrium directly into the left atrium through the  foramen ovale  (an open conduit between the paired atria) or through the  ductus arteriosus  (a shunt between the pulmonary artery and the aorta). [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2994", "contents": "When the lungs expand at birth, the pulmonary pressure drops and blood is drawn from the right atrium into the right ventricle and through the pulmonary circuit. Over the course of several months, the foramen ovale closes, leaving a shallow depression known as the  fossa ovalis . [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2995", "contents": "A number of medical conditions may affect the pulmonary circulation:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2996", "contents": "The pulmonary circulation is archaically known as the \"lesser circulation\" which is still used in non-English literature. [ 14 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2997", "contents": "The discovery of the pulmonary circulation has been attributed to many scientists with credit distributed in varying ratios by varying sources. In much of modern medical literature, the discovery is credited to English physician  William Harvey  (1578 \u2013 1657 CE) based on the comprehensive completeness and correctness of his model, despite its relative recency. [ 16 ] [ 17 ]  Other sources credit one or more of Greek philosopher  Hippocrates  (460 \u2013 370 BCE), Arab physician  Ibn al-Nafis  (1213 \u2013 1288 CE), Syrian physician  Qusta ibn Luqa  or Spanish physician  Michael Servetus  (c. 1509 \u2013 1553 CE). [ 18 ] [ 19 ] [ 20 ] [ 21 ]  Several figures such as Hippocrates and al-Nafis receive credit for accurately predicting or developing specific elements of the modern model of pulmonary circulation: Hippocrates [ 20 ]  for being the first to describe pulmonary circulation as a discrete system separable from systemic circulation as a whole and al-Nafis [ 22 ]  for making great strides over the understanding of those before him and towards a rigorous model. There is a great deal of subjectivity involved in deciding at which point a complex system is \"discovered\", as it is typically elucidated in piecemeal form so that the very first description, most complete or accurate description, and the most significant forward leaps in understanding are all considered acts of discovery of varying significance. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_2998", "contents": "Early descriptions of the cardiovascular system are found throughout several ancient cultures. The earliest known description of the role of air in circulation was produced in  Egypt  in 3500 BCE. At the time, the Egyptians believed that the heart was the origin of many channels that connected different parts of the body to each other and transported air \u2013 as well as urine, blood, and the soul \u2013 between them. [ 23 ]  The  Edwin Smith Papyrus  (1700 BCE), named for American Egyptologist  Edwin Smith  (1822 \u2013 1906 CE) who purchased the scroll in 1862, provided evidence that Egyptians believed that the heartbeat created a pulse that transported the above substances throughout the body. [ 24 ]  A second scroll, the  Ebers Papyrus  (c. 1550 BCE), also emphasized the importance of the heart and its connection to vessels throughout the body and described methods to detect cardiac disease through pulse abnormalities. Although they had knowledge of the heartbeat, vessels, and pulse, the Egyptians attributed the movement of substances through the vessels to air that resided in these channels, rather than to the heart's exertion of pressure. [ 25 ]  The Egyptians knew that air played an important role in circulation but did not yet have a conception of the role of the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_2999", "contents": "The next addition to the historical understanding of pulmonary circulation arrived with the Ancient Greeks. Physician  Alcmaeon  (520 \u2013 450 BCE) proposed that the brain, not the heart, was the connection point for all of the vessels in the body. He believed that the function of these vessels was to bring the \"spirit\" (\" pneuma \") and air to the brain. [ 23 ] [ 26 ]   Empedocles  (492 \u2013 432 BCE), a philosopher, proposed a series of pipes, impermeable to blood but continuous with blood vessels, that carried the pneuma throughout the body. He proposed that this spirit was internalized by pulmonary respiration. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3000", "contents": "Hippocrates  was the first to describe pulmonary circulation as a discrete system, separable from systemic circulation, in his  Corpus Hippocraticum , which is often regarded as the foundational text of modern medicine. [ 20 ]  Hippocrates developed the view that the liver and spleen produced blood, and that this traveled to the heart to be cooled by the lungs that surrounded it. [ 19 ]  He described the heart as having two ventricles connected by an interventricular septum, and depicted the heart as the nexus point of all of the vessels of the body. He proposed that some vessels carried only blood and that others carried only air. He hypothesized that these air-carrying vessels were divisible into the pulmonary veins, which carried in air to the left ventricle, and the pulmonary artery, which carried in air to the right ventricle and blood to the lungs. He also proposed the existence of two atria of the heart functioning to capture air. He was one of the first to begin to accurately describe the anatomy of the heart and to describe the involvement of the lungs in circulation. His descriptions built substantially on previous and contemporaneous efforts but, by modern standards, his conceptions of pulmonary circulation and of the functions of the parts of the heart were still largely inaccurate. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3001", "contents": "Greek philosopher and scientist  Aristotle  (384 \u2013 322 BCE) followed Hippocrates and proposed that the heart had three ventricles, rather than two, that all connected to the lungs. [ 23 ]  Greek physician  Erasistratus  (315 \u2013 240 BCE) agreed with Hippocrates and Aristotle that the heart was the origin of all of the vessels in the body but proposed a system in which air was drawn into the lungs and traveled to the left ventricle via pulmonary veins. It was transformed there into the pneuma and distributed throughout the body by arteries, which contained only air. [ 24 ]  In this system, veins distributed blood throughout the body, and thus blood did not circulate, but rather was consumed by the organs. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3002", "contents": "The Greek physician  Galen  (129 \u2013 c. 210 CE) provided the next insights into pulmonary circulation. Though many of his theories, like those of his predecessors, were marginally or completely incorrect, his theory of pulmonary circulation dominated the medical community's understanding for hundreds of years after his death. [ 24 ]  Galen contradicted Erasistratus before him by proposing that arteries carried both air and blood, rather than air alone (which was essentially correct, leaving aside that blood vessels carry constituents of air and not air itself). [ 19 ]  He proposed that the liver was the originating point of all blood vessels. He also theorized that the heart was not a pumping muscle but rather an organ through which blood passed. [ 24 ]  Galen's theory included a new description of pulmonary circulation: air was inhaled into the lungs where it became the pneuma. Pulmonary veins transmitted this pneuma to the left ventricle of the heart to cool the blood simultaneously arriving there. This mixture of pneuma, blood, and cooling produced the vital spirits that could then be transported throughout the body via arteries. Galen further proposed that the heat of the blood arriving in the heart produced noxious vapors that were expelled through the same pulmonary veins that first brought the pneuma. [ 27 ]  He wrote that the right ventricle played a different role to the left: it transported blood to the lungs where the impurities were vented out so that clean blood could be distributed throughout the body. Though Galen's description of the anatomy of the heart was more complete than those of his predecessors, it included several mistakes. Most notably, Galen believed that blood flowed between the two ventricles of the heart through small, invisible pores in the interventricular septum. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3003", "contents": "The next significant developments in the understanding of pulmonary circulation did not arrive until centuries later. Persian polymath  Avicenna  (c. 980 \u2013 1037 CE) wrote a medical encyclopedia entitled  The Canon of Medicine . In it, he translated and compiled contemporary medical knowledge and added some new information of his own. [ 22 ]  However, Avicenna's description of pulmonary circulation reflected the incorrect views of Galen. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3004", "contents": "The Arab physician, Ibn al-Nafis, wrote the  Commentary on Anatomy in   Avicenna's   Canon  in 1242 in which he provided possibly the first known description of the system that remains substantially congruent with modern understandings, in spite of its flaws. Ibn al-Nafis made two key improvements on Galen's ideas. First, he disproved the existence of the pores in the interventricular septum that Galen had believed allowed blood to flow between the left and right ventricles. Second, he surmised that the only way for blood to get from the right to the left ventricle in the absence of interventricular pores was a system like pulmonary circulation. He also described the anatomy of the lungs in clear and basically correct detail, which his predecessors had not. [ 22 ]  However, like Aristotle and Galen, al-Nafis still believed in the quasi-mythical concept of vital spirit and that it was formed in the left ventricle from a mixture of blood and air. Despite the enormity of Ibn al-Nafis's improvements on the theories that preceded him, his commentary on  The Canon  was not widely known to Western scholars until the manuscript was discovered in  Berlin ,  Germany , in 1924. As a result, the ongoing debate among Western scholars as to how credit for the discovery should be apportioned failed to include Ibn al-Nafis until, at earliest, the mid-20th century (shortly after which he came to enjoy a share of this credit). [ 19 ] [ 22 ]  In 2021, several researchers described a text predating the work of al-Nafis,  fargh- beyn-roh va nafs , in which there is a comparable report on pulmonary circulation. The researchers argue that its author, Qusta ibn Luqa, is the best candidate for the discoverer of pulmonary circulation on a similar basis to arguments in favour of al-Nafis generally. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3005", "contents": "It took centuries for other scientists and physicians to reach conclusions that were similar to and then more accurate than those of al-Nafis and ibn Luqa. This later progress, constituting the gap between medieval and modern understanding, occurred throughout Europe. Italian polymath  Leonardo da Vinci  (1452 \u2013 1519 CE) was one of the first to propose that the heart was just a muscle, rather than a vessel of spirits and air, but he still subscribed to Galen's ideas of circulation and defended the existence of interventricular pores. [ 23 ]  The Flemish physician  Andreas Vesalius  (1514 \u2013 1564 CE) published corrections to Galen's view of circulatory anatomy, questioning the existence of interventricular pores, in his book  De humani corporis fabrica libri septem  in 1543. [ 27 ]  Spanish  Michael Servetus , after him, was the first European physician to accurately describe pulmonary circulation. [ 18 ]  His assertions largely matched those of al-Nafis. In subsequent centuries, he has frequently been credited with the discovery, but some historians have propounded the idea that he potentially had access to Ibn al-Nafis's work while writing his own texts. [ 19 ]  Servetus published his findings in  Christianismi Restituto  (1553): a theological work that was considered heretical by Catholics and Calvinists alike. As a result, both book and author were burned at the stake and only a few copies of his work survived. [ 19 ]  Italian physician  Realdo Colombo  (c. 1515 \u2013 1559 CE) published a book,  De re anatomica libri XV,  in 1559 that accurately described pulmonary circulation. It is still a matter of debate among historians as to whether Colombo reached his conclusions alone or based them to an unknown degree on the works of al-Nafis and Servetus. [ 19 ] [ 23 ]  Finally, in 1628, the influential British physician  William Harvey  (1578 \u2013 1657 AD) provided at the time the most complete and accurate description of pulmonary circulation of any scholar worldwide in his treatise  Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus . At the macroscopic level, his model is still recognizable in and reconcilable with modern understandings of pulmonary circulation. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3006", "contents": "Media related to  Pulmonary circulation  at Wikimedia Commons"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3007", "contents": "The factors that determine the values for  alveolar  pO 2  and  pCO 2  are:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3008", "contents": "The partial pressures (in  torr ) for a human at rest:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3009", "contents": "(P A O 2 )"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3010", "contents": "The alveolar oxygen  partial pressure  is lower than the atmospheric O 2  partial pressure for two reasons."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3011", "contents": "The alveolar pO 2  is not routinely measured but is calculated from blood gas measurements by the  alveolar gas equation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3012", "contents": "The partial pressure of carbon dioxide, along with the  pH , can be used to differentiate between  metabolic acidosis ,  metabolic alkalosis ,  respiratory acidosis , and  respiratory alkalosis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3013", "contents": "Hypoventilation  exists when the ratio of carbon dioxide production to alveolar ventilation increases above normal values \u2013 greater than 45mmHg. If pH is also less than 7.35 this is  respiratory acidosis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3014", "contents": "Hyperventilation  exists when the same ratio decreases \u2013 less than 35mmHg. If the pH is also greater than 7.45 this is  respiratory alkalosis . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3015", "contents": "A  pulmonary shunt  is the passage of deoxygenated blood from the  right side of the heart  to the  left  without participation in gas exchange in the pulmonary capillaries. It is a pathological condition that results when the  alveoli  of parts of the  lungs  are  perfused  with blood as normal, but  ventilation  (the supply of air) fails to supply the perfused region.  In other words, the  ventilation/perfusion ratio  (the ratio of air reaching the alveoli to blood perfusing them) of those areas is zero. [ 1 ] [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3016", "contents": "A pulmonary shunt often occurs when the alveoli fill with fluid, causing parts of the lung to be unventilated although they are still perfused. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3017", "contents": "Intrapulmonary shunting is the main cause of  hypoxemia  (inadequate blood oxygen) in  pulmonary edema  and conditions such as  pneumonia  in which the lungs become  consolidated . [ 2 ]   The shunt fraction is the percentage of  cardiac output  that is not completely oxygenated. [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3018", "contents": "In pathological conditions such as  pulmonary contusion , the shunt fraction is significantly greater [ clarification needed ]  and even breathing 100% oxygen does not fully oxygenate the blood. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3019", "contents": "Intrapulmonary shunt is specifically shunting where some of the blood flow through the lungs is not properly oxygenated. Other shunts may occur where venous and arterial blood mix but completely bypass the lungs (extrapulmonary shunt). [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3020", "contents": "If every alveolus was perfectly ventilated and all blood from the right ventricle were to pass through fully functional pulmonary capillaries, and there was unimpeded diffusion across the alveolar and capillary membrane, there would be a theoretical maximum blood gas exchange, and the alveolar P O 2  and arterial P O 2  would be the same. The formula for shunt describes the deviation from this ideal. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3021", "contents": "A normal lung is imperfectly ventilated and perfused, and a small degree of intrapulmonary shunting is normal. Anatomical shunting occurs when blood supply to the lungs via the  pulmonary arteries  is returned via the pulmonary veins without passing through the pulmonary capillaries, thereby bypassing alveolar gas exchange. Capillary shunting is blood that passes through capillaries of unventilated alveoli [ 4 ]  or deoxygenated blood flowing directly from pulmonary arterioles to nearby pulmonary veins through anastomoses, bypassing the alveolar capillaries. [ 5 ]  In addition, some of the  smallest cardiac veins  drain directly into the left ventricle of the  human heart . This drainage of deoxygenated blood straight into the systemic circulation is why the arterial P O 2  is normally slightly lower than the alveolar P O 2 , known as the  alveolar\u2013arterial gradient , a useful clinical sign in determining the cause of  hypoxemia . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3022", "contents": "The alveolar-arterial (A-a) gradient measures the difference between oxygen concentrations in the alveoli and the arterial system. This is an important clinical method of narrowing the differential diagnosis for hypoxemia. [ 7 ]  The gradient calculation is as follows:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3023", "contents": "Where PAO2 represents the alveolar oxygen pressure and PaO2 represents the arterial oxygen pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3024", "contents": "The alveolar oxygen pressure is not easily measured directly and is therefor estimated using the alveolar gas equation. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3025", "contents": "Where PAO2 represents alveolar oxygen pressure, Patm represents atmospheric pressure (at sea level 760 mm Hg), PH2O represents partial pressure of water (approximately 45 mm Hg), FiO2 represents the fraction of inspired oxygen (for room air, 0.21), PaCO2 represents the partial pressure of carbon dioxide in the alveoli (in normal physiological conditions around 40 to 45 mmHg), and where RQ represents the respiratory quotient, which is generally assumed to be 0.8. The arterial oxygen pressure (PaO2) and arterial carbon dioxide pressure (PaCO2) can be directly measured using an arterial blood gas test (ABG) or estimated via the venous blood gas test (VBG), and since carbon dioxide rapidly diffuses in and out of the lungs, arterial carbon dioxide pressure and alveolar carbon dioxide pressure are effectively equal. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3026", "contents": "The A-a gradient should theoretically be zero in a healthy person, but almost never is. A normal person will have an A-a gradient estimated by: Normal Gradient = (Age in years/4) + 4. If the A-a gradient is significantly higher than the result of this equation, the person likely has a disorder of the  alveoli , causing oxygen to be unable to diffuse into the blood. If the person has a normal A-a gradient but still has hypoxemia, then there is probably a cause unrelated to the alveoli, such as  hypoventilation ,  obstructive lung disease , or  shunting ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3027", "contents": "An irregular distribution of ventilation can occur in  asthma ,  bronchiolitis ,  atelectasis , and other conditions, [ 9 ]  which  have the effect of reducing the amount of oxygen present in some alveoli relative to others. If the normal perfusion of these alveoli were to persist, the blood in those regions would be less oxygenated than blood in the normally ventilated alveioli, and the combined blood oxygenation after mixing would be lower than normal.  A pulmonary shunt occurs when this imbalance is undercompensated. The normal response of pulmonary blood vessels sensing a low oxygen saturation is to  constrict , slowing the flow through the underoxygenated areas, thereby giving it time to increase saturation and increasing relative flow through those areas with more effective oxygenation, resulting in a higher combined oxygenation. [ 10 ] [ 11 ]  If there is no oxygen available in the alveoli, the blood cannot be oxygenated and any blood flowing through such areas of the lung is considered an intrapulmonary shunt."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3028", "contents": "While in a pulmonary shunt, the  ventilation/perfusion ratio  is zero, lung units with a V/Q (where V\u00a0=\u00a0ventilation, and Q\u00a0=\u00a0perfusion) ratio of less than 0.005 are indistinguishable from shunt from a gas exchange perspective. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3029", "contents": "When alveoli fill with fluid, they are unable to participate in gas exchange with blood, causing local or regional hypoxia, thus triggering vasoconstriction. This vasoconstriction is triggered by a smooth muscle reflex, as a consequence of the low oxygen concentration itself. Blood is then redirected away from this area, which poorly matches ventilation and perfusion, to areas which are being ventilated."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3030", "contents": "A decrease in perfusion relative to ventilation (as occurs in  pulmonary embolism , for example) is an example of increased  dead space . [ 12 ]  Dead space is a space where gas exchange does not take place, such as the trachea; it is ventilation without perfusion. A pathological example of dead zone would be a capillary blocked by an embolus. Although ventilation at that area is unaffected, blood will not be able to flow through that capillary; therefore, at that zone there will be no gas exchange. Dead zones may be corrected by supplying 100% inspired oxygen; when a capillary is blocked, the blood inside of it does not flow and upstream blood distributes between other capillaries that are exchanging gases effectively. The resulting blood that flows through them will not be 100% saturated, as it contains some unoxygenated blood (the one that came from the blocked capillary). For this reason, blood will actually be able to obtain the extra oxygen supplied to the patient. [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3031", "contents": "Pulmonary shunting causes the blood supply leaving a shunted area of the lung to have lower levels of  oxygen  and higher levels of  carbon dioxide  (i.e., the normal  gas exchange  does not occur)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3032", "contents": "A pulmonary shunt occurs as a result of blood flowing right-to-left through cardiac openings or in pulmonary arteriovenous malformations. [ clarification needed ]  The shunt which means V/Q\u00a0=\u00a00 for that particular part of the lung field under consideration results in de-oxygenated blood going to the heart from the lungs via the pulmonary veins."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3033", "contents": "If giving 100% oxygen for five to ten minutes doesn't raise the arterial tension of oxygen more than it does the alveolar pressure of oxygen then the defect in the lung is because of a pulmonary shunt. This is because although the oxygen partial pressure of alveolar gas has been changed by giving pure supplemental oxygen, the arterial gas oxygen concentration will not increase that much because the V/Q mismatch still exists and it will still add some de-oxygenated blood to the arterial system via the shunt. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3034", "contents": "Pulmonary stretch receptors  are  mechanoreceptors  found in the  lungs ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3035", "contents": "When the lung expands, the receptors initiate the  Hering-Breuer reflex , which reduces the  respiratory rate . This signal is transmitted by  vagus nerve . Increased firing from the stretch receptors also increases production of  pulmonary surfactant .\n Intercostal muscles  and  thoracic diaphragm  receive impulses from the  respiratory center , stretch receptors in the lungs send impulses to the respiratory center giving information about the state of the lungs. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3036", "contents": "Pulmonary surfactant  is a surface-active complex of  phospholipids  and  proteins  formed by  type II alveolar cells . [ 1 ]  The proteins and lipids that make up the  surfactant  have both  hydrophilic  and  hydrophobic  regions. By  adsorbing  to the air-water  interface  of  alveoli , with hydrophilic head groups in the water and the hydrophobic tails facing towards the air, the main lipid component of the surfactant,  dipalmitoylphosphatidylcholine  (DPPC), reduces  surface tension ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3037", "contents": "As a medication,  pulmonary surfactant  is on the  WHO Model List of Essential Medicines , the most important medications needed in a basic  health system . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3038", "contents": "Alveoli can be compared to gas in water, as the alveoli are wet and surround a central air space.  The  surface tension  acts at the air-water interface and tends to make the bubble smaller (by decreasing the surface area of the interface). The gas pressure ( P ) needed to keep an equilibrium between the collapsing force of  surface tension  ( \u03b3 ) and the expanding force of gas in an alveolus of radius  r  is expressed by the  Young\u2013Laplace equation :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3039", "contents": "Compliance  is the ability of  lungs  and  thorax  to expand. \nLung compliance is defined as the volume change per unit of pressure change across the lung. Measurements of lung volume obtained during the controlled inflation/deflation of a normal lung show that the volumes obtained during deflation exceed those during inflation, at a given pressure. This difference in inflation and deflation volumes at a given pressure is called  hysteresis  and is due to the air-water surface tension that occurs at the beginning of inflation. However, surfactant decreases the alveolar  surface tension , as seen in cases of premature infants with  infant respiratory distress syndrome .  The normal surface tension for water is 70 dyn/cm (70\u00a0mN/m) and in the lungs, it is 25 dyn/cm (25\u00a0mN/m); however, at the end of the expiration, compressed surfactant phospholipid molecules decrease the surface tension to very low, near-zero levels. Pulmonary surfactant thus greatly reduces  surface tension , increasing compliance allowing the lung to inflate much more easily, thereby reducing the work of breathing.  It reduces the pressure difference needed to allow the lung to inflate. The lung's compliance, and ventilation decrease when  lung tissue  becomes diseased and  fibrotic . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3040", "contents": "As the alveoli increase in size, the surfactant becomes more spread out over the surface of the liquid.  This increases surface tension effectively slowing the rate of expansion of the alveoli.  This also helps all alveoli in the lungs expand at the same rate, as one that expands more quickly will experience a large rise in surface tension slowing its rate of expansion.  It also means the rate of shrinking is more regular as if one reduces in size more quickly the surface tension will reduce more, so other alveoli can contract more easily than it can. Surfactant reduces surface tension more readily when the alveoli are smaller because the surfactant is more concentrated."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3041", "contents": "Surface tension draws fluid from capillaries to the alveolar spaces. Surfactant reduces fluid accumulation and keeps the airways dry by reducing surface tension. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3042", "contents": "Surfactant immune function is primarily attributed to two proteins:  SP-A  and  SP-D . These proteins can bind to sugars on the surface of pathogens and thereby  opsonize  them for uptake by phagocytes. It also regulates inflammatory responses and interacts with the adaptive immune response. Surfactant degradation or inactivation may contribute to enhanced susceptibility to lung inflammation and infection. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3043", "contents": "Dipalmitoylphosphatidylcholine  (DPPC) is a  phospholipid  with two 16-carbon saturated chains and a  phosphate  group with quaternary amine group attached. The DPPC is the strongest surfactant molecule in the pulmonary surfactant mixture. It also has a higher compaction capacity than the other phospholipids, because the apolar tail is less bent. Nevertheless, without the other substances of the pulmonary surfactant mixture, the DPPC's  adsorption  kinetics is very slow. This happens primarily because the phase  transition temperature  between  gel  to  liquid crystal  of pure DPPC is  41.5\u00a0\u00b0C, which is higher than the  human body's temperature  of 37\u00a0\u00b0C. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3044", "contents": "Phosphatidylcholine molecules form ~85% of the lipid in surfactant and have saturated acyl chains. Phosphatidylglycerol (PG) forms about 11% of the lipids in the surfactant, it has unsaturated fatty acid chains that fluidize the lipid monolayer at the interface. Neutral lipids and cholesterol are also present. The components for these lipids diffuse from the blood into type II alveolar cells where they are assembled and packaged for secretion into secretory organelles called  lamellar bodies . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3045", "contents": "Proteins  make up the remaining 10% of the surfactant.  Half of this 10% is  plasma proteins  but the rest is formed by the  apolipoproteins , surfactant proteins SP-A, SP-B, SP-C, and SP-D. The apolipoproteins are produced by the secretory pathway in type II cells. They undergo much post-translational modification, ending up in the lamellar bodies. These are concentric rings of lipid and protein, about 1\u00a0\u03bcm in diameter."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3046", "contents": "The SP proteins reduce the critical temperature of DPPC's  phase transition  to a value lower than 37\u00a0\u00b0C, [ 10 ]  which improves its adsorption and interface spreading velocity. [ 11 ] [ 12 ]  The compression of the interface causes a phase change of the surfactant molecules to liquid-gel or even gel-solid. The fast adsorption velocity is necessary to maintain the integrity of the gas exchange region of the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3047", "contents": "Each SP protein has distinct functions, which act  synergistically  to keep an interface rich in DPPC during lung's expansion and contraction. Changes in the surfactant mixture composition alter the pressure and temperature conditions for phase changes and the phospholipids' crystal shape as well. [ 13 ]  Only the liquid phase can freely spread on the surface to form a monolayer. Nevertheless, it has been observed that if a lung region is abruptly expanded the floating crystals crack like \" icebergs \". Then the SP proteins selectively attract more DPPC to the interface than other phospholipids or cholesterol, whose surfactant properties are worse than DPPC's. The SP also fastens the DPPC on the interface to prevent the DPPC from being squeezed out when the surface area decreases  [ 12 ]  This also reduces the interface compressibility. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3048", "contents": "There are a number of types of pulmonary surfactants available. Ex-situ measurements of  surface tension  and  interfacial rheology  can help to understand the functionality of pulmonary surfactants. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3049", "contents": "Synthetic pulmonary surfactants"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3050", "contents": "Animal derived surfactants"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3051", "contents": "Even though the surface tension can be greatly reduced by pulmonary surfactant, this effect will depend on the surfactant's concentration on the interface. The interface concentration has a saturation limit, which depends on temperature and mixture composition. Because during ventilation there is a variation of the lung surface area, the surfactant's interface concentration is not usually at the level of saturation. The surface increases during inspiration, which consequently opens space for new surfactant molecules to be recruited to the interface. Meanwhile, during expiration the surface area decreases at a rate which is always in excess of the rate at which the surfactant molecules are driven from the interface into the water film. Thus, the surfactant density at the air water interface remains high and is relatively preserved throughout expiration, decreasing the surface tension even further. This also explains why the compliance is greater during expiration than during inspiration.  [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3052", "contents": "SP molecules contribute to increasing the surfactant interface adsorption kinetics, when the concentration is below the  saturation  level. They also make  weak bonds  with the surfactant molecules at the interface and hold them longer there when the interface is compressed. Therefore, during ventilation, surface tension is usually lower than at equilibrium. Therefore, the surface tension varies according to the volume of air in the lungs, which protects them from atelectasis at low volumes and tissue damage at high volume levels. [ 11 ] [ 13 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3053", "contents": "Surfactant production in humans begins in  type II cells  during the  alveolar sac  stage of lung development.  Lamellar bodies  appear in the cytoplasm at about 20 weeks gestation. [ 16 ]  These lamellar bodies are secreted by  exocytosis  into the  alveolar lining fluid , where the surfactant forms a meshwork of  tubular myelin [ 17 ] [ 18 ]   Full term  infants are estimated to have an alveolar storage pool of approximately 100\u00a0mg/kg of surfactant, while preterm infants have an estimated 4\u20135\u00a0mg/kg at birth. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3054", "contents": "Club cells  also produce a component of lung surfactant. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3055", "contents": "Alveolar surfactant has a half-life of 5 to 10 hours once secreted. It can be both broken down by macrophages and/or reabsorbed into the lamellar structures of type II pneumocytes. Up to 90% of surfactant DPPC (dipalmitoylphosphatidylcholine) is recycled from the alveolar space back into the type II pneumocyte. This process is believed to occur through  SP-A  stimulating receptor-mediated,  clathrin  dependent  endocytosis . [ 21 ]  The other 10% is taken up by alveolar macrophages and digested."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3056", "contents": "In late 1920s von Neergaard [ 22 ]  identified the function of the pulmonary surfactant in increasing the compliance of the lungs by reducing surface tension. However the significance of his discovery was not understood by the scientific and medical community at that time. He also realized the importance of having low surface tension in lungs of newborn infants. Later, in the middle of the 1950s, Pattle and  Clements  rediscovered the importance of surfactant and low surface tension in the lungs. At the end of that decade it was discovered that the lack of surfactant caused  infant respiratory distress syndrome  (IRDS). [ 23 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3057", "contents": "Respiratory adaptation  is the specific change that the  respiratory system  undergoes in response to the demands of  physical exertion . Intense physical exertion, such as that involved in  fitness training , places elevated demands on the respiratory system. Over time, this results in respiratory changes as the system adapts to these requirements. [ 1 ]  These changes ultimately result in an increased exchange of  oxygen  and  carbon dioxide , which is accompanied by an increase in  metabolism . [ 2 ]  Respiratory adaptation is a physiological determinant of peak endurance performance, and in elite athletes, the pulmonary system is often a limiting factor to exercise under certain conditions. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3058", "contents": "Respiratory adaptation begins almost immediately after the initiation of the physical  stress  associated with exercise. This triggers signals from the  motor cortex  that stimulate the respiratory center of the  brain stem , in conjunction with feedback from the  proprioreceptors  in the muscles and joints of the active limbs. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3059", "contents": "With higher intensity training,  breathing rate  is increased in order to allow more air to move in and out of the lungs, which enhances gas exchange.  Endurance training  typically results in an increase in the respiration rate. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3060", "contents": "With adaptation,  lung capacity  increases, allowing a greater quantity of air to move in and out. Endurance training typically results in an increase in  tidal volume . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3061", "contents": "Muscles involved in respiration, including the  diaphragm  and  intercostal muscles , increase in strength and endurance. This results in an improved ability to breathe in more air, for longer amounts of time with less fatigue.  Aerobic training  typically improves the endurance of respiratory muscles, whereas  anaerobic training  tends to increase the size and strength of respiratory muscles.  [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3062", "contents": "Exercise increases the  vascularization  of the lungs. This allows the more blood flow in and out of the lungs. This enhances the uptake of oxygen, since there is greater surface area for blood to bind with  haemoglobin . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3063", "contents": "Respiratory adaptation results an increase in the number of  alveoli , which enables more gas exchange to occur. This is coupled with an increase in alveolar oxygen tension. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3064", "contents": "A  respiratory pressure meter  measures the maximum  inspiratory  and  expiratory  pressures that a patient can generate at either the mouth (MIP and MEP) or inspiratory pressure a patient can generate through their nose via a sniff maneuver (SNIP). These measurements require patient cooperation and are known as volitional tests of  respiratory muscle  strength.  Handheld devices  displaying the measurement achieved in centimetres of water pressure ( cmH 2 O ) and the pressure trace created, allow quick patient testing away from the traditional  pulmonary  laboratory and are useful for ward-based,  out-patient  and  preoperative  assessment, as well as for use by  pulmonologists  and  physiotherapists ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3065", "contents": "The principal advantage of volitional tests is that they give an estimate of inspiratory or expiratory muscle strength, are simple to perform, and are well tolerated by patients. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3066", "contents": "Impairment of inspiratory and expiratory respiratory muscles is a common clinical finding, not only in patients with  neuromuscular disease  but also in patients with primary disease of the  lung parenchyma  or airways. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3067", "contents": "Patients with  neuromuscular  or  metabolic diseases  are at risk of developing  skeletal and respiratory muscle weakness . In neuromuscular diseases close attention should be paid to the involvement of both the inspiratory and the expiratory muscles. In patients with  multiple sclerosis  for example,  abdominal  (and hence expiratory) muscle weakness is a hallmark of the disease, and is related to clinical problems such as mucus retention. In  lung diseases , such as  cystic fibrosis  and  COPD , inspiratory muscle weakness is often present. When patients are malnourished or exposed to  corticosteroids , weakness of the respiratory muscles is also seen in these diseases."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3068", "contents": "Measuring respiratory muscle strength is a long-established method of assessing the mechanics of breathing. Respiratory muscle dysfunction (i.e., reduced strength or endurance) should be distinguished from lung function abnormalities and measured separately. Measurement of respiratory muscle function is important in the diagnosis of respiratory muscle disease or respiratory muscle dysfunction. It may also be helpful in the assessment of the impact of  chronic diseases  or their treatment on the respiratory muscles. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3069", "contents": "Maximal inspiratory pressure  (MIP), also known as  negative inspiratory force  (NIF), is the maximum pressure that can be generated against an occluded (closed or obstructed) airway beginning at  functional residual capacity  (the  volume  of air present in the  lungs  at the end of passive expiration). It is a marker of respiratory muscle function and strength, [ 4 ]  represented by  cmH 2 O  and measured with a  manometer . MIP is an important and  noninvasive  index of  diaphragm  strength and an independent tool for diagnosing many illnesses. [ 5 ]  Typical MIPs in adult males can be estimated from the equation M IP  = 142 - (1.03 x Age) cmH 2 O, where age is in years. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3070", "contents": "This test is performed at RV ( Residual Volume ), the amount of air remaining in the patient's lungs after fully exhaling. The patient then inhales as hard and as fast as possible with maximal sustained effort for longer than 1 second, and the pressure is the highest achieved during that time. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3071", "contents": "This test is performed at  TLC (total lung capacity) . The patient inhales fully to prepare, and then exhales as hard and as fast as possible with maximal sustained effort for longer than 1 second. The exhaled pressure is the highest achieved during that time. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3072", "contents": "Sniff nasal inspiratory pressure (SNIP) refers to short, sharp voluntary inspiratory maneuver (inhalation) through one or both un-occluded (not closed or obstructed) nostrils. The tests are performed at FRC (functional residual capacity), at the end of tidal expiration. The measurement recorded is the peak pressure. This test is particularly suited to neuromuscular weakness because it doesn't require a mouthpiece and because it is easily mastered by the vast majority of patients. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3073", "contents": "The  respiratory quotient  ( RQ  or  respiratory coefficient ) is a  dimensionless number  used in calculations of  basal metabolic rate  (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body, when the body is in a steady state. Such measurements, like measurements of oxygen uptake, are forms of indirect  calorimetry . It is measured using a  respirometer . The respiratory quotient value indicates which macronutrients are being metabolized, as different energy pathways are used for fats, carbohydrates, and proteins. [ 1 ]  If metabolism consists solely of lipids, the respiratory quotient is approximately 0.7, for proteins it is approximately 0.8, and for carbohydrates it is 1.0. Most of the time, however, energy consumption is composed of both fats and carbohydrates. The approximate respiratory quotient of a mixed diet is 0.8. [ 1 ]  Some of the other factors that may affect the respiratory quotient are energy balance, circulating insulin, and insulin sensitivity. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3074", "contents": "It can be used in the  alveolar gas equation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3075", "contents": "The  respiratory exchange ratio  ( RER ) is the  ratio  between the  metabolic  production of  carbon dioxide  (CO 2 ) and the uptake of  oxygen  (O 2 ). [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3076", "contents": "The ratio is determined by comparing exhaled gases to room air. Measuring this ratio is equal to RQ only at rest or during mild to moderate  aerobic exercise  without the accumulation of  lactate . The loss of accuracy during more intense  anaerobic exercise  is among others due to factors including the  bicarbonate buffer system . The body tries to compensate for the accumulation of lactate and minimize the acidification of the blood by expelling more CO 2  through the  respiratory system . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3077", "contents": "The RER can exceed 1.0 during intense exercise. A value above 1.0 cannot be attributed to the substrate metabolism, but rather to the aforementioned factors regarding bicarbonate buffering. [ 5 ]  Calculation of RER is commonly done in conjunction with exercise tests such as the  VO 2  max test . This can be used as an indicator that the participants are nearing  exhaustion  and the limits of their cardio-respiratory system. An RER greater than or equal to 1.0 is often used as a secondary endpoint criterion of a VO 2  max test. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3078", "contents": "The respiratory quotient ( RQ ) is the ratio:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3079", "contents": "RQ  = CO 2 eliminated  / O 2 consumed"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3080", "contents": "where the term \"eliminated\" refers to carbon dioxide (CO 2 ) removed from the body in a steady state."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3081", "contents": "In this calculation, the CO 2  and O 2  must be given in the same units, and in quantities proportional to the number of molecules. Acceptable inputs would be either  moles , or else volumes of gas at standard temperature and pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3082", "contents": "Many metabolized substances are compounds containing only the elements  carbon ,  hydrogen , and  oxygen . Examples include  fatty acids ,  glycerol ,  carbohydrates ,  deamination  products, and  ethanol . For complete oxidation of such compounds, the chemical equation is"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3083", "contents": "C x H y O z  + (x + y/4 - z/2) O 2  \n\u2192 x CO 2  + (y/2) H 2 O"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3084", "contents": "and thus metabolism of this compound gives an RQ of x/(x + y/4 - z/2)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3085", "contents": "For glucose, with the molecular formula, C 6 H 12 O 6 , the complete oxidation equation is C 6 H 12 O 6  + 6 O 2  \n\u2192 6 CO 2  + 6 H 2 O. Thus, the RQ= 6 CO 2 / 6 O 2 =1."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3086", "contents": "For oxidation of a fatty acid molecule, namely  palmitic acid : [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3087", "contents": "A RQ near 0.7 indicates that  fat  is the predominant fuel source, a value of 1.0 is indicative of  carbohydrate  being the predominant fuel source, and a value between 0.7 and 1.0 suggests a mix of both fat and carbohydrate. [ 6 ]  In general a mixed diet corresponds with an RER of approximately 0.8. [ 7 ]  For fats, the RQ depends on the specific fatty acids present.  Amongst the commonly stored fatty acids in vertebrates, RQ varies from 0.692 ( stearic acid ) to as high as 0.759 ( docosahexaenoic acid ).  Historically, it was assumed that 'average fat' had an RQ of about 0.71, and this holds true for most mammals including humans.  However, a recent survey showed that aquatic animals, especially fish, have fat that should yield higher RQs on oxidation, reaching as high as 0.73 due to high amounts of docosahexaenoic acid. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3088", "contents": "The range of respiratory coefficients for organisms in metabolic balance usually ranges from 1.0 (representing the value expected for pure carbohydrate oxidation) to ~0.7 (the value expected for pure fat oxidation). In general, molecules that are more oxidized (e.g., glucose) require less oxygen to be fully metabolized and, therefore, have higher respiratory quotients. Conversely, molecules that are less oxidized (e.g., fatty acids) require more oxygen for their complete metabolism and have lower respiratory quotients. See  BMR  for a discussion of how these numbers are derived. A mixed diet of fat and carbohydrate results in an average value between these numbers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3089", "contents": "RQ  value corresponds to a caloric value for each liter (L) of CO 2  produced. If O 2  consumption numbers are available, they are usually used directly, since they are more direct and reliable estimates of energy production."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3090", "contents": "RQ  as measured includes a contribution from the energy produced from protein. However, due to the complexity of the various ways in which different amino acids can be metabolized, no single  RQ  can be assigned to the oxidation of protein in the diet."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3091", "contents": "Insulin, which increases lipid storage and decreases fat oxidation, is positively associated with increases in the respiratory quotient. [ 2 ]  A positive energy balance will also lead to an increased respiratory quotient. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3092", "contents": "Practical applications of the respiratory quotient can be found in severe cases of  chronic obstructive pulmonary disease , in which patients spend a significant amount of energy on respiratory effort. By increasing the proportion of fats in the diet, the respiratory quotient is driven down, causing a relative decrease in the amount of CO 2  produced. This reduces the respiratory burden to eliminate CO 2 , thereby reducing the amount of energy spent on respirations. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3093", "contents": "Respiratory Quotient can be used as an indicator of over or underfeeding. Underfeeding, which forces the body to utilize fat stores, will lower the respiratory quotient, while overfeeding, which causes  lipogenesis , will increase it. [ 10 ]  Underfeeding is marked by a respiratory quotient below 0.85, while a respiratory quotient greater than 1.0 indicates overfeeding. This is particularly important in patients with compromised respiratory systems, as an increased respiratory quotient significantly corresponds to increased respiratory rate and decreased  tidal volume , placing compromised patients at a significant risk. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3094", "contents": "Because of its role in metabolism, respiratory quotient can be used in analysis of liver function and diagnosis of liver disease. In patients with  liver cirrhosis , non-protein respiratory quotient (npRQ) values act as good indicators in the prediction of overall survival rate. Patients having a npRQ < 0.85 show considerably lower survival rates as compared to patients with a npRQ > 0.85. [ 11 ]  A decrease in npRQ corresponds to a decrease in glycogen storage by the liver. [ 11 ]  Similar research indicates that non-alcoholic fatty liver diseases are also accompanied by a low respiratory quotient value, and the non protein respiratory quotient value was a good indication of disease severity. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3095", "contents": "Recently the respiratory quotient is also used from aquatic scientists to illuminate its environmental applications. Experimental studies with natural  bacterioplankton  using different single substrates suggested that RQ is linked to the elemental composition of the respired compounds. [ 12 ]  By this way, it is demonstrated that bacterioplankton RQ is not only a practical aspect of Bacterioplankton Respiration determination, but also a major ecosystem state variable that provides unique information about  aquatic ecosystem  functioning. [ 12 ]  Based on the stoichiometry of the different metabolized substrates, the scientists can predict that  dissolved oxygen  (O 2 ) and  carbon dioxide  (CO 2 ) in aquatic ecosystems should covary inversely due to the processing of  photosynthesis  and  respiration . [ 13 ]  Using this quotient we could shed light on the metabolic behavior and the simultaneous roles of chemical and physical forcing that shape the  biogeochemistry  of aquatic ecosystems. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3096", "contents": "Moving from a molecular and cellular level to an ecosystem level, various processes account for the exchange of O 2  and CO 2  between the biosphere and atmosphere. Field measurements of the concurrent consumption of oxygen (-\u0394O 2 ) and production of carbon dioxide (\u0394CO 2 ) can be used to derive an apparent respiratory quotient (ARQ). [ 14 ]  This value reflects a cumulative effect of not only the  aerobic respiration  of all organisms (microorganisms and higher consumers) in the sample, but also all the other  biogeochemical  processes which consume O 2  without a corresponding CO 2  production and vice versa influencing the observed RQ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3097", "contents": "[ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3098", "contents": "The  respiratory rate  is the rate at which  breathing  occurs; it is set and controlled by the  respiratory center  of the brain. A person's respiratory rate is usually measured in breaths per minute."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3099", "contents": "The respiratory rate in  humans  is measured by counting the number of breaths for one minute through counting how many times the chest rises.  A  fibre-optic  breath rate sensor can be used for monitoring patients during a  magnetic resonance imaging  scan. [ 1 ]  Respiration rates may increase with  fever , illness, or other medical conditions. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3100", "contents": "Inaccuracies in respiratory measurement have been reported in the literature. [ 3 ]  One study compared respiratory rate counted using a 90-second count period, to a full minute, and found significant differences in the rates. [ citation needed ] .  Another study found that rapid respiratory rates in babies, counted using a  stethoscope , were 60\u201380% higher than those counted from beside the cot without the aid of the stethoscope. [ citation needed ]  Similar results are seen with animals when they are being handled and not being handled\u2014the invasiveness of touch apparently is enough to make significant changes in breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3101", "contents": "Various other methods to measure respiratory rate are commonly used, including impedance  pneumography , [ 4 ]  and  capnography  which are commonly implemented in patient monitoring. In addition, novel techniques for automatically monitoring respiratory rate using wearable sensors are in development, such as estimation of respiratory rate from the  electrocardiogram ,  photoplethysmogram , or  accelerometry  signals. [ 5 ] [ 6 ] [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3102", "contents": "Breathing rate is often interchanged with the term breathing frequency. However, this should not be considered the frequency of breathing because realistic breathing signal is composed of many frequencies. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3103", "contents": "For humans, the typical respiratory rate for a healthy adult at rest is 12\u201315 breaths per minute. [ 10 ]  The  respiratory center  sets the quiet  respiratory rhythm  at around two seconds for an inhalation and three seconds exhalation. This gives the lower of the average rate at 12 breaths per minute."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3104", "contents": "Average resting respiratory rates by age are: [ 11 ] [ self-published source ] [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3105", "contents": "Respiratory minute volume  is the volume of air which is  inhaled  (inhaled minute volume) or  exhaled  (exhaled minute volume) from the  lungs  in one minute."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3106", "contents": "The value of respiratory rate as an indicator of potential respiratory dysfunction has been investigated but findings suggest it is of limited value."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3107", "contents": "One study found that only 33% of people presenting to an emergency department with an  oxygen saturation  below 90% had an increased respiratory rate. [ 14 ]  An evaluation of respiratory rate for the differentiation of the severity of illness in babies under 6 months found it not to be very useful. Approximately half of the babies had a respiratory rate above 50 breaths per minute, thereby questioning the value of having a \"cut-off\" at 50 breaths per minute as the indicator of serious respiratory illness."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3108", "contents": "It has also been reported that factors such as  crying ,  sleeping , agitation and age have a significant influence on the respiratory rate. [ citation needed ]  As a result of these and similar studies the value of respiratory rate as an indicator of serious illness is limited."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3109", "contents": "Nonetheless, respiratory rate is widely used to monitor the physiology of acutely-ill hospital patients. It is measured regularly to facilitate identification of changes in physiology along with other  vital signs . This practice has been widely adopted as part of early warning systems. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3110", "contents": "The  Root effect  is a physiological phenomenon that occurs in  fish   hemoglobin , named after its discoverer R. W. Root.  It is the phenomenon where an increased  proton  or  carbon dioxide  concentration (lower  pH ) lowers hemoglobin's affinity and carrying capacity for  oxygen . [ 1 ] [ 2 ]   The Root effect is to be distinguished from the  Bohr effect  where only the affinity to oxygen is reduced. Hemoglobins showing the Root effect show a loss of cooperativity at low pH. This results in the  Hb-O 2  dissociation curve  being shifted downward and not just to the right. At low pH, hemoglobins showing the Root effect don't become fully oxygenated even at oxygen tensions up to 20kPa. [ 2 ]  This effect allows hemoglobin in fish with  swim bladders  to unload oxygen into the swim bladder against a high oxygen gradient. [ 3 ]   The effect is also noted in the choroid  rete , the network of  blood vessels  which carries oxygen to the  retina . [ 3 ]  In the absence of the Root effect,  retia  will result in the diffusion of some oxygen directly from the arterial blood to the venous blood, making such systems less effective for the concentration of oxygen. [ 4 ]  It has also been hypothesized that the loss of affinity is used to provide more oxygen to red muscle during acidotic stress. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3111", "contents": "Smoker's macrophages  are  alveolar macrophages  whose characteristics, including appearance, cellularity,  phenotypes ,  immune response , and other functions, have been affected upon the exposure to  cigarettes . [ 1 ]  These altered immune cells are derived from several signaling pathways and are able to induce numerous  respiratory diseases . They are involved in  asthma ,  chronic obstructive pulmonary diseases  (COPD),  pulmonary fibrosis , and  lung cancer . [ 2 ]  Smoker\u2019s macrophages are observed in both firsthand and secondhand smokers, so anyone exposed to cigarette contents, or  cigarette smoke extract  (CSE), would be susceptible to these macrophages, thus in turns leading to future complications. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3112", "contents": "Alveolar macrophages are crucial in processing inhaled substances including cigarette chemicals and  particulate matter . [ 4 ]  The chemicals in tobacco, such as  nicotine ,  tar , and  carbon monoxide , stimulate several physiological pathways, which influence the recruitment and functions of these macrophages. Some of the smoker\u2019s macrophages are recruited from the circulating  monocytes  while some are the original alveolar macrophages residing in the lung. The biochemical processes also lead to  immunomodulation  and dysregulated repair processes, so the malfunction of macrophages renders individuals more susceptible to infections. [ 5 ] [ 2 ]  In addition, these inhaled substances can enter the bloodstream, especially nicotine which is rapidly transported to the brain, leading to addiction;  it will subsequently distributed throughout the body, leading to carcinoma in the future. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3113", "contents": "The morbidity of cigarette smoking is nearly 50% with 7 million first-hand smokers and 1.2 millions second hand smokers killed each year. [ 8 ]  Regardless of active or passive smokers, macrophage accumulation is found in the lungs. [ 3 ] [ 5 ]  The diagnostic methods for smoke-related diseases include  bronchoalveolar lavage  which can also be used for examining smoker's macrophages in addition to augmented inflammatory cells in the alveolar lumen. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3114", "contents": "The uptake of tar from cigarettes accumulates in alveolar macrophages and causes autofluorescence. [ 4 ]  The intensity of fluorescence, however, is independent of cigarette exposure. This indicates a maximum capacity of tar uptake; excess tar cannot be retained by macrophages. Another pigment in smoker\u2019s macrophage is  hemosiderin  which is involved in iron homoeostasis. Hemosiderin-laden pigmented macrophages are yellowish brown and found in the bronchiole and peribronchiolar alveolar space. [ 9 ]  The presence of these dirty macrophages has been a characteristic of many smoke-related lung diseases. [ 9 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3115", "contents": "A macrophage can be  polarized  into the classic M1 or M2 phenotype, and this phenomenon can be seen in cigarette consumption. [ 2 ]  In this polarization scheme, lower M1 markers and higher M2 markers have been observed. [ 4 ]  The reprogram of macrophage implies a dysregulated inflammation that can damage healthy lung cells."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3116", "contents": "Macrophage polarization is mediated by three major signaling pathways:  NF-\u03baB ,  MAPK , and  JAK/STAT . [ 2 ]  Each signaling cascade can lead to different results depending on the length of smoke history. It is therefore important to evaluate the characteristics of research participants and specify the experimental conditions when examining smoker\u2019s macrophages. It is anticipated that cigarette smoking inhibits signal transduction which alters gene expression and cytokine profile with increasing M2-like phenotype. This trait is involved in anti-inflammation and tissue repair, but this can also be pro-fibrotic. [ 11 ]  However, some studies found variation in the conventional polarization and found dual polarization in multiple diseases, yet the direction and extent of polarization are also different across diseases. [ 4 ]  Despite the contradiction, treatments targeting the polarization process have promising results."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3117", "contents": "In long-term smoking or established diseases, not only does CSE decrease the production of  pro-inflammatory cytokines , but also impairs  TLR2  and  TLR4  signaling. [ 2 ]  Its inhibitory effect on NF-\u03baB also induces  apoptosis  of alveolar macrophage. Prolonged exposure to CSE hence leads to M2 polarization. Meanwhile, NF-\u03baB pathways will be activated with low concentration of CSE or in previously unexposed individuals. The increased activity of NF-\u03baB upregulates the production of pro-inflammatory cytokines  TNF-\u03b1 ,  IL-1\u03b2 , and  IL-8 . The short-term exposure attracts macrophages and  neutrophils  to the lung with a 4-fold increase in cellularity. [ 4 ] [ 2 ]  Short duration also biases polarization towards M1 phenotype. The number of immune cells however will be normalized in 6 months, demonstrating the shift in signaling direction."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3118", "contents": "Similar time and dose dependent effects of CSE are exerted on macrophage polarization through the MAPK signaling pathway which involves  JNK  and ERK as intermediate signaling molecules. [ 2 ]  In diseased conditions due to long-term smoking, the inactivation of JNK reduces the levels of  reactive nitrogen species  and pro-inflammatory cytokines with more M2-like phenotype. However, brief exposure to CSE triggers the activation of ERK that increases  MUC1 , TNF-a, and IL-8 levels to produce inflammatory effects."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3119", "contents": "Cigarette contents also modulate multiple  STAT proteins  activities. [ 2 ]  In response to the smoking, STAT3 and STAT6 signaling are stimulated to potentiate M2-like phenotype with elevated  IL-6 ,  IL-10 ,  IL-12 , and  TGF-b . In the meantime, the toxic nitrogenous chemicals and oxidative stress would be reduced. In post-smoke situations, reduction in STAT1 is associated with M1-like phenotype and the downregulation of  IFN-\u03b3  signaling."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3120", "contents": "Nicotine in cigarettes modulates the above signaling pathways by binding to  \u03b1-7 nicotinic receptors  on macrophage or neurons, hence activating the  cholinergic anti-inflammatory pathway . [ 12 ]  Changes can thus be directly mediated by binding of nicotine to macrophage or indirectly via the  Vagus nerve . Upon binding, the inhibition of the NF-\u03baB and activation of JAK2/STAT3 pathways lead to over-inhibition of pro-inflammatory cytokines and thus an imbalance toward  anti-inflammatory cytokines . The result may be lethal if inflammation is not controlled."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3121", "contents": "Cigarettes contain a small amount of iron, but cumulatively a larger quantity in daily smoking. [ 13 ]  The increasing iron exposure in the lung and airway affects both respiratory and systemic  iron homeostasis  by modifying cellular response. Although direct etiologic link has not been established, there is a 4-fold increase in intracellular iron level and a concomitant iron release observed in smoker\u2019s macrophage. [ 4 ] [ 13 ]  While iron-loading affects macrophage activation and functions, excessive extracellular iron favors bacterial growth. Normally, activated alveolar macrophage secretes  lipocalin-2  which traps bacterial  siderophores  and prevents bacterial iron uptake. Iron imbalance locally in the lung thus results in higher risk of infection."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3122", "contents": "Hemosiderin is the iron storage in smoker's macrophage rather than  ferritin . It is formed during hemorrhage or abnormal metabolism of ferritin. [ 14 ] [ 15 ]  Indeed, buildup of iron causes oxidative stress resulting in lung damage and mitochondrial dysfunction. [ 13 ]  The level of hemosiderin-laden macrophage is also associated with  pulmonary hemodynamics parameters  which is used to evaluate pulmonary hypertension in the early stage of diseases. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3123", "contents": "Iron homeostasis has been associated with macrophage polarization and reprogramming despite unclear causality in cigarette iron. [ 13 ]  M1 macrophage demonstrates high  TF ,  HAMP , and  FTH1  gene activities that mediates iron uptake. M2 macrophage on the other hand expresses  FPN1  which causes iron release. Supplementing iron to mice predisposes macrophage to M2 phenotype and inhibits M1-mediated inflammation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3124", "contents": "The immune functions in smoker\u2019s macrophages are compromised, so the airway pathogens are more likely to accumulate and cause infection. [ 17 ]  Smoker\u2019s macrophages have reduced expression of  HLA-DR antigens , causing immunosuppression. [ 18 ] [ 19 ]  In addition, nicotine impairs the phagocytosis of  M. tuberculosis  and also induces immunosuppression via the activation of alpha-7 nicotinic receptors. [ 4 ] [ 17 ]  Meanwhile, due to the impaired TLR2 and TLR4 signaling, macrophages fail to recognize pathogens, so there is a decrease in pathogen clearance. [ 17 ]  Therefore, smokers are prone to  acute respiratory tract infection  and  community acquired pneumonia . [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3125", "contents": "Asthma has been proven to have a causal relationship with smoking due to the modified inflammation reaction. [ 21 ]  Alveolar macrophages will be excessively recruited onto the airway wall, leading to a narrower airway for oxygen to pass through. Some patients may also be affected by airway remodeling. Smoker's macrophages affect the elastic fibers in the mucus layer of the airways, tightening the lumen and causing asthma. Symptoms of asthma include wheezing, coughing, and chest discomfort. To ameliorate the situation, drugs that either suppress the inflammatory response or relaxes the airway will be administrated, so air can pass through. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3126", "contents": "Smoking is found to be the most important causative factor leading to COPD. [ 23 ]  Because of the altered inflammatory response of the macrophages, smoking induces inflammation across the entire airway, which in turns obstructs the airflow. Symptoms of COPD include persistent coughing, wheezing, chest infections and breathlessness. Treatments for COPD usually focus on the source of the problem, which is smoking, thus the general treatment is going through smoking rehabilitation which including  nicotine replacement therapy , mental therapy for advice, and support to quit smoking. In certain urgent cases, direct constriction also occurs, in which  bronchodilators  allow the airway to dilate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3127", "contents": "Tobacco smoking has been associated with cancer mainly along the respiratory tract, but may also lead to cancer in the bladder and renal pelvis. [ 24 ]  Upon smoking, carcinogenic chemicals are inhaled, affecting the inflammation response. As inflammation plays an important role in inducing cancer, with smoking affecting the inflammatory response of macrophages in the lungs, the dysregulated inflammatory response poses a higher risk in developing cancer along the airway. Symptoms of cancer mediated by cancer include lumps on the body, sudden weight loss, persistent coughing and tough swallowing. Treatments for cancer are generally surgery,  chemotherapy  and  radiation therapy . These treatments directly target the cancer cells to kill the cancer prior to smoking rehabilitation programs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3128", "contents": "Smoking cessation  is one the most effective methods for managing numerous smoke-related diseases and other immune diseases such as  AIDs . [ 25 ] [ 26 ]  It brings both short term and long term benefits as the mucus clearance is improved in 48 hours and the mortality risk of lung cancer is halved in 10 years. [ 25 ]  In addition, the immune system starts to recover in 15 days as the inhibitory effects of cigarettes on macrophages are removed. [ 27 ]  The risks of morbidity and mortality of infectious diseases are significantly reduced in 1 year and become comparable with non-smokers after 5 years of quitting. [ 20 ]  Meanwhile, the life expectancy after smoking cessation increased by 10 years with the reduced risks of these diseases. [ 28 ]  Furthermore, early cessation in the age of 25-34 enhances the survival rate at the age of 35 by 20-30% compared with an average smoker. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3129", "contents": "Cigarette smoking has been extensively researched to understand the mechanisms of how it affects the macrophages and causes diseases. Meanwhile, novel therapies are being developed to target the molecular pathways. [ 2 ]  Future treatments have higher specificity and can potentially reverse the changes to macrophage and the cytokine profile, hence improving the clinical outcomes of related diseases. In the meantime, governments around the globe are encouraging smoking cessation and some progress is made. [ 30 ]  However, the psychological challenge for smokers to commit to quitting is often omitted. [ 31 ]  For instance, smoking cessation has been associated with depression while individuals may also experience withdrawal symptoms. [ 31 ] [ 32 ]  The psychological aspect of smoking could be further investigated to formulate a better rehabilitation strategy to aid smoking cessation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3130", "contents": "Sniffing  is a perceptually-relevant behavior, defined as the active sampling of odors through the  nasal cavity  for the purpose of information acquisition. This behavior, displayed by all terrestrial vertebrates, is typically identified based upon changes in respiratory frequency and/or amplitude, [ 1 ] [ 2 ]   and is often studied in the context of odor guided behaviors and olfactory perceptual tasks. Sniffing is quantified by measuring intra-nasal pressure or flow or air [ 3 ] [ 4 ] [ 5 ] [ 6 ]   or, while less accurate, through a strain gauge on the chest to measure total respiratory volume. [ 7 ]  Strategies for sniffing behavior vary depending upon the animal, with small animals (rats, mice, hamsters) displaying sniffing frequencies ranging from 4 to 12\u00a0Hz [ 2 ] [ 3 ] [ 8 ]  but larger animals (humans) sniffing at much lower frequencies, usually less than 2\u00a0Hz. [ 7 ] [ 9 ]  Subserving sniffing behaviors, evidence for an \"olfactomotor\" circuit in the brain exists, [ 10 ] [ 11 ]   wherein perception or expectation of an odor can trigger brain  respiratory center  to allow for the modulation of sniffing  frequency  and  amplitude  and thus acquisition of odor information. Sniffing is analogous to other stimulus sampling behaviors, including visual  saccades , active touch, and  whisker  movements in small animals (viz., whisking). [ 12 ] [ 13 ]   Atypical sniffing has been reported in cases of neurological disorders, especially those disorders characterized by impaired motor function and olfactory perception. [ 14 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3131", "contents": "The behavior of sniffing incorporates changes in air flow within the  nose . This can involve changes in the depth of  inhalation  and the frequency of inhalations. Both of these entail modulations in the manner whereby air flows within the nasal cavity and through the nostrils. As a consequence, when the air being breathed is odorized, odors can enter and leave the nasal cavity with each sniff. The same applies regardless of what gas is being inhaled, including  toxins  and solvents, and other industrial chemicals which may be inhaled as a form of drug or  substance abuse . [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3132", "contents": "The act of sniffing is considered distinct from  respiration  on several grounds. In humans, one can assess the occurrence of a sniff based upon volitional control of air movement through the nose. [ 17 ]  In these cases, human subjects can be asked to inhale for a certain amount of time, or in a particular pattern. [ 7 ]  Some animals are  obligate nasal breathers , wherein the only air for respiration must arrive into the lungs via the nose. This includes rats and mice. Thus, in these animals the distinction between a breath and a sniff is not clear and could be argued to be indistinguishable. [ 18 ]  (See  sniffing in small animals .)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3133", "contents": "Sniffing is observed among all terrestrial vertebrates, wherein they inhale environmental air. [ 19 ]   Sniffing may also occur in underwater environments wherein an animal may exhale air from within its  lungs  and nasal cavity to acquire odors within an aquatic environment and then re-inhale this air. [ 20 ]  (See  sniffing in small animals .)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3134", "contents": "While sniffing behavior is often observed and discussed within the context of acquiring odor information, sniffing is also displayed during the performance of motivated behaviors and upon deep brain electrical stimulation of brain reward centers. For instance, prior to obtaining a food reward, mice and rabbits increase their sniffing frequency [ 3 ] [ 21 ]    in a manner independent of seeking odor information. Sniffing behavior is also displayed by animals upon involuntary electrical stimulation of numerous brain structures. [ 22 ]   Thus, while sniffing is often considered a critical part of  olfaction , its link with motivated and reward behaviors suggests it plays a role in other behaviors."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3135", "contents": "Studies into the perceptual correlates of sniffing on human olfaction did not reach the mainstream scientific community until the 1950s. Frank Jones, an American psychologist, published a paper demonstrating the interplay between parameters of sniffing and odor detection thresholds. He found that deep sniffs, consisting of a large volume of air, allowed for consistent and accurate detection of odors. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3136", "contents": "One of the earliest reports of exploring sniffing in non-human animals was provided by Welker in his 1964 article, Analysis of sniffing in the albino rat. [ 1 ]  In this study, Welker used video recordings of rats during presentation with odors and other stimuli to explore the chest movements as an index of sniffing. This was the first paper to report that rats can sniff at frequencies reaching 12\u00a0Hz upon detection of odors and during free exploration. This paper also provided early evidence that the rhythm of sniffing was coupled with other sensory behaviors, such as whisking, or the movement of the whiskers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3137", "contents": "While behavioral and psycho-physical studies into sniffing and its influence on odor perception began to surface, much less work was being performed to explore the influence of sniffing behaviors on the physiological processing of odors within the brain. Early recordings from the  olfactory bulbs  of hedgehogs by Lord  Edgar Adrian , who previously won the 1932 Nobel Prize along with  Sir Charles Sherrington  for their work on the functions of neurons, revealed that  neural oscillations  within the hedgehog olfactory bulb were entrained to the respiratory cycle. [ 24 ]   Further, odor-evoked oscillations (including an exhaled puff from a pipe), were amplified along with the respiratory cycle. These data gave evidence that information processing within the brain, particularly that of odors, was linked with respiration - establishing the integral nature of sniffing for the physiological processing of odors. About 20 years later,  Max Mozell  published a series of studies wherein he further proposed that the flow rate and the  sorption  properties of odorants interplay to affect the location of odorant binding to  olfactory receptor neurons  in the nose and consequentially odor input to the brain. [ 25 ]   Later, evidence that single neurons in the olfactory bulb, the brain's first relay station for odor information, are entrained with respiration was presented, establishing a solid basis for the control of odor input to the brain and the processing of odors by sniffing. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3138", "contents": "There are multiple methods available for measuring sniffing. While these methods are applicable for most animal models (mice to humans), selection of appropriate sniff measurement methods should be determined by experimental need for precision."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3139", "contents": "Perhaps the simplest method for determining the moment of sniffing is video-based. High resolution video of small animals (e.g., rats) during immobile respiration enables approximations of sniffing, including identification of individual sniff events. [ 1 ]  Similar methods can be employed to identify fast, high frequency sniffing during states of  arousal  and stimulus investigation. [ 1 ]  This method, however, does not provide direct evidence for sniffing and is not reliable in larger animals (rabbits to humans)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3140", "contents": "Sensors to measure chest expansion during inhalation provide direct information of sniff cycles. [ 27 ]   These methods include mechanical and optical devices. Mechanical devices for sniffing measurements are  piezo  foils placed under the chests of small animals and  strain gauge  around the chests of larger animals. In both cases, a positive increase in signal output (voltage) can be identified and used to index inhalation events. Alternatively, a photo  transducer  can be placed on the opposite side of an animal's chest from a light source (e.g., a  Light-emitting diode ). In this design, a decrease in signal reflects inhalation (chest expansion) as the chest would interrupt the light passage to the photo transducer."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3141", "contents": "As a direct measurement of sniffing, early studies favored the use of microphones placed/secured external to the  anterior nares , the external openings of the  nasal cavity . This method has advantages to directly index air leaving the nares (increase in microphone output), yet is mostly non-invasive. Due to this non-invasive nature of microphone measures, these methods have been employed in dogs during odor tracking exercises [ 28 ]    and are useful for measuring sniffing on a temporary basis in other large animals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3142", "contents": "The most precise methods to date to measure sniffing involve direct intranasal measures through use of a temperature probe, called a  thermocouple , or a pressure sensor. These can be inserted temporarily into the nares or implanted surgically. [ 4 ] [ 6 ]  The basic principles of operation are shared between the temperature and pressure devices. Inhalation of ambient air provides cool temperature into the nasal cavity, whereas exhalation of inhaled air provides warm temperature into the nasal cavity and simultaneously an increase in intranasal pressure as air from the lungs is forced out of the nostrils. Placement of these sensors close to the  olfactory epithelium  of animals allows measures of odorized air transients as they reach the  olfactory receptors [ 4 ] [ 29 ]   and thus are common methods for measuring sniffing in the context of  sensory neuroscience  and psychological studies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3143", "contents": "The earliest published study of sniffing behavior in small animals was performed in  laboratory rats  using video-based measures. [ 1 ]  In this study robust changes in respiratory frequency were reported to occur during exploration of an open arena and novel odors. Resting respiration occurs ~2 times/second (Hz), and increases to about 12\u00a0Hz are noted during states of exploration and arousal. Similar transitions in sniffing frequency are observed in freely exploring mice, [ 3 ]  which, however, maintain generally higher sniffing frequencies than rats (3 [rest] to 15\u00a0Hz [exploration] vs 2 to 12\u00a0Hz)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3144", "contents": "Transitions in sniffing frequency are observed in animals performing odor-guided tasks. Studies of recording sniffing in the context of odor-guided tasks involve implanting intranasal temperature and pressure sensors into the nasal cavity of animals and either measuring odor-orienting responses (fast sniffing) [ 29 ]   or sniffing during performance in operant odor-guided tasks. [ 3 ] [ 4 ] [ 30 ] [ 31 ]  Alternatively, animals can be conditioned to insert their  snouts  into an air-tight chamber with a pressure transducer embedded within to access nasal transients, while simultaneously odors are presented to measure responses while nose-poking. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3145", "contents": "Notably, several studies have reported that modulation in sniffing frequency may be just as great in context of anticipation of odor sampling as during sampling of odors. [ 18 ] [ 31 ]  Similar changes in sniffing frequency are even seen in animals presented with novel auditory stimuli, [ 32 ]  suggesting a relationship between sniffing and arousal."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3146", "contents": "While sniffing is generally thought to occur solely in terrestrial animals, semi-aquatic rodents ( American water shrew ) also display sniffing behaviors during underwater odor-guided tasks. [ 20 ]  Shrews inhale-exhale small amounts of air in a precise and coordinated fashion while tracking an underwater odor trail. This occurs through the inhalation of air above ground, to allow air to volatilize odors in an environment otherwise void of air."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3147", "contents": "Measurements of sniffing simultaneously with physiological measures from olfactory centers in the brain have provided information on how sniffing modulates the access and processing of odors at the neural level. Inhalation is necessary for odor input to the brain. [ 29 ]  Further, odor input through the brain is temporally linked to the respiratory cycle, with bouts of activity occurring with each inhalation. [ 26 ]  This linkage between sniffing frequency and odor processing provides a mechanism for the control of odor input into the brain by respiratory frequency [ 4 ]   and possibly amplitude, though this is not well established."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3148", "contents": "The nature of sniffing regulates odor  perception  in humans [ 7 ] [ 23 ]   and in fact, in humans, a single sniff is often sufficient for optimal odor perception. [ 33 ]   For instance, a deep, steady inhalation of a faint odor allows a more potent percept than a shallow inhalation. Similarly, more frequent sniffs provide a faster percept of the odor environment than only sniffing once every 3 seconds. These examples have been supported by empirical studies (see above) and have provided insights into methods whereby humans may change their sniffing strategies to modulate odor perception. [ 7 ] [ 23 ] [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3149", "contents": "Odor inhalation evokes activity throughout olfactory structures in humans. [ 9 ]   Neuroimaging  studies lack resolution to determine the impacts of sniffing frequency on the structure of odor input through the brain, although imaging studies have revealed that the motor act of sniffing is anatomically independent of sniff-evoked odor perception. [ 9 ]  Implications for this include the shared but distributed pathways for odor processing in the brain."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3150", "contents": "Sniffing is fundamentally controlled by  respiratory centers  in the  brainstem , including the  Pre-Botzinger complex  which governs inhalation/exhalation patterns. [ 34 ]   Activity from respiratory brain stem structures then modulates nervous activity to control lung contraction. To exert changes to respiration, and thereby evoke sniffing behavior, volitional centers in the  cerebral cortex  must stimulate brain stem structures. It is through this simple pathway that the decision to inhale or sniff may occur."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3151", "contents": "The rapid modulation of sniffing upon inhalation of a novel odor or an irritating odor is evidence for an \"olfactomotor\" loop in the brain. [ 10 ] [ 35 ]   In this loop, novel odor-evoked sniffing behavior can occur rapidly upon perception of a novel odor, one of interest, or an odor which is aversive."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3152", "contents": "Sniffing, as an active sampling behavior, is often grouped along with other behaviors utilized to acquire sensory stimuli. For instance, sniffing has been compared to rapid eye movements, or  saccades , in the ability for both methods to provide rapid \"snapshots\" of information to the brain. [ 12 ]  This analogy, though, may be imprecise since small animals (e.g., mice) make odor-based decisions (through sniffing) while also making visual decisions, yet do not saccade. Sniffing is also fundamentally similar to active touch, including swiping ones finger along a surface to scan texture."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3153", "contents": "In part due to the interrelatedness of the respiratory brain stem structures with other  central pattern generators  responsible for governing some other active sampling behaviors, sniffing in animals often occurs at similar frequencies (2 to 12\u00a0Hz) and in a phasic relationship to the active sampling behaviors of whisking and licking. [ 1 ]  Whisking and sniffing are tightly correlated in their occurrence, [ 1 ]  with sniff inhalations occurring during whisker protraction. Due to the metabolic need to coordinate breathing and swallowing, small animals (rats and mice) often lick at similar frequencies of sniffing (4 to 8\u00a0Hz) and swallow in between inhalations or during brief periods of  apnea  (cessation of breathing). [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3154", "contents": "Few studies have explored the impact of  neurological disorders  on sniffing behavior, although numerous neurological disorders affect respiration. Humans with  Parkinson's disease  have abnormal sniffing capabilities (i.e., reduced volume and flow rate) which may underlie olfactory perceptual impairments in the disease. [ 14 ]  Studies into sniffing in mouse models of  Alzheimer's disease [ 15 ]  and also humans [ 37 ]   have not found major effects of Alzheimer's pathology on both basal respiration and odor-evoked sniffing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3155", "contents": "Spirometry  (meaning  the measuring of breath ) is the most common of the  pulmonary function tests  (PFTs). It measures  lung  function, specifically the amount (volume) and/or speed (flow) of air that can be inhaled and exhaled. Spirometry is helpful in assessing breathing patterns that identify conditions such as  asthma ,  pulmonary fibrosis ,  cystic fibrosis , and  COPD . It is also helpful as part of a system of  health surveillance , in which breathing patterns are measured over time. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3156", "contents": "Spirometry generates pneumotachographs, which are charts that plot the volume and flow of air coming in and out of the lungs from one inhalation and one exhalation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3157", "contents": "The spirometry test is performed using a device called a  spirometer , [ 2 ]  which comes in several different varieties. Most spirometers display the following graphs, called spirograms:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3158", "contents": "The basic forced volume vital capacity (FVC) test varies slightly depending on the equipment used. It can be in the form of either closed or open circuit. Regardless of differences in testing procedure providers are recommended to follow the  ATS/ERS Standardisation of Spirometry . The standard procedure ensures an accurate and objectively collected set of data, based on a common reference, to reduce incompatibility of the results when shared across differing medical groups."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3159", "contents": "The patient is asked to put on soft nose clips to prevent air escape and a breathing sensor in their mouth forming an air tight seal. Guided by a technician, the patient is given step by step instructions to take an abrupt maximum effort inhale, followed by a maximum effort exhale lasting for a target of at least 6 seconds. When assessing possible  upper airway obstruction , the technician will direct the patient to make an additional rapid inhalation to complete the round. The timing of the second inhale can vary between persons depending on the length of the proceeding exhale. In some cases each round of test will be proceeded by a period of normal, gentle breathing for additional data."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3160", "contents": "Clinically useful results are highly dependent on patient cooperation and effort and must be repeated for a minimum of three times to ensure  reproducibility  with a general limit of ten attempts. Given variable rates of effort, the results can only be underestimated given an effort output greater than 100% is not possible. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3161", "contents": "Due to the need for patient cooperation and an ability to understand and follow instructions, spirometry can typically only be done in cooperative children when they at least 5 years old [ 3 ] [ 4 ]  or adults without physical or mental impairment preventing effective diagnostic results. In addition,  General anesthesia  and various forms of sedation are not compatible with the testing process."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3162", "contents": "Another limitation is that persons with intermittent or mild asthma can present normal spirometry values between acute exacerbation, reducing spirometry's effectiveness as a diagnostic tool in these circumstances. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3163", "contents": "Spirometry can also be part of a  bronchial challenge test , used to determine  bronchial  hyperresponsiveness to either rigorous exercise, inhalation of cold/dry air, or with a pharmaceutical agent such as  methacholine  or  histamine ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3164", "contents": "To assess the reversibility of a particular condition, a  bronchodilator  can be administered before performing another round of tests for comparison. This is commonly referred to as a  reversibility test , or a  post bronchodilator test  (Post BD), and is an important part in diagnosing asthma versus COPD."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3165", "contents": "Other complementary lung functions tests include  plethysmography  and  nitrogen washout ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3166", "contents": "Spirometry is indicated for the following reasons:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3167", "contents": "Forced expiratory maneuvers may aggravate some medical conditions. [ 9 ]  Spirometry should not be performed when the individual presents with:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3168", "contents": "The most common parameters measured in spirometry are vital capacity (VC), forced vital capacity (FVC), forced expiratory volume (FEV) at timed intervals of 0.5, 1.0 (FEV1), 2.0, and 3.0 seconds, forced expiratory flow 25\u201375% (FEF 25\u201375) and maximal voluntary ventilation (MVV), [ 10 ]  also known as Maximum breathing capacity. [ 11 ]  Other tests may be performed in certain situations."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3169", "contents": "Results are usually given in both raw data (litres, litres per second) and percent predicted\u2014the test result as a percent of the \"predicted values\" for the patients of similar characteristics (height, age, sex, and sometimes race and weight). The interpretation of the results can vary depending on the physician and the source of the predicted values. Generally speaking, results nearest to 100% predicted are the most normal, and results over 80% are often considered normal. Multiple publications of predicted values have been published and may be calculated based on age, sex, weight and ethnicity.  However, review by a doctor is necessary for accurate diagnosis of any individual situation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3170", "contents": "A bronchodilator is also given in certain circumstances and a pre/post graph comparison is done to assess the effectiveness of the bronchodilator. See the example printout."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3171", "contents": "Functional residual capacity  (FRC) cannot be measured via spirometry, but it can be measured with a  plethysmograph  or dilution tests (for example, helium dilution test)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3172", "contents": "Forced  vital capacity  (FVC) is the volume of air that can forcibly be blown out after full inspiration, [ 13 ]  measured in liters. FVC is the most basic maneuver in spirometry tests."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3173", "contents": "FEV1 is the volume of air that can forcibly be blown out in first 1-second, after full inspiration. [ 13 ]  Average values for FEV1 in healthy people depend mainly on sex and age, according to the diagram.\nValues of between 80% and 120% of the average value are considered normal. [ 14 ]  Predicted normal values for FEV1 can be calculated and depend on age, sex, height, mass and ethnicity as well as the research study that they are based on."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3174", "contents": "FEV1/FVC  is the ratio of FEV1 to FVC. In healthy adults this should be approximately 70\u201380% (declining with age). [ 15 ]  In obstructive diseases (asthma, COPD, chronic bronchitis, emphysema) FEV1 is diminished because of increased airway resistance to expiratory flow; the FVC may be decreased as well, due to the premature closure of airway in expiration, just not in the same proportion as FEV1 (for instance, both FEV1 and FVC are reduced, but the former is more affected because of the increased airway resistance). This generates a reduced value (<70%, often ~45%). In restrictive diseases (such as  pulmonary fibrosis ) the FEV1 and FVC are both reduced proportionally and the value may be normal or even increased as a result of decreased lung compliance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3175", "contents": "A derived value of FEV1 is  FEV1% predicted  (FEV1%), which is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of the same age, height, gender, and race. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3176", "contents": "Forced expiratory flow   (FEF) is the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration.\nIt can be given at  discrete times , generally defined by what fraction of the forced vital capacity (FVC) has been exhaled.\nThe usual discrete intervals are 25%, 50% and 75% (FEF25, FEF50 and FEF75), or 25% and 50% of FVC that has been exhaled.\nIt can also be given as a mean of the flow during an interval, also generally delimited by when specific fractions remain of FVC, usually 25\u201375% (FEF25\u201375%). Average ranges in the healthy population depend mainly on sex and age, with FEF25\u201375% shown in diagram at left. Values ranging from 50 to 60% and up to 130% of the average are considered normal. [ 14 ]  Predicted normal values for FEF can be calculated and depend on age, sex, height, mass and ethnicity as well as the research study that they are based on."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3177", "contents": "MMEF  or  MEF  stands for maximal (mid-)expiratory flow and is the peak of expiratory flow as taken from the flow-volume curve and measured in liters per second. It should theoretically be identical to  peak expiratory flow  (PEF), which is, however, generally measured by a peak flow meter and given in liters per minute. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3178", "contents": "Recent research suggests that FEF25-75% or FEF25-50% may be a more sensitive parameter than FEV1 in the detection of obstructive small airway disease. [ 17 ] [ 18 ]   However, in the absence of concomitant changes in the standard markers, discrepancies in mid-range expiratory flow may not be specific enough to be useful, and current practice guidelines recommend continuing to use FEV1, VC, and FEV1/VC as indicators of obstructive disease. [ 19 ] [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3179", "contents": "More rarely, forced expiratory flow may be given at intervals defined by how much remains of total lung capacity. In such cases, it is usually designated as e.g. FEF70%TLC, FEF60%TLC and FEF50%TLC. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3180", "contents": "Forced inspiratory flow 25\u201375% or 25\u201350% (FIF 25\u201375% or 25\u201350%) is similar to FEF 25\u201375% or 25\u201350% except the measurement is taken during inspiration. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3181", "contents": "Peak expiratory flow  (PEF) is the maximal flow (or speed) achieved during the maximally forced expiration initiated at full inspiration, measured in liters per minute or in liters per second."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3182", "contents": "Tidal volume  is the amount of air inhaled or exhaled normally at rest. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3183", "contents": "Total lung capacity  (TLC) is the maximum volume of air present in the lungs. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3184", "contents": "Diffusing capacity  (or  DLCO ) is the carbon monoxide uptake from a single inspiration in a standard time (usually 10 seconds). During the test the person inhales a test gas mixture that consisting of regular air that includes an inert  tracer gas  and CO, less than one percent. Since hemoglobin has a greater affinity to CO than oxygen the breath-hold time can be only 10 seconds, which is a sufficient amount of time for this transfer of CO to occur. Since the inhaled amount of CO is known, the exhaled CO is subtracted to determine the amount transferred during the breath-hold time. The tracer gas is analyzed simultaneously with CO to determine the distribution of the test gas mixture. This test will pick up diffusion impairments, for instance in pulmonary fibrosis. [ 22 ]  This must be corrected for anemia (a low hemoglobin concentration will reduce DLCO) and pulmonary hemorrhage (excess RBC's in the interstitium or alveoli can absorb CO and artificially increase the DLCO capacity). Atmospheric pressure and/or altitude will also affect measured DLCO, and so a correction factor is needed to adjust for standard pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3185", "contents": "Maximum voluntary ventilation (MVV) is a measure of the maximum amount of air that can be inhaled and exhaled within one minute. For the comfort of the patient this is done over a 15-second time period before being extrapolated to a value for one minute expressed as liters/minute. Average values for males and females are 140\u2013180 and 80\u2013120 liters per minute respectively. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3186", "contents": "When estimating static lung compliance, volume measurements by the spirometer needs to be complemented by  pressure transducers  in order to simultaneously measure the  transpulmonary pressure . When having drawn a curve with the relations between changes in volume to changes in transpulmonary pressure, C st  is the slope of the curve during any given volume, or, mathematically, \u0394V/\u0394P. [ 23 ]  Static lung compliance is perhaps the most sensitive parameter for the detection of abnormal pulmonary mechanics. [ 24 ]  It is considered normal if it is 60% to 140% of the average value in the population for any person of similar age, sex and body composition. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3187", "contents": "In those with acute respiratory failure on mechanical ventilation, \"the static compliance of the total respiratory system is conventionally obtained by dividing the tidal volume by the difference between the 'plateau' pressure measured at the airway opening (PaO) during an occlusion at end-inspiration and positive end-expiratory pressure (PEEP) set by the ventilator\". [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3188", "contents": "Forced Expiratory Time (FET) \nForced Expiratory Time (FET) measures the length of the expiration in seconds."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3189", "contents": "Slow vital capacity (SVC) \nSlow  vital capacity  (SVC) is the maximum volume of air that can be exhaled slowly after slow maximum inhalation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3190", "contents": "Maximal pressure (P max  and  P i )"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3191", "contents": "P max  is the asymptotically maximal pressure that can be developed by the respiratory muscles at any lung volume and P i  is the maximum inspiratory pressure that can be developed at specific lung volumes. [ 26 ]  This measurement also requires pressure transducers in addition. It is considered normal if it is 60% to 140% of the average value in the population for any person of similar age, sex and body composition. [ 14 ]  A derived parameter is the  coefficient of retraction (CR)  which is P max /TLC . [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3192", "contents": "Mean transit time (MTT) \nMean transit time is the area under the flow-volume curve divided by the forced vital capacity. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3193", "contents": "Maximal inspiratory pressure (MIP) \nMIP, also known as  negative inspiratory force (NIF) , is the maximum pressure that can be generated against an occluded airway beginning at functional residual capacity (FRC). It is a marker of respiratory muscle function and strength. [ 28 ]  Represented by centimeters of water pressure (cmH2O) and measured with a  manometer . Maximum inspiratory pressure is an important and noninvasive index of  diaphragm  strength and an independent tool for diagnosing many illnesses. [ 29 ]  Typical maximum inspiratory pressures in adult males can be estimated from the equation, M IP  = 142 - (1.03 x Age) cmH 2 O, where age is in years. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3194", "contents": "1DFW ,  1KMR ,  1RG3 ,  1RG4 ,  1SSZ ,  2DWF ,  2JOU ,  2M0H ,  2M1T"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3195", "contents": "6439"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3196", "contents": "20388"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3197", "contents": "ENSG00000168878"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3198", "contents": "ENSMUSG00000056370"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3199", "contents": "P07988"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3200", "contents": "P50405"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3201", "contents": "NM_000542 NM_198843 NM_001367281"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3202", "contents": "NM_001282071 NM_147779"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3203", "contents": "NP_000533 NP_942140 NP_001354210"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3204", "contents": "NP_001269000 NP_680088"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3205", "contents": "Surfactant protein B  is an essential lipid-associated protein found in  pulmonary surfactant .  Without it, the  lung  would not be able to inflate after a deep breath out. [ 5 ]  It rearranges  lipid  molecules in the fluid lining the lung so that tiny air sacs in the lung, called  alveoli , can more easily inflate. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3206", "contents": "SP-B is encoded by  SFTPB , a single, 11425  nucleotide  long  gene  on  chromosome 2 . [ 7 ]   Mutations  in this gene are the basis for several of the lung conditions mentioned above.  Both  frameshift mutations  and several  single nucleotide polymorphisms  (SNPs) have been found correlated to a variety of lung conditions. A frame shift mutation responsible for congenital alveolar proteinosis (CAP) was identified by Kattan et al. [ 8 ]  Many SNP's have been identified in relation to lung conditions. They have been correlated to severe influenza, neonatal respiratory distress syndrome, mechanical ventilation necessity, and more. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3207", "contents": "Surfactant protein B (SP-B) is a small protein, weighing about 8  kDa . [ 10 ]   Proteins  are composed of building blocks called  amino acids , and SP-B is composed of 79 of them ( Valine ,  alanine ,  phenylalanine ,  leucine ,  isoleucine , and  tryptophan  being found in the highest levels). Nine of these carry with them a positive charge, and two carry a negative charge, leaving a protein with a net (total) charge of +7. [ 5 ]  In the body, two molecules of SP-B stick together and form what is called a  homodimer . [ 11 ]  These are found embedded into membranes and other lipid structures, SP-B is a highly  hydrophobic , avoiding contact with water."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3208", "contents": "SP-B is the mature form of a large precursor protein called proSP-B.  Synthesized in the  endoplasmic reticulum  of  type II pneumocytes , proSP-B weighs approximately 40 kDa and is cut down to the size of mature SP-B in the  golgi apparatus  through a process called  post-translational modification . [ 5 ]  ProSP-B is also created in another type of lung cell called a Club cell, but these cells are unable to edit proSP-B into SP-B. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3209", "contents": "SP-B is a  saposin-like  protein, which is a group of related proteins known particularly for binding to membranes with negative charges and facilitating either the fusion or  lysis  (breaking) of the membrane.  More well known proteins in this family include saposin-C, NK-lysin, and amoebopore. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3210", "contents": "SP-B plays a critical role in the functioning of healthy lungs, and its absence inevitably leads to lung conditions, most common of which being acute respiratory distress syndrome (ARDS).  Because of this, SP-B's function has been well researched, and has been found to exist in three parts. Beyond these three functions, it is worth noting that SP-B is also thought to have some anti-inflammatory function, though it is not well defined. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3211", "contents": "The  surface tension  at the border between the fluid lining and the inhaled gas (gas/fluid interface) in alveoli determines the motion of the alveoli as a whole.  According to Lapace's Law, high surface tension in the gas/fluid interface of alveoli prevents the alveoli from inflating, which causes lung collapse. [ 13 ]  lipid arrangement in the fluid lining of alveoli is the primary determining factor of this surface tension since the lipids form a thin film ( monolayer ) on the surface of the fluid lining at the gas/fluid interface. Different lipids allow for different ranges of motion and can be compacted different. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3212", "contents": "SP-B plays a role in this by selected certain lipids and inserting them into the gas/fluid interface.  The lipid shown to be most needed on this surface ( Dipalmitoylphosphatidylcholine ) does not easily move to the gas/fluid interface, but SP-B helps ease and speed up this process. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3213", "contents": "SP-B also indirectly reduces surface tension by organizing the lipids underneath the surface of the gas/fluid interface in structures called  tubular myelin . [ 5 ]  Effectively, SP-B cuts and pastes pieces of the  lipid bilayers  to form the three dimensional structure of the tubular myelin. This structure is the support and lipid source for the gas/fluid interface, where surface tension is a critical factor in lung function."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3214", "contents": "Beyond arranging lipids in a way that reduces surface tension, SP-B actually directly interferes with attractive forces between water molecules. [ 12 ]  This disruption in the cohesion of water minimizes further the surface tension at the gas/fluid interface."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3215", "contents": "Lamellar bodies  are groups of lipids and protein that are structurally similar to tubular myelin, but are found inside instead of outside the  type II pneumocytes .  Similarly to its function in organizing tubular myelin, SP-B arranges lipids into the lamellar body structure. [ 6 ]  Basically, SP-B plays a role in the  organogenesis  (formation of structure) of lamellar bodies.  The lamellar bodies are then secreted into the fluid lining the interior of alveoli, and become tubular myelin.  This role is critical for making  pulmonary surfactant  (see below)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3216", "contents": "Acute respiratory distress syndrome , respiratory syncytial virus infection, familial lung disease, and pneumocystis infection are examples of deficiencies in and issues with SP-B that are correlated with lung issues. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3217", "contents": "Because so many lung conditions are associated with issues around SP-B, synthetic replacements have been researched, created, and manufactured.  It has been shown that 21 amino acid long  peptides  with positive charge and intermittent hydrophobic regions mimicking SP-B can minimize surface tension at the gas/fluid interface, and surfactant replacements for surfactant deficient patients has been used to save lives. [ 16 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3218", "contents": "Once lung distress has occurred, SP-B has been shown to be effective as a  biomarker  in the blood stream. [ 10 ]   Higher levels of SP-B indicate some kind of lung distress, and can even indicate if the patient is currently a smoker. [ 18 ]  This may be useful in the future to predict  atherosclerosis , a solidifying of vascular tissue that has negative effects on the heart."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3219", "contents": "SP-B is a critical protein for lung function, and is found in the context of  pulmonary surfactant .  Understanding surfactant is important to gaining a full understanding of SP-B.  Surfactant is a mixture of lipids and proteins that coats the inside of alveoli and is essential for life due to its key role in preventing alveolar collapse at low lung volumes. [ 19 ] [ 7 ]   In the absence of surfactant, the surface tension at the gas/fluid interface prevents inhalation at  standard pressure , but surfactant minimizes surface tension to values near zero and allows for normal breathing. [ 20 ]  It is also known to have a role in both the immune response and inflammation control."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3220", "contents": "Surfactant deficiency is a common cause of respiratory disease.   Respiratory distress syndrome  (RDS) is a particularly well-known instance of surfactant deficiency because it has a high  mortality rate  among  preterm  babies, a variety of other conditions are related to surfactant levels and composition. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3221", "contents": "Surfactant is composed of primarily lipids (90% by weight), and proteins make up only the remaining 10%. The following two sections will address the lipid and protein components respectively."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3222", "contents": "Lipids  are a broad category of mid-sized molecules that are  hydrophobic  or  amphipathic .  In surfactant, two subcategories of lipids are relevant: phospholipids and sterols.  Sterols are represented by cholesterol, which has an important role in the overall structure and motion of the lipids as a whole, but is vastly outnumbered by the phospholipids in surfactant."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3223", "contents": "DPPC ( dipalmitoylphosphatidylcholine ), as mentioned above, is a lipid with very useful stabilizing and compacting attributes.  SP-B works primarily with this lipid, and moves it to the gas/fluid interface where it minimized surface tension. [ 6 ]  Essentially, DPPC is so important for lung function because it can shrink or expand to fit the space necessary, and a continually shrinking and expanding lung requires components like this."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3224", "contents": "Other lipids found commonly in surfactant include  phosphatidylglycerol  (PG),  phosphatidylinositol  (PI),  phosphatidylethanolamine  (PE), and  phosphatidylserine  (PS)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3225", "contents": "SP-B is one of four proteins commonly found in surfactant, the other three being  surfactant protein A  (SP-A),  surfactant protein C  (SP-C), and  surfactant protein D  (SP-D). [ 7 ]  These four are highly interconnected in their functions in surfactant. For example, though the mechanism is not yet understood, SP-B functions in the  post-translational modification  of SP-C, and mature SP-C is not formed without SP-B. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3226", "contents": "SP-C assists in the functions of SP-B, and is most similar to SP-B of the three other surfactant proteins. It is smaller, only 35 amino acids long, and is found embedded in lipid structures much like SP-B. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3227", "contents": "SP-A and SP-D, known together as  collectins , are more distinct from SP-B than SP-C. They are hydrophilic, so they are found in the solution, and function in immune response instead of lipid arrangement and surface tension reduction. [ 20 ] [ 19 ]   SP-A is actually a name for two very similar proteins, SP-A1 and SP-A2."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3228", "contents": "Along with SP-A, B, C, and D, blood plasma proteins are found in very small quantities in surfactant as well. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3229", "contents": "Tidal volume  (symbol  V T  or  TV ) is the volume of air inspired and expired with each passive breath. [ 1 ]  It is typically assumed that the volume of air inhaled is equal to the volume of air exhaled such as in the figure on the right. In a healthy, young human adult, tidal volume is approximately 500\u00a0ml per inspiration at rest or 7\u00a0ml/kg of body mass. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3230", "contents": "Tidal volume plays a significant role during  mechanical ventilation  to ensure adequate ventilation without causing trauma to the lungs. Tidal volume is measured in milliliters and ventilation volumes are estimated based on a patient's ideal body mass. Measurement of tidal volume can be affected (usually overestimated) by leaks in the  breathing circuit  or the introduction of additional gas, for example during the introduction of  nebulized  drugs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3231", "contents": "Ventilator-induced lung injury such as  Acute lung injury  (ALI) / Acute Respiratory Distress Syndrome  (ARDS) can be caused by ventilation with very large tidal volumes in normal lungs, as well as ventilation with moderate or small volumes in previously injured lungs, and research shows that the incidence of ALI increases with higher tidal volume settings in nonneurologically impaired patients. \n. [ 3 ]   Similarly A 2018 systematic review by  The Cochrane Collaboration  provided evidence that low tidal volume ventilation reduced post operative pneumonia and reduced the requirement for both invasive and non invasive ventilation after surgery [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3232", "contents": "Initial settings of mechanical ventilation:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3233", "contents": "Protective lung ventilation strategies should be applied with V T  6ml/kg to 8ml/kg with RR = 12 to 20 and an average starting target minute ventilation of 7 L/min. [ citation needed ] [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3234", "contents": "Protective lung volumes apply 6ml/kg to 8ml/kg with a rate high enough for proper alveolar ventilation but does not create or aggravate intrinsic Positive End-Expiry Pressure (PEEP). [ citation needed ] [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3235", "contents": "Protective lung ventilation strategies apply. V T  6 to 8\u00a0ml/kg or as low as 5\u00a0ml/kg in severe cases. Permissive hypercapnia can be employed in an attempt to minimize aggressive ventilation leading to lung injury. Higher PEEPs are often required however not all ARDS patients require the same PEEP levels. [ clarification needed ]  Patient should be started on 6\u00a0ml/kg and PEEP increased until plateau pressure is 30\u00a0cm\u00a0H 2 0 in most severe cases. [ citation needed ] [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3236", "contents": "Transpulmonary pressure  is the difference between the  alveolar pressure  and the  intrapleural pressure  in the  pleural cavity . During human ventilation, air flows because of  pressure gradients ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3237", "contents": "P tp  = P alv  \u2013 P ip"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3238", "contents": "Where P tp  is transpulmonary pressure, P alv  is alveolar pressure, and P ip  is intrapleural pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3239", "contents": "Since atmospheric pressure is relatively constant, pressure in the lungs must be higher or lower than atmospheric pressure for air to flow between the atmosphere and the  alveoli . \nIf 'transpulmonary pressure' = 0 (alveolar pressure = intrapleural pressure), such as when the lungs are removed from the chest cavity or air enters the intrapleural space (a  pneumothorax ), the lungs collapse as a result of their inherent  elastic recoil . Under physiological conditions the transpulmonary pressure is always positive; intrapleural pressure is always negative and relatively large, while alveolar pressure moves from slightly negative to slightly positive as a person breathes. For a given lung volume, the transpulmonary pressure is equal and opposite to the elastic recoil pressure of the lung."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3240", "contents": "The transpulmonary pressure vs volume curve of inhalation (usually plotted as volume as a function of pressure) is different from that of exhalation, the difference being described as  hysteresis . Lung volume at any given pressure during inhalation is less than the lung volume at any given pressure during exhalation. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3241", "contents": "Transpulmonary pressure can be measured by placing  pressure transducers . The alveolar pressure is estimated by measuring the pressure in the airways while  holding one's breath . [ 2 ]  The intrapleural pressure is estimated by measuring the pressure inside a balloon placed in the  esophagus . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3242", "contents": "Measurement of transpulmonary pressure assists in  spirometry  in availing for calculation of  static lung compliance ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3243", "contents": "Tuft cells  are  chemosensory cells  in the  epithelial lining of the intestines . Similar tufted cells are found in the  respiratory epithelium  where they are known as  brush cells . [ 1 ]  The name \"tuft\" refers to the brush-like  microvilli  projecting from the cells. Ordinarily there are very few tuft cells present but they have been shown to greatly increase at times of a  parasitic infection . [ 2 ]  Several studies have proposed a role for tuft cells in defense against parasitic infection. In the intestine, tuft cells are the sole source of secreted  interleukin 25  (IL-25). [ 3 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3244", "contents": "ATOH1  is required for tuft cell specification but not for maintenance of a mature differentiated state, and knockdown of  Notch  results in increased numbers of tuft cells. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3245", "contents": "The human gastrointestinal (GI) tract is full of tuft cells for its entire length. These cells were located between the crypts and villi. On the basal pole of all cells was expressed  DCLK1 . They did not have the same morphology as was describe in animal studies but they showed an apical brush border the same thickness. Colocalization of synaptophysin and DCLK1 were found in the  duodenum , this suggests that these cells play a neuroendocrine role in this region. A specific marker of intestinal tuft cells is microtubule kinase - Double cortin-like kinase 1 (DCLK1). Tuft cells that are positive in this kinase are important in gastrointestinal chemosensation, inflammation or can make repairs after injuries in the intestine. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3246", "contents": "One key to understanding the role of tuft cells is that they share many characteristics with chemosensory cells in taste buds. For instance, they express many taste receptors and taste signaling apparatus. This might suggest that tuft cells could function as chemoreceptive cells that can sense many chemical signals around them. However, with more new research suggests that tuft cells can also be activated by the taste receptor apparatus. These can also be triggered by different small molecules, such as  succinate  and  aeroallergens . Tuft cells have been known to secrete various molecules which are important for biological functions. Due to this, tuft cells act as danger sensors and trigger a secretion of biologically active mediators. Despite this, the signals and the mediators that they secrete are wholly dependent on context. For example, tuft cells that are in the  urethra  respond to bitter compounds, through activation of the taste receptor. This then results in a rise in intracellular Ca2+\u00a0 and the release of  acetylcholine . It is thought that this then triggers an activation of various other cells in the proximity which then leads to bladder detrusor reflex and a greater emptying of the  bladder . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3247", "contents": "It has been discovered that the tuft cells in the intestines of mice are activated by parasitic infections. This leads to a secretion of  IL25 . IL25, being the key activator of innate lymphoid cells type 2. This then initiates and amplifies type-2 cytokine response, characterized by secretion of cytokines from ILC2 cells. [ 7 ]  Tissue remodeling during type-2 immune response is based on cytokine interleukin (IL)-13. This interleukin is produced mainly by group 2  innate lymphoid cells  (ILC2s) and type 2  helper T cells  (Th2s) located in  lamina propria . Also during worm infection, the amount of tuft cells dramatically rises. Hyperplasia of tuft cells and goblet cells is a hallmark of type 2 infection and is regulated by a feed-forward signalling circuit. IL-25 produced by tuft cells induces IL-13 production by ILC2s in the lamina propria. IL-13 then interact with uncommitted epithelial progenitors to affect their lineage selection toward goblet and tuft cells. As a result, the IL-13 is responsible for dramatic remodeling enterocyte epithelium to epithelium which are dominated by tuft and goblet cells. Without IL-25 from tuft cells worm clearance is delayed. The type-2 immune response is based on tuft cells and the response is severely reduced without the presence of these cells, which confirm the important physiologic function for these cells during worm infection. [ 8 ]  Activation of Th2 cells is an important part of this feed-forward loop. The activation of tuft cells in the intestine is connected with metabolite succinate, which is produced by a parasite and binds to the specific tuft cells receptor Sucnr1 on their surface. Also, the role of intestinal tuft cells can be important for local regeneration in the intestine after an infection. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3248", "contents": "Tuft cells were identified for the first time in the  trachea  and  gastrointestinal tract  in rodent, due to their typical morphology, by  electron microscopy . The characteristic tubulovesicular system and apical bundle of  microfilaments  which are connected to tuft by long and thick microvilli, reaching into the lumen, gave them their name. [ 1 ]  This figure gave these cells their name and the whole of tufted morphology. The distribution and size of tuft cell microvilli are very different from  enterocytes  that neighbour them. Also tuft cells, in comparison with enterocytes, do not have a terminal web at the base of apical microvilli. [ 9 ]  Other characteristics of tuft cells are: quite narrow apical membrane which cause the tuft cells to be viewed as pinched at the top, prominent microfilaments from  actin  which extend to the cell and finish just above the nucleus, vast but largely empty apical vesicles which make a tubulovesicular network, on the apical side of the cells' nucleus is a  Golgi apparatus , deficiency of rough  endoplasmic reticulum  and  desmosomes  with tight junction which fixes tuft cells to their neighbours. [ 8 ]  The shape of the tuft cell body varies and depends on the organ. Tuft cells in the intestine are cylindric and narrow at the apical and basal ends. Alveolar tuft cells are flatter in comparison with intestinal and gall bladder tuft cells have a cuboidal shape. Differences in tuft cells can reflect their organ's specific functions. Tuft cells express chemosensory proteins, like  TRPM5  and \u03b1-gustducin. These proteins indicate that neighbouring neurons can innervate tuft cells. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3249", "contents": "Tuft cells can be identified by staining for cytokeratin 18, neurofilaments, actin filaments, acetylated tubulin, and DCLK1 to differentiate between tuft cells and enterocytes. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3250", "contents": "Tuft cells are found in the intestine, and stomach, and as pulmonary brush cells in the respiratory tract, from nose to alveoli. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3251", "contents": "A loss of tolerance to antigens that appear in the environment cause  inflammatory bowel disease  (IBD) and  Crohn's disease  (CD) in people who are more genetically susceptible. Helminth colonization inducts a type-2 immune response, causes mucosal healing and achieves clinical remission. During an intense infection, tuft cells can make their own specification and the hyperplasia of tuft cells is a key response to the expulsion of the worm. This shows that the modulation of tuft cell function may be effective in the treatment of Crohn's Disease. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3252", "contents": "Tuft cells have been shown to use taste receptors in the detection of many different helminth species. The clearance of helminth in mice that lacked taste receptor function (Trpm5 or/-gustducin\u00a0 KO) \u00a0 or enough tuft cells (Pou2f3 KO) was impaired compared to that of wild-type mice. This shows that tufts cells are important in playing a protective role during the helminth infections. It was observed that IL-25 derived from tuft cells was mediating the protective response, initiating type 2 immune responses. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3253", "contents": "Tuft cells were first discovered in the  trachea  of the  rat , and in the  mouse   stomach . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3254", "contents": "In the late 1920s, Dr. Chlopkov\u00a0was\u00a0tracking a project on developmental stages of goblet cells which are in the intestines. In the microscope he found a cell with a bundle of unusually long microvilli rising into the intestinal lumen. He thought he had found an early stage intestinal  goblet cell  but it was actually the first report of a new epithelial lineage which we now call the tuft cell. In 1956, two scientists, Rhodin and Dalhamn, described tuft cells in the rat trachea; later\u00a0the same year J\u00e4rvi\u00a0and Keyril\u00e4inen found\u00a0similar cells in the mouse stomach. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3255", "contents": "Tuft cells are generally located in the columnar epithelium organs derived from  endoderm . In rodents, they have been definitively been found: for example, in the trachea, the thymus, the glandular stomach, the gall bladder, the small intestine, the colon, the auditory tube, the pancreatic duct and the urethra. Tuft cells are most of the time isolated cells and take <1% of the epithelium. In the mouse gall bladder and rat bile and pancreatic duct, the tuft cells are more abundant but still isolated. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3256", "contents": "In  respiratory physiology , the  ventilation/perfusion ratio  ( V/Q ratio ) is a  ratio  used to assess the efficiency and adequacy of the  ventilation-perfusion coupling  and thus the matching of two variables:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3257", "contents": "The V/Q ratio can therefore be defined as the ratio of the amount of air reaching the alveoli per minute to the amount of blood reaching the alveoli per minute\u2014a ratio of  volumetric flow rates . These two variables, V and Q, constitute the main determinants of the blood oxygen (O 2 ) and carbon dioxide (CO 2 ) concentration."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3258", "contents": "The V/Q ratio can be measured with a two-part  ventilation/perfusion scan  (V/Q scan). [ 1 ]  Using a small amount of inhaled or injected radioactive material called a  tracer  for visualization, a V/Q scan is a type of  nuclear medical imaging  that allows for localization and characterization of blood flow ( perfusion scan ) and measurement of airflow (ventilation scan) within the lungs. [ 2 ]  V/Q scans are primarily used for the diagnosis of a blood clot in the lungs, called a  pulmonary embolism . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3259", "contents": "A  V/Q mismatch  can cause  Type 1 respiratory failure ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3260", "contents": "Ideally, the oxygen provided via ventilation would be just enough to saturate the blood fully. In the typical adult, 1 litre of blood can hold about 200 mL of oxygen; 1 litre of dry air has about 210 mL of oxygen. Therefore, under these conditions, the ideal ventilation perfusion ratio would be about 0.95. If one were to consider humidified air (with less oxygen), then  the ideal v/q ratio would be in the vicinity of 1.0 , thus leading to concept of  ventilation-perfusion equality  or  ventilation-perfusion matching . This matching may be assessed in the lung as a whole, or in individual or in sub-groups of gas-exchanging units in the lung. On the other side  Ventilation-perfusion mismatch  is the term used when the ventilation and the perfusion of a gas exchanging unit are not matched."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3261", "contents": "The actual values in the lung vary depending on the position within the lung. If taken as a whole, the typical value is approximately 0.8. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3262", "contents": "Because the lung is centered vertically around the  heart , part of the lung is superior to the heart, and part is inferior. This has a major impact on the V/Q ratio: [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3263", "contents": "In a subject standing in orthostatic position (upright) the apex of the lung shows higher V/Q ratio, while at the base of the lung the ratio is lower but nearer to the optimal value for reaching adequate blood oxygen concentrations. While both ventilation and perfusion increase going from the apex to the base, perfusion increases to a greater degree than ventilation, lowering the V/Q ratio at the base of the lungs. The principal factor involved in the creation of this V/Q gradient between the apex and the base of the lung is  gravity  (this is why V/Q ratios change in positions other than the orthostatic position)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3264", "contents": "Gravity and the weight of the lung act on ventilation by increasing pleural pressure at the base (making it less negative) and thus reducing the alveolar volume. The lowest part of the lung in relation to gravity is called the dependent region. In the dependent region smaller alveolar volumes mean the alveoli are more  compliant  (more distensible) and so capable of more oxygen exchange. The apex, though showing a higher oxygen partial pressure, ventilates less efficiently since its compliance is lower and so smaller volumes are exchanged."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3265", "contents": "The impact of gravity on pulmonary perfusion expresses itself as the  hydrostatic pressure  of the blood passing through the branches of the pulmonary artery in order to reach the apical and basal areas of the lungs, acting synergistically with the pressure developed by the right ventricle. Thus at the apex of the lung the resulting pressure can be insufficient for developing a flow (which can be sustained only by the negative pressure generated by venous flow towards the left atrium) or even for preventing the collapse of the vascular structures surrounding the alveoli, while the base of the lung shows an intense flow due to the higher pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3266", "contents": "Of note, few conditions constitute \"pure\" shunt or dead space as they would be incompatible with life, and thus the term  V/Q mismatch  is more appropriate for conditions in between these two extremes."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3267", "contents": "Ventilation\u2013perfusion coupling  is the relationship between  ventilation  and  perfusion  in the  respiratory  and  cardiovascular systems . [ 1 ]  Ventilation is the movement of air in and out of the  lungs  during breathing. [ 2 ]  Perfusion is the process of  pulmonary blood circulation , which  reoxygenates blood , allowing it to transport oxygen to  body tissues . Lung structure,  alveolar organization , and  alveolar capillaries  contribute to the physiological mechanism of ventilation and perfusion. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3268", "contents": "Ventilation\u2013perfusion coupling maintains a constant  ventilation/perfusion ratio  near 0.8 on average, with regional variation within the lungs due to gravity. When the ratio gets above or below 0.8, it is considered abnormal ventilation-perfusion coupling, also known as a  ventilation\u2013perfusion mismatch . [ 3 ]   Lung diseases ,  cardiac shunts , and  smoking  can cause a ventilation\u2013perfusion mismatch that results in significant symptoms and diseases; treatments include  bronchodilators  and  oxygen therapy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3269", "contents": "Ventilation-Perfusion coupling involves organs of the  respiratory system  and  cardiovascular system . The  respiratory system  and major airways participating in ventilation include the nostril, nasal cavity, mouth, pharynx, larynx, trachea, bronchus, and lungs. Within the lungs, the  ventilation  process specifically involves organs like respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli. For the perfusion process, the circulatory organs of the  cardiovascular system  such as the heart, pulmonary arteries, pulmonary veins, and alveolar capillaries are involved. The alveolar capillary specifically participates in  perfusion  to get in contact with the alveoli for the gas exchange and oxygen delivery to the body tissues. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3270", "contents": "The lung structure is important for the mechanism of ventilation-perfusion coupling.  Pleura  (plural: pleurae) is a single membrane surrounding the lung. It folds back to form two layers, and each layer is called  parietal pleura  and  visceral pleura .  The pleural cavity  refers to the area between the parietal and visceral pleura, and  pleural fluid  fills the pleural cavity to lubricate the pleural surface and provide surface tension. These functions ensure the safety of the lungs and proper inspiration. [ 4 ]  The  diaphragm  and  intercostal thoracic muscles  alter the lung's pressure gradient, which generates ventilation driving force. The bottom region near the  diaphragm  is known as the 'base' of the lung, and the top of the lung near the upper lobe is referred to as the 'apex' of the lung."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3271", "contents": "Ventilation  (or breathing) is the air movement between the lungs and the atmospheric air, facilitating  gas exchange  . The air rushes into the lungs through  inhalation  (inspiration) and is pushed out through  exhalation  (expiration). [ 2 ]  During ventilation, the air movement is generated by the air pressure gradient between the atmosphere and the lungs produced by thoracic muscles and  diaphragm   contraction . Air is pushed in and out of the lungs as air flows from the higher pressured region to the lower pressured region. During  inhalation , the  diaphragm   contraction  causes an increase in the  thoracic cavity  volume. This decreases the pressure inside the lungs, forcing the air to flow into the lungs. During  exhalation , the  diaphragm  relaxation causes a decrease in the  thoracic cavity  volume. The increased lung pressure pushes the air out of the lungs. [ 2 ]  The primary function of ventilation is the replacement of the stale gases in the lungs with oxygen-rich air through the removal of carbon dioxide for oxygenation of the blood. [ 5 ]  The oxygen is then supplied to the entire body through the  circulatory system ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3272", "contents": "Perfusion  is the delivery of oxygen-rich blood to the body tissues through the  lymphatic system  or  circulatory system . [ 6 ]  The primary function of perfusion is the efficient removal of  cellular waste  and nutrition supply during  gas exchange . Perfusion occurs during heart  contraction  when the oxygenated blood is pumped into the  arteries . The  arteries  deliver the blood to the  capillary bed  of the  tissues , where the oxygen is removed by  diffusion . [ 7 ]  Oxygen in the  alveoli  is diffused down the  concentration  gradient and transported into the blood through the pulmonary  capillaries . Once oxygen enters the bloodstream, it dissolves in  plasma  by binding to  hemoglobin  (Hb) of  red blood cells  and transported to body  tissues . [ 8 ]   Then the deoxygenated blood returns to the heart via  veins , and perfusion begins again after the blood is re-oxygenated through the ventilation process."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3273", "contents": "Ventilation\u2013perfusion coupling is the relationship between ventilation and perfusion, represented by the  ventilation-perfusion ratio (V/Q). Ventilation rate (V) is the total gas volume that enters and leaves the  alveoli  in a given amount of time, commonly measured per minute. To calculate the ventilation rate, the  tidal volume  (inhaled or exhaled gas volume during normal breath) is multiplied by the frequency of breaths per minute, which is represented by the formula:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3274", "contents": "Ventilation rate =  Tidal volume  (L) x breath per minute (breath/min) = L/min. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3275", "contents": "Perfusion rate (Q) is the total blood volume that enters the  alveolar   capillaries  per unit time (1 minute) during the  gas exchange . Therefore, the  ventilation-perfusion ratio  represents the volume of gas that enters the  alveoli  compared to the volume of blood that enters the  alveoli  per minute."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3276", "contents": "The ideal  V/Q ratio  is 1, the most efficient state of pulmonary function when the amount of oxygen entering the lungs equals the amount of oxygen delivered to the body. Furthermore, adequate achievement of ventilation and perfusion matching is essential as it ensures the continuous supply of oxygen and withdrawal of  waste products  from the body. Thus, strict regulation of ventilation and perfusion is needed for efficient  gas exchange ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3277", "contents": "On average, 4 liters of oxygen (V) and 5 liters of blood (Q) enter the  alveoli  in a minute, thus the normal  V/Q ratio  is 0.8. [ 10 ]  It is considered abnormal when the ratio is greater or smaller than 0.8 and is referred to as ventilation-perfusion mismatch(V/Q mismatch). Further information on V/Q mismatch can be found in the clinical significance section below."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3278", "contents": "While the ideal  V/Q ratio  is 1, the ratio in the normal lungs of the healthy individual is approximately 0.8, meaning that the ventilation and perfusion do not equal perfectly. Due to gravity, lower lungs have a relatively greater amount of blood, and upper lungs(apex) have a relatively greater amount of air. Thus, the blood in the lower lungs(base) is not fully oxygenated, and the oxygen of air in the upper is not fully extracted, decreasing the  V/Q ratio. [ 1 ]  Compared to the lungs' apex, the ventilation rate is 50% greater at the base. The  V/Q ratio  in the apex is roughly 3.3 and 0.63 in the base, which indicates that perfusion is greater than ventilation towards the base, and the ventilation rate is greater than perfusion towards the apex. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3279", "contents": "Towards the base of the lungs, the fluid volume in the  pleural cavity  increases due to gravity, resulting in greater  intrapleural pressure . As a result,  alveoli  expand less and become more compliant at the base, improving ventilation. Perfusion also increases as gravity pulls down the blood towards the base. Overall, both ventilation and perfusion rate are enhanced towards the lungs' base. However, the perfusion rate rises more, resulting in decreased  V/Q ratio.  Towards the apex of the lungs, the  hydrostatic pressure  is reduced due to gravity, which lowers the blood flow, thus decreasing perfusion. Since ventilation exceeds perfusion, the  V/Q ratio  is increased at the apex of the lungs. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3280", "contents": "When the  ventilation-perfusion ratio  is abnormally higher or lower than the normal range (0.8), it is called the  ventilation-perfusion mismatch , which may cause a significant impact on health."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3281", "contents": "There are two types of V/Q mismatch."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3282", "contents": "Firstly,  dead space  occurs when the ventilation exceeds perfusion due to deficient perfusion. Dead space refers to the volume not taking part in gas exchange. [ 11 ]  Alveolar dead space and insufficient perfusion result in a  V/Q ratio  above 0.8 with decreased fresh oxygen in the alveoli. [ 1 ]  This might have been caused by  blood clotting ,  heart failure ,  pulmonary emphysema , or damage in alveolar  capillaries . [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3283", "contents": "Secondly, the  pulmonary shunt  is caused by zero or low  V/Q ratio  due to insufficient ventilation and excess perfusion. Improper ventilation lowers blood oxygenation and oxygen supply to body tissues. Although 100% oxygen is inspired, a pulmonary shunt prevents oxygen from being delivered to the alveoli and blood capillaries. It likely results in  hypoxemia  (low oxygen level), and the common symptoms of ventilation-perfusion mismatch include dizziness, headache, and fatigue. [ 13 ]  Respiratory symptoms like  wheezing , rapid breathing, and shortness of breath may make breathing harder. Moreover, the patient may experience blue or grey-colored skin, reduced energy level,  spatial disorientation , or  confusion . [ medical citation needed ]  Low  V/Q ratio  may have been caused by  pneumonia ,  pulmonary edema ,  asthma , or the blockage of the  bronchus . [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3284", "contents": "Many factors contribute to causing V/Q mismatch. However, the most common causes can be divided into lung disease, cardiac shunt, and others."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3285", "contents": "COPD ( chronic obstructive pulmonary disease ) is a chronic lung condition that groups breathing issues caused by obstructive airflow. Difficulty in breathing results in low ventilation(low V/Q ratio) at the alveolar level, and its symptoms include breathing difficulty,  chronic cough , and  wheezing . Smoking (long-term exposure to chemical irritants) can cause  COPD , increasing the risk of lung cancer and heart disease. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3286", "contents": "Asthma  is a common inflammatory disease causing the airway to swell and disturb breathing and ventilation(low V/A ratio). The cause is unrevealed, but allergens such as pollen, mold, respiratory infections, and air pollutants(cigarette smoke) are potential stimulators. Symptoms are shortness of breath, chest tightness, coughing, and  wheezing . [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3287", "contents": "Pulmonary embolism  is blood clots occurring in the lungs. Restricted blood flow in the pulmonary circulation results in alveoli ventilated but not perfused, thus, increasing the V/Q ratio and decreasing gas exchange. It can cause  hypoxemia (low oxygen level) and damage part of the lung, which may be treated with  anticoagulants . Common symptoms are shortness of breath, chest pain, anxiety, irregular heartbeat,  heart racing ,  headache, memory loss, and confusion in the brain. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3288", "contents": "ARDS ,  pneumonia , chronic  bronchitis ,  pulmonary edema , and  airway obstruction  are lung diseases that also commonly cause a  ventilation-perfusion mismatch . [ 17 ]  Lung diseases abnormally alter the ventilation or perfusion and disrupt the maintenance of the normal V/Q ratio."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3289", "contents": "Deoxygenated blood typically moves to the lungs for oxygenation(fresh oxygen supply). The  right-to-left shunt  is an abnormal blood circulation that enables deoxygenated blood to pass from the right side to the left side of the heart and skips the lungs. Thus, no oxygenation occurs, and reduced gas exchange results in  hypoxemia  as fresh oxygen cannot reach the shunted blood. [ 18 ]  It results in ventilation without perfusion and a higher V/Q ratio."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3290", "contents": "Long exposure to cigarette smoke induces airway inflammation and enlargement, which eventually restricts airflow and associates a high risk of V/Q mismatch. Also,  obstructive sleep apnea  is a sleep-related breathing disorder experiencing reduced breathing while asleep due to obstruction of the upper airway. It typically has a higher risk in people with obesity. Symptoms are loud snoring, choking, breathing interruptions, headaches, and drowsiness when awake. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3291", "contents": "Several therapeutic pathways are developed to treat V/Q mismatch. The most common treatments are bronchodilators and oxygen therapy.  Bronchodilators  improve breathing by relaxing lung muscles or widening the airways. It is usually applied through inhalers and is mostly used to treat  asthma  and  chronic obstructive pulmonary disease . [ 19 ]   Oxygen therapy  provides supplemental pure oxygen to improve the low blood oxygen level to ease breathing. It is useful for patients experiencing sleep apnea, pneumonia, and asthma. [ 20 ]   Corticosteroids ,  antibiotics ,  pulmonary rehabilitation therapy ,  anticoagulants , and surgery can also serve as a medical treatment for  ventilation-perfusion mismatch -related symptoms and diseases. [ medical citation needed ]  Treatment may last for the short or long-term."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3292", "contents": "A pulmonary ventilation-perfusion scan (lung V/Q scan) can be used to diagnose the  V/Q mismatch . A ventilation scan is used to measure airflow spread and a perfusion scan for blood flow distribution in the lungs. A radioactive tracer is used to scan the whole lung and the ventilation and perfusion function. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3293", "contents": "In the  respiratory system , ventilation/perfusion (V/Q) mismatch refers to the pathological discrepancy between  ventilation  (V) and  perfusion  (Q) resulting in an abnormal  ventilation/perfusion (V/Q) ratio . Ventilation is a measure of the amount of inhaled air that reaches the  alveoli , while perfusion is a measure of the amount of deoxygenated blood that reaches the alveoli through the  capillary beds . [ 1 ]  Under normal conditions,  ventilation-perfusion coupling  keeps ventilation (V) at approximately 4 L/min and normal perfusion (Q) at approximately 5 L/min. Thus, at rest, a normal V/Q ratio is 0.8. [ 2 ]  Any deviation from this value is considered a V/Q mismatch. Maintenance of the V/Q ratio is crucial for preservation of effective pulmonary gas exchange and maintenance of oxygenation levels. A mismatch can contribute to hypoxemia and often signifies the presence or worsening of an underlying pulmonary condition. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3294", "contents": "In a condition such as  pulmonary embolism , the pulmonary blood flow is affected, thus the ventilation of the lung is adequate, however there is a perfusion defect. Gas exchange thus becomes highly inefficient leading to  hypoxemia , as measured by arterial oxygenation. A  ventilation perfusion scan  or lung  scintigraphy  can be used to diagnose areas of lungs being ventilated but not adequately perfused. This results in a raised  Alveolar-arterial (A-a) gradient  which is responsive to supplemental oxygen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3295", "contents": "In conditions with right to left shunts, there are also ventilation perfusion defects with high A-a gradients. Hypoxemia is difficult to correct with supplemental oxygen and is associated with a widened A-a gradient. In cases of right to left shunts more of deoxygenated blood mixes with oxygenated blood from the lungs and thus to a small extent the condition might neutralize the high A-a gradient with pure oxygen therapy.\nPatient with  parenchymal lung diseases  will have an increased A-a gradient with moderate response to oxygen therapy."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3296", "contents": "A patient with hypoventilation will have complete response to 100% oxygen therapy."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3297", "contents": "To differentiate between a ventilation perfusion mismatch or not, a lung scan is performed. The ventilation and perfusion are measured separately. If both scans are done simultaneously then it is called as V/Q scan. Ventilation Scan is done first as it is easy to wash out  tracer gas  from lungs with the help of hyperventilation than clearing the tracer radioactive material from blood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3298", "contents": "Indication: It is most commonly done in suspected case of pulmonary embolism."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3299", "contents": "Results:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3300", "contents": "Results are reported in following way:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3301", "contents": "Through ventilation and perfusion scans, the abnormal area of lung may be localized. A provisional diagnosis of  COPD ,  asthma  or  pulmonary embolisms  may be made. Treatment of these underlying conditions may address ventilation perfusion mismatch. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3302", "contents": "Management of the condition may vary. If ventilation is abnormal or low, increasing the  tidal volume  or the rate may result in the poorly ventilated area receiving an adequate amount of air, which ultimately leads to an improved V/Q ratio. [ citation needed ]  Conversely, if perfusion scan is of low quality showing low perfusion to lung as in case of hypovolemia, treatment of the conditions is by giving it fluid and using inotropes in case of shock.  [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3303", "contents": "In  kinesiology , the  ventilatory threshold  (VT1) refers to the point during exercise at which the volume of air breathed out (expiratory  ventilation ) starts to increase at an exponentially greater rate than VO 2  (breath-by-breath volume of oxygen (O 2 )). [ 1 ]  VT1 is thought to reflect a person's  anaerobic threshold  \u2014 the point at which the oxygen supplied to the muscles no longer meets its oxygen requirements at a given work rate \u2014 and therefore  lactate threshold  \u2014 the point at which  lactate  begins to accumulate in the blood, because with ongoing dependence on anaerobic glycolysis, increasing amounts of  CO2  need to be exhaled to accommodate its production during the conversion of lactic acid to lactate. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3304", "contents": "As the intensity level of the activity being performed increases, breathing becomes faster; more steadily first and then more rapid as the intensity increases. When breathing surpasses normal ventilation rate, one has reached ventilatory threshold. For most people this threshold lies at exercise intensities between 50% and 75% of VO 2  max. A major factor affecting one's ventilatory threshold is their maximal ventilation (amount of air entering and exiting lungs). This is dependent on their personal experience with the activity and how physically fit the person is. Comparison studies of more athletic people have shown that your ventilatory threshold occurs at a higher intensity if you are more active or have been training for that exercise; although, in some cases shorter continuous tests can be used because of rapid alterations in ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3305", "contents": "Frangolias DD,\nRhodes EC\nSchool of Human Kinetics, University of British Columbia, Vancouver, Canada.\nMedicine and Science in Sports and Exercise [1995, 27(7):1007-1013]:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3306", "contents": "A government experiment to test ventilatory threshold was held between November and December 2004. Subjects included 32 physically active males (age: 22.3; TV: 180.5; TM: 75.5 kg; VO2max: 57.1 mL/kg/min) encountered a continuous test of increasing loads on a treadmill, cardiorespiratory and other variables were observed using ECG (recording of the electrical activity of the heart) and gas analyzer. During the test, subjects were asked to point at a scale from 6 to 20 reflecting their feeling of discomfort. The RPE threshold was recorded as constant value of 12-13. Averages of ventilatory and RPE threshold were conveyed by parameters that were monitored and then compared by using t-test for dependent samples. No significant difference was found between mean values of ventilatory and RPE threshold, when they were expressed by parameters such as: speed, load, heart rate, absolute and relative oxygen consumption. The conclusion of this experiment was: the fixed value (12-13) of RPE scale may be used to detect the exercise intensity that corresponds to ventilatory threshold."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3307", "contents": "Maximum oxygen intake, VO 2 , is one of the best measures of cardiovascular fitness and maximal aerobic power. VO 2  max averages around 35\u201340 mL/(kg\u2219 min) in a healthy male and 27\u201331 mL/ (kg\u2219 min) in a healthy female. These scores can improve with training. Factors that affect your VO 2  max are age, sex, fitness, training, and genetics. While scores in the upper 80s and 90s have been recorded by legendary endurance athletes such as  Greg Lemond ,  Miguel Indurain , and  Steve Prefontaine , most competitive endurance athletes have scores in the mid to high 60s. Cycling, rowing, swimming and running are some of the main sports that push VO 2  levels to the maximum. Ventilatory threshold and lactate threshold are expressed as a percentage of VO 2  max; beyond this percentage the ability to sustain the work rate rapidly declines as high intensity but short duration energy systems such as glycolysis and ATP-PC are relied on more heavily."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3308", "contents": "Vital capacity  (VC) is the maximum amount of air a person can expel from the lungs after a maximum  inhalation . It is equal to the sum of  inspiratory reserve volume ,  tidal volume , and  expiratory reserve volume . It is approximately equal to Forced Vital Capacity (FVC). [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3309", "contents": "A person's vital capacity can be measured by a wet or regular  spirometer . In combination with other physiological measurements, the vital capacity can help make a diagnosis of underlying  lung disease . Furthermore, the vital capacity is used to determine the severity of respiratory muscle involvement in  neuromuscular disease , and can guide treatment decisions in  Guillain\u2013Barr\u00e9 syndrome  and  myasthenic crisis . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3310", "contents": "A normal adult has a vital capacity between 3 and 5\u00a0litres. [ 3 ]  A human's vital capacity depends on age, sex, height, mass, and possibly ethnicity. [ 4 ]  However, the dependence on ethnicity is poorly understood or defined, as it was first established by studying black  slaves  in the 19th century [ 5 ]  and may be the result of conflation with environmental factors. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3311", "contents": "Lung volumes  and lung capacities refer to the volume of air associated with different phases of the respiratory cycle. Lung volumes are directly measured, whereas lung capacities are inferred from volumes."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3312", "contents": "The vital capacity can be used to help differentiate causes of lung disease. In  restrictive lung disease  the vital capacity is decreased. In  obstructive lung disease  it is usually normal or only slightly decreased. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3313", "contents": "Vital capacity increases with height and decreases with age. Formulas to estimate vital capacity are: [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3314", "contents": "v \n \n c \n \n f \n e \n m \n a \n l \n e \n \n \n = \n ( \n 21.78 \n \u2212 \n 0.101 \n a \n ) \n \u22c5 \n h \n \n \n \n \n v \n \n c \n \n m \n a \n l \n e \n \n \n = \n ( \n 27.63 \n \u2212 \n 0.112 \n a \n ) \n \u22c5 \n h \n \n \n \n \n \n \n {\\displaystyle {\\begin{aligned}vc_{female}=(21.78-0.101a)\\cdot h\\\\vc_{male}=(27.63-0.112a)\\cdot h\\\\\\end{aligned}}} \n \n \nwhere  \n \n \n \n v \n c \n \n \n {\\displaystyle vc} \n \n  is approximate vital capacity in cm 3 ,  \n \n \n \n a \n \n \n {\\displaystyle a} \n \n  is age in years, and  \n \n \n \n h \n \n \n {\\displaystyle h} \n \n  is height in cm."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3315", "contents": "Several studies have been made to measure and predict vital capacity:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3316", "contents": "V\u0307O 2  max  (also  maximal oxygen consumption ,  maximal oxygen uptake  or  maximal aerobic capacity ) is the maximum rate of  oxygen consumption  attainable during physical exertion. [ 1 ] [ 2 ]  The name is derived from three abbreviations: \"V\u0307\" for  volume  (the dot over the V indicates \"per unit of time\" in  Newton's notation ), \"O 2 \" for  oxygen , and \"max\" for maximum and usually normalized per kilogram of body mass. A similar measure is  V\u0307O 2  peak  ( peak oxygen consumption ), which is the measurable value from a session of physical exercise, be it incremental or otherwise. It could match or underestimate the actual V\u0307O 2  max. Confusion between the values in older and popular fitness literature is common. [ 3 ]  The capacity of the lung to exchange oxygen and carbon dioxide is constrained by the rate of   blood oxygen transport  to active tissue."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3317", "contents": "The measurement of V\u0307O 2  max in the laboratory provides a quantitative value of endurance fitness for comparison of individual training effects and between people in  endurance training . Maximal oxygen consumption reflects  cardiorespiratory fitness  and  endurance  capacity in exercise performance. Elite athletes, such as  competitive distance runners ,  racing cyclists  or  Olympic cross-country skiers , can achieve V\u0307O 2  max values exceeding 90\u00a0mL/(kg\u00b7min), while some endurance animals, such as  Alaskan huskies , have V\u0307O 2  max values exceeding 200\u00a0mL/(kg\u00b7min)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3318", "contents": "In  physical training , especially in its academic literature, V\u0307O 2  max is often used as a reference level to quantify exertion levels, such as 65% V\u0307O 2  max as a threshold for sustainable exercise, which is generally regarded as more rigorous than  heart rate , but is more elaborate to measure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3319", "contents": "V\u0307O 2  max is expressed either as an absolute rate in (for example) litres of oxygen per minute (L/min) or as a relative rate in (for example) millilitres of oxygen per kilogram of the body  mass  per minute (e.g., mL/(kg\u00b7min)). The latter expression is often used to compare the performance of endurance sports athletes. However, V\u0307O 2  max generally does not vary linearly with body mass, either among individuals within a species or among species, so comparisons of the performance capacities of individuals or species that differ in body size must be done with appropriate statistical procedures, such as  analysis of covariance . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3320", "contents": "Accurately measuring V\u0307O 2  max involves a physical effort sufficient in duration and intensity to fully tax the aerobic energy system. In general clinical and athletic testing, this usually involves a graded exercise test in which exercise intensity is progressively increased while measuring:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3321", "contents": "V\u0307O 2  max is measured during a  cardiopulmonary exercise test  (CPX test). The test is done on a  treadmill  or  cycle ergometer . In untrained subjects, V\u0307O 2  max is 10% to 20% lower when using a cycle ergometer compared with a treadmill. [ 4 ]  However, trained cyclists' results on the cycle ergometer are equal to or even higher than those obtained on the treadmill. [ 5 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3322", "contents": "The classic V\u0307O 2  max, in the sense of Hill and Lupton (1923), is reached when oxygen consumption remains at a steady state (\"plateau\") despite an increase in workload. The occurrence of a plateau is not guaranteed and may vary by person and sampling interval, leading to modified protocols with varied results. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3323", "contents": "V\u0307O 2  may also be calculated by the  Fick equation :\n \n \n \n \n \n \n \n \n V \n \u02d9 \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n = \n Q \n \u00d7 \n \u00a0 \n ( \n \n C \n \n a \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n C \n \n v \n \n \n \n \n O \n \n 2 \n \n \n \n \n \n \n ) \n \n \n {\\displaystyle {\\ce {{\\dot {V}}O2}}=Q\\times \\ (C_{a}{\\ce {O2}}-C_{v}{\\ce {O2}})} \n \n , when these values are obtained during exertion at a maximal effort. Here  Q  is the  cardiac output  of the heart,  C a O 2  is the arterial oxygen content, and  C v O 2  is the venous oxygen content. ( C a O 2  \u2013  C v O 2 ) is also known as the  arteriovenous oxygen difference ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3324", "contents": "The Fick equation may be used to measure V\u0307O 2  in critically ill patients, but its usefulness is low even in non-exerted cases. [ 8 ]  Using a breath-based VO 2  to estimate cardiac output, on the other hand, seems to be reliable enough. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3325", "contents": "The necessity for a subject to exert maximum effort in order to accurately measure V\u0307O 2  max can be dangerous in those with compromised respiratory or cardiovascular systems; thus,  sub-maximal tests  for  estimating  V\u0307O 2  max have been developed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3326", "contents": "An estimate of V\u0307O 2  max is based on maximum and resting heart rates. In the Uth  et al.  (2004) formulation, it is given by: [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3327", "contents": "This equation uses the ratio of maximum heart rate (HR max ) to resting heart rate (HR rest ) to predict V\u0307O 2  max. The researchers cautioned that the conversion rule was based on measurements on well-trained men aged 21 to 51 only, and may not be reliable when applied to other sub-groups. They also advised that the formula is most reliable when based on actual measurement of maximum heart rate, rather than an age-related estimate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3328", "contents": "The Uth constant factor of 15.3 is given for well-trained men. [ 10 ]  Later studies have revised the constant factor for different populations. According to Voutilainen  et al.  2020, the constant factor should be 14 in around 40-year-old normal weight never-smoking men with no cardiovascular diseases, bronchial asthma, or cancer. [ 11 ] \nEvery 10 years of age reduces the coefficient by one, as well as does the change in body weight from normal weight to obese or the change from never-smoker to current smoker. Consequently, V\u0307O 2  max of 60-year-old obese current smoker men should be estimated by multiplying the HR max  to HR rest  ratio by 10."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3329", "contents": "Kenneth H. Cooper  conducted a study for the  United States Air Force  in the late 1960s. One of the results of this was the  Cooper test  in which the distance covered running in 12 minutes is measured. [ 12 ]  Based on the measured distance, an estimate of V\u0307O 2  max [in mL/(kg\u00b7min)] can be calculated by inverting the linear regression equation, giving us:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3330", "contents": "where  d 12  is the distance (in metres) covered in 12 minutes."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3331", "contents": "An alternative equation is:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3332", "contents": "where  d \u2032 12  is distance (in miles) covered in 12 minutes."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3333", "contents": "There are several other reliable tests and V\u0307O 2  max calculators to estimate V\u0307O 2  max, most notably the  multi-stage fitness test  (or  beep  test). [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3334", "contents": "Estimation of V\u0307O 2  max from a timed one-mile track walk (as fast as possible) in decimal minutes ( t , e.g.: 20:35 would be specified as 20.58), sex, age in years, body weight in pounds ( BW , lbs), and 60-second heart rate in beats-per-minute ( HR , bpm) at the end of the mile. [ 14 ]  The constant  x  is 6.3150 for males, 0 for females."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3335", "contents": "Correlation coefficient   r  for the generalized formula is 0.88."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3336", "contents": "Men have a V\u0307O 2  max that is 26% higher (6.6 mL/(kg\u00b7min)) than women for treadmill and 37.9% higher (7.6 mL/(kg\u00b7min)) than women for cycle ergometer on average. [ 15 ]  V\u0307O 2  max is on average 22% higher (4.5 mL/(kg\u00b7min)) when measured using a treadmill compared with a cycle ergometer. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3337", "contents": "The average untrained healthy male has a V\u0307O 2  max of approximately 35\u201340 mL/(kg\u00b7min). [ 16 ] [ 17 ]  The average untrained healthy female has a V\u0307O 2  max of approximately 27\u201331 mL/(kg\u00b7min). [ 16 ]  These scores can improve with training and decrease with age, though the degree of trainability also varies widely. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3338", "contents": "In sports where endurance is an important component in performance, such as  road cycling ,  rowing ,  cross-country skiing , swimming, and  long-distance running , world-class athletes typically have high V\u0307O 2  max values. Elite male runners can consume up to 85 mL/(kg\u00b7min), and female elite runners can consume about 77\u00a0mL/(kg\u00b7min). [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3339", "contents": "Norwegian cyclist  Oskar Svendsen  holds the record for the highest V\u0307O 2  ever tested with 97.5 mL/(kg\u00b7min). [ 20 ] [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3340", "contents": "V\u0307O 2  max has been measured in other animal species. During loaded swimming, mice had a V\u0307O 2  max of around 140 mL/(kg\u00b7min). [ 22 ]   Thoroughbred horses  had a V\u0307O 2  max of around 193 mL/(kg\u00b7min) after 18 weeks of high-intensity training. [ 23 ]   Alaskan huskies  running in the  Iditarod Trail Sled Dog Race  had V\u0307O 2  max values as high as 240\u00a0mL/(kg\u00b7min). [ 24 ]  Estimated V\u0307O 2  max for  pronghorn antelopes  was as high as 300\u00a0mL/(kg\u00b7min). [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3341", "contents": "The factors affecting V\u0307O 2  may be separated into supply and demand. [ 26 ]  Supply is the transport of oxygen from the lungs to the  mitochondria  (combining  pulmonary function ,  cardiac output ,  blood volume , and capillary density of the skeletal muscle) while demand is the rate at which the mitochondria can reduce oxygen in the process of  oxidative phosphorylation . [ 26 ]  Of these, the supply factors may be more limiting. [ 26 ] [ 27 ]  However, it has also been argued that while trained subjects are probably supply limited, untrained subjects can indeed have a demand limitation. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3342", "contents": "General characteristics that affect V\u0307O 2  max include age,  sex , fitness and training, and altitude. V\u0307O 2  max can be a poor predictor of performance in runners due to variations in  running economy  and  fatigue  resistance during prolonged exercise. The body works as a system. If one of these factors is sub-par, then the whole system's normal capacity is reduced. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3343", "contents": "The drug  erythropoietin  (EPO) can boost V\u0307O 2  max by a significant amount in both humans and other mammals. [ 29 ]  This makes EPO attractive to athletes in  endurance sports , such as professional cycling. EPO has been  banned since the 1990s  as an illicit  performance-enhancing substance , but by 1998 it had become widespread in cycling and led to the  Festina affair [ 30 ] [ 31 ]  as well as being mentioned ubiquitously in the  USADA  2012 report on the  U.S. Postal Service Pro Cycling Team . [ 32 ]   Greg LeMond  has suggested establishing a baseline for riders' V\u0307O 2  max (and other attributes) to detect abnormal performance increases. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3344", "contents": "V\u0307O 2  max/peak is widely used as an indicator of cardiorespiratory fitness (CRF) in select groups of athletes or, rarely, in people under assessment for disease risk. In 2016, the  American Heart Association  (AHA) published a scientific statement recommending that CRF \u2013 quantifiable as V\u0307O 2  max/peak \u2013 be regularly assessed and used as a clinical vital sign; ergometry (exercise wattage measurement) may be used if V\u0307O 2  is unavailable. [ 34 ]  This statement was based on evidence that lower fitness levels are associated with a higher risk of cardiovascular disease, all-cause mortality, and mortality rates. [ 34 ]  In addition to risk assessment, the AHA recommendation cited the value for measuring fitness to validate  exercise prescriptions ,  physical activity  counseling, and improve both management and health of people being assessed. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3345", "contents": "A 2023  meta-analysis  of  observational   cohort studies  showed an inverse and independent association between V\u0307O 2  max and all-cause mortality risk. [ 35 ]  Every one  metabolic equivalent  increase in estimated cardiorespiratory fitness was associated with an 11% reduction in mortality. [ 35 ]  The top third of V\u0307O 2  max scores represented a 45% lower mortality in people compared with the lowest third. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3346", "contents": "As of 2023, V\u0307O 2  max is rarely employed in routine clinical practice to assess cardiorespiratory fitness or mortality due to its considerable demand for resources and costs. [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3347", "contents": "British physiologist  Archibald Hill  introduced the concepts of maximal oxygen uptake and oxygen debt in 1922. [ 38 ] [ 27 ]  Hill and German physician  Otto Meyerhof  shared the 1922  Nobel Prize in Physiology or Medicine  for their independent work related to muscle energy metabolism. [ 39 ]  Building on this work, scientists began measuring oxygen consumption during exercise. Key contributions were made by Henry Taylor at the  University of Minnesota , Scandinavian scientists  Per-Olof \u00c5strand  and  Bengt Saltin  in the 1950s and 60s, the  Harvard Fatigue Laboratory , German universities, and the Copenhagen Muscle Research Centre. [ 40 ] [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3348", "contents": "Work of breathing  (WOB) is the energy expended to  inhale  and  exhale  a  breathing gas . It is usually expressed as work per unit volume, for example, joules/litre, or as a work rate (power), such as joules/min or equivalent units, as it is not particularly useful without a reference to volume or time. It can be calculated in terms of the pulmonary pressure multiplied by the change in pulmonary volume, or in terms of the oxygen consumption attributable to breathing. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3349", "contents": "In a normal resting state the work of breathing constitutes about 5% of the total body oxygen consumption. It can increase considerably due to illness [ 3 ]  or constraints on gas flow imposed by  breathing apparatus ,  ambient pressure , or  breathing gas  composition."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3350", "contents": "The normal relaxed state of the lung and chest is partially empty. Further exhalation requires muscular work.\nInhalation is an active process requiring work. [ 4 ]  Some of this work is to overcome frictional resistance to flow, and part is used to deform elastic tissues, and is stored as potential energy, which is recovered during the passive process of exhalation,  Tidal breathing  is breathing that does not require active muscle contraction during exhalation. The required energy is provided by the stored elastic energy. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3351", "contents": "When there is increased gas flow resistance, the optimal respiratory rate decreases."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3352", "contents": "This work (generally during the inhalation phase) is stored as potential energy which is recovered during exhalation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3353", "contents": "A pressure difference is required to overcome the frictional resistance to gas flow due to viscosity, inertial resistance due to density, and to provide non-elastic components of movement of the airway tissues to accommodate pulmonary volume change."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3354", "contents": "Dynamic airway compression occurs when  intrapleural pressure  equals or exceeds  alveolar pressure , which causes dynamic collapsing of the  lung  airways. It is termed  dynamic  given the  transpulmonary pressure  (alveolar pressure \u2212 intrapleural pressure) varies based on factors including  lung volume ,  compliance ,  resistance , existing pathologies, etc. [ 6 ]  It occurs during forced  expiration  when intrapleural pressure is greater than  atmospheric pressure  (positive  barometric  values), and not during passive expiration when intrapleural pressure remains at subatmospheric pressures (negative barometric values). Clinically, dynamic compression is most commonly associated to the wheezing sound during forced expiration such as in individuals with  chronic obstructive pulmonary disorder  (COPD). [ 7 ] [ 8 ]  The density of the gas also influences the pressure reduction in the airways, and a higher density causes a greater drop in pressure for a given volumetric flow rate, which has consequences in ambient pressure diving, and can limit ventilation at densities over 6g/litre. It can be exacerbated by a negative static lung load. The effect is modeled by the  Starling resistor [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3355", "contents": "Work is defined as a force applied over a distance. The SI unit of work is the Joule, equivalent to a force of 1 Newton exerted along a distance of 1 metre.  In gas flow across a constant section this equates to a volume flowing against a pressure: [ note 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3356", "contents": "Work = Pressure x Volume"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3357", "contents": "and Power = Work / time"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3358", "contents": "with SI units for Power: Watts = Joules per second"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3359", "contents": "The term \"work of breathing\" should be more accurately referred to as the \"power of breathing,\" unless it is in reference to the work associated with a specific number of breaths or a given interval of time. It is important to differentiate between the terms \"breathing rate\" and \"breathing frequency.\" Although the two are frequently used interchangeably, \"breathing rate\" refers to the respiratory rate and is described in breaths per minute (BPM). On the other hand, \"breathing frequency\" refers to the frequency composition of a single breath and is described in hertz. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3360", "contents": "Because measuring the work of breathing requires complex instrumentation, measuring it in patients with acute serious illness is difficult and risky.  Instead, physicians determine if the work of breathing is increased by gestalt or by examining the patient looking for signs of increased breathing effort. These signs include nasal flaring, the contraction of  sternomastoid , and  thoraco-abdominal paradox . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3361", "contents": "Work of breathing is affected by several factors in underwater diving at ambient pressure. There are physiological effects of immersion, physical effects of ambient pressure and breathing gas mixture, and mechanical effects of the gas supply system. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3362", "contents": "The properties of the lung can vary if a pressure differential exists between the breathing gas supply and the ambient pressure on the chest. The relaxed internal pressure in the lungs is equal to the pressure at the mouth, and in the immersed diver, the pressure on the chest may vary from the pressure at the mouth depending on the attitude of the diver in the water. This pressure difference is the static lung load or hydrostatic imbalance. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3363", "contents": "A negative static lung load occurs when the gas supply pressure is lower than the ambient pressure at the chest, and the diver needs to apply more effort to inhale. The small negative pressure differential inside the air passages induces blood engorgement of the distensible lung blood vessels, reducing the compliance of the lung tissue and making the lung stiffer than normal, therefore requiring more muscular effort to move a given volume of gas through the airways. This effect can occur in an upright open-circuit diver, where the chest is deeper than the regulator, and in a rebreather diver if the chest is deeper than the  counterlung  and will increase the work of breathing and in extreme cases lead to dynamic airway compression. The effects of positive static lung load in these circumstances have not been clearly demonstrated, but may delay this effect. [ 12 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3364", "contents": "Density of a given gas mixture is proportional to absolute pressure at a constant temperature throughout the range of respirable pressures, and resistance to flow is a function of flow velocity, density and viscosity. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3365", "contents": "As density increases, the amount of pressure difference required to drive a given flow rate increases. When the density exceeds about 6g/litre the exercise tolerance of the diver becomes significantly reduced, [ 12 ]  and by 10\u00a0g/litre it is marginal. At this stage even moderate exertion may cause a carbon dioxide buildup that cannot be reversed by increased ventilation, as the work required to increase ventilation produces more carbon dioxide than is eliminated by the increased ventilation, and flow may be choked by the effects of dynamic airway compression. In some cases the person may resort to coughing exhalation to try to increase flow. This effect can be delayed by using lower density gas such as helium in the breathing mix to keep the combined density below 6\u00a0g/litre. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3366", "contents": "On air or nitrox, maximum ventilation drops to about half at 30\u00a0m, equivalent to 4 bar absolute and gas density of about 5.2\u00a0g/litre. The 6\u00a0g/litre recommended soft limit occurs at about 36\u00a0m and by the recommended recreational diving depth limit of 40\u00a0m, air and nitrox density reaches 6.5\u00a0g/litre [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3367", "contents": "The  maximum voluntary ventilation  and  breathing capacity  are approximately inversely proportional to the square root of gas density, which for a given gas is proportional to absolute pressure. Use of a low density gas like helium or hydrogen to replace nitrogen in the mixture helps not only to reduce the narcotic effects, but also the density and thereby the work of breathing. To be non-combustible, there must be less than 4% by volume of oxygen n a hydrogen rich mixture. The presence and concentration of other diluents such as nitrogen or helium does not affect the flammability limit in a hydrogen rich mixture. [ 13 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3368", "contents": "In the  diving  industry the performance of  breathing apparatus  is often referred to as work of breathing. In this context it generally means the external work of an average single breath taken through the specified apparatus for given conditions of ambient pressure, underwater environment, flow rate during the breathing cycle, and gas mixture - underwater divers may breathe oxygen-rich  breathing gas  to reduce the risk of  decompression sickness , or gases containing  helium  to reduce  narcotic effects . [ 15 ] [ 16 ] [ 17 ]  Helium also has the effect of reducing the work of breathing by reducing density of the mixture, though helium's viscosity is fractionally greater than nitrogen's. [ 18 ] [ 19 ]  Standards for these conditions exist and to make useful comparisons between breathing apparatus they must be tested to the same standard."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3369", "contents": "Free-flow systems; In a  free-flow breathing apparatus , the user breathes from the volume of ambient pressure gas in front of the face. If the supply is adequate, exhaled gas is flushed away by fresh gas flow, and only fresh gas is inhaled \u2013 there is no dead space. Work of breathing is affected by gas density due to pressure and gas composition, and there may be positive or negative static lung loading, but there is no additional external work of breathing due to airflow through the breathing apparatus. Surface-supplied divers who will be working hard underwater often use free-flow systems for this reason."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3370", "contents": "Demand systems:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3371", "contents": "Recirculating systems: Work of breathing of a  rebreather  has two main components: Resistive work of breathing is due to the flow restriction of the gas passages causing resistance to flow of the breathing gas, and exists in all applications where there is no externally powered ventilation. Hydrostatic work of breathing is only applicable to diving applications, and is due to difference in pressure between the lungs of the diver and the  counterlungs  of the rebreather. This pressure difference is generally due to a difference in hydrostatic pressure caused by a difference in depth between lung and counterlung, but can be modified by ballasting the moving side of a  bellows counterlung . [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3372", "contents": "Resistive work of breathing is the sum of all the restrictions to flow due to bends, corrugations, changes of flow direction, valve cracking pressures, flow through scrubber media, etc., and the resistance to flow of the gas, due to inertia and viscosity, which are influenced by density, which is a function of molecular weight and pressure. Rebreather design can limit the mechanical aspects of flow resistance, particularly by the design of the  scrubber , counterlungs and breathing hoses. Diving rebreathers are influenced by the variations of work of breathing due to gas mixture choice and depth. Helium content reduces work of breathing, and increased depth increases work of breathing. Work of breathing can also be increased by excessive wetness of the scrubber media, usually a consequence of a leak in the breathing loop, or by using a grain size of absorbent that is too small. Both of these factors cause restrictions to the gas flow. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3373", "contents": "The semi-closed rebreather systems developed by  Dr\u00e4gerwerk  in the early 20th century as a scuba gas supply for  Standard diving dress , using oxygen or nitrox, and the US Navy Mark V Heliox helmet developed in the 1930s for deep diving, circulated the breathing gas through the helmet and scrubber by using an  injector  system where the added gas entrained the loop gas and produced a stream of scrubbed gas past the diver inside the helmet, which eliminated external dead space and resistive work of breathing, but was not suitable for high breathing rates. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3374", "contents": "Factors which influence the work of breathing of an underwater breathing apparatus include density and viscosity of the gas, flow rates, cracking pressure (the pressure differential required to open the demand valve), and back pressure over exhaust valves. [ 12 ]  Diver orientation affects the relative depths of lungs and regulator or breathing loop, which can cause variation between positive and negative pressure breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3375", "contents": "Work of breathing of a diver has a physiological component as well as the equipment component. for a given breathing gas mixture, the density will increase with an increase in depth. A higher gas density requires more effort to accelerate the gas in the transitions between inhalation and exhalation. To minimise the work of breathing the flow velocity can be reduced, but this will reduce RMV unless the depth of breathing is increased to compensate. Slow deep breathing improves efficiency of respiration by increasing gas turnover in the alveoli, and exertion must be limited to match the gas transfer possible from the RMV which can be comfortably maintained over long periods. Exceeding this maximum continuous exertion may lead to carbon dioxide buildup, which can cause accelerated breathing rate, with increased turbulence, leading to lower efficiency, reduced RMV and higher work of breathing in a positive feedback loop. At extreme depths this can occur even at relatively low levels of exertion, and it may be difficult or impossible to break the cycle. The resulting stress can be a cause of panic as the perception is of an insufficient gas supply due to carbon dioxide buildup though oxygenation may be adequate. [ 23 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3376", "contents": "Negative static lung load increases work of breathing and can vary depending on the relative depth of the regulator diaphragm to the lungs in open circuit equipment, and the relative depth of the counterlung to the lungs in a rebreather. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3377", "contents": "Gas density at ambient pressure is a limiting factor on the ability of a diver to effectively eliminate carbon dioxide at depth for a given work of breathing. [ 12 ]  At increased ambient pressure the increased breathing gas density causes greater airway resistance. Maximum exercise ventilation and maximum voluntary ventilation are reduced as a function of density, which for a given gas mixture is proportional to pressure. Maximum voluntary ventilation is approximated by a square root function of gas density. Exhalation flow rate is limited by effort independent turbulent flow. Once this occurs further attempts to increase flow rate are actively counterproductive and contribute to further accumulation of carbon dioxide. The effects of negative static lung load are amplified by increased gas density. [ 21 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3378", "contents": "To reduce risk of hypercapnia, divers may adopt a breathing pattern that is slower and deeper than normal rather than fast and shallow, as this gives maximum gas exchange per unit effort by minimising turbulence, friction, and dead space effects. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3379", "contents": "Carbon dioxide is a product of cell metabolism which is eliminated by gas exchange in the lungs while breathing. The rate of production is variable with exertion, but there is a basic minimum. If the rate of elimination is less than the rate of production, the levels will increase, and produce symptoms of toxicity such as headache, shortness of breath and mental impairment, eventually loss of consciousness, which can lead to drowning. In diving there are factors which increase carbon dioxide production (exertion), and factors which can impair elimination, making divers particularly vulnerable to carbon dioxide toxicity. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3380", "contents": "Oxygen is consumed and carbon dioxide produced in the same quantities underwater as at the surface for the same amount of work, but breathing requires work, and work of breathing can be much greater underwater, and work of breathing is similar to other forms of work in the production of carbon dioxide. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3381", "contents": "The ability of a diver to respond to increases in work of breathing is limited. As work of breathing increases, the additional carbon dioxide produce in doing this work pushes up the need for higher elimination rate, which is proportional to ventilation, in the case of negligible carbon dioxide in the inspired air. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3382", "contents": "Carbon dioxide production by the tissues is a simple function of tissue metabolism and oxygen consumption. The more work done in a tissue, the more oxygen will be consumed and the more carbon dioxide will be produced.  Carbon dioxide removal  in the alveoli depends on the partial pressure gradient for carbon dioxide diffusion between blood and the alveolar gas. This gradient is maintained by flushing carbon dioxide out of the alveoli during breathing, which depends on replacing air in the alveoli with more carbon dioxide by air with less carbon dioxide. The more air moved in and out of the alveoli during breathing, the more carbon dioxide is flushed out, and the greater the pressure gradient between the venous blood and alveolar gas that drives carbon dioxide diffusion from the blood. Maintenance of the correct carbon dioxide levels is critically dependent on adequate lung ventilation, and there are multiple aspects of diving that can interfere with adequate ventilation of the lungs. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3383", "contents": "Carbon dioxide retention as a consequence of excessively high work of breathing may cause direct symptoms of carbon dioxide toxicity, and synergistic effects with nitrogen narcosis and CNS oxygen toxicity which is aggravated by cerebral vasodilation due to high carbon dioxide levels causing increased dosage of oxygen to the brain. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3384", "contents": "The  ANSTI machine  is used for automated testing of underwater breathing apparatus. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3385", "contents": "The  zones of the lung  divide the  lung  into four vertical regions, based upon the relationship between the pressure in the  alveoli  (PA), in the  arteries  (Pa), in the  veins  (Pv) and the pulmonary  interstitial  pressure (Pi):"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3386", "contents": "This concept is generally attributed to an article by West et al. in 1964, [ 1 ]  but was actually proposed two years earlier by Permutt et al. [ 2 ]  In this article, Permutt suggests \"The pressure in the pulmonary arteries and veins is less at the top than at the bottom of the lung.  It is quite likely that there is a portion of the lung toward the top in an upright subject in which the pressure in the pulmonary arteries is less than alveolar pressure.\""}
+{"id": "WikiPedia_Pulmonology$$$corpus_3387", "contents": "The concept is as follows:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3388", "contents": "Alveolar pressure  (PA) at end expiration is equal to atmospheric pressure (0\u00a0cm H 2 O differential pressure, at zero flow), plus or minus 2\u00a0cm H 2 O (1.5\u00a0mmHg) throughout the lung. On the other hand, gravity causes a gradient in blood pressure between the top and bottom of the lung of 20\u00a0mmHg in the erect position (roughly half of that in the supine position). Overall, mean pulmonary venous pressure is ~5\u00a0mmHg. Local venous pressure falls to -5 at the apexes and rises to +15\u00a0mmHg at the bases, again for the erect lung.\nPulmonary blood pressure is typically in the range  25\u201310\u00a0mmHg with a mean pressure of 15\u00a0mmHg. Regional arterial blood pressure is typically in the range 5\u00a0mmHg near the apex of the lung to 25\u00a0mmHg at the base."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3389", "contents": "Zone 1 is not observed in the normal healthy human lung. In normal health pulmonary arterial (Pa) pressure exceeds alveolar pressure (PA) in all parts of the lung. It is generally only observed when a person is ventilated with positive pressure or hemorrhage. In these circumstances, blood vessels can become completely collapsed by alveolar pressure (PA) and blood does not flow through these regions. They become alveolar  dead space ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3390", "contents": "Zone 2 is the part of the lungs about 3\u00a0cm above the heart. In this region blood flows in pulses. At first there is no flow because of obstruction at the venous end of the capillary bed. Pressure from the arterial side builds up until it exceeds alveolar pressure and flow resumes. This dissipates the capillary pressure and returns to the start of the cycle. Flow here is sometimes compared to a  starling resistor  or waterfall effect."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3391", "contents": "Zone 3 comprises the majority of the lungs in health. There is no external resistance to blood flow and blood flow is continuous throughout the cardiac cycle. Flow is determined by the Ppa-Ppv difference (Ppa - Ppv), which is constant down this portion of the lung. However, transmural pressure across the wall of the blood vessels increases down this zone due to gravity. Consequently the vessels wall are more stretched so the caliber of the vessels increases causing an increase in flow due to lower resistance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3392", "contents": "Zone 4 can be seen at the lung bases at low lung volumes or in  pulmonary edema . Pulmonary interstitial pressure (Pi) rises as lung volume decreases due to reduced radial tethering of the lung  parenchyma . Pi is highest at the base of the lung due to the weight of the above lung tissue. Pi can also rise due to an increased volume of 'leaked' fluid from the pulmonary vasculature ( pulmonary edema ). An increase in Pi causes extraalveolar blood vessels to reduce in caliber, in turn causing blood flow to decrease (extraalveolar blood vessels are those blood vessels outside alveoli).  Intraalveolar blood vessels (pulmonary capillaries) are thin walled vessels adjacent to alveoli which are subject to the pressure changes described by zones 1-3. Flow in zone 4 is governed by the arteriointerstitial pressure difference (Pa \u2212 Pi). This is because as Pi rises, the arterial caliber is reduced, thereby increasing resistance to flow. The Pa/Pv difference remains unchanged since Pi is applied over both vessels."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3393", "contents": "The  ventilation/perfusion ratio  (V/Q ratio) is higher in zone #1 (the  apex of lung ) when a person is standing than it is in zone #3 (the  base of lung ) because perfusion is nearly absent. However, ventilation and perfusion are highest in base of the lung, resulting in a comparatively lower V/Q ratio."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3394", "contents": "An  endobronchial valve  ( EBV ) is a small, one-way valve, which may be  implanted  in an  airway  feeding the  lung  or part of lung. The valve allows air to be breathed out of the section of lung supplied, and prevents air from being breathed in. This leaves the rest of the lung to expand more normally and avoid air-trapping.  Endobronchial valves are typically implanted using a flexible delivery  catheter  advanced through a  bronchoscope  in minimally invasive  bronchoscopic lung volume reduction  procedures in the treatment of severe  emphysema . The valves are also removable if they are not working properly."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3395", "contents": "The one-way endobronchial valve is typically implanted such that on  exhalation  air is able to flow through the valve and out of the lung compartment that is fed by that airway, but on  inhalation , the valve closes and blocks air from entering that lung compartment. Thus, an implanted endobronchial valve typically helps a lung compartment to empty itself of air. This has been shown to be beneficial in the treatment of  emphysema , where lungs lose their elasticity and thus cannot contract sufficiently to exhale air, leading to air trapping and hyperinflation. When one or more diseased portions of an emphysematous lung are made to deflate and collapse, other healthier portions of the lung have more room in the chest cavity to inhale and exhale, pressure is removed from the  diaphragm , and even the heart may function better as the hyperinflated lung becomes smaller. [ 1 ]  The amount of residual volume reduction achieved, correlates with the effects on  FEV1 , quality of life and exercise capacity. [ 2 ]  Endobronchial valves have also been shown to be beneficial in treatment of persistent air leaks in the lungs. Their use in the treatment of  tuberculosis  and its complications has been studied resulting in promising outcomes but further studies are needed. [ 3 ]  Endobronchial valves may be the first successful medical device treatment of emphysema, a disease that affects millions of people worldwide and has no known cure, being managed traditionally by  lung transplantation  and/or  lung volume reduction surgery  (though some people do not meet the eligibility requirements for one or both of these invasive procedures). [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3396", "contents": "Although endobronchial isolation techniques for emphysema were developed in the early 2000s, [ 6 ]  specific valves were developed primarily by the start-up medical device company Emphasys Medical (now Pulmonx - Redwood City, California) as a  minimally invasive  alternative to lung volume reduction surgery for emphysema. In lung volume reduction surgery, one or more diseased portion(s) of a lung are  excised . Endobronchial valves were designed to replicate the effects of that procedure without requiring incisions, by simply allowing the most diseased portions of the lung to collapse. Emphasys was purchased by Pulmonx in 2009, and Pulmonx currently markets the Zephyr\u00ae endobronchial valve (developed by Emphasys) in Europe, Australia, China and many other locations outside the U.S. Pulmonx also sells the Chartis\u00ae Pulmonary Assessment System, which is an assessment tool used with endobronchial valves to help physicians target appropriate lung compartments for treatment. [ 2 ]  Another company, Spiration (Seattle, Washington), developed a different type of endobronchial valve and was acquired by Olympus in 2010."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3397", "contents": "A  plethysmograph  is an instrument for measuring changes in volume within an  organ  or whole body (usually resulting from fluctuations in the amount of blood or air it contains). The word is derived from the Greek \"plethysmos\" (increasing, enlarging, becoming full), and \"graphein\" (to write). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3398", "contents": "Pulmonary plethysmographs are commonly used to measure the  functional residual capacity  (FRC) of the  lungs \u2014the volume in the lungs when the muscles of respiration are relaxed\u2014and total lung capacity. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3399", "contents": "In a traditional plethysmograph (or \"body box\"), the test subject, or patient, is placed inside a sealed chamber the size of a small telephone booth with a single mouthpiece.  At the end of normal expiration, the mouthpiece is closed.  The patient is then asked to make an inspiratory effort.  As the patient tries to inhale (a maneuver which looks and feels like panting), the lungs expand, decreasing pressure within the lungs and increasing lung volume. This, in turn, increases the pressure within the box since it is a closed system and the volume of the box compartment has decreased to accommodate the new volume of the subject."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3400", "contents": "With cabinless plethysmography, the patient is seated next to a desktop testing device and inserts the mouthpiece into their mouth. The patient takes a series of normal tidal breaths for approximately one minute. During this tidal breathing, a series of rapid interruptions occurs, with a shutter opening and closing, measuring pressure and volume. [ 3 ]  Lung volume measurements taken with cabinless plethysmography are considered equivalent to body plethysmography. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3401", "contents": "Boyle's law  is used to calculate the unknown volume within the lungs.  First, the change in volume of the chest is computed.  The initial pressure of the box times its volume is considered equal to the known pressure after expansion times the unknown new volume.  Once the new volume is found, the original volume minus the new volume is the change in volume in the box and also the change in volume in the chest.  With this information, Boyle's law is used again to determine the original volume of gas in the chest: the initial volume (unknown) times the initial pressure is equal to the final volume times the final pressure. Starting from this principle, it can be shown [ 5 ]  that the functional residual capacity is a function of the changes in volume and pressures as follows:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3402", "contents": "F \n R \n C \n = \n \n K \n \n V \n \n \n \n \n \n \u0394 \n \n V \n \n b \n o \n x \n \n \n \n \n \u0394 \n \n P \n \n m \n o \n u \n t \n h \n \n \n \n \n \n , \n \n K \n \n V \n \n \n \u2248 \n \n P \n \n B \n a \n r \n o \n m \n e \n t \n r \n i \n c \n \n \n \n \n {\\displaystyle FRC=K_{V}{\\frac {\\Delta V_{box}}{\\Delta P_{mouth}}},K_{V}\\approx P_{Barometric}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3403", "contents": "The difference between full and empty lungs can be used to assess diseases and airway passage restrictions.  An obstructive disease will show increased FRC because some airways do not empty normally, while a restrictive disease will show decreased FRC.  Body plethysmography is particularly appropriate for patients who have air spaces which do not  communicate with the bronchial tree; in such patients  helium dilution  would give an incorrectly low reading."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3404", "contents": "Another important parameter, which can be calculated with a body plethysmograph is the airway resistance. During inhalation the chest expands, which increases the pressure within the box. While observing the so-called resistance loop (cabin pressure and flow), diseases can easily be recognized. If the resistance loop becomes planar, this shows a bad  compliance  of the lung. A  COPD , for instance, can easily be discovered because of the unique shape of the corresponding resistance loop. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3405", "contents": "Some plethysmograph devices are attached to  arms ,  legs  or other extremities and used to determine circulatory capacity.\nIn water plethysmography an extremity, e.g. an arm, is enclosed in a water-filled chamber where volume changes can be detected. Air plethysmography uses a similar principle but based on an air-filled long cuff, which is more convenient but less accurate.\nAnother practical device is mercury-filled strain gauges used to continuously measure circumference of the extremity, e.g. at mid calf.\n Impedance plethysmography  is a non-invasive method used to detect  venous thrombosis  in these areas of the body."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3406", "contents": "Another common type of plethysmograph is the  penile plethysmograph . This device is used to measure changes in blood flow in the  penis . Although some researchers use this device to assess  sexual arousal  and  sexual orientation , courts that have considered penile plethysmography generally rule that the technique is not sufficiently reliable for use in court. [ 6 ]  An approximate female equivalent to penile plethysmography is  vaginal photoplethysmography , which optically measures blood flow in the vagina. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3407", "contents": "Plethysmography is a widely used method in basic and  preclinical research  to study respiration. Several techniques are used:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3408", "contents": "Whole-body plethysmography is used to measure respiratory parameters in conscious unrestrained subjects, including quantification of  bronchoconstriction ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3409", "contents": "The standard plethysmograph sizes are for the study of mice, rats and guinea pigs. On request, larger plethysmographs can also be manufactured for other animals, such as rabbits, dogs, pigs, or primates."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3410", "contents": "The plethysmograph has two chambers, each fitted with a  pneumotachograph . The subject is placed in one of them (subject chamber) and the other remains empty (reference chamber)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3411", "contents": "The pressure change is measured by a differential pressure transducer with one port exposed to the subject chamber and the other to the reference chamber. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3412", "contents": "The double-chamber plethysmograph (dcp) measures respiratory parameters in a conscious restrained subject, including  airway resistance  and conductance. Different sizes of plethysmograph exist to study mice, rats or guinea pigs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3413", "contents": "The head-out configuration is identical to the standard configuration described above except that there is no head chamber."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3414", "contents": "Of course the collar seal [ further explanation needed ]  is still applied, so that the body chamber remains airtight. With only a thoracic signal, all parameters can be obtained except for specific airway resistance (SRaw) and specific airway conductance (Sgaw)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3415", "contents": "In anesthetized plethysmography, lung resistance and dynamic compliance are measured directly because the subject is anesthetized."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3416", "contents": "Depending on the level of sedation, the subject may be spontaneously breathing (SB configuration) or under mechanical ventilation (MV configuration).\nA flow signal and a pressure signal are required to calculate compliance and resistance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3417", "contents": "Cerebral venous blood flow has been recently studied trying to establish a connection between  Chronic cerebrospinal venous insufficiency  and  multiple sclerosis . The small study is not big enough to establish a conclusion, but some association has been shown. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3418", "contents": "A  spirometer  is an apparatus for measuring the  volume  of  air  inspired and expired by the  lungs . A spirometer measures ventilation, the movement of air into and out of the lungs. The spirogram will identify two different types of abnormal ventilation patterns, obstructive and restrictive. There are various types of spirometers that use a number of different methods for measurement (pressure transducers, ultrasonic, water gauge)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3419", "contents": "A spirometer is the main piece of equipment used for basic Pulmonary Function Tests (PFTs). Lung diseases such as  asthma ,  bronchitis , and  emphysema  may be ruled out from the tests. In addition, a spirometer often is used for finding the cause of shortness of breath, assessing the effect of contaminants on lung function, the effect of medication, and evaluating progress for disease treatment. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3420", "contents": "The earliest attempt to measure lung volume can be dated back to the period A.D. 129\u2013200.   Claudius Galen , a Roman physician and philosopher, did a volumetric experiment on human ventilation. He had a child breathe in and out of a bladder and found that the volume did not change. The experiment proved inconclusive."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3421", "contents": "Even with the numerical precision that a spirometer can provide, determining pulmonary function relies on differentiating the abnormal from the normal. Measurements of lung function can vary both within and among groups of people, individuals, and spirometer devices. Lung capacity, for instance, may vary temporally, increasing and then decreasing in one person's lifetime. As a result, ideas about what constitutes \"normal\" are based on one's understanding about the sources of variabilities and can be left to interpretation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3422", "contents": "Traditionally, sources of variation have been understood in discrete categories, such as age, height, weight, gender, geographical region (altitude), and race or ethnicity. Global efforts were made in the early twentieth century to standardize these sources to enable proper diagnosis and accurate evaluation of pulmonary function. However, rather than further aiming to understand the causes of such variations, the primary approach for dealing with observed differences in lung capacity has been to \"correct for\" them. Using results from comparative population studies, attributes are empirically factored together into a \"correction factor\". This number is then used to form a personalized 'reference value' that defines what is considered normal for one individual. Practitioners may thereby find the percent deviation from this predicted value, known as 'percent of predicted,\u2019 and determine whether someone\u2019s lung function is abnormally poor or excellent. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3423", "contents": "In particular, 'race correction' or 'ethnic adjustment' effectively has been computer-programmed into the modern-day spirometer. Preconceived notions that 'white' people have greater pulmonary function are embedded in spirometer measurement interpretation and have only been reinforced through this  medical stereotyping . In the United States, spirometers use correction factors of 10-15% for those identified as 'black' and 4-6% for those identified as 'Asian.' [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3424", "contents": "In 1960, the European Community for Coal and Steel (ECCS) first recommended guidelines for spirometry. [ 7 ]  The organization then published predicted values for parameters such as spirometric indices, residual volume, total lung capacity, and functional residual capacity in 1971. [ 8 ]  The American Thoracic Society/European Respiratory Society also recommends race-specific reference values when available. [ 9 ]  Even today, the National Institute for Occupational Safety and Health\u2019s Spirometry Training Guide that is linked to the Centers for Disease Control and Prevention\u2019s website notes the use of race correction and a race-specific reference value in step four of \"normal\" spirometry. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3425", "contents": "The use of reference values and discrete categorizations of sources of variability has been motivated by ideas of anthropometry and vital capacity. Studies have looked specifically at the relationship between anthropometric variables and lung function parameters. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3426", "contents": "The use of reference values has thus far not accounted for the social labelling of race and ethnicity. Often, determinations are subjective or silently ascribed by a practitioner. Another concern of using reference values is misdiagnosis. [ 12 ]  This was an important factor in the management and control of compensation for miners in Britain in the interwar period. In this politically loaded context, in which new X-ray technology could not be fully trusted, the spirometer represented secure evidence of respiratory disease in numerical terms that could be used in the complex compensation network. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3427", "contents": "Evaluation of vital capacity has influenced other sectors of life other than medicine as well, including evaluation of life insurance applicants and diagnosis of tuberculosis. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3428", "contents": "Regarding gender, some population studies have indicated no difference based on gender. [ 11 ]  Notably, spirometers have been used to evaluate vital capacity in India since 1929, recording a statistically significant difference between males (21.8 mL/cm) and females (18 mL/cm). [ 14 ]  Additionally, by 1990, around half of pulmonary training programs in both the United States and Canada adjusted for race and ethnicity. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3429", "contents": "The spirometer popularized notions of 'race corrections' and 'ethnic adjustments,' which suggested that black individuals have weaker lungs than white individuals. For example, Thomas Jefferson noted physical distinctions between different races such as a 'difference in the structure of the pulmonary apparatus,' which made black individuals 'more tolerant of heat and less so of cold, than the whites.' [ 16 ]  Jefferson's theories encouraged speculation on the natural conditioning of blacks for agricultural labor on southern plantations in the U.S. [ 17 ]  Samuel Cartwright, a slavery apologist and plantation owner, used the spirometer to make the claim that black people consumed less oxygen than white people [ 18 ]  in addition to racial 'peculiarities' he laid out in the  New Orleans Medical and Surgical Journal  that described racial differences in the respiratory system and the implication of them on labor. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3430", "contents": "South African studies also used the spirometer to address racial and class differences. Eustace H. Cluver conducted vital capacity measurement research at the University of Witwatersrand [ 20 ]  and found that poor white people had physical unfitness but that it was attributable to environmental issues rather than genetics. Using these studies, Cluver argued to the South African Association for the Advancement of Science during World War Two that improving both nutrition and physical training programs could help produce wealth and win the war by increasing the working capacity of individuals across all races as their labor was necessary to achieve these ends. [ 21 ]  Racism and the spirometer intersected again in these studies when further research was conducted on the effects of physical training on poor white recruits; vital capacity studies showed that 'the poor-white is biologically sound and can be turned into a valuable citizen' [ 22 ]  but no comment was made on the outcome of black South Africans."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3431", "contents": "Beyond the United States and South Africa, the spirometer was used in racial studies in India in the 1920s. Researchers found that the vital capacity of Indians was smaller than that of Westerners. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3432", "contents": "Many have questioned whether the current standards are sufficient and accurate. [ 24 ] [ 25 ]  As a multiethnic society develops, racial and ethnic origin as a factor becomes more and more problematic to utilize. [ 26 ]  Ideas connecting ethnicity to lack of nutrition and birthplace in a poor country become invalid as people immigrate to or may be born in richer nations. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3433", "contents": "This type of spirometer gives a more accurate measurement for the components of lung volumes as compared to other conventional spirometers. A person is enclosed in a small space when the measurement is taken."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3434", "contents": "This spirometer measures the flow rate of gases by detecting pressure differences across fine mesh. One advantage of this spirometer is that the subject can breathe fresh air during the experiment. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3435", "contents": "Electronic spirometers have been developed that compute airflow rates in a channel without the need for fine meshes or moving parts. They operate by measuring the speed of the airflow with techniques such as ultrasonic transducers, or by measuring pressure difference in the channel. These spirometers have greater accuracy by eliminating the momentum and resistance errors associated with moving parts such as windmills or flow valves for flow measurement. They also allow improved hygiene by allowing fully disposable air flow channels."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3436", "contents": "This spirometer is specially designed to encourage improvement of one's lung function."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3437", "contents": "This device is useful for measuring how well a person's lungs expel air."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3438", "contents": "This type of spirometer is used especially for measuring  forced vital capacity  without using water; it has broad measurements ranging from 1000 ml to 7000 ml. It is more portable and lighter than traditional water-tank type spirometers. This spirometer should be held horizontally while taking measurements because of the presence of a rotating disc."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3439", "contents": "This instrument is used to measure vital capacity. It has a double walled metallic cylindrical chamber filled with water between two cylinders. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3440", "contents": "The  venturi mask , also known as an  air-entrainment mask , is a  medical device  to deliver a known  oxygen  concentration to patients on controlled  oxygen therapy . [ 1 ] [ 2 ]  The mask was invented by  Moran Campbell  at  McMaster University Medical School  as a replacement for intermittent oxygen treatment. Dr. Campbell was fond of quoting  John Scott Haldane 's description of intermittent oxygen treatment; \"bringing a drowning man to the surface \u2013 occasionally\". [ 3 ] [ 4 ]  By contrast the venturi mask offered a constant supply of oxygen at a much more precise range of concentrations."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3441", "contents": "Venturi masks are used to deliver a specified  fraction of inspired oxygen ( F I O 2 ) . Many masks are color-coded and have a recommended oxygen flow specified on them. [ 5 ]  When used with this oxygen flow, the mask should provide the specified  F I O 2 . Other brands of mask have a rotating attachment that controls the air  entrainment  window, affecting the concentration of oxygen. This system is often used with air-entrainment nebulizers to provide humidification and oxygen therapy. The total flow of gas (oxygen plus the entrained air) will be greater than the patient's peak inspiratory flow so the delivered  F I O 2  is independent of their respiratory pattern. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3442", "contents": "A controlled  F I O 2  is particularly important for patients whose ventilation is dependent on  hypoxic drive , [ 5 ]  as may be seen in patients with  chronic obstructive pulmonary disease . Administration of too much oxygen may lead to a reduction in their  respiratory rate  and  retention of carbon dioxide , and ultimately to reduced consciousness or even death. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3443", "contents": "The mechanism of action is variously described with reference to the  venturi effect  or  Bernoulli's principle . [ 7 ]  However, a fixed performance oxygen delivery system works on the principle of  jet mixing . Where the flow of moving oxygen meets the static air, viscous shearing causes a predictable amount of the air to be dragged into the flow. [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3444", "contents": "The  American Association for Respiratory Care  ( AARC ) is a  non profit organization  and is the only professional organization supporting  Respiratory Care  in the United States. In addition to attempting to help lobby for beneficial legislation nationally and locally, the AARC is trying to promote the profession as a whole to increase interest and membership. [ 1 ]  The AARC began in 1943, as the  Inhalation Technician Association  and has evolved rapidly and repeatedly since. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3445", "contents": "\"The American Association for Respiratory Care (AARC) will continue to be the leading national and international professional association for respiratory care. The AARC will encourage and promote professional excellence, advance the science and practice of respiratory care, and serve as an advocate for patients, their families, the public, the profession and the respiratory therapist.\" [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3446", "contents": "The AAIT began publishing a journal called  Inhalation Therapy  in 1956."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3447", "contents": "The University of Chicago Hospital forms the Inhalation Therapy Association (ITA) in 1946 and in 1947 the ITA is chartered as a non-profit entity in the state of Illinois.\nThe ITA was renamed American Association of Inhalation Therapists (AAIT) in 1954, and changed its name again in 1966 to  American Association of Inhalation Therapy (still AAIT).\nThe AAIT was renamed the American Association of Respiratory Therapy (AART) in 1973 and finally took the current name of American Association of Respiratory Care in 1986."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3448", "contents": "The AARC has several organizations with which they have an affiliation; [ clarification needed ]  some of these include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3449", "contents": "The  American College of Chest Physicians  ( CHEST ) is a medical association in the United States consisting of  physicians  and non-physician specialists in the field of chest medicine, which includes  pulmonology ,  critical care medicine , and  sleep medicine .  The group was founded in 1935. [ 1 ]  It has a membership of over 19,000. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3450", "contents": "The  American Lung Association  is a voluntary health organization whose mission is to save lives by improving lung health and preventing lung disease through education, advocacy and research. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3451", "contents": "The organization was founded in 1904 to fight  tuberculosis  (TB) as the National Association for the Study and Prevention of Tuberculosis (NASPT) by  Edward Livingston Trudeau , [ 2 ]  Robert Hall Babcock, Henry Martyn Hall,  Lawrence Flick , and  S. Adolphus Knopf . Earlier in 1892, Flick had founded the Pennsylvania Society for the Prevention of Tuberculosis, the world's first society dedicated to the preventing TB. In 1907, the Lung Association began their  Christmas Seal  campaign to raise money for a small TB sanatorium in Delaware.  Emily Bissell , a Red Cross volunteer at the time, created holiday seals to sell at the post office for a penny a piece. By the end of her fundraising campaign, she had raised more than ten times the amount needed to save the sanatorium, and the tradition of Christmas Seals was launched. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3452", "contents": "The NASPT was renamed the National Tuberculosis Association (NTA) in 1918, and then the National Tuberculosis and Respiratory Disease Association (NTRDA) in 1968; it adopted its current name in 1973. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3453", "contents": "The association is a defender of the  Clean Air Act . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3454", "contents": "In October 2018, the association launched its school-based initiative, \"Yoga Power\", a program designed to increase awareness of the importance of lung health, at Woodward Elementary School in Delaware, Ohio. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3455", "contents": "A modified version of the  Cross of Lorraine  serves as the Lung Association's logo. [ 7 ]  The Paris, France, physician Gilbert Sersiron suggested its use in 1902 as a symbol for the \"crusade\" against tuberculosis. The double barred cross was originally used in the coat of arms of  Godfrey of Bouillon , Duke of Lower Lorraine, a leader of the first crusade and elected ruler of Jerusalem after its capture in 1099. [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3456", "contents": "The national tagline \"Fighting for Air\" was introduced in 2010 to emphasize the organization's role in reducing particulate pollution in the atmosphere and in public places. [ 10 ]  While the Cross of Lorraine was colored red since its adoption, it was changed to blue in 2021. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3457", "contents": "The American Lung Association is a public health organization funded by contributions from individual donors, corporations, foundations and government agency grants. One of its best-known  fundraising  campaigns is its  Christmas Seals  program, which has been an annual fundraising and public awareness tool for tuberculosis and  lung disease  since 1907."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3458", "contents": "The  Lake Tour Bike Trek  is an annual bicycle ride held at  Illinois  in early June with all donations going towards the American Lung Association of Illinois. [ 11 ]  The  Trek Across Maine , a similar bicycle ride in Maine, has raised more than $24 million since 1985. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3459", "contents": "The National Association for the Study and Prevention of Tuberculosis held their ninth annual meeting in Washington, D.C., May 8 and 9, 1913. In attendance were Association President Homer Folks, Honorary Vice President  Theodore Roosevelt , Vice Presidents Robert Hall Babcock,  Sir William Osler  and  Edward R. Baldwin , Treasurer William H. Baldwin, Secretary  Henry Barton Jacobs . Notable life members included  Andrew Carnegie ,  Henry C. Frick , Mrs. H. Knickerbocker,  Louis Marshall , Francis E. May,  Cyrus H. McCormick ,  Henry Phipps ,  John D. Rockefeller ,  Rodman Wanamaker ,  Felix M. Warburg . The association members recommended a public health committee be formed by The National Association for the Study and Prevention of Tuberculosis and be officially sanctioned by the  United States House of Representatives . In addition, they adopted the double red cross emblem formally as the symbol for the association and its fight against  tuberculosis . The National Association for the Study and Prevention of Tuberculosis executive offices were located at 105 East 22nd Street, New York, New York. [ 13 ] \nHenry Martyn Hall of  Pittsburgh, Pennsylvania , is one of the ten original founders and was honored at the 50th Anniversary Annual Meeting of the National Tuberculosis Association at  Atlantic City, New Jersey , in 1954. [ 14 ]   U.S. President   Grover Cleveland  was an honorary vice president from 1905 to 1908; U.S. President  Theodore Roosevelt  was an honorary vice president from 1905 to 1919. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3460", "contents": "The  American Respiratory Care Foundation  is a non-profit organization founded by the  American Association for Respiratory Care [ 1 ]  formed to provide funding for research in the field of  pulmonology  and  respiratory care . [ 2 ]   Formed in 1974 as the American Respiratory Therapy Foundation and then changed to the American Respiratory Care Foundation in 1986. [ 3 ]   The ARCF is a partner with the United States  Environmental Protection Agency , who has awarded grants to the ARCF in order to help fund research directly related to  asthma  and asthma education. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3461", "contents": "The International Fellowship Program was established in 1990 as a method of expanding  respiratory care  practices internationally by inviting physicians and nurses among other health professionals  to shadow  respiratory therapists  to observe the practice and application in medicine. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3462", "contents": "The  American Thoracic Society  ( ATS ) is a  nonprofit organization  focused on improving care for  pulmonary diseases , critical illnesses and  sleep-related breathing disorders . It was established in 1905 as the"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3463", "contents": "American Sanatorium Association , and changed its name in 1938 to the  American Trudeau Society . In 1960, it changed its name again to the American Thoracic Society.  Originally the medical section of the  American Lung Association , the Society became independently incorporated in 2000 as a 501 (c) (3) organization."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3464", "contents": "Pulmonology ,  critical care ,  sleep medicine ,  infectious disease ,  pediatrics ,  allergy / immunology ,  thoracic surgery ,  behavioral science ,  environmental  and  occupational medicine ,  physiology ,  molecular biology , among others. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3465", "contents": "More than 15,000 physicians, research scientists, and nurses and other allied healthcare professionals (32 percent of whom work outside  the United States ). [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3466", "contents": "The interests of members are represented by the Society's 14 specialty-specific assemblies and 2 sections. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3467", "contents": "With the overarching goal of advancing the Society's mission, each chapter represents a state or other geographical area and includes, in its membership ATS members. [ 4 ]  The ATS also works to engage its members around the globe."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3468", "contents": "4 peer-reviewed journals:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3469", "contents": "The Society offers  Continuing medical education  credits and nursing contact hours through its annual international conference."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3470", "contents": "The ATS advocates for improved respiratory health for patients in the United States and around the globe. The Society is actively involved securing funds for basic and clinical research, establishing global  tuberculosis  and  tobacco control  policies, enforcing the  Clean Air Act , and lobbying for fair reimbursement for physician services under  Medicare  and other insurers. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3471", "contents": "The ATS Patient Information Series is available electronically on the ATS website."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3472", "contents": "Asociaci\u00f3n Argentina de Medicina Respiratoria , the \"Argentina Association for Respiratory Medicine\"  ( AAMR ) was formed in 1999 and is the professional association for  Pulmonologists  and  respiratory therapists  in  Argentina .  Working with the American Journal of Medicine and the  American Association for Respiratory Care , the AAMR promotes and credentials respiratory clinicians of all types in Argentina. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3473", "contents": "Associazione Italiana Pneumologi Ospedalieri  is the professional organization for accreditation of  pulmonology  ( pneumology ) from  pulmonologists  to  respiratory therapists  in  Italy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3474", "contents": "[ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3475", "contents": "Associazione Scientifica Interdisciplinare per lo Studio delle Malattie Respiratorie  is the premiere  thoracic  society of  Italy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3476", "contents": "This article about an organisation based in Italy is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3477", "contents": "This article about a medical organization or association is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3478", "contents": "Breathing Games  is an  open access  health  commons  that aims to promote respiratory health through  games for health  and  open source hardware  released under  copyleft  licences. [ 1 ] [ 2 ]  Breathing Games leads collaborations with hospitals and universities in Canada, France, [ 3 ]  Switzerland, Italy and South Korea, and is a member of the Global Alliance against chronic Respiratory Diseases. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3479", "contents": "The commons builds on  open collaboration  and  peer production [ 5 ] [ 6 ]  to design and develop education and treatment games and hardware for asthma, [ 7 ]  cystic fibrosis, [ 8 ] [ 9 ]  and  COPD . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3480", "contents": "In 2020, Breathing Games organized a joint event between the Geneva Health Forum and Open Geneva to promote open-source health technologies. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3481", "contents": "Breathing Games is presented through its collaboration with the peer to peer network Sensorica in the documentary A new Economy, directed by Trevor Meier. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3482", "contents": "In March 2019, the Swiss Television reports on an event organized by Breathing Games during the OpenGeneva festival. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3483", "contents": "Breathing Games is funded by public research funds (Canadian Institutes of Health Research, [ 14 ]  French Hospitals Federation \u2013 Fonds FHF, [ 15 ]  European Union OpenCare [ 16 ] ) and by a private foundation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3484", "contents": "In 2019, Breathing Games was a Citypreneurs finalist, a contest hosted by the City of Seoul and United Nations agencies to find solutions to the global goals. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3485", "contents": "The  British Thoracic  [ a ]  Society  ( BTS ) was formed in 1982 by the amalgamation of the British Thoracic Association and the Thoracic Society. [ 1 ]  It is a  registered charity  and a  company limited by guarantee . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3486", "contents": "The Society's main charitable objective is to improve the care of people with  respiratory  disorders, which it aims to achieve by:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3487", "contents": "BTS is a  membership organisation , with over 4,000 members from the respiratory health sector (as of December\u00a02022 [update] ). These include  doctors ,  nurses ,  physiotherapists , pharmacists, speech and language therapists, scientists and other professionals with an interest in respiratory disease. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3488", "contents": "The Society also works in partnership with a range of organisations to achieve its objectives. These partners include other respiratory health professional groups, organisations representing patients and carers, medical and surgical  Royal Colleges  and other specialist societies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3489", "contents": "BTS holds two annual conferences; the Summer Meeting in the last week of June and the Winter Meeting which takes place at the  Queen Elizabeth II Conference Centre  in  London  at the end of November. These Meetings bring together medical professionals with an interest in respiratory medicine."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3490", "contents": "The Summer Meeting has a main focus on education and training, with clinical updates and the opportunity for a multi-disciplinary audience to discuss key issues and share good practice."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3491", "contents": "The BTS Winter Meeting attracts over 2000 delegates each year and is the UK's primary respiratory scientific meeting, with the emphasis on presenting updates on current respiratory research and  symposia  from leading researchers from all over the world. Young Investigators and Medical Students are encouraged to put forward abstracts and prizes are awarded in each category."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3492", "contents": "There is also a wide-ranging programme of  short courses , many of which are now available to complete online."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3493", "contents": "The  Canadian Board for Respiratory Care  ( CBRC ) was founded in 1989 as a non-profit organization which produces examinations for credentialing for practicing  respiratory care . [ 1 ]   The Board also has collaborated with other organizations on matters related to respiratory therapy education.  [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3494", "contents": "The  Canadian Society of Respiratory Therapists  ( CSRT ), known in French as la Soci\u00e9t\u00e9 canadienne des th\u00e9rapeutes respiratoires, is the national  professional association  for  respiratory therapists  in Canada. With a vision of empowering respiratory therapists to provide exemplary leadership and care, the CSRT focuses on providing respiratory therapists with a voice at the national, provincial and local levels; a professional community for respiratory therapists to collaborate and learn; the tools and resources to deliver evidence-informed care and on providing excellent service to members. [ 1 ]  It represents respiratory therapists and publicly promotes the profession to the federal, provincial/territorial governments and decision-makers. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3495", "contents": "The CSRT is the credentialing body for respiratory therapists working in non-regulated jurisdictions in Canada, conferring the Registered Respiratory Therapist credential. [ 3 ]  It also confers the national Certified Clinical Anesthesia Assistant designation. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3496", "contents": "The CSRT is the publisher of the open-access journal the  Canadian Journal of Respiratory Therapy . This journal is indexed in PMC (Pubmed Central), Scopus/Embase, Google Scholar, CINAHL, and the Directory of Open Access Journals. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3497", "contents": "The CSRT publishes position statements  on topics of importance to cardiorespiratory health and the profession."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3498", "contents": "The CSRT hosts the annual national conference  for respiratory therapists in Canada. This large annual gathering of respiratory therapists and other professionals involved in respiratory care from across Canada and internationally offers a variety of educational presentations, networking and social events, interactions with vendors, and opportunities for its communities of practice to meet and innovate. \nThe CSRT proclaims the last week in October as Respiratory Therapy Week, a week to celebrate and promote the profession."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3499", "contents": "The CSRT is a recipient of the Canadian Society of Association Executives Excellence Award (2019) for its innovative and efficient infrastructure renewal project. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3500", "contents": "This article about an organization in Canada is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3501", "contents": "Canadian Thoracic Society  ( CTS ) is a national not-for-profit medical association representing researchers and healthcare professionals in the field of  respirology . [ 1 ]  It was established when the Canadian Tuberculosis Association, now The Lung Association, recognized the need for a medical association as evidenced by the increase in attendance of both medical and non-medical members at the annual meetings."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3502", "contents": "In September 2021, CTS called for legislation to require healthcare workers to receive a  COVID-19 vaccine  as a condition of continued employment. [ 2 ]  The position paper published by CTS urged \"all levels of government\" across Canada to mandate full vaccination, stating it was the most effective way to prevent against serious illness and death from  COVID-19 . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3503", "contents": "CTS publishes  clinical practice guidelines  (CPG) for care of various respiratory conditions including  asthma  and  chronic obstructive pulmonary disease  (COPD). [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3504", "contents": "CTS is led by a board of directors and executive committee. Leadership for the 2022-2023 fiscal year include: [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3505", "contents": "The  College and Association of Respiratory Therapists of Alberta  is a corporation with delegated provincial government authority to regulate the profession of respiratory therapy pursuant with the Health Professions Act and the Respiratory Therapists Profession Regulation. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3506", "contents": "The  European Respiratory Society , or  ERS , is a  non-profit organization  with offices in Lausanne, Brussels and Sheffield. It was founded in 1990 in the field of  respiratory medicine . The organization was formed with the merger of the  Societas Europaea Physiologiae Clinicae Respoiratoriae  (founded in 1966) and the  European Society of Pneumology  (founded 1981). The organization's membership is made up of medical professionals and scientists working in the area of respiratory medicine. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3507", "contents": "ERS founded the  European Lung Foundation  (ELF) in 2000. [ 2 ]  The foundation aims to bring together patients and the public with respiratory professionals to positively influence lung health."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3508", "contents": "The ERS publishes academic journals and books as well as hosting events aimed at educating health professionals, including a large annual congress. The organization's stated goal is to \"promote lung health in order to alleviate suffering from disease and drive standards for respiratory medicine globally\". [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3509", "contents": "The ERS publishes a range of  journals , books and one-off projects."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3510", "contents": "In addition to these publications, the ERS previously published two editions the  European Lung White Book  - a survey of the impact of respiratory disease across Europe, and has published the one-off booklets Air Quality and Health and the European Respiratory Roadmap as well as the European COPD Audit Report and reports on global respiratory health, published on behalf of the  Forum of International Respiratory Societies ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3511", "contents": "The  European Sleep Apnea Database  (ESADA) (also referred to with spelling  European Sleep Apnoea Database [ 1 ] [ 2 ]  and  European Sleep Apnoea Cohort [ 3 ] [ 4 ] ) is a collaboration between European sleep centres as part of the  European Cooperation in Science and Technology  (COST) Action B 26. The main contractor of the project is the  Sahlgrenska Academy  at  Gothenburg University , Institute of Medicine, Department of Internal Medicine, and the co-ordinator is  Jan Hedner , MD,  PhD , Professor of Sleep Medicine. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3512", "contents": "The book  Clinical Genomics: Practical Applications for Adult Patient Care  said ESADA was an example initiatives which afford an \"excellent opportunity\" for future collaborative research into  genetic  aspects of  obstructive sleep apnea syndrome  (OSAS). [ 1 ]  Both the  European Respiratory Society  and the European Sleep Research Society have noted the impact for research cooperative efforts of the database resource. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3513", "contents": "In 2006 the European Sleep Apnea Database (ESADA) began as an initiative between 27 European sleep study facilities to combine information and compile it into one shared resource. [ 5 ] [ 6 ]  It was formed as part of the  European Cooperation in Science and Technology  (COST) Action B 26. [ 2 ] [ 7 ]  In addition to financial help from COST, the initiative received assistance from companies  Philips Respironics  and  ResMed . [ 8 ]  The database storing the association's resource information is located in  Gothenburg ,  Sweden . [ 8 ]  The group's goal was twofold: to serve as a reference guide to those researching sleep disorders, and to compile information about how different caregivers treat patients with sleep apnea. [ 2 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3514", "contents": "5,103 patients were tracked from March 2007 to August 2009. [ 7 ]  Data collected on these patients included symptoms experienced, medication, medical history, and sleep data, all inputted into an online format for further analysis. [ 7 ]  Database researchers reported on their methodology and results in 2010 to the  American Thoracic Society , on their observed findings regarding percentages of metabolic and cardiovascular changes related to patients with obstructive sleep apnea. [ 9 ]  The 2010 research resulted from collaboration between 22 study centres across 16 countries in Europe involving 27 researchers. [ 9 ]  The primary participants who presented to the American Thoracic Society included researchers from:  Sahlgrenska University Hospital ,  Gothenburg ,  Sweden ;  Technion \u2013 Israel Institute of Technology ,  Haifa ,  Israel ; National TB & Lung Diseases Research Institute,  Warsaw ,  Poland ; CNR Institute of Biomedicine and Molecular,  Palermo ,  Italy ; Instituto Auxologico Italiano, Ospedale San Luca,  Milan ,  Italy ; and St. Vincent University Hospital,  Dublin ,  Ireland . [ 9 ]  Their analysis was published in 2010 in the  American Journal of Respiratory and Critical Care Medicine . [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3515", "contents": "In 2011 there were 22 sleep disorder centres in  Europe  involved in the collaboration. [ 2 ] [ 7 ]  The group published research in 2011 analyzing the percentage of patients with sleep apnea that have  obesity . [ 7 ]  By 2012 the database maintained information on over 12,500 patients in Europe; it also contained  DNA samples  of 2,600 individuals. [ 8 ]  ESADA was represented in 2012 at the 21st annual meeting of the European Sleep Research Society in  Paris ,  France , and was one of four European Sleep Research Networks that held a session at the event. [ 10 ]  Pierre Escourrou and Fadia Jilwan wrote a 2012 article for the  European Respiratory Journal  after studying data from ESADA involving 8,228 total patients from 23 different facilities. [ 11 ]  They analyzed whether  polysomnography  was a good measure for  hypopnea  and sleep apnea. [ 11 ]  Researchers from the department of  pulmonary diseases  at  Turku University Hospital  in  Turku ,  Finland  compared variations between sleep centres in the ESADA database and published their findings in the  European Respiratory Journal . [ 12 ]  They looked at the traits of 5,103 patients from 22 centres. [ 12 ]  They reported on the average age of patients in the database, and the prevalence by region of performing sleep study with cardiorespiratory polygraphy. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3516", "contents": "The database added a centre in  Hamburg, Germany  in 2013 managed by  physician  Holger Hein. [ 6 ]  The group's annual meeting in 2013 was held in  Edinburgh ,  United Kingdom  and was run by Renata Riha. [ 6 ]  By March 2013, there were approximately 13,000 total patients being studied in the program, with about 200 additional patients being added into the database each month. [ 5 ]  Analysis published by researchers from Italy and Sweden in September 2013 in the  European Respiratory Journal  analyzed if there was a correlation between  renal function  problems and obstructive sleep apnea. [ 13 ]  They analyzed data from 17 countries in Europe representing 24 sleep centres and 8,112 total patients. [ 13 ]  They tested whether patients of different types of demographics with other existing health problems had a change in probability of kidney function problems, if they concurrently had obstructive sleep apnea. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3517", "contents": "In 2014, researchers released data studying 5,294 patients from the database compared prevalence of sleep apnea with increased  blood sugar . [ 14 ]  Their results were published in the  European Respiratory Journal . [ 3 ] [ 4 ]  They studied  glycated hemoglobin  levels in the patients and compared them with measured severity in sleep apnea. [ 15 ]  The researchers analyzed glycated hemoglobin levels among a class of individuals with less severe sleep apnea and those with a higher determined amount of sleep apnea problems. [ 14 ]  As of 20 March 2014 the database included information on a total of 15,956 patients. [ 6 ]  A 2014 article in the  European Respiratory Journal  drawing from the ESADA analyzed whether lack of adequate oxygen during a night's sleep was an indicator for  high blood pressure . [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3518", "contents": "In the 2013 book  Clinical Genomics: Practical Applications for Adult Patient Care , ESADA is said to be an example of the kind of initiative which affords an \"excellent opportunity\" for future collaborative research into  genetic  aspects of  obstructive sleep apnea syndrome  (OSAS). [ 1 ]  Both the  European Respiratory Society  and the European Sleep Research Society have noted the impact for research cooperative efforts of the database resource. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3519", "contents": "The  Extracorporeal Life Support Organization  ( ELSO ) is a  non profit organization  established in 1989 supporting health care professionals and scientists who are involved in  extracorporeal membrane oxygenation  (ECMO). [ 1 ]   ELSO maintains a registry of both facilities and specialists trained to provide ECMO services.  ELSO also maintains registry information that is used to support clinical research, support regulatory agencies, and support individual ELSO centers.  ELSO provides educational programs for active centers as well as for facilities who may be involved in the transfer of patients to higher levels of care. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3520", "contents": "In addition to the North American-based ELSO organization, chapters have been developed to represent the regional needs of ELSO in the rest of the world.  Current chapters [ 3 ]  include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3521", "contents": "Since 1989, ELSO has maintained a registry of clinical characteristics and outcomes of patients supported with ECMO.  A history of the ELSO registry has been published and demonstrates how it evolved over time from paper documentation, to a modern database with web based data entry. [ 8 ]   Data managers at each of the ELSO centers use detailed database definitions and a point-of-entry data warning system to minimize errors in data entry, as well as full record validation triggered upon submission of the record to ensure all mandatory fields are completed.  The ELSO registry has been instrumental in improving ECMO care, post-cardiac arrest management, pediatric  ventricular assist devices , and  organ transplantation . [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3522", "contents": "The last formally published ELSO Registry report was in 2017, and contained clinical characteristics, complications, and outcomes of 78,397 patients supported with ECMO. [ 10 ]   Demonstrating the rapid growth of ECMO, at the beginning of 2020, the ELSO Registry contained information on 129,037 patients from 435 member centers across the world. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3523", "contents": "With the onset of the COVID-19 pandemic, the ELSO registry began collecting data on the worldwide use of ECMO for patients with COVID-19 and reporting this data on the  ELSO website  in real time.  In September 2020, the outcomes of 1,035 COVID-19 patients supported with ECMO from 213 experienced centers in 36 different countries were published in  The Lancet , and demonstrated 38% mortality, which is similar to many other respiratory diseases treated with ECMO. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3524", "contents": "ELSO promulgates guidelines [ 13 ]  for the care of patients on ECMO.  They include overall guidelines about setting up a program, proper equipment, and patient care for certain medical conditions.  Additional education on ECMO topics is provided through ELSO published textbooks and training manuals for ECMO specialists. [ 14 ]   ELSO recognizes centers with exceptional programs, systems, processes, and outcomes with the Award for Excellence in Life Support. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3525", "contents": "ELSO provides position statements on:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3526", "contents": "The  Forum of International Respiratory Societies  is a respiratory health advocacy organization which consists of the following organizations: [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3527", "contents": "The Forum was established in 2002 [ 1 ]  and has more than 70,000 members worldwide. [ 2 ]  It is based in  Lausanne, Switzerland . [ 3 ] \nIn 2010, the Forum dubbed the year 2010 the \"Year of the Lung\". [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3528", "contents": "The  Deutsche Gesellschaft f\u00fcr Pneumologie und Beatmungsmedizin  ( DGP , \"German  Respiratory  Society\") is the largest and oldest medical professional organization for respiratory disorders in the German-speaking world and serves as a forum for all medical practitioners and scientists in the field of respiratory medicine. Almost 28% of the more than 3,000 members are women.  Pneumologie  has been the official journal of the German Respiratory Society since 1981."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3529", "contents": "The DGP seeks \"to promote the study, research and teaching, training and continuing education, prevention, care and rehabilitation in the field of respiratory medicine, including  intensive care medicine  with the focus on mechanical ventilatory support\". [ 1 ]  It promotes \"cooperation between medical and allied professional groups\" within the field, represents the interests of the field in the public domain and works closely with \"other bodies and professional associations\". [ 2 ]  The DGP's activities include organizing congresses for professionals in the field of respiratory medicine, issuing  guidelines  and statements and promoting young doctors and researchers as well as allied health professionals. Besides improving standards of  medical education  at the university level as well as of specialist postgraduate training, the society focuses on improving the standard of information and preventative measures in respect of all aspects of respiratory  health ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3530", "contents": "The annual congress of the DGP is its key event and is organized by a congress president elected for this purpose and a programme commission, who plan the congress in conjunction with the scientific sections of the DGP. In recent years, more than 3,000 people have attended the annual DGP congresses (record figure: 3,500 in 2011). Since 2009 e-posters and other presentations have been available online. [ 3 ]  Apart from presentations on specialized topics and the educational  postgraduate programme , the supplementary programme includes the so-called  Lung  Run."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3531", "contents": "The award ceremonies of two of the DGP\u2019s partner institutions take place during the annual congress. The  Deutsche Lungenstiftung e.V.  (\"German Lung Foundation\") awards prizes for a doctoral thesis and for secondary-school creativity as well as the Wilhelm and Ingeborg Roloff Prize for media reporting on respiratory health. The  Deutsche Atemwegsliga e.V.  (\"German Airway League\") awards a  research scholarship  in clinical respiratory medicine. [ 4 ]  In 2009 the DGP introduced two annual research prizes, one for basic  scientific research  and one for  clinical research , each worth \u20ac10,000, which are also awarded at the annual congress."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3532", "contents": "In compliance with the educational and  awareness-raising mission  laid down in its statutes, the Society promotes cooperation with professional and specialist organizations with similar objectives, including the  Deutsche Atemwegsliga e.V.  (DAL), the  Deutsche Lungenstiftung e.V.  (DLS), the  Deutsches Zentralkomitee zur Bek\u00e4mpfung der Tuberkulose e.V.  (DZK, \"German Central Committee against  Tuberculosis \") and the  Bundesverband der Pneumologen  (\"Federal Association of Pneumologists\"). [ 5 ]  The DGP is also the co-founder of initiatives such as the  Deutscher Lungentag  (\"German Lung Day\"), the  Institut f\u00fcr Lungenforschung  (ILF, \"Institute for Lung Research\") and the  Aktionsb\u00fcndnis Nichtrauchen e.V.  (ABNR, the \"Alliance for  Non-smoking \"). The DGP also successfully pushed for the creation of the  Deutsches Zentrum f\u00fcr Lungenforschung  (DZL, \"German Centre for Lung Research\"), an association initiated by the  Federal Ministry of Education and Research  (BMBF) that brings together scientists working in lung research in Germany inside and outside the universities. [ 6 ]  The DGP also organizes concerted actions to promote pulmonary research, strengthen the position of respiratory medicine in medical education and training and to  lobby politicians  and parties for e.g. the protection of non-smokers. The DGP maintains close relations with international organizations such as the  European Respiratory Society  (ERS), the Union Europ\u00e9enne des M\u00e9dicins Sp\u00e9cialistes (UEMS), the  American Lung Association , the  American Thoracic Society , the  American College of Chest Physicians , the  British Thoracic Society  and the  International Union against Tuberculosis and Lung Diseases . The DGP participates as an organization in projects of these bodies, and individual DGP members have fulfilled and continue to fulfil important functions, for instance the publication of the European Lung White Book of the ERS (2nd edition 2013) or the ERS HERMES programme (Harmonized Education in Respiratory Medicine for European Specialists)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3533", "contents": "Since its foundation, the DGP has focused on the development of pneumology as an independent medical speciality, including teaching medical students as well as specialist training and post-graduate education and training, as well as on the establishment of more autonomous respiratory medicine departments in university hospitals. To facilitate the start of young physicians interested in respiratory medicine, the DGP has established a forum, the working group for promoting junior doctors and researchers, as well as a training academy, the Respiratory Medicine Training Academy, that organizes its own educational and scientific programme and runs a dedicated website for young pneumology professionals. [ 7 ]  To ensure that Germany does not fall behind international developments in the specialty, the DGP proactively encourages greater emphasis on teaching of respiratory medicine to medical students and the creation of separate university professorships in pneumology. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3534", "contents": "The roots of the DGP go back to the  Vereinigung der Lungenheilanstalts\u00e4rzte  (\"Association of Tuberculosis  Sanatorium   Physicians \") founded by, among others, Ludolph Brauer (1865\u20131951) in 1910. In 1920 it formed a working alliance with the  Deutsche Gesellschaft der Tuberkulose\u00e4rzte  (\"German Society of Tuberculosis Physicians\"), and in 1925 the two organizations merged to form the  Deutsche Tuberkulose-Gesellschaft  (DTG \u2013 \"German Tuberculosis Society\"). At the beginning of the twentieth century tuberculosis was the second most common cause of death in Germany. Since the nineteenth century the disease had been a regular topic in  medical diagnostics  and  therapy . Factors such as the publicity given to tuberculosis at congresses of the German Society of  Internal Medicine  (DGIM), the discovery of the  bacillus  that caused tuberculosis ( Mycobacterium tuberculosis ) by  Robert Koch  in 1882, the popularization of the sanatorium movement in Germany by Peter Dettweiler from 1892 onwards and the foundation of the predecessor of the DZK (1895) were milestones in the fight against the disease. The key principle was not so much the promotion of specialized research activities as an interdisciplinary approach to \"gather together the knowledge of tuberculosis scattered and hidden in all the different disciplines\". [ 9 ] \nThe official celebration of the founding of the DTG took place in  Danzig  in 1925 on the occasion of a joint meeting of the coalition of the tuberculosis sanatorium physicians and the tuberculosis  public health  specialists under the chairmanship of Otto Ziegler (1879\u20131931), medical director of the Heidehaus Sanatorium.\nThe DPG explicitly made a point of working not only with physicians, but also with \"representatives of the  medical sciences  (in particular universities)\". [ 10 ]  It hoped that greater cooperation at both the medical level \u2013 a \"unanimous collaboration between care institutions, sanatoria and clinics\" [ 11 ]  \u2013 and at the level of political parties and organizations would send a clear message to the authorities and the general public. It also emphasized the significance of  phthisiology , the forerunner of  pneumology , as a separate medical speciality. Among the founders of the DTG were renowned tuberculosis specialists such as Ludolph Brauer, Otto Ziegler, Franz Redeker, Johannes Ritter, Oskar Pischinger and Ernst von Romberg and  surgeons  such as  Ferdinand Sauerbruch . Initially, activities focused on DTG meetings, the detailed minutes (\"proceedings\") of which appeared in  Beitr\u00e4ge zur Klinik der Tuberkulose  (\"Contributions to the Clinic for Tuberculosis\") published by Ludolph Brauer."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3535", "contents": "As managing director from 1925 to 1945, Julius E. Kayser-Petersen (1886\u20131954) not only played a central role in the DTG, but as secretary-general of the  Reichs-Tuberkulose-Ausschuss  (\"National Committee on Tuberculosis\") and other key positions influenced the tuberculosis policy of the  Nazi regime . Under Kayser-Petersen's leadership, membership of the DTG rose rapidly from 379 in 1925 to more than 1,000 in 1941. The DTG's main activity was organizing the congresses, at least up to 1941, when they were suspended due to the war.\nConference topics in this period included the inheritability of tuberculosis (TB), tuberculosis sufferers' \"suitability for work and marriage\" and the possibility of giving them a special status (\"compulsory detention\")."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3536", "contents": "The dangers of  smoking , which  Fritz Lickint  (1898\u20131960) convincingly proved in case studies in the 1920s, and the  anti-tobacco campaign of Nazi Germany , culminated in the recommendation of a complete  ban on smoking  in all tuberculosis sanatoria and clinics in 1939."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3537", "contents": "During the Nazi era, TB was no longer seen as a disease of the poor; it was suddenly considered a sign of a person's \" asocial \" nature. Nazi politicians had proclaimed that it was every German citizen's \"duty to be healthy\", and being ill became tantamount a \"dereliction of duty\" and a \"failure\". TB sufferers who were regarded as being \"incurable\" and \" recalcitrant \" were  stigmatised  as being \"asocial bacillus spreaders\" who had to be dealt with using \"compulsory measures\". The  Nazi ideology  saw them as being worthless to the \"Aryan German  people's community \"; they were socially neglected, sometimes systematically starved and even singled out to be murdered in euthanasia centres and  concentration camps . Doctors (among them GRS members) took part. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3538", "contents": "In 2018, the GRS published a book about the role of the GRS during the Nazi era. They also published an abridged version in English. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3539", "contents": "The DTG was dissolved in 1945, and congresses resumed only in 1947 after the Society was re-established under the chairmanship of Franz Ickert (1883\u20131954).\nRenewed rampant tuberculosis dominated the work of the DTG in the  postwar period . Despite different approaches, the  prevalence  of the disease followed a similar pattern in both German states. Whereas the  German Democratic Republic  (GDR) sought to combat tuberculosis through  statewide centralized preventive measures  ( BCG vaccination  and  serial X-ray screening ), the  Federal Republic of Germany  achieved dramatic results with the early use of new tuberculosis  antibiotics . [ 14 ]  As tuberculosis rates fell in both German states in the 1950s, sanatoria were gradually replaced by special chest hospitals that focused on diseases such as  lung cancer ,  asthma ,  chronic bronchitis  and  emphysema  (COPD),  interstitial lung disease  and general environmental and occupational lung diseases.\nThis evolution in developments is reflected in changes in the names of the two scientific respiratory societies in East and West Germany. Initially, the names contained only the term tuberculosis; lung disease was added in the early 1960s, and finally the terms \" respiratory diseases  and tuberculosis\" (1980 West) and \"bronchopulmonary diseases and tuberculosis\" (1976 East), respectively."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3540", "contents": "With the founding of the  Wissenschaftliche Tuberkulose-Gesellschaft in der Deutsche Demokratische Republik  (\"Scientific Tuberculosis Society in the German Democratic Republic\") in 1957, the DTG split into an East German and a West German organization, which were reunited in 1991. [ 15 ]  Although external factors such as standards of health care and opportunities for professional exchanges dictated different development paths, there were also parallels, e.g. the wider focus on other lung diseases ( pneumonia  and  pulmonary hypertension ) and new techniques in pulmonary function diagnostics and  endoscopy , improvements in graduate training for specialists (basic training in internal medicine, followed by training in respiratory medicine) and the introduction of specialist working groups and the development of guidelines and recommendations. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3541", "contents": "The DGP integrated medical advances in pulmonary function diagnostics,  bronchoscopy ,  oxygen long-term therapy  and  computer tomography  into its work, as did other forums such as the  Gesellschaft f\u00fcr Lungen- und Atemwegsforschung  (\"Society for Lung and  Airway  Research\"). From the mid-1970s the DGP's activities stagnated, as reflected in the drop in membership (lowest level 1984: 900). This changed only in the mid-1990s, following the merger of the two German societies to form the  Deutsche Gesellschaft f\u00fcr Pneumologie  (DGP, \"German Respiratory Society\") in 1991 and efforts initiated by a group of young pneumologists to reform the organization and structure of the DGP in 1992. [ 17 ]  Reforms included the introduction of scientific sections, the appointment of a congress president, the restructuring of the annual congress with plenary sessions, symposiums, hot-topic sessions and workshops and participation in  anti-smoking PR campaigns  of the  Deutsche Lungenstiftung  (\"German Lung Foundation\"), e.g. Be Smart Don\u2019t Start. The increase in the number of congress participants (see Annual congress above) and members testifies to the positive impact of these changes: In the past 20 years membership has almost tripled (1992: 1,117; 2002: 2,063; 2012: 3,093). [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3542", "contents": "The work of the honorary members of the board of directors and the full-time management has the support of a scientific advisory committee made up of representatives of the leading respiratory organizations in Germany and the scientific sections. The work of the 15 scientific sections and 9 working groups that focus on different aspects of respiratory medicine and on professional relationships is crucial for the DPG. In particular the scientific sections reflect the cross-links between respiratory medicine and other medical specialties, highlight key issues within the DGP and serve as forums for scientific exchange, joint research projects and initiatives on DGP policy. The sections, each of which is, as a rule, headed by two spokespersons, offer their members regular postgraduate educational programmes and draw up the guidelines approved and published by the DGP.\nThe following  sections  have been established since 1994:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3543", "contents": "Working group priorities  are: 1. graduate and postgraduate training and education in respiratory medicine, 2. the role of  quality assurance  and DRG in respiratory medicine, 3. spiroergometry, 4. women pneumologists, 5. tobacco prevention and cessation, 6.  palliative medicine , 7. promoting young doctors and scientists, 8.  respiratory therapists , 9.  telemedicine  in respiratory medicine."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3544", "contents": "Since 1980 the DGP, often in cooperation with other organizations (DAL, DZK), has drawn up more than 100 guidelines and recommendations, which are coordinated by a guidelines group formed especially for this purpose. Examples of cooperative projects include the so-called 2009 CAP guideline [ 19 ]  and the 2010 guideline  \"Pr\u00e4vention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms\"  (\"Prevention, diagnosis, therapy and follow-up of lung cancer\"). [ 20 ]  The  \"Leitlinie zur Diagnostik und Therapie der idiopathischen Lungenfibrose\"  (\"Guideline for diagnosis and management of idiopathic pulmonary fibrosis\") has also appeared in 2013. [ 21 ]  In addition to position papers and statements on current specific lung-related topics, the DGP publishes recommendations on e.g.  \"Infektionspr\u00e4vention bei Tuberkulose\"  (\"Tuberculosis infection control\", 2012) [ 22 ]  and  \"Belastungsuntersuchungen in der Pneumologie\"  (\"Exercise testing in respiratory medicine\", 2013). [ 23 ]  The DGP was also involved in the publication of the German \"Lung White Book\" in 1996; the fourth edition will appear in autumn 2013."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3545", "contents": "The  Irish Thoracic Society  ( ITS ) is the official society for professionals involved in the care of people with chronic or acute respiratory disease in  Ireland .  Membership of the Society is drawn from respiratory physicians, internal medicine physicians, pediatricians, thoracic surgeons, general practitioners, junior doctors, nurses, physiotherapists, pharmacists, dietitians, pulmonary function and  respiratory therapists , scientists and other healthcare providers who specialize or have an interest in respiratory disease and care throughout  Ireland  - North and South. [ 1 ] \nIt is self-governing and not affiliated with any regulatory body. It was established by a (then) junior doctor in 2008 and no demonstration/evidence of expertise is required for membership."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3546", "contents": "The  Kazakhstan National Respiratory Society  founded in 1985 works with the  Central-Asian Pulmonologists Association  and the  Euro-Asian Respiratory Society .  The society is maintained by the  Ministry of Health of the Republic of Kazakhstan ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3547", "contents": "This  health -related article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3548", "contents": "This article about an organization in Kazakhstan is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3549", "contents": "Lambda Beta Society  ( \u039b\u0392 ) is a national  honor society  sponsored and maintained by the  National Board for Respiratory Care  (NBRC). [ 1 ]   It is an honor society specifically recognizing undergraduate achievement in  Respiratory Care  related colleges.  Lambda Beta Society was formed in 1986 and has over 100 chapters in the United States as of 2011.  Membership requires the undergraduate student to be a student of respiratory care and be in the top 25 percentile of their class. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3550", "contents": "The name was chosen to represent sustaining \u201clife and breath\u201d.\nLambda (\u039b) is the Greek letter \u201cL\u201d, and beta (\u0392) is the Greek letter \u201cB\u201d. [ 3 ]  The society's colors are blue and green. Its motto is \"life and breath\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3551", "contents": "This article about a United States health organization is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3552", "contents": "A list of organizations for the advancement of respiratory care."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3553", "contents": "Lovelace Biomedical Research Institute  is a private  contract research organization  that is part of  Touro University  and  New York Medical College  (NYMC). It was founded after WWII in  Albuquerque, New Mexico  by two physicians, William Randolph Lovelace I and his nephew, surgeon  William Randolph Lovelace II . LRRI originally performed  not-for-profit   biomedical research  into the prevention, treatment and cure of  respiratory disease . The organization expanded with military grants into the  research and development  of  CBRNe , setting up a lab inside  Kirtland Air Force Base , preclinical contract research for  drug development , clinical trials and in 1998, the study of mental illness by providing neuroimaging and  big data analysis  with  machine learning ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3554", "contents": "The  U.S. Department of Agriculture  (USDA) found LRRI violated the  Animal Welfare Act  on multiple occasions since 2008. In 2018, its name appeared in the European  dieselgate  scandal, as it had tested the health effect of   diesel exhaust  exposure on monkeys for three German car manufacturers using  emissions cheating  technology."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3555", "contents": "In August 2022, it was announced that the  Lovelace Research Institute had joined Touro University and New York Medical College (NYMC)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3556", "contents": "Lovelace Biomedical currently [ when? ]  has two main locations, both located in  Albuquerque, New Mexico . It employs over 500 staff in New Mexico. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3557", "contents": "Most of Lovelace's funding comes from the United States government and private grants. [ 1 ] [ 2 ] \nAs of 2008 [update]  it was spending more than $60 million to fight against respiratory diseases such as  asthma ,  emphysema ,  lung cancer ,  bronchitis  and  allergies . [ 3 ] [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3558", "contents": "As of 2018 Lovelace consists of numerous companies per its website: [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3559", "contents": "Between March 2008 and April 2009 the  U.S. Department of Agriculture  (USDA) found LRRI violated the  Animal Welfare Act  on nine occasions, including the death of a monkey, and escape of another monkey. [ 17 ]  In 2011, LRRI was fined close to $22,000, and in 2015, federal inspectors reported that it investigated because an untrained technician\u2019s actions resulted in the death of a research dog. [ 18 ]  From August 2012 to March 2014, the DOA found that five monkeys and four rabbits died at LRRI, violating the federal Animal Welfare Act six times. [ 19 ]  In 2012, Lovelace reduced the number of monkeys from 951 to 646, the number of dogs from 293 to 183 within a short period per USDA animal inventory reports. [ 20 ] \nAs of 2014, Lovelace still used 431 primates and outnumbered all US institutions performing primate experiments like  Battelle Memorial Institute  (270) or USAMRIID (249). [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3560", "contents": "In January 2018, the NYT reported that in 2014, the LRRI studied the health effect of up to four hours of  diesel exhaust  exposure on 10 monkeys. An organization called the  European Research Group on Environment and Health in the Transport Sector  (EUGT) paid for the research, and was jointly funded by  Volkswagen ,  Daimler  and  BMW . [ 22 ]  The LRRI declined an interview, but confirmed conducting animal testing in a statement that said scientists unknowingly tested exhaust of an  emissions cheating  vehicle built by Volkswagen and that it was \"nearly duped into \u2018compromised\u2019 Volkswagen diesel research\". The study has not been published yet. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3561", "contents": "The Lovelace Respiratory Research Institute traces its roots to the arrival of William Randolph Lovelace I to Sunnyside- Fort Sumner  New Mexico in 1906 as a company physician for the  Santa Fe Railroad  and a construction project with the Lantry Sharp Construction Company. He sought the Southwest because he was advised to live in a dry, sunny climate to cure his  tuberculosis . Lovelace aspired to develop a multispecialty clinical center. In 1912, Albuquerque had become  New Mexico \u00b4s largest city and in 1913, Lovelace moved to Albuquerque to establish a private practice which became the  Lovelace Clinic , the Southwest's first center of specialty medicine, specifically treating tuberculosis. [ 24 ] :\u200a5\u201317"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3562", "contents": "In 1908, his extended family, including his brother Edgar and Edgar's infant son,  William Randolph Lovelace II  (Randy), moved to New Mexico. In 1934, this nephew received his M.D. from  Harvard University , was appointed Chief of Surgery at  Mayo Clinic  and in 1946 after his two sons succumbed to  polio , he and his wife moved back to Albuquerque. He joined his uncle\u00b4s medical clinic on the condition, that the clinic expand to the three-part mission of not only health care, but also research, and education. The nonprofit Lovelace Foundation for Medical Education and Research was founded with Lovelace\u00b4s friend  Clayton Sam White  as director and after 1965, its president until 1974. Don Kilgore was director of clinical medicine at the foundation from 1965 onward. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3563", "contents": "Through grants from the United States government agencies and private companies, multiple properties were purchased in the Southeast corner of Albuquerque, one of which is currently [ when? ]  the site of LRRI's North Campus. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3564", "contents": "The  Lockheed U-2  pilots were sent to the Lovelace Clinic for a week-long physical examination. \"Many of the tests which we pioneered were later made a part of the astronaut's physicals.\" [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3565", "contents": "In 1959, under a contract to  NASA  32 candidate pilots underwent a seven-day series of psychological and physiological tests at Lovelace clinic from which the seven  Project Mercury  astronauts were selected. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3566", "contents": "In 1964, the Lovelace Foundation entered a long-term program with the Division of Biology and Medicine of the  Atomic Energy Commission  to study the effects of inhaling  radioactive  particles; It set up the  Fission Product Inhalation Laboratory  inside  Kirtland Air Force Base . [ 28 ] \nIn the 1970s, the facility was renamed the \"Inhalation Toxicology Research Institute\" (ITRI) as it studied inhalation of non-radioactive materials. In 1996 it eventually became the Lovelace Respiratory Research Institute\" (LRRI). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3567", "contents": "Currently, [ when? ]  LRRI is the nation's largest independent, not-for-profit organization conducting basic and applied research on the causes and treatments of respiratory illness and disease. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3568", "contents": "The mission of LRRI is to serve humanity through research on the prevention, treatment, and cure of respiratory disease."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3569", "contents": "Manitoba Association of Registered Respiratory Therapists  is Manitoba's professional and licensing body governed by the Respiratory Therapy Act of Manitoba. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3570", "contents": "This  Manitoba -related article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3571", "contents": "The  National Board for Respiratory Care (NBRC Inc.  is a  non-profit  organization formed in 1960 with the purpose of awarding and maintaining credentialing for  Respiratory Therapists  in the  United States . [ 1 ]   The NBRC is the only organization in the United States which develops certification examinations for  Registered Respiratory Therapists  (RRTs) and  Certified Respiratory Therapists  (CRTs).  The NBRC also offers additional specialization credentialing for  respiratory practitioners  that hold its certifications.  The CRT and RRT designations are the standard credential in respiratory care for licensure requirements in the portions of the  United States  that have enacted a  Respiratory Care Act .  States that license  respiratory therapists  sometimes require the practitioner to maintain their NBRC credentialing to maintain their license to practice. [ 2 ]   The NBRC is headquartered in  Overland Park, Kansas .  It has been in the  Kansas City metropolitan area  since 1974.  The NBRC is located at 10801 Mastin St, Suite 300, Overland Park, KS 66210. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3572", "contents": "Certification is the entry level and is separated as such by the NBRC.   Certified Respiratory Therapists  and Certified  Pulmonary Function Technologists  may require oversight and supervision by their advanced-practice counterparts. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3573", "contents": "The term the NBRC uses to designate an advanced practitioner is \"registered\" and the addition to an advanced practitioner registry which is not permanent but has a re-certification fee associated with it.    Registered Respiratory Therapist  and  Registered Pulmonary Function Technologist  are currently the advanced credentialings maintained by the NBRC."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3574", "contents": "The NBRC has sub-specialties for the  Respiratory Therapist  designations.  Both the CRT and the RRT are eligible to sit for additional credentialing but the CRT still requires the same supervision by the RRT in clinical applications."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3575", "contents": "NBRC examinations are developed by NBRC staff and administered by  AMP, a PSI business ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3576", "contents": "Candidates must have a minimum of an associate degree from a respiratory therapy education program supported by the Committee on Accreditation for Respiratory Care (CoARC) to be eligible for the TMC Examination. Credentialed practitioners may then apply for state  licensure . [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3577", "contents": "Catharina Serafin [ 1 ]  was a Prussian lady who had an  enchondroma  removed from her cardiac region, leaving the  chest wall  open except from a thin skin layer. This allowed the German physician  Hugo von Ziemssen  in 1892 to do the first  cardiac pacing  experiments ever, giving understanding to how the  heart  works electrically."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3578", "contents": "Though this image is subject to copyright, its use is covered by the U.S. fair use laws, and the stricter requirements of Wikipedia's non-free content policies, because:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3579", "contents": "Asociaci\u00f3n Argentina de Medicina Respiratoria"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3580", "contents": "http://www.aamr.org.ar/registro_enfermedades_respiratorias.php"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3581", "contents": "Use of the logo here does not imply endorsement of the organization by Wikipedia or the  Wikimedia Foundation , nor vice versa.\n Fair use \n //en.wikipedia.org/wiki/File:Asociaci%C3%B3n_Argentina_de_Medicina_Respiratoria_logo.jpg"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3582", "contents": "Use of the logo here does not imply endorsement of the organization by Wikipedia or the  Wikimedia Foundation , nor vice versa.\n Fair use \n //en.wikipedia.org/wiki/File:Associazione_Italiana_Pneumologi_Ospedalieri.jpg"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3583", "contents": "Use of the logo here does not imply endorsement of the organization by Wikipedia or the  Wikimedia Foundation , nor vice versa.\n Fair use \n //en.wikipedia.org/wiki/File:Irish_Thoracic_Society_(logo).png"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3584", "contents": "A  chest injury , also known as  chest trauma , is any form of physical  injury  to the  chest  including the  ribs ,  heart  and  lungs . Chest injuries account for 25% of all deaths from traumatic injury. [ 1 ]  Typically chest injuries are caused by blunt mechanisms such as direct, indirect, compression, contusion, deceleration, or blasts [ 2 ]  caused by  motor vehicle collisions  or penetrating mechanisms such as  stabbings . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3585", "contents": "Chest injuries can be classified as  blunt  or  penetrating . Blunt and penetrating injuries have different  pathophysiologies  and clinical courses."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3586", "contents": "Specific types of injuries include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3587", "contents": "Most blunt injuries are managed with relatively simple interventions like  tracheal intubation  and  mechanical ventilation  and  chest tube  insertion. Diagnosis of blunt injuries may be more difficult and require additional investigations such as  CT scanning . Penetrating injuries often require  surgery , and complex investigations are usually not needed to come to a diagnosis. Patients with penetrating trauma may deteriorate rapidly, but may also recover much faster than patients with blunt injury."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3588", "contents": "Chest trauma outcomes depend on the severity of the chest injury as well as associated injuries (such as head or spinal trauma) and the patient\u2019s general health condition."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3589", "contents": "Early management in specialist centres offers better survival. Management is a mixture of medical (eg pain relief, respiratory support, chest drainage and antibiotics), non-medical (physiotherapy and rehabilitation) and surgical (fixation of rib fractures if appropriate and operative treatment of cardiac, lung, airway, diaphragm and oesophageal injuries)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3590", "contents": "Those who survive chest trauma and are discharged from hospital have a long-term survival comparable to the general population. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3591", "contents": "A  blunt cardiac injury  is an injury to the heart as the result of  blunt trauma , typically to the anterior chest wall. It can result in a variety of specific injuries to the heart, the most common of which is a  myocardial contusion , which is a term for a  bruise  (contusion) to the heart after an injury. [ 1 ]  Other injuries which can result include septal defects and  valvular failures . [ 2 ]  The right ventricle is thought to be most commonly affected due to its anatomic location as the most anterior surface of the heart. Myocardial contusion is not a specific diagnosis and the extent of the injury can vary greatly. Usually, there are other chest injuries seen with a myocardial contusion such as  rib fractures ,  pneumothorax , and  heart valve  injury. [ 3 ]  When a myocardial contusion is suspected, consideration must be given to any other chest injuries, which will likely be determined by clinical signs, tests, and imaging."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3592", "contents": "The signs and symptoms of a myocardial contusion can manifest in different ways in people which may also be masked by the other injuries. [ 3 ]  It is recommended that people with blunt chest trauma receive an  electrocardiogram  to determine if there are any irregularities with cardiac function. [ 3 ]  The presentation of an  abnormal heart rhythm  after sustaining a myocardial contusion can be delayed for up to 72 hours. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3593", "contents": "The most common cause of blunt cardiac injury (BCI) is due to motor vehicle collisions. [ 4 ]  In evaluating causes for BCI, it is important to understand how the heart is situated within the thorax. It is protected to a certain degree by bony structures like the sternum, ribs and spine, thereby offering it significant protection and thus requiring substantial amounts of force to cause BCI. Motor vehicle collisions are implicated in most causes of BCI as significant deceleration can result in the heart tearing from its attachments to surrounding structures. It is important to note that there should be a high index of suspicion for BCI when evaluating injuries to the thoraco-abdominal area. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3594", "contents": "Possible mechanisms for BCI include direct, indirect, bidirectional, deceleration, blast, crush, concussive, or combined. [ 4 ]  A direct injury is the most common and occurs most likely near the end of diastole, during ventricular filling. Indirect injury results from increased preload on the heart secondary to spikes in venous circulation which can then lead to rupture of the heart. Bidirectional injuries are a result of compressive forces on the heart by both the spine and the sternum. Deceleration injuries occur when the heart is forcibly torn from its attachments, thereby leading to tears of the muscle and arteries. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3595", "contents": "Commotio cordis is a condition seen in young, male athletes that results from BCI, and leads to sudden cardiac death within the context of benign changes of the heart on autopsy and no preexisting conditions. [ 5 ]  The impact of BCI in this condition likely puts the heart in  ventricular fibrillation , thereby resulting in death. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3596", "contents": "Structural and electrical disturbances are typical of BCI. Examples of structural injuries include intramural hematomas (which are benign and self-limiting in most cases), papillary muscle rupture, and septal injuries. Common electrical disturbances include  premature ventricular contraction  and transient  bundle branch blocks . It is important for the clinician to monitor the patient\u2019s EKG and conduct a thorough cardiovascular exam to evaluate for murmurs and abnormal heart sounds in these cases. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3597", "contents": "In evaluating the patient with suspected BCI, important symptoms to look for include chest pain, shortness of breath, palpitations and at times, typical anginal symptoms. Cardiac risk factors can also help stratify the possibilities of such an injury. Medication histories should also be noted, as rhythm control agents can mask tachycardias that normally present with BCI. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3598", "contents": "Common physical exam findings include tachypnea, abnormal lung sounds, tenderness to palpation of the chest wall, bruising, and fractures. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3599", "contents": "An ECG is recommended in those with possible BCI. Abnormal ECG findings should prompt the clinician to then place the patient on continuous telemetry monitoring. Troponin levels should also be ordered. Important to note, negative findings on both ECG and troponin levels do not exclude BCI, as symptoms may present later. If both ECG and troponin levels are abnormal, an appropriate next step in evaluation would involve ordering an  echocardiography . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3600", "contents": "As mentioned under Evaluation, an abnormal ECG and elevated troponin levels should elicit continued cardiac monitoring to look for possible arrhythmias or cardiac failure. If an arrhythmia is found, the patient should be treated as if he/she is a non-BCI patient with repletion of electrolytes, monitoring of acid-base status, and administration of medications as indicated. If clinical evaluation deems a patient severely compromised, an urgent cardiology evaluation must be made. Surgical intervention may also be required in some situations (rupture,  tamponade ), with  pericardiocentesis  as an appropriate next step in management. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3601", "contents": "Complications for BCI are rare but can include delayed rupture of the heart, complete AV block,  heart failure ,  pericardial effusion  and  constrictive pericarditis . It is advised that patients thus be reevaluated in 3-6 months post-injury. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3602", "contents": "Cardiac tamponade , also known as  pericardial tamponade  ( / \u02cc t \u00e6 m . p \u0259 \u02c8 n e\u026a d / [ 4 ] ), is a compression of the  heart  due to  pericardial effusion  (the build-up of  pericardial fluid  in the  sac around the heart ). [ 2 ]  Onset may be rapid or gradual. [ 2 ]  Symptoms typically include those of  obstructive shock  including  shortness of breath , weakness,  lightheadedness , and cough. [ 1 ]  Other symptoms may relate to the underlying cause. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3603", "contents": "Common causes of cardiac tamponade include  cancer ,  kidney failure ,  chest trauma ,  myocardial infarction , and  pericarditis . [ 2 ] [ 5 ]  Other causes include  connective tissues diseases ,  hypothyroidism ,  aortic rupture ,  autoimmune disease , and complications of  cardiac surgery . [ 2 ] [ 6 ]  In Africa,  tuberculosis  is a relatively common cause. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3604", "contents": "Diagnosis may be suspected based on  low blood pressure ,  jugular venous distension , or quiet  heart sounds  (together known as  Beck's triad ). [ 2 ] [ 1 ] [ 7 ]  A  pericardial rub  may be present in cases due to inflammation. [ 2 ]  The diagnosis may be further supported by specific  electrocardiogram  (ECG) changes,  chest X-ray , or an  ultrasound of the heart . [ 2 ]  If fluid increases slowly the pericardial sac can expand to contain more than 2 liters; however, if the increase is rapid, as little as 200 mL can result in tamponade. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3605", "contents": "Tamponade is a medical emergency. [ 5 ]  When it results in symptoms, drainage is necessary. [ 8 ]  This can be done by  pericardiocentesis , surgery to create a  pericardial window , or a  pericardiectomy . [ 2 ]  Drainage may also be necessary to rule out infection or cancer. [ 8 ]  Other treatments may include the use of  dobutamine  or in those with  low blood volume ,  intravenous fluids . [ 1 ]  Those with few symptoms and no worrisome features can often be closely followed. [ 2 ]  The frequency of tamponade is unclear. [ 9 ]  One estimate from the United States places it at 2 per 10,000 per year. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3606", "contents": "Onset may be rapid (acute) or more gradual (subacute). [ 10 ] [ 2 ]  Signs of cardiac tamponade typically include those of  cardiogenic shock  including  shortness of breath , weakness,  lightheadedness , cough [ 1 ]  and those of  Beck's triad  e.g. jugular vein distention, quiet heart sounds and  hypotension . Other symptoms may relate to the underlying cause. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3607", "contents": "Other general signs of shock (such as  fast heart rate ,  shortness of breath  and decreasing  level of consciousness ) may also occur. However, some of these signs may not be present in certain cases. A fast heart rate, although expected, may be absent in people with  uremia  and  hypothyroidism . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3608", "contents": "According to Reddy and co-authors, cardiac tamponade and its progression can be described in 3 different phases. [ 11 ]  In phase I, the required filling pressure increases due to the high stiffness of the ventricles. This is because of the accumulation of pericardial fluid in the pericardial cavity. During phase II, the pericardial pressure exceeds the ventricular filling pressure caused by the further accumulation of pericardial fluid. This results in a decrease in cardiac input and output. A further decrease of cardiac input and output is typical in phase III of the progression of cardiac tamponade. This is caused by the equilibration of left ventricular filling and pericardial pressure, leading to \u201csevere deterioration of end-organ perfusion.\u201d [ 11 ]  Some of the symptoms, as a consequence, include abdominal pain due to liver engorgement."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3609", "contents": "Cardiac tamponade is caused by a large or uncontrolled  pericardial effusion , i.e. the buildup of fluid inside the pericardium. [ 12 ]  This commonly occurs as a result of  chest trauma  (both blunt and penetrating), [ 13 ]  but can also be caused by  myocardial infarction ,  myocardial rupture ,  cancer  (most often  Hodgkin lymphoma ),  uremia ,  pericarditis , or cardiac surgery, [ 12 ]  and rarely occurs during retrograde  aortic dissection , [ 14 ]  or while the person is taking anticoagulant therapy. [ 15 ]  The effusion can occur rapidly (as in the case of trauma or myocardial rupture), or over a more gradual period of time (as in cancer). The fluid involved is often  blood , but  pus  is also found in some circumstances. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3610", "contents": "One of the most common settings for cardiac tamponade is in the first 7 days after heart surgery. [ 16 ]   After heart surgery,  chest tubes  are placed to drain blood.  These chest tubes, however, are prone to clot formation.  When a chest tube becomes occluded or clogged, the blood that should be drained can accumulate around the heart, leading to tamponade. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3611", "contents": "The pericardium, the double-walled sac surrounding the heart, consists of a fibrous pericardium layer on the outside and a double-layered serous pericardium on the inside. [ 18 ]  Between the two layers of the serous pericardium is the pericardial space, which is filled with lubricating serous fluid that prevents friction as the heart contracts. [ 19 ]  The outer layer of the heart is made of fibrous tissue [ 20 ]  which does not easily stretch, so once excess fluid begins to enter the pericardial space, pressure starts to increase. [ 12 ]  Consequently, the heart becomes compressed due to its inability to fully relax. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3612", "contents": "If fluid continues to accumulate, each successive diastolic period leads to less blood entering the ventricles. Eventually, increasing pressure on the heart forces the  septum  to bend in towards the  left ventricle , leading to a decrease in  stroke volume . [ 12 ]  This causes the development of  obstructive shock , which if left untreated may lead to  cardiac arrest  (often presenting as  pulseless electrical activity ). [ 22 ]  The decrease in stroke volume can also ultimately lead to a decrease in cardiac output, which could be signaled by tachycardia and hypotension. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3613", "contents": "The three classic signs, known as  Beck's triad , are  low blood pressure , jugular-venous distension, and muffled  heart sounds . [ 24 ]  Other signs may include  pulsus paradoxus  (a drop of at least 10 mmHg in arterial blood pressure with inspiration), [ 12 ]  and  ST segment  changes on the  electrocardiogram , [ 24 ]  which may also show low voltage  QRS complexes . [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3614", "contents": "Tamponade can often be diagnosed radiographically.  Echocardiography , which is the diagnostic test of choice, often demonstrates an enlarged pericardium or collapsed ventricles. A large cardiac tamponade will show as an enlarged globular-shaped heart on chest x-ray. During inspiration, the negative pressure in the  thoracic cavity  will cause increased pressure into the right ventricle.  This increased pressure in the right ventricle will cause the interventricular septum to bulge towards the left ventricle, leading to decreased filling of the left ventricle. At the same time, right ventricle volume is markedly diminished and sometimes it can collapse. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3615", "contents": "Initial diagnosis of cardiac tamponade can be challenging, as there is a broad  differential diagnosis . [ 10 ]  The differential includes possible diagnoses based on symptoms, time course, mechanism of injury, patient history. Rapid onset cardiac tamponade may also appear similar to pleural effusions,  obstructive shock , shock, pulmonary embolism, and  tension pneumothorax . [ 13 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3616", "contents": "If symptoms appeared more gradually, the differential diagnosis includes acute  heart failure . [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3617", "contents": "In a person with trauma presenting with  pulseless electrical activity  in the absence of hypovolemia and tension pneumothorax, the most likely diagnosis is cardiac tamponade. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3618", "contents": "In addition to the diagnostic complications afforded by the wide-ranging differential diagnosis for chest pain, diagnosis can be additionally complicated by the fact that people will often be weak or faint at presentation. For instance, a fast rate of breathing and difficulty breathing on exertion that progresses to air hunger at rest can be a key diagnostic symptom, but it may not be possible to obtain such information from people who are unconscious or who have convulsions at presentation. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3619", "contents": "Initial treatment given will usually be supportive in nature, for example administration of  oxygen , and monitoring. There is little care that can be provided pre-hospital other than general treatment for shock. Some teams have performed an emergency  thoracotomy  to release clotting in the  pericardium  caused by a penetrating chest injury. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3620", "contents": "Prompt diagnosis and treatment is the key to survival with tamponade.  Some pre-hospital providers will have facilities to provide  pericardiocentesis , which can be life-saving.  If the person has already suffered a  cardiac arrest , pericardiocentesis alone cannot ensure survival, and so rapid evacuation to a hospital is usually the more appropriate course of action. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3621", "contents": "Initial management in hospital is by pericardiocentesis. [ 13 ]  This involves the insertion of a needle through the skin and into the pericardium and aspirating fluid under ultrasound guidance preferably. This can be done laterally through the intercostal spaces, usually the fifth, or as a subxiphoid approach. [ 27 ] [ 28 ]  A left parasternal approach begins 3 to 5\u00a0cm left of the sternum to avoid the left internal mammary artery, in the 5th  intercostal space . [ 29 ]  Often, a  cannula  is left in place during resuscitation following initial drainage so that the procedure can be performed again if the need arises. If facilities are available, an emergency  pericardial window  may be performed instead, [ 13 ]  during which the pericardium is cut open to allow fluid to drain. Following stabilization of the person, surgery is provided to seal the source of the bleed and mend the pericardium. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3622", "contents": "Following heart surgery, the amount of chest tube drainage is monitored.  If the drainage volume drops off, and the blood pressure goes down, this can suggest a tamponade due to chest tube clogging.  In that case, the person is taken back to the operating room for an emergency reoperation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3623", "contents": "If aggressive treatment is offered immediately and no complications arise (shock, AMI or arrhythmia, heart failure, aneurysm, carditis, embolism, or rupture), or they are dealt with quickly and fully contained, then adequate survival is still a distinct possibility. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3624", "contents": "The frequency of tamponade is unclear. [ 9 ]  One estimate from the United States places it at 2 per 10,000 per year. [ 3 ]  It is estimated to occur in 2% of those with stab or gunshot wounds to the chest. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3625", "contents": "Commotio cordis  ( Latin , \"agitation / disruption of the heart\") is a rare disruption of  heart rhythm  that occurs as a result of a blow to the area directly over the heart (the  precordial region ) at a critical instant during  the cycle of a heartbeat . [ 1 ]  The condition is 97% fatal if not treated within three minutes. [ 2 ]  This sudden rise in intracavitary pressure leads to disruption of normal  heart electrical activity , followed instantly by  ventricular fibrillation , complete disorganization of the heart's pumping function, and cardiac arrest. It is not caused by mechanical damage to the heart muscle or surrounding organs and is not the result of heart disease."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3626", "contents": "Its incidence in the United States is fewer than 20 cases per year, often occurring in boys participating in sports, most commonly in baseball when a ball strikes a player in the chest."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3627", "contents": "Commotio cordis can occur only upon impact within a narrow window of about 40  milliseconds  in the cardiac electrical cycle, explaining why it is so rare. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3628", "contents": "If  cardiopulmonary resuscitation  (CPR) combined with use of an on-site  automated external defibrillator  is employed within three minutes of the impact, survival from commotio cordis can be as high as 58 percent. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3629", "contents": "There are only 10\u201320 cases annually in the United States. [ 1 ]  These cases occur mostly in boys and young men (mean age 15), usually during sports participation. [ 1 ]  It occurs most frequently in baseball when the hard ball strikes an unprotected chest, although there have been cases of commotio cordis in players using a chest protector. [ 1 ]  It is usually caused by a projectile, but can also be caused by a blow from another player's elbow or other body part. Being less developed, the thorax of an adolescent is likely more prone to this injury than a mature adult. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3630", "contents": "Over a period of assessment from 2006\u20132012, the survival rate was 58 percent, which was an improvement over the years 1993\u20132006 when only 34 percent of victims survived. [ 3 ] [ 4 ]  This increase is likely due to prompt CPR, access to  defibrillation , and higher public awareness of this phenomenon. [ 1 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3631", "contents": "Due to ventricular fibrillation and resultant cessation of the  cardiac output  to vital organs, commotio cordis has a high fatality rate, indicated by two studies to be 72\u201375 percent, with survival decreasing substantially if effective resuscitation was not performed within three minutes of the impact event. [ 3 ] [ 2 ]  In a United States timeline analysis, survival was only ten percent over the years 1970\u20131993, while during 1994\u20132012, survival improved to 34 percent. [ 3 ]  A 2009 paper reported that survival drops to 3% when resuscitation is delayed beyond 3 minutes. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3632", "contents": "Higher survival rates correlated with immediate resuscitation by using CPR and an on-site  automated external defibrillator \u2014the survival rate was forty percent if resuscitation was performed within three minutes of the impact injury, contrasted with only five percent survival if resuscitation was delayed to more than three minutes after the impact. [ 3 ]  During the early 21st century, survival rates continued to improve to 58 percent of cases. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3633", "contents": "Commotio cordis is a very rare event, but nonetheless it is often considered when an athlete presents with  sudden cardiac death . Some of the sports which have a risk for this cause of trauma are baseball,  American football , association football (soccer),  ice hockey ,  polo ,  rugby football ,  cricket , softball,  pelota ,  lacrosse ,  boxing ,  professional wrestling ,  hurling  and martial arts (see  Touch of Death ). Children are especially vulnerable, possibly due to the mechanical properties of their  thoracic skeleton . [ 1 ] [ 5 ]  From 1996 to spring 2007, the US National Commotio Cordis Registry had 188 cases recorded, with about half occurring during  organized sports . [ 6 ]  Almost all (96%) of the victims were male, the mean age of the victims during that period was 14.7 years, and fewer than one in five survived the incident. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3634", "contents": "Baseball is the most common sport in which commotio cordis occurs in regions where it is played, particularly among teenage boys who are  batting  or playing the positions of  pitcher  or  catcher . [ 1 ]  Commotio cordis may occur in other sports via impacts to the chest by elbows or heads. [ 1 ]  It has also been reported outside of sports when there is sudden impact to the chest wall by hard objects or  fists . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3635", "contents": "St. Louis Blues   defenceman   Chris Pronger  experienced commotio cordis during  a playoff game on May 11, 1998 , against the  Detroit Red Wings  when a  slapshot  from  Dmitri Mironov  struck his chest. Pronger went into cardiac arrest and was unconscious for 20 seconds while he was resuscitated by members of both the Blues' and Red Wings' training staff. [ 7 ] [ 8 ]  Pronger made a full recovery after an overnight stay at  Henry Ford Hospital  in  Detroit  and would be cleared to play again four days later. The incident ultimately had a negligible effect on his career, which lasted until 2011. Another high-profile incident occurred on January 2, 2023, during  Monday Night Football  when  Buffalo Bills   safety   Damar Hamlin  experienced commotio cordis after  Cincinnati Bengals   wide receiver   Tee Higgins 's helmet struck him in the chest as he was making a tackle. [ 9 ]  Hamlin collapsed and went into cardiac arrest, and his life was saved by the Bills' training staff administering CPR and employing an  automated external defibrillator  (AED). [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3636", "contents": "In experimental animal models in pigs studying impacts by a hard ball to the chest wall, impacts that occurred directly over the center of the  left ventricle , where there is no overlying lung tissue, were the most likely to cause ventricular fibrillation. [ 1 ]  Impacts not over the heart did not cause ventricular fibrillation. [ 1 ]  Ventricular fibrillation was more easily induced in smaller, leaner animals. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3637", "contents": "The velocity of the impact by a hard object is a critical factor for the onset of commotio cordis: impacts at 40 miles per hour (64 kilometres per hour) were the most likely to cause ventricular fibrillation in an animal model. [ 1 ]  At velocities of 20 miles per hour (32\u00a0km/h), ventricular fibrillation did not occur."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3638", "contents": "Impact energies of at least 50  joules  (37  foot-pounds force ) may cause cardiac arrest when applied at the right time and location of the  precordium  of an adult. [ 11 ]  The 50-joule threshold, however, can be considerably lower when the victim's heart is under  ischemic  conditions, such as in  coronary artery  insufficiency. [ 11 ]   Contusion  of the heart, involving possible rupture of a heart chamber or damage to a heart valve as may occur in a violent vehicle accident, may be called  contusio cordis  (from  Latin  for \"bruising of the heart\"), but is unrelated to commotio cordis. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3639", "contents": "Commotio cordis may also occur in other situations, such as in children who are physically abused, cases of  torture , and frontal collisions of motor vehicles (the impact of the steering wheel against the thorax, although this has decreased substantially with the use of  safety belts  and  air bags ). In one fatality, the impact to the chest was the result of an exploding  whipped cream  canister. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3640", "contents": "In contrast, the  precordial thump  (hard blows given over the precordium with a closed fist to revert cardiac arrest) is a sanctioned procedure for emergency resuscitation by trained health professionals witnessing a monitored arrest when no equipment is at hand, endorsed by the latest guidelines of the  International Liaison Committee on Resuscitation . It has been discussed controversially, as\u2014in particular in severe hypoxia\u2014it may cause the opposite effect (i.e., a worsening of rhythm\u2014commotio cordis). In a normal adult, the energy range involved in the precordial thump is five to ten times below that associated with commotio cordis. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3641", "contents": "The deviation of commotio cordis from the normal electrical rhythm of the heart is assessed scientifically in laboratory studies by analysis of the  electrocardiograph (ECG)   T wave  (see ECG image). [ 1 ]  Only chest impacts occurring on a narrow band of the ECG during the upslope of the T wave (40  milliseconds  (ms) before the peak of the T wave to the instant of the actual peak) will cause the ventricular fibrillation of commotio cordis, with an increased probability occurring when an impact happens from 30 to 10 ms before the peak of the T wave. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3642", "contents": "These factors influence the onset of commotio cordis: [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3643", "contents": "The small window of vulnerability in the cardiac electrical cycle explains why it is a rare event. [ 1 ]  Considering that the total cardiac cycle has a duration of one second (for a base  heart rate  of 60 beats per minute), the probability of impact trauma within the window of vulnerability is 1\u20133 percent only. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3644", "contents": "The  cellular  mechanisms of commotio cordis are not fully understood. However, it is widely recognized that it may be related to the mechanical impact, or stretch, on the myocardial tissue cell membranes. This impact is believed to activate the stretch-activated, pressure\u2013sensitive proteins called  ion channels . [ 1 ]  Changes in ion channels lead to altered  repolarization  in the heart's electrical activity, which in some cases, if occurring right at the trailing edge of a previous electrical cycle, can induce ventricular fibrillation, also known as stretch-induced VF. [ 1 ] [ 13 ] [ 14 ]  Since the trailing edge of the preceding electrical cycle travels over the ventricular surface, the critical window for mechanical induction of ventricular fibrillation varies locally across the ventricle. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3645", "contents": "For some sports participation in which hard balls are used, such as baseball or  lacrosse , softer, more  pliable  balls may reduce the impact trauma causing commotio cordis. [ 1 ]  The shape of the impact object may be modified for some conditions, such as by using a flat object \u2013 which did not induce ventricular fibrillation upon impact in preliminary research \u2013 whereas spherical objects with smaller  radii  were more likely to induce ventricular fibrillation. [ 1 ]  Safety baseballs having lower degrees of hardness, e.g., softer, pliable and elastic balls used for  Tee-ball  or more pliable baseballs for older age groups, may reduce the risk of commotio cordis. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3646", "contents": "The risk of impact may be reduced by improved coaching techniques, such as teaching young batters to turn away from the ball to avoid errant pitches in baseball. Defensive players in lacrosse and hockey may be coached to avoid using their chest to block the ball or puck. Starting in 2017, high school lacrosse players are penalized, and play is stopped immediately if they enter their own goal crease with the apparent intent of blocking shots or acting as goalkeeper. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3647", "contents": "Chest protectors and vests are designed to reduce trauma from blunt bodily injury, but many commercially available chest protectors do not offer protection from commotio cordis and may offer a false sense of security. [ 1 ]  A 2010 study found that almost 20 percent of the victims in competitive football, baseball, lacrosse, and hockey were wearing protectors. [ 5 ]  A 2017 study found that specially-designed chest protectors do reduce the risk of commotio cordis, but do not offer 100 percent protection. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3648", "contents": "In 2017, the  National Operating Committee on Standards for Athletic Equipment (NOCSAE)  finalized a new standard outlining  performance requirements and test methods for chest protectors used in baseball and lacrosse, ND200  Standard Test Method and Performance Specification Used in Evaluating the Performance Characteristics of Chest Protectors for Commotio Cordis . [ 17 ]   Beginning in 2021,  US Lacrosse  made chest protectors that meet the NOCSAE ND200 standard a requirement for all goalies, and expanded coverage in 2022 to require all players to wear such a chest protector. [ 18 ]   In 2018, the  National Federation of State High School Associations (NFHS)  changed their baseball rules to require the catcher to wear a chest protector that meets the NOCSAE ND200 standard requirements. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3649", "contents": "Automated external defibrillators  (AED) and prompt CPR helped to increase the survival rate to 58 percent. [ 3 ]  CPR and defibrillation must be started urgently (within three minutes) to avoid death of the person impacted. [ 3 ]  To assure life-saving procedures and equipment are in place at events where impact injuries are possible, clinical recommendations state that \"communities and  school districts  reexamine the need for accessible automatic defibrillators and CPR-trained coaches at organized sporting events for children.\" [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3650", "contents": "Several people have been charged and convicted for the deaths of victims of commotio cordis, even when the blows rendered were never given with an intent to kill. [ 21 ]  In 1992, Italian hockey player Miran Schrott died after a blow to his chest from the stick of Italian-Canadian player  Jimmy Boni . Boni was charged with  culpable homicide , and eventually pleaded guilty to manslaughter, paying a $1,300 fine and $175,000 restitution to Schrott's family. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3651", "contents": "Diaphragmatic rupture  (also called  diaphragmatic injury  or  tear ) is a tear of the  diaphragm , the muscle across the bottom of the ribcage that plays a crucial role in  breathing . Most commonly, acquired diaphragmatic tears result from  physical trauma . Diaphragmatic rupture can result from blunt or penetrating trauma and occurs in about 0.5% of all people with trauma. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3652", "contents": "Diagnostic techniques include  X-ray ,  computed tomography , and surgical techniques such as an explorative surgery. Diagnosis is often difficult because signs may not show up on X-ray, or signs that do show up appear similar to other conditions. Signs and symptoms include chest and abdominal pain, difficulty breathing, and decreased lung sounds. When a tear is discovered, surgery is needed to repair it."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3653", "contents": "Injuries to the diaphragm are usually accompanied by other injuries, and they indicate that more severe injury may have occurred. The outcome often depends more on associated injuries than on the diaphragmatic injury itself. Since the pressure is higher in the  abdominal cavity  than the  chest cavity , rupture of the diaphragm is almost always associated with herniation of abdominal organs into the chest cavity, which is called a  diaphragmatic hernia . This herniation can interfere with breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3654", "contents": "Symptoms may include pain, [ 3 ]   orthopnea , (shortness of breath when lying flat), [ 4 ]  and  coughing . In people with herniation of abdominal organs, signs of intestinal blockage or  sepsis  in the abdomen may be present. [ 5 ]  Bowel sounds may be heard in the chest, and shoulder or  epigastric  pain may be present. When the injury is not noticed right away, the main symptoms are those that indicate  bowel obstruction . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3655", "contents": "Diaphragmatic rupture may be caused by  blunt trauma ,  penetrating trauma , and by  iatrogenic  causes (as a result of medical intervention), for example during surgery to the abdomen or chest. [ 6 ]  It has also occurred spontaneously at the time of pregnancy or for no discernible reason. [ 2 ]  Injury to the diaphragm is reported to be present in 8% of cases of blunt chest trauma. [ 7 ]  In cases of blunt trauma,  vehicle accidents  and falls are the most common causes. [ 6 ]  Penetrating trauma has been reported to cause 12.3\u201320% of cases, but it has also been proposed as a more common cause than blunt trauma; discrepancies could be due to varying regional, social, and economic factors in the areas studied. [ 8 ]   Stab  and  gunshot wounds  can cause diaphragmatic injuries. [ 6 ]  Clinicians are trained to suspect diaphragmatic rupture particularly if  penetrating trauma  has occurred to the lower  chest  or upper  abdomen . [ 9 ]  With penetrating trauma, the contents of the abdomen may not herniate into the chest cavity right away, but they may do so later, causing the presentation to be delayed. [ 6 ]  Since the diaphragm moves up and down during breathing, penetrating trauma to various parts of the torso may injure the diaphragm; penetrating injuries as high as the third rib and as low as the twelfth have been found to injure the diaphragm. [ 10 ]  Iatrogenic cases have occurred as a complication of medical procedures involving the thorax or abdomen. It has occurred as a complication of  thoracentesis  and  radiofrequency ablation . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3656", "contents": "Although the mechanism is unknown, it is proposed that a blow to the abdomen may raise the pressure within the abdomen so high that the diaphragm ruptures. [ 6 ]  Blunt trauma creates a large pressure gradient between the abdominal and thoracic cavities; this gradient, in addition to causing the rupture, can also cause abdominal contents to herniate into the thoracic cavity. Abdominal contents in the  pleural space  interfere with heart function and lung function. High intrathoracic pressure results in an increase in right atrial pressure, disrupting the filling of the heart and venous return of blood. [ 4 ]  As venous return determines cardiac output, this results in a reduction of cardiac output. [ 11 ]  If  ventilation  of the lung on the side of the tear is severely inhibited,  hypoxemia  (low blood oxygen) results. [ 4 ]  Usually, the rupture is on the same side as an impact. [ 10 ]  A blow to the side is three times more likely to cause diaphragmatic rupture than a blow to the front. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3657", "contents": "Physical examinations are not accurate, as there is usually no specific physical sign that can be used to diagnose this condition. [ 3 ]  Thoracoscopic and laparoscopic methods can be accurate. [ 12 ]   Chest X-ray  is known to be unreliable in diagnosing diaphragmatic rupture; [ 4 ]  it has low  sensitivity and specificity  for the injury. [ 5 ]  Often another injury such as  pulmonary contusion  masks the injury on the X-ray film. [ 6 ]  Half the time, initial X-rays are normal; in most of those that are not,  hemothorax  or  pneumothorax  is present. [ 4 ]  A  nasogastric tube  from the stomach may appear on the film in the chest cavity; this sign is  pathognomonic  for diaphragmatic rupture, but it is rare. [ 4 ]  The X-ray is better able to detect the injury when taken from the back with the person upright, but this is not usually possible because the person is usually not stable enough; thus it is usually taken from the front with the person lying supine. [ 5 ]   Positive pressure ventilation  helps keep the abdominal organs from herniating into the chest cavity, but this also can prevent the injury from being discovered on an X-ray. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3658", "contents": "A  CT scan  has an increased accuracy of diagnosis over X-ray, [ 7 ]  but no specific findings on a CT scan exist to establish a diagnosis. [ 9 ]  The free edge of a ruptured diaphragm may curl and become perpendicular to the chest wall, a sign known as a dangling diaphragm. A herniated organ may constrict at the location of a rupture, a sign known as the collar sign. If the liver herniates through a rupture on the right side, it may produce two signs known as the hump and band signs. The hump sign is a form of the collar sign on the right. The band sign is a bright line that intersects the liver.  it is believed to result due to the ruptured diaphragm compressing. [ 13 ]   Although CT scanning increases chances that diaphragmatic rupture will be diagnosed before surgery, the rate of diagnosis before surgery is still only 31\u201343.5%. [ 7 ]  Another diagnostic method is  laparotomy , but this misses diaphragmatic ruptures up to 15% of the time. [ 4 ]  Often diaphragmatic injury is discovered during a laparotomy that was undertaken because of another abdominal injury. [ 4 ]  Because laparotomies are more common in those with penetrating trauma than compared to those who experienced a blunt force injury, diaphragmatic rupture is found more often in these people. [ 14 ]   Thoracoscopy  is more reliable in detecting diaphragmatic tears than laparotomy and is especially useful when chronic diaphragmatic hernia is suspected. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3659", "contents": "Between 50 and 80% of diaphragmatic ruptures occur on the left side. [ 5 ]  It is possible that the  liver , which is situated in the right upper quadrant of the abdomen, cushions the diaphragm. [ 6 ]  However, injuries occurring on the left side are also easier to detect in X-ray films. [ 4 ]  Half of diaphragmatic ruptures that occur on the right side are associated with liver injury. [ 5 ]  Injuries occurring on the right are associated with a higher rate of death and more numerous and serious accompanying injuries. [ 10 ]  Bilateral diaphragmatic rupture, which occurs in 1\u20132% of ruptures, is associated with a much higher death rate ( mortality ) than injuries that occur on just one side. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3660", "contents": "Since the diaphragm is in constant motion with respiration, and because it is under tension, lacerations will not heal on their own. [ 10 ]  The injury usually becomes larger with time if not repaired. [ 2 ]  The main goals of surgery are to repair any injuries to the diaphragm and to move any herniated abdominal organs back to their original place. [ 12 ]  This is done by debriding nonviable tissue and closing the rupture. [ 3 ]  Most of the time, the injury is repaired during  laparotomy . [ 9 ]  Early surgery is important, as diaphragmatic atrophy and adhesions occur over time. Sutures are used in the repair. [ 12 ]  Other injuries, such as  hemothorax , may present a more immediate threat and may need to be treated first if they accompany diaphragmatic rupture. [ 6 ]   Video-assisted thoracoscopy  may be used. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3661", "contents": "In most cases, isolated diaphragmatic rupture is associated with good outcome if it is surgically repaired. [ 6 ]  The death rate ( mortality ) for diaphragmatic rupture after blunt and penetrating trauma is estimated to be 15\u201340% and 10\u201330% respectively, but other injuries play a large role in determining outcome. [ 6 ]  Herniation of abdominal organs is present in 3\u20134% of people with  abdominal trauma  who present to a trauma center. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3662", "contents": "Diaphragmatic injuries are present in 1\u20137% of people with significant blunt trauma [ 6 ]  and an average of 3% of abdominal injuries. [ 9 ]  A high  body mass index  may be associated with a higher risk of diaphragmatic rupture in people involved in vehicle accidents. [ 6 ]  Over 90% occur due to trauma from vehicle accidents. Due to the great force needed to rupture the diaphragm, [ 3 ]  it is rare for the diaphragm alone to be injured, especially in blunt trauma; other injuries are associated in as many as 80\u2013100% of cases. [ 4 ] [ 7 ]  In fact, if the diaphragm is injured, it is an indication that more severe injuries to organs may have occurred. Thus, the mortality after a diagnosis of diaphragmatic rupture is 17%, with most deaths due to lung complications. [ 7 ]  Common associated injuries include  head injury , injuries to the  aorta ,  fractures  of the  pelvis  and  long bones , and  lacerations  of the  liver  and  spleen . [ 4 ]  Associated injuries can occur in over three quarters of cases. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3663", "contents": "In 1579,  Ambroise Par\u00e9  made the first description of diaphragmatic rupture in a French artillery captain who had been shot eight months before his death.  He died from complications of the rupture. Using autopsies, Par\u00e9 also described diaphragmatic rupture in people who had suffered blunt and penetrating trauma. Reports of diaphragmatic herniation due to injury date back at least as far as the 17th century. Petit was the first to establish the difference between acquired and  congenital diaphragmatic hernia , which results from a congenital malformation of the diaphragm. In 1888, Naumann repaired a hernia of the stomach into the left chest that was caused by trauma. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3664", "contents": "Diaphragmatic rupture is a common and well-known complication of blunt abdominal trauma in cats and dogs. The organs that herniate into the pleural cavity are determined by the location of the rupture. They are most commonly circumferential tears that occur at the attachment of the diaphragm and rib. Is these cases, the organs that herniate may include the  liver ,  small intestine ,  stomach ,  spleen ,  omentum , and/or  uterus . Dorsal tears are uncommon, and may cause a kidney to herniate into the thorax. Symptoms include difficulty breathing, vomiting, collapse, and an absence of palpable organs in the abdomen. Symptoms can worsen quickly and be lethal, especially in the case of severe bleeding,  bruised heart , or strangulation of herniated intestine. It is also possible that there may only be subtle signs, and the condition  is only incidentally detected  months to years after the injury during a medical scan. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3665", "contents": "Flail chest  is a life-threatening medical condition that occurs when a segment of the  rib cage breaks  due to  trauma  and becomes detached from the rest of the  chest wall . Two of the  symptoms  of flail chest are  chest pain  and  shortness of breath . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3666", "contents": "It occurs when multiple adjacent ribs are broken in multiple places, separating a segment, so a part of the chest wall moves independently. The number of ribs that must be broken varies by differing definitions: some sources say at least two adjacent ribs are broken in at least two places, [ 2 ]  some require three or more ribs in two or more places. [ 3 ]  The flail segment moves in the opposite direction to the rest of the chest wall: because of the ambient pressure in comparison to the pressure inside the lungs, it goes in while the rest of the chest is moving out, and vice versa. This so-called \"paradoxical breathing\" [ 4 ]  is painful and increases the work involved in breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3667", "contents": "Flail chest is usually accompanied by a  pulmonary contusion , a bruise of the lung tissue that can interfere with blood oxygenation. [ 5 ]  Often, it is the contusion, not the flail segment, that is the main cause of respiratory problems in people with both injuries. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3668", "contents": "Surgery to fix the fractures appears to result in better outcomes. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3669", "contents": "Two of the  symptoms  of flail chest are  chest pain  and  shortness of breath . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3670", "contents": "The characteristic paradoxical motion of the flail segment occurs due to pressure changes associated with respiration that the rib cage normally resists:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3671", "contents": "Paradoxical motion is a late sign of flail segment; therefore, an absence of paradoxical motion does not mean the patient does not have a flail segment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3672", "contents": "The constant motion of the ribs in the flail segment at the site of the fracture is extremely painful, and, untreated, the sharp broken edges of the ribs are likely to eventually puncture the pleural sac and lung, possibly causing a  pneumothorax . The concern about \"mediastinal flutter\" (the shift of the  mediastinum  with paradoxical diaphragm movement) does not appear to be merited. [ 8 ]  Pulmonary contusions are commonly associated with flail chest and that can lead to  respiratory failure . This is due to the paradoxical motions of the chest wall from the fragments interrupting normal breathing and chest movement. Typical paradoxical motion is associated with stiff lungs, which requires extra work for normal breathing, and increased lung resistance, which makes air flow difficult. [ 9 ]  The respiratory failure from the flail chest requires  mechanical ventilation  and a longer stay in an intensive care unit. [ 10 ]  It is the damage to the lungs from the flail segment that is life-threatening."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3673", "contents": "The most common causes of flail chest injuries are  vehicle collisions , which account for 76% of flail chest injuries. [ 11 ]  Another main cause of flail chest injuries is falling.  This mainly occurs in the  elderly , who are more impacted by the falls as a result of their weak and frail  bones , unlike their younger counterparts who can fall without being impacted as severely. Falls account for 14% of flail chest injuries. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3674", "contents": "Flail chest typically occurs when three or more adjacent ribs are fractured in two or more places, allowing that segment of the thoracic wall to displace and move independently of the rest of the chest wall. Flail chest can also occur when ribs are fractured proximally in conjunction with disarticulation of  costal cartilages  distally. For the condition to occur, generally there must be a significant force applied over a large surface of the thorax to create the multiple anterior and posterior rib fractures. Rollover and crushing injuries most commonly break ribs at only one point, whereas for flail chest to occur a significant impact is required, breaking the ribs in two or more places. [ 12 ]  This can be caused by forceful accidents such as the aforementioned vehicle collisions or significant falls. In the elderly, it can be caused by  deterioration  of bone, although rare. In children, the majority of flail chest injuries result from common blunt force traumas or metabolic bone diseases, including a group of genetic disorders known as  osteogenesis imperfecta . [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3675", "contents": "Diagnosis is by physical examination performed by a physician. The diagnosis may be assisted or confirmed by use of medical imaging with either plain X ray or CT scan.\nParadoxial movements of flail segments.\nCrepitus and tenderness near fractured ribs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3676", "contents": "Treatment of the flail chest initially follows the principles of  advanced trauma life support . Further treatment includes:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3677", "contents": "A person may be  intubated  with a  double lumen tracheal tube . In a double lumen endotracheal tube, each lumen may be connected to a different ventilator. Usually one side of the chest is affected more than the other, so each lung may require drastically different pressures and flows to adequately ventilate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3678", "contents": "Surgical fixation can help in significantly reducing the duration of ventilatory support and in conserving the pulmonary function. [ 15 ] \nSurgical intervention has also been shown to reduce the need for tracheostomy, reduces the time spent in the intensive care unit following a traumatic flail chest injury and could reduce the risk of acquiring pneumonia after such an event. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3679", "contents": "In order to begin a rehabilitation program for a flail chest it is important to treat the person's pain so they are able to perform the proper exercises. Due to the underlying conditions that the flail segment has caused onto the respiratory system,  chest physiotherapy  is important to reduce further complications.  Proper positioning of the body is key, including postural alignment for proper drainage of mucous secretions. [ 17 ]   The therapy will consist of a variety of postural positioning and changes in order to increase normal breathing.  Along with postural repositioning, a variety of breathing exercises are also very important in order to allow the chest wall to reposition itself back to normal conditions.  Breathing exercises will also include coughing procedures. [ 17 ]   Furthermore,  range of motion  exercises are given to reduce the  atrophy  of the musculature. [ 18 ]   With progression, resistance exercises are added to the regimen to the shoulder and arm of the side containing the injury.  Moreover, trunk exercises will be introduced while sitting and will progress to during standing. [ 19 ]  Hip flexion exercises can be done to expand the thorax. This is done by lying supine on a flat surface, flexing the knees and hips and bringing them in toward the chest. The knees should come in toward the chest while the person inhales, and exhale when the knees are lowered. [ 19 ]  This exercise can be done in 3 sets of 6\u20138 repetitions with a pause in between sets. The person should always make sure to maintain controlled breaths. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3680", "contents": "Eventually, the person will be progressed to walking and posture correction while walking. [ 19 ]   Before the person is discharged from the hospital, the person should be able to perform mobility exercises to the core and should have attained good posture."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3681", "contents": "The death rate of people with flail chest depends on the severity of their condition, ranging from 10 to 25%. [ 1 ] \nA systematic review comparing the safety and effectiveness of surgical fixation versus non-surgical methods for the treatment of flail chest, reported that there was no statistically significant difference in the reported deaths between patients treated surgically and those treated non-surgically i.e. with conservative management methods. The results of the systematic review suggested that surgical intervention reduces the need for tracheostomy, reduces the time spent in the intensive care unit following a traumatic flail chest injury and could reduce the risk of acquiring pneumonia after such an event. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3682", "contents": "Approximately 1 out of 13 people admitted to the  hospital  with fractured ribs are found to have flail chest. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3683", "contents": "Hemopericardium  refers to  blood  in the  pericardial  sac of the  heart . It is clinically similar to a  pericardial effusion , and, depending on the volume and rapidity with which it develops, may cause  cardiac tamponade . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3684", "contents": "The condition can be caused by full-thickness  necrosis  (death) of the  myocardium  (heart muscle) after  myocardial infarction ,  chest trauma , [ 2 ]  and by over-prescription of  anticoagulants . [ 3 ] [ 4 ]  Other causes include ruptured  aneurysm of sinus of Valsalva  and other  aneurysms  of the  aortic arch . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3685", "contents": "Hemopericardium can be diagnosed with a chest  X-ray  or a chest  ultrasound , and is most commonly treated with  pericardiocentesis . [ 6 ]   While hemopericardium itself is not deadly, it can lead to  cardiac tamponade , a condition that is fatal if left untreated. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3686", "contents": "Symptoms of hemopericardium often include difficulty breathing, abnormally rapid breathing, and fatigue, each of which can be a sign of a serious medical condition not limited to hemopericardium. [ 6 ]  In many cases, patients also report feeling chest pressure and have an abnormally elevated  heart rate . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3687", "contents": "Hemopericardium has been reported to result from various afflictions including  chest trauma , free wall rupture after a  myocardial infarction , bleeding into the  pericardial sac  following a type A  aortic dissection , and as a complication of invasive  cardiac  procedures. [ 6 ]  Acute  leukemia  has also been reported as a cause of the condition. [ 7 ]  Several cases of hemopericardium have also been reported as a side-effect of  anticoagulants . [ 6 ]  Patients should be made aware of this fact when prescribed these drugs. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3688", "contents": "Hemopericardium is a condition that affects the  cardiovascular system . It typically begins with  blood  accumulating in the  pericardial sac  posterior to the  heart , and eventually expands to surround the entire heart. [ 6 ]  The fluid build-up then causes pressure within the  pericardial sac  to increase. If the pressure becomes greater than the intracardiac pressure of the heart, compression of the adjacent cardiac chambers can occur. [ 6 ]   This compression, called  cardiac tamponade , is often associated with hemopericardium and can be fatal if not diagnosed and treated promptly. [ 6 ]  Early signs of this compression include right atrial inversion during  ventricular   systole  followed by  diastolic  compression of the  right ventricular outflow tract . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3689", "contents": "There have also been cases reported in which hemopericardium was noted as an initial manifestation of  essential thrombocythemia . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3690", "contents": "Hemopericardium can be diagnosed using  echocardiography , a  cardiac ultrasound . [ 6 ]  Chest  X-rays  are also often taken when hemopericardium is suspected and would reveal an  enlarged heart . [ 6 ]   Other observable signs include rapid  heart rate ,  jugular venous distension , low  blood pressure , and  pulsus paradoxus . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3691", "contents": "When discovered, hemopericardium is usually treated by  pericardiocentesis , a procedure wherein a needle is used to remove the fluid from the  pericardial sac . [ 6 ]  This procedure typically utilizes an 8-cm, 18-gauge needle that is inserted between the  xiphoid process  and the left  costal margin  until it enters the  pericardial sac , when it can then be used to drain the fluid from the sac. [ 6 ]   A  catheter  is often left in the  pericardium  to continue draining any remaining fluid after the initial procedure. [ 7 ]  The catheter can be removed when the hemopericardium no longer persists.  The underlying causes of the condition, such as over-prescription of  anticoagulants , must be addressed as well so that the hemopericardium does not return. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3692", "contents": "While hemopericardium itself is not fatal, it may lead to  cardiac tamponade , which can be deadly if not treated promptly.  One study found that  cardiac tamponade  was fatal in 13.3% of cases in which it was not caused by a  malignant   disease . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3693", "contents": "Studies have shown that hemopericardium can occur spontaneously in people with  essential thrombocythemia , although this is relatively rare. [ 7 ]   It is a more common occurrence in patients who have been over-prescribed  anticoagulants . [ 6 ]  Regardless of the underlying cause of the hemopericardium,  pericardiocentesis  has shown to be the best treatment method for the condition. [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3694", "contents": "Hemopneumothorax , or  haemopneumothorax , is the condition of having both air ( pneumothorax ) and blood ( hemothorax ) in the chest cavity. A hemothorax, pneumothorax, or the combination of both can occur due to an injury to the lung or chest. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3695", "contents": "The pleural space is located anatomically between the visceral membrane, which is firmly attached to the lungs, and the parietal membrane which is firmly attached to the chest wall (a.k.a. ribcage and intercostal muscles, muscles between the ribs).  The pleural space contains pleural fluid.  This fluid holds the two membranes together by surface tension, as much as a drop of water between two sheets of glass prevents them from separating.  Because of this, when the intercostal muscles move the ribcage outward, the lungs are pulled out as well, dropping the pressure in the lungs and pulling air into the bronchi, when we 'breathe in'.  The pleural space is maintained in a constant state of negative pressure (in comparison to atmospheric pressure)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3696", "contents": "If the chest wall, and thus the pleural space, is punctured, blood, air or both can enter the pleural space.  Air and/or blood rushes into the space in order to equalise the pressure with that of the atmosphere.  As a result, the fluid is disrupted and the two membranes no longer adhere to each other.  When the rib cage moves out, it no longer pulls the lungs with it.  Thus the lungs cannot expand, the pressure in the lungs never drops and no air is pulled into the bronchi.  Respiration is not possible.  The affected lung, which has a great deal of elastic tissue, shrivels in what is referred to as a collapsed lung. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3697", "contents": "If you have an injury or trauma to your chest, your doctor may order a chest X-ray to help see if fluid or air is building up within the chest cavity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3698", "contents": "Other diagnostic tests may also be performed to further evaluate the fluid in around the lungs, for instance a chest CT scan or an ultrasound. An ultrasound of the chest will show the amount of fluid and its exact location."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3699", "contents": "Treatment for this condition is the same as for hemothorax and pneumothorax independently: by  tube thoracostomy , the insertion of a chest drain through an incision made between the ribs, into the intercostal space.  A chest tube must be inserted to drain blood and air from the pleural space so it can return to a state of negative pressure and function normally. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3700", "contents": "Commonly, surgery is needed to close off whatever injuries caused the blood and air to enter the cavity (e.g. stabbing, broken ribs)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3701", "contents": "A  hemothorax  (derived from  hemo-  [blood] +  thorax  [chest], plural  hemothoraces ) is an accumulation of blood within the  pleural cavity . The symptoms of a hemothorax may include chest pain and difficulty breathing, while the clinical signs may include reduced breath sounds on the affected side and a  rapid heart rate . Hemothoraces are usually caused by an injury, but they may occur spontaneously due to  cancer  invading the pleural cavity, as a result of a  blood clotting disorder , as an unusual manifestation of  endometriosis , in response to  pneumothorax , or rarely in association with other conditions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3702", "contents": "Hemothoraces are usually diagnosed using a  chest X-ray , but they can be identified using other forms of imaging including  ultrasound , a  CT scan , or an  MRI . They can be differentiated from other forms of fluid within the pleural cavity by  analysing a sample of the fluid , and are defined as having a  hematocrit  of greater than 50% that of the person's blood. Hemothoraces may be treated by draining the blood using a  chest tube . Surgery may be required if the bleeding continues. If treated, the prognosis is usually good. Complications of a hemothorax include  infection within the pleural cavity  and the  formation of scar tissue ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3703", "contents": "The lungs are surrounded by two layers of tissue called the  pulmonary pleurae . In most healthy people, these two layers are tightly apposed, separated only by a small amount of  pleural fluid . In certain disease states, the space between these two layers, called the  pleural cavity , swells with fluid. This accumulation of fluid in the pleural cavity is called  pleural effusion . [ 1 ]  Pleural effusions are given specific names depending on the nature of the fluid:  hydrothorax  for  serous fluid ,  pyothorax  for pus, hemothorax for blood, and  urinothorax  for urine."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3704", "contents": "Signs and symptoms include anxiety, rapid breathing, restlessness, shock, and pale, cool, clammy skin. [ 2 ]  When the affected area is percussed, a dull feeling may be observed. Neck veins may be flat and breathing sounds reduced. It can also cause a collapsed lung ( atelectasis ). [ 3 ]  Massive hemothorax, often defined as over 1.5 liters of blood initially when an intercostal drain is placed, or a bleeding rate greater than 200ml per hour, can result in shock with two causes: massive bleeding resulting from hypovolemic shock, and venous pressure from the retained blood, impairing blood flow. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3705", "contents": "Hemothoraces are classified in three broad categories according to the cause and in order of frequency: traumatic, iatrogenic, or nontraumatic. All three categories have the potential to affect major arteries and result in death by blood loss. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3706", "contents": "Hemothorax is most often caused by blunt or penetrating trauma to the chest. [ 6 ]  In blunt traumatic cases, hemothorax typically occurs when  rib fracture  damages the  intercostal vessels  or the intraparenchymal pulmonary vessel, while in penetrating trauma, hemothorax occurs due to injuries directly affecting blood vessels in the thoracic wall, lung parenchyma, or the heart. [ 5 ]  If large blood vessels such as the aorta are damaged, the blood loss can be massive. [ 7 ]  Minor chest trauma can cause hemothorax when the blood's ability to clot is diminished as result either of  anticoagulant  medications or when there are bleeding disorders such as  hemophilia . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3707", "contents": "Iatrogenic  hemothorax can occur as a complication of heart and lung surgery, for example the rupture of lung arteries caused by the placement of catheters, thoracotomy, thoracostomy, or  thoracentesis . The most common iatrogenic causes include subclavian venous catheterizations and chest tube placements, with an occurrence rate of around 1%. [ 5 ]  Sometimes, a Swan-Ganz catheter causes rupture of the pulmonary artery, causing a massive hemothorax. [ 6 ]  It can also be caused by other procedures like  pleural ,  lung , or  transbronchial  biopsies,  CPR , [ 9 ]   Nuss procedure , [ 10 ]  or endoscopic treatment of  esophageal varices . [ 9 ]  Iatrogenic hemothorax is more common in people who have chronic kidney disease in the intensive care unit. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3708", "contents": "Less frequently, hemothoraces may occur spontaneously. Nontraumatic hemothoraces most frequently occur as a complication of some forms of cancer if the tumour invades the pleural space. [ 9 ]  Cancers responsible for hemothoraces include  angiosarcomas ,  schwannomas ,  mesothelioma ,  thymomas ,  germ cell tumours , and  lung cancer . Significant hemothoraces can occur with spontaneous rupture of small vessels when the blood's ability to clot is diminished as result of  anticoagulant  medications. [ 8 ]  In cases caused by anticoagulant therapy, the hemothorax becomes noticeable 4\u20137 days after anticoagulant therapy is started. In cases of hemothorax complicating pulmonary embolism treatment, the hemothorax is usually on the side of the original embolism. [ 6 ]  Those with an abnormal accumulation of air within the pleural space (a pneumothorax) can bleed into the cavity, which occurs in about 5% of cases of spontaneous pneumothorax, [ 8 ]  especially when  lung bullae  rupture. [ 11 ]  The resulting combination of air and blood within the pleural space is known as a  hemopneumothorax . [ 8 ]  Bone growth in  exostosis  can create sharp edges, which can result in hemothorax by damaging adjacent arteries. It can occur  postpartum  due to the change in thoracic pressure during labor. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3709", "contents": "Vascular causes of hemothorax include rupture of the descending aorta, in which case it initially involves the left pleural and mediastinal area due to the close vicinity of the pleural cavity. Rarely, a rupture of the thoracic aorta can result in a hemothorax, but the bleeding usually occurs in the pericardial space. [ 8 ]  Spontaneous tearing of blood vessels is more likely to occur in those with disorders that weaken blood vessels such as some forms of  Ehlers-Danlos syndrome , disorders that lead to malformed blood vessels as seen in  Rendu-Osler-Weber syndrome , or in bleeding disorders such as hemophilia and  Glanzmann thrombasthenia . Other rare causes of hemothorax include  neurofibromatosis type 1  and  extramedullary hematopoiesis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3710", "contents": "Rarely, hemothoraces can arise due to  extrapelvic endometriosis , a condition in which  tissue  similar to the lining that normally covers the inside of the  uterus  forms in unusual locations outside the pelvis. [ 12 ]  Endometriotic tissue that implants on the pleural surface can bleed in response to the hormonal changes of the menstrual cycle, causing what is known as a  catamenial  hemothorax as part of  thoracic endometriosis [ 12 ]  along with  catamenial pneumothorax , catamenial  hemoptysis , and  lung nodules  of endometriosis. [ 13 ]  Catamenial hemothorax represents 14% of cases of thoracic endometriosis syndrome [ 14 ]  while catamenial pneumothorax is seen in 73%, catamenial hemoptysis in 7%, and pulmonary nodules in 6%. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3711", "contents": "When a hemothorax occurs, blood enters the pleural cavity. The blood loss from the  circulation  has several effects. Firstly, as blood builds up within the pleural cavity, it begins to interfere with the normal movement of the lungs, preventing one or both lungs from fully expanding and thereby interfering with the normal transfer of oxygen and carbon dioxide to and from the blood. [ 15 ]  Secondly, blood that has been lost into the pleural cavity can no longer be circulated. Hemothoraces can lead to significant blood loss \u2013 each half of the thorax can hold more than 1500 milliliters of blood, representing more than 25% of an average adult's total blood volume. [ 16 ]  The body may struggle to cope with this blood loss, and tries to compensate by maintaining blood pressure by forcing the heart to pump harder and faster, and by squeezing or  constricting small blood vessels  in the arms and legs. [ 17 ]  These compensatory mechanisms can be recognised by a rapid resting heart rate and cool fingers and toes. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3712", "contents": "If the blood within the pleural cavity is not removed, it will eventually  clot . This clot tends to stick the parietal and visceral pleura together and has the potential to lead to scarring within the pleura, which if extensive leads to the condition known as a  fibrothorax . [ 19 ]  Following the initial loss of blood, a small hemothorax may irritate the pleura, causing additional fluid to seep out, leading to a bloodstained  pleural effusion . [ 20 ]  Furthermore, as enzymes in the  pleural fluid  begin to break down the clot, the protein concentration of the pleural fluid increases. As a result, the  osmotic pressure  of the pleural cavity increases, causing fluid to leak into the pleural cavity from the surrounding tissues. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3713", "contents": "Hemothoraces are most commonly detected using a  chest X-ray , although  ultrasound  is sometimes used in an emergency setting. [ 22 ]  It can be suspected in any person with any form of chest trauma. [ 6 ]  However, plain X-rays may miss smaller hemothoraces while other imaging modalities such as  computed tomography  (CT), or magnetic resonance imaging may be more sensitive. [ 22 ]  In cases where the nature of an effusion is in doubt, a sample of fluid can be aspirated and analysed in a procedure called  thoracentesis . [ 8 ]  Physical examination is used initially. Auscultation has been reported to have an accuracy of nearly 100% in diagnosing hemopneumothorax. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3714", "contents": "A chest X-ray is the most common technique used to diagnosis a hemothorax. [ 23 ]  X-rays should ideally be taken in an upright position (an erect chest X-ray), but may be performed with the person lying on their back (supine) if an erect chest X-ray is not feasible. On an erect chest X-ray, a hemothorax is suggested by blunting of the  costophrenic angle  or partial or complete opacification of the affected half of the thorax. On a supine film the blood tends to layer in the pleural space, but can be appreciated as a haziness of one half of the thorax relative to the other. [ 5 ]  A small hemothorax may be missed on a chest X-ray as several hundred milliliters of blood can be hidden by the  diaphragm  and abdominal viscera on an erect film. Supine X-rays are even less sensitive and as much as one liter of blood can be missed on a supine film. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3715", "contents": "Ultrasonography  may be used to detect hemothorax and other pleural effusions. This technique is of particular use in the critical care and trauma settings as it provides rapid, reliable results at the bedside. [ 23 ]  Ultrasound is more  sensitive  than chest x-ray in detecting hemothorax. [ 25 ]  Ultrasound can cause issues in people who are morbidly  obese  or have subcutaneous emphysema. When CT is unavailable in the current setting or the person cannot be moved to the scan, ultrasound is used. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3716", "contents": "Computed tomography (CT or CAT) scans may be useful for diagnosing retained hemothorax as this form of imaging can detect much smaller amounts of fluid than a plain chest X-ray. However, CT is less used as a primary means of diagnosis within the trauma setting, as these scans require a critically ill person to be transported to a scanner, are slower, and require the subject to remain supine. [ 23 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3717", "contents": "Magnetic resonance imaging (MRI) can be used to differentiate between a hemothorax and other forms of pleural effusion, and can suggest how long the hemothorax has been present for. Fresh blood can be seen as a fluid with low T1 but high T2 signals, while blood that has been present for more than a few hours displays both low T1 and T2 signals. [ 27 ]  MRI is used infrequently in the trauma setting due to the prolonged time required to perform an MRI, and the deterioration in image quality that occurs with motion. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3718", "contents": "Although imaging techniques can demonstrate that fluid is present within the pleural space, it may be unclear what this fluid represents. To establish the nature of the fluid, a sample can be removed by inserting a needle into the pleural cavity in a procedure known as a  thoracentesis  or pleural tap. In this context, the most important assessment of the pleural fluid is the percentage by volume that is taken up by red blood cells (the  hematocrit ) A hemothorax is defined as having a hematocrit of at least 50% [ 6 ]  of that found in the affected person's blood, although the hematocrit of a chronic hemothorax may be between 25 and 50% if additional fluid has been secreted by the pleura. [ 8 ]  Pleural fluid can dilute hemothoraces in as low as 3\u20134 days. [ 5 ]  The red blood cells in the effusion spontaneously break down. [ 11 ]  Distinguishing the pleural fluid from blood by colour is impossible when the hematocrit value is over 5%. [ 3 ]  For these reasons, even if there is a hematocrit value under 50%, further investigations can be done in order to figure out if there is a source of bleeding. [ 5 ]  Hematocrit can be roughly calculated by dividing the red blood cell count of the pleural fluid by 100,000. [ 6 ]  Thoracentesis is the test most commonly used to diagnose a hemothorax in animals. [ 28 ]  Hemothorax can itself be a rare complication of thoracentesis if the intercostal artery is punctured. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3719", "contents": "The treatment of a hemothorax depends largely on the extent of bleeding. While small hemothoraces may require little in the way of treatment, larger hemothoraces may require fluid resuscitation to replace the blood that has been lost, drainage of the blood within the pleural space using a procedure known as a tube  thoracostomy , and potentially surgery in the form of a  thoracotomy  or  video-assisted thoracoscopic surgery  (VATS) to prevent further bleeding. [ 6 ] [ 23 ] [ 15 ] [ 8 ]  Occasionally,  transcatheter arterial embolization  may be used to stop ongoing arterial bleeding. Additional treatment options include antibiotics to reduce the risk of infection and  fibrinolytic therapy  to break down clotted blood within the pleural space. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3720", "contents": "Blood in the cavity can be removed by inserting a drain ( chest tube ) in a procedure called a tube thoracostomy. This procedure is indicated for most causes of hemothorax, but should be avoided in aortic rupture which should be managed with immediate surgery. [ 30 ]  The thoracostomy tube is usually placed between the ribs in the sixth or seventh  intercostal space  at the  mid-axillary line . [ 15 ]  It is important to avoid a chest tube becoming obstructed by clotted blood as obstruction prevents adequate drainage of the pleural space. Clotting occurs as the  clotting cascade  is activated when the blood leaves the blood vessels and comes into contact with the pleural surface, injured lung or chest wall, or the thoracostomy tube. Inadequate drainage may lead to a retained hemothorax, increasing the risk of infection within the pleural space ( empyema ) or the formation of scar tissue (fibrothorax). [ 31 ]  Thoracostomy tubes with a diameter of 24\u201336 F (large-bore tubes) should be used, as these reduce the risk of blood clots obstructing the tube. Manual manipulation of chest tubes (referred to as milking, stripping, or tapping) is commonly performed to maintain an open tube, but no conclusive evidence has demonstrated that this improves drainage. [ 8 ]  If a chest tube does become obstructed, the tube can be cleared using open or closed techniques. [ 32 ]  Tubes should be removed as soon as drainage has stopped, as prolonged tube placement increases the risk of empyema. [ 33 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3721", "contents": "About 10\u201320% of traumatic hemothoraces require surgical management. [ 6 ]  Larger hemothoraces, or those that continue to bleed following drainage, may require surgery. This surgery may take the form of a traditional open-chest procedure (a thoracotomy), but may be performed using video-associated thoracoscopic surgery (VATS). While there is no universally accepted cutoff for the volume of blood loss required before surgery is indicated, generally accepted indications include more than 1500 mL of blood drained from a thoracostomy, bleeding rate of over 500mL/hr in the first hour followed by over 200 mL, hemodynamic instability, or the need for repeat blood transfusions. [ 8 ] [ 6 ]  VATS is less invasive and cheaper than an open thoracotomy, and can reduce the length of hospital stay, but a thoracotomy may be preferred when  hypovolemic shock  is present, [ 3 ]  in order to watch bleeding. [ 34 ]  The procedure should ideally be performed within 72 hours of the injury as delay may increase the risk of complications. [ 19 ]  In clotted hemothorax, VATS is the generally preferred procedure to remove the clot, and is indicated if the hemothorax fills 1/3 or more of a hemithorax. The ideal time to remove a clot using VATS is at 48\u201396 hours, but can be attempted up to nine days after the injury. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3722", "contents": "Thoracentesis is no longer used in the  treatment  of hemothorax, although it may still be used to treat small hemothoraces. [ 5 ]  In catamenial hemothorax, the bleeding is typically self-limiting and mild. Most people with the condition are stable and can be treated with hormonal therapies. They are only partially effective. Surgical removal of the endometrial tissue may be necessary in recurrent cases. However, the disease frequently recurs. [ 11 ]  Resuscitation with intravenous fluids or with  blood products  may be required. In fulminant cases, transfusions may be administered before admission to the hospital. Clotting abnormalities, such as those caused by anticoagulant medications, should be reversed. [ 35 ]  Prophylactic antibiotics are given for 24 hours in the case of trauma. [ 19 ]  Blood clots may be retained within the pleural cavity despite chest tube drainage. [ 6 ]  They are a risk factor for complications like fibrothorax and empyema. [ 3 ]  Such retained clots should be removed, preferably with  video-assisted thoracoscopic surgery  (VATS). If VATS is unavailable, an alternative is  fibrinolytic therapy  such as  streptokinase  or  urokinase  given directly into the pleural space seven to ten days after the injury. [ 6 ]  The issues with fibrinolytic therapy include having a high cost and lengthened hospital stay. [ 6 ]  Residual clot that does not dissipate in response to fibrinolytics may require surgical removal in the form of  decortication . [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3723", "contents": "The prognosis following a hemothorax depends on its size, the treatment given, and the underlying cause. While small hemothoraces may cause few problems, in severe cases an untreated hemothorax may be rapidly fatal due to uncontrolled blood loss. If left untreated, the accumulation of blood may put pressure on the  mediastinum  and the trachea, limiting the heart's ability to fill. However, if treated, the prognosis following a traumatic hemothorax is usually favourable and dependent on other non-thoracic injuries that have been sustained at the same time, the age of the person, and the need for  mechanical ventilation . [ 36 ]  Hemothoraces caused by benign conditions such as endometriosis have a good prognosis, while those caused by neurofibromatosis type 1 has a 36% rate of death, and those caused by aortic rupture are often fatal. [ 8 ]  Penetrating trauma is significantly less common, and has a much higher death rate, with up to 90% dying before arriving at the hospital.  Gunshot wounds  are associated with a higher death rates compared to  stab wounds . In cases of penetrating trauma involving the heart, less than 1% survive. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3724", "contents": "Complications can occur following a hemothorax, and are more likely to occur if the blood has not been adequately drained from the pleural cavity. Blood that remains within the pleural space can become infected, and is known as an  empyema . [ 3 ]  It occurs in 3\u20134% of traumatic cases, [ 9 ]  and 27-33% of retained hemothoraces. [ 37 ]  It is more likely in people who develop shock, had a contaminated pleural space during the injury, persistent  bronchopleural fistulae , and lung contusions. The likelihood of it can be reduced by keeping thoracostomy tubes sterile and by keeping the pleural surfaces close together to prevent fluid or blood from accumulating between the surfaces. [ 6 ]  The retained blood can irritate the pleura, causing scar tissue ( adhesions ) to form. If extensive, this scar tissue can encase the lung, restricting movement of the chest wall, and is then referred to as a  fibrothorax . [ 3 ]  Less than 1 percent of cases go on to develop a fibrothorax. Cases with hemopneumothorax or infection more often develop fibrothorax. After the chest tube is removed, over 10% of cases develop pleural effusions that are mostly self-limited and leave no lasting complications. In such cases, thoracentesis is performed to eliminate the possibility of an infection being present. [ 9 ]  Other potential complications include  atelectasis ,  lung infection , pneumothorax,  sepsis ,  respiratory distress ,  hypotension ,  tachycardia ,  pneumonia , adhesions, and impaired lung function. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3725", "contents": "Trauma to the thorax results in approximately 16,000 to 30,000 deaths every year. [ 5 ]  There are about 300,000 cases of hemothorax in the U.S every year.  Polytrauma  (injury to multiple body systems) involves chest injuries in 60% of cases and commonly leads to hemothorax. [ 19 ]  In a case study, 37% of people hospitalized for blunt chest trauma had traumatic hemothorax. Hemothorax commonly occurs with a displaced rib fracture. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3726", "contents": "In horses, hemothorax is uncommon and usually traumatic. [ 38 ] [ 39 ]  It may occur along with pneumothorax. [ 40 ]  It is mainly diagnosed by ultrasound. Treatment involves supportive care, correction of the underlying cause, and occasionally drainage. The prognosis is variable."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3727", "contents": "Hemothorax is usually caused by trauma to the thorax. [ 41 ]  It can result from any injury that involves the pleural, intercostal, intervertebral,  cardiac , [ 38 ]  or thoracic wall muscle. [ 41 ]  It can rarely be caused by diaphragmatic rupture that results in abdominal herniation. Hemothorax can be caused by cancers involving the thoracic, pulmonary, and mediastinal wall. The most common cancer resulting in hemothorax is a  hemangiosarcoma . [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3728", "contents": "Clinical signs and symptoms may be variable and cause-dependant. They may include rapid breathing, pain, and shallow breathing in cases with a rib fracture. [ 40 ]  In the case of extensive bleeding, signs of hypovolemia may occur, [ 39 ]  and rapid death may result within hours. [ 42 ]  In less acute cases with slower bleeding,  anemia  and  hypoproteinemia  may gradually develop. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3729", "contents": "Ultrasound can detect blood in the pleural cavity. Blood in the thorax is shown by a uniform area without  flocculation . [ 40 ]  Pleural effusions without blood are usually hypoechoic.  Echogenicity  is indicated by cellular debris and/or fibrin. Bloody pleural effusions are shows by a swirling, hyperechoic pattern. [ 38 ]  When a stethoscope is used ( auscultation ), the heartbeat sounds are faint. When percussion is performed, it produces a dull area. However, especially in traumatic cases, percussion may be painful. Although nonspecific, physical examinations may show reduced lung sounds and muffled, widespread heart sounds. Similar signs and symptoms may occur when other fluids are in the pleural cavity. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3730", "contents": "Treatment includes correction of the underlying cause. Drainage is not always required, [ 43 ]  but can be performed in case of infection or fluid levels resulting in respiratory compromise. However, drainage in contraindicated in cases caused by clotting disorders. [ 40 ]  Additionally, broad spectrum antibiotics can be given in the case of open trauma or pulmonary rupture. [ 42 ]  Supportive care may be required. It may include intranasal oxygen, painkillers, blood transfusions, and fluids. In order to avoid fluid overload, fluids are given slowly. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3731", "contents": "The prognosis significantly depends on the underlying cause of the hemothorax. In cases caused by uncomplicated thoracic trauma, the prognosis may be good, but the prognosis is worse in cases that are complicated by  pleuritis . Cases caused by cancer or clotting disorders have a poor prognosis, [ 40 ]  as do cases with massive bleeding due to injury to the heart or very large blood vessels. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3732", "contents": "Myocardial rupture  is a laceration of the  ventricles  or  atria  of the  heart , of the  interatrial  or  interventricular septum , or of the  papillary muscles .  It is most commonly seen as a serious  sequela  of an acute  myocardial infarction  (heart attack)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3733", "contents": "It can also be caused by trauma. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3734", "contents": "Symptoms of myocardial rupture are recurrent or persistent  chest pain ,  syncope , and  distension of jugular vein . Sudden death caused by a myocardial rupture is sometimes preceded by no symptoms. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3735", "contents": "The most common cause of myocardial rupture is a recent  myocardial infarction , with the rupture typically occurring three to five days after infarction. [ 3 ]  Other causes of rupture include cardiac trauma,  endocarditis  (infection of the heart), [ 4 ] [ 5 ]   cardiac tumors , infiltrative diseases of the heart, [ 4 ]  and  aortic dissection . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3736", "contents": "Risk factors for rupture after an acute myocardial infarction include female gender, [ 6 ] [ 7 ]  advanced age of the individual, [ 6 ] [ 7 ]  first ischemic event, and a low  body mass index . [ 6 ]   Other presenting signs associated with myocardial rupture include a pericardial friction rub, sluggish flow in the coronary artery after it is opened i.e. revascularized with an  angioplasty , the  left anterior descending artery  being often the cause of the acute MI, [ 6 ] [ 7 ] [ 8 ]  and delay of revascularization greater than 2 hours. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3737", "contents": "Due to the acute hemodynamic deterioration associated with myocardial rupture, the diagnosis is generally made based on physical examination, changes in the vital signs, and clinical suspicion.  The diagnosis can be confirmed with  echocardiography .  The diagnosis is ultimately made at autopsy. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3738", "contents": "Myocardial ruptures can be classified as one of three types. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3739", "contents": "Another method for classifying myocardial ruptures is by the anatomical portion of the heart that has ruptured.  By far the most dramatic is rupture of the free wall of the left or right ventricles, as this is associated with immediate hemodynamic collapse and death secondary to acute  pericardial tamponade .  Rupture of the interventricular septum will cause a  ventricular septal defect .  Rupture of a papillary muscle will cause acute  mitral regurgitation . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3740", "contents": "The rupture will most often occur near the edge of the necrotic myocardium where it abuts healthy (but hyperemic) myocardium where the inflammatory response is at its greatest.  Further, the rupture will occur in an area of greatest  shear stress .  Within the left ventricle, these areas are adjacent to both anterior and posterior papillary muscles (regardless of whether the papillary muscle is involved in the infarction). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3741", "contents": "Left ventricular free wall rupture almost always results in hemopericardium (the exception being in the scenario where the patient has had prior open heart surgery and has obliterative fibrous pericardial adhesions; these would prevent egress of blood) and pericardial tamponade.  An accumulation of as little as 75 ml of blood, acquired acutely in a patient without pre-existing pericardial effusion, is sufficient to produce tamponade (wherein the ventricles are incapable of filling and are thus incapable of producing adequate stroke volume). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3742", "contents": "The treatment for myocardial rupture is supportive in the immediate setting and surgical correction of the rupture, if feasible. [ citation needed ]   A certain small percentage of individuals do not seek medical attention in the acute setting and survive to see the physician days or weeks later.  In this setting, it may be reasonable to treat the rupture medically and delay or avoid surgery completely, depending on the individual's  comorbid  medical issues. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3743", "contents": "The prognosis of myocardial rupture is dependent on a number of factors, including which portion of the myocardium is involved in the rupture.  In one case series, if myocardial rupture involved the free wall of the  left ventricle , the  mortality rate  was 100.0%. [ 6 ]   The chances of survival rise dramatically if the patient: 1. has a witnessed initial event; 2. seeks early medical attention; 3. has an accurate diagnosis by the emergentologist; and 4. happens to be at a facility that has a cardiac surgery service (by whom a quick repair of the rupture can be attempted).  Even if the individual survives the initial hemodynamic sequelae of the rupture, the 30\u2011day mortality is still significantly higher than if rupture did not occur. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3744", "contents": "The incidence of myocardial rupture has decreased in the era of urgent revascularization and aggressive  pharmacological therapy  for the treatment of an acute myocardial infarction.  However, the decrease in the incidence of myocardial rupture is not uniform; there is a slight increase in the incidence of rupture if thrombolytic agents are used to abort a myocardial infarction. [ 10 ]   On the other hand, if  primary percutaneous coronary intervention  is performed to abort the infarction, the incidence of rupture is significantly lowered. [ 7 ]   The incidence of myocardial rupture if PCI is performed in the setting of an acute myocardial infarction is about 1 percent. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3745", "contents": "A  pneumatocele  is a cavity in the  lung parenchyma  filled with air that may result from pulmonary trauma during  mechanical ventilation . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3746", "contents": "Gas-filled, or air-filled lesions in  bone  are known as  pneumocysts . [ 2 ]  When a pneumocyst is found in a bone it is called an  intraosseous pneumocyst , or a  vertebral pneumocyst  when found in a  vertebra . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3747", "contents": "A pneumatocele results when a  lung laceration , a cut or tear in the lung tissue, fills with air. [ 4 ]  A rupture of a small airway creates the air-filled cavity. [ 1 ]  Pulmonary lacerations that fill with blood are called  pulmonary hematomas . [ 4 ]  In some cases, both pneumatoceles and  hematomas  exist in the same injured lung. [ 5 ]  A pneumatocele can become enlarged, for example when the patient is mechanically ventilated or has  acute respiratory distress syndrome , in which case it may not go away for months. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3748", "contents": "Intraosseous pneumatocysts in the bone are rare and of unclear origin. They are benign and usually  without symptoms . [ 3 ]  They are also found around a sacroiliac joint, and there has been one reported case of an  acetabular  pneumocyst. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3749", "contents": "Diagnosis can be made using  chest X-ray ; the lesion shows up as a small, round area filled with air. [ 1 ]   Computed tomography  can give a more detailed understanding of the lesion. [ 1 ]   Differential diagnoses  \u2013 other conditions that could cause similar symptoms as pneumatocele include  lung cancer ,  tuberculosis , [ 7 ]  and a  lung abscess [ 1 ]  in the setting of  hyper IgE syndrome  (aka Job's syndrome), as a complication of COVID-19 pneumonitis, [ 8 ]  or on its own, often caused by  Staphylococcus aureus  infection during  cystic fibrosis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3750", "contents": "Treatment typically is supportive and includes monitoring and observation. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3751", "contents": "Al-Tarawneh, Emad; AL-Qudah, Mohammad; Hadidi, Fadi (March 2014).  \"Incidental Intraosseous Pneumatocyst with gas-density-fluid level in an adolescent: a case report and review of the literature\" .  Journal of Radiology Case Reports .  8  (3):  16\u2013 22.  doi : 10.3941/jrcr.v8i3.1540 .  PMC \u00a0 4035364 .  PMID \u00a0 24967024 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3752", "contents": "A  pneumothorax  is an abnormal collection of air in the  pleural space  between the  lung  and the  chest wall . [ 3 ]  Symptoms typically include sudden onset of sharp, one-sided  chest pain  and  shortness of breath . [ 2 ]  In a minority of cases, a one-way valve is formed by an area of damaged  tissue , and the amount of air in the space between chest wall and lungs increases; this is called a tension pneumothorax. [ 3 ]  This can cause a steadily worsening  oxygen shortage  and  low blood pressure . This leads to a type of shock called  obstructive shock , which can be fatal unless reversed. [ 3 ]  Very rarely, both lungs may be affected by a pneumothorax. [ 6 ]  It is often called a \" collapsed lung \", although that term may also refer to  atelectasis . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3753", "contents": "A primary spontaneous pneumothorax is one that occurs without an apparent cause and in the absence of significant  lung disease . [ 3 ]  A secondary spontaneous pneumothorax occurs in the presence of existing lung disease. [ 3 ] [ 7 ]  Smoking increases the risk of primary spontaneous pneumothorax, while the main underlying causes for secondary pneumothorax are  COPD ,  asthma , and  tuberculosis . [ 3 ] [ 4 ]  A traumatic pneumothorax can develop from  physical trauma  to the  chest  (including a  blast injury ) or from a  complication of a healthcare intervention . [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3754", "contents": "Diagnosis of a pneumothorax by  physical examination  alone can be difficult (particularly in smaller pneumothoraces). [ 10 ]  A  chest X-ray ,  computed tomography  (CT) scan, or  ultrasound  is usually used to confirm its presence. [ 5 ]  Other conditions that can result in similar symptoms include a  hemothorax  (buildup of  blood  in the pleural space),  pulmonary embolism , and  heart attack . [ 2 ] [ 11 ]  A large  bulla  may look similar on a chest X-ray. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3755", "contents": "A small spontaneous pneumothorax will typically resolve without treatment and requires only monitoring. [ 3 ]  This approach may be most appropriate in people who have no underlying lung disease. [ 3 ]  In a larger pneumothorax, or if there is shortness of breath, the air may be removed with a  syringe  or a  chest tube  connected to a one-way valve system. [ 3 ]  Occasionally,  surgery  may be required if tube drainage is unsuccessful, or as a preventive measure, if there have been repeated episodes. [ 3 ]  The surgical treatments usually involve  pleurodesis  (in which the layers of  pleura  are induced to stick together) or  pleurectomy  (the surgical removal of pleural membranes). [ 3 ]  About 17\u201323 cases of pneumothorax occur per 100,000 people per year. [ 3 ] [ 5 ]  They are more common in men than women. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3756", "contents": "A primary spontaneous pneumothorax (PSP) tends to occur in a young adult without underlying lung problems, and usually causes limited symptoms. Chest pain and sometimes mild breathlessness are the usual predominant presenting features. [ 12 ] [ 13 ]  In newborns  tachypnea ,  cyanosis  and grunting are the most common presenting symptoms. [ 14 ]  People who are affected by a PSP are often unaware of the potential danger and may wait several days before seeking medical attention. [ 15 ]  PSPs more commonly occur during changes in  atmospheric pressure , explaining to some extent why episodes of pneumothorax may happen in clusters. [ 13 ]  It is rare for a PSP to cause a tension pneumothorax. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3757", "contents": "Secondary spontaneous pneumothoraces (SSPs), by definition, occur in individuals with significant underlying lung disease. Symptoms in SSPs tend to be more severe than in PSPs, as the unaffected lungs are generally unable to replace the loss of function in the affected lungs.  Hypoxemia  (decreased blood-oxygen levels) is usually present and may be observed as  cyanosis  (blue discoloration of the lips and skin).  Hypercapnia  (accumulation of carbon dioxide in the blood) is sometimes encountered; this may cause  confusion  and \u2013 if very severe \u2013 may result in  comas . The sudden onset of breathlessness in someone with  chronic obstructive pulmonary disease  (COPD),  cystic fibrosis , or other serious lung diseases should therefore prompt investigations to identify the possibility of a pneumothorax. [ 12 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3758", "contents": "Traumatic pneumothorax most commonly occurs when the chest wall is pierced, such as when a  stab wound  or  gunshot wound  allows air to enter the  pleural space , or because some other mechanical injury to the lung compromises the integrity of the involved structures. Traumatic pneumothoraces have been found to occur in up to half of all cases of chest trauma, with only  rib fractures  being more common in this group. The pneumothorax can be occult (not readily apparent) in half of these cases, but may enlarge \u2013 particularly if  mechanical ventilation  is required. [ 13 ]  They are also encountered in people already receiving mechanical ventilation for some other reason. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3759", "contents": "Upon  physical examination ,  breath sounds  (heard with a  stethoscope ) may be diminished on the affected side, partly because air in the pleural space dampens the transmission of sound. Measures of the conduction of vocal vibrations to the surface of the chest may be altered.  Percussion  of the chest may be perceived as hyperresonant (like a booming drum), and  vocal resonance  and  tactile fremitus  can both be noticeably decreased. Importantly, the volume of the pneumothorax may not be well  correlated  with the intensity of the symptoms experienced by the victim, [ 15 ]  and physical signs may not be apparent if the pneumothorax is relatively small. [ 13 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3760", "contents": "Tension pneumothorax is generally considered to be present when a pneumothorax (primary spontaneous, secondary spontaneous, or traumatic) leads to significant impairment of  respiration  and/or  blood circulation . [ 16 ]  This causes a type of circulatory shock, called  obstructive shock . Tension pneumothorax tends to occur in clinical situations such as ventilation, resuscitation, trauma, or in people with lung disease. [ 15 ]  It is a  medical emergency  and may require immediate treatment without further investigations (see  Treatment section ). [ 15 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3761", "contents": "The most common findings in people with tension pneumothorax are chest pain and respiratory distress, often with an increased  heart rate  ( tachycardia ) and rapid breathing ( tachypnea ) in the initial stages. Other findings may include quieter breath sounds on one side of the chest, low  oxygen levels  and  blood pressure , and displacement of the  trachea  away from the affected side. Rarely, there may be  cyanosis ,  altered level of consciousness , a hyperresonant percussion note on examination of the affected side with reduced expansion and decreased movement, pain in the  epigastrium  (upper abdomen), displacement of the  apex beat  (heart impulse), and resonant sound when tapping the  sternum . [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3762", "contents": "Tension pneumothorax may also occur in someone who is receiving mechanical ventilation, in which case it may be difficult to spot as the person is typically receiving  sedation ; it is often noted because of a sudden deterioration in condition. [ 16 ]  Recent studies have shown that the development of tension features may not always be as rapid as previously thought. Deviation of the trachea to one side and the presence of raised  jugular venous pressure  (distended neck veins) are not reliable as clinical signs. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3763", "contents": "Spontaneous pneumothoraces are divided into two types:  primary , which occurs in the absence of known lung disease, and  secondary , which occurs in someone with underlying lung disease. [ 17 ]  The cause of primary spontaneous pneumothorax is unknown, but established risk factors include being of the male sex,  smoking , and a  family history  of pneumothorax. [ 18 ]  Smoking either  cannabis  or  tobacco  increases the risk. [ 3 ]  The various suspected underlying mechanisms are discussed  below . [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3764", "contents": "Secondary spontaneous pneumothorax occurs in the setting of a variety of lung diseases. The most common is  chronic obstructive pulmonary disease  (COPD), which accounts for approximately 70% of cases. [ 18 ]  The following known lung diseases may significantly increase the risk for pneumothorax."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3765", "contents": "In children, additional causes include  measles ,  echinococcosis , inhalation of a  foreign body , and certain  congenital malformations  ( congenital pulmonary airway malformation  and  congenital lobar emphysema ). [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3766", "contents": "11.5% of people with a spontaneous pneumothorax have a family member who has previously experienced a pneumothorax. Several hereditary conditions \u2013  Marfan syndrome ,  homocystinuria ,  Ehlers\u2013Danlos syndromes ,  alpha 1-antitrypsin deficiency  (which leads to  emphysema ), and  Birt\u2013Hogg\u2013Dub\u00e9 syndrome  \u2013 have all been linked to familial pneumothorax. [ 20 ]  Generally, these conditions cause other signs and symptoms as well, and pneumothorax is not usually the primary finding. [ 20 ]  Birt\u2013Hogg\u2013Dub\u00e9 syndrome is caused by mutations in the  FLCN   gene  (located at  chromosome 17p 11.2), which encodes a protein named  folliculin . [ 19 ] [ 20 ]   FLCN  mutations and lung lesions have also been identified in familial cases of pneumothorax where other features of Birt\u2013Hogg\u2013Dub\u00e9 syndrome are absent. [ 19 ]  In addition to the genetic associations, the  HLA   haplotype  A 2 B 40  is also a genetic predisposition to PSP. [ 21 ] [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3767", "contents": "A traumatic pneumothorax may result from either  blunt trauma  or  penetrating injury  to the chest wall. [ 13 ]  The most common mechanism is the penetration of sharp bony points at a new  rib fracture , which damages lung tissue. [ 18 ]  Traumatic pneumothorax may also be observed in those  exposed to blasts , even when there is no apparent injury to the chest. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3768", "contents": "Traumatic pneumothoraces may be classified as \"open\" or \"closed\". In an open pneumothorax, there is a passage from the external environment into the pleural space through the chest wall. When air is drawn into the pleural space through this passageway, it is known as a \"sucking chest wound\". A closed pneumothorax is when the chest wall remains intact. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3769", "contents": "Pneumothorax was reported as an adverse event caused by misplaced  nasogastric feeding tubes .  Avanos Medical 's feeding tube placement system, the CORTRAK* 2 EAS, was recalled in May 2022 by the  FDA  due to adverse events reported, including pneumothorax, leading to 60 injuries and 23 people dying as communicated by the FDA. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3770", "contents": "Medical procedures, such as inserting a  central venous catheter  into one of the chest veins or taking  biopsy  samples from lung tissue, may also lead to pneumothorax. The administration of  positive pressure ventilation , either  mechanical ventilation  or  non-invasive ventilation , can result in  barotrauma  (pressure-related injury) leading to a pneumothorax. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3771", "contents": "Divers  who breathe from an underwater apparatus are supplied with breathing gas at  ambient pressure , which results in their lungs containing gas at higher than atmospheric pressure. Divers breathing compressed air (such as when  scuba diving ) may develop a pneumothorax as a result of  barotrauma  from ascending just 1 metre (3\u00a0ft) while breath-holding with their lungs fully inflated. [ 25 ]  An additional problem in these cases is that those with other features of  decompression sickness  are typically treated in a  diving chamber  with  hyperbaric therapy ; this can lead to a small pneumothorax rapidly enlarging and causing features of tension. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3772", "contents": "Pneumothorax is more common in neonates than in any other age group. The incidence of symptomatic neonatal is estimated to be around 1-3 per 1000 live births. Prematurity, low birth weight and asphyxia are the major risk factors, and a majority of newborn infant cases occur during the first 72 hours of life. [ 26 ] [ 27 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3773", "contents": "The  thoracic cavity  is the space inside the chest that contains the lungs, heart, and numerous major blood vessels. On each side of the cavity, a pleural membrane covers the surface of lung ( visceral pleura ) and also lines the inside of the chest wall ( parietal pleura ). Normally, the two layers are separated by a small amount of lubricating  serous fluid . The lungs are fully inflated within the cavity because the pressure inside the airways ( intrapulmonary pressure ) is higher than the pressure inside the pleural space ( intrapleural pressure ). Despite the low pressure in the pleural space, air does not enter it because there are no natural connections to air-containing passages, and the pressure of gases in the bloodstream is too low for them to be forced into the pleural space. [ 13 ]  Therefore, a pneumothorax can only develop if air is allowed to enter, through damage to the chest wall or to the lung itself, or occasionally because  microorganisms  in the pleural space produce gas. [ 13 ]  Once air enters the pleural cavity, the intrapleural pressure increases, resulting in the difference between the intrapulmonary pressure and the intrapleural pressure (defined as the  transpulmonary pressure ) to equal zero, which cause the lungs to deflate in contrast to a normal transpulmonary pressure of ~4\u00a0mm Hg. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3774", "contents": "Chest-wall defects are usually evident in cases of injury to the chest wall, such as stab or bullet wounds (\"open pneumothorax\"). In secondary spontaneous pneumothoraces, vulnerabilities in the  lung tissue  are caused by a variety of disease processes, particularly by rupturing of  bullae  (large air-containing lesions) in cases of severe  emphysema . Areas of  necrosis  (tissue death) may precipitate episodes of pneumothorax, although the exact mechanism is unclear. [ 12 ]  Primary spontaneous pneumothorax (PSP) has for many years been thought to be caused by \" blebs \" (small air-filled lesions just under the pleural surface), which were presumed to be more common in those classically at risk of pneumothorax (tall males) due to mechanical factors. In PSP, blebs can be found in 77% of cases, compared to 6% in the general population without a history of PSP. [ 29 ]  As these healthy subjects do not all develop a pneumothorax later, the hypothesis may not be sufficient to explain all episodes; furthermore, pneumothorax may recur even after surgical treatment of blebs. [ 13 ]  It has therefore been suggested that PSP may also be caused by areas of disruption (porosity) in the pleural layer, which are prone to rupture. [ 12 ] [ 13 ] [ 29 ]  Smoking may additionally lead to  inflammation  and  obstruction  of  small airways , which account for the markedly increased risk of PSPs in smokers. [ 15 ]  Once air has stopped entering the pleural cavity, it is gradually reabsorbed. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3775", "contents": "Tension pneumothorax occurs when the opening that allows air to enter the pleural space functions as a one-way valve, allowing more air to enter with every breath but none to escape. The body compensates by increasing the  respiratory rate  and  tidal volume  (size of each breath), worsening the problem. Unless corrected, hypoxia (decreased oxygen levels) and  respiratory arrest  eventually follow. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3776", "contents": "The symptoms of pneumothorax can be vague and inconclusive, especially in those with a small PSP; confirmation with  medical imaging  is usually required. [ 15 ]  In contrast, tension pneumothorax is a medical emergency and may be treated before imaging \u2013 especially if there is severe hypoxia, very low blood pressure, or an impaired level of consciousness. In tension pneumothorax, X-rays are sometimes required if there is doubt about the  anatomical location  of the pneumothorax. [ 16 ] [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3777", "contents": "A plain  chest radiograph , ideally with the  X-ray  beams being projected from the back (posteroanterior, or \"PA\"), and during maximal inspiration (holding one's breath), is the most appropriate first investigation. [ 30 ]  It is not believed that routinely taking images during expiration would confer any benefit. [ 31 ]  Still, they may be useful in the detection of a pneumothorax when clinical suspicion is high but yet an inspiratory radiograph appears normal. [ 32 ]  Also, if the PA X-ray does not show a pneumothorax but there is a strong suspicion of one, lateral X-rays (with beams projecting from the side) may be performed, but this is not routine practice. [ 15 ] [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3778", "contents": "It is not unusual for the  mediastinum  (the structure between the lungs that contains the heart, great blood vessels, and large airways) to be  shifted away  from the affected lung due to the pressure differences. This is  not  equivalent to a tension pneumothorax, which is determined mainly by the constellation of symptoms, hypoxia, and  shock . [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3779", "contents": "The size of the pneumothorax (i.e. the volume of air in the pleural space) can be determined with a reasonable degree of accuracy by measuring the distance between the chest wall and the lung. This is relevant to treatment, as smaller pneumothoraces may be managed differently. An air rim of 2\u00a0cm means that the pneumothorax occupies about 50% of the hemithorax. [ 15 ]  British professional guidelines have traditionally stated that the measurement should be performed at the level of the  hilum  (where blood vessels and airways enter the lung) with 2\u00a0cm as the cutoff, [ 15 ]  while American guidelines state that the measurement should be done at the  apex  (top) of the lung with 3\u00a0cm differentiating between a \"small\" and a \"large\" pneumothorax. [ 33 ]  The latter method may overestimate the size of a pneumothorax if it is located mainly at the apex, which is a common occurrence. [ 15 ]  The various methods correlate poorly but are the best easily available ways of estimating pneumothorax size. [ 15 ] [ 19 ]  CT scanning (see below) can provide a more accurate determination of the size of the pneumothorax, but its routine use in this setting is not recommended. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3780", "contents": "Not all pneumothoraces are uniform; some only form a pocket of air in a particular place in the chest. [ 15 ]  Small amounts of fluid may be noted on the chest X-ray ( hydropneumothorax ); this may be blood ( hemopneumothorax ). [ 13 ]  In some cases, the only significant abnormality may be the \" deep sulcus sign \", in which the normally small space between the chest wall and the  diaphragm  appears enlarged due to the abnormal presence of fluid. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3781", "contents": "A  CT scan  is not necessary for the diagnosis of pneumothorax, but it can be useful in particular situations. In some lung diseases, especially emphysema, it is possible for abnormal lung areas such as bullae (large air-filled sacs) to have the same appearance as a pneumothorax on chest X-ray, and it may not be safe to apply any treatment before the distinction is made and before the exact location and size of the pneumothorax is determined. [ 15 ]  In trauma, where it may not be possible to perform an upright film, chest radiography may miss up to a third of pneumothoraces, while CT remains very  sensitive . [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3782", "contents": "A further use of CT is in the identification of underlying lung lesions. In presumed primary pneumothorax, it may help to identify blebs or  cystic lesions  (in anticipation of treatment, see below), and in secondary pneumothorax, it can help to identify most of the causes listed above. [ 15 ] [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3783", "contents": "Ultrasound  is commonly used in the evaluation of people who have sustained physical trauma, for example with the  FAST protocol . [ 34 ]  Ultrasound may be more sensitive than chest X-rays in the identification of pneumothorax after  blunt trauma  to the chest. [ 35 ]  Ultrasound may also provide a rapid diagnosis in other emergency situations, and allow the quantification of the size of the pneumothorax. Several particular features on ultrasonography of the chest can be used to confirm or exclude the diagnosis. [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3784", "contents": "The treatment of pneumothorax depends on a number of factors and may vary from discharge with early follow-up to immediate  needle decompression  or insertion of a  chest tube . Treatment is determined by the severity of symptoms and indicators of  acute  illness, the presence of underlying lung disease, the estimated size of the pneumothorax on X-ray, and \u2013 in some instances \u2013 on the personal preference of the person involved. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3785", "contents": "In traumatic pneumothorax, chest tubes are usually inserted. If mechanical ventilation is required, the risk of tension pneumothorax is greatly increased and the insertion of a chest tube is mandatory. [ 13 ] [ 40 ]  Any open chest wound should be covered with an airtight seal, as it carries a high risk of leading to tension pneumothorax. Ideally, a  dressing  called the \"Asherman seal\" should be utilized, as it appears to be more effective than a standard \"three-sided\" dressing. The Asherman seal is a specially designed device that adheres to the chest wall and, through a valve-like mechanism, allows air to escape but not to enter the chest. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3786", "contents": "Tension pneumothorax is usually treated with urgent needle decompression. This may be required before transport to the hospital, and can be performed by an  emergency medical technician  or other trained professional. [ 16 ] [ 41 ]  The needle or  cannula  is left in place until a chest tube can be inserted. [ 16 ] [ 41 ]  Critical care teams are able to incise the chest to create a larger conduit as performed when placing a chest drain, but without inserting the chest tube. This is called a simple thoracostomy. [ 42 ]  If tension pneumothorax leads to  cardiac arrest , needle decompression or simple thoracostomy is performed as part of resuscitation as it may restore  cardiac output . [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3787", "contents": "Small spontaneous pneumothoraces do not always require treatment, as they are unlikely to proceed to  respiratory failure  or tension pneumothorax, and generally resolve spontaneously. This approach is most appropriate if the estimated size of the pneumothorax is small (defined as <50% of the volume of the hemithorax), there is no  breathlessness , and there is no underlying lung disease. [ 19 ] [ 33 ]  It may be appropriate to treat a larger PSP conservatively if the symptoms are limited. [ 15 ]  Admission to hospital is often not required, as long as clear instructions are given to return to hospital if there are worsening symptoms. Further investigations may be performed as an  outpatient , at which time X-rays are repeated to confirm improvement, and advice given with regard to preventing recurrence (see below). [ 15 ]  Estimated rates of resorption are between 1.25% and 2.2% the volume of the cavity per day. This would mean that even a complete pneumothorax would spontaneously resolve over a period of about 6\u00a0weeks. [ 15 ]  There is, however, no high quality evidence comparing conservative to non conservative management. [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3788", "contents": "Secondary pneumothoraces are only treated conservatively if the size is very small (1\u00a0cm or less air rim) and there are limited symptoms. Admission to the hospital is usually recommended.  Oxygen  given at a high flow rate may accelerate resorption as much as fourfold. [ 15 ] [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3789", "contents": "In a large PSP (>50%), or in a PSP associated with breathlessness, some guidelines recommend that reducing the size by aspiration is equally effective as the insertion of a chest tube. This involves the administration of  local anesthetic  and inserting a needle connected to a three-way tap; up to 2.5\u00a0liters of air (in adults) are removed. If there has been significant reduction in the size of the pneumothorax on subsequent X-ray, the remainder of the treatment can be conservative. This approach has been shown to be effective in over 50% of cases. [ 12 ] [ 15 ] [ 19 ]  Compared to tube drainage, first-line aspiration in PSP reduces the number of people requiring hospital admission, without increasing the risk of complications. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3790", "contents": "Aspiration may also be considered in secondary pneumothorax of moderate size (air rim 1\u20132\u00a0cm) without breathlessness, with the difference that ongoing observation in hospital is required even after a successful procedure. [ 15 ]  American professional guidelines state that all large pneumothoraces \u2013 even those due to PSP \u2013 should be treated with a chest tube. [ 33 ]  Moderately sized  iatrogenic  traumatic pneumothoraces (due to medical procedures) may initially be treated with aspiration. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3791", "contents": "A  chest tube  (or intercostal drain) is the most definitive initial treatment of a pneumothorax. These are typically inserted in an area under the  axilla  (armpit) called the \" safe triangle \", where damage to internal organs can be avoided; this is delineated by a horizontal line at the level of the nipple and two muscles of the chest wall ( latissimus dorsi  and  pectoralis major ). Local anesthetic is applied. Two types of tubes may be used. In spontaneous pneumothorax, small-bore (smaller than 14\u00a0 F , 4.7\u00a0mm diameter) tubes may be inserted by the  Seldinger technique , and larger tubes do not have an advantage. [ 15 ] [ 47 ]  In traumatic pneumothorax, larger tubes (28\u00a0F, 9.3\u00a0mm) are used. [ 41 ]  When chest tubes are placed due to either blunt or penetrating trauma,  antibiotics  decrease the risks of infectious complications. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3792", "contents": "Chest tubes are required in PSPs that have not responded to needle aspiration, in large SSPs (>50%), and in cases of tension pneumothorax. They are connected to a  one-way valve  system that allows air to escape, but not to re-enter, the chest. This may include a bottle with water that functions like a  water seal , or a  Heimlich valve . They are not normally connected to a negative pressure circuit, as this would result in rapid re-expansion of the lung and a risk of  pulmonary edema  (\"re-expansion pulmonary edema\"). The tube is left in place until no air is seen to escape from it for a period of time, and X-rays confirm re-expansion of the lung. [ 15 ] [ 19 ] [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3793", "contents": "If after 2\u20134\u00a0days there is still evidence of an air leak, various options are available. Negative pressure suction (at low pressures of \u201310 to \u201320\u00a0 cmH 2 O ) at a high flow rate may be attempted, particularly in PSP; it is thought that this may accelerate the healing of the leak. Failing this, surgery may be required, especially in SSP. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3794", "contents": "Chest tubes are used first-line when pneumothorax occurs in people with  AIDS , usually due to underlying  pneumocystis pneumonia  (PCP), as this condition is associated with prolonged air leakage. Bilateral pneumothorax (pneumothorax on both sides) is relatively common in people with pneumocystis pneumonia, and surgery is often required. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3795", "contents": "It is possible for a person with a chest tube to be managed in an  ambulatory care  setting by using a Heimlich valve, although research to demonstrate the equivalence to hospitalization has been of limited quality. [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3796", "contents": "Pleurodesis  is a procedure that permanently eliminates the pleural space and attaches the lung to the chest wall. No long-term study (20 years or more) has been performed on its consequences. Good results in the short term are achieved with a  thoracotomy  (surgical opening of the chest) with identification of any source of air leakage and stapling of blebs followed by pleurectomy (stripping of the pleural lining) of the outer pleural layer and pleural abrasion (scraping of the pleura) of the inner layer. During the healing process, the lung adheres to the chest wall, effectively obliterating the pleural space. Recurrence rates are approximately 1%. [ 12 ] [ 15 ]  Post-thoracotomy pain is relatively common."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3797", "contents": "A less invasive approach is  thoracoscopy , usually in the form of a procedure called  video-assisted thoracoscopic surgery  (VATS). The results from VATS-based pleural abrasion are slightly worse than those achieved using thoracotomy in the short term, but produce smaller scars in the skin. [ 12 ] [ 15 ]  Compared to open thoracotomy, VATS offers a shorter in-hospital stays, less need for postoperative pain control, and a reduced risk of lung problems after surgery. [ 15 ]  VATS may also be used to achieve chemical pleurodesis; this involves insufflation of  talc , which activates an inflammatory reaction that causes the lung to adhere to the chest wall. [ 12 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3798", "contents": "If a chest tube is already in place, various agents may be instilled through the tube to achieve chemical  pleurodesis , such as talc,  tetracycline ,  minocycline  or  doxycycline . Results of chemical pleurodesis tend to be worse than when using surgical approaches, [ 12 ] [ 15 ]  but talc pleurodesis has been found to have few negative long-term consequences in younger people. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3799", "contents": "If pneumothorax occurs in a smoker, this is considered an opportunity to emphasize the markedly increased risk of recurrence in those who continue to smoke, and the many benefits of  smoking cessation . [ 15 ]  It may be advisable for someone to remain off work for up to a week after a spontaneous pneumothorax. If the person normally performs heavy manual labor, several weeks may be required. Those who have undergone pleurodesis may need two to three weeks off work to recover. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3800", "contents": "Air travel  is discouraged for up to seven days after complete resolution of a pneumothorax if recurrence does not occur. [ 15 ]   Underwater diving  is considered unsafe after an episode of pneumothorax unless a preventive procedure has been performed. Professional guidelines suggest that pleurectomy be performed on both lungs and that  lung function tests  and CT scan normalize before diving is resumed. [ 15 ] [ 33 ]  Aircraft pilots may also require assessment for surgery. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3801", "contents": "For newborn infants with pneumothorax, different management strategies have been suggested including careful observation,  thoracentesis  (needle aspiration), or insertion of a  chest tube . [ 27 ]  Needle aspiration may reduce the need for a chest tube, however, the effectiveness and safety of both invasive procedures have not been fully studied. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3802", "contents": "A preventative procedure ( thoracotomy  or thoracoscopy with pleurodesis) may be recommended after an episode of pneumothorax, with the intention to prevent recurrence.  Evidence  on the most effective treatment is still conflicting in some areas, and there is variation between treatments available in Europe and the US. [ 12 ]  Not all episodes of pneumothorax require such interventions; the decision depends largely on estimation of the risk of recurrence. These procedures are often recommended after the occurrence of a second pneumothorax. [ 51 ]  Surgery may need to be considered if someone has experienced pneumothorax on both sides (\"bilateral\"), sequential episodes that involve both sides, or if an episode was associated with pregnancy. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3803", "contents": "The annual age-adjusted  incidence rate  (AAIR) of PSP is thought to be three to six times as high in males as in females. Fishman [ 52 ] [ 53 ]  cites AAIR's of 7.4 and 1.2 cases per 100,000 person-years in males and females, respectively. Significantly above-average height is also associated with increased risk of PSP \u2013 in people who are at least 76 inches (1.93 meters) tall, the AAIR is about 200 cases per 100,000 person-years. Slim build also seems to increase the risk of PSP. [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3804", "contents": "The risk of contracting a first spontaneous pneumothorax is elevated among male and female smokers by factors of approximately 22 and 9, respectively, compared to matched non-smokers of the same sex. [ 54 ]  Individuals who smoke at higher intensity are at higher risk, with a \"greater-than-linear\" effect; men who smoke 10 cigarettes per day have an approximate 20-fold increased risk over comparable non-smokers, while smokers consuming 20 cigarettes per day show an estimated 100-fold increase in risk. [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3805", "contents": "In secondary spontaneous pneumothorax, the estimated annual AAIR is 6.3 and 2.0 cases per 100,000 person-years for males and females, [ 21 ] [ 55 ]  respectively, with the risk of recurrence depending on the presence and severity of any underlying lung disease. Once a second episode has occurred, there is a high likelihood of subsequent further episodes. [ 12 ]  The incidence in children has not been well studied, [ 19 ]  but is estimated to be between 5 and 10 cases per 100,000 person-years. [ 56 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3806", "contents": "Death from pneumothorax is very uncommon (except in tension pneumothoraces). British statistics show an annual mortality rate of 1.26 and 0.62 deaths per million person-years in men and women, respectively. [ 15 ]  A significantly increased risk of death is seen in older people and in those with secondary pneumothoraces, when the lung collapses due to another underlying health condition such as  chronic lung disease . [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3807", "contents": "An early description of traumatic pneumothorax secondary to rib fractures appears in  Imperial Surgery  by Turkish surgeon  \u015eerafeddin Sabuncuo\u011flu  (1385\u20131468), which also recommends a method of simple aspiration. [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3808", "contents": "Pneumothorax was described in 1803 by  Jean Marc Gaspard Itard , a student of  Ren\u00e9 Laennec , who provided an extensive description of the clinical picture in 1819. [ 58 ]  While Itard and Laennec recognized that some cases were not due to  tuberculosis  (then the most common cause), the concept of spontaneous pneumothorax in the absence of tuberculosis (primary pneumothorax) was reintroduced by the Danish physician Hans Kj\u00e6rgaard in 1932. [ 15 ] [ 29 ] [ 59 ]  In 1941, the surgeons Tyson and Crandall introduced pleural abrasion for the treatment of pneumothorax. [ 15 ] [ 60 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3809", "contents": "Prior to the advent of  anti-tuberculous medications , pneumothoraces were intentionally caused by healthcare providers in people with tuberculosis in an effort to collapse a  lobe , or entire  lung , around a cavitating  lesion . This was known as \"resting the lung\". It was introduced by the Italian surgeon  Carlo Forlanini  in 1888 and publicized by the American surgeon  John Benjamin Murphy  in the early 20th century (after discovering the same procedure independently). Murphy used the (then) recently discovered X-ray technology to create pneumothoraces of the correct size. [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3810", "contents": "The word  pneumothorax  comes from Greek  pneumo-  'air' and  thorax  'chest'. [ 62 ]  Its plural is  pneumothoraces ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3811", "contents": "Non-human animals may experience both spontaneous and traumatic pneumothorax. Spontaneous pneumothorax is, as in humans, classified as primary or secondary, while traumatic pneumothorax is divided into open and closed (with or without chest wall damage). [ 63 ]  The diagnosis may be apparent to the  veterinary physician  because the animal exhibits difficulty breathing in, or has shallow breathing. Pneumothoraces may arise from lung lesions (such as bullae) or from trauma to the chest wall. [ 64 ]  In horses, traumatic pneumothorax may involve both hemithoraces, as the  mediastinum  is incomplete and there is a direct connection between the two halves of the chest. [ 65 ]  Tension pneumothorax \u2013 the presence of which may be suspected due to rapidly deteriorating heart function, absent lung sounds throughout the thorax, and a barrel-shaped chest \u2013 is treated with an incision in the animal's chest to relieve the pressure, followed by insertion of a chest tube. [ 66 ]  For spontaneous pneumothorax the use of CT for diagnosis has been described for dogs [ 67 ]  and Kunekune pigs. [ 68 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3812", "contents": "A  pulmonary contusion , also known as  lung contusion , is a  bruise  of the  lung , caused by  chest trauma . As a result of damage to  capillaries , blood and other fluids accumulate in the lung tissue.  The excess fluid interferes with  gas exchange , potentially leading to inadequate oxygen levels ( hypoxia ).  Unlike  pulmonary laceration , another type of lung injury, pulmonary contusion does not involve a cut or tear of the lung tissue."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3813", "contents": "A pulmonary contusion is usually caused directly by  blunt trauma  but can also result from explosion injuries or a  shock wave  associated with  penetrating trauma . With the use of explosives during World Wars I and II, pulmonary contusion resulting from blasts gained recognition. In the 1960s its occurrence in civilians began to receive wider recognition, in which cases it is usually caused by traffic accidents. The use of seat belts and airbags reduces the risk to vehicle occupants."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3814", "contents": "Diagnosis is made by studying the cause of the injury,  physical examination  and  chest radiography . Typical signs and symptoms include direct effects of the physical trauma, such as chest pain and  coughing up blood , as well as signs that the body is not receiving enough oxygen, such as  cyanosis .  The contusion frequently heals on its own with supportive care. Often nothing more than supplemental oxygen and close monitoring is needed; however,  intensive care  may be required. For example, if breathing is severely compromised,  mechanical ventilation  may be necessary.  Fluid replacement  may be required to ensure adequate blood volume, but fluids are given carefully since  fluid overload  can worsen  pulmonary edema , which may be lethal."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3815", "contents": "The severity ranges from mild to severe: small contusions may have little or no impact on health, yet pulmonary contusion is the most common type of potentially lethal chest trauma. It occurs in 30\u201375% of severe chest injuries. The risk of death following a pulmonary contusion is between 14 and 40%. Pulmonary contusion is usually accompanied by other injuries. Although associated injuries are often the cause of death, pulmonary contusion is thought to cause death directly in a quarter to half of cases. Children are at especially high risk for the injury because the relative flexibility of their bones prevents the chest wall from absorbing force from an impact, causing it to be transmitted instead to the lung.  Pulmonary contusion is associated with complications including  pneumonia  and  acute respiratory distress syndrome , and it can cause long-term respiratory disability."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3816", "contents": "Pulmonary contusion and laceration are injuries to the lung tissue.  Pulmonary laceration , in which lung tissue is torn or cut, differs from pulmonary contusion in that the former involves disruption of the  macroscopic  architecture of the lung, [ 1 ]  while the latter does not. [ 2 ]  When lacerations fill with blood, the result is  pulmonary hematoma , a collection of blood within the lung tissue. [ 3 ]  Contusion involves hemorrhage in the  alveoli  (tiny air-filled sacs responsible for absorbing oxygen), but a  hematoma  is a discrete clot of blood not interspersed with lung tissue. [ 4 ]   A collapsed lung can result when the  pleural cavity  (the space outside the lung) accumulates blood ( hemothorax ) or air ( pneumothorax ) or both ( hemopneumothorax ). These conditions do not inherently involve damage to the lung tissue itself, but they may be associated with it.  Injuries to the chest wall are also distinct from but may be associated with lung injuries. Chest wall injuries include  rib fractures  and  flail chest , in which multiple ribs are broken so that a segment of the ribcage is detached from the rest of the chest wall and moves independently."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3817", "contents": "Presentation may be subtle; people with mild contusion may have no symptoms at all. [ 5 ]  However, pulmonary contusion is frequently associated with  signs  (objective indications) and  symptoms  (subjective states), including those indicative of the lung injury itself and  of accompanying injuries.  Because  gas exchange  is impaired, signs of low blood  oxygen saturation , such as low concentrations of oxygen in  arterial blood gas  and  cyanosis  (bluish color of the skin and mucous membranes) are commonly associated. [ 6 ]   Dyspnea  (painful breathing or difficulty breathing) is commonly seen, [ 6 ]  and tolerance for exercise may be lowered. [ 7 ]   Rapid breathing  and  a rapid heart rate  are other signs. [ 8 ] [ 9 ]   With more severe contusions,  breath sounds  heard through a stethoscope may be decreased, or  rales  (an abnormal crackling sound in the chest accompanying breathing) may be present. [ 6 ] [ 10 ]  People with severe contusions may have  bronchorrhea  (the production of watery  sputum ). [ 11 ]  Wheezing and coughing are other signs. [ 12 ]   Coughing up blood  or bloody sputum is present in up to half of cases. [ 12 ]   Cardiac output  (the volume of blood pumped by the heart) may be reduced, [ 11 ]  and  hypotension  (low blood pressure) is frequently present. [ 6 ]  The area of the chest wall near the contusion may be   tender [ 13 ]  or painful due to associated chest wall injury."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3818", "contents": "Signs and symptoms take time to develop, and as many as half of cases are  asymptomatic  at the initial presentation. [ 5 ]  The more severe the injury, the more quickly symptoms become apparent. In severe cases, symptoms may occur as quickly as three or four\u00a0hours after the trauma. [ 11 ]   Hypoxemia  (low oxygen concentration in the arterial blood) typically becomes progressively worse over 24\u201348\u00a0hours after injury. [ 14 ]  In general, pulmonary contusion tends to worsen slowly over a few days, [ 4 ]  but it may also cause rapid deterioration or death if untreated. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3819", "contents": "Pulmonary contusion is the most common injury found in blunt chest trauma, [ 15 ]  occurring in 25\u201335% of cases. [ 16 ]  It is usually caused by the rapid deceleration that results when the moving chest strikes a fixed object. [ 12 ]  About 70% of cases result from motor vehicle collisions, [ 17 ]  most often when the chest strikes the inside of the car. [ 6 ]   Falls, [ 17 ]  assaults, [ 18 ]  and sports injuries are other causes. [ 19 ]   Pulmonary contusion can also be caused by explosions; the organs most vulnerable to  blast injuries  are those that contain gas, such as the lungs. [ 20 ]   Blast lung is severe pulmonary contusion, bleeding, or  edema  with damage to alveoli and blood vessels, or a combination of these. [ 21 ]  This is the primary cause of death among people who initially survive an explosion. [ 22 ]   Unlike other mechanisms of injury in which pulmonary contusion is often found alongside other injuries, explosions can cause pulmonary contusion without damage to the chest wall. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3820", "contents": "In addition to  blunt trauma ,  penetrating trauma  can cause pulmonary contusion. [ 23 ]   Contusion resulting from penetration by a rapidly moving projectile usually surrounds the path along which the projectile traveled through the tissue. [ 24 ]  The  pressure wave  forces tissue out of the way, creating a temporary  cavity ; the tissue readily moves back into place, but it is damaged.  Pulmonary contusions that accompany gun and knife wounds are not usually severe enough to have a major effect on outcome; [ 25 ]   penetrating trauma causes less widespread lung damage than does blunt trauma. [ 17 ]  An exception is shotgun wounds, which can seriously damage large areas of lung tissue through a blast injury mechanism. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3821", "contents": "The physical processes behind pulmonary contusion are poorly understood. However, it is known that lung tissue can be crushed when the chest wall bends inward on impact. [ 26 ]  Three other possible mechanisms have been suggested: the  inertial  effect, the  spalling  effect, and the  implosion  effect."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3822", "contents": "Contusion usually occurs on the lung directly under the site of impact, but, as with  traumatic brain injury , a  contrecoup  contusion may occur at the site opposite the impact as well. [ 24 ]  A blow to the front of the chest may cause contusion on the back of the lungs because a shock wave travels through the chest and hits the curved back of the chest wall; this reflects the energy onto the back of the lungs, concentrating it. (A similar mechanism may occur at the front of the lungs when the back is struck.) [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3823", "contents": "The amount of energy transferred to the lung is determined in a large part by the compliance (flexibility) of the chest wall. [ 24 ]  Children's chests are more flexible because their ribs are more elastic and there is less  ossification  of their intercostal  cartilage . [ 13 ]   Therefore, their chest walls bend, absorbing less of the force and transmitting more of it to the underlying organs. [ 13 ] [ 32 ]  An adult's more bony chest wall absorbs more of the force itself rather than transmitting it. [ 32 ]  Thus children commonly get pulmonary contusions without fractures overlying them, while elderly people are more likely to develop fractures than contusions. [ 14 ] [ 24 ]  One study found that pulmonary contusions were accompanied by fractures 62% of the time in children and 80% of the time in adults. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3824", "contents": "Pulmonary contusion results in bleeding and fluid leakage into lung tissue, which can become stiffened and lose its normal elasticity.  The water content of the lung increases over the first 72\u00a0hours after injury, potentially leading to frank  pulmonary edema  in more serious cases. [ 20 ]  As a result of these and other pathological processes, pulmonary contusion progresses over time and can cause hypoxia (insufficient oxygen)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3825", "contents": "In contusions, torn  capillaries  leak fluid into the tissues around them. [ 33 ]  The membrane between alveoli and capillaries is torn; damage to this  capillary\u2013alveolar membrane  and small blood vessels causes blood and fluids to leak into the alveoli and the  interstitial space  (the space surrounding cells) of the lung. [ 11 ]   With more severe trauma, there is a greater amount of edema, bleeding, and tearing of the alveoli. [ 17 ]   Pulmonary contusion is characterized by  microhemorrhages  (tiny bleeds) that occur when the  alveoli  are traumatically separated from airway structures and blood vessels. [ 24 ]  Blood initially collects in the interstitial space, and then edema occurs by an hour or two after injury. [ 30 ]  An area of bleeding in the contused lung is commonly surrounded by an area of edema. [ 24 ]  In normal  gas exchange ,  carbon dioxide   diffuses  across the  endothelium  of the capillaries, the interstitial space, and across the alveolar epithelium; oxygen diffuses in the other direction. Fluid accumulation interferes with gas exchange, [ 34 ]  and can cause the alveoli to fill with proteins and collapse due to edema and bleeding. [ 24 ]  The larger the area of the injury, the more severe respiratory compromise will be. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3826", "contents": "Pulmonary contusion can cause parts of the lung to  consolidate , alveoli to collapse, and  atelectasis  (partial or total lung collapse) to occur. [ 35 ]   Consolidation occurs when the parts of the lung that are normally filled with air fill with material from the pathological condition, such as blood. [ 36 ]  Over a period of hours after the injury, the alveoli in the injured area thicken and may become consolidated. [ 24 ]  A decrease in the amount of  surfactant  produced also contributes to the collapse and consolidation of alveoli; [ 16 ]  inactivation of surfactant increases their  surface tension . [ 31 ]  Reduced production of surfactant can also occur in surrounding tissue that was not originally injured. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3827", "contents": "Inflammation  of the lungs, which can result when components of blood enter the tissue due to contusion, can also cause parts of the lung to collapse.   Macrophages ,  neutrophils , and other  inflammatory cells  and blood components can enter the lung tissue and release factors that lead to inflammation, increasing the likelihood of respiratory failure. [ 37 ]   In response to inflammation, excess  mucus  is produced, potentially plugging parts of the lung and leading to their collapse. [ 24 ]   Even when only one side of the chest is injured, inflammation may also affect the other lung. [ 37 ]   Uninjured lung tissue may develop edema, thickening of the septa of the alveoli, and other changes. [ 38 ]   If this inflammation is severe enough, it can lead to dysfunction of the lungs like that seen in acute respiratory distress syndrome. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3828", "contents": "Normally, the  ratio of ventilation to perfusion  is about one-to-one; the volume of air entering the alveoli ( ventilation ) is about equal to that of blood in the capillaries around them ( perfusion ). [ 40 ]   This ratio is reduced in pulmonary contusion; fluid-filled alveoli cannot fill with air, oxygen does not fully saturate the  hemoglobin , and the blood leaves the lung without being fully oxygenated. [ 41 ]  Insufficient inflation of the lungs, which can result from inadequate mechanical ventilation or an associated injury such as flail chest, can also contribute to the ventilation/perfusion mismatch. [ 31 ]  As the mismatch between ventilation and perfusion grows, blood oxygen saturation is reduced. [ 41 ]   Pulmonary hypoxic vasoconstriction, in which blood vessels near the hypoxic alveoli  constrict  (narrow their diameter) in response to the lowered oxygen levels, can occur in pulmonary contusion. [ 27 ]   The  vascular resistance  increases in the contused part of the lung, leading to a decrease in the amount of blood that flows into it, [ 38 ]   directing blood to better-ventilated areas. [ 27 ]  Although reducing blood flow to the unventilated alveoli is a way to compensate for the fact that blood passing unventilated alveoli is not oxygenated, [ 27 ]  the oxygenation of the blood remains lower than normal. [ 40 ]   If it is severe enough, the hypoxemia resulting from fluid in the alveoli cannot be corrected just by giving supplemental oxygen; this problem is the cause of a large portion of the fatalities that result from trauma. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3829", "contents": "To diagnose pulmonary contusion, health professionals use clues from a physical examination, information about the event that caused the injury, and  radiography . [ 17 ]   Laboratory findings may also be used; for example, arterial blood gasses may show insufficient oxygen and excessive carbon dioxide even in someone receiving supplemental oxygen. [ 35 ]   However, blood gas levels may show no abnormality early in the course of pulmonary contusion. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3830", "contents": "Chest X-ray  is the most common method used for diagnosis, [ 37 ]  and may be used to confirm a diagnosis already made using  clinical signs . [ 20 ]   Consolidated areas appear white on an X-ray film. [ 42 ]   Contusion is not typically restricted by the anatomical boundaries of the lobes or segments of the lung. [ 27 ] [ 43 ] [ 44 ]   The X-ray appearance of pulmonary contusion is similar to that of  aspiration , [ 32 ]  and the presence of  hemothorax  or  pneumothorax  may obscure the contusion on a radiograph. [ 25 ]  Signs of contusion that progress after 48\u00a0hours post-injury are likely to be actually due to aspiration, pneumonia, or ARDS. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3831", "contents": "Although chest radiography is an important part of the diagnosis, it is often not sensitive enough to detect the condition early after the injury. [ 35 ]  In a third of cases, pulmonary contusion is not visible on the first chest radiograph performed. [ 7 ]  It takes an average of six\u00a0hours for the characteristic white regions to show up on a chest X-ray, and the contusion may not become apparent for 48\u00a0hours. [ 7 ] [ 27 ] [ 43 ]  When a pulmonary contusion is apparent in an X-ray, it suggests that the trauma to the chest was severe and that a CT scan might reveal other injuries that were missed with X-ray. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3832", "contents": "Computed tomography  (CT scanning) is a more sensitive test for pulmonary contusion, [ 6 ] [ 33 ]  and it can identify  abdominal , chest, or other injuries that accompany the contusion. [ 38 ]  In one study, chest X-ray detected pulmonary contusions in 16.3% of people with serious blunt trauma, while CT detected them in 31.2% of the same people. [ 45 ]  Unlike X-ray, CT scanning can detect the contusion almost immediately after the injury. [ 43 ]  However, in both X-ray and CT a contusion may become more visible over the first 24\u201348\u00a0hours after trauma as bleeding and edema into lung tissues progress. [ 46 ]  CT scanning also helps determine the size of a contusion, which is useful in determining whether a patient needs mechanical ventilation; a larger volume of contused lung on CT scan is associated with an increased likelihood that ventilation will be needed. [ 43 ]   CT scans also help differentiate between contusion and  pulmonary hematoma , which may be difficult to tell apart otherwise. [ 47 ]  However, pulmonary contusions that are visible on CT but not chest X-ray are usually not severe enough to affect outcome or treatment. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3833", "contents": "Pulmonary  ultrasound , performed at the bedside or on the accident scene, is being explored as a diagnosis for pulmonary contusion.  Its use is still not widespread, being limited to facilities which are comfortable with its use for other applications, like pneumothorax, airway management, and hemothorax.  Accuracy has been found to be comparable to  CT scanning . [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3834", "contents": "Prevention of pulmonary contusion is similar to that of other chest trauma.  Airbags in combination with seat belts can protect vehicle occupants by preventing the chest from striking the interior of the vehicle during a collision, and by distributing forces involved in the crash more evenly across the body. [ 6 ]   However, in rare cases, an airbag causes pulmonary contusion in a person who is not properly positioned when it deploys. [ 50 ]   Child restraints such as carseats protect children in vehicle collisions from pulmonary contusion. [ 51 ]  Equipment exists for use in some sports to prevent chest and lung injury; for example, in softball the catcher is equipped with a chest protector. [ 52 ]   Athletes who do not wear such equipment, such as basketball players, can be trained to protect their chests from impacts. [ 52 ]  Protective garments can also prevent pulmonary contusion in explosions. [ 53 ]  Although traditional  body armor  made from rigid plates or other heavy materials protects from projectiles generated by a blast, it does not protect against pulmonary contusion, because it does not prevent the blast's shock wave from being transferred to the lung. [ 53 ]   Special body armor  has been designed for military personnel at high risk for blast injuries; these garments can prevent a shock wave from being propagated across the chest wall to the lung, and thus protect wearers from blast lung injuries. [ 53 ]  These garments alternate layers of materials with high and low  acoustic impedance  (the product of a material's density and a wave's velocity through it) in order to \"decouple\" the blast wave, preventing its propagation into the tissues. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3835", "contents": "No treatment is known to speed the healing of a pulmonary contusion; the main care is supportive. [ 39 ]    Attempts are made to discover injuries accompanying the contusion, [ 20 ]  to prevent additional injury, and to provide supportive care while waiting for the contusion to heal. [ 39 ]   Monitoring, including keeping track of  fluid balance , respiratory function, and oxygen saturation using  pulse oximetry  is also required as the patient's condition may progressively worsen. [ 54 ]  Monitoring for complications such as  pneumonia  and acute respiratory distress syndrome is of critical importance. [ 55 ]  Treatment aims to prevent  respiratory failure  and to ensure adequate blood  oxygenation . [ 16 ] [ 23 ]   Supplemental oxygen can be given and it may be warmed and humidified. [ 41 ]   When the contusion does not respond to other treatments,  extracorporeal membranous oxygenation  may be used, pumping blood from the body into a machine that oxygenates it and removes carbon dioxide prior to pumping it back in. [ 56 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3836", "contents": "Positive pressure ventilation , in which air is forced into the lungs, is needed when oxygenation is significantly impaired.  Noninvasive  positive pressure ventilation including  continuous positive airway pressure  (CPAP) and  bi-level positive airway pressure  (BiPAP), may be used to improve oxygenation and treat atelectasis: air is blown into the airways at a prescribed pressure via a face mask. [ 39 ]  Noninvasive ventilation has advantages over  invasive  methods because it does not carry the risk of infection that intubation does, and it allows normal coughing, swallowing, and speech. [ 39 ]  However, the technique may cause complications;  it may force air into the stomach or cause aspiration of stomach contents, especially when  level of consciousness  is decreased. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3837", "contents": "People with  signs of inadequate  respiration  or oxygenation may need to be  intubated [ 7 ]  and  mechanically ventilated . [ 12 ]  Mechanical ventilation aims to reduce pulmonary edema and increase oxygenation. [ 27 ]  Ventilation can reopen collapsed alveoli, but it is harmful for them to be repeatedly opened, and positive pressure ventilation can also damage the lung by overinflating it. [ 57 ]   Intubation is normally reserved for when respiratory problems occur, [ 7 ]  but most significant contusions do require intubation, and it may be done early in anticipation of this need. [ 4 ]  People with pulmonary contusion who are especially likely to need ventilation include those with prior severe  lung disease  or kidney problems; the elderly; those with a lowered level of consciousness; those with low blood oxygen or high carbon dioxide levels; and those who will undergo operations with  anesthesia . [ 41 ]   Larger contusions have been correlated with a need for ventilation for longer periods of time. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3838", "contents": "Pulmonary contusion or its complications such as acute respiratory distress syndrome may cause lungs to lose  compliance  (stiffen), so higher pressures may be needed to give normal amounts of air [ 4 ]  and oxygenate the blood adequately. [ 33 ]   Positive end-expiratory pressure  (PEEP), which delivers air at a given pressure at the end of the expiratory cycle, can reduce edema and keep alveoli from collapsing. [ 13 ]   PEEP is considered necessary with mechanical ventilation; however, if the pressure is too great it can expand the size of the contusion [ 17 ]  and injure the lung. [ 39 ]  When the compliance of the injured lung differs significantly from that of the uninjured one, the lungs can be ventilated independently with two ventilators in order to deliver air at different pressures; this helps avoid injury from overinflation while providing adequate ventilation. [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3839", "contents": "The administration of  fluid therapy  in individuals with pulmonary contusion is controversial. [ 41 ]  Excessive fluid in the circulatory system ( hypervolemia ) can worsen  hypoxia  because it can cause fluid leakage from injured capillaries (pulmonary edema), which are more permeable than normal. [ 31 ] [ 43 ]  However, low blood volume ( hypovolemia ) resulting from insufficient fluid has an even worse impact, potentially causing hypovolemic  shock ; for people who have lost large amounts of blood, fluid resuscitation is necessary. [ 41 ]   A lot of the evidence supporting the idea that fluids should be withheld from people with pulmonary contusion came from animal studies, not  clinical trials  with humans; human studies have had conflicting findings on whether fluid resuscitation worsens the condition. [ 20 ]   Current recommendations suggest giving enough fluid to ensure sufficient blood flow but not giving any more fluid than necessary. [ 15 ]   For people who do require large amounts of  intravenous  fluid, a  catheter  may be placed in the  pulmonary artery  to measure the pressure within it. [ 6 ]   Measuring pulmonary artery pressure allows the clinician to give enough fluids to prevent shock without exacerbating edema. [ 59 ]   Diuretics , drugs that increase urine output to reduce excessive fluid in the system, can be used when fluid overload does occur, as long as there is not a significant risk of shock. [ 15 ]   Furosemide , a diuretic used in the treatment of pulmonary contusion, also relaxes the  smooth muscle  in the veins of the lungs, thereby decreasing pulmonary  venous resistance  and reducing the pressure in the pulmonary capillaries. [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3840", "contents": "Retaining secretions in the airways can worsen hypoxia [ 60 ]  and lead to infections. [ 4 ]   Thus, an important part of treatment is  pulmonary toilet , the use of suction, deep breathing, coughing, and other methods to remove material such as mucus and blood from the airways. [ 7 ]   Chest physical therapy  makes use of techniques such as breathing exercises, stimulation of coughing, suctioning, percussion, movement, vibration, and drainage to rid the lungs of secretions, increase oxygenation, and expand collapsed parts of the lungs. [ 61 ]  People with pulmonary contusion, especially those who do not respond well to other treatments, may be positioned with the uninjured lung lower than the injured one to improve oxygenation. [ 43 ]  Inadequate pulmonary toilet can result in pneumonia. [ 40 ]  People who do develop infections are given antibiotics. [ 17 ]  No studies have yet shown a benefit of using antibiotics as a preventative measure before infection occurs, although some doctors do recommend prophylactic antibiotic use even without scientific evidence of its benefit. [ 13 ]  However, this can cause the development of  antibiotic resistant  strains of bacteria, so giving antibiotics without a clear need is normally discouraged. [ 20 ]  For people who are at especially high risk of developing infections, the  sputum  can be  cultured  to test for the presence of infection-causing bacteria; when they are present, antibiotics are used. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3841", "contents": "Pain control  is another means to facilitate the elimination of secretions. A chest wall injury can make coughing painful, increasing the likelihood that secretions will accumulate in the airways. [ 62 ]   Chest injuries also contribute to  hypoventilation  (inadequate breathing) because the chest wall movement involved in breathing adequately is painful. [ 62 ] [ 63 ]  Insufficient expansion of the chest may lead to  atelectasis , further reducing oxygenation of the blood. [ 35 ]   Analgesics  (pain medications) can be given to reduce pain. [ 12 ]  Injection of anesthetics into nerves in the chest wall, called  nerve blockade , is another approach to pain management; this does not depress respiration the way some pain medications can. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3842", "contents": "Pulmonary contusion usually resolves itself [ 23 ]  without causing permanent complications; [ 1 ]  however it may also have long-term ill effects on respiratory function. [ 38 ] [ 65 ]  Most contusions resolve in five to seven\u00a0days after the injury. [ 1 ]   Signs detectable by radiography are usually gone within 10\u00a0days after the injury\u2014when they are not, other conditions, such as pneumonia, are the likely cause. [ 27 ]   Chronic lung disease correlates with the size of the contusion and can interfere with an individual's ability to return to work. [ 24 ]   Fibrosis  of the lungs can occur, resulting in  dyspnea  (shortness of breath), low blood oxygenation, and reduced  functional residual capacity  for as long as six years after the injury. [ 38 ]  As late as four years post-injury, decreased functional residual capacity has been found in most pulmonary contusion patients studied. [ 43 ]  During the six months after pulmonary contusion, up to 90% of people have difficulty breathing. [ 27 ] [ 43 ]  In some cases, dyspnea persists for an indefinite period. [ 7 ]   Contusion can also permanently reduce the  compliance of the lungs . [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3843", "contents": "Pulmonary contusion can result in respiratory failure\u2014about half of such cases occur within a few hours of the initial trauma. [ 43 ]  Other severe complications, including infections and acute respiratory distress syndrome (ARDS) occur in up to half of cases. [ 31 ]   Elderly people and those who have heart, lung, or kidney disease prior to the injury are more likely to stay longer in hospital and have complications from the injury. Complications occur in 55% of people with heart or lung disease and 13% of those without. [ 37 ]  Of people with pulmonary contusion alone, 17% develop ARDS, while 78% of people with at least two additional injuries develop the condition. [ 6 ]  A larger contusion is associated with an increased risk. In one study, 82% of people with 20% or more of the lung volume affected developed ARDS, while only 22% of people with less than 20% did so. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3844", "contents": "Pneumonia , another potential complication, develops in as many as 20% of people with pulmonary contusion. [ 13 ]  Contused lungs are less able to remove bacteria than uninjured lungs, predisposing them to infection. [ 67 ]  Intubation and mechanical ventilation further increase the risk of developing pneumonia; the tube is passed through the nose or mouth into the airways, potentially tracking bacteria from the mouth or sinuses into them. [ 39 ]  Also, intubation prevents coughing, which would clear bacteria-laden secretions from the airways, and secretions pool near the tube's cuff and allow bacteria to grow. [ 39 ]  The sooner the  endotracheal tube  is removed, the lower the risk of pneumonia, but if it is removed too early and has to be put back in, the risk of pneumonia rises. [ 39 ]  People who are at risk for  pulmonary aspiration  (e.g. those with lowered level of consciousness due to head injuries) are especially likely to get pneumonia. [ 39 ]  As with ARDS, the chances of developing pneumonia increase with the size of the contusion. [ 7 ]  Children and adults have been found to have similar rates of complication with pneumonia and ARDS. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3845", "contents": "A large amount of force is required to cause pulmonary contusion; a person injured with such force is likely to have other types of injuries as well. [ 23 ]  In fact, pulmonary contusion can be used to gauge the severity of trauma. [ 25 ]   Up to three quarters of cases are accompanied by other chest injuries, [ 39 ]  the most common of these being hemothorax and pneumothorax. [ 37 ]   Flail chest is usually associated with significant pulmonary contusion, [ 15 ]  and the contusion, rather than the chest wall injury, is often the main cause of respiratory failure in people with these injuries. [ 69 ]  Other indications of  thoracic  trauma may be associated, including  fracture of the sternum  and bruising of the chest wall. [ 63 ]   Over half of  fractures of the scapula  are associated with pulmonary contusion. [ 27 ]    The contusion is frequently found underlying fracture sites. [ 35 ]   When accompanied by a fracture, it is usually concentrated into a specific location\u2014the contusion is more diffuse when there is no fracture. [ 31 ] [ 43 ]   Pulmonary lacerations  may result from the same blunt or penetrating forces that cause contusion. [ 6 ]   Lacerations can result in pulmonary hematomas; these are reported to develop in 4\u201311% of pulmonary contusions. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3846", "contents": "Pulmonary contusion is found in 30\u201375% of severe cases of chest injury, making it the most common serious injury to occur in association with  thoracic  trauma. [ 6 ]  Of people who have multiple injuries with an  injury severity score  of over 15, pulmonary contusion occurs in about 17%. [ 20 ]  It is difficult to determine the death rate ( mortality ) because pulmonary contusion rarely occurs by itself. [ 17 ]  Usually, deaths of people with pulmonary contusion result from other injuries, commonly traumatic brain injury. [ 24 ]   It is controversial whether pulmonary contusion with  flail chest  is a major factor in mortality on its own or whether it merely contributes to mortality in people with multiple injuries. [ 70 ]   The estimated mortality rate of pulmonary contusion ranges from 14 to 40%, depending on the severity of the contusion itself and on associated injuries. [ 11 ]   When the contusions are small, they do not normally increase the chance of death or poor outcome for people with blunt chest trauma; however, these chances increase with the size of the contusion. [ 37 ]   One study found that 35% of people with multiple significant injuries including pulmonary contusion die. [ 17 ]  In another study, 11% of people with pulmonary contusion alone died, while the number rose to 22% in those with additional injuries. [ 6 ]   Pulmonary contusion is thought to be the direct cause of death in a quarter to a half of people with multiple injuries ( polytrauma ) who die. [ 71 ]   An accompanying flail chest increases the  morbidity  and mortality to more than twice that of pulmonary contusion alone. [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3847", "contents": "Pulmonary contusion is the most common cause of death among vehicle occupants involved in accidents, [ 72 ]  and it is thought to contribute significantly in about a quarter of deaths resulting from vehicle collisions. [ 25 ]   As vehicle use has increased, so has the number of auto accidents, and with it the number of chest injuries. [ 39 ]  However an increase in the number of airbags installed in modern cars may be decreasing the incidence of pulmonary contusion. [ 6 ]   Use of child restraint systems has brought the approximate incidence of pulmonary contusion in children in vehicle accidents from 22% to 10%. [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3848", "contents": "Differences in the bodies of children and adults lead to different manifestations of pulmonary contusion and associated injuries; for example, children have less body mass, so the same force is more likely to lead to trauma in multiple body systems. [ 31 ]    Since their chest walls are more flexible, children are more vulnerable to pulmonary contusion than adults are, [ 23 ]  and thus suffer from the injury more commonly. [ 30 ]  Pulmonary contusion has been found in 53% of children with chest injuries requiring hospitalization. [ 73 ]  Children in forceful impacts suffer twice as many pulmonary contusions as adults with similar injury mechanisms, yet have proportionately fewer rib fractures. [ 13 ]   The rates of certain types of injury mechanisms differ between children and adults; for example, children are more often hit by cars as pedestrians. [ 31 ]   Some differences in children's physiology might be advantageous (for example they are less likely to have other medical conditions), and thus they have been predicted to have a better outcome. [ 74 ]  However, despite these differences, children with pulmonary contusion have similar mortality rates to adults. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3849", "contents": "In 1761, the Italian anatomist  Giovanni Battista Morgagni  was first to describe a lung injury that was not accompanied by injury to the chest wall overlying it. [ 20 ]  Nonetheless, it was the French military surgeon  Guillaume Dupuytren  who is thought to have coined the term  pulmonary contusion  in the 19th\u00a0century. [ 71 ]   It still was not until the early 20th\u00a0century that pulmonary contusion and its clinical significance began to receive wide recognition. [ 70 ]  With the use of explosives during World War I came many casualties with no external signs of chest injury but with significant bleeding in the lungs. [ 70 ]   Studies of World War I injuries by D.R. Hooker showed that pulmonary contusion was an important part of the concussive injury that results from explosions. [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3850", "contents": "Pulmonary contusion received further attention during World War II, when the bombings of Britain caused blast injuries and associated respiratory problems in both soldiers and civilians. [ 20 ]  Also during this time, studies with animals placed at varying distances from a blast showed that protective gear could prevent lung injuries. [ 65 ]  These findings suggested that an impact to the outside of the chest wall was responsible for the internal lesions. [ 65 ]  In 1945, studies identified a phenomenon termed \"wet lung\", in which the lungs accumulated fluid and were simultaneously less able to remove it. [ 20 ] [ 75 ]  They attributed the respiratory failure often seen in blunt chest trauma in part to excessive fluid resuscitation, and the question of whether and how much to administer fluids has remained controversial ever since. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3851", "contents": "During the Vietnam War, combat again provided the opportunity for study of pulmonary contusion; research during this conflict played an important role in the development of the modern understanding of its treatment. [ 20 ]   The condition also began to be more widely recognized in a non-combat context in the 1960s, and symptoms and typical findings with imaging techniques such as X-ray were described. [ 20 ]   Before the 1960s, it was believed that the respiratory insufficiency seen in flail chest was due to \"paradoxical motion\" of the flail segment of the chest wall (the flail segment moves in the opposite direction as the chest wall during respiration), so treatment was aimed at managing the chest wall injury, not the pulmonary contusion. [ 56 ]  For example,  positive pressure ventilation  was used to stabilize the flail segment from within the chest. [ 15 ] [ 39 ]  It was first proposed in 1965 that this respiratory insufficiency is most often due to injury of the lung rather than to the chest wall, [ 20 ]   and a group led by J.K. Trinkle confirmed this hypothesis in 1975. [ 38 ]   Hence the modern treatment prioritizes the management of pulmonary contusion. [ 70 ]   Animal studies performed in the late 1960s and 1970s shed light on the pathophysiological processes involved in pulmonary contusion. [ 65 ]   Studies in the 1990s revealed a link between pulmonary contusion and persistent respiratory difficulty for years after the injury in people in whom the injury coexisted with flail chest. [ 15 ]   In the next decade studies demonstrated that function in contused lungs improves for years after the injury. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3852", "contents": "A  pulmonary hematoma  is a collection of  blood  within the  tissue  of the  lung .  It may result when a  pulmonary laceration  fills with blood. [ 1 ]   A lung laceration filled with air is called a  pneumatocele . [ 1 ]   In some cases, both pneumatoceles and hematomas exist in the same injured lung. [ 2 ]   Pulmonary hematomas take longer to heal than simple pneumatoceles and commonly leave the lungs scarred. [ 1 ]   A  pulmonary contusion  is another cause of bleeding within the lung tissue, but these result from microhemorrhages, multiple small bleeds, and the bleeding is not a discrete mass but rather occurs within the lung tissue.  An indication of more severe damage to the lung than pulmonary contusion, a hematoma also takes longer to clear. [ 3 ]  Unlike contusions, hematomas do not usually interfere with  gas exchange  in the lung, but they do increase the risk of  infection  and  abscess  formation. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3853", "contents": "A  pulmonary laceration  is a  chest injury  in which  lung  tissue is torn or cut. [ 1 ]  An injury that is potentially more serious than  pulmonary contusion , pulmonary  laceration  involves disruption of the architecture of the lung, [ 2 ]  while pulmonary contusion does not. [ 3 ]   Pulmonary laceration is commonly caused by  penetrating trauma  but may also result from forces involved in  blunt trauma  such as  shear stress .  A cavity filled with blood, air, or both can form. [ 2 ]  The injury is diagnosed when collections of air or fluid are found on a  CT scan  of the chest. Surgery may be required to stitch the laceration, to drain blood, or even to remove injured parts of the lung.  The injury commonly heals quickly with few problems if it is given proper treatment; however it may be associated with scarring of the lung or other complications."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3854", "contents": "Complications are not common but include infection,  lung abscess , and  bronchopleural fistula  (a  fistula  between the  pleural space  and the  bronchial tree ). [ 4 ]   A bronchopleural fistula results when there is a communication between the laceration, a bronchiole, and the pleura; it can cause air to leak into the pleural space despite the placement of a chest tube. [ 4 ]   The laceration can also enlarge, as may occur when the injury creates a valve that allows air to enter the laceration, progressively expanding it. [ 4 ]   One complication,  air embolism , in which air enters the bloodstream, is potentially fatal, especially when it occurs on the left side of the heart. [ 5 ]   Air can enter the circulatory system through a damaged  vein  in the injured chest and can travel to any organ; it is especially deadly in the heart or brain. [ 5 ]   Positive pressure ventilation  can cause pulmonary embolism by forcing air out of injured lungs and into blood vessels. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3855", "contents": "Pulmonary laceration is a common result of  penetrating trauma  but may also be caused by  blunt trauma ;  broken ribs  may perforate the lung, or the tissue may be torn due to  shearing forces [ 5 ]  that result from different rates of acceleration or deceleration of different tissues of the lung. [ 6 ]  Violent compression of the chest can cause lacerations by rupturing or shearing the lung tissue. [ 4 ]   Pulmonary laceration may result from blunt and penetrating forces that occur in the same injury and may be associated with pulmonary contusion. [ 7 ] [ 8 ]  Lacerations of the lung tissue can also occur by compression of the alveoli against the ribs or spine. [ 4 ]  As with contusions, pulmonary lacerations usually occur near solid structures in the chest such as ribs. [ 2 ]  Pulmonary laceration is suspected when rib fractures are present. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3856", "contents": "A pulmonary laceration can cause air to leak out of the lacerated lung [ 10 ]   and into the  pleural space , if the laceration goes through to it. [ 8 ]  Pulmonary laceration invariably results in  pneumothorax  (due to torn  airways ),  hemothorax  (due to torn  blood vessels ), or a  hemopneumothorax  (with both blood and air in the chest cavity). [ 11 ]  Unlike hemothoraces that occur due to pulmonary contusion, those due to lung laceration may be large and long lasting. [ 12 ]  However, the lungs do not usually bleed very much because the blood vessels involved are small and the pressure within them is low. [ 5 ]   Therefore, pneumothorax is usually more of a problem than hemothorax. [ 8 ]  A pneumothorax may form or be turned into a  tension pneumothorax  by  mechanical ventilation , which may force air out of the tear in the lung. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3857", "contents": "The laceration may also close up by itself, which can cause it to trap blood and potentially form a  cyst  or  hematoma . [ 8 ]   Because the lung is elastic, the tear forms a round cyst called a  traumatic air cyst  that may be filled with air, or blood and air, and that usually shrinks over a period of weeks or months. [ 13 ]  Lacerations that are filled with air are called  pneumatoceles , and those that are filled with blood are called  pulmonary hematomas . [ 14 ]  In some cases, both pneumatoceles and hematomas exist in the same injured lung. [ 12 ]   A pneumatocele can become enlarged, for example when the patient is mechanically ventilated or has  acute respiratory distress syndrome , in which case it may not go away for months. [ 12 ]   Pulmonary hematomas take longer to heal than simple pneumatoceles and commonly leave the lungs scarred. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3858", "contents": "Over time, the walls of lung lacerations tend to grow thicker due to edema and bleeding at the edges. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3859", "contents": "Pulmonary laceration may not be visible using  chest X-ray  because an associated  pulmonary contusion  or  hemorrhage  may mask it. [ 1 ] [ 9 ]  As the lung contusion clears (usually within two to four days), lacerations begin to become visible on chest X-ray. [ 3 ]   CT scanning  is more sensitive and better at detecting pulmonary laceration than  X-rays  are, [ 1 ] [ 5 ] [ 12 ] [ 15 ]   and often reveals multiple lacerations in cases where chest X-ray showed only a contusion. [ 12 ]  Before CT scanning was widely available, pulmonary laceration was considered unusual because it was not common to find with X-ray alone. [ 12 ]  On a CT scan, pulmonary lacerations show up in a contused area of the lung, [ 9 ]  typically appearing as cavities filled with air or fluid [ 16 ]  that usually have a round or ovoid shape due to the lung's elasticity. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3860", "contents": "Hematomas appear on chest radiographs as smooth masses that are round or ovoid in shape. [ 1 ]   Like lacerations, hematomas may initially be hidden on X-ray by lung contusions, but they become more apparent as the contusion begins to heal. [ 1 ]   Pneumatoceles have a similar shape to that of hematomas but have thin, smooth walls. [ 17 ]   Lacerations may be filled completely with blood, completely with air, or partially with both. [ 4 ]   Lacerations filled with both blood and air display a distinctive air-fluid level. [ 4 ]   A single laceration may occur by itself, or many may be present, creating an appearance like Swiss cheese in the radiography of the lung. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3861", "contents": "Pulmonary laceration is usually accompanied by  hemoptysis  (coughing up blood or of blood-stained sputum). [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3862", "contents": "Thoracoscopy  may be used in both diagnosis and treatment of pulmonary laceration. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3863", "contents": "A healing laceration may resemble a  lung nodule  on radiographs, but unlike pulmonary nodules, lacerations decrease in size over time on radiographs. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3864", "contents": "In 1988, a group led by R.B. Wagner divided pulmonary lacerations into four types based on the manner in which the person was injured and indications found on a  CT scan . [ 18 ]  In type 1 lacerations, which occur in the mid lung area, the air-filled lung bursts as a result of sudden compression of the chest. [ 18 ]   Also called compression-rupture lacerations, type 1 are the most common type and usually occur in a central location of the lung. [ 1 ]   They tend to be large, ranging in size from 2\u20138\u00a0cm. [ 19 ]   The shearing stress in type 2 results when the lower chest is suddenly compressed and the lower lung is suddenly moved across the  vertebral  bodies. [ 18 ] [ 19 ]   Type 2, also called compression-shear, [ 1 ]  tends to occur near the spine and have an elongated shape. [ 19 ]  Type 2 lacerations usually occur in younger people with more flexible chests. [ 6 ]  Type 3, which are caused by punctures from fractured ribs, occur in the area near the chest wall underlying the broken rib. [ 18 ]  Also called rib penetration lacerations, type 3 lacerations tend to be small [ 1 ]  and accompanied by pneumothorax. [ 18 ]  Commonly, more than one type 3 laceration will occur. [ 19 ]  Type 4, also called adhesion tears, [ 1 ]  occur in cases where a  pleuropulmonary adhesion  had formed prior to the injury, in which the chest wall is suddenly fractured or pushed inwards. [ 19 ]    They occur in the  subpleural  area and result from shearing forces at sites of transpleural adhesion. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3865", "contents": "As with other chest injuries such as pulmonary contusion, hemothorax, and pneumothorax, pulmonary laceration can often be treated with just supplemental oxygen, ventilation, and drainage of fluids from the chest cavity. [ 20 ]  A  thoracostomy tube  can be used to remove blood and air from the chest cavity. [ 21 ]  About 5% of cases require surgery, called  thoracotomy . [ 11 ]  Thoracotomy is especially likely to be needed if a lung fails to re-expand; if pneumothorax, bleeding, or coughing up blood persist; or in order to remove clotted blood from a hemothorax. [ 11 ]   Surgical treatment includes suturing, [ 11 ]  stapling, oversewing, and wedging out of the laceration. [ 8 ]   Occasionally, surgeons must perform a  lobectomy , in which a lobe of the lung is removed, or a  pneumonectomy , in which an entire lung is removed. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3866", "contents": "Full recovery is common with proper treatment. [ 20 ]  Pulmonary laceration usually heals quickly after a chest tube is inserted and is usually not associated with major long-term problems. [ 8 ]   Pulmonary lacerations usually heal within three to five weeks, [ 12 ]  and lacerations filled with air will commonly heal within one to three weeks but on occasion take longer. [ 1 ]  However, the injury often takes weeks or months to heal, and the lung may be  scarred . [ 2 ]    Small pulmonary lacerations frequently heal by themselves if material is removed from the  pleural  space, but surgery may be required for larger lacerations that do not heal properly or that bleed. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3867", "contents": "A  rib fracture  is a  break  in a  rib  bone. [ 1 ]  This typically results in chest pain that is worse with inspiration. [ 1 ]   Bruising  may occur at the site of the break. [ 3 ]  When several ribs are broken in several places a  flail chest  results. [ 4 ]  Potential complications include a  pneumothorax ,  pulmonary contusion , and  pneumonia . [ 2 ] [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3868", "contents": "Rib fractures usually occur from a direct blow to the chest such as during a  motor vehicle collision  or from a  crush injury . [ 2 ] [ 1 ]  Coughing or  metastatic cancer  may also result in a broken rib. [ 1 ]  The middle ribs are most commonly fractured. [ 5 ] [ 1 ]  Fractures of the first or second ribs are more likely to be associated with complications. [ 6 ]  Diagnosis can be made based on symptoms and supported by  medical imaging . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3869", "contents": "Pain control  is an important part of treatment. [ 7 ]  This may include the use of  paracetamol  (acetaminophen),  NSAIDs , or  opioids . [ 2 ]  A  nerve block  may be another option. [ 1 ]  While fractured ribs can be wrapped, this may increase complications. [ 1 ]  In those with a flail chest, surgery may improve outcomes. [ 8 ] [ 9 ]  They are a common injury following trauma. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3870", "contents": "Rib fractures can occur with or without direct trauma during recreational activity.  Cardiopulmonary resuscitation  (CPR) has also been known to cause thoracic injury, including but not limited to rib and  sternum fractures . They can also occur as a consequence of diseases such as cancer or  rheumatoid arthritis . An exceptionally powerful cough, such as that which can occur in  whooping cough , may also result in a broken rib. While for elderly individuals a fall can cause a rib fracture, in adults automobile accidents are a common event for such an injury. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3871", "contents": "Signs of a broken rib may include: [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3872", "contents": "Plain  X-rays  often pick up displaced fractures but often miss undisplaced fractures. [ 13 ]   CT scanning  is generally able to pick up both types of fractures. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3873", "contents": "Because children have more flexible chest walls than adults do, their ribs are more likely to bend than to break; therefore the presence of rib fractures in children is evidence of a significant amount of force and may indicate severe  thoracic  injuries such as  pulmonary contusion . [ 4 ]  Rib fractures are also a sign of more serious injury in elderly people. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3874", "contents": "There is no specific treatment for rib fractures, but various supportive measures can be taken. In simple rib fractures, pain can lead to reduced movement and cough suppression; this can contribute to formation of secondary chest infection. [ 15 ]  Flail chest is a potentially life-threatening injury and will often require a period of  assisted ventilation . [ 16 ]  Flail chest and first rib fractures are high-energy injuries and should prompt investigation of damage to underlying  viscera  (e.g., lung  contusion ) or remotely (e.g., cervical spine injury). Spontaneous fractures in athletes generally require a cessation of the cause, e.g., time off rowing, while maintaining cardiovascular fitness. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3875", "contents": "Nerve blocks may be used to help with pain and reduce respiratory complications  related to rib fractures. [ 17 ]   These include  rhomboid intercostal block , [ 18 ]   epidural anesthesia ,  paravertebral block , erector spinae plane block and  serratus anterior plane block . [ 19 ] [ 20 ] [ 21 ]  There is very little evidence to support the use of one nerve block over another on the basis of analgesia or safety. [ 22 ] [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3876", "contents": "Treatment options for internal fixation/repair of rib fractures include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3877", "contents": "Slipping rib syndrome  ( SRS ) is a condition in which the  interchondral ligaments  are weakened or disrupted and have increased laxity, causing the costal cartilage tips to  subluxate  (partially dislocate). This results in pain or discomfort due to pinched or irritated  intercostal nerves , straining of the  intercostal muscles , and  inflammation . The condition affects the 8th, 9th, and 10th ribs, referred to as the  false ribs , with the 10th rib most commonly affected."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3878", "contents": "Slipping rib syndrome was first described by  Edgar Ferdinand Cyriax  in 1919; however, the condition is rarely recognized and frequently overlooked. A study estimated the prevalence of the condition to be 1% of clinical diagnoses in a  general medicine  clinic and 5% in a  gastroenterology  clinic, with a separate study finding it to be 3% in a mixed specialty  general medicine  and  gastroenterology  clinic. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3879", "contents": "The condition has also been referred to as  Cyriax syndrome ,  clicking rib syndrome ,  painful rib syndrome ,  interchondral subluxation , or  displaced ribs . The term \"slipping rib syndrome\" was coined by surgeon  Robert Davies-Colley  in 1922, which has been popularly quoted since."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3880", "contents": "The presentation of slipping rib syndrome varies for each individual and can present at one or both sides of the rib cage, with symptoms appearing primarily in the abdomen and back. [ 3 ]  Pain is most commonly presented as episodic and varies from a minor nuisance to severely impacting quality of life. [ 1 ] [ 4 ]  It has been reported that symptoms can last from minutes to hours. [ 3 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3881", "contents": "One of the commonly reported symptoms of this condition is the sensation of \"popping\" or \"clicking\" of the lower ribs as a result of  subluxation  of the  cartilaginous joints . [ 1 ] [ 3 ]  Individuals with SRS report an intense, sharp pain that can  radiate  from the chest to the back, and may be reproducible by pressing on the affected rib(s). [ 4 ] [ 6 ]  A dull, aching sensation has also been reported by some affected individuals. [ 3 ]  Certain postures or movements may exacerbate the  symptoms , such as stretching, reaching, coughing, sneezing ,  lifting, bending, sitting, sports activities, and respiration. [ 1 ] [ 3 ] [ 4 ]  There have also been reports of  vomiting  and  nausea  associated with the condition. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3882", "contents": "The  causes  of slipping rib syndrome are unclear, [ 8 ]  although several risk factors have been suggested. The condition often accompanies a history of  physical trauma . This observation could explain reports of the condition among athletes, as they are at increased risk for trauma, especially for certain  full-contact sports  such as  hockey ,  wrestling , and  American football . [ 7 ]  There have also been reports of slipping rib syndrome among other athletes, such as swimmers, which could plausibly result from repetitive upper body movements coupled with high physical demands. [ 3 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3883", "contents": "Reported incidents, in which no history of traumatic impact to the chest wall has been described, are considered a gradual onset condition. [ 8 ]  Slipping rib syndrome may also result from the presence of a  birth defect , such as an unstable  bifid rib . [ 9 ]  Generalized  hypermobility  has also been suggested to be a possible further risk factor. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3884", "contents": "Diagnosing slipping rib syndrome is predominantly clinical, [ 10 ] [ 11 ]  with a  physical examination  of the affected rib being the most commonly utilized. A technique known as the \"hooking maneuver\" is commonly used amongst  medical professionals  to diagnose slipping rib syndrome. The examiner will hook their fingers under the  costal margin , then pull in an  anterior  (outward) and  superior  (upward) direction, with a positive result when movement or pain is replicated during this action. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3885", "contents": "Plain  radiographs ,  CT scans ,  MRI , and standard  ultrasound , are all unable to visualize the  cartilage  affected by SRS; however, they are often used to exclude other conditions. [ 3 ]  Dynamic ultrasound is occasionally used to evaluate the dynamic  laxity  or displacement of the cartilage; [ 10 ]  however, it has been said to be not much superior to that of a physical examination from an experienced physician, as a diagnosis is dependent on the technician's expertise and knowledge of the condition. [ 9 ]  A positive result of a dynamic ultrasound for slipping rib syndrome requires an observed subluxation of the cartilage, which may be elicited with the  Valsalva ,  crunch , or other maneuvers. [ 12 ] [ 13 ]   Nerve blocking injections  have also been utilized as a diagnostic method by noting the absence of pain following an injection to the intercostal nerves of the affected ribs. [ 14 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3886", "contents": "Slipping rib syndrome is often confused with  costochondritis  and  Tietze syndrome , as they also involve the cartilage of the thoracic wall. Costochondritis is a common cause of  chest pain , consisting of up to 30% of chest pain complaints in emergency departments. The pain is typically diffused with the upper  costochondral  or  sternocostal  junctions most frequently involved, unlike slipping rib syndrome, which involves the lower rib cage. Tietze syndrome differs from these conditions as it is often associated with inflammation and  swelling  of the costochondral, sternocostal, and  sternoclavicular  joints, whereas individuals with slipping rib syndrome or costochondritis will exhibit no swelling. Tietze syndrome typically involves the second and third ribs and is usually a result of  infectious ,  rheumatologic , or  neoplastic  processes. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3887", "contents": "A condition referred to as  twelfth rib syndrome  is similar to slipping rib syndrome; however, it affects the  floating ribs  (11\u201312) which do not have any attachments to the  sternum . Some researchers classify slipping rib syndrome and twelfth rib syndrome into a group referred to as painful rib syndrome, others classify twelfth rib syndrome as a subtype of slipping rib syndrome, and some considering the two to be separate conditions altogether. The two disorders have different presentation and diagnostic criteria, such that a diagnosis for twelfth rib syndrome does not include the hooking maneuver and typically presents as  lower back ,  abdominal , and groin pain. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3888", "contents": "Other differential diagnosis includes  pleurisy ,  rib fracture ,  gastric ulcer ,  cholecystitis ,  esophagitis , and hepatosplenic abnormalities. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3889", "contents": "Treatment modalities for slipping rib syndrome range from conservative measures to surgical procedures."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3890", "contents": "Conservative measures are often the first forms of treatment offered to patients with slipping rib syndrome, especially those in which symptoms are minor. [ 16 ]  Often the patients will be reassured and recommended to limit activity, use ice, and take  pain medication  such as  nonsteroidal anti-inflammatory drugs  (NSAIDs). [ 4 ]  Further measures such as  osteopathic manipulation treatment  (OMT),  physical therapy ,  chiropractic treatment , and  acupuncture , are other non-invasive methods that have been used to treat SRS, with the goal of these treatments typically being relief or symptom management.  Topical medications  are occasionally used, such as  Diclofenac  gel and  lidocaine  transdermal patches, which have been noted to provide temporary relief of symptoms. [ 3 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3891", "contents": "Minimally invasive procedures  have been used for individuals with moderate slipping rib syndrome. [ 4 ]  Nerve blocking injections consisting of  steroidal  or  local anesthetic  agents have been commonly reported as a treatment to avoid surgical intervention. [ 4 ] [ 8 ]  This minimally invasive intervention is seen as temporary, with repeated injections necessary to prevent the resurgence of symptoms. [ 4 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3892", "contents": "Surgical intervention is often performed in cases where other treatment modalities have failed to provide a solution. [ 7 ] [ 11 ]  There are four types of surgical procedures noted in current literature: costal cartilage removal,  rib resection ,  laparoscopic  costal cartilage removal, and rib stabilization with plating. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3893", "contents": "Costal cartilage removal, or excision, was first attempted in 1922 by Davies-Colley and has been the technique used by several surgeons since then. This method of surgical repair includes removal of the cartilage affected from the  sternum  to the boned portion of the rib, with or without preserving the  perichondrium . Rib resection differentiates from costal cartilage removal as it removes a small bone portion of the affected rib(s). [ 1 ]   Laparoscopic  costal cartilage removal is a  minimally invasive , intra-abdominal approach to treating the condition. The affected cartilage is excised from the sternocostal junction to the costochondral junction. [ 17 ]  It is to be noted that within studies that have performed these procedures, some individuals may experience recurrence of symptoms. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3894", "contents": "An alternative technique known as rib stabilization with plating is used to prevent subluxation of the affected rib(s) while preserving  thorax  mobility. It was first used to treat individuals who have undergone previous resection surgeries but experienced a recurrence of symptoms. In this procedure, the ribs are stabilized using a bio-absorbable plate that is anchored onto a stable non-affected rib located above the affected rib(s). The plates are vertically placed onto the ribs and secured using non-absorbable sutures. [ 1 ] [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3895", "contents": "A more recent technique of rib stabilization with suturing, colloquially known as the Hansen Method after its creator, is used to bring the affected rib(s) to their normal anatomy. The method uses an orthopedic tape suture to tie the slipped rib around a higher, unaffected rib(s) to stabilize it. This method is similar in concept to the aforementioned method of stabilization with plating; however, the suture is not bioabsorbable. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3896", "contents": "Slipping rib syndrome is considered to be underdiagnosed and frequently overlooked. [ 1 ] [ 20 ]  Past literature has noted the condition to be rare or uncommon, but one 1980 study estimated SRS to have 1% of clinical diagnoses in new patients at a  general medicine  clinic and 5% at a specialty  gastroenterology  clinic, with the prevalence being even higher for patients referred to the specialty clinic after multiple negative investigations. [ 1 ] [ 21 ]  A separate study from 1993 found that slipping rib syndrome accounted for 3% of new referrals to a mixed specialty general medicine and gastroenterology clinic. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3897", "contents": "It is unclear whether SRS is more common in women as some studies report an equal gender distribution while others report the condition to occur more often in females. [ 1 ] [ 2 ] [ 21 ]  It has been suggested by some researchers that there is a hormonal connection between hormones and the increased ligament laxity observed in females during pregnancy, though this theory has yet to be upheld or explored. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3898", "contents": "Slipping rib syndrome was first mentioned in 1919 by  Edgar Ferdinand Cyriax , an  orthopedic  physician and  physiotherapist , who described a chest pain associated with a \"popping\" or \"clicking\" sensation. [ 9 ] [ 22 ]  The condition was originally named after him, Cyriax syndrome, but has used multiple names since then, including clicking rib syndrome, painful rib syndrome, interchondral subluxation, and displaced ribs. [ 23 ]  The name \"slipping rib syndrome\" was first used by surgeon  Robert Davies-Colley  and gained popularity, becoming the most commonly quoted term for the condition. [ 8 ]  Davies-Colley was also the first to describe an operation for slipping rib syndrome, a costal cartilage removal. [ 3 ] [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3899", "contents": "The \"hooking maneuver\" was noted in 1977 by Heinz & Zavala to be useful for slipping rib syndrome as an accurate diagnostic method. [ 4 ] [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3900", "contents": "A  sternal fracture  is a  fracture  of the  sternum  (the breastbone), located in the center of the  chest .  The injury, which occurs in 5\u20138% of people who experience significant blunt  chest trauma , may occur in vehicle accidents, when the still-moving chest strikes a steering wheel or dashboard [ 1 ]  or is injured by a seatbelt.  Cardiopulmonary resuscitation  (CPR),  has also been known to cause thoracic injury, including sternum and  rib fractures . Sternal fractures may also occur as a  pathological fracture , in people who have weakened bone in their sternum, due to another disease process. [ 2 ]   Sternal fracture can interfere with breathing by making it more painful; however, its primary significance is that it can indicate the presence of serious associated internal injuries, especially to the heart and  lungs . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3901", "contents": "Signs and symptoms include  crepitus  (a crunching sound made when broken bone ends rub together), [ 1 ]  pain,  tenderness ,  bruising , and swelling over the fracture site. [ 4 ]   The fracture may visibly move when the person breathes, and it may be bent or deformed, [ 4 ]  potentially forming a \"step\" at the junction of the broken bone ends that is detectable by  palpation . [ 3 ]  Associated injuries such as those to the heart may cause symptoms such as abnormalities seen on electrocardiograms. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3902", "contents": "The upper and middle parts of the sternum are those most likely to fracture, [ 5 ]  but most sternal fractures occur below the  sternal angle . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3903", "contents": "Because of the high frequency of associated injuries, clinicians are taught to suspect that a patient has multiple severe injuries if a sternal fracture is present. [ 4 ]   Sternal fracture is commonly associated with injuries to the heart and lungs; if a person is injured with enough force to fracture the sternum, injuries such as  myocardial  and  pulmonary contusions  are likely. [ 1 ]  Other associated injuries that may occur include damage to  blood vessels  in the chest,  myocardial rupture ,  head  and  abdominal injuries ,  flail chest , [ 1 ]  and  vertebral  fracture. [ 2 ]  Sternal fractures may also accompany rib fractures and are high-energy enough injuries to cause  bronchial tears  (ruptures of the  bronchioles ). [ 6 ]  They may hinder breathing. [ 6 ]  Due to the associated injuries, the  mortality rate  for people with sternal fracture is high, at an estimated 25\u201345%. [ 1 ]   However, when sternal fractures occur in isolation, their outcome is very good. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3904", "contents": "There is controversy over the question of whether the presence of sternal fracture is an indication of cardiac injuries. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3905", "contents": "Vehicle collisions  are the usual cause of sternal fracture; [ 3 ]  the injury is estimated to occur in about 3% of auto accidents. [ 8 ]  The chest of a driver who is not wearing a seat belt may strike the steering wheel, and the shoulder component of a seatbelt may injure the chest if it is worn without the lap component. [ 3 ]  It was common enough for the sternum to be injured by the seatbelt that it was included in the 'safety belt syndrome', [ 9 ]  a pattern of injuries caused by  seat belts  in vehicle accidents. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3906", "contents": "The injury can also occur when the chest suddenly flexes, in the absence of an impact. [ 2 ]  In the case of an injury sustained during CPR, the most common injuries sustained are rib fractures, with literature suggesting an incidence between 13% and 97%, and sternal fractures, with an incidence between 1% and 43%. [ 11 ]  Additionally, injury to the sternum may be made more likely if there are other disease processes in place that have weakened the bone - in this case, the fracture that occurs is termed a  pathologic fracture . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3907", "contents": "X-rays of the chest  are taken in people with chest trauma and symptoms of sternal fractures, and these may be followed by  CT scanning . [ 13 ]   Since X-rays taken from the front may miss the injury, they are taken from the side as well. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3908", "contents": "Management involves treating associated injuries; people with sternal fractures but no other injuries do not need to be hospitalized. [ 4 ]  However, because it is common for cardiac injuries to accompany sternal fracture, heart function is monitored with electrocardiogram. [ 15 ]   Fractures that are very painful or extremely out of place can be operated on to fix the bone fragments into place, [ 4 ]  but in most cases treatment consists mainly of reducing pain and limiting movement. [ 5 ]  The fracture may interfere with breathing, requiring  tracheal intubation  and  mechanical ventilation . [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3909", "contents": "People who experience a  pathologic fracture  will be investigated for the cause of the underlying disease, if it is unknown. Treatment of any underlying disease, such as chemotherapy if indicated for bone cancer, may help to improve the pain of a sternal fracture.  [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3910", "contents": "In 1864, E. Guilt published a handbook recording sternal fractures as a rare injury found in severe trauma. [ 9 ]   The injury became more common with the introduction and wide use of automobiles and the subsequent rise in traffic accidents. [ 9 ]   A rise in sternal fractures has also been seen with an increase in the frequency of  laws requiring that seat belts be worn . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3911", "contents": "Injury of the  thoracic aorta  refers to any injury which affects the portion of the  aorta  which lies within the  chest cavity . Injuries of the thoracic aorta are usually the result of  physical trauma ; however, they can also be the result of a pathological process. The main causes of this injury are  deceleration  (such as a car accident) and  crush injuries . There are different grades to injuries to the aorta depending on the extent of injury, and the treatment whether surgical or medical depends on that grade. [ 1 ]  It is difficult to determine if a patient has a thoracic injury just by their symptoms, but through imaging and a physical exam the extent of injury can be determined. [ 2 ]  All patients with a thoracic aortic injury need to be treated either surgically with endovascular repair or open surgical repair or with medicine to keep their blood pressure and heart rate in the appropriate range. [ 3 ]  However, most patients that have a thoracic aortic injury do not live for 24 hours. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3912", "contents": "Injuries to the aorta are usually the result of trauma, such as  deceleration  and crush injuries. Deceleration injuries almost always occur during high speed impacts, such as those in  motor vehicle crashes  and falls from a substantial height. Several mechanical processes can occur and are reflected in the injury itself. A more recently proposed mechanism is that the aorta can be compressed between bony structures (such as the  manubrium ,  clavicle , and first  rib ) and the  spine . In the  ascending aorta  (the portion of the aorta which is almost vertical), one mechanism of injury is torsion (a two-way twisting). [ 5 ]  There are clinical predictors of an aortic injury. [ 6 ]  The predictors include if a patient is older than 50, was an unrestrained patient, has hypotension, has a thoracic injury requiring thoracotomy, has a spinal injury, or has a head injury. [ 6 ]  If four of these criteria are met their likelihood for an aortic injury is 30% [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3913", "contents": "The aortic wall is made up of three different components the inner layer (intima), the muscle layer (media), and the outer layer (adventitia). A traumatic injury to the thoracic aorta can cause disruption of any of these parts. Therefore, aortic injury is on a scale from injury to a part of the inner layer to a complete tear of all three layers. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3914", "contents": "There are 4 grades of aortic injury. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3915", "contents": "In addition to the 4 grades of aortic injury, the risk of rupture can also be categorized. If both the inner layer and the muscle layer of the aortic wall are both involved in the injury then the injury is categorized as significant aortic injury. [ 8 ]  If just the inner layer and a portion of the muscle layer are involved in the injury then the injury is characterized as minimal aortic injury. [ 8 ]  Radiographically this would be seen as an intimal flap less than 1\u00a0cm in size. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3916", "contents": "Between the mobile ascending aorta and the relatively fixed descending thoracic aorta is the aortic isthmus. When there is a sudden deceleration the mobile ascending aorta pushes forward creating a whiplash effect on the aortic isthmus. [ 9 ]  However, a different mechanism is involved when the ascending aorta proximal to the isthmus is torn. When there is a rapid deceleration the heart is pushed to the left posterior chest. This causes a sudden increase in intra-aortic pressure and can cause aortic rupture. This is known as the water hammer effect. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3917", "contents": "Based on the location of the injury in the thorax subsequent injuries can take place. If the injury is in the descending thoracic aorta this could lead to a hemothorax. [ 4 ]  Where as an injury to the ascending aorta could lead to hemoperricardium and subsequent tamponade or could compress the SVC. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3918", "contents": "It is difficult to rely on symptoms to diagnose a thoracic aortic injury. However some symptoms do include severe chest pain, cough, shortness of breath, difficulty swallowing due to compression of the esophagus, back pain, and hoarseness due to involvement of the recurrent laryngeal nerve. [ 4 ]  There might be external signs such as bruising on the anterior chest wall due to a traumatic injury. [ 9 ]  Clinical signs are uncommon and nonspecific but can include generalized hypertension due to the injury involving the sympathetic afferent nerves in the aortic isthmus. [ 9 ]  A murmur can also be audible as turbulent blood flow goes over the tear. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3919", "contents": "There are inconsistencies in the terminology of aortic injury. There are several terms which are interchangeably used to describe injury to the aorta such as  tear ,  laceration ,  transection , and  rupture .  Laceration  is used as a term for the consequence of a tear, whereas a  transection  is a section across an  axis  or  cross section . For all intents and purposes, the latter is used when a tear occurs across all or nearly all of the  circumference  of the aorta.  Rupture  is defined as a forcible disruption of tissue. Some disagree with the usage of  rupture  as they believe it implies that a tear is incompatible with life; however, the term accurately gauges the severity of tears in the aorta. A rupture can be either complete or partial, and can be classified further by the position of the tear. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3920", "contents": "The gold standard for diagnosis of thoracic aortic injury is aortography. This method involves inserting a catheter into the aorta and directly injecting contrast material. The primary benefit of aortography is the ability to precisely determine the location of injury for surgical planning. [ 4 ]  Another imaging modality is CT angiogram which has a sensitivity of 100%. [ 4 ]  A CT angiogram relies on timing the CT scan after a bolus of IV contrast is administered from a peripheral IV site. Since a CT angiogram has a sensitivity of 100% and less invasive due to the peripheral placement of the IV line than aortagraphy it is the primary imaging choice. [ 4 ]  This allows visualization of the aorta and provides precise locations of traumatic injury. [ 9 ]  A CT angiogram does show both direct and indirect signs of aortic injury. The indirect sign that you can see is effacement of fat due to a hematoma. [ 2 ]  This sign should clue in a radiologist that there is an underlying injury. Some direct signs from a CT include having an intimal flap, irregularity of the shape of the aorta, filling defects secondary to a thrombus, or out pouching of the aorta. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3921", "contents": "However, non contrasted CT scans, chest X-rays, and transesophageal echos can also be used. Chest X-rays most sensitive finding is a widened mediastinum of greater than 8\u00a0cm. [ 4 ]  An apical cap and displacement of the trachea to either side of the chest from midline can also be seen. [ 9 ]  A normal chest X-ray, however, does not exclude a diagnosis of thoracic aortic injury. [ 4 ]  A chest X-ray can also be useful to diagnose subsequent problems caused by aortic rupture such as pneumothorax or hemothorax. [ 9 ]  Non contrasted CT scans might show an intimal flap, periaortic hematoma, luminal filling defect, aortic contour abnormality, pseudoaneurysm, contained rupture, vessel wall disruption, active extravasation of intravenous contrast from the aorta and is therefore useful to assess for minimal aortic injury. [ 9 ]  Trans esophageal echos are useful in patients that are hemodynamically unstable, but the sensitivity and specificity of this study varies based on clinical user. [ 4 ]  The trans esophageal echo relies on placement an ultrasound probe into the patient's esophagus in order to get an ultrasound of the heart. If esophageal injury is expected, the patient has a facial injury, or if the patient has difficulty maintaining their away then the trans esophageal echo is contraindicated. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3922", "contents": "The first line treatment for patients with thoracic aortic injury is maintaining the patient's airway with intubation and treating secondary injuries such as a hemothorax. [ 4 ]  After ensuring the patient has a patent airway and other life-threatening injuries are treated then treatment for the aortic injury can be started."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3923", "contents": "Due to the constant risk of sudden rupture or exsanguination urgent treatment is necessary. A patient can either undergo endovascular repair or surgical repair. [ 9 ]  Endovascular repair is the current gold standard due to increased success rates and lower complications. [ 9 ] [ 1 ]  Patients that are able to undergo endovascular repair without contraindications should proceed with it. [ 1 ]  Repair should be delayed if there is life-threatening intra-abdominal or intracranial bleeding or if the patient is at risk for infection. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3924", "contents": "Endovascular repair is done by first gaining vascular access usually through the femoral artery. [ 8 ]  A catheter is inserted to the point of injury and a luminal stent is deployed. [ 1 ]  Blood is then able to be pumped through the stent and prevent the aortic wall from rupturing. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3925", "contents": "Surgical repair is done by way of a thoracotomy or opening of the chest wall. [ 8 ]  From this point multiple methods can be used, but the most successful methods enable distal perfusion to prevent ischemia. [ 8 ]  When the surgery is performed a constant check of blood flow to the parts of the body away from the injury should be monitored to know if oxygenation is occurring. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3926", "contents": "While waiting for surgery careful regulation of blood pressure and heart rate is necessary. [ 3 ]  Systolic blood pressure should be maintained between 100 and 120 mmHg allowing for perfusion distal to the injury but decreasing the risk of rupture while the heart rate should be kept under 100 beats per minute. Esmolol is first choice to maintain blood pressure and heart rate due to its short time of action, but if the blood pressure is not within range adding nitroprusside sodium can be added as a second agent. [ 9 ]  The treatment is similar to what is done for aortic dissections. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3927", "contents": "If the patient has minimal aortic injury then the patient can be managed non surgically. [ 8 ]  Rather the patient can be followed with serial images. If the patient does develop a more severe injury including a full thickness injury through the media layer then the patient should be treated with surgery. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3928", "contents": "Thoracic aortic injury is the 2nd leading cause of death involving both blunt trauma. 80% of patients that have a thoracic aortic injury will die immediately. [ 4 ]  Of the patients that do make it to be evaluated only 50% will survive 24 hours. [ 1 ]  Of the patients that do survive the first 24 hours 14% develop paraplegia. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3929", "contents": "Thoracic aortic injury is most commonly caused by a penetrating trauma in up to 90% of cases. [ 10 ]  Of these cases around 28% are confined to the thoracic portion of the aorta including the ascending aorta, aorta arch, and the descending aorta. [ 10 ]  Of the thoracic aortic injuries the ligament arteriosum is the most common location followed by the portion of the aorta after the origin of the left subclavian artery. [ 10 ]  The most common mechanism leading to thoracic aortic injury is a motor vehicle collision. Other mechanisms include airplane crashes, falling from a large height and landing on a hard surface, or any injury that causes substantial pressure to the sternum. [ 10 ]  The incidence of thoracic aortic injuries is approximately 1 in 100,000. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3930", "contents": "Tracheobronchial injury  is damage to the  tracheobronchial tree  (the  airway  structure involving the  trachea  and  bronchi ). [ 2 ]  It can result from  blunt  or  penetrating  trauma to the neck or  chest , [ 3 ]  inhalation of harmful fumes or  smoke , or  aspiration  of liquids or objects. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3931", "contents": "Though rare, TBI is a serious condition; it may cause obstruction of the airway with resulting life-threatening  respiratory insufficiency . [ 2 ]  Other injuries accompany TBI in about half of cases. [ 5 ]  Of those people with TBI who die, most do so before receiving emergency care, either from airway obstruction,  exsanguination , or from injuries to other vital organs. Of those who do reach a hospital, the  mortality rate  may be as high as 30%. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3932", "contents": "TBI is frequently difficult to  diagnose  and treat. [ 7 ]  Early diagnosis is important to prevent  complications , which include  stenosis  (narrowing) of the airway,  respiratory tract infection , and damage to the lung tissue. Diagnosis involves procedures such as  bronchoscopy ,  radiography , and  x-ray computed tomography  to visualize the tracheobronchial tree.  Signs  and  symptoms  vary based on the location and severity of the injury; they commonly include  dyspnea  (difficulty breathing),  dysphonia  (a condition where the voice can be hoarse, weak, or excessively breathy), coughing, and abnormal  breath sounds . In the emergency setting,  tracheal intubation  can be used to ensure that the airway remains open. In severe cases, surgery may be necessary to repair a TBI. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3933", "contents": "Signs and symptoms vary depending on what part of the tracheobronchial tree is injured and how severely it is damaged. [ 6 ]  There are no direct signs of TBI, but certain signs suggest the injury and raise a clinician's suspicion that it has occurred. [ 8 ]  Many of the signs and symptoms are also present in injuries with similar injury mechanisms such as pneumothorax. [ 9 ]  Dyspnea and  respiratory distress  are found in 76\u2013100% of people with TBI, and  coughing up blood  has been found in up to 25%. [ 10 ]  However, isolated TBI does not usually cause profuse bleeding; if such bleeding is observed it is likely to be due to another injury such as a ruptured large  blood vessel . [ 2 ]  The patient may exhibit dysphonia or have diminished breath sounds, and  rapid breathing  is common. [ 3 ]  Coughing may be present, [ 11 ]  and  stridor , an abnormal, high-pitched breath sound indicating obstruction of the upper airway can also occur. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3934", "contents": "Damage to the airways can cause  subcutaneous emphysema  (air trapped in the  subcutaneous tissue  of the skin) in the abdomen, chest, neck, and head. [ 2 ]  Subcutaneous emphysema, present in up to 85% of people with TBI, [ 10 ]  is particularly indicative of the injury when it is only in the neck. [ 13 ]  Air is trapped in the chest cavity outside the lungs (pneumothorax) in about 70% of TBI. [ 4 ] [ 10 ]  Especially strong evidence that TBI has occurred is failure of a pneumothorax to resolve even when a  chest tube  is placed to rid the chest cavity of the air; it shows that air is continually leaking into the chest cavity from the site of the tear. [ 11 ]  Air can also be trapped in the  mediastinum , the center of the chest cavity ( pneumomediastinum ). [ 4 ]  If air escapes from a penetrating injury to the neck, a definite diagnosis of TBI can be made. [ 10 ]   Hamman's sign , a sound of crackling that occurs in time with the heartbeat, may also accompany TBI. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3935", "contents": "Injuries to the tracheobronchial tree within the chest may occur due to penetrating forces such as  gunshot wounds , but are more often the result of blunt trauma. [ 6 ]  TBI due blunt forces usually results from high-energy impacts such as falls from height and  motor vehicle accidents ; the injury is rare in low-impact mechanisms. [ 2 ]  Injuries of the trachea cause about 1% of traffic-related deaths. [ 4 ]  Other potential causes are falls from high places and injuries in which the chest is crushed. [ 15 ]  Explosions are another cause. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3936", "contents": "Gunshot wounds are the commonest form of penetrating trauma that cause TBI. [ 15 ]  Less commonly, knife wounds and shrapnel from motor vehicle accidents can also penetrate the airways. [ 6 ]  Most injuries to the trachea occur in the neck, [ 3 ]  because the airways within the chest are deep and therefore well protected; however, up to a quarter of TBI resulting from penetrating trauma occurs within the chest. [ 10 ]  Injury to the cervical trachea usually affects the anterior (front) part of the trachea. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3937", "contents": "Certain medical procedures can also injure the airways; these include tracheal intubation, bronchoscopy, and  tracheotomy . [ 4 ]  The back of the trachea may be damaged during tracheotomy. [ 18 ]  TBI resulting from tracheal intubation (insertion of a tube into the trachea) is rare, and the mechanism by which it occurs is unclear. [ 19 ]  However, one likely mechanism involves an  endotracheal tube  catching in a fold of membrane and tearing it as it is advanced downward through the airway. [ 20 ]  When an endotracheal tube tears the trachea, it typically does so at the posterior (back) membranous wall. [ 17 ]  Unlike TBI that results from blunt trauma, most iatrogenic injuries to the airway involve longitudinal tears to the back of the trachea or tears on the side that pull the membranous part of the trachea away from the cartilage. [ 20 ]  Excessive pressure from the cuff of an endotracheal tube can reduce blood supply to the tissues of the trachea, leading to  ischemia  and potentially causing it to become ulcerated,  infected , and, later, narrowed. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3938", "contents": "The  mucosal lining  of the trachea may also be injured by inhalation of hot gases or harmful fumes such as  chlorine gas . [ 17 ]  This can lead to  edema  (swelling),  necrosis  (death of the tissue), scar formation, and ultimately stenosis. [ 17 ]  However, TBI due to inhalation, foreign body aspiration, and medical procedures is uncommon. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3939", "contents": "The structures in the tracheobronchial tree are well protected, so it normally takes a large amount of force to injure them. [ 6 ]  In blunt trauma, TBI is usually the result of violent compression of the chest. [ 5 ] [ 10 ]  Rapid  hyperextension  of the neck, usually resulting from vehicle crashes, can also injure the trachea, and trauma to the neck can crush the trachea against the vertebrae. [ 10 ]  A crush injury of the larynx or cervical trachea can occur in head-on collisions when the neck is hyperextended and strikes the steering wheel or dashboard; this has been called a \"dashboard injury\". [ 10 ]  The larynx and cervical trachea may also be injured in front-on collisions by the seat belt. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3940", "contents": "Although the mechanism is not well understood, TBI due to blunt trauma is widely thought to be caused by any combination of three possible mechanisms: an increase in pressure within the airways,  shearing , and pulling apart. [ 11 ]  The first type of injury, sometimes called an \"explosive rupture\", may occur when the chest is violently compressed, for example when a driver strikes the steering wheel in a vehicle accident [ 4 ]  or when the chest is crushed. [ 21 ]  The pressure in the airways, especially the larger airways (the trachea and bronchi), quickly rises as a result of the compression, [ 22 ]  because the  glottis  reflexively closes off the airways. [ 2 ]  When this pressure exceeds the elasticity of the tissues, they burst; thus the membranous part of the trachea is more commonly affected by this mechanism of injury than cartilaginous portions. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3941", "contents": "The second mechanism may occur when the chest is suddenly  decelerated , as occurs in vehicle accidents, producing a shearing force. [ 22 ]  The lungs are mobile in the chest cavity but their movement is more restricted near the  hilum . [ 22 ]  Areas near the  cricoid cartilage  and carina are fixed to the  thyroid cartilage  and the  pericardium  respectively; thus if the airways move, they can tear at these points of fixation. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3942", "contents": "The third mechanism occurs when the chest is compressed from front to back, causing it to widen from side to side. [ 10 ]  The lungs adhere to the chest wall because of the negative pressure between them and the pleural membranes lining the inside of the chest cavity; thus when the chest widens, they are pulled apart. [ 10 ]  This creates tension at the carina; the airway tears if this tensile force exceeds its elasticity. [ 10 ]  This mechanism may be the cause of injury when the chest is crushed. [ 22 ]  Most TBI are probably due to a combination of these three mechanisms. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3943", "contents": "When airways are damaged, air can escape from them and be trapped in the surrounding tissues in the neck (subcutaneous emphysema) and mediastinum (pneumomediastinum); if it builds up to high enough pressures there, it can compress the airways. [ 2 ]  Massive air leaks from a ruptured airway can also compromise the circulation by preventing blood from returning to the heart from the head and lower body; this causes a potentially deadly reduction in the amount of blood the heart is able to pump out. [ 7 ]  Blood and other fluids can build up in the airways, and the injury can interfere with the patency of the airway and interfere with its continuity. [ 2 ]  However, even if the trachea is completely transected, the tissues surrounding it may hold it together enough for adequate air exchange to occur, at least at first. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3944", "contents": "The trachea and bronchi form the tracheobronchial tree. The trachea is situated between the lower end of the  larynx  and the center of the chest, where it splits into the two bronchi at a ridge called the  carina . The trachea is stabilized and kept open by rings made of  cartilage  that surround the front and sides of the structure; these rings are not closed and do not surround the back, which is made of membrane. [ 21 ]  The bronchi split into smaller branches and then to bronchioles that supply air to the  alveoli , the tiny air-filled sacs in the lungs responsible for absorbing  oxygen . An arbitrary division can be made between the  intrathoracic  and  cervical  trachea at the  thoracic inlet , an opening at the top of the  thoracic cavity . [ 17 ]  Anatomical structures that surround and protect the tracheobronchial tree include the lungs, the  esophagus , large blood vessels, the  rib cage , the  thoracic spine , and the  sternum . [ 17 ]  Children have softer tracheas and a more elastic tracheobronchial trees than adults; this elasticity, which helps protect the structures from injury when they are compressed, may contribute to the lower  incidence  of TBI in children. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3945", "contents": "Rapid diagnosis and treatment are important in the care of TBI; [ 6 ]  if the injury is not diagnosed shortly after the injury, the risk of complications is higher. [ 11 ]  Bronchoscopy is the most effective method to diagnose, locate, and determine the severity of TBI, [ 6 ] [ 10 ]  and it is usually the only method that allows a definitive diagnosis. [ 23 ]  Diagnosis with a flexible bronchoscope, which allows the injury to be visualized directly, is the fastest and most reliable technique. [ 8 ]  In people with TBI, bronchoscopy may reveal that the airway is torn, or that the airways are blocked by blood, or that a bronchus has collapsed, obscuring more  distal  (lower) bronchi from view. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3946", "contents": "Chest x-ray  is the initial imaging technique used to diagnose TBI. [ 17 ]  The film may not have any signs in an otherwise asymptomatic patient. [ 15 ]  Indications of TBI seen on radiographs include deformity in the trachea or a defect in the tracheal wall. [ 17 ]  Radiography may also show cervical emphysema, air in the tissues of the neck. [ 2 ]  X-rays may also show accompanying injuries and signs such as fractures and subcutaneous emphysema. [ 2 ]  If subcutaneous emphysema occurs and the  hyoid bone  appears in an X-ray to be sitting unusually high in the throat, it may be an indication that the trachea has been severed. [ 4 ]  TBI is also suspected if an endotracheal tube appears in an X-ray to be out of place, or if its cuff appears to be more full than normal or to protrude through a tear in the airway. [ 17 ]  If a bronchus is torn all the way around, the lung may collapse outward toward the chest wall (rather than inward, as it usually does in pneumothorax) because it loses the attachment to the bronchus which normally holds it toward the center. [ 6 ]  In a person lying face-up, the lung collapses toward the  diaphragm  and the back. [ 23 ]  This sign, described in 1969, is called fallen lung sign and is  pathognomonic  of TBI (that is, it is diagnostic for TBI because it does not occur in other conditions); however it occurs only rarely. [ 6 ]  In as many as one in five cases, people with blunt trauma and TBI have no signs of the injury on chest X-ray. [ 23 ]   CT scanning  detects over 90% of TBI resulting from blunt trauma, [ 3 ]  but neither X-ray nor CT are a replacement for bronchoscopy. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3947", "contents": "At least 30% of TBI are not discovered at first; [ 4 ]  this number may be as high as 50%. [ 24 ]  In about 10% of cases, TBI has no specific signs either clinically or on chest radiography, and its detection may be further complicated by concurrent injuries, since TBI tends to occur after high-energy accidents. [ 2 ]  Weeks or months may go by before the injury is diagnosed, even though the injury is better known than it was in the past. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3948", "contents": "Lesions can be  transverse , occurring between the rings of the trachea, longitudinal or spiral. They may occur along the membranous part of the trachea, the main bronchi, or both. [ 2 ]  In 8% of ruptures, lesions are complex, occurring in more than one location, with more than one type of lesion, or on both of the main bronchi and the trachea. [ 2 ]  Transverse tears are more common than longitudinal or complex ones. [ 17 ]  The laceration may completely transect the airway or it may go only partway around. Partial tears that do not go all the way around the circumference of the airway do not allow a lacerated airway to become completely detached; tears that encircle the whole airway can allow separation to occur. [ 23 ]  Lacerations may also be classified as complete or incomplete. [ 4 ]  In an incomplete lesion, a layer of tissue surrounding the bronchus remains intact and can keep the air in the airway, preventing it from leaking into the areas surrounding the airways. [ 14 ]  Incomplete lacerations may require closer scrutiny to detect [ 24 ]  and may not be diagnosed right away. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3949", "contents": "Bronchial injuries are divided into those that are accompanied by a disruption of the  pleura  and those that are not; in the former, air can leak from the hole in the airway and a  pneumothorax  can form. [ 15 ]  The latter type is associated with more minor signs; pneumothorax is small if it occurs at all, and although function is lost in the part of the lung supplied by the injured bronchus, unaffected parts of the lungs may be able to compensate. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3950", "contents": "Most TBI that results from blunt trauma occurs within the chest. [ 10 ]  The most common tracheal injury is a tear near the carina or in the membranous wall of the trachea. [ 15 ]  In blunt chest trauma, TBI occurs within 2.5\u00a0cm of the carina 40\u201380% of the time. [ 2 ]  The injury is more common in the right main bronchus than the left, possibly because the former is near  vertebrae , which may injure it. [ 2 ]  Also, the  aorta  and other tissues in the mid chest that surround the left main bronchus may protect it. [ 22 ]  Another possibility is that people with left main bronchus injuries are more likely to also have other deadly injuries and therefore die before reaching hospital, making them less likely to be included in studies that determine rates of injuries. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3951", "contents": "Vehicle occupants who wear seat belts have a lower incidence of TBI after a motor vehicle accident. [ 25 ]  However, if the strap is situated across the front of the neck (instead of the chest), this increases the risk of tracheal injury. [ 10 ]  Design of medical instruments can be modified to prevent iatrogenic TBI, and medical practitioners can use techniques that reduce the risk of injury with procedures such as tracheotomy. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3952", "contents": "Treatment of TBI varies based on the location and severity of injury and whether the patient is stable or having trouble breathing, [ 2 ]  but ensuring that the airway is patent so that the patient can breathe is always of paramount importance. [ 10 ]  Ensuring an open airway and adequate ventilation may be difficult in people with TBI. [ 3 ]  Intubation, one method to secure the airway, may be used to bypass a disruption in the airway in order to send air to the lungs. [ 3 ]  If necessary, a tube can be placed into the uninjured bronchus, and a single lung can be ventilated. [ 3 ]  If there is a penetrating injury to the neck through which air is escaping, the trachea may be intubated through the wound. [ 10 ]  Multiple unsuccessful attempts at conventional (direct)  laryngoscopy  may threaten the airway, so alternative techniques to visualize the airway, such as  fiberoptic  or  video  laryngoscopy, may be employed to facilitate tracheal intubation. [ 10 ]  If the upper trachea is injured, an incision can be made in the trachea (tracheotomy) or the  cricothyroid membrane  ( cricothyrotomy , or cricothyroidotomy) in order to ensure an open airway. [ 6 ]  However, cricothyrotomy may not be useful if the trachea is lacerated below the site of the artificial airway. [ 10 ]  Tracheotomy is used sparingly because it can cause complications such as infections and narrowing of the trachea and larynx. [ 26 ]  When it is impossible to establish a sufficient airway, or when complicated surgery must be performed,  cardiopulmonary bypass  may be used\u2014blood is pumped out of the body,  oxygenated  by a machine, and pumped back in. [ 26 ]  If a pneumothorax occurs, a chest tube may be inserted into the pleural cavity to remove the air. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3953", "contents": "People with TBI are provided with supplemental oxygen and may need  mechanical ventilation . [ 13 ]  Employment of certain measures such as  Positive end-expiratory pressure  (PEEP) and ventilation at higher-than-normal pressures may be helpful in maintaining adequate oxygenation. [ 3 ]  However, such measures can also increase leakage of air through a tear, and can stress the sutures in a tear that has been surgically repaired; therefore the lowest possible airway pressures that still maintain oxygenation are typically used. [ 3 ]  The use of high frequency ventilation has been reported. [ 27 ]  Mechanical ventilation can also cause  pulmonary barotrauma  when high pressure is required to ventilate the lungs. [ 3 ]  Techniques such as  pulmonary toilet  (removal of  secretions ), fluid management, and treatment of pneumonia are employed to improve  pulmonary compliance  (the elasticity of the lungs). [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3954", "contents": "While TBI may be managed without surgery, surgical repair of the tear is considered standard in the treatment of most TBI. [ 3 ] [ 28 ]  It is required if a tear interferes with ventilation; if  mediastinitis  (inflammation of the tissues in the mid-chest) occurs; or if subcutaneous or mediastinal emphysema progresses rapidly; [ 3 ]  or if air leak or large pneumothorax is persistent despite chest tube placement. [ 12 ]  Other indications for surgery are a tear more than one third the circumference of the airway, tears with loss of tissue, and a need for positive pressure ventilation. [ 26 ]  Damaged tissue around a rupture (e.g. torn or scarred tissue) may be removed in order to obtain clean edges that can be surgically repaired. [ 22 ]   Debridement  of damaged tissue can shorten the trachea by as much as 50%. [ 29 ]  Repair of extensive tears can include sewing a flap of tissue taken from the membranes surrounding the heart or lungs (the pericardium and pleura, respectively) over the sutures to protect them. [ 2 ]  When lung tissue is destroyed as a result of TBI complications,  pneumonectomy  or  lobectomy  (removal of a lung or of one lobe, respectively) may be required. [ 30 ]  Pneumonectomy is avoided whenever possible due to the high rate of death associated with the procedure. [ 3 ]  Surgery to repair a tear in the tracheobronchial tree can be successful even when it is performed months after the trauma, as can occur if the diagnosis of TBI is delayed. [ 3 ]  When airway stenosis results after delayed diagnosis, surgery is similar to that performed after early diagnosis: the stenotic section is removed and the cut airway is repaired. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3955", "contents": "Most people with TBI who die do so within minutes of the injury, due to complications such as pneumothorax and insufficient airway and to other injuries that occurred at the same time. [ 5 ]  Most late deaths that occur in TBI are attributed to  sepsis  or  multiple organ dysfunction syndrome  (MODS). [ 2 ]  If the condition is not recognized and treated early, serious complications are more likely to occur; for example, [ 30 ]   pneumonia  and  bronchiectasis  may occur as late complications. [ 3 ]  Years can pass before the condition is recognized. [ 9 ] [ 30 ]  Some TBI are so small that they do not have significant clinical manifestations; they may never be noticed or diagnosed and may heal without intervention. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3956", "contents": "If  granulation tissue  grows over the injured site, it can cause stenosis of the airway, after a week to a month. [ 4 ]  The granulation tissue must be surgically excised. [ 26 ]  Delayed diagnosis of a bronchial rupture increases risk of infection and lengthens hospital stay. [ 29 ]  People with a narrowed airway may develop dyspnea, coughing,  wheezing , respiratory tract infection, and difficulty with clearing secretions. [ 10 ]  If the bronchiole is completely obstructed,  atelectasis  occurs: the alveoli of the lung collapse. [ 4 ]  Lung tissue distal to a completely obstructed bronchiole often does not become infected. Because it is filled with mucus, this tissue remains functional. [ 22 ]  When the secretions are removed, the affected portion of the lung is commonly able to function almost normally. [ 30 ]  However, infection is common in lungs distal to a partially obstructed bronchiole. [ 22 ]  Infected lung tissue distal to a stricture can be damaged, and wheezing and coughing may develop due to the narrowing. [ 15 ]  In addition to pneumonia, the stenosis may cause bronchiectasis, in which bronchi are dilated, to develop. [ 22 ]  Even after an airway with a stricture is restored to normal, the resulting loss of lung function may be permanent. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3957", "contents": "Complications may also occur with treatment; for example, a  granuloma  can form at the suture site. [ 2 ]  Also, the sutured wound can tear again, as occurs when there is excessive pressure in the airways from ventilation. [ 2 ]  However, for people who do receive surgery soon after the injury to repair the lesion, outcome is usually good; the long-term outcome is good for over 90% of people who have TBI surgically repaired early in treatment. [ 10 ]  Even when surgery is performed years after the injury, the outlook is good, with low rates of death and disability and good chances of preserving lung function. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3958", "contents": "Rupture of the trachea or bronchus is the most common type of blunt injury to the airway. [ 22 ]  It is difficult to determine the incidence of TBI: in as many as 30\u201380% of cases, death occurs before the person reaches a hospital, and these people may not be included in studies. [ 3 ]  On the other hand, some TBI are so small that they do not cause significant symptoms and are therefore never noticed. [ 30 ]  In addition, the injury sometimes is not associated with symptoms until complications develop later, further hindering estimation of the true incidence. [ 6 ]  However, autopsy studies have revealed TBI in 2.5\u20133.2% of people who died after trauma. [ 3 ]  Of all neck and chest traumas, including people that died immediately, TBI is estimated to occur in 0.5\u20132%. [ 30 ]  An estimated 0.5% of  polytrauma  patients treated in  trauma centers  have TBI. [ 10 ]  The incidence is estimated at 2% in blunt chest and neck trauma and 1\u20132% in penetrating chest trauma. [ 10 ]  Laryngotracheal injuries occur in 8% of patients with penetrating injury to the neck, and TBI occurs in 2.8% of blunt chest trauma deaths. [ 6 ]  In people with blunt trauma who do reach a hospital alive, reports have found incidences of 2.1% and 5.3%. [ 2 ]  Another study of blunt chest trauma revealed an incidence of only 0.3%, but a mortality rate of 67% (possibly due in part to associated injuries). [ 6 ]  The incidence of iatrogenic TBI (that caused by medical procedures) is rising, and the risk may be higher for women and the elderly. [ 31 ]  TBI results about once every 20,000 times someone is intubated through the mouth, but when intubation is performed emergently, the incidence may be as high as 15%. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3959", "contents": "The mortality rate for people who reach a hospital alive was estimated at 30% in 1966; [ 2 ]  more recent estimates place this number at 9%. [ 22 ]  The number of people reaching a hospital alive has increased, perhaps due to improved  prehospital  care or specialized treatment centers. [ 10 ]  Of those who reach the hospital alive but then die, most do so within the first two hours of arrival. [ 9 ]  The sooner a TBI is diagnosed, the higher the mortality rate; this is likely due to other accompanying injuries that prove fatal. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3960", "contents": "Accompanying injuries often play a key role in the outcome. [ 10 ]  Injuries that may accompany TBI include  pulmonary contusion  and  laceration ; and  fractures of the sternum ,  ribs  and  clavicles . [ 2 ]   Spinal cord injury ,  facial trauma ,  traumatic aortic rupture ,  injuries to the abdomen , lung, and  head  are present in 40\u2013100%. [ 17 ]  The most common accompanying injury is esophageal perforation or rupture (known as  Boerhaave syndrome ), which occurs in as many as 43% of the penetrating injuries to the neck that cause tracheal injury. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3961", "contents": "Throughout most of history, the mortality rate of TBI was thought to be 100%. [ 5 ]  However, in 1871 a healed TBI was noted in a duck that had been killed by a hunter, thus demonstrating that the injury could be survived, at least in the general sense. [ 6 ]  This report, made by Winslow, was the first record in the medical literature of a bronchus injury. [ 22 ]  In 1873, Seuvre made one of the earliest reports of TBI in the medical literature: a 74-year-old woman whose chest was crushed by a wagon wheel was found on autopsy to have an  avulsion  of the right bronchus. [ 22 ]  Long-term survival of the injury was unknown in humans until a report was made of a person who survived in 1927. [ 5 ] [ 6 ]  In 1931, a report made by Nissen described successful removal of a lung in a 12-year-old girl who had had narrowing of the bronchus due to the injury. [ 22 ]  Repair of TBI was probably first attempted in 1945, when the first documented case of a successful suturing of a lacerated bronchus was made. [ 6 ]  Prior to 1950, the mortality rate was 36%; it had fallen to 9% by 2001; [ 3 ] [ 22 ]  this improvement was likely due to improvements in treatments and surgical techniques, including those for injuries commonly associated with TBI. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3962", "contents": "A  transmediastinal gunshot wound  (TMGSW) is a  penetrating injury  to a person's  thorax  in which a  bullet  enters the  mediastinum , possibly damaging some of the major structures in this area.  Hemodynamic  instability has been reported in about 50% of cases with a  mortality rate  ranging from 20% to 49%. Some studies have shown marked improvement in the mortality rate of patients who survived transfer to the operating room rather than being treated surgically in the ER."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3963", "contents": "Complications caused by a TMGSW can range from mild to life-threatening depending on which structures are damaged. It can be rapidly lethal if a major structure is involved. Some of the possible complications caused by a TMGSW are:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3964", "contents": "Previously, every stable patient who suffered a TMGSW received extensive evaluation that included  chest radiography , oesophagography, esophagoscopy,  angiography ,  bronchoscopy , or  cardiac ultrasound . Grossman et al. found evidence that the trajectory of the bullet can be delineated with the use of  computed tomographic scan  (CT). Subsequently, other studies demonstrated the use of CT as a screening tool for stable patients who suffered TMGSW is a reliable tool for ruling out, diagnosing, and avoiding missed injuries. For example, Stassen et al. showed data of 22 stable patients who were screened with CT, chest X-ray and  abdominal ultrasound ; seven patients showed a positive CT scan and required additional evaluation, and of these seven patients, three required surgical management. [ 1 ]  Additionally the work of Burack et al., [ 2 ]  whose evaluation of stable patients with penetrating injuries to the mediastinum \u2014 this time including stab wounds \u2014 relied mostly on CT and ultrasound, showed similar results. The work of Ibirogba et al. did so, as well. [ 3 ]  Recent data suggest that the use of CT scan with some additional noninvasive techniques, such as ultrasound and chest roentgenogram, are reliable screening tools to decide whether patients need further evaluation.  [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3965", "contents": "The criteria to define a patient as stable or unstable could have variations from institution to institution.  For example, Burack  et al.  used a list of six criteria in his paper that defined an unstable hemodynamic state:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3966", "contents": "One common criteria found in literature is a sustained systolic  blood pressure  of less than 100 mmHg, but this can be an oversimplification. Patients with clinical evidence of possible TMGSW that are considered unstable receive no further evaluation and are taken to surgery immediately. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3967", "contents": "Stable patients are evaluated with CT, ultrasound, and/or chest X-ray as the institution's protocol specifies. When this initial survey is negative, patients can be observed with conservative management. In many cases, chest tubes are required due to concomitant lesions in the  pleural cavity . If possible lesions are found (for example, a missile track near the  trachea  or  esophagus , or pneumomediastinum), further investigation follows with oesophagography, esophagoscopy, angiography, or bronchoscopy as needed to rule out or confirm such a lesion, and decide whether surgical repair is warranted."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3968", "contents": "Unstable patients are managed by operative exploration of the mediastinum. Moribund patients go through an emergency department  thoracotomy . This measure is taken because at their arrival in the emergency room, these patients are in such critical condition that they would not survive long enough to be transferred to an operating room. Outcome is very poor. Burack  et al. [ 2 ]  reported only 2.8% survival of such patients in his study. In a study by Van Waes et al., (which included all thoracic-penetrating injuries, not just transmediastinal) survival after emergency department thoracotomy was 25%. [ 4 ]  In other circumstances the unstable patient is immediately transferred to the operating room for exploration by thoracotomy or sternotomy. Survival rate has been reported as high as 75 percent when the patient is able to reach the OR. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3969", "contents": "Traumatic aortic rupture , also called  traumatic aortic disruption  or  transection ,  is a condition in which the  aorta , the largest  artery  in the body, is torn or ruptured as a result of trauma to the body. The condition is frequently fatal due to the profuse  bleeding  that results from the rupture.  Since the aorta branches directly from the  heart  to supply  blood  to the rest of the body, the pressure within it is very great, and blood may be pumped out of a tear in the blood vessel very rapidly. This can quickly result in  shock  and death.  Thus traumatic aortic rupture is a common killer in  automotive accidents  and other traumas, [ 1 ]  with up to  18% of deaths that occur in automobile collisions being related to the injury. [ 2 ]   In fact, aortic disruption due to blunt  chest trauma  is the second leading cause of injury death behind  traumatic brain injury . [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3970", "contents": "Aortic rupture  can also be caused by non-traumatic mechanisms, particularly  abdominal aortic aneurysm  rupture."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3971", "contents": "Symptoms are often unreliable, but include severe tearing chest pain; cough;  dyspnea  (shortness of breath);  dysphagia  (difficulty swallowing); back pain; and hoarseness. Blood pressure is usually high in the upper body, but low in the lower body. A widened  mediastinum  and a massive left  hemothorax  are often found in an X-ray. There can be bruising of the anterior chest wall, and a  systolic murmur  can be heard on the bottom of the heart. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3972", "contents": "The injury is usually caused by high speed impacts such as those that occur in vehicle collisions and serious falls. [ 1 ]   It may be due to different rates of deceleration of the heart and the aorta, which is in a fixed position. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3973", "contents": "By far the most common site for tearing in traumatic aortic rupture is the  proximal descending aorta , near where the left  subclavian artery  branches off from the aorta. [ 7 ]  The tethering of the aorta by the  ligamentum arteriosum  makes the site prone to shearing forces during sudden deceleration. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3974", "contents": "A study of people who died after traumatic aortic rupture found that in 55\u201365% of cases the damage was at the aortic isthmus and in 10\u201314% it was in the  ascending aorta  or  aortic arch . [ 4 ]   An angiogram will often show an irregular outpouching beyond the takeoff of the left subclavian artery at the aortic isthmus, representing an aortic  pseudoaneurysm  caused by the trauma.  Damage can also be in the lower thoracic or abdominal aorta. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3975", "contents": "The aorta is not always torn completely through; it may also tear some but not all layers of the arterial wall, sometimes forming a  false aneurysm . [ 4 ]   A sub- intimal  hemorrhage is the least serious type. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3976", "contents": "Being the mildest form, it often does not weaken the wall of the aorta and may heal on its own. Usually, it occurs in the  descending aorta . It was originally defined as a small intimal flap with less than one centimeter length and with little or no  haematoma . It is 10-28% of aortic injuries. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3977", "contents": "The condition is difficult to detect and may go unnoticed, because many patients have no specific symptoms. Diagnosis is further complicated by the fact that many patients with the injury experienced multiple other serious injuries as well, [ 10 ]  so the attention of hospital staff may be distracted from the possibility of aortic rupture. In fact most cases occur along with other injuries. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3978", "contents": "A common symptom is unusually high blood pressure in the upper body and very low blood pressure in lower limbs. Another sign is  kidney failure  where the  creatinine  level shoots very high and urine output becomes negligible. In most cases, however, the doctors would misinterpret kidney failure as due to issues with the kidney itself and may recommend dialysis. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3979", "contents": "Though not completely reliable, chest  X-rays  are the first-line investigation, [ 4 ]  initially used to diagnose this condition when the patient is unstable and cannot be sent to the CT bay.  The preferred method of diagnosis used to be  CT angiogram  until it was found to cause complications in some people. As of 2013 [update]  it is reserved for when  CT scans  are inconclusive. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3980", "contents": "The classical findings on a chest X-ray will be widened mediastinum, [ 4 ]  apical cap, and displacement of the trachea, left main bronchus, or nasogastric tube. A normal chest x-ray does not exclude transection, but will diagnose conditions such as pneumothorax or hydrothorax. The aorta may also be torn at the point where it is connected to the heart.  The aorta may be completely torn away from the heart, but patients with such injuries rarely survive  very long after the injury; thus it is much more common for hospital staff to treat patients with partially torn aortas. [ 1 ]  When the aorta is partially torn, it may form a \"pseudoaneurysm\".  In patients who do live long enough to be seen in a hospital, a majority have only a partially torn blood vessel, with the outermost  adventitial  layer still intact. [ 2 ]   In some of these patients, the adventitia and nearby structures within the chest may serve to prevent severe  bleeding . [ 2 ]  After trauma, the aorta can be assessed by a CT angiogram or a direct angiogram, in which contrast is introduced into the aorta via a catheter."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3981", "contents": "Traumatic aortic rupture is treated with surgery.  However,  morbidity  and  mortality rates  for surgical repair of the aorta for this condition are among the highest of any cardiovascular surgery. [ 3 ]   For example, surgery is associated with a high rate of  paraplegia , [ 11 ]  because the  spinal cord  is very sensitive to  ischemia  (lack of blood supply), and the nerve tissue can be damaged or killed by the interruption of the blood supply during surgery. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3982", "contents": "A less invasive option for treatment is  endovascular repair , which does not require open  thoracotomy  and can be safer for people with other injuries to organs. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3983", "contents": "Since high  blood pressure  could exacerbate an incomplete tear in the aorta or even separate it completely from the heart, which would almost inevitably kill the patient, hospital staff take measures to keep the blood pressure low. [ 1 ]   Such measures include giving  pain medication , keeping the patient calm, and avoiding procedures that could cause gagging or  vomiting . [ 1 ]   Beta blockers  and  vasodilators  can be given to lower the blood pressure, and  intravenous fluids  that might normally be given are foregone to avoid raising it. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3984", "contents": "In 1959, Passaro reported the first successful surgical repair of a torn aorta. Kirsh, in 1976, reported a 70% success rate in surgery to repair a torn aorta, based on 10 years of experience as a surgeon. Therefore, for those who make it to the hospital (85% do not), are successfully diagnosed in time and are quickly operated upon, the chances of survival are higher. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3985", "contents": "In some cases, intimal tears may resolve on their own. Therefore, conservative treatment like antihypertensives are usually initiated. There is limited data on the treatment of this type of aortic injury. In some places, endovascular repair is also an option for treatment. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3986", "contents": "Death occurs immediately after traumatic rupture of the thoracic aorta 75%\u201390% of the time since bleeding is so severe, and 80\u201385% of patients die before arriving at a hospital. [ 2 ]  Of those who live to reach a hospital, 23% die at the time of or shortly after arrival. [ 4 ]   In the US, an estimated 7,500\u20138,000 cases occur yearly, of which 1,000\u20131,500 make it to a hospital alive; these low numbers make it difficult to estimate the efficacy of surgical options. [ 4 ]   However, if surgery is performed in time, it can offer a chance of survival. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3987", "contents": "Though there is a concern that a small, stable tear in the aorta could enlarge and cause complete rupture of the aorta and heavy bleeding, this may be less common than previously believed as long as the blood pressure does not get too high. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3988", "contents": "There have been five rare cases of a traumatic aortic rupture going undiagnosed of more than a year, and presenting with chest and back pain. They had  pseudoaneurysms  or large aneurysms that caused pain. Asymptomatic chronic traumatic aneurysms are not always a risk for sudden death unless too large. Growing aneurysms, symptomatic or not, have a risk of rupture so the treatment is surgical removal. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3989", "contents": "Traumatic cardiac arrest  ( TCA ) is a condition in which the  heart  has  ceased  to beat due to  blunt  or  penetrating trauma , such as a  stab wound  to the  thoracic  area. [ 1 ]  It is a  medical emergency  which will always result in death without prompt advanced medical care.  Even with prompt medical intervention, survival without  neurological  complications is rare. [ 2 ]  In recent years, protocols have been proposed to improve survival rate in patients with traumatic cardiac arrest, though the variable causes of this condition as well as many coexisting injuries can make these protocols difficult to standardize. [ 3 ]  Traumatic cardiac arrest is a complex form of  cardiac arrest  often derailing from  advanced cardiac life support  in the sense that the emergency team must first establish the cause of the traumatic arrest and reverse these effects, for example hypovolemia and haemorrhagic shock due to a penetrating injury. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3990", "contents": "Traumatic cardiac arrest can occur in patients following any severe blunt or penetrating  injury to the chest . Following the traumatic event, the heart ceases to pump blood through the body. Unlike medical cardiac arrest, there are several potentially reversible causes that may result in cardiac arrest in the setting of trauma. Clinicians will rapidly assess for these causes, and interventions will be directed to the specific cause. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3991", "contents": "In both blunt and penetrating trauma, massive  internal  or  external bleeding  may decrease the volume of blood is available to be pumped by the heart to the body. This is considered  preload  dependent arrest. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3992", "contents": "Tension pneumothorax  is caused when air is able to enter the space between the  lung  and the  chest wall , but is not able to escape. The increasing pressure within the chest cavity prevents blood from returning from the body to fill the heart."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3993", "contents": "Hemothorax  occurs when injury to the chest results in bleeding into the thoracic cavity. Similar to tension pneumothorax, increasing pressure prevents the return of blood from circulation to the heart."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3994", "contents": "In the setting of trauma,  cardiac tamponade  results from an acute  pericardial effusion , the accumulation of blood within the sac that surrounds the heart. As this sac is filled with fluid, the pressure on the heart is increased, and the chambers of the heart are unable to fill with blood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3995", "contents": "Inability to maintain  oxygenation  in trauma patients may be a result of  airway  compromise due to mechanical injury or obstruction or due to loss of the  respiratory drive  from  cervical spine  or  peripheral nerve injury . [ 4 ]  These conditions result in the  hypoxia  that may lead to cardiac arrest."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3996", "contents": "Patients will present following a traumatic event most often with  pulseless electrical activity  (PEA). Patients will exhibit low blood pressure with pulses that cannot be palpated. Patients will progress into  asystole  if the underlying condition is not reversed. Other non-specific signs and symptoms associated with impending traumatic cardiac arrest may include sweating,  altered mental status ,  rapid  or  slow breathing , and signs of trauma (bruising,  laceration , fractures, etc.). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_3997", "contents": "Diagnosis of traumatic cardiac arrest is initially made with  electrocardiogram  with EMS or in the emergency department. Clinicians will also order diagnostic testing that may include  chest x-ray , bedside ultrasound and  echocardiogram , and blood gas levels. A  type and cross  will be ordered to match the patient to receive blood transfusion if necessary."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3998", "contents": "Other work-up involved in diagnosis of a trauma patient may include  e-FAST ,  RUSH exam ,  CBC , pelvic X-ray, and  CT  of the head, neck, chest, abdomen, and pelvis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_3999", "contents": "Treatment of traumatic cardiac arrest is guided by  advanced trauma life support guidelines . Standard advanced cardiac life support guidelines are inappropriate for use in traumatic cardiac arrest, as they are directed primarily at treating pathology originating within the heart itself. [ 5 ]  As clinicians begin to intervene, they will simultaneously seek reversible causes of the arrest. Management begins by establishing multiple points of IV access and evaluating the patient's airway and breathing. Other interventions may include  thoracostomy  and  thoracotomy , as well as treatment of the underlying cause of arrest."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4000", "contents": "Basic life support  is commonly initiated by bystanders and first responders, but the role of basic life support in traumatic cardiac arrest is unclear. Basic life support is targeted to maintain oxygenation and circulation throughout the body, which can be lifesaving in cases of medical cardiac arrest, but does not address the frequent large volume blood loss encounters in many cases of traumatic cardiac arrest. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4001", "contents": "Chest compressions  are considered the most important initial intervention in cases of medical cardiac arrest, however studies evaluating their efficacy have excluded patients with traumatic cardiac arrest. Chest compressions work to replace the cardiac function of pumping blood throughout the body, however cases where the heart is either unable to fill with blood or the total blood volume is depleted, this intervention may be ineffective. Additionally, as many of the interventions targeted at specific causes of arrest are centered around procedures performed around the patient's chest, head, and neck, compressions may interfere with definitive management. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4002", "contents": "Current guidelines tailored to treatment of specific causes of traumatic cardiac arrest have improved outcomes for patients, however these guidelines may be difficult to apply in a standardized manner due to differences in pre-hospital care and the wide variety of causes of traumatic cardiac arrest compared to medical cardiac arrest. [ 3 ]  Evolving algorithms are directed at quickly identifying incidences of cardiac arrest with a traumatic source and rapidly intervening to address reversible causes. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4003", "contents": "Historically, traumatic cardiac arrest was thought to lead invariably to death. More recently, evolutions of advanced trauma life support guidelines and improved understanding of the underlying causes of traumatic cardiac arrest have improved outcomes for patients. [ 5 ]  Recent studies suggest that the survival rate for traumatic cardiac arrest is similar to that of all-cause cardiac arrest. [ 6 ]  There is wide variability in the estimated survival rate based on factors that include initiation of pre-hospital care and nature of injury. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4004", "contents": "Many patients who survive traumatic cardiac arrest may develop long-term neurological damage resulting from lack of circulation to the nervous system during the arrest. This damage may range from moderate disability to a persistent vegetative state. A 2012 review suggests that while survival rates of traumatic cardiac arrest are higher in children, so is the incidence of neurological complication. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4005", "contents": "Traumatic asphyxia , or  Perte's syndrome , [ 1 ]  is a medical emergency caused by an intense compression of the  thoracic cavity , causing  venous  back-flow from the right side of the heart into the veins of the neck and the brain. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4006", "contents": "Traumatic asphyxia is characterized by  cyanosis  in the upper extremities, neck, and head as well as  petechiae  in the  conjunctiva .  Patients can also display  jugular venous distention  and facial  edema . [ 3 ]  Associated injuries include  pulmonary contusion ,  myocardial contusion ,  hemo / pneumothorax , and  broken ribs . [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4007", "contents": "Traumatic asphyxia occurs when a powerful compressive force is applied to the thoracic cavity. This is most often seen in  motor vehicle accidents , as well as industrial and farming accidents. However, it can be present anytime a significant pressure is applied to the thorax."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4008", "contents": "The sudden impact on the thorax causes an increase in  intrathoracic pressure . [ 4 ]   In order for traumatic asphyxia to occur, a  Valsalva maneuver  is required when the traumatic force is applied. [ 6 ]  Exhalation against the closed glottis along with the traumatic event causes air that cannot escape from the thoracic cavity. Instead, the air causes increased venous back-pressure, which is transferred back to the heart through the  right atrium , to the  superior vena cava  and to the head and neck veins and capillaries. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4009", "contents": "Patients are seen with a cyanotic discoloration of the shoulder skin and neck and face, jugular distention, bulging of the eyeballs, and swelling of the tongue and lips. The latter two are resultants of edema, caused by excessive blood accumulating in the veins of the head and neck and venous stasis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4010", "contents": "For individuals who survive the initial crush injury, survival rates are high for traumatic asphyxia. [ 4 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4011", "contents": "The  history of tuberculosis  encompasses the origins of the disease,  tuberculosis (TB)  through to the vaccines and treatments methods developed to contain and mitigate its impact."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4012", "contents": "Throughout history, the disease  tuberculosis  has been variously known as consumption, phthisis, and the White Plague. It is generally accepted that the causative agent,  Mycobacterium tuberculosis  originated from other, more primitive organisms of the same genus  Mycobacterium ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4013", "contents": "In 2014, results of a new DNA study of a tuberculosis genome reconstructed from remains in southern Peru suggest that human tuberculosis is less than 6,000 years old. Even if researchers theorise that humans first acquired it in Africa about 5,000 years ago, [ 1 ]  there is evidence that the first tuberculosis infection happened about 9,000 years ago. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4014", "contents": "Tuberculosis (TB)  spread to other humans along trade routes. It also spread to domesticated animals in Africa, such as goats and cows. Seals and sea lions that bred on African beaches are believed to have acquired the disease and carried it across the Atlantic to South America. Hunters would have been the first humans to contract the disease there. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4015", "contents": "Scientific work investigating the evolutionary origins of the  Mycobacterium tuberculosis  complex has concluded that the most recent common ancestor of the complex was a human-specific  pathogen , which underwent a  population bottleneck . Analysis of mycobacterial interspersed repetitive units has allowed dating of the bottleneck to approximately 40,000 years ago, which corresponds to the period subsequent to the expansion of  Homo sapiens  out of Africa. This analysis of mycobacterial interspersed repetitive units also dated the  Mycobacterium bovis  lineage as dispersing approximately 6,000 years ago, which may be linked to animal domestication and early farming. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4016", "contents": "Human bones from the  Neolithic  show presence of the bacteria. There has also been a claim of evidence of lesions characteristic of tuberculosis in a 500,000-year-old  Homo erectus  fossil, although this finding is controversial. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4017", "contents": "Results of a genome study reported in 2014 suggest that tuberculosis is newer than previously thought. Scientists were able to recreate the genome of the bacteria from remains of 1,000-year-old skeletons in southern Peru. In dating the DNA, they found it was less than 6,000 years old. They also found it related most closely to a tuberculosis strain in seals, and have theorized that these animals were the mode of transmission from Africa to South America. [ 1 ]  The team from University of T\u00fcbingen believe that humans acquired the disease in Africa about 5,000 years ago. [ 1 ]  Their domesticated animals, such as goats and cows, contracted it from them. Seals acquired it when coming up on African beaches for breeding, and carried it across the Atlantic. In addition, TB spread via humans on the trade routes of the Old World. Other researchers have argued there is other evidence that suggests the tuberculosis bacteria is older than 6,000 years. [ 1 ]  This TB strain found in Peru is different from that prevalent today in the Americas, which is more closely related to a later Eurasian strain likely brought by European colonists. [ 5 ]  However, this result is criticised by other experts from the field, [ 1 ]  for instance because there is evidence of the presence of Mycobacterium tuberculosis in 9,000 year old skeletal remains. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4018", "contents": "Although relatively little is known about its frequency before the 19th century, its incidence is thought to have peaked between the end of the 18th century and the end of the 19th century. Over time, the various cultures of the world gave the illness different names:  phthisis  (Greek), [ 6 ]   consumptio  (Latin),  yaksma  (India), and  chaky oncay  (Incan), each of which make reference to the \"drying\" or \"consuming\" effect of the illness,  cachexia ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4019", "contents": "In the 19th century, TB's high mortality rate among young and middle-aged adults and the surge of  Romanticism , which stressed feeling over reason, caused many to refer to the disease as the \"romantic disease\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4020", "contents": "In 2008, evidence for tuberculosis infection was discovered in human remains from the Neolithic era dating from 9,000 years ago, in  Atlit Yam , a settlement in the eastern Mediterranean. [ 7 ]  This finding was confirmed by morphological and molecular methods; to date it is the oldest evidence of tuberculosis infection in humans."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4021", "contents": "Evidence of the infection in humans was also found in a cemetery near Heidelberg, in the  Neolithic  bone remains that show evidence of the type of angulation often seen with spinal tuberculosis. [ 8 ]  Some authors call tuberculosis the first disease known to mankind."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4022", "contents": "Signs of the disease have also been found in Egyptian mummies dated between 3000 and 2400 BC. [ 9 ]  The most convincing case was found in the mummy of priest Nesperehen, discovered by Grebart in 1881, which featured evidence of spinal tuberculosis with the characteristic  psoas  abscesses. [ 10 ]  Similar features were discovered on other mummies like that of the priest Philoc and throughout the cemeteries of  Thebes . It appears likely that  Akhenaten  and his wife  Nefertiti  both died from tuberculosis, and evidence indicates that hospitals for tuberculosis existed in Egypt as early as 1500 BC. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4023", "contents": "The  Ebers papyrus , an important Egyptian medical treatise from around 1550 BC, describes a pulmonary consumption associated with the cervical lymph nodes. It recommended that it be treated with the surgical lancing of the cyst and the application of a ground mixture of acacia seyal, peas, fruits, animal blood, insect blood, honey and salt."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4024", "contents": "The  Old Testament  mentions a consumptive illness that would affect the Jewish people if they stray from God. It is listed in the section of curses given before they enter the land of Canaan. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4025", "contents": "The first references to tuberculosis in non-European civilization is found in the  Vedas . The oldest of them ( Rigveda , 1500 BC) calls the disease  yaksma . [ 13 ]  The  Atharvaveda  called it  balasa . It is in the Atharvaveda that the first description of  scrofula  was given. [ 14 ]  The  Sushruta Samhita , compiled during the period ca. 200 BCE - 500 CE, [ 15 ]  recommended that the disease be treated with breast milk, various meats, alcohol and rest. [ 16 ]  The  Yajurveda  advised affected individuals to move to higher altitudes. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4026", "contents": "The  Classical Chinese  word  l\u00e0o   \u7646  \"consumption; tuberculosis\" was the common name in  traditional Chinese medicine  and  f\u00e8iji\u00e9h\u00e9   \u80ba\u7d50\u6838  (lit. \"lung knot kernel\")  \"pulmonary tuberculosis\" is the modern medical term.  Lao  is compounded in names like  xulao   \u865b \u7646 with \"empty; void\",   l\u00e1ob\u00ecng  \u7646 \u75c5  with \"sickness\",  l\u00e1ozh\u00e0i  \u7646 \u7635  with \"[archaic] sickness\", and  feilao   \u80ba \u7646 with \"lungs\". Zhang and Unschuld explain that the medical term  xulao  \u865b\u7646 \"depletion exhaustion\" includes infectious and consumptive pathologies, such as  laozhai  \u7646\u7635 \"exhaustion with consumption\" or  laozhaichong  \u7646\u7635\u87f2 \"exhaustion consumption bugs/worms\". [ 17 ]  They retrospectively identify  feilao  \u80ba\u7646 \"lung exhaustion\" and infectious  feilao chuanshi  \u80ba\u7646\u50b3\u5c38 \"lung exhaustion by corpse [evil] transmission as \"consumption/tuberculosis\". [ 18 ]  Describing foreign loanwords in early medical terminology, Zhang and Unschuld note the phonetic similarity between Chinese  feixiao  \u80ba\u6d88 (from  Old Chinese   **p\u02b0ot-ssew ) \"lung consumption\" and ancient Greek  phthisis  \"pulmonary tuberculosis\". [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4027", "contents": "The   Huangdi Neijing  classic Chinese medical text ( c. \u2009400 BCE  \u2013 260 CE), traditionally attributed to the mythical  Yellow Emperor , describes a disease believed to be tuberculosis, called  xulao bing  (\u865b\u7646\u75c5 \"weak consumptive disease\"), characterized by persistent cough, abnormal appearance, fever, a weak and fast pulse, chest obstructions, and shortness of breath. [ 20 ] [ verification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4028", "contents": "The  Huangdi Neijing  describes an incurable disease called  huaifu  \u58de\u5e9c \"bad palace\", which commentators interpret as tuberculous. \"As for a string which is cut, its sound is hoarse. As for wood which has become old, its leaves are shed. As for a disease which is in the depth [of the body], the sound it [generates] is hiccup. When a man has these three [states], this is called 'destroyed palace'. Toxic drugs do not bring a cure; short needles cannot seize [the disease]. [ 21 ]  Wang Bing's commentary explains that  fu  \u5e9c \"palace\" stands for  xiong  \u80f8 \"chest\", and  huai  \"destroy\" implies \"injure the palace and seize the disease\". The  Huangdi Neijing  compiler Yang Shangshan notes, \"The [disease] proposed here very much resembles tuberculosis ... Hence [the text] states: poisonous drugs bring no cure; it cannot be seized with short needles.\" [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4029", "contents": "The  Shennong Bencaojing  pharmacopeia ( c. \u2009200 \u2013250 CE), attributed to the legendary inventor of agriculture  Shennong  \"Divine Farmer\", also refers to tuberculosis [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4030", "contents": "The  Zhouhou beiji fang  \u8098\u540e\u5907\u6025\u65b9 \"Handbook of Prescriptions for Emergencies\", attributed to the Daoist scholar  Ge Hong  (263\u2013420), uses the name of  shizhu  \u5c38\u75b0 \"corpse disease; tuberculosis\" and describes the symptoms and contagion:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4031", "contents": "\"This disease has many changing symptoms varying from thirty-six to ninety-nine different kinds. Generally it gives rise to a high fever, sweating, asthenia, unlocalised pains, making all positions difficult. Gradually, after months and years of suffering, this lingering disease brings about death to the sufferer. Afterwards it is transferred to others until the whole family is wiped out.\" [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4032", "contents": "Song dynasty  (920\u20131279) Daoist priest-doctors first recorded that tuberculosis, called  sh\u012bzh\u00e0i  \u5c38\u7635 (lit. \"corpse disease\") \"disease which changes a living being into a corpse\", [ 25 ]  was caused by a specific parasite or pathogen, centuries earlier than their contemporaries in other countries. The  Duanchu shizhai pin  \u65b7\u9664\u5c38\u7635\u54c1 \"On the Extermination of the Corpse Disease\" is the 23rd chapter in Daoist collection  Wushang xuanyuan santian Yutang dafa  \u7121\u4e0a\u7384\u5143\u4e09\u5929\u7389\u5802\u5927\u6cd5 \"Great Rites of the Jade Hall of the Three Heavens of the Supreme Mysterious Origins\" ( Daozang  number 103). The text has a preface dated 1126, written by the Song dynasty  Zhengyi Dao  master Lu Shizhong \u8def\u6642\u4e2d, who founded the Yutang dafa \u7389\u5802\u5927\u6cd5 tradition, but internal evidence reveals that the text could not have been written before 1158. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4033", "contents": "The disaster of the contagious disease, which changes a living being into a corpse, is caused by the infectious [nature] of the nine [kinds of] parasites ( ch'ung  \u87f2). It is also caused by overworking one's mind and exhausting one's energy, injuring one's  ch'i  and loosening one's sperm\u2014all of which happen to common folk. When the original vitality is being [gradually] exhausted, the evil aura begins to be transmitted through the affected vital  ch'i  [of the sick body]. ... The aspects of the illness vary, and the causes of contamination are different. Rooms and food are capable of gradual contamination, and the clothes worn by the indisposed are twined easily with the infectious  ch'i  and these two become inseparable. ... The symptoms of the disease: When it begins, the sufferer coughs and pants; he spits blood [pulmonary hemorrhage]; he is emaciated and skinny; cold and fever affect him intermittently, and his dreams are morbid. This is the evidence that this person is suffering from the disease which is also known as  wu-ch'uan  \u5c4b\u50b3 [contagious disease contracted from a sick-room]. ... The disease may be contracted by a healthy person who happens to have slept in the same bed with the patient, or worn his clothes. After the death of the sufferer, the clothes, curtains, bed or couch, vessels and utensils used by him are known to have been contaminated by and saturated with the polluted  ch'i  in which the noxious  ku  \u8831 [parasites or germs] take their abode. Stingy people wish to keep them for further use, and the poorer families cannot afford to get rid of them and buy everything anew. Isn't this lamentable, since it creates the cause of the great misfortune yet to come! [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4034", "contents": "This passage refers to the cause of TB in ancient medical terminology of  jiuchong  \u4e5d\u87f2 \"Nine Worms\" and  gu  \u8831 \"supernatural agents causing disease\", and  qi .  The Nine Worms generically meant \"bodily parasites; intestinal worms\" and were associated with the  sanshi  \u4e09\u5c38 \" Three Corpses \" or  sanchong  \u4e09\u87f2 \"Three Worms\", which were believed to be biospiritual parasites that live in the human body and seek to hasten their host's death.\nDaoist medical texts give different lists and descriptions of the Nine Worms. The  Boji fang  \u535a\u6fdf\u65b9 \"Prescriptions for Universal Dispensation\", collected by Wang Gun\u738b\u889e (fl. 1041), calls the supposed TB pathogen  laochong  \u7646\u87f2 \"tuberculosis worms\". [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4035", "contents": "This  Duanchu shizhai pin  chapter (23/7b-8b) explains that the present Nine Worms does not refer to the intestinal  weichong  \u80c3\u87f2 \"stomach worms\",  huichong  \u86d4\u87f2 \"coiling worm;  roundworm \", or  cun baichong  \u5bf8\u767d\u87f2 \"inch-long white worm;  nematode \", and says the supposed six TB worms are \"six kinds\" of parasites, but the next chapter (24/20a-21b) says they are \"six stages/generations\" of reproduction. [ 29 ]  Daoist priests allegedly cured tuberculosis through drugs, acupuncture, and burning  fulu  \"supernatural talismans/charms\". Burning magic talismans would cause the TB patient to cough, which was considered an effective treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4036", "contents": "To cure the disease, it is necessary to produce a spout of smoke by burning off thirty-six charms, and instruct the patient to inhale and to swallow up its fumes, whether he likes it or not. By the time all charms are used up, the smoke should also be dispersed. It may be difficult for the patient to bear the odour of the smoke at first, but once he gets used to such a smell, it does not really matter. Whenever the patient feels that there is phlegm in his throat, he is advised to cough and spit it out. If the patient is greatly affected by the symptoms, it will be good if his spittle is thick and if he can spit it out. When the patient is less affected by the wicked  ch'i , he does not have much phlegm to eject, but if he is deeply affected, he tends to vomit and to expectorate heavily until everything is cleared up, and then his illness is cured. When the wicked element is rooted out, it does not need to be fumigated any more [with charms]. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4037", "contents": "In addition, Daoist healers would burn talismans in order to fumigate the clothes and belongings of the deceased, and would warn the tuberculosis patient's family to throw away everything into a  changliu shui  \u9577\u6d41\u6c34 \"everflowing stream\". According to Liu Ts'un-yan, [ 31 ]  \"This proves that the priests of the time actually wanted to destroy all the belongings of the deceased, using charms as a camouflage.\""}
+{"id": "WikiPedia_Pulmonology$$$corpus_4038", "contents": "Hippocrates , in Book 1 of his  Of the Epidemics,  describes the characteristics of the disease: fever, colourless urine, cough resulting in a thick sputa, and loss of thirst and appetite. He notes that most of those affected became delirious before they died from the disease. [ 32 ]  Hippocrates and many other at the time believed phthisis to be hereditary in nature. [ 33 ]  Aristotle disagreed, believing the disease was contagious."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4039", "contents": "Pliny the Younger  wrote a letter to Priscus in which he details the symptoms of phthisis as he saw them in Fannia:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4040", "contents": "The attacks of fever stick to her, her cough grows upon her, she is in the highest degree emaciated and enfeebled."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4041", "contents": "Galen  proposed a series of therapeutic treatments for the disease, including:  opium  as a sleeping agent and painkiller;  blood letting ; a diet of barley water, fish, and fruit. He also described the phyma (tumor) of the lungs, which is thought to correspond to the tubercles that form on the lung as a result of the disease. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4042", "contents": "Vitruvius  noted that \"cold in the windpipe, cough, plurisy, phthisis, [and] spitting blood\", were common diseases in regions where the wind blew from north to northwest, and advised that walls be so built as to shelter individuals from the winds. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4043", "contents": "Aretaeus  was the first person to rigorously describe the symptoms of the disease in his text  De causis et signis diuturnorum morborum : [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4044", "contents": "Voice hoarse; neck slightly bent, tender, not flexible, somewhat extended; fingers slender, but joints thick; of the bones alone the figure remains, for the fleshy parts are wasted; the nails of the fingers crooked, their pulps are shrivelled and flat...Nose sharp, slender; cheeks prominent and red; eyes hollow, brilliant and glittering; swollen, pale or livid in countenance; the slender parts of the jaws rest on the teeth as, as if smiling; otherwise of cadaverous aspect..."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4045", "contents": "In his other book  De curatione diuturnorum morborum , he recommends that affected individuals travel to high altitudes, travel by sea, eat a good diet and drink plenty of milk. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4046", "contents": "In South America, reports of a study in August 2014 revealed that TB had likely been spread via seals that contracted it on beaches of Africa, from humans via domesticated animals, and carried it across the Atlantic. A team at the  University of T\u00fcbingen  analyzed tuberculosis DNA in 1,000-year-old skeletons of the  Chiribaya culture  in southern Peru; so much genetic material was recovered that they could reconstruct the genome. They learned that this TB strain was related most closely to a form found only in seals. [ 1 ]  In South America, it was likely contracted first by hunters who handled contaminated meat. This TB is a different strain from that prevalent today in the Americas, which is more closely related to a later Eurasian strain. [ 5 ] [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4047", "contents": "Prior to this study, the first evidence of the disease in South America was found in remains of the  Arawak  culture around 1050 BC. [ 39 ]  The most significant finding belongs to the mummy of an 8 to 10-year-old Nascan child from Hacienda Agua Sala, dated to 700 AD. Scientists were able to isolate evidence of the bacillus. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4048", "contents": "During the Middle Ages, no significant advances were made regarding tuberculosis.  Avicenna  and  Rhazes  continued to consider the disease both contagious and difficult to treat.  Arnaldus de Villa Nova  described etiopathogenic theory directly related to that of Hippocrates, in which a cold humor dripped from the head into the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4049", "contents": "In  Medieval   Hungary , the Inquisition recorded the trials of pagans. A document from the 12th century recorded an explanation of the cause of illness. The pagans said that tuberculosis was produced when a dog-shaped demon occupied the person's body and started to eat his lungs. When the possessed person coughed, then the demon was barking, and getting close to his objective, which was to kill the victim. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4050", "contents": "Monarchs were seen as religious figures with magical or curative powers. It was believed that  royal touch , the touch of the  sovereign  of England or France, could cure diseases due to the  divine right of sovereigns . [ 41 ]  King  Henry IV of France  usually performed the rite once a week, after taking communion. [ 42 ]  So common was this practice of royal healing in France, that  scrofula  became known as the \" mal du roi \" or the \"King's Evil\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4051", "contents": "Initially, the touching ceremony was an informal process. Sickly individuals could petition the court for a royal touch and the touch would be performed at the King's earliest convenience. At times, the  King of France  would touch affected subjects during his royal walkabout. The rapid spread of tuberculosis across France and England, however, necessitated a more formal and efficient touching process. By the time of  Louis XIV of France , placards indicating the days and times the King would be available for royal touches were posted regularly; sums of money were doled out as charitable support. [ 42 ] [ 43 ]  In England, the process was extremely formal and efficient. As late as 1633, the  Book of Common Prayer  of the  Anglican Church  contained a Royal Touch ceremony. [ 44 ]  The  monarch  (king or queen), sitting upon a canopied throne, touched the affected individual, and presented that individual with a  coin  \u2013 usually an  Angel , a gold coin the value of which varied from about 6  shillings  to about 10 shillings \u2013 by pressing it against the affected's neck. [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4052", "contents": "Although the ceremony was of no medical value, members of the royal courts often propagandized that those receiving the royal touch were miraculously healed.  Andr\u00e9 du Laurens , the senior physician of Henry IV, publicized findings that at least half of those that received the royal touch were cured within a few days. [ 45 ]  The royal touch remained popular into the 18th century. Parish registers from  Oxfordshire , England include not only records of baptisms, marriages, and deaths, but also records of those eligible for the royal touch. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4053", "contents": "Girolamo Fracastoro  became the first person to propose, in his work  De contagione  in 1546, that phthisis was transmitted by an invisible  virus . Among his assertions were that the  virus  could survive between  two or three years  on the clothes of those with the disease and that it was usually transmitted through direct contact or the discharged fluids of the infected, what he called  fomes . He noted that phthisis could be contracted without either direct contact or fomes, but was unsure of the process by which the disease propagated across distances. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4054", "contents": "Paracelsus  advanced the belief that tuberculosis was caused by a failure of an internal organ to accomplish its alchemical duties. When this occurred in the lungs, stony precipitates would develop causing tuberculosis in what he called the  tartaric  process. [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4055", "contents": "Franciscus Sylvius  began differentiating between the various forms of tuberculosis (pulmonary, ganglion). He was the first person to recognize that the skin ulcers caused by scrofula resembled tubercles seen in phthisis, [ 48 ]  noting that \"phthisis is the scrofula of the lung\" in his book  Opera Medica , published posthumously in 1679. Around the same time,  Thomas Willis  concluded that all diseases of the chest must ultimately lead to consumption. [ 49 ]  Willis did not know the exact cause of the disease but he blamed it on sugar [ 50 ]  or an acidity of the blood. [ 48 ]   Richard Morton  published  Phthisiologia, seu exercitationes de Phthisi tribus libris comprehensae  in 1689, in which he emphasized the tubercle as the true cause of the disease. So common was the disease at the time that Morton is quoted as saying \"I cannot sufficiently admire that anyone, at least after he comes to the flower of his youth, can  [ sic ] dye without a touch of consumption.\" [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4056", "contents": "In 1720,  Benjamin Marten  proposed in  A New Theory of Consumptions more Especially of Phthisis or Consumption of the Lungs  that the cause of tuberculosis was some type of  animalcula \u2014microscopic living beings that are able to survive in a new body (similar to the ones described by  Anton van Leeuwenhoek  in 1695). [ 52 ]  The theory was roundly rejected and it took another 162 years before Robert Koch demonstrated it to be true."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4057", "contents": "In 1768,  Robert Whytt  gave the first clinical description of tuberculosis meningitis [ 53 ]  and, in 1779,  Percivall Pott , an English surgeon, described the vertebral lesions that carry his name. [ 43 ]  In 1761,  Leopold Auenbrugger , an Austrian physician, developed the percussion method of diagnosing tuberculosis, [ 54 ]  a method rediscovered some years later in 1797 by  Jean-Nicolas Corvisart  of France. After finding it useful, Corvisart made it readily available to the academic community by translating it into French. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4058", "contents": "William Stark  proposed that ordinary lung tubercles could eventually evolve into ulcers and cavities, believing that the different forms of tuberculosis were simply different manifestations of the same disease. Unfortunately, Stark died at the age of 30 (while studying  scurvy ) and his observations were discounted. [ 56 ]  In his  Systematik de speziellen Pathologie und Therapie ,  J. L. Sch\u00f6nlein , Professor of Medicine in Zurich, proposed that the word \"tuberculosis\" be used to describe the condition of tubercles. [ 57 ] [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4059", "contents": "The incidence of tuberculosis grew progressively during the Middle Ages and Renaissance, displacing  leprosy , peaking between the 18th and 19th century as field workers moved to the cities looking for work. [ 43 ]  When he released his study in 1808, William Woolcombe was astonished at the prevalence of tuberculosis in 18th-century England. [ 59 ]  Of the 1,571 deaths in the English city of  Bristol  between 1790 and 1796, 683 were due to tuberculosis. [ 60 ]  Remote towns, initially isolated from the disease, slowly succumbed. The consumption deaths in the village of Holycross in  Shropshire  between 1750 and 1759 were one in six (1:6); ten years later, 1:3. In the metropolis of London, 1:7 died from consumption at the dawn of the 18th century, by 1750 that proportion grew to 1:5.25 and surged to 1:4.2 by around the start of the 19th century. [ 61 ]  The  Industrial Revolution  coupled with poverty and squalor created the optimal environment for the propagation of the disease."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4060", "contents": "In the 18th and 19th century, tuberculosis (TB) had become  epidemic  in  Europe , showing a seasonal pattern. [ 62 ] [ 63 ] [ 64 ] [ 65 ]  In the 18th century, TB had a mortality rate as high as 900 deaths (800\u20131000) per 100,000 population per year in  Western Europe , including in places like  London ,  Stockholm  and  Hamburg . [ 62 ] [ 63 ] [ 64 ]  A similar death rate occurred in  North America . [ 63 ]  In the  United Kingdom , epidemic TB may have peaked around 1750, as suggested by mortality data. [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4061", "contents": "In the 19th century, TB killed about a quarter of the adult population of Europe. [ 66 ]  In western continental Europe, epidemic TB may have peaked in the first half of the 19th century. [ 65 ]  In addition, between 1851 and 1910, around four million died from TB in  England  and  Wales  \u2013 more than one third of those aged 15 to 34 and half of those aged 20 to 24 died from TB. [ 62 ]  By the late 19th century, 70\u201390% of the urban populations of Europe and  North America  were infected with the  Mycobacterium tuberculosis , and about 80% of those individuals who developed active TB died of it. [ 67 ]  However, mortality rates began declining in the late 19th century throughout Europe and the  United States . [ 67 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4062", "contents": "At the time, tuberculosis was called  the robber of youth,  because the disease had higher death rate among young people. [ 62 ] [ 64 ]  Other names included  the   Great White Plague  and  the White Death , where the \"white\" was due to the extreme  anaemic  pallor of those infected. [ 62 ] [ 64 ] [ 68 ]  In addition, TB has been called by many as the \"Captain of All These Men of Death\". [ 62 ] [ 64 ] [ 68 ] [ 69 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4063", "contents": "\"Chopin coughs with infinite grace.\""}
+{"id": "WikiPedia_Pulmonology$$$corpus_4064", "contents": "It was during this century that tuberculosis was dubbed the White Plague, [ 70 ]   mal de vivre , and  mal du si\u00e8cle . It was seen as a \"romantic disease\". Individuals with tuberculosis were thought to have heightened sensitivity. The slow progress of the disease allowed for a \"good death\" as those affected could arrange their affairs. [ 71 ]  The disease began to represent spiritual purity and temporal wealth, leading many young, upper-class women to purposefully pale their skin to achieve the consumptive appearance. British poet  Lord Byron  wrote, \"I should like to die from consumption\", helping to popularize the disease as the disease of artists. [ 72 ]   George Sand  doted on her phthisic lover,  Fr\u00e9d\u00e9ric Chopin , calling him her \"poor melancholy angel\". [ 73 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4065", "contents": "In France, at least five novels were published expressing the ideals of tuberculosis: Dumas's  La Dame aux cam\u00e9lias , Murger's  Sc\u00e8nes de la vie de Boh\u00e8me , Hugo's  Les Mis\u00e9rables , the  Goncourt brothers '  Madame Gervaisais  and  Germinie Lacerteux , and Rostand's  L'Aiglon . The portrayals by Dumas and Murger in turn inspired operatic depictions of consumption in Verdi's  La traviata  and Puccini's  La boh\u00e8me .  Even after medical knowledge of the disease had accumulated, the redemptive-spiritual perspective of the disease has remained popular [ 74 ]  (as seen in the 2001 film  Moulin Rouge  based in part on  La traviata ; the 2013 film  The Wind Rises , based in part on a 1937 novel about tuberculosis; and the  musical adaptations  of  Les Mis\u00e9rables )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4066", "contents": "In large cities the poor had high rates of tuberculosis.  Public-health physicians and politicians typically blamed both the poor themselves and their ramshackle tenement houses (conventillos) for the spread of the dreaded disease.  People ignored public-health campaigns to limit the spread of contagious diseases, such as the prohibition of spitting on the streets, the strict guidelines to care for infants and young children, and quarantines that separated families from ill loved ones. [ 75 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4067", "contents": "Though removed from the cultural movement, the scientific understanding advanced considerably. By the end of the 19th century, several major breakthroughs gave hope that a cause and cure might be found."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4068", "contents": "One of the most important physicians dedicated to the study of phthisiology was  Ren\u00e9 Laennec , who died from the disease at the age of 45, after contracting tuberculosis while studying contagious patients and infected bodies. [ 76 ]  Laennec invented the  stethoscope [ 54 ]  which he used to corroborate his auscultatory findings and prove the correspondence between the pulmonary lesions found on the lungs of autopsied tuberculosis patients and the respiratory symptoms seen in living patients. His most important work was  Trait\u00e9 de l'Auscultation M\u00e9diate  which detailed his discoveries on the utility of pulmonary auscultation in diagnosing tuberculosis. This book was promptly translated into English by  John Forbes  in 1821; it represents the beginning of the modern scientific understanding of tuberculosis. [ 73 ]  Laennec was named professional chair of  H\u00f4pital Necker  in September 1816 and today he is considered the greatest French clinician. [ 77 ] [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4069", "contents": "Laennec's work put him in contact with the vanguard of the French medical establishment, including  Pierre Charles Alexandre Louis . Louis would go on to use statistical methods to evaluate the different aspects of the disease's progression, the efficacy of various therapies and individuals' susceptibility, publishing an article in the  Annales d'hygi\u00e8ne publique  entitled \"Note on the Relative Frequency of Phthisis in the Two Sexes\". [ 79 ]  Another good friend and co-worker of Laennec,  Gaspard Laurent Bayle , published an article in 1810 entitled  Recherches sur la Pthisie Pulmonaire , in which he divided pthisis into six types: tubercular phthisis, glandular phthisis, ulcerous phthisis, phthisis with melanosis, calculous phthisis, and cancerous phthisis. He based his findings on more than 900 autopsies. [ 70 ] [ 80 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4070", "contents": "In 1869,  Jean Antoine Villemin  demonstrated that the disease was indeed contagious, conducting an experiment in which tuberculous matter from human cadavers was injected into laboratory rabbits, which then became infected. [ 81 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4071", "contents": "On 24 March 1882, Robert Koch revealed the disease was caused by an infectious agent. [ 73 ]  In 1895,  Wilhelm R\u00f6ntgen  discovered the X-ray, which allowed physicians to diagnose and track the progression of the disease, [ 82 ]  and although an effective medical treatment would not come for another fifty years, the incidence and mortality of tuberculosis began to decline. [ 83 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4072", "contents": "Villemin's experiments had confirmed the contagious nature of the disease and had forced the medical community to accept that tuberculosis was indeed an infectious disease, transmitted by some etiological agent of unknown origin. In 1882, Prussian physician  Robert Koch  utilized a new staining method and applied it to the sputum of tuberculosis patients, revealing for the first time the causal agent of the disease:  Mycobacterium tuberculosis , or Koch's bacillus. [ 85 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4073", "contents": "When he began his investigation, Koch knew of the work of Villemin and others who had continued his experiments like Julius Conheim and Carl Salmosen. He also had access to the \"pthisis ward\" at the Berlin Charit\u00e9 Hospital. [ 86 ]  Before he confronted the problem of tuberculosis, he worked with the disease caused by anthrax and had discovered the causal agent to be  Bacillus anthracis . During this investigation he became friends with Ferdinand Cohn, the director of the Institute of Vegetable Physiology. Together they worked to develop methods of culturing tissue samples. 18 August 1881, while staining tuberculous material with  methylene blue , he noticed oblong structures, though he was not able to ascertain whether it was just a result of the coloring. To improve the contrast, he decided to add  Bismarck Brown , after which the oblong structures were rendered bright and transparent. He improved the technique by varying the concentration of alkali in the staining solution until the ideal viewing conditions for the bacilli was achieved."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4074", "contents": "After numerous attempts he was able to incubate the bacteria in  coagulated blood serum  at 37 degrees Celsius. He then inoculated laboratory rabbits with the bacteria and observed that they died while exhibiting symptoms of tuberculosis, proving that the bacillus, which he named  tuberculosis bacillus , was in fact the cause of tuberculosis. [ 87 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4075", "contents": "He made his result public at the  Physiological Society of Berlin  on 24 March 1882, in a famous lecture entitled  \u00dcber Tuberculose , which was published three weeks later. Since 1882, 24 March has been known as  World Tuberculosis Day . [ 88 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4076", "contents": "On 20 April 1882, Koch presented an article entitled  Die \u00c4tiologie der Tuberculose  in which he demonstrated that  Mycobacterium  was the single cause of tuberculosis in all of its forms. [ 87 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4077", "contents": "In 1890 Koch developed  tuberculin , a purified protein derivative of the bacteria. [ 89 ]   Data on experimental inquiry published in Deutsche Landwirthschafts-Zeitung provided immediate practical industry benefits in the form of the  Tuberculin test  as an aide to  diagnosis  in both sick and healthy cattle. [ 90 ]  Tuberculin proved to be an ineffective means of immunization but in 1908,  Charles Mantoux  found it was an effective  intradermic test  for diagnosing tuberculosis. [ 91 ] [ 92 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4078", "contents": "If the importance of a disease for mankind is measured from the number of fatalities which are due to it, then tuberculosis must be considered much more important than those most feared infectious diseases, plague, cholera, and the like. Statistics have shown that 1/7 of all humans die of tuberculosis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4079", "contents": "The advancement of scientific understanding of tuberculosis, and its contagious nature created the need for institutions to house affected individuals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4080", "contents": "The first proposal for a tuberculosis facility was made in paper by  George Bodington  entitled  An essay on the treatment and cure of pulmonary consumption, on principles natural, rational and successful  in 1840. In this paper, he proposed a dietary, rest, and medical care program for a hospital he planned to found in  Maney . [ 93 ]  Attacks from numerous medical experts, especially articles in  The Lancet , disheartened Bodington and he turned to plans for housing the insane. [ 94 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4081", "contents": "Around the same time in the United States, in late October and early November 1842, Dr.  John Croghan , the owner of  Mammoth Cave , brought 15 tuberculosis patients into the cave in the hope of curing the disease with the constant temperature and purity of the cave air. [ 95 ]  Patients were lodged in stone huts, and each was supplied with a slave to bring meals. [ 96 ]  One patient, A. H. P. Anderson, wrote glowing reviews of the cave experience: [ 97 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4082", "contents": "[S]ome of the invalids eat at their pavilions while others in better health attend regularly the table d'hote which is very good indeed, having a considerable variety and being almost daily (I've noted but 2\u20133 omissions) graced with a saddle of venison or other game."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4083", "contents": "By late January, early February 1843, two patients were dead and the rest had left. Departing patients died anywhere from three days to three weeks after resurfacing; John Croghan died of tuberculosis at his  Louisville  residence in 1849. [ 98 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4084", "contents": "Hermann Brehmer , a German physician, was convinced that tuberculosis arose from the difficulty of the heart to correctly irrigate the lungs. He therefore proposed that regions well above sea level, where the atmospheric pressure was less, would help the heart function more effectively. With the encouragement of explorer  Alexander von Humboldt  and his teacher  J. L. Sch\u00f6nlein , the first anti-tuberculosis sanatorium was established in 1854, 650 meters above sea level, at  G\u00f6rbersdorf . [ 99 ]  Three years later he published his findings in a paper  Die chronische Lungenschwindsucht und Tuberkulose der Lunge: Ihre Ursache und ihre Heilung ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4085", "contents": "Brehmer and one of his patients,  Peter Dettweiler , became proponents for the sanatorium movement, and by 1877, sanatoriums began to spread beyond Germany and throughout Europe. Dr.  Edward Livingston Trudeau  subsequently founded the  Adirondack Cottage Sanitorium  in  Saranac Lake, New York  in 1884. One of Trudeau's early patients was author  Robert Louis Stevenson ; his fame helped establish Saranac Lake as a center for the treatment of tuberculosis. In 1894, after a fire destroyed Trudeau's small home laboratory, he organized the Saranac Laboratory for the Study of Tuberculosis; renamed the  Trudeau Institute , the laboratory continues to study infectious diseases. [ 100 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4086", "contents": "Peter Dettweiler went on to found his own sanatorium at  Falkenstein  in 1877 and in 1886 published findings claiming that 132 of his 1022 patients had been completely cured after staying at his institution. [ 101 ]  Eventually, sanatoriums began to appear near large cities and at low altitudes, like the  Sharon Sanatorium  in 1890 near Boston. [ 102 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4087", "contents": "Sanatoriums were not the only treatment facilities. Specialized tuberculosis clinics began to develop in major metropolitan areas. Sir Robert Philip established the  Royal Victoria Dispensary for Consumption  in  Edinburgh  in 1887.  Dispensaries  acted as special sanatoriums for early tuberculosis cases and were opened to lower income individuals. The use of dispensaries to treat middle and lower-class individuals in major metropolitan areas and the coordination between various levels of health services programs like hospitals, sanatoriums, and tuberculosis colonies became known as the \"Edinburgh Anti-tuberculosis Scheme\". [ 103 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4088", "contents": "At the beginning of the 20th century, tuberculosis was one of the UK's most urgent health problems. A royal commission was set up in 1901, The Royal Commission Appointed to Inquire into the Relations of Human and Animal Tuberculosis. Its remit was to find out whether tuberculosis in animals and humans was the same disease, and whether animals and humans could infect each other. By 1919, the Commission had evolved into the  UK's Medical Research Council ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4089", "contents": "In 1902, the International Conference on Tuberculosis convened in Berlin. Among various other acts, the conference proposed the  Cross of Lorraine  be the international symbol of the fight against tuberculosis. National campaigns spread across Europe and the United States to tamp down on the continued prevalence of tuberculosis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4090", "contents": "After the establishment in the 1880s that the disease was contagious, TB was made a  notifiable disease  in Britain; there were campaigns to stop spitting in public places, and the infected poor were pressured to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention. [ 104 ]  Whatever the purported benefits of the fresh air and labor in the sanatoria, even under the best conditions, 50% of those who entered were dead within five years (1916). [ 104 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4091", "contents": "The promotion of  Christmas Seals  began in Denmark during 1904 as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907\u20131908 to help the  National Tuberculosis Association  (later called the  American Lung Association )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4092", "contents": "In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into  spittoons .  Public health measures were inaugurated to track and control the prevalence of tuberculosis in livestock that could be transmitted to humans."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4093", "contents": "The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by  Albert Calmette  and  Camille Gu\u00e9rin  in 1906. It was called \"BCG\" ( Bacille Calmette-Gu\u00e9rin ). The  BCG vaccine  was first used on humans in 1921 in France, [ 105 ]  but it was not until after World War II that BCG received widespread acceptance in Great Britain and Germany. [ 106 ]  In the early days of the British  National Health Service  X-ray examination for TB increased dramatically but rates of vaccination were initially very low. In 1953 it was agreed that secondary school pupils should be vaccinated, but by the end of 1954 only 250,000 people had been vaccinated. By 1956 this had risen to 600,000, about half being school children. [ 107 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4094", "contents": "In Italy,  Salvioli's diffusing vaccine  ( Vaccino Diffondente Salvioli ; VDS) was used from 1948 until 1976. It was developed by Professor Gaetano Salvioli (1894\u20131982) of the  University of Bologna ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4095", "contents": "As the century progressed, some surgical interventions, including the  pneumothorax  or  plombage  technique\u2014collapsing an infected lung to \"rest\" it and allow the lesions to heal\u2014were used to treat tuberculosis. [ 108 ]  Pneumothorax was not a new technique by any means. In 1696,  Giorgio Baglivi  reported a general improvement in tuberculosis patients after they received sword wounds to the chest.  F.H. Ramadge  induced the first successful therapeutic pneumothorax in 1834, and reported subsequently the patient was cured. It was in the 20th century, however, that scientists sought to rigorously investigate the effectiveness of such procedures.  Carlo Forlanini  experimented with his artificial pneumothorax technique from 1882 to 1888 and this started to be followed only years later. [ 109 ]  In 1939, the  British Journal of Tuberculosis  published a study by  Oli Hjaltested  and  Kjeld T\u00f6rning  on 191 patients undergoing the procedure between 1925 and 1931; in 1951, Roger Mitchell published several articles on the therapeutic outcomes of 557 patients treated between 1930 and 1939 at  Trudeau Sanatorium  in  Saranac Lake . [ 110 ]  The search for a medicinal cure, however, continued in earnest."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4096", "contents": "During the  Nazi occupation of Poland ,  SS-Obergruppenf\u00fchrer   Wilhelm Koppe  organized the execution of more than 30,000 Polish patients with tuberculosis \u2013 little knowing or caring that a cure was nearly at hand. In Canada, doctors continued to surgically remove TB in the indigenous patients during the 1950s and 60s, even though the procedure was no longer performed on non-Indigenous patients. [ 111 ] [ 112 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4097", "contents": "In 1944  Albert Schatz ,  Elizabeth Bugie , and  Selman Waksman  isolated  streptomycin  produced by a bacterial strain  Streptomyces griseus .  Streptomycin was the first effective antibiotic against  M. tuberculosis . [ 113 ]  This discovery is generally considered the beginning of the modern era of tuberculosis. [ 113 ]   Para-aminosalicylic acid , discovered in 1946, was used in combination with Streptomycin to reduce the emergence of drug resistant variants, which greatly improved patient outcomes. [ 114 ]  The true revolution began some years later, in 1952, with the development of  isoniazid , the first oral mycobactericidal drug. [ 113 ]  The advent of  rifampin  in the 1970s hastened recovery times, and significantly reduced the number of tuberculosis cases until the 1980s."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4098", "contents": "The British epidemiologist  Thomas McKeown  had shown that \"treatment by streptomycin reduced the number of deaths since it was introduced (1948\u201371) by 51 per cent...\". [ 115 ]  However, he also showed that the mortality from TB in England and Wales had already declined by 90 to 95% before streptomycin and BCG-vaccination were widely available, and that the contribution of antibiotics to the decline of mortality from TB was actually very small:  ' ...for the total period since cause of death was first recorded (1848\u201371) the reduction was 3.2 per cent ' . [ 115 ] :\u200a82\u200a  These figures have since been confirmed for all western countries (see for example the decline in TB mortality in the USA) and for all then known infectious diseases. McKeown explained the decline in mortality from infectious diseases by an improved standard of living, particularly by better nutrition, and by better hygiene, and less by medical intervention.  McKeown, who is considered as the father of social medicine, [ 116 ]  has advocated for many years, that with drugs and vaccines we may win the battle but will lose the war against Diseases of Poverty. [ 117 ]  Thereto, efforts and resources should be primarily directed toward improving the standard of living of people in low resource countries, and toward improving their environment by providing clean water, sanitation, better housing, education, safety and justice, and access to medical care.  Particularly the work of Nobel laureates  Robert W. Fogel  (1993) [ 118 ] [ 119 ] [ 120 ] [ 121 ]  and  Angus Deaton  (2015) [ 116 ]  have greatly contributed to the recent reappreciation of the McKeown thesis. A negative confirmation of the McKeown thesis was that increased pressure on wages by IMF loans to post-communist Eastern Europe were strongly associated with a rise in TB incidence, prevalence and mortality. [ 122 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4099", "contents": "In the United States there was dramatic reduction in tuberculosis cases by the 1970s. As early as the 1900s, public health campaigns were launched to educate people about the contagion. In later decades, posters, pamphlets and newspapers continued to inform people about the risk of contagion and methods to avoid it, including increasing public awareness about the importance of good hygiene. Though improved awareness of good hygiene practices reduced the number of cases, the situation was worse in the poor neighborhoods. Public clinics were set up to improve awareness and provide screenings. In Scotland, Dr  Nora Wattie  led the public health innovations both at local [ 123 ]  and national level. [ 124 ]  This resulted in sharp declines through the 1920s and 1930s. [ 125 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4100", "contents": "Hopes that the disease could be completely eliminated were dashed in the 1980s with the rise of  drug-resistant  strains. Tuberculosis cases in Britain, numbering around 117,000 in 1913, had fallen to around 5,000 in 1987, but cases rose again, reaching 6,300 in 2000 and 7,600 cases in 2005. [ 126 ]  Due to the elimination of public health facilities in New York and the emergence of HIV, there was a resurgence of TB in the late 1980s. [ 127 ]  The number of patients failing to complete their course of drugs was high. New York had to cope with more than 20,000 TB patients with  multidrug-resistant  strains (resistant to, at least, both rifampin and isoniazid)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4101", "contents": "In response to the resurgence of tuberculosis, the World Health Organization issued a declaration of a global health emergency in 1993. [ 128 ]  Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide. [ 129 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4102", "contents": "Pneumotherapy  is the medical use of compressed or rarefied gases, and was at one time used to treat people suffering from  pneumothorax  (lung collapse). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4103", "contents": "Targeted lung denervation (TLD)  is a procedure, that is currently being studied, to try to improve  chronic obstructive pulmonary disease  (COPD). [ 1 ]  Evidence to support its use is insufficient as of 2015. [ 1 ]  TLD is intended to block airway nerves of the  parasympathetic nervous system  to try to relax the airways. [ 2 ]  The procedure is done using a balloon catheter through a  bronchoscope  and uses  radio frequency  energy. The bronchoscope is passed through the person's mouth and into their lungs. A dual-cooled  radiofrequency ablation  catheter is passed through the bronchoscope to provide the treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4104", "contents": "Bruce Borland  (November 4, 1958 \u2013 October 25, 1999) was an American  golf course  designer who worked for  Jack Nicklaus . He died in the  1999 South Dakota Learjet crash  on October 25, 1999, while traveling with golf  Hall of Famer   Payne Stewart ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4105", "contents": "Borland was raised in the  Peoria, Illinois , area. He took a fascination with golf at an early age, building and maintaining a  putting green  in his parents' backyard, tending to it meticulously. Borland went on to graduate from the  University of Illinois at Urbana-Champaign , with a degree in  Landscape Architecture . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4106", "contents": "After graduation, he moved to the Chicago area and began designing golf courses for several firms."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4107", "contents": "In 1989, Borland opened his own design firm,  ProDesign , just a year later he was offered a design position with Jack Nicklaus at  Golden Bear International . Borland worked on many of the famous Jack Nicklaus \"Signature\" golf courses, as well as other stateside and Indonesian courses."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4108", "contents": "Over his career, Borland designed or worked on several golf courses. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4109", "contents": "In 1999, Borland  was killed in a Learjet 35  with Payne Stewart while flying from  Orlando, Florida , to  Dallas, Texas , before the Tour Championship. He died of  hypoxia , a lack of oxygen, before the plane crashed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4110", "contents": "This biographical article relating to American golf is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4111", "contents": "Georgy Timofeyevich Dobrovolsky  ( Russian :  \u0413\u0435\u043e\u0440\u0433\u0438\u0439 \u0422\u0438\u043c\u043e\u0444\u0435\u0435\u0432\u0438\u0447 \u0414\u043e\u0431\u0440\u043e\u0432\u043e\u043b\u044c\u0441\u043a\u0438\u0439 ; 1 June 1928\u00a0\u2013 30 June 1971) [ 1 ]  was a Soviet  cosmonaut  who commanded the three-man crew of the  Soyuz 11  spacecraft. They became the world's first space station crew aboard  Salyut 1 , but died of  asphyxiation  because of an accidentally opened valve. They were the first and only humans to have died in space."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4112", "contents": "Dobrovolsky,   Viktor Patsayev  and  Vladislav Volkov  flew on the  Soyuz 11  mission and were the world's third crew to  die during a space flight ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4113", "contents": "After a normal  re-entry , the capsule was opened and the crew was found dead. [ 2 ]  It was discovered that a valve had opened just prior to leaving orbit that had allowed the capsule's atmosphere to  vent away into space , suffocating the crew. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4114", "contents": "Dobrovolsky's ashes were placed in an urn in the  Kremlin Wall Necropolis  on  Red Square  in Moscow. [ 4 ]  Among the pallbearers were  Alexei Leonov  (who had been the prime-crew commander scheduled to launch on Soyuz 11),  Vladimir Shatalov ,  Andriyan Nikolayev , and American astronaut  Thomas P. Stafford . [ 4 ]   Dobrovolsky was posthumously awarded the title of  Hero of the Soviet Union , the  Order of Lenin , and the title of  Pilot-Cosmonaut of the USSR ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4115", "contents": "This biographical  Hero of the Soviet Union  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4116", "contents": "Hawthorne Charles Gray  (February 16, 1889 \u2013 November 4, 1927) was a  captain  in the  United States Army Air Corps . [ 1 ]  On May 4, 1927, he succeeded in setting a new altitude record in a silk, rubberized, and aluminum-coated  balloon  launched from  Scott Field  near  Belleville, Illinois , reaching a human world altitude record of 42,470\u00a0ft (12.94\u00a0km). This record was not recognized by the  FAI  because Gray parachuted out of the balloon and did not land with his vehicle as per FAI rules. On November 4, 1927, Gray broke his own record by reaching more than 43,000\u00a0ft (13.1\u00a0km), but died during his descent after his  oxygen  supply became depleted. [ 1 ] [ 2 ] [ 3 ]  The record was recognized by the  National Aeronautical Association , but not by the F\u00e9d\u00e9ration A\u00e9ronautique Internationale because the dead  aeronaut  \"was not in personal possession of his instruments.\" [ 2 ]  Gray was posthumously awarded the  Distinguished Flying Cross  for his three ascents on March 9, May 4 and November 4. [ 1 ] [ 2 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4117", "contents": "Gray was born on February 16, 1889, in  Pasco, Washington . [ 5 ]  He was the son of  William Polk Gray  (1845\u20131929), a prominent  steamboat   captain  in the  Northwestern United States , and Oceana Falkland Bush. [ 6 ] [ 7 ]  Hawthorne Gray was a graduate of the  University of Idaho . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4118", "contents": "Gray served as an officer in the  Idaho National Guard  and enlisted in the  United States Army  in 1915, serving as an  infantry   private  in the  Pancho Villa Expedition  of 1916. [ 5 ] [ 8 ]  Gray was commissioned a  second lieutenant  on June 2, 1917, and transferred with the rank of captain to what was then the  United States Army Air Service  in 1920. [ 5 ]  He began piloting balloons in 1921. [ 8 ]  He placed third in the 1926  National Balloon Race  and second in the 1926  Gordon Bennett balloon race . [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4119", "contents": "On March 9, 1927, Gray set an unofficial altitude record of 28,510\u00a0ft (8.69\u00a0km) in a balloon launched from Scott Field, but passed out from  hypoxia  in the thin air, regaining consciousness only just in time to drop  ballast  and slow his fall after the balloon descended on its own. [ 1 ] [ 2 ] [ 10 ]  On May 4, Gray set an unofficial record for highest altitude reached by a human being, as he attained 42,470\u00a0ft (12.94\u00a0km) in a balloon over Belleville. Because of the rapid descent of the balloon, Gray parachuted out at 8,000 feet (2,400\u00a0m), disqualifying him from recognition by the F\u00e9d\u00e9ration A\u00e9ronautique Internationale (FAI), which required that the balloonist land with his craft. [ 1 ] [ 2 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4120", "contents": "On November 4, Gray attempted to set an official record. He rose at about 4\u00a0mph (6.4\u00a0km/h), half the speed he used for his March 9 flight. [ 4 ]  Between 30,000 feet (9,100\u00a0m) and 34,000\u00a0ft (10.4\u00a0km) Gray threw over an empty oxygen cylinder for ballast, and the canister snapped his radio antenna, cutting him off from the ground. [ 1 ]  After reaching an altitude of 40,000\u00a0ft (12.2\u00a0km), he lost consciousness. His final journal entry read \u201cSky deep blue, sun very bright, sand all gone.\u201d [ 1 ]  His dead body was found in the balloon basket in a tree near  Sparta, Tennessee , the next day. [ 2 ] [ 8 ] [ 10 ]  The balloon's  barographs  showed that Gray had reached a height between 43,000 (13.1\u00a0km) and 44,000\u00a0ft (13.4\u00a0km). [ 1 ]  There were various theories about the cause of Gray's death. He may have severed his oxygen hose accidentally while cutting open bags of sand ballast. [ 11 ]  It is also possible that Gray became too cold and tired to open the valve on one of his oxygen tanks, or that an internal organ was ruptured by decreasing pressure. Aeronaut  Albert Leo Stevens  believed that Gray died during descent or on impact. [ 1 ]  The Scott Field board of inquiry which investigated Gray's death concluded that he died because his clock stopped, causing him to lose track of his time on oxygen and exhaust his supply. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4121", "contents": "Gray was posthumously awarded the  Distinguished Flying Cross  and buried in  Arlington National Cemetery . [ 12 ] [ 1 ] [ 4 ]  His widowed wife and three remaining sons received his Army Air Corps insurance and $2,700, the equivalent of six months\u2019 pay. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4122", "contents": "Gray was married to Miriam Lorette Maddux. They had a son, John Maddux Gray, who died when he was a year old. Gray was survived by his widow and three other sons. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4123", "contents": "Marvin Frederick Hamlisch  (June 2, 1944\u00a0\u2013 August 6, 2012) was an American composer and conductor. He is one of a handful of people to win  Emmy ,  Grammy ,  Oscar  and  Tony  awards, a feat dubbed the \" EGOT \". He and composer  Richard Rodgers  are the only people to have won those prizes and a  Pulitzer Prize  (\" PEGOT \"). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4124", "contents": "Hamlisch was born in  Manhattan , to  Viennese -born  Jewish  parents Lilly (n\u00e9e Schachter) and Max Hamlisch. [ 2 ]  His father was an  accordionist  and bandleader. Hamlisch was a  child prodigy ; by age five, he began mimicking the piano music he heard on the radio. A few months before he turned seven, in 1951, he was accepted into what is now the  Juilliard School Pre-College Division . [ 3 ]  His favorite musicals growing up were  My Fair Lady ,  Gypsy ,  West Side Story , and  Bye Bye Birdie . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4125", "contents": "Hamlisch attended  Queens College , earning his Bachelor of Arts degree in 1967. [ 3 ]  His first job was as a rehearsal pianist for  Funny Girl  with  Barbra Streisand . Even on tour he would take time to book Kenny Veenstra's Progressive Music Studio to send musical ideas back to \"Babs\" in NY. Shortly afterward, producer  Sam Spiegel  hired him to play piano at parties, and later to score Spiegel's 1968 film  The Swimmer . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4126", "contents": "Liza Minnelli 's 1964  debut album  included \"The Travelin' Life\", a song Hamlisch wrote in his teens (originally titled \"Travelin' Man\"). [ 5 ]  His first hit arrived when he was 21 years old: \" Sunshine, Lollipops and Rainbows \", co-written with Howard Liebling and recorded by  Lesley Gore . It reached No. 13 on the  Billboard  Hot 100  in the summer of 1965. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4127", "contents": "His first film score was for 1968's  The Swimmer . [ 6 ]  He also wrote music for several early  Woody Allen  films, including  Take the Money and Run  (1969) and  Bananas  (1971)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4128", "contents": "Hamlisch and Liebling co-wrote the song \" California Nights \", which was recorded by Lesley Gore for her 1967 hit album of the same name. The  Bob Crewe -produced single peaked at No. 16 on the  Hot 100  in March 1967, two months after Gore had performed the song on the  Batman  television series, in which she guest-starred as an accomplice to  Julie Newmar 's  Catwoman ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4129", "contents": "Among Hamlisch's better-known works during the 1970s were adaptations of  Scott Joplin 's  ragtime  music for the film  The Sting , including its theme song, \" The Entertainer \". It hit No. 1 on  Billboard ' s Adult Contemporary chart and No. 3 on the Hot 100, selling nearly 2 million copies in the U.S. alone. He had great success in 1973, winning two  Academy Awards  for the  title song  and the score for the motion picture  The Way We Were  and an Academy Award for the adaptation score for  The Sting . [ 7 ]  He won four  Grammy Awards  in 1974, two for \"The Way We Were\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4130", "contents": "In 1975, he wrote the original theme music for  Good Morning America ; the show used it for 12 years. He co-wrote \" Nobody Does It Better \" for  The Spy Who Loved Me  (1977) with his then-girlfriend  Carole Bayer Sager , which would be nominated for an Oscar. [ 6 ]  In the 1980s, he had success with the scores for  Ordinary People  (1980) and  Sophie's Choice  (1982). He also received an Academy Award nomination in 1986 for the film version of  A Chorus Line ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4131", "contents": "In 1985, he worked on  D.A.R.Y.L. , a 1985 film about a boy who is in fact a U.S. military robot. He also worked on the score for  The Informant!  (2009), starring  Matt Damon  and directed by  Steven Soderbergh . [ 6 ]  Late in his life, he wrote a children's book  Marvin Makes Music,  which included the original music \"The Music in My Mind\" with words by Rupert Holmes; and the score for the  HBO  film  Behind the Candelabra  (2013), also directed by Soderbergh and starring Matt Damon and  Michael Douglas  as  Liberace ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4132", "contents": "Hamlisch's first major stage work was in 1972 playing piano for  Groucho Marx  at  Carnegie Hall  for  An Evening with Groucho . Hamlisch acted as both  straight man  and accompanist while Marx, at age 81, reminisced about his career in show business. [ 8 ]  The performances were released as a two-record set, and remained very popular. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4133", "contents": "He then composed the scores for the 1975  Broadway  musical  A Chorus Line , for which he won both a  Tony Award  and a  Pulitzer Prize ; and for the 1978 musical  They're Playing Our Song , loosely based on his relationship with  Carole Bayer Sager . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4134", "contents": "At the beginning of the 1980s, his romantic relationship with Bayer Sager ended, but their songwriting relationship continued. The 1983 musical  Jean Seberg , based on the life of the real-life actress, failed in its London production at the UK's  National Theatre  and never played in the U.S. [ 11 ]  In 1986,  Smile  was a mixed success and had a short run on Broadway. [ 6 ]  The musical version of Neil Simon's  The Goodbye Girl  (1993) closed after only 188 performances, although he received a  Drama Desk  nomination, for Outstanding Music. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4135", "contents": "Shortly before his death, Hamlisch finished scoring a musical theatre version of  The Nutty Professor , based on the 1963 film. [ 13 ]  The show played in July and August 2012, at the  Tennessee Performing Arts Center  (TPAC) in  Nashville , aiming for a Broadway run. [ 13 ] [ 14 ] [ 15 ]  The book is by  Rupert Holmes , and the production was directed by  Jerry Lewis . [ 16 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4136", "contents": "Hamlisch was musical director and arranger of Barbra Streisand's 1994 concert tour of the U.S. and England as well as of the television special,  Barbra Streisand: The Concert , for which he received two of his Emmys. He also conducted several tours of  Linda Ronstadt  during this period, most notably on her successful 1996  Dedicated to the One I Love  tour of arenas and stadiums. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4137", "contents": "Hamlisch held the position of Principal Pops Conductor for the  Pittsburgh Symphony Orchestra , [ 19 ]  the  Milwaukee Symphony Orchestra , [ 20 ]  the  San Diego Symphony , [ 21 ]  the  Seattle Symphony , [ 22 ]  the  Dallas Symphony Orchestra , [ 23 ]   Buffalo Philharmonic Orchestra , [ 24 ]  The  National Symphony Orchestra  Pops, [ 25 ]   The Pasadena Symphony and Pops , [ 26 ]  and the  Baltimore Symphony Orchestra . [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4138", "contents": "On July 23, 2011, Hamlisch conducted his debut concert for  Pasadena Symphony and Pops  at  The Rose Bowl  in Pasadena, California. Hamlisch replaced  Rachael Worby . [ 28 ]   At the time of his death, he was preparing to assume responsibilities as Principal Pops Conductor for The  Philly POPS ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4139", "contents": "Hamlisch is one of ten people to win three or more Oscars in one night and the only one other than a director or screenwriter to do so. Hamlisch also won two  Golden Globes . He earned ten  Golden Globe Award  nominations, winning twice for  Best Original Song , with \"Life Is What You Make It\" in 1972 and \" The Way We Were \" in 1974. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4140", "contents": "He shared the Pulitzer Prize for Drama in 1976 with  Michael Bennett ,  James Kirkwood ,  Nicholas Dante , and  Edward Kleban  for his musical contribution to the original Broadway production of  A Chorus Line . [ 6 ]  Hamlisch received a Lifetime Achievement Award in 2009 at the World Soundtrack Awards in  Ghent , Belgium. He was also inducted into the  Long Island Music Hall of Fame  in 2008. [ 30 ]  In 2008, he appeared as a judge in the Canadian reality series  Triple Sensation  which aired on  CBC . The show was aimed to provide a training  bursary  to a talented young man or woman with the potential to be a leader in song, dance, and acting. [ 31 ] [ 32 ]  In 2008, Hamlisch was also inducted into the  American Theater Hall of Fame . [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4141", "contents": "Hamlisch's relationship with lyricist  Carole Bayer Sager  inspired the musical  They're Playing Our Song . [ 34 ]   He was also in a relationship with actress  Emma Samms . [ 35 ] [ failed verification ]   He was in a relationship with television personality  Cyndy Garvey  after her breakup with her husband,  Steve Garvey . [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4142", "contents": "In May 1989, Hamlisch married  Terre Blair , a native of  Columbus, Ohio , and graduate of Otterbein College, who was the  weather and news anchor  for that city's ABC affiliate,  WSYX -Channel 6. [ 37 ] [ 38 ] [ 39 ]  The marriage lasted until his death. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4143", "contents": "After a brief illness, Hamlisch collapsed in Los Angeles on August 6, 2012, and died later that day at  Ronald Reagan UCLA Medical Center  at age 68. [ 41 ] [ 42 ]  According to Hamlisch's death certificate, the cause of death was determined to be  respiratory arrest , with  hypertension  and  cerebral hypoxia  as contributing factors. [ 42 ] [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4144", "contents": "The  Associated Press  described him as having written \"some of the best-loved and most enduring songs and scores in movie history\". [ 44 ]  Barbra Streisand released a statement praising Hamlisch, stating it was \"his brilliantly quick mind, his generosity and delicious sense of humor that made him a delight to be around\". [ 6 ]   Aretha Franklin  called him \"classic and one of a kind\", and one of the \"all-time great\" arrangers and producers. [ 45 ]  The head of the  Pasadena Symphony and Pops  commented that Hamlisch had \"left a very specific\u00a0... original mark on American music and added to the great American songbook with works he himself composed\". [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4145", "contents": "At 8:00\u00a0p.m.  EDT  on August 8, the marquee lights of the 40 Broadway theaters were dimmed for one minute in tribute to Hamlisch, [ 46 ] [ 47 ]  an honor traditionally accorded upon their death to those considered to have made significant contributions to the theater arts. [ 48 ] [ 49 ] [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4146", "contents": "Barbra Streisand ,  Aretha Franklin , and  Liza Minnelli  took turns singing songs by Hamlisch during a memorial service for the composer on September 18, 2012. [ 51 ]  At the  2013 Academy Awards , Streisand sang \" The Way We Were \" in Hamlisch's memory. On June 2, 2013, a tribute was held in New York City to remember Hamlisch in advance of the first anniversary of his death. [ 52 ]  At the tribute, Staples Players, a high school theatre group from  Staples High School  in  Westport, Connecticut  performed a selection of material from  A Chorus Line . Other veterans of the screen and stage also performed at the event. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4147", "contents": "Hamlisch was the primary conductor for the Pittsburgh Pops from 1995 until his death. [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4148", "contents": "The  Dallas Symphony Orchestra  performed a rare Hamlisch classical symphonic suite titled  Anatomy of Peace  ( Symphonic Suite in one Movement For Full Orchestra/Chorus/Child Vocal Soloist ) on November 19, 1991. [ 55 ]  It was also performed at Carnegie Hall in 1993, [ 34 ]   and in Paris in 1994 to commemorate  D-Day . [ 56 ]  The work was recorded by the Dallas Symphony Orchestra in 1992. [ 57 ]   The Anatomy of Peace  was a book by  Emery Reves  which expressed the  world-federalist  sentiments shared by  Albert Einstein  and many others in the late 1940s, in the period immediately following  World War II . [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4149", "contents": "Anne Celeste Heche [ 2 ]  ( / h e\u026a t\u0283 /   \u24d8   HAYTCH ; [ 3 ] [ 4 ] [ 5 ]  May 25, 1969\u00a0\u2013 August 11, 2022 [ a ] ) was an American actress, known for her roles across a variety of genres in film, television, and theater. She was the recipient of  Daytime Emmy ,  National Board of Review , and  GLAAD Media Awards , in addition to nominations for a  Tony Award  and a  Primetime Emmy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4150", "contents": "Heche began her professional acting career on the  NBC  soap opera  Another World  (1987\u20131991), earning a  Daytime Emmy Award  for her portrayal of twins  Vicky Hudson  and  Marley Love . She made her film debut in 1993 with a small role in  The Adventures of Huck Finn . Heche's profile rose in 1997 with appearances in  Donnie Brasco ,  Volcano ,  I Know What You Did Last Summer , and  Wag the Dog . In 1998, she had starring roles in the romantic adventure  Six Days, Seven Nights  and the drama-thriller  Return to Paradise ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4151", "contents": "From 1999 to 2001, Heche focused on directing, most notably a segment of the  HBO  television film  If These Walls Could Talk 2  (2000). She was nominated for a  Tony Award  for her starring role in the 2004  Broadway  revival of  Twentieth Century , as well as a  Primetime Emmy Award  that same year for her appearance in the television film  Gracie's Choice . Other film appearances included  Prozac Nation  (2001),  John Q.  (2002),  Birth  (2004),  Spread  (2009),  Cedar Rapids  (2011),  Catfight  (2016), and  My Friend Dahmer  (2017). Heche also starred on a number of television series, such as  The WB 's  Everwood  (2004\u20132005),  ABC 's  Men in Trees  (2006\u20132008), and  NBC 's  The Brave  (2017\u20132018). In 2020, she appeared as a contestant on the  29th season  of  Dancing with the Stars , finishing in 13th place."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4152", "contents": "Events in Heche's personal life often upstaged her acting career. She was in a high-profile relationship with comedian  Ellen DeGeneres  between 1997 and 2000, with the pair being described by  The Advocate  as \"the first gay supercouple\". [ 10 ]  Immediately following her split from DeGeneres, she suffered a highly publicized  psychotic break . [ 11 ]  In 2001, Heche published a memoir titled  Call Me Crazy , in which she alleged extensive sexual abuse by her father. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4153", "contents": "On August 5, 2022, Heche was critically injured in a high-speed car crash. She died at a Los Angeles hospital on August 11, 2022, at the age of 53. [ a ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4154", "contents": "Anne Celeste Heche was born on May 25, 1969, in  Aurora, Ohio , the youngest of five children of Donald \"Don\" Joe Heche and  Nancy Heche  ( n\u00e9e  Prickett). [ 13 ] [ 14 ]  During her early childhood, the Heche family lived in various towns around Ohio, including suburbs of  Cleveland  and  Akron . [ 15 ]  Heche's parents were  fundamentalist Christians  and the family was raised in a deeply religious environment, [ 16 ] [ 17 ] [ 18 ]  a situation that she later likened to being \"raised in a  cult \". [ 19 ]  At the same time, her father led an unstable lifestyle, often changing professions and prone to frequent  get-rich-quick schemes , [ 20 ] [ 21 ]  though also with a real gift for music that led to jobs as a  choir director  in several churches. [ 20 ] [ 22 ]  Heche noted in her memoir that her family changed  denominations  several times depending on which church her father found work in. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4155", "contents": "Because of Don Heche's often unstable lifestyle and financial situation, the family moved numerous times during her childhood. [ 16 ] [ 17 ] [ 24 ]  One of his financial schemes led the family to resettle in the  Atlantic City, New Jersey , area in 1977, first in  Ventnor City  and later  Ocean City . [ 24 ] [ 25 ] [ 26 ]  One of Anne's first jobs was at a  boardwalk  hamburger stand, where she would sing songs from  Annie  to attract customers. [ 24 ] [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4156", "contents": "The Heche family's precarious financial situation led to the  foreclosure  of a home her father owned and later their  eviction  from a rental home. They moved in with a family from their church who offered them a place to live as an act of charity. [ 28 ] [ 29 ]  Anne's mother  separated  from her father and demanded he leave the household. Her mother and all of the children then took jobs to support the family and be able to live on their own. [ 17 ]  Anne found work at a  dinner theater  in  Swainton , her first professional acting job, earning $100 a week (about $300 per week in 2022 dollars). [ 24 ] [ 30 ] [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4157", "contents": "Don Heche moved to  New York City , where Anne and her sisters would occasionally visit him, noticing his declining health. He claimed it was cancer, when in fact he had developed late-stage  AIDS . Although he lived as a gay man in New York, Don kept his sexuality and the nature of his illness from his family. They did not know about his diagnosis and had not even heard of AIDS until coming across an article on the disease in  The New York Times  about a month before his death. [ 32 ] [ 33 ] [ 34 ]  Don died from AIDS-related complications on March 3, 1983, aged 45. [ 35 ]  In a 1998 interview, Anne reflected that her father being  closeted  ultimately \"destroyed his happiness and our family. But it did teach me to tell the truth. Nothing else is worth anything.\" [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4158", "contents": "Three months after her father's death, Anne's 18-year-old brother Nathan was killed in a car crash when his vehicle missed a curve and struck a tree. [ 31 ] [ 37 ]  The remainder of her immediate family subsequently moved to Chicago to be closer to other family members. [ 38 ] [ 39 ]  Anne, her mother and her older sister Abigail, who had left college, were all living together in a one-bedroom apartment, which lacked privacy and which Anne would compare to living in a  dorm room . [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4159", "contents": "Heche attended the  progressive   Francis W. Parker School , where she continued to be active in theater, performing in such plays as  Thornton Wilder 's  The Skin of Our Teeth  and  Irwin Shaw 's  Bury the Dead . [ 41 ] [ 42 ] [ 43 ]  When she was aged 16, a  talent scout  spotted her in a school play and invited her to audition for the daytime soap opera  As the World Turns . Heche flew to New York with her mother, auditioned, and was offered a part. She was not able to accept the offer, as it would have entailed moving with her family to New York in the middle of her school year and having her mother leave a new job at a  brokerage firm . In her memoir, Heche notes that she really wanted to move out on her own and \"escape [her] mother's grasp\", but this was not an option while she was still a minor. [ 31 ] [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4160", "contents": "In 1987, at the end of her  senior year , Heche was offered another audition, this time for the soap opera  Another World . She was offered a role after two auditions and accepted, in spite of her mother's opposition. She moved to New York City and started work on the series, in her debut television role, just days after her high school graduation. [ 41 ] [ 42 ] [ 45 ]  In a later interview she stated, \"I did my time with my mom in a one-bedroom, skanky apartment and I was done.\" [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4161", "contents": "Heche performed on  Another World  in the  dual role  of twins  Vicky Hudson  and  Marley Love . [ 42 ] [ 46 ] [ 47 ]  She continued on the series for nearly four years, from 1987 to 1991. [ 46 ] [ 47 ]  She received several awards for her work on  Another World , including a  Daytime Emmy Award for Outstanding Younger Actress in a Drama Series  in 1991. [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4162", "contents": "Heche was unsure about her future as an actress after leaving  Another World , having not performed in any other onscreen roles during her time on the soap opera and not having any acting jobs in place at the time she decided to leave. She knew that she did not want to continue in soap operas, something that was considered fairly insignificant in the larger world of professional acting. As a backup plan, she applied to and received an offer of acceptance from  Parsons School of Design  in New York City. However, right after applying to design school, she was offered a small  supporting role  in the  Hallmark Hall of Fame  television film adaptation of the  Willa Cather  novel  O Pioneers! , featuring  Jessica Lange . Heche decided to take that offer rather than attend design school and to continue with her career as an actress. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4163", "contents": "Heche received news of her Daytime Emmy Award for  Another World  while in  Nebraska  filming  O Pioneers! . \"Does this mean I'm an actress?\" was her response in a telephone call with her agent following the news. The agent suggested that she relocate from New York City to Los Angeles, which she did days after shooting was completed on the film. [ 49 ]   O Pioneers!  would air in February 1992 and was Heche's first TV movie. Her performance garnered some positive critical notice. [ 50 ]  After completing  O Pioneers! , Heche starred in a  guest appearance  in an episode of  Murphy Brown . [ 51 ] [ 52 ]  Though this episode was shot after  O Pioneers! , it aired in November 1991 and hence was her  primetime television  debut and her first screen appearance outside of  Another World . After her  Murphy Brown  appearance, however, she felt that guest spots on television episodes would be detrimental to her long-term career success and mostly avoided TV guest spots [ 52 ]  until the 2000s. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4164", "contents": "Heche also starred in several roles in Los Angeles theater productions in 1991 and 1992, including \"Us & Them\", a  Generation X   slice-of-life  piece, [ 52 ] [ 54 ]  and  Getting Away With Murder , a stage adaptation of the  James M. Cain  stories  Dead Man  and  The Baby in the Icebox , which were produced as part of the  Mark Taper Forum \u2013sponsored \"Sundays at the Itchey Foot\" series. [ 55 ] [ 56 ]  In early 1993, Heche made her theatrical film debut in the little-seen  independent film   An Ambush of Ghosts , directed by  Everett Lewis . [ 57 ]  Soon afterward, she appeared in the  Disney  film  The Adventures of Huck Finn  with  Elijah Wood . Over the next two years, she performed mainly  bit parts  in feature films such as  A Simple Twist of Fate  (1994) and larger  supporting roles  in cable television movies such as  Girls in Prison  (1994) and  Kingfish: A Story of Huey P. Long  (1995)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4165", "contents": "Heche appeared in her first lead role (albeit receiving third billing) in  Donald Cammell 's straight-to-video  erotic thriller   Wild Side  (1995), alongside  Christopher Walken  and  Joan Chen . The film gained some notoriety for its inclusion of a very strong  lesbian   sex scene  between Heche and Chen. [ 58 ] [ 59 ]  In 1996, Heche had the starring role as a college student contemplating an abortion in a segment of the  HBO   anthology film   If These Walls Could Talk , co-starring  Jada Pinkett Smith  and  Cher . [ 60 ]  Also that year, she appeared opposite  Catherine Keener  portraying childhood best friends in the independent film  Walking and Talking . The  limited-release  film garnered favorable reviews from critics and is number 47 on  Entertainment Weekly ' s \"Top 50 Cult Films of All-Time\" list. [ 61 ]  Heche gained positive notice from film critic Alison Macor of  The Austin Chronicle , who wrote in her review that she \"is destined for larger film roles\". [ 62 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4166", "contents": "In 1997, Heche starred in what has been described as her  breakthrough role  in the hit crime drama  Donnie Brasco  as the wife of the main character, an  FBI  undercover agent played by  Johnny Depp . Critic  Janet Maslin  of  The New York Times  wrote that Heche \"does well with what could have been the thankless role\". [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4167", "contents": "By the late 1990s, Heche continued to find recognition and commercial success as she took on supporting roles in three other 1997 high-profile film releases\u2014 Volcano ,  I Know What You Did Last Summer  and  Wag the Dog . The disaster film  Volcano , about the formation of a volcano in Los Angeles, had her star with  Tommy Lee Jones  and  Gaby Hoffmann , playing a  seismologist . While critical response towards the film was mixed, it grossed US$122\u00a0million at the international box office. [ 64 ]  Heche portrayed the minor role of a backwoods loner in the slasher thriller  sleeper hit   I Know What You Did Last Summer , starring  Jennifer Love Hewitt ,  Sarah Michelle Gellar ,  Ryan Phillippe , and  Freddie Prinze Jr.  Despite her limited screen time in the film, Heche was considered a \"standout\" by some reviewers, [ 65 ]  such as Derek Eller of  Variety . [ 66 ]  She obtained the part of a presidential advisor opposite  Robert De Niro  and  Dustin Hoffman  in the political satire  Wag the Dog , a role that was originally written for a man. [ 67 ]  Budgeted at US$15\u00a0million, the film made US$64\u00a0million. [ 68 ]  She received the  National Board of Review Award for Best Supporting Actress  in 1997 for her roles in  Donnie Brasco  and  Wag the Dog ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4168", "contents": "Heche's first lead role in a major film came in the 1998 romantic adventure  Six Days, Seven Nights , where she appeared opposite  Harrison Ford , portraying a New York City journalist who ends up with a pilot (Ford) on a deserted island following a crash landing. [ 69 ]  She had been cast in the film one day before her  same-sex relationship  with  Ellen DeGeneres  went public. [ 70 ]  Although she was cast in a second starring role shortly thereafter as  Vince Vaughn 's love interest in the drama  Return to Paradise  (1998), Heche felt that her relationship with DeGeneres destroyed her prospects as a leading woman. [ 71 ]  According to Heche, \"People said, 'You're not getting a job because you're gay'.\" [ 72 ]  She commented: \"How could that destroy my career? I still can't wrap my head around it.\" [ 71 ]   Six Days, Seven Nights  received mixed reviews, but grossed US$74.3\u00a0million in North America and US$164.8\u00a0million worldwide. [ 73 ]  On her appearance in the dramatic thriller  Return to Paradise , a writer for  The New York Times  remarked, \"as Ms. Heche's formidable Beth Eastern does her best to manipulate the other characters on [costar  Joaquin Phoenix 's character] behalf,  Return to Paradise  takes on the abstract weightiness of an ethical debate rather than the visceral urgency of a thriller.\" [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4169", "contents": "Heche starred in  Gus Van Sant 's  Psycho  (1998), a  remake  of the  1960 film  directed by  Alfred Hitchcock . In the updated version, she took on the role originally played by  Janet Leigh  as  Marion Crane , an embezzler who arrives at an old motel run by serial killer  Norman Bates  (played by Vince Vaughn in their second collaboration).  Psycho  earned negative reviews, and despite a US$60\u00a0million budget it made US$37.1\u00a0million worldwide. [ 75 ]  In an otherwise negative  Times  review of the film, Janet Maslin felt that Heche was \"refreshingly cast in Marion's role\", while noting that her portrayal was \"almost as demure as Ms. Leigh's, yet she's also more headstrong and flirty.\" [ 76 ]  Heche's 1998 films were the only theatrically released films in which she had a leading role. [ 77 ]  She also starred opposite  Ed Harris  in the 1999 film,  The Third Miracle , directed by  Agnieszka Holland . [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4170", "contents": "Heche spent much of the 1998 to 2001 working on film directing projects, often writing her own screenplays. She pulled back from acting roles during this period and had relatively few acting appearances from 1999 to 2001. [ 17 ]  Her first effort at writing and directing was a 1998 short film titled  Stripping for Jesus , which was about an evangelical Christian stripper who writes Bible verses on her body so as to reach clients \"in a language that they understand\". [ 79 ]  According to Heche, the film was a  metaphor  for \"my life as I saw it\". The film was fully self-financed. [ 80 ]  Heche starred in the film along with  Suzanne Krull  and  Karen Black . [ 79 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4171", "contents": "Heche's next several films were made for cable television and featured then-partner Ellen DeGeneres in varying degrees of participation. The first of these (and the one with the widest release) came in 2000, when Heche directed a segment of  If These Walls Could Talk 2  for HBO. An anthology film, it consisted of a series of segments about lesbian life in individual years over several decades. In Heche's segment, \" 2000 \", DeGeneres and  Sharon Stone  starred as a contemporary lesbian couple trying to have a baby together via  artificial insemination . [ 81 ]  DeGeneres was also one of the executive producers of the film. In 2001, Heche directed another anthology film segment, this time part of  On the Edge , a  Showtime  anthology of science fiction stories directed by different actresses. [ 82 ]  Heche's segment, titled  Reaching Normal , was her screenplay adaptation of the short story  Command Performance  by  Walter M. Miller Jr. [ 83 ]  The segment features  Andie MacDowell  and  Paul Rudd  in the story of a housewife who enters into a  telepathic   extramarital affair ; the segment includes a cameo appearance by DeGeneres. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4172", "contents": "Heche also directed a documentary that was to be released in 2001,  Ellen DeGeneres: American Summer , about DeGeneres' 2000 stand-up comedy tour. [ 85 ]  The project was never completed. [ 86 ]  DeGeneres, who financed the documentary, states that she \"burned\" the film after attempting to salvage the project following the couple's split, but that the memories that it brought back were too painful. [ 87 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4173", "contents": "Most of Heche's roles in the early 2000s were in independent films and television; she played the role of Dr. Sterling in the  film adaptation  of  Elizabeth Wurtzel 's autobiography about depression,  Prozac Nation , with  Christina Ricci  and Jessica Lange. Premiered at the 2001  Toronto International Film Festival , the film received a DVD release in 2005. She appeared as a hospital administrator in the  thriller   John Q. , about a father and husband ( Denzel Washington ) whose son is diagnosed with an enlarged heart. The production made US$102.2 million at the worldwide box office, [ 88 ]  despite negative reviews by critics. [ 89 ]  In 2001, Heche obtained a recurring role in the fourth season of the television series  Ally McBeal . [ 90 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4174", "contents": "In 2002, Heche made her  Broadway  debut in a production of the  Pulitzer Prize -winning drama  Proof , in the role of a young woman who has inherited her father's mathematical genius and mental illness.  The New York Times  found Heche to be \"consequential\" in her portrayal and compared her to  Mary-Louise Parker  and  Jennifer Jason Leigh , who had previously played the character, stating: \"[...] Ms. Heche, whose stage experience is limited and who is making her New York stage debut at 33, plays the part with a more appeasing ear and more conventional timing, her take on the character is equally viable. Her Catherine is a case of arrested development, impatient, aggressively indignant, impulsive\". [ 91 ]  In 2004, Heche received a  Primetime Emmy Award  nomination for Best Supporting Actress for her performance in the  Lifetime  movie  Gracie's Choice , as well as a  Saturn Award  nomination for Best Actress for her performance in the  CBS  television film  The Dead Will Tell . In the same year, she performed on Broadway opposite  Alec Baldwin  in revival of the play  Twentieth Century ,  about a successful and egomaniacal Broadway director (Baldwin), who has transformed a chorus girl (Heche) into a leading lady. For her performance, she was nominated for the 2004  Tony Award for Best Actress in a Play . [ 92 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4175", "contents": "Also in 2004, Heche appeared alongside  Nicole Kidman  and  Cameron Bright  in the well-received independent drama  Birth . She took on the recurring role on  The WB  drama  Everwood  during its 2004\u201305 season, and then a recurring role on  Nip/Tuck  as an ex-mob wife and  Witness Protection Program  subject who requires plastic surgery. Heche continued her television work with Hallmark Hall of Fame  Christmas film   Silver Bells  (2005) [ 93 ]  and in the Lifetime television film  Fatal Desire  (2006), about an ex-cop, played by  Eric Roberts , who meets a woman on an online dating site who attempts to get him to kill her husband. [ 94 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4176", "contents": "Heche appeared in the small-scale  dramedy   Sexual Life  (2005), chronicling modern romantic life and co-starring  Azura Skye  and  Elizabeth Banks . The film was screened on the film festival circuit and received a television premiere. In 2006 she began work on her own series,  Men in Trees , in which she played a New York author who, after finding out her fianc\u00e9 is cheating on her, moves to a small town in  Alaska  which happens to be abundant with single men and few women.  Men in Trees  was canceled in May 2008, after a season shortened by the  writer's strike . During the airing of the show, Heche starred in the romantic comedy  What Love Is  (2007) [ 95 ]  and in  Toxic Skies  (2008), a science-fiction thriller based on the  chemtrails   conspiracy theory . [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4177", "contents": "Heche appeared as the girlfriend of a narcissistic  gigolo  in the  sex comedy   Spread  (2009), co-starring  Ashton Kutcher . [ 97 ]  The film received a limited release in North American theaters while it made US$12 million at the worldwide box office. [ 98 ]  Matthew Turney of  View London  felt that \"[t]here's also terrific support\" from Heche in what he described as an \"enjoyable, sharply written and beautifully shot LA drama\". [ 99 ]  Also in 2009, she was cast in the HBO dramedy series  Hung , in a supporting role as the ex-wife of a financially struggling high school coach-turned- male prostitute , portrayed by  Thomas Jane . The series received favorable reviews and aired until 2011. [ 100 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4178", "contents": "Heche's cameo appearance as the CEO of an important company in the well-received comedy  The Other Guys  (2010), starring  Will Ferrell  and  Mark Wahlberg , was followed by a much larger role in the independent comedy  Cedar Rapids  (2011), where she portrayed a seductive insurance agent with whom a naive and idealistic man (played by  Ed Helms ) becomes smitten. The  Sundance -premiered production garnered critical praise and was an  arthouse  success. [ 101 ] [ 102 ]  David Rooney of  The Hollywood Reporter  remarked in his review for the film, \"while Heche shines brightest in more brittle mode, as in HBO's  Hung , she strikes a sweet balance between Joan's mischievous and maternal sides\". [ 103 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4179", "contents": "In the drama  Rampart  (2011), Heche starred with  Woody Harrelson  and  Cynthia Nixon , as one of the two former wives of a corrupt police officer (Harrelson), who also happen to be sisters. The film had a selected theatrical run following its premiere at the  36th Toronto International Film Festival , and garnered an overall positive response; [ 104 ] [ 105 ]   The San Francisco Chronicle , remarked that Heche and her other female co-stars, \"allow Harrelson to shine \u2013 he has always had a way of preening for women \u2013 and he brings out the best in them\". [ 106 ]  She also starred in Lifetime film  Girl   Fight  (2011), alongside  Jodelle Ferland  and  James Tupper . Heche then had the leading role in the comedy  That's What She Said  (2012), which premiered at the  Sundance Film Festival , [ 107 ]  followed by the role of the girlfriend of a former pro golfer ( Colin Firth ) in  Arthur Newman  (also 2012). [ 108 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4180", "contents": "Heche starred with  James Tupper ,  Jennifer Stone , and  Rebekah Brandes  in the supernatural horror film  Nothing Left to Fear  (2013), about a family's life in a new town being interrupted by an unstable man of the cloth. The film received a release for  video-on-demand  and selected theaters. [ 109 ]  It was panned by critics, [ 110 ]  and the  Los Angeles Times  remarked that both Heche and Tupper \"should write apology notes to their fans\". [ 109 ]  Also in 2013, Heche headlined the short-lived  NBC  sitcom  Save Me , in which she starred as a  Midwestern  housewife who believes that she is channeling God. [ 111 ]  She played the waitress friend of a recovering gambling addict ( Jason Statham ) in the action thriller  Wild Card  (2014). [ 112 ]  Distributed for a VOD and limited release in certain parts of North America only, the film only grossed US$6.7\u00a0million internationally on a $30\u00a0million budget. [ 113 ]  Heche also had a recurring guest-role on  The Michael J. Fox Show  before its cancellation. In 2013, she signed a first look deal with  Universal Television . [ 114 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4181", "contents": "USA Network 's  action-adventure  drama series,  Dig , had Heche portray the head of the FBI field office in  Jerusalem  whose agents uncover a 2,000-year-old conspiracy while investigating an  archaeologist 's murder. The six-episode series premiered in late 2014. [ 115 ]  The following year, Heche guest-starred in the  ABC  thriller series  Quantico  playing the role of  criminal profiler , Dr. Susan Langdon. [ 116 ]  On September 27, 2016, she starred in the post-apocalyptic action drama  Aftermath , which debuted on Canada's  Space  network and on United States'  Syfy . Heche played Karen Copeland, a  United States Air Force  pilot who must navigate  Armageddon , with her university-professor husband Josh (James Tupper) and their three nearly adult children. Neither  Dig  nor  Aftermath  was renewed for a second season. [ 117 ] [ 118 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4182", "contents": "Heche filmed the supporting part as the lead singer for a Broadway musical in  Opening Night  (2016) with  Topher Grace . The  musical comedy  was screened at the  Los Angeles Film Festival . [ 119 ] [ 120 ]  In another independent film, the comedy  Catfight  (2016), Heche starred opposite  Sandra Oh , portraying one of two bitter rivals who pursue a grudge match that spans a lifetime. Like Heche's previous projects, the film premiered on the film-festival circuit and received a VOD and limited release, [ 121 ]  to largely favorable reviews from critics. [ 122 ]  The  Los Angeles Times  wrote: \"Oh and Heche are great here, giving performances entirely lacking in vanity and self-consciousness. They aren't afraid to get ugly, both in their treatment of everyone around them as well as in their post-brawl bruises, which makes them that much funnier.\" [ 123 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4183", "contents": "In 2017, Heche played a supporting role in  My Friend Dahmer  as Joyce, the mentally ill mother of the teenaged  Jeffrey Dahmer  ( Ross Lynch ). [ 124 ]  She received positive reviews for her performance, with  The Hollywood Reporter  calling her \"nerve-jangling perfection\" [ 125 ]  and  Empire  calling her \"entertainingly off-kilter\". [ 126 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4184", "contents": "On September 25, 2017, Heche debuted as the series lead playing  DIA  Deputy Director Patricia Campbell in the military/espionage thriller  The Brave , which lasted for one season on  NBC . [ 127 ]  In 2018, she joined the television series  Chicago P.D.  in a supporting role. [ 128 ]  In late 2020, Heche competed as one of the celebrities in the  29th season  of  Dancing with the Stars , but was eliminated from the contest after the fourth week. [ 129 ] [ 130 ]  The following year, she co-starred in an  ensemble cast  in Lindsay Gossling's  13 Minutes  about four families struggling with multiple dilemmas in a fictional  Oklahoma  town just before a devastating  tornado  hits. [ 131 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4185", "contents": "At the time of her death in August 2022, Heche had completed filming several films that were still in post-production and where she would appear posthumously. [ 132 ]  One of these films was  Girl in Room 13  that aired as part of Lifetime's \"Ripped from the Headlines\" film series. The movie is about  human trafficking  and was dedicated in memory of Heche. [ 133 ]   Wildfire: The Legend of the Cherokee Ghost Horse  is slated to be the final screen performance for Heche, which is a family-appeal film based on the song \" Wildfire \" by  Michael Martin Murphey . She also appeared with  Alec Baldwin  in the disaster action film  Supercell , released on March 17, 2023."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4186", "contents": "In 2001, Heche published a memoir titled  Call Me Crazy , [ 134 ]  which discussed her family and career background, as well as disclosed her history of mental illness and alleged  childhood sexual abuse  by her father. [ 86 ]  In 2021, on her  Better Together  podcast, she said that she was working on a second memoir tentatively titled  Call Me Sane . [ 135 ]  In September 2022, the second memoir, now titled  Call Me Anne , was submitted in manuscript form shortly before her death and was announced for a January 2023 publication. [ 136 ] [ 137 ] [ 138 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4187", "contents": "Heche also narrated several  audiobooks , notably, a self-narrated audiobook of  Call Me Crazy , [ 139 ]  as well as narrating audiobook versions of  Stephen King 's  The Girl Who Loved Tom Gordon  (1999) and  Tess Gerritsen 's  Vanish  (2005; co-narrated by Ilyana Kadushin). [ 140 ]  In 2017, Heche hosted a weekly radio show on  SiriusXM  with  Jason Ellis  entitled  Love and Heche . [ 141 ]  In late 2020, Heche and Heather Duffy Boylston launched a  podcast  titled  Better Together . [ 5 ] [ 142 ] [ 143 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4188", "contents": "Heche's mother, Nancy Heche, has been a Christian therapist since 1997, and since 2005 has focused on \"overcoming homosexuality\", frequently speaking at events sponsored by evangelical Christian and  Christian right  groups, notably the  ex-gay  ministry  Love Won Out . [ 18 ] [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4189", "contents": "Heche had four older siblings, three of whom predeceased her. The eldest,  Susan Bergman  (1957\u20132006), died of a  brain tumor . Bergman was a university lecturer in  literature  and a  Christian writer , whose 1994 memoir titled  Anonymity  described their closeted gay father and the effects that his legacy had on the rest of the family. [ 144 ] [ 145 ] [ 146 ] [ 147 ]  Another sister, Cynthia, died of a heart defect at two months. [ 31 ]  Heche's only brother, Nathan (1965\u20131983), died in a car crash at age 18, three months after the death of their father. Heche said his death was a suicide, though her mother and surviving siblings dispute this. [ 148 ] [ 149 ] [ 150 ]  Abigail is the fourth sibling, followed by Anne. [ 151 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4190", "contents": "Heche was  estranged  from the surviving members of her family for many years. A rift with her mother began when she first disclosed her relationship with Ellen DeGeneres. The rift deepened when she alleged sexual abuse by her father in  Call Me Crazy , creating a rift with her two sisters as well. Heche said she had been estranged from her mother since she confronted her about the sexual abuse. [ 12 ]  Heche's mother said it was Anne who cut off communication. [ 152 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4191", "contents": "In her 2001 memoir, Heche wrote that her mother was in denial about the alleged sexual abuse. For example, when she contracted  genital herpes  as an infant, her mother insisted that it was a  diaper rash  and refused to take her to a doctor. [ 153 ]  Heche also wrote that her father repeatedly raped her from the time she was an infant until she was 12. [ 17 ]  When she was asked, \"But why would a gay man rape a girl?\" in a 2001 interview with  The Advocate , Heche replied, \"I don't think he was just a gay man. I think he was  sexually deviant . My belief was that my father was gay and he had to cover that up. I think he was sexually abusive. The more he couldn't be who he was, the more that came out of him in [the] ways that it did.\" [ 154 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4192", "contents": "Heche's mother has denied her daughter's allegations and responded in a discussion of the book on an  internet forum : \"I am trying to find a place for myself in this writing, a place where I as Anne's mother do not feel violated or scandalized. I find no place among the lies and blasphemies in the pages of this book.\" [ 12 ] [ 152 ]  Anne's sister Abigail added, \"It is my opinion that my sister Anne truly believes, at this moment, what she has asserted about our father's past behavior; however, at the same time, I would like to point out that Anne, in the past, has expressed doubts herself about the accuracy of such memories. Based on my experience and her own expressed doubts, I believe that her memories regarding our father are untrue. And I can state emphatically, regardless of Anne's beliefs, that the assertion that our mother knew about such behavior is absolutely false.\" [ 12 ] [ 152 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4193", "contents": "In 2009, Heche told  The New York Times :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4194", "contents": "My mother had a very tragic life. Three of her five children are dead, and her husband is dead. That she is attempting to change gay people into straight people is, in my opinion, a way to keep the pain of the truth out. People wonder why I am so forthcoming with the truths that have happened in my life, and it's because the lies that I have been surrounded with and the denial that I was raised in, for better or worse, bore a child of truth and love. My mother preaches to this day the opposite of that core of my life. It is no mistake that she still stands up against love. And one wonders why I'm not rushing to have her meet my children. [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4195", "contents": "In 2011, Heche told  The Daily Telegraph  that she had reconciled with her remaining sister Abigail, but doubted she would be able to repair her relationship with her mother. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4196", "contents": "Elliot and  Natalie Bergman , of the band  Wild Belle , are Heche's nephew and niece. In 2017, she said that their album  Dreamland  was her favorite album and described herself as a \"proud aunt\". [ 155 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4197", "contents": "Heche was in a relationship with  Lindsey Buckingham  of  Fleetwood Mac  for about one year in the early 1990s [ 156 ]  and also in a relationship with  Steve Martin , whom she had met on the set of  A Simple Twist of Fate , for about two years during the mid-1990s. [ 157 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4198", "contents": "Heche's relationship with DeGeneres and the events following their breakup became subjects of widespread media interest. [ 69 ] [ 158 ] [ 159 ]  They were described as \"the world's first gay  supercouple \". [ 10 ]  Heche and DeGeneres started dating in 1997, and at one point said they would get a  civil union  if such became legal in  Vermont . [ 160 ]  They broke up in August 2000. [ 161 ] [ 162 ]  Heche stated that all of her other romantic relationships were with men. [ 31 ] [ 163 ]  In the memoir  Call Me Anne , submitted shortly before her death, she wrote that she never identified as a lesbian and did not regard the terms \"gay\" or \"straight\" as relevant to her. [ 136 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4199", "contents": "Heche claims that there was professional fallout due to her relationship with DeGeneres. She recounts that she was warned not to attend the 1997 premiere of  Volcano  with DeGeneres, and when the couple did so anyway, they were escorted out before the film had ended. [ 164 ] [ 165 ] [ 166 ]  Heche said that she was told that she would be denied the part in  Six Days, Seven Nights  for going public with her romance with DeGeneres, but landed the role nevertheless. [ 164 ]  However, Heche did not work in a studio picture for 10 years afterward. [ 165 ] [ 166 ]  In a later podcast, Heche claimed that DeGeneres tried to put her in an institution [ 135 ]  and that she was effectively blacklisted from  DeGeneres' talk show , which negatively affected her career as studios were reluctant to hire her for films they would be unable to publicize on the widely viewed program. [ 167 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4200", "contents": "In 2000, Heche left DeGeneres for Coleman \"Coley\" Laffoon, a cameraman whom she met when she hired him as part of the camera crew for the television documentary  Ellen DeGeneres: American Summer , which she was directing. On September 1, 2001, she and Laffoon married. [ 67 ]  They had a son, Homer Heche Laffoon, in March 2002. [ 67 ] [ 168 ]  Laffoon filed for divorce in February 2007, after five and a half years of marriage. [ 169 ]  In a separate court filing, he said that Heche \"exhibited bizarre and delusional behavior for which she refuses to seek professional help.\" [ 170 ]  The divorce was finalized in March 2009. [ 171 ] [ 172 ] [ 173 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4201", "contents": "Heche left Laffoon for  Men in Trees  co-star James Tupper. [ 174 ]  During their relationship, Heche described herself and Tupper as being \"eternally engaged\". [ 175 ]  She and Tupper had a son, Atlas Heche Tupper, in March 2009. [ 176 ] [ 177 ]  Tupper and Heche separated in January 2018. [ 178 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4202", "contents": "Heche and former  Hung  co-star  Thomas Jane  announced that they were in a relationship in 2019; they were together into 2020, but had separated by the time of her death. [ 179 ] [ 180 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4203", "contents": "In her memoir  Call Me Crazy , Heche discusses her struggles with mental health issues and the long-term effect of her childhood abuse. She wrote that she had blocked out much of her childhood [ 181 ]  and had first gone into therapy during her time on  Another World , undergoing various types of therapy through the mid-1990s. [ 182 ]  Heche soon began  Reichian   body psychotherapy , and wrote that the release of  body memories  through this technique helped her  recover memories  of her alleged sexual abuse and confront the emotional aftermath of childhood trauma. [ 183 ]  This process was later continued through guided  LSD therapy , which she claimed had led to a full recovery of childhood memories. [ 184 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4204", "contents": "Heche underwent another crisis that began about the time she had finished filming  Donnie Brasco , in which she said that she began hearing  God speaking directly  to her. [ 185 ]  In this state, she said that she was told that she had an inner being called \"Celestia\" who was an  incarnation  of God and the  Second Coming  of Jesus. She believed that it was her mission to enlighten humanity and that she had achieved fame in order to fulfill this role. [ 186 ]  Heche's initial experience of hearing and being directed by what she claimed was God lasted for twelve days, [ 185 ]  and her spiritual experiences and  alter ego  as Celestia continued for another four years. [ 187 ]  During this time, Heche claimed to have had experiences with  glossolalia ,  automatic writing  and  drawing ,  clairvoyance , the ability to  psychically heal  others and having  stigmata  appear on her feet. [ 188 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4205", "contents": "On August 19, 2000, immediately following her separation from DeGeneres, [ 161 ]  Heche drove on  Interstate 5  from Los Angeles to the  San Joaquin Valley . Exiting where she later said she \"had been told\" to go, she ended up in  Cantua Creek , a rural area in western  Fresno County, California . [ 189 ] [ 190 ]  Heche left her vehicle at the side of a rural road and, wearing only a bra and shorts, walked 1.5 miles (2.4\u00a0km) in extremely hot weather without water, before feeling  dehydrated  and knocking on the door of a ranch house. [ 189 ] [ 191 ]  The homeowner recognized Heche from  Six Days, Seven Nights  and was astonished that a celebrity would show up at her \"in the middle of nowhere\" location. [ 189 ] [ b ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4206", "contents": "After the homeowner let Heche in and gave her a glass of water, Heche took off her shoes and requested to take a shower, with which the homeowner obliged. [ 189 ] [ 192 ]  She assumed that Heche was not  under the influence  of alcohol or drugs, but Heche later revealed to officers that she had taken  ecstasy . [ 86 ] [ 193 ]  After taking a shower, Heche entered the living room, asked for a pair of slippers, and suggested that they should watch a movie. [ 189 ]  Unsure of what to do after Heche had been at the house for a half an hour without contacting anyone, the resident contacted the  Fresno County Sheriff's Department . [ 189 ]  Heche later told the deputies that she was \"God, and was going to take everyone back to heaven\u2026in a spaceship.\" [ 193 ]  She was then taken to  Fresno 's University Medical Center by ambulance and was admitted to its  psychiatric unit , but she was released within a few hours. [ 189 ] [ 194 ]  The unit's personnel described the incident as a  psychotic break . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4207", "contents": "Heche stated that she was  insane  for the first 31 years of her life, and that her insanity was triggered by the sexual abuse that her father subjected her to during her childhood. [ 195 ] [ 196 ]  In a series of nationally televised interviews to promote  Call Me Crazy  in September 2001, she stated that she created a fantasy world called the \"Fourth Dimension\" and the alter ego \"Celestia\" to make herself feel safe. [ 12 ] [ 197 ]  Heche said she recovered from her mental health concerns following the incident in Cantua Creek and had put her alter ego behind her. [ 86 ] [ 197 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4208", "contents": "In a January 2018 interview on the podcast  Allegedly with Theo Von and Matthew Cole Weiss , Heche alleged that  Harvey Weinstein  had  exposed himself  to her and demanded  oral sex , and claimed to have been fired from an unspecified  Miramax  film in retaliation after she refused Weinstein's advances. She said that there were many other incidents of  sexual harassment  that took place during her career and stated that her survival of childhood sexual abuse had given her the strength to stand up to unwanted advances such as those made by Weinstein. A spokesman for Weinstein said that he had been \"friendly\" with Heche, but denied all of her allegations. [ 198 ] [ 199 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4209", "contents": "On August 5, 2022, Heche was involved in a sequence of three motor vehicle collisions in the  Mar Vista  neighborhood of Los Angeles, the final collision being the most serious, inflicting critical injuries on Heche and destroying a house. [ 200 ] [ 201 ] [ 202 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4210", "contents": "The first collision took place when Heche's vehicle struck an apartment garage and caused minor damage. A video released by  TMZ  shows her vehicle, a  Mini Clubman , [ 203 ]  at the scene of the collision and an unidentified man repeatedly shouting, \"Out of the car!\" at the driver. The vehicle then reversed and left the scene of the collision. The driver in the photo released by TMZ was identified as Heche. [ 201 ] [ 203 ] [ 204 ] [ 205 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4211", "contents": "TMZ also reported a second  hit-and-run  in which Heche's Mini struck a  Jaguar  without stopping, though without injury to the other driver. An accompanying video shows the Mini speeding down an alleyway and nearly hitting a pedestrian. [ 206 ]  A  doorbell  video recorded in the moments before the final crash shows Heche's vehicle driving along a neighborhood street at a very high speed, followed a few seconds later by the sound of a crash. [ 200 ] [ 204 ] [ 207 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4212", "contents": "In the final crash, Heche's vehicle struck a house, broke through a wall and embedded itself 30 feet (9.1\u00a0m) into the building, trapping Heche inside. The vehicle caught fire, which rapidly spread through the entire building. The resulting house fire took 65 minutes to be fully extinguished and required 59 firefighters. [ 201 ] [ 202 ] [ 208 ] [ 209 ]  Firefighters were unable to access and fully  extricate  Heche from the vehicle for 45 minutes after their arrival on the scene, and initially were not aware that a person was trapped in the vehicle itself. [ 210 ]  Heche had sustained severe burns and  smoke inhalation  injuries by the time she was rescued. [ 201 ] [ 202 ]  The house was left  structurally compromised  and uninhabitable. [ 203 ] [ 204 ] [ 208 ]  The tenant living in the house was in the rear of the structure at the time of the collision and only sustained minor injuries, but her attorney said that she and her pets \"almost lost their lives\" and that she had lost all of her personal property in the fire. [ 202 ] [ 209 ] [ 211 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4213", "contents": "Law enforcement officials initially stated that Heche was \"deemed to be under the influence and acting erratically\" at the time of the crashes. [ 201 ]  The  Los Angeles Police Department  said that a preliminary blood analysis showed the presence of both  cocaine  and  narcotics , including  fentanyl , in her system; however, the coroner's report concluded that she was not impaired at the time of the crash.  [ 212 ] [ 213 ] [ 214 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4214", "contents": "As Heche was being removed from the crash scene, she was filmed sitting up on the stretcher and struggling with firefighters while she was being wheeled into the ambulance but lost consciousness soon afterward. [ 207 ] [ 215 ]  Heche was taken to  Ronald Reagan UCLA Medical Center  for emergency care, and then to Grossman Burn Center at  West Hills Hospital  for specialized  burn center  care. [ 210 ]  On August 8, a representative for Heche said that she was in a coma in  critical condition , requiring  medical ventilation  for  pulmonary injury  sustained in the accident. [ 216 ] [ 217 ]  The representative also said that prior reports that Heche was in \" stable condition \" were \"inaccurate\". [ 217 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4215", "contents": "On August 11, the representative said that Heche was not expected to survive an  anoxic brain injury  she had sustained, but that she was being kept on  life support  to determine if her organs were viable for donation, in accordance with her expressed wish to be an  organ donor . [ 218 ] [ 219 ]  Heche was declared  brain dead  a few hours later, but remained on life support to assess organ donor viability and locate recipients. [ 213 ] [ 220 ] [ 221 ] [ 222 ]  Heche was considered  legally dead  at that time under California law. [ 223 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4216", "contents": "Police had investigated the crash as a felony DUI collision but said there would be no more investigative efforts after Heche was declared brain-dead. [ 224 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4217", "contents": "On August 14, it was announced that organ recipients had been found and that her body would undergo the organ donation procedure that day. [ 225 ]  To honor her organ donation, hospital staff held an  honor walk  for Heche. [ 226 ]  That evening, her publicist announced that she had been \"peacefully taken off life support.\" The office of the Los Angeles County Medical Examiner-Coroner recorded the cause of death as \" inhalation  and  thermal injuries \", with \" sternal fracture  due to  blunt trauma \" listed as an \"other significant condition\", and ruled her  death an accident . [ 2 ] [ 6 ] [ 227 ] [ 228 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4218", "contents": "On December 6, 2022, the  Los Angeles County Department of Medical Examiner-Coroner  announced the results of Heche's  autopsy , stating that she was not impaired by illicit substances at the time of the incident and that no active drugs were found in her system. An inactive  metabolite  of cocaine was found through a blood test taken when Heche arrived at the hospital, which the coroner's office said indicates the drug was used in the past, but not at the time of the crash.  Cannabinoids  were detected in Heche's urine but not in the blood test, which was consistent with prior use, but not during the time of the incident. Fentanyl was also detected in Heche's system, but it was determined that it was from treatment she received at the hospital. [ 229 ] [ 230 ] [ 231 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4219", "contents": "Heche's  cremated  remains were  interred  in a  mausoleum  at  Hollywood Forever Cemetery [ 232 ]  on May 14, 2023. [ 233 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4220", "contents": "On August 31, 2022, Heche's older son Homer Heche Laffoon filed a  petition  in the  Los Angeles County   probate court  claiming that Heche had died  intestate , asking that he be named her estate's  administrator . Laffoon's lawyer also stated that they wished to have a third party appointed  guardian  ad litem  for Heche's younger son (and Laffoon's half-brother), Atlas Heche Tupper. [ 234 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4221", "contents": "On September 15, Heche's former boyfriend,  James Tupper , filed a petition raising objections to Laffoon's. He argued that an email sent by Heche in 2011 describing her wishes in the event of her death should be treated as her will. [ 235 ] [ 236 ]  Tupper's petition challenged Laffoon's qualifications to administer the estate, claiming that at 20 years of age he lacked the maturity required of an administrator, and that Laffoon's lack of personal assets and income would render him unable to post the required  bond . Tupper concluded that he wished to act as  executor  and hire a professional  fiduciary  to manage the estate. [ 235 ] [ 236 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4222", "contents": "Lynne Mishele, the tenant of the house into which Heche crashed filed lawsuits against Heche's estate, seeking \"compensatory damages\" of $2 million. [ 237 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4223", "contents": "In November 2022, the court appointed Homer Heche Laffoon as general administrator of his mother's estate. [ 238 ]  In early 2024, Laffoon stated the estate cannot pay its debt of over $6 million, including the $2 million in damages sought by Mishele. [ 224 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4224", "contents": "Elem Germanovich Klimov  (Russian:  \u042d\u043b\u0435\u043c \u0413\u0435\u0440\u043c\u0430\u043d\u043e\u0432\u0438\u0447 \u041a\u043b\u0438\u043c\u043e\u0432 ; 9 July 1933 \u2013 26 October 2003) was a Soviet and Russian filmmaker. He studied at the  Gerasimov Institute of Cinematograph , and was married to film director  Larisa Shepitko . Klimov is best known for his final film,  Come and See  ( \u0418\u0434\u0438 \u0438 \u0441\u043c\u043e\u0442\u0440\u0438 ), which follows a teenage boy in  German-occupied Byelorussia  during  World War Two  and which received universal acclaim. His work also includes black comedies, children's movies, and period dramas. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4225", "contents": "Elem Klimov was born in  Stalingrad  into a  Russian  family, to German Stepanovich Klimov, an investigator who worked at the  Central Control Commission of the Communist Party of the Soviet Union , and Kaleria Georgievna Klimova. His parents were staunch communists and his first name was an acronym derived from the names of  Engels ,  Lenin  and  Marx . [ 1 ] [ 2 ] [ 3 ]  Nevertheless, his brother German Klimov stated that his name comes from Elam Harnish \u2014 a character of the  Burning Daylight  novel by  Jack London , since their mother was a fan of his. [ 4 ]  During the  Battle of Stalingrad , he, his mother and his baby brother were evacuated from their home and crossed the  Volga  on a makeshift raft. [ 2 ] [ 3 ]  Klimov would later draw on these experiences for his 1985 film  Come and See . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4226", "contents": "Klimov's first feature film, 1964's  Welcome, or No Trespassing  (known in the United Kingdom as  No Holiday for Inochkin ) was a satire on Soviet  bureaucracy  in the guise of a children's  summer camp  adventure story. The film was briefly banned, having been deemed an insult to the  Communist Party of the Soviet Union ; however, the ban was rescinded after  Nikita Khrushchev  had a private viewing and authorized its release. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4227", "contents": "Klimov's second film,  Adventures of a Dentist  (1965), was a  dark  comedy about a dentist who is derided by his colleagues for his natural talent of painlessly pulling out teeth. The implication, that society inevitably ostracizes those that are gifted, horrified the censors who told Klimov to change it. When Klimov refused, the film was given the lowest classification, \"category three\", which meant that it was shown in only 25\u201378 movie theatres. [ 5 ] [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4228", "contents": "Next, Klimov began making a film about  Grigori Rasputin  called  Agony . The road to release took him nine years and many rewrites. Although finished in 1975, the final edit was not released in the USSR until 1985, due to suppressive measures partly because of its  orgy  scenes and partly because of its relatively nuanced portrait of  Emperor Nicholas II . [ 2 ]  It had been shown in western Europe a few years before. In 1976, Klimov finished a film begun by his teacher  Mikhail Romm  before the latter's death called  And Still I Believe... ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4229", "contents": "In 1979, Klimov's wife  Larisa Shepitko , who recently won the  Golden Bear  at the  Berlin International Film Festival  for her 1977 film  The Ascent , died in a car accident while directing a film based on a novel by  Valentin Rasputin  called  Farewell to Matyora . His wife's death had a profound impact on Klimov, and all his subsequent films were tragedies. A year after her death, Klimov filmed a 25-minute tribute to his wife entitled \"Larisa\" (1980), and subsequently finished directing the film she had started. Despite being shelved for two years after completion,  Farewell  was still released in 1983. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4230", "contents": "Klimov's final film,  Come and See , was released in 1985 to worldwide acclaim [ 1 ]  and won the Golden Prize at the  14th Moscow International Film Festival . [ 3 ] [ 6 ]  The film depicts the experiences of a 15-year-old boy joining the resistance in German-occupied Byelorussia in 1943. Speaking of how the film drew on his own childhood experience of the war, Klimov said, \"As a young boy, I had been in hell... Had I included everything I knew and shown the whole truth, even I could not have watched it.\" [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4231", "contents": "In 1986, fresh from the success of  Come and See , and with the changes brought by  perestroika  in the air, Klimov was chosen by his colleagues to be the First Secretary of the Filmmakers' Union following the  V Congress of the Soviet Filmmakers . According to some critics and filmmakers, the congress was conducted by  Alexander Yakovlev , one of the grey cardinals of perestroika who was unofficially presented there, consulting the activists from time to time. [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4232", "contents": "Klimov's leadership saw the belated release of many of the previously banned films and the reinstatement of several directors who had fallen out of political favor. [ 3 ]  This period is widely considered as the start of decline of Soviet cinema and the rise of the so-called \" chernukha \u00a0[ ru ] \" (roughly \"black stuff\"), works of artists and journalists, who, freed by  glasnost , exposed Soviet reality in the most pessimistic possible light. Klimov was still frustrated by the obstacles that still remained in his way and gave up his post in 1988 to  Andrei Smirnov , saying that he wanted to make films again. Klimov completed no more films after  Come and See . While he had plans to make more films in the late 1980s, he said in 2000 that he had \"lost interest in making films. Everything that was possible I felt I had already done.\" [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4233", "contents": "In 1957, Klimov graduated from the Higher Institute of Aviation in Moscow. [ 1 ] [ 2 ]  He considered a career in journalism before settling on cinema. [ 3 ]  He enrolled at the state film school, the Gerasimov Institute of Cinematography, where he studied under acclaimed director  Efim Dzigan . [ 1 ] [ 2 ]  While a student at the institute, Klimov met  Larisa Shepitko , whom he would later marry. [ 2 ]  Their son Anton was born in 1973."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4234", "contents": "In 1983, he was a member of the jury at the  33rd Berlin International Film Festival . [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4235", "contents": "He died on 26 October 2003 from  brain hypoxia , after six weeks in a coma. [ 2 ]  He was buried at the  Troyekurovskoye Cemetery . [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4236", "contents": "The  execution of Alan Eugene Miller  (January 20, 1965 \u2013 September 26, 2024) took place in the U.S. state of  Alabama  by  nitrogen hypoxia . It was the second execution in both the world and state to use this particular method, following the  execution of Kenneth Eugene Smith  in January 2024. [ 2 ]  Miller was convicted of the August 1999 murders of three men in  Pelham, Alabama , and was sentenced to death in 2000. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4237", "contents": "On August 5, 1999, Miller, armed with a  .40-caliber   Glock  pistol, [ 4 ]  shot and killed two of his co-workers, 32-year-old Lee Holdbrooks and 28-year-old Christopher Yancy, at a heating and air-conditioning distributor, then drove five miles to a business where he had previously worked and shot and killed his former supervisor, 39-year-old Terry Jarvis. [ 5 ] [ 6 ]  Holdbrooks was shot six times, Yancy was shot three times, and Jarvis was shot five times. [ 7 ]  After the shooting, Miller drove off, only to be pulled over later that day on the side of an Alabama highway after being spotted by police. It required four officers and four sets of handcuffs to subdue him. [ 8 ]  According to trial testimony, Miller's supposed motive behind the murders was that he believed the men were spreading rumors about him being  gay . [ 3 ]  A psychiatrist hired by Miller's defense found he suffered from severe mental illness. [ 9 ]  At the time of the shootings, he was employed as a delivery truck driver at Ferguson Enterprises in Pelham. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4238", "contents": "Miller was scheduled to be executed via  lethal injection  on September 22, 2022, but his execution was called off after prison staff failed to establish intravenous access to deliver a lethal injection. [ 9 ] [ 11 ]  It was concluded they would not be able to complete the execution by the midnight deadline. [ 9 ]  Miller filed a federal lawsuit following the failed execution attempt. [ 12 ]  In November 2022, the state of Alabama agreed it would not use lethal injection to execute Miller and would instead use nitrogen gas. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4239", "contents": "Miller was executed by nitrogen hypoxia at the  Holman Correctional Facility  in  Atmore, Alabama , on September 26, 2024. [ 2 ]  He was pronounced dead at 6:38\u00a0p.m. local time. [ 13 ] [ 14 ]  For his  last meal  he had a hamburger steak, a baked potato, and french fries. [ 15 ]  His final words were, \"I didn't do anything to be in here.\" [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4240", "contents": "It marked the second time that Alabama executed a condemned inmate using nitrogen hypoxia following the  execution of Kenneth Eugene Smith  in January 2024. [ 2 ] [ 16 ] [ 17 ]  According to witness Lauren Gill, \"Miller visibly struggled for roughly two minutes, shaking and pulling at his restraints. He then spent the next 5-6 min intermittently gasping for air.\" [ 18 ]  Alabama Corrections Commissioner John Q. Hamm said the shaking movements were anticipated. \"Just like in [Kenneth Eugene] Smith we talked about there is going to be involuntarily body movements as the body is depleted of oxygen. So that was nothing we did not expect,\" Hamm said, explaining the nitrogen gas flowed for 15 minutes. \"Everything went according to plan and according to our protocol.\" [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4241", "contents": "Miller's execution was the 1,600th execution in the United States since the resumption of executions in 1976. [ 20 ]  He was the last of five inmates to be executed across the United States in the span of one week, the most inmates executed within a week since  July 2003 . [ 20 ]  The others were  Freddie Eugene Owens  in South Carolina on September 20,  Marcellus Williams  in Missouri and  Travis Mullis  in Texas on September 24, and  Emmanuel Littlejohn  in Oklahoma on the morning of September 26. [ 20 ] [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4242", "contents": "Viktor Ivanovich Patsayev  ( Russian :  \u0412\u0438\u043a\u0442\u043e\u0440 \u0418\u0432\u0430\u043d\u043e\u0432\u0438\u0447 \u041f\u0430\u0446\u0430\u0435\u0432 ; 19 June 1933\u00a0\u2013 30 June 1971) [ 1 ]  was a Soviet  cosmonaut  who flew on the  Soyuz 11  mission and was part of the third space crew to  die during a space flight . On board the space station  Salyut 1  he operated the Orion 1 Space Observatory (see  Orion 1 and Orion 2 Space Observatories ); he became the first man to operate a telescope outside the Earth's atmosphere."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4243", "contents": "After a normal  re-entry , the capsule was opened and the crew was found dead. [ 2 ]  It was discovered that a valve had opened just prior to leaving orbit that had allowed the capsule's atmosphere to  vent away into space , suffocating the crew. [ 3 ]  One of Patsayev's hands was found to be bruised, and he may have been trying to shut the valve manually at the time he lost consciousness."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4244", "contents": "Patsayev's ashes were interred in the  Kremlin Wall  on  Red Square  in Moscow. [ 4 ]  He was posthumously awarded the title of  Hero of the Soviet Union , the  Order of Lenin  and the title of  Pilot-Cosmonaut of the USSR . The lunar crater  Patsaev  and the minor planet  1791 Patsayev  are named for him. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4245", "contents": "An account of Patsayev's life and space career appears in the 2003 book  Fallen Astronauts: Heroes Who Died Reaching for the Moon  by  Colin Burgess ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4246", "contents": "Joan Alexandra Molinsky [ 1 ]  (June 8, 1933 \u2013 September 4, 2014), known professionally as  Joan Rivers , was an American comedian, actress, producer, writer, and television host. She was noted for her blunt, often controversial comedic persona that was heavily self-deprecating and acerbic, especially towards celebrities and politicians, delivered in her signature  New York accent . She is considered a pioneer of women in comedy. [ 2 ] [ 3 ]  She received an  Emmy Award  and a  Grammy Award , as well as nomination for a  Tony Award ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4247", "contents": "Rivers started her career in  comedy clubs  in  Greenwich Village  alongside her peers  George Carlin ,  Woody Allen , and  Richard Pryor . [ 4 ]  She then rose to prominence in 1965 as a guest on  The Tonight Show . Hosted by her mentor,  Johnny Carson , the show established Rivers's comedic style. In 1986, with her own rival program,  The Late Show with Joan Rivers , Rivers became the first woman to host a late night network television talk show. She subsequently hosted  The Joan Rivers Show  (1989\u20131993), winning a  Daytime Emmy  for Outstanding Talk Show Host.  From the mid-1990s, she became known for her comedic  red carpet  awards show celebrity interviews. [ 5 ] [ 6 ]  Rivers co-hosted the  E!  celebrity fashion show  Fashion Police  from 2010 to 2014 and starred in the reality series  Joan & Melissa: Joan Knows Best?  (2011\u20132014) with daughter  Melissa Rivers ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4248", "contents": "In addition to marketing a line of jewelry and apparel on the  QVC  shopping channel, Rivers authored 12 best-selling books and three LP comedy albums under her own name:  Mr. Phyllis and Other Funny Stories  (Warner Bros 1965),  The Next to Last Joan Rivers Album  (Buddah 1969), and  What Becomes a Semi-Legend Most?  (Geffen 1983).  She was nominated in 1984 for a  Grammy Award  for her album  What Becomes a Semi-Legend Most?  and was nominated in 1994 for the  Tony Award for Best Actress in a Play  for her performance of the title role in  Sally Marr  ... and Her Escorts . In 2009, Rivers competed alongside her daughter Melissa on the  second season  of  The Celebrity Apprentice , ultimately winning the season. In 2015, Rivers posthumously received a  Grammy Award for Best Spoken Word Album  for her book,  Diary of a Mad Diva . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4249", "contents": "In 1968,  The New York Times  television critic  Jack Gould  called Rivers \"quite possibly the most intuitively funny woman alive\". [ 8 ] [ 9 ]  In 2017,  Rolling Stone  magazine ranked her sixth on its list of the 50 best stand-up comics of all time, [ 10 ]  and in October the same year, she was inducted into the  Television Academy Hall of Fame . She is the subject of the documentary  Joan Rivers: A Piece of Work  (2010)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4250", "contents": "Joan Alexandra Molinsky was born on June 8, 1933, in  Brooklyn , New York, [ 11 ] [ 12 ] [ 13 ]  to  Russian Jewish  immigrants Beatrice (n\u00e9e Grushman) and Meyer C. Molinsky, a doctor. [ 13 ] [ 14 ]  She had an elder sister named Barbara Waxler. [ 15 ] [ 16 ] [ 17 ]  Rivers spent her early life in  Prospect Heights [ 18 ]  and  Crown Heights [ 19 ]  in Brooklyn. At the age of eight, she created her first alter ego,  J. Sondra Meredith . [ 20 ] [ 21 ] [ 22 ]  She attended the  Brooklyn Society for Ethical Culture  School, a progressive and now-defunct school, and  Adelphi Academy  of Brooklyn, a college preparatory day school, where she was co-chair of her school, due to her past experiences in theatrical activities. Within two years, she performed in the School  Cavalcades , and in 1949, aged 16, she was vice president of the Dramatic Club. [ 23 ]  She graduated from the Adelphi Academy of Brooklyn, in 1951, at 18. In her adolescence, Rivers relocated with her family to  Larchmont , north of New York City. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4251", "contents": "Rivers  matriculated  at  Connecticut College ; it was a family legacy to attend the institution, as her sister had done. [ 24 ]  Rivers has stated in interviews that she was  overweight  throughout her childhood, adolescence and in college, [ 20 ]  and that it had a profound impact on her  body image , which she struggled with throughout her life. [ 25 ]  After two years, she transferred to  Barnard College , where she graduated in 1954 with a  B.A.  in  English literature  and  anthropology ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4252", "contents": "Rivers repeatedly said, and it was reported in  The Washington Post , [ 12 ]  that she graduated  summa cum laude  and as a member of  Phi Beta Kappa ; [ 13 ]  however, biographers James Spada and Leslie Bennetts found that these were fabrications, as with other statements such as sharing a lesbian kiss in a play with  Barbra Streisand  (they did both appear in a play named  Driftwood , but were never on stage at the same time). [ 26 ] [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4253", "contents": "Before entering show business, Rivers worked at various jobs such as a tour guide at  Rockefeller Center , [ 28 ]  a writer/proofreader at an advertising agency [ 29 ]  and a fashion consultant at  Bond Clothing Stores . [ 13 ] [ 30 ]  During this period, agent Tony Rivers advised her to change her name, so she chose Joan Rivers as her stage name. [ 31 ]  She stated that he stopped sending her to audition because of this. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4254", "contents": "During the late 1950s, Rivers appeared in a short  off-Broadway  play called  Driftwood  alongside  Barbra Streisand . According to an interview with  Adweek , the play ran for six weeks at the playwright Maurice Tei Dunn's apartment on 49th Street in New York. [ 33 ] [ 27 ]  In the early 1960s, Rivers performed at various comedy clubs in  Greenwich Village , including  The Bitter End ,  The Gaslight Cafe [ 34 ]  and  The Duplex . It was during this period that she befriended fellow comedians  Woody Allen  and  George Carlin , often sharing meals with them. Rivers also had the opportunity to work alongside renowned musicians  Bob Dylan ,  Barbra Streisand ,  Carly Simon , and  Simon & Garfunkel  in the Village. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4255", "contents": "Between 1963 and 1964, Rivers joined forces with Jim Connell and  Jake Holmes  in the  cabaret  act \"Jim, Jake & Joan\". Their appearance at The Bitter End in 1964 led to their inclusion in the motion picture  Once Upon A Coffee House , marking Rivers' first credit in a  feature film . However, the group disbanded soon after. Holmes later recalled an incident that led to their separation: \"We were supposed to perform at a rally for  Bobby Kennedy , who was  running for New York senator in 1964 . Joan showed up wearing a [Republican Senate nominee Kenneth]  Keating  button, and Jim told her to remove it. She refused, staunchly sticking to her political beliefs, and Jim said, 'Who needs you, anyway?' That was the end of Jim, Jake & Joan...\" [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4256", "contents": "Rivers also made a guest appearance on  The Tonight Show , hosted by  Jack Paar , [ 37 ]  which originated in New York. In 1965, she worked as a gag writer and participant on  Candid Camera , where she played the role of \"the bait\" to lure people into humorous situations for the show. After seven auditions over three years, she finally made her first appearance on  The Tonight Show  with its new host,  Johnny Carson , on February 17, 1965. [ 38 ]  Rivers considered this episode to be her breakthrough, as Carson famously told her, \"you're gonna be a star.\" [ 39 ]  She became a frequent guest on the show and developed a close friendship with Carson."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4257", "contents": "Her profile skyrocketed in the following years, and she began to make frequent guest appearances on popular shows like  The Ed Sullivan Show ,  The Mike Douglas Show ,  The Dick Cavett Show , and  Girl Talk  with  Virginia Graham . She even wrote material for the  puppet  mouse  Topo Gigio . In addition, she had a small role in the cult drama film  The Swimmer  (1968), alongside  Burt Lancaster . Around the same time, she hosted a short-lived  syndicated  daytime  talk show  called  That Show with Joan Rivers , which premiered on September 16, 1968. Each episode had a unique theme, and Rivers opened with a monologue related to that day's topic, then hosted celebrity interviews. [ 40 ] [ 41 ]  The show also featured an expert on the subject and a celebrity guest. Early episodes featured prominent figures such as Johnny Carson,  Jerry Lewis ,  Joel Grey ,  Don Rickles , and  Godfrey Cambridge . [ 42 ]  During the mid-1960s, she released at least two  comedy albums :  The Next to Last Joan Rivers Album  and  Rivers Presents Mr. Phyllis & Other Funny Stories . [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4258", "contents": "By the 1970s, Rivers continued to be a prominent fixture on television. Along with her other guest-spots on the late-night circuit, she also made appearances on  The Carol Burnett Show , had a semi-regular stint on  Hollywood Squares  and guest-starred on  Here's Lucy . Rivers made her Broadway debut in the play  Fun City,  which opened on January 2, 1972, and co-starred  Gabriel Dell ,  Rose Marie  and  Paul Ford . It ran for only nine performances amid a negative critical reception. Though a  New York Times  reviewer criticized the production as \"frenetic to the point of being frazzled,\" he praised Rivers as \"a deft comedy writer\" and \"a very funny lady\". [ 44 ]  From 1972 to 1976, she narrated  The Adventures of Letterman , an animated segment for  The Electric Company ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4259", "contents": "In 1973, Rivers co-wrote the made-for-television movie  The Girl Most Likely To... , [ 20 ]  a black comedy starring  Stockard Channing  as an ugly girl who becomes beautiful after undergoing plastic surgery, and takes revenge on people who previously mistreated her. The film, based on Rivers' story, [ 20 ]  became a ratings success and has been considered a \" cult classic \". [ 45 ]  She also wrote a thrice-weekly column for  The Chicago Tribune  from 1973 to 1976, and published her first book,  Having a Baby Can Be a Scream , in 1974; she described it as a \"catalogue of gynaecological anxieties\". [ 46 ]  In 1978, Rivers made her directorial debut [ 47 ]  with the comedy  Rabbit Test , which she also wrote and which starred her friend  Billy Crystal  in his film debut as the world's first pregnant man. The film earned 12 million dollars at the box office. [ 48 ]   Janet Maslin  of  The New York Times  concluded: \"Miss Rivers has turned to directing without paying much heed to whether a whole movie constructed from one-liners is worth even the sum of its parts.\" [ 49 ]  During the same decade, she was the opening act for singers  Helen Reddy ,  Robert Goulet ,  Paul Anka ,  Mac Davis , and  Sergio Franchi  on the  Las Vegas Strip . [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4260", "contents": "During the early and mid-1980s, Rivers found further success in stand-up and television, though the decade subsequently proved to be controversial for her. The year 1983, in particular, was very successful; she performed at  Carnegie Hall  in February, [ 51 ]  did the March stand-up special  An Audience with Joan Rivers , hosted the April 9 episode of  Saturday Night Live , and released the best-selling comedy album  What Becomes a Semi-Legend Most? , which reached No. 22 on the U.S.  Billboard  200  and was nominated for a  Grammy Award for Best Comedy Album . [ 52 ]  By August 1983, Carson established Rivers as his first permanent guest host on  The Tonight Show . At the time, she spoke of her primary  Tonight Show  life as having been \"Johnny Carson's daughter\", a reference to his longtime mentoring of her. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4261", "contents": "During the 1980s and 1990s, Rivers served on the advisory board of the  National Student Film Institute . [ 53 ] [ 54 ]  A friend of  Nancy Reagan , Rivers attended a  state dinner  in 1983, and later performed at a luncheon at the  1984 Republican National Convention . [ 55 ]  In 1984, Rivers published a best-selling humor book,  The Life and Hard Times of Heidi Abramowitz , a mock memoir of her brassy, loose comedy character, which was mostly jokes about promiscuity \u2013 of a type that would have been considered unacceptable even in  burlesque  a generation earlier. A television special based on the character, a mock tribute called  Joan Rivers and Friends Salute Heidi Abramowitz: Tramp of the Century , later aired on  Showtime . [ 56 ]  She later wrote her next book,  Enter Talking , which was released in 1986, and described her rise to stardom and the evolution of her comedic persona. [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4262", "contents": "In 1986, the move came that ended Rivers' longtime friendship with Johnny Carson. The soon-to-launch  Fox Television Network  announced that it was giving her a late night talk show,  The Late Show Starring Joan Rivers , making Rivers the first woman to have her own late-night talk show on a major network. [ 58 ] [ 59 ]  The new network planned to broadcast the show 11 p.m. to midnight  Eastern Time , making her a Carson competitor. Carson learned of the show from Fox and not from Rivers. In the documentary  Johnny Carson: King of Late Night , Rivers said that she only called Carson to discuss the matter after learning that he may have already heard about it and that he immediately hung up on her. \"And he never spoke to me again.  He took it as a complete betrayal,\" said Joan. In the same interview, she said that she later came to believe that maybe she should have asked for his blessing before taking the job. Rivers was banned from ever appearing on  The Tonight Show  for the rest of Carson's tenure and the entire runs of Carson's first two successors  Jay Leno  and  Conan O'Brien  out of respect for Carson. Rivers did not appear on  The Tonight Show  again until February 17, 2014, at the age of 80, when she made a brief appearance on new host  Jimmy Fallon 's first episode. [ 60 ]  On March 27, 2014, Rivers returned to the show for an interview."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4263", "contents": "The Late Show Starring Joan Rivers  premiered on October 9, 1986, but Rivers' tenure was short-lived. When Rivers challenged Fox executives, who wanted to fire her husband  Edgar Rosenberg  as the show's producer, the network fired them both on May 15, 1987."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4264", "contents": "On August 14, 1987, Rosenberg committed suicide in Philadelphia; Rivers blamed the tragedy on his \"humiliation\" by Fox. Shortly after Rosenberg's suicide the magazine  GQ  published what was purported to be an interview with Rivers, written by \"Bert Hacker\". The piece quoted Rivers saying terrible things about her dead spouse. One quote was \"Listen, when I think of the way he makes me crazy, I really wonder if they didn't execute the wrong  Rosenbergs .\" In fact, Bert Hacker was a pseudonym used by former Nixon speechwriter and sometime comic  Ben Stein , who had never met Rivers and simply made up the entire account. Rivers sued Stein for  libel  and won an undisclosed amount which was distributed to charities she designated. [ 61 ] [ 62 ]  Rivers credited Nancy Reagan with helping her after her husband's suicide. [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4265", "contents": "During the airing of her late-night show, Rivers made the voice-over role of Dot Matrix in the science-fiction comedy  Spaceballs  (1987), a parody based (mainly) on  Star Wars . The film, directed and co-starring  Mel Brooks , was a critical and commercial success, later becoming a \"cult classic\". [ 64 ]  After the Fox controversy, her career went into hiatus. Rivers subsequently appeared on various television shows, including the  Pee-wee's Playhouse  Christmas Special  in December 1989. She also appeared as one of the center square occupants on the 1986\u201389 version of  The  Hollywood Squares , hosted by  John Davidson . On September 5, 1989,  The Joan Rivers Show ,  her daytime television program, premiered in  broadcast syndication . The show, which ran for five seasons, was a success and earned Rivers the  Daytime Emmy  in 1990 for Outstanding Talk Show Host. [ 65 ]   Entertainment Weekly ,  in a September 1990 article, asserted: \" The Joan Rivers Show  is a better showcase for her funny edginess than her doomed 1988 Fox nighttime program was. The best thing about her daytime talker is that Rivers'  stream-of-consciousness  chattiness is allowed to guide the show \u2014 you never know where the conversation is going to go.\" [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4266", "contents": "In addition to winning the Emmy for  The Joan Rivers Show , Rivers starred in the made-for-television comedy  How to Murder a Millionaire , which premiered in May 1990 on  CBS . In the film, co-starring  Alex Rocco  and  Telma Hopkins , she took on the role of a  Beverly Hills  matron possessed with the idea her husband is trying to kill her. [ 67 ]  Also in 1990, she started to design jewelry, clothing and beauty products for the shopping channel  QVC . On this professional endeavor, Rivers said: \"In those days, only dead celebrities went on [QVC]. My career was over. I had bills to pay. ... It also intrigued me at the beginning\". [ 68 ]  The sales of Rivers' products exceeded $1 billion by 2014, making her one of the network's top sellers. [ 69 ]  In 1991, she wrote her next book,  Still Talking , which described the cancellation of her late-night show and her husband's suicide. [ 70 ]  Until 1993, she received five additional Emmy nominations for her daytime talk-show  The Joan Rivers Show  \u2014 two for Outstanding Writing \u2013 Special Class and three for Outstanding Talk Show Host. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4267", "contents": "In 1994, Rivers and daughter  Melissa  first hosted the  E!  Entertainment Television pre-awards show for the  Golden Globe Awards [ 71 ]  and, beginning in 1995, E!'s annual  Academy Awards  pre-awards show as well. [ 71 ]  Rivers and her daughter quickly became credited for revolutionizing the  red carpet  as a space to showcase designers' work and celebrity interactions. \"Joan and Melissa were the first people who came out and made it more of a true conversation between star and reporter\", E!'s Senior Vice President of production, Gary Snegaroff, remarked to  Vanity Fair . \"They asked about what [actresses] were wearing because that's what the magazines would cover after the fact, and turned it into a candid conversation on the carpet where anything could happen\". [ 72 ]  Rivers and Melissa, at the time, both portrayed themselves in the made-for-television drama  Tears and Laughter: The Joan and Melissa Rivers Story , which chronicled the aftermath of Rosenberg's suicide. It aired on  NBC  on May 15, 1994. [ 73 ]  The next year, she wrote her book  Jewelry by Joan Rivers . [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4268", "contents": "Influenced by the stand-up comedy of  Lenny Bruce , Rivers co-wrote and starred in a play about Bruce's mother  Sally Marr , who was also a comic and influenced her son's development as a comic. After 27 previews,  Sally Marr\u00a0... and Her Escorts,  a play \"suggested by the life of Sally Marr\" ran on Broadway for 50 performances in May and June 1994. [ 75 ]  The production received mixed reviews, but her performance was applauded by critics.  The  Chicago Sun Times  found Rivers to be \"compelling\" as an actress [ 76 ]  while  The New York Times  wrote: \"... [S]he is exuberant, fearless and inexhaustible. If you admire performers for taking risks, then you can't help but applaud her efforts\". [ 77 ]  Rivers was nominated for a  Drama Desk Award  as Outstanding Actress in a Play and a  Tony Award  for Best Actress in a Play for playing Marr. [ 78 ]  Beginning in March 1997, Rivers hosted her own radio show on  WOR  in New York City for several years, [ 79 ]  and wrote three self-help books:  Bouncing Back: I've Survived Everything ... and I Mean Everything ... and You Can Too!  in 1997, [ 80 ]   From Mother to Daughter: Thoughts and Advice on Life, Love and Marriage  in 1998, [ 81 ]  and  Don't Count the Candles: Just Keep the Fire Lit! , in 1999. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4269", "contents": "Rivers was a guest speaker at the opening of the American Operating Room Nurses' San Francisco Conference in 2000, and by the first part of the decade, she continued to host the awards' red carpet for the  E!  channel. Between 2002 and 2004, she embarked on tour with her one-person comedy show  Joan Rivers: Broke and Alone , which was presented in the United Kingdom ( Edinburgh  and London) and in the United States (Los Angeles, and  Boston ), to generally positive reviews. [ 83 ]   The Telegraph  felt that her \"hilarious assaults on fellow celebrities and tirades about the perils of ageing and plastic surgery are well worth the expense\", [ 84 ]  while  The Guardian  remarked that \"Rivers returned triumphant, a victorious heavyweight after a great fight, conscious that she is still the champion\". [ 85 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4270", "contents": "In 2003, Rivers left the network red-carpet show for a three-year contract (valued at $6\u20138 million) to cover award shows' red carpet events for the  TV Guide Channel . [ 86 ]  Meanwhile, Rivers guest-starred as herself in several television series, including  Curb Your Enthusiasm ,  Nip/Tuck , and  Boston Legal , [ 87 ] [ 88 ] [ 89 ]  and also voiced herself for a brief scene in the 2004 animated fantasy film  Shrek 2 . [ 90 ]  In 2004, Rivers was part of the formal receiving party when  Ronald Reagan  was placed  in state  at the  United States Capitol . [ 91 ] [ 92 ]  On December 3, 2007, Rivers performed at the 79th Royal Variety Show at the  Liverpool Empire Theatre , England, with  Queen Elizabeth II  and  Prince Philip  present. [ 93 ]  She wrote and starred in the play  Joan Rivers: A Work in Progress by a Life in Progress , which was directed by  Sean Foley , and presented through 2008 at the  Geffen Playhouse  in Los Angeles, the  Edinburgh Festival Fringe  and the  Leicester Square Theatre , to a mixed critical reception. [ 94 ] [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4271", "contents": "In 2008, Rivers was invited to take part in a comedy event celebrating  Prince Charles ' 60th Birthday titled,  We Are Most Amused . She was the only American alongside  Robin Williams  invited to take part in the event. Other comedians included  John Cleese , who served as the master of ceremonies,  Eric Idle ,  Rowan Atkinson , and  Bill Bailey . Those in attendance included  Prince Charles ,  Camilla, Duchess of Cornwall  and  Prince Harry ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4272", "contents": "Throughout the decade, Rivers often appeared in various television game shows, including  8 Out of 10 Cats ,  Big Brother: Celebrity Hijack , and  Celebrity Family Feud , in which she competed with her daughter against  Ice-T  and  Coco . In 2009, Rivers and daughter Melissa were contestants on season eight of  Celebrity Apprentice . During the season, each celebrity raised money for a charity of his or her choice; Rivers selected God's Love We Deliver. [ 96 ]  After a  falling out  with poker player  Annie Duke , following Melissa's on-air firing (elimination) by Donald Trump, Rivers left the  green room  telling  Clint Black  and  Jesse James  that she would not be in the next morning. Rivers later returned to the show and on May 3, 2009, she became a finalist in the series. The other finalist was Duke. [ 97 ] [ 98 ]  On the season finale, which aired live on May 10, Rivers was announced the winner and hired to be the 2009 Celebrity Apprentice."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4273", "contents": "Also in 2009, Rivers was a special \"pink-carpet\" presenter for the broadcast of the  Sydney Gay and Lesbian Mardi Gras  parade, was  roasted  in a  Comedy Central special , and her reality show,  How'd You Get So Rich? , premiered on  TV Land . The program, which ran for two seasons, followed Rivers traveling around the United States interviewing self-made millionaires. [ 99 ]  She also wrote two books in 2009:  Murder at the Academy Awards (R): A Red Carpet Murder Mystery  and  Men Are Stupid ... And They Like Big Boobs: A Woman's Guide to Beauty Through Plastic Surgery (with Valerie Frankel) ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4274", "contents": "A documentary film about Rivers,  Joan Rivers: A Piece of Work , premiered at the  Sundance Film Festival  on January 25, 2010. [ 100 ] \nThe film follows Rivers for 14 months, mostly during the 76th year of her life, [ 101 ]  and made an effort to \"[peel] away the mask\" and expose the \"struggles, sacrifices and joy of living life as a ground breaking female performer\". [ 102 ]  The film was released in a  limited release  on June 11, 2010, and was acclaimed by critics for providing \"an honest, behind-the-scenes look at [Rivers]' career \u2014 and at show business in general\". [ 103 ]  Beginning on September 10, 2010, Rivers co-hosted the  E!  show  Fashion Police , along with  Giuliana Rancic ,  Kelly Osbourne , and  George Kotsiopoulos , commenting on celebrity fashion. The show started as a half-hour program but due to its success with viewers, it was expanded to one hour on March 9, 2012. The August 26, 2014 episode of  Fashion Police , about the  66th Primetime Emmy Awards  and the 2014  MTV Movie Awards , was her last television appearance before her death. [ 104 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4275", "contents": "In 2011, Rivers appeared in a commercial for  Go Daddy , which debuted during the broadcast of  Super Bowl XLV , [ 105 ]  and was featured as herself in the season two episode of  Louis C.K. 's self-titled show  Louie  entitled \" Joan \", where she performed on stage and gave C.K. comedy advice.  The A.V. Club ' s  Nathan Rabin  described the episode as a \"funny and deeply moving exploration of the existential dilemma of the stand-up comic and a valentine to the artform.\" Also in 2011, Rivers and her daughter starred in the reality show  Joan & Melissa: Joan Knows Best? , which premiered on  WE tv . The series follows her moving in with her daughter to California to be closer to her family. The show ran for four seasons until 2014. On the December 4, 2011 episode of  The Simpsons , \" The Ten-Per-Cent Solution \", Rivers took on the role of Annie Dubinsky, an agent trying to revive  Krusty 's career. [ 106 ]  Hayden Childs of  The A.V. Club  praised the choice of having Rivers guest star since she was able to \"employ her trademark humor within the world of  The Simpsons  without hijacking the plot or satire\". [ 107 ]  In 2012, she guest-starred in two episodes of two series:  Drop Dead Diva  and  Hot in Cleveland ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4276", "contents": "Rivers released her 11th book  I Hate Everyone...Starting with Me  on June 5, 2012. It received generally positive reviews and made  The New York Times  Best Seller list  for several weeks.  The New York Times  remarked that there were \"more punch lines per paragraph than any book I've read in years\", [ 108 ]  and  Publishers Weekly  felt that \"Rivers is equally passionate and opinionated on every subject she discusses. Hilarious and undeniably original\". [ 109 ]  On August 7, 2012, Rivers showed up in  Burbank, California  to protest that the warehouse club  Costco  would not sell the book. She handcuffed herself to a shopping cart and shouted through a megaphone. The police were called to the scene and she left without incident; no arrests were made. [ 110 ]  On March 5, 2013, she launched the online talk show  In Bed with Joan  on YouTube. In it, Rivers invited a different guest to talk to her in bed about different things including their past, their love life and their career."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4277", "contents": "Rivers released her 12th book,  Diary of a Mad Diva , on July 1, 2014, which also made  The NY Times  Best Seller list. [ 111 ]  For the book, she posthumously won the  Grammy Award for Best Spoken Word Album  in 2015. Before her death, she filmed a part, along with other female comedians, for the documentary  Makers: Women in Comedy , which premiered on PBS in October 2014. [ 112 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4278", "contents": "He was an epiphany. Lenny told the truth. It was a total affirmation for me that I was on the right track long before anyone said it to me. He supplied the revelation that personal truth can be the foundation of comedy, that outrageousness can be cleansing and healthy. It went off inside me like an enormous flash."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4279", "contents": "During her 55-year career as a comedian, her tough-talking style of satirical humor was both praised and criticized as truthful, yet too personal, too gossipy, and very often abrasive. Nonetheless, with her ability to \"tell it like it is\", she became a pioneer of contemporary stand-up comedy. Commenting about her style, she told biographer  Gerald Nachman , \"Maybe I started it. We're a very gossipy culture. All we want to know now is private lives.\" [ 114 ]  However, her style of humor, which often relied on making jokes about her own life and  satirizing  the lives of celebrities and public figures, was sometimes criticized as insensitive. Her jokes about  Elizabeth Taylor  and  Adele 's weight, for instance, were often commented on, although Rivers would never apologize for her humor. [ 115 ] [ 116 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4280", "contents": "Rivers, who was Jewish, was also criticized for making jokes about  the Holocaust  and later explained, \"This is the way I remind people about the Holocaust. I do it through humor\", adding, \"my husband lost his entire family in the Holocaust.\" [ 117 ]  Her joke about the victims of the  Ariel Castro kidnappings  similarly came under criticism, but she again refused to apologize, [ 118 ]  stating, \"I know what those girls went through. It was a little stupid joke.\" [ 119 ]  She received multiple death threats throughout her career. [ 120 ]  Rivers accepted such criticism as the price of using social satire as a form of humor: \"I've learned to have absolutely no regrets about any jokes I've ever done\u00a0... You can tune me out, you can click me off, it's OK. I am not going to bow to  political correctness . But you do have to learn, if you want to be a satirist, you can't be part of the party.\" [ 121 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4281", "contents": "As an unknown stand-up comedian out of college, she struggled for many years before finding her comic style. She did stints in the  Catskills  and found that she disliked the older style of comedy at the time, such as  Phyllis Diller 's, who she nevertheless felt was a pioneer female comedian. [ 122 ]  Her breakthrough came at  The Second City  in Chicago in 1961, where she was dubbed \"the best girl since  Elaine May \", who also got her start there. But May became her and fellow comedian  Treva Silverman 's role model, as Rivers saw her as \"an assertive woman with a marvelous, fast mind and, at the same time, pretty and feminine\". [ 122 ]  It was also there that she learned \"self reliance\", she said, \"that I didn't have to talk down in my humor\" and could still earn an income by making intelligent people laugh. \"I was really born as a comedian at Second City. I owe it my career.\" [ 123 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4282", "contents": "In early 1965, at the suggestion of comedian  Bill Cosby , Johnny Carson gave Rivers, whom he billed as a comedy writer, her debut appearance on his show. [ 124 ] [ 125 ]  Cosby, who knew Rivers from their early stand-up days, described her as \"an intelligent girl without being a weirdo...a human being, not a kook.\" [ 126 ]  Sitting alongside Johnny after her monologue, she displayed an intimate, conversational style which he appreciated, and she was invited back eight more times that year. [ 124 ]   Time  magazine compared her humor to that of  Woody Allen , by expressing \"how to be neurotic about practically everything\", but noting that \"her style and femininity make her something special.\" Rivers also compared herself to Allen, stating: \"He was a writer, which I basically was...and talking about things that affected our generation that nobody else talked about.\" [ 126 ]   The New York Times  critic  Charles L. Mee  likewise compared her to Allen, explaining that her \"style was personal, an autobiographical  stream-of-consciousness \". [ 124 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4283", "contents": "According to biographer  Victoria Price , Rivers' humor was notable for taking aim at and overturning what had been considered acceptable female behavior. She broke through long-standing taboos in humor, which paved the way for other women, including  Roseanne Barr ,  Ellen DeGeneres  and  Rosie O'Donnell . [ 127 ]  Rivers became closely associated with her  catchphrase : \"Can we talk?\". [ 128 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4284", "contents": "Rivers was one of only four Americans invited to the  Wedding of Prince Charles and Camilla Parker Bowles  on April 9, 2005. [ 129 ]  Rivers was licensed to carry a gun in New York City. She was threatened with the loss of the license after an altercation with a car rental clerk in 2002. [ 130 ]  She was a registered  Republican . [ 131 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4285", "contents": "Rivers' first marriage was in 1956 to James Sanger, the son of a  Bond Clothing Stores  merchandise manager. [ 13 ] [ 132 ]  The marriage lasted six months [ 13 ] [ 133 ]  and was annulled on the basis that Sanger did not want children and had not informed Rivers before the wedding. [ 134 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4286", "contents": "Rivers married  Edgar Rosenberg  on July 15, 1965. [ 135 ]  Their only child,  Melissa Rivers , was born on January 20, 1968. Joan Rivers had one grandson, Cooper, born Edgar Cooper Endicott in 2000. [ 136 ]  Along with his mother and grandmother, Cooper was featured in the  WE tv  series  Joan & Melissa: Joan Knows Best? [ 137 ]  Rivers was married to Rosenberg until his suicide in 1987, four days after she asked him for a separation. [ 138 ] [ 139 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4287", "contents": "In a 2012 interview with  Howard Stern , Rivers said she had several extramarital affairs when married to Rosenberg, including a one-night stand with actor  Robert Mitchum  in the 1960s and an affair with actor  Gabriel Dell . [ 140 ]  In the 1990s, she was in an eight-year relationship with the commissioner of the  New York State Office of Parks and Recreation , disabled World War II veteran  Orin Lehman  of the  Lehman family . [ 141 ] [ 142 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4288", "contents": "In her book  Bouncing Back , Rivers described how she developed  bulimia nervosa  after Rosenberg's 1987 suicide, and the subsequent death of her  psychologist , with whom she had developed a close friendship, of an AIDS related illness. [ 25 ]  Additionally, Rivers' relationship with her daughter had been strained at the time, as Melissa blamed her for her father's death. According to Rivers, the confluence of events resulted in her contemplating suicide in her California home. [ 25 ]  \"I got the gun out, the whole thing,\" she recalled in a 2008 interview. \"And [then] my dog came and sat in my lap...and that was a big turning point in my life. My little, stupid dog, a  Yorkie , who I adored, literally came and sat on my lap. ...and literally, he saved my life. Truly saved my life.\" [ 25 ]  Rivers eventually recovered with counseling and the support of her family. [ 143 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4289", "contents": "In a 2002 ITV  biography , Rivers reveals that she is the great niece (on her mother's side) of singer  Happy Fanny Fields . She says that, \"(Fanny) was the star of the family; she came over to the United States and married very, very rich and became very grand.  But, she was the one person  No\u00ebl Coward  wanted to meet when he hit the United States.\" [ 144 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4290", "contents": "As a philanthropist, Rivers supported causes which included  HIV/AIDS  activism, [ 12 ]  and in May 1985, she appeared along with  Nichols and May  at a  Comic Relief  benefit for the new  AIDS Medical Foundation  in New York City, where tickets at the  Shubert Theatre  sold for as much as $500. [ 145 ]  She supported the  Elton John AIDS Foundation [ 146 ]  and God's Love We Deliver, which delivers meals to HIV/AIDS patients in New York City. [ 147 ] [ 148 ]  In 2008, she was commended by the City of  San Diego, California  for her philanthropic work on behalf of HIV/AIDS, where the HIV/AIDS community called her its \" Joan of Arc \". [ 149 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4291", "contents": "Additionally, she served as an Honorary Director of the  American Foundation for Suicide Prevention . [ 147 ] [ 150 ]  She also supported  Guide Dogs for the Blind , a non-profit organization which provides  guide dogs  to blind people. [ 147 ]  She donated to Jewish charities, animal welfare efforts, and suicide prevention causes. [ 12 ]  Among the other non-profit organizations which she helped were  Rosie's Theater Kids ,  Habitat for Humanity ,  Human Rights Campaign [ 146 ]  and the  Boy Scouts of America . [ 151 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4292", "contents": "Rivers was open about her multiple cosmetic surgeries and had been a patient of plastic surgeon  Steven Hoefflin  since 1983. She had her nose thinned while still at college; her next procedure, an  eye lift , was performed in 1965 (when she was in her 30s) as an attempt to further her career. [ 152 ] [ 153 ]  When promoting her book,  Men Are Stupid...And They Like Big Boobs: A Woman's Guide to Beauty Through Plastic Surgery , described by  The New York Times Magazine  as \"a detailed and mostly serious guide to eye lifts, tummy tucks and other forms of  plastic surgery \", she quipped: \"I've had so much plastic surgery, when I die they will donate my body to  Tupperware .\" [ 154 ] [ 155 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4293", "contents": "On August 28, 2014, Rivers experienced serious complications and stopped breathing while undergoing what was scheduled to be a minor throat procedure at an outpatient clinic in  Yorkville, Manhattan . [ 156 ] [ 157 ]  Resuscitated an hour later, Rivers was transferred to  Mount Sinai Hospital  in  East Harlem  and later put on  life support . [ 158 ]  She died on September 4 at Mount Sinai, never having awakened from a medically  induced coma . [ 159 ]  The  New York City Medical Examiner's Office  said that she died from brain damage caused by a lack of  oxygen . [ 160 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4294", "contents": "After nearly two months of investigations, federal officials said on November 10 that the clinic made a number of mistakes both before and during the procedure. Among those were the clinic's failure to respond to Rivers' deteriorating  vital signs , including a severe drop in her  blood pressure , possibly administering an incorrect  anesthetic  dosage, performing a surgical procedure without her consent, and other medical-clinic irregularities. [ 161 ] [ 162 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4295", "contents": "On September 7, after the cremation of Rivers' body at  Garden State Crematory  in North Bergen, New Jersey, [ 163 ]  a private memorial service took place at  Temple Emanu-El  in Manhattan. [ 164 ] [ 165 ]  The service was attended by an estimated 1,500 people. [ 165 ]  The guest list included Rivers' many celebrity friends and public figures such as  Howard Stern ,  Louis C.K. ,  Whoopi Goldberg ,  Barbara Walters ,  Diane Sawyer ,  Joy Behar ,  Michael Kors ,  Matthew Broderick ,  Sarah Jessica Parker ,  Rosie O'Donnell ,  Bernadette Peters ,  Kathy Griffin , and  Donald Trump . [ 166 ]  The musical performances included  Hugh Jackman  singing \"Quiet Please, There's a Lady On Stage\", as well as the  New York City Gay Men's Chorus  singing show tunes. [ 164 ]  Talk show host Howard Stern, who delivered the eulogy, described Rivers as \"brassy in public [and] classy in private\u00a0... a troublemaker, trail blazer, pioneer for comics everywhere,\u00a0... [who] fought the stereotypes that women can't be funny.\" [ 167 ]  Daughter Melissa read a comedic note to her mother as part of her eulogy. [ 168 ]  Some of Rivers' ashes were scattered by her daughter in  Wyoming . [ 169 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4296", "contents": "On January 26, 2015, Melissa Rivers filed a  malpractice   lawsuit  against the clinic and the doctors who performed surgery on her mother. [ 170 ]  The suit was settled for an undisclosed amount in May 2016, with the doctors accepting responsibility for Rivers' death. [ 171 ] [ 172 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4297", "contents": "Upon Rivers' death, friends, fans, family and celebrities paid tribute. [ 173 ] [ 174 ]  Numerous comedians recognized Rivers' influence on their career, including  Kathy Griffin , who considered Rivers her \"mentor\", noting, \"She brought a fearlessness and a brand of humor into our homes that we really need.\" [ 175 ]   Chris Rock  said \"she was the hippest comedian from the time she started to the day she died\". Describing her as a force in comedy, he added, \"No man ever said, 'Yeah, I want to go on after Joan.' No, Joan Rivers closed the show every night.\" [ 176 ]  Other comedians recalled working with her on stage and television decades earlier: stand-up performer  Don Rickles  said \"working with her and enjoying the fun times of life with her was special\".  Carol Burnett  called Rivers \"the poster child for the  Energizer Bunny \". [ 177 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4298", "contents": "Numerous talk show hosts, including  David Muir ,  Graham Norton ,   Jimmy Fallon ,  Jimmy Kimmel ,  Oprah Winfrey ,  Sally Jessy Raphael ,  Wendy Williams ,  Geraldo Rivera ,  Regis Philbin ,  Arsenio Hall ,  Ellen DeGeneres , and  David Letterman , paid tribute to Rivers, often including video clips of her appearances. Letterman called her a \"real pioneer for other women looking for careers in stand-up comedy. And talk about guts.\" [ 178 ]   Conan O'Brien  discussed Rivers' legacy with fellow comedian and lifelong friend  Chris Hardwick  on  Conan , while  Seth Meyers  recalled Rivers' appearance on  his talk show , saying, \"I have not sat next to anyone who told more jokes faster than Joan Rivers did when she was here.\" [ 179 ]  On  The Daily Show , host  Jon Stewart  noted her contributions to comedy: \"There are very few people in my business that you can say are, or were, actually groundbreaking talents. Joan Rivers was one of them.\" [ 179 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4299", "contents": "Radio host  Howard Stern , who delivered the eulogy at her funeral, devoted an entire one-hour show to Rivers. [ 180 ]  Stern sought help from comedian  Louis C.K. , another friend of Rivers', before giving the eulogy. [ 181 ]  When Stern spoke at the funeral, he began the eulogy with, \"Joan Rivers had a dry vagina\", a joke that was intended, and reportedly received by guests, as a humorous honoring of Rivers' comedic sensibility. [ 182 ] [ 183 ]   Sarah Silverman  paid tribute to Rivers while hosting  Saturday Night Live ; in one sketch, she portrayed Rivers in Heaven. [ 184 ]  Long-time friend, comedian, fellow talk show hostess and television personality  Whoopi Goldberg  tweeted: \"My friend Joan Rivers has passed away\". She said: \"Once again to quote  Billy Crystal ...There are no words.\" [ 185 ]  Comedian Louis C.K. released a statement saying, \"I looked up to her.  I learned from her. I loved her. I liked her.  And I already miss her very much. It really fucking sucks that she had to die all of a sudden.\" [ 186 ] \n Amy Schumer , speaking at the 2014  Glamour  magazine \"Woman of the Year Awards\" ceremony in  Carnegie Hall , paid tribute to Rivers, calling her the bravest female comedian. [ 187 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4300", "contents": "Political figures giving tribute to Rivers included former First Lady  Nancy Reagan , who said she was one of the \"funniest people I ever knew\". [ 188 ]  Upon hearing of her death,  Charles, Prince of Wales  and his wife  Camilla  said she was \"utterly irreplaceable\". [ 129 ]  Israel's Prime Minister  Benjamin Netanyahu  noted that besides bringing laughter to millions of people around the world, she was \"proud of her Jewish heritage\". [ 189 ]   Donald Trump  attended her funeral and  tweeted  that she \"was an amazing woman and a great friend\". [ 190 ]  After her mother's death, Melissa Rivers said she received a letter from President  Barack Obama  in which he wrote, despite being a frequent target of Rivers' jokes: \"not only did she make us laugh, she made us think\". [ 191 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4301", "contents": "In a subsequent interview with  The Huffington Post , Melissa Rivers cited  Courtney Love 's public tribute to her mother as her favorite, adding: \"I loved seeing that outpouring from these women, especially the ones who took the heat on  Fashion Police , because it meant they got it. It meant they loved her. It meant they saw the humor.\" [ 192 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4302", "contents": "Joan Rivers was strongly influenced by  Lenny Bruce . [ 76 ]  As a female comic, Rivers felt indebted to, but also very distinct from, other female standups and comedians including  Phyllis Diller  (a close friend and companion),  Fanny Brice ,  Sophie Tucker , [ 193 ]   Pearl Williams ,  Belle Barth , [ 193 ]   Totie Fields ,  Jean Carroll ,  Minnie Pearl ,  Jackie \"Moms\" Mabley ,  Johnny Carson ,  Zsa Zsa Gabor , [ 194 ]   Bob Newhart , [ 194 ]   Woody Allen ,  Don Rickles ,  Imogene Coca ,  Elaine May ,  Carol Burnett , and  Gracie Allen . Rivers's early comedy in particular was influenced by  vaudeville ,  Borscht Belt , and proto-feminist comedy of the early-1900s. [ 195 ] [ 196 ] [ 197 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4303", "contents": "In the 1960s and 1970s, Rivers was in a comedy circuit with  Lenny Bruce ,  Woody Allen ,  Richard Pryor ,  George Carlin , and  Dick Cavett . Though she counted them as peers and friends, she never felt included due to sexist practices within the industry. [ 198 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4304", "contents": "Mainstream comedians and contemporaries who have claimed that Rivers was an influence on them include:  Kathy Griffin ,  Sarah Silverman ,  Margaret Cho , [ 199 ]   Whitney Cummings ,  Chris Hardwick ,  Joy Behar ,  Amy Schumer , [ 193 ]   Whoopi Goldberg ,  Chelsea Handler , [ 200 ]   Louis C.K. ,  Roseanne Barr , [ 200 ]   Greg Proops [ 201 ]  and  David Letterman . She is considered a pioneer of women in comedy by many critics and journalists. [ 202 ] [ 203 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4305", "contents": "Audiobooks"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4306", "contents": "All are authored and read by Joan Rivers, except where noted."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4307", "contents": "Note:  Emmy nominations for Outstanding Writing \u2013 Special Class shared with Toem Perew and Hester Mundis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4308", "contents": "The  execution of Kenneth Eugene Smith  (July 4, 1965 \u2013 January 25, 2024) took place in the U.S. state of  Alabama  by  nitrogen hypoxia . It was the first execution in the world to use this particular method. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4309", "contents": "Smith was convicted of the March 18, 1988  contract killing  of Elizabeth Sennett in  Colbert County, Alabama . Charles Sennett Sr., Elizabeth's husband, recruited Billy Gray Williams to murder his wife. Williams in turn recruited Smith and John Forrest Parker to assist in the murder. Smith and Parker carried out the murder and stabbed Elizabeth Sennett to death at her home in Colbert County. A week after Elizabeth's murder, Charles Sennett Sr. killed himself when he learned he was a suspect in the murder. Billy Gray Williams was sentenced to life imprisonment without the possibility of parole and died in prison in November 2020. Smith and John Forrest Parker were both sentenced to death. Parker was executed via  lethal injection  in June 2010. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4310", "contents": "In November 2022, Smith was scheduled to be executed by lethal injection, but the execution was stayed after the execution team was unable to connect the intravenous lines to Smith in the time available before the expiration of the  death warrant  issued by the  Alabama Supreme Court . As part of a settlement between the state and Smith, the state agreed not to pursue Smith's execution by lethal injection (the default primary method of execution in Alabama) and instead utilize a secondary novel method of execution,  nitrogen hypoxia . [ 4 ]  After losing his final appeal to the  Supreme Court of the United States , Smith was ultimately executed by nitrogen hypoxia on January 25, 2024, becoming the first person to be executed by that method. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4311", "contents": "Reverend Charles Sennett Sr. hired Billy Gray Williams, one of his tenants, to murder his wife, 45-year-old Elizabeth Dorlene Sennett. [ 6 ]  To carry out the plan, Williams hired Kenneth Smith and John Forrest Parker to assist him. [ 6 ]  Sennett was going to pay each of the men $1,000 for the murder. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4312", "contents": "On March 18, 1988, Elizabeth Sennett was found with fatal injuries in her home in  Colbert County, Alabama . [ 6 ]  Earlier, Smith and Parker arrived at the Sennetts' home and told Elizabeth that Charles had allowed them to survey the grounds for hunting purposes. Elizabeth called Charles who told her to let the two men in. Charles had provided the men with funds to buy a firearm to kill Elizabeth. However, Smith and Parker opted to spend the money on drugs. Instead of a firearm, they used a six-inch survival knife and various items within the home to murder her. [ 7 ]  While the men were walking around the grounds, Elizabeth stayed inside. The two men then knocked on the door and asked to use the bathroom, which Elizabeth agreed to. While Parker was in the bathroom, Smith crept up on Elizabeth and decided to beat her. As Elizabeth struggled for her life; a \"fireplace set, a walking cane, and a piece of galvanized pipe\" were used to beat her. Parker also later joined Smith in beating her. After Elizabeth was beaten, she was then stabbed eight times with the survival knife, which caused her death. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4313", "contents": "Sheriff Ronnie May was one of the first people to arrive on the scene and he was unable to find a pulse for Elizabeth; however, when emergency medical technicians arrived, they found a pulse. [ 6 ]  May stated that Charles Sennett \"almost fell\" when he was told that Elizabeth had a pulse. [ 6 ]  May then rode with Elizabeth in the ambulance and she was declared dead by doctors at the hospital. [ 6 ]  May said that Sennett \"fought it and she fought hard.\" [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4314", "contents": "Investigators thought that the home looked staged to make it appear that there had been a  home invasion ; the men took a videocassette recorder and a stereo. [ 6 ]  May remembered meeting Charles Sennett a few weeks prior to the incident when they were investigating another murder and had to ask Sennett to leave several times. [ 6 ]  Investigators received a call from  Crime Stoppers  that gave them the suspects' names. [ 6 ]  On March 25, investigators brought Sennett in for questioning, but he denied involvement. When Sennett went to leave, someone asked if Sennett knew Kenneth Smith and Sennett turned red. [ 6 ]  Sennett left the interview and went to his church, where he met with his sons and their families and admitted to having an affair and having their mother killed. [ 6 ]  Sennett then went to the parking lot, got in his truck, and fatally shot himself. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4315", "contents": "Investigators received a search warrant to search Smith's home and found a  video recorder  from the Sennetts' home. [ 6 ]  Smith and Parker provided information to the police about Elizabeth's death. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4316", "contents": "Smith was tried and convicted in  Jefferson County  on a change of venue from Colbert County to reduce pre-trial publicity. [ 1 ]  The jury in Smith's first trial found Smith guilty of the murder of Elizabeth Dorlene Sennett and recommended to the trial judge that he be executed by a vote of 10\u20132. [ 10 ]  For inmates convicted before 2017, the jury issued a sentencing recommendation; if fewer than 10 jurors vote for a death sentence then that constitutes a life sentence. The judge, however, is not bound by the jury's recommendation, but gives it weight before making the ultimate sentencing decision. Smith was sentenced to death in 1989; however, the conviction and sentence were vacated on appeal in 1992. In Smith's second trial, the jury in Smith's case recommended a life sentence by a 11\u20131 vote; the judge overruled their recommendation and sentenced him to death in 1996. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4317", "contents": "Parker was also sentenced to death [ 12 ]  and Williams was sentenced to life imprisonment without the possibility of parole. [ 6 ] [ 13 ] [ 14 ]  Parker was  executed on June 10, 2010 , via  lethal injection . [ 6 ] [ 15 ]  Williams died in prison in November 2020 from an undisclosed illness. [ 3 ]  By November 2022, Smith exhausted all avenues of appeal regarding the second conviction and sentence."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4318", "contents": "Smith was initially scheduled to be executed by  lethal injection  on November 17, 2022. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4319", "contents": "Despite the fact that Smith had a motion to stay his execution pending before the  U.S. Court of Appeals for the Eleventh Circuit , at 7:45\u00a0p.m. on November 17, 2022, a lawyer for the Alabama Department of Corrections emailed Smith's lawyers to let them know they were preparing him for execution. [ 16 ]  Smith spoke with his wife, and at 7:57\u00a0p.m. prison guards ended his phone call with her. [ 16 ]  Smith was handcuffed and shackled and taken to the  execution chamber . [ 16 ]  Two minutes later, at 7:59\u00a0p.m. the Eleventh Circuit issued a stay of execution, which Smith's lawyers immediately provided to the Alabama Department of Corrections. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4320", "contents": "The Department of Corrections replied that they had received notice of the stay, but did not inform Smith or allow him to speak with his lawyers, instead keeping him strapped to a gurney in the execution chamber. [ 16 ]  At 10:00\u00a0p.m. the execution team entered and attempted to place an  IV  into Smith's arm. At approximately 10:20\u00a0p.m. the United States Supreme Court lifted the Eleventh Circuit's stay of execution. Smith told a member of the execution team that they were inserting the needle into his muscle, but the team member told him that was not true. [ 16 ]  The team then moved Smith into an inverted crucifixion position and left the room, returning after a few minutes to inject him with an unknown substance, despite Smith's objection. [ 16 ]  Another individual began repeatedly stabbing Smith's collarbone with a needle, attempting to place a central IV line. [ 16 ]  The results were unsuccessful and at approximately 11:20\u00a0p.m. Smith's execution was called off. [ 16 ]  Smith was unable to walk or lift his arms on his own, and was sweating and hyperventilating. [ 16 ]  This marked the third consecutive  botched execution  by the state of Alabama. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4321", "contents": "Following the incident,  Alabama Governor   Kay Ivey  ordered a review of Alabama's execution process. Governor Ivey also asked the Alabama Supreme Court to amend state court rules governing death warrants to allow Department of Corrections personnel additional time to carry out executions. [ 16 ]  The Alabama Supreme Court approved the amendment on January 12, 2023. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4322", "contents": "A second death warrant was later finalized, ordering Smith to be put to death on January 25, 2024, by nitrogen hypoxia, which was a secondary execution method in Alabama and had never been administered since its implementation. On January 10, 2024, a federal judge ruled that Alabama could proceed with the execution of Smith using nitrogen gas. [ 17 ] [ 18 ]  On January 24, 2024, the Supreme Court refused to hear his appeal and denied his request for a  stay of execution . [ 19 ] [ 20 ]  On the other hand, rights groups and the  United Nations  were concerned that the never-used method of nitrogen gas execution might lead to \"cruel, inhuman or degrading treatment or even torture\", and Smith's lawyers earlier argued in the failed Supreme Court appeal that it was unconstitutional to conduct a second execution attempt on Smith after he survived the first. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4323", "contents": "On January 25, Smith's final appeal to stave off his execution was once again rejected by the Supreme Court, and his death sentence was scheduled to be carried out on the same evening at 6 p.m.  CST . Chuck Sennett, one of the victim's two sons, stated in response that Smith should pay the price for killing his mother, who he felt was overlooked in light of the planned execution method of nitrogen hypoxia. [ 22 ] [ 23 ]  Governor Ivey had earlier declined to grant Smith clemency, which would have commuted Smith's death sentence to life imprisonment. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4324", "contents": "Smith ate his  last meal \u2014steak, hash browns, and eggs\u2014eight hours before he was put to death, and he received a final visit from his wife and sons. [ 24 ]  Smith's spiritual advisor, Reverend Jeff Hood, told the  Associated Press  that Smith was at peace despite his fear of the risks of execution by nitrogen hypoxia, and accepted his imminent fate. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4325", "contents": "Smith was strapped to a gurney wearing a full-face mask. His last words were said to be, \"Tonight, Alabama causes humanity to take a step backwards. Thank you for supporting me. Love all of you.\" [ 2 ]  The nitrogen gas was administered beginning at 7:57 p.m. [ 26 ]  Some witnesses commented that Smith looked as if he was conscious for several minutes [ 27 ] [ 26 ]  and \"thrashed violently on the gurney\", [ 2 ]  breathing heavily for several minutes before his breathing was no longer visible. [ 27 ]  Smith appeared to lose consciousness at 8:02 p.m. [ 26 ]  It appeared death occurred when movement of Smith ceased at 8:08\u00a0p.m. [ 26 ]  The curtain to the witness room closed at 8:15\u00a0p.m. [ 28 ]  He was pronounced dead at 8:25\u00a0p.m. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4326", "contents": "Alabama Corrections Commissioner John Q. Hamm told the media that the alleged sightings of Smith's convulsion and shaking appeared to be involuntary movements, and these effects were expected based on the research made on nitrogen hypoxia. Hamm also claimed Smith held his breath for approximately four minutes which led to a stronger response from Smith's body. [ 30 ]  State Attorney General  Steve Marshall  also backed the claim and stated that this proved that the death penalty by nitrogen gas was an \"effective and humane method of execution\". Ivey also said in a media conference that justice had been served and hoped that Sennett's family could find closure after Smith's execution. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4327", "contents": "In a statement after Smith's execution, one of Sennett's two sons, Michael Sennett, stated that justice had been served for his mother and that Smith deserved to face the consequences for his crime. He added that although his mother cannot be brought back to life with Smith's death, he was glad that the ordeal was finally over after more than three decades since his mother was killed, and the family had long forgiven Smith and all the other perpetrators involved. Smith's remains were subsequently released to the Escambia County Coroner for an autopsy at the Mobile Laboratory of the Department of Forensic Sciences. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4328", "contents": "An autopsy of Smith's body was conducted by the Alabama Department of Forensic Sciences. The autopsy showed Smith exhibited signs of  negative-pressure pulmonary edema , had \"dark maroon blood\" and fluid present in his lungs along with \"marked congestion\", and had \"frothy fluid\" in his  trachea . Another death row inmate scheduled to die by nitrogen hypoxia in Alabama in November 2024,  Carey Dale Grayson , hired an expert to analyze Smith's autopsy results in August 2024. After a review, the expert called the results \"highly concerning.\" [ 33 ] [ 34 ]  Brian McAlary, an  anesthesiologist , wrote in an argument on Grayson's behalf that Smith likely panicked due to an automatic response to the inability to breathe oxygen and that Smith's panic may have been avoided if he had been given a sedative prior to his execution. A second expert, Thomas Andrew, the chief medical examiner of New Hampshire, agreed that Smith should have been sedated before his execution because nitrogen hypoxia introduces \"a sense of the absence of oxygen,  air hunger , and all of the panic and discomfort that is part and parcel of that way of dying.\" [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4329", "contents": "Volker T\u00fcrk , the  United Nations High Commissioner for Human Rights , condemned Alabama's use of nitrogen gas to administer Smith's death penalty and stated that the method had amounted to a potential form of torture and degrading punishment. [ 35 ] [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4330", "contents": "After Smith's execution, several other states became open to the possibility of legally carrying out nitrogen gas executions. Notably, lawmakers from  Ohio , where a moratorium has been in effect since the state's  last execution in 2018 , were considering to legalize nitrogen gas as a new method of execution aside from lethal injection. [ 37 ] [ 38 ] [ 39 ]  Four months later,  Alan Eugene Miller , another death row inmate who was found guilty of fatally shooting three people in 1999, was also scheduled to be executed by nitrogen gas in Alabama. [ 40 ]  On September 26, 2024, Miller was executed by nitrogen gas, becoming the second person after Smith to be executed using this method. [ 41 ]   Carey Dale Grayson , who was 19 when he murdered a hitchhiker in 1994, was executed by nitrogen gas, becoming the third person in Alabama on November 21, 2024. [ 42 ] [ 43 ] [ 44 ]  Convicted serial rapist and killer  Demetrius Terrence Frazier , whose execution was scheduled on February 6, 2025, is set to be the fourth person to face a nitrogen gas execution. [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4331", "contents": "On 17 February 2023, an abandoned lorry carrying illegal immigrants believed to be from  Afghanistan  as well as timber was discovered near Lokorsko, a village 12 miles north-east of Sofia in  Sofia City Province , Bulgaria. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4332", "contents": "Eighteen of the immigrants were dead and 34 others were taken to hospitals in Sofia. [ 1 ]  The deceased died due to a combination of lack of oxygen in an enclosed space and difficulty breathing due to the tight quarters. [ 3 ]  Bulgarian police arrested four people. [ 2 ]  Six people were charged with human trafficking charges shortly after the discovery, which included the truck driver and his companion. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4333", "contents": "This article about  Bulgarian history  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4334", "contents": "This article about a transport accident is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4335", "contents": "This article about transport is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4336", "contents": "John Christopher Stevens  (April 18, 1960 [ 2 ] \u00a0\u2013 September 11, 2012) was an American  career diplomat  and lawyer who served as the  U.S. Ambassador to Libya  from May 22, 2012, to September 11, 2012. [ 3 ] [ 4 ]  Stevens was killed when the U.S. Special Mission in  Benghazi, Libya , was  attacked by members of Ansar al-Sharia on September 11\u201312, 2012 ., [ 3 ] [ 5 ]  making Stevens the eighth  U.S. Ambassador to be killed while in office . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4337", "contents": "Stevens was born on April 18, 1960, in  Grass Valley, California , the eldest of three siblings born to Jan S. Stevens, a California Assistant Attorney General, [ 7 ]  and his wife Mary J. Stevens (n\u00e9e Floris; born 1937), [ 8 ]  from a  West Coast  family of French, Swedish and  Chinook  ancestry. [ 9 ]  Stevens was raised in  Northern California  and had two younger siblings, Anne (born 1962) and Thomas (born 1965). [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4338", "contents": "Stevens' parents divorced in 1975, and both remarried. Stevens himself never married. [ 7 ]  His mother, a cellist, joined the  Marin  Symphony Orchestra (1969\u20142004), [ 11 ]  and in 1976 married  Robert Commanday , a music critic with the  San Francisco Chronicle . [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4339", "contents": "Stevens was an  AFS Intercultural Programs  exchange student in Spain during summer of 1977, and graduated from  Piedmont High School [ 14 ]  in 1978. He earned  BA  degree in history in 1982 at the  University of California, Berkeley , where he was a member of  Alpha Tau Omega  fraternity. From 1983 to 1985, he taught English as a  Peace Corps  volunteer in Morocco. He graduated with  JD  degree from  University of California, Hastings College of Law  in 1989, and received  MS  degree from the  National War College  of  National Defense University  in 2010."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4340", "contents": "Prior to joining the  United States Foreign Service , Stevens was an  international trade  attorney based in Washington, D.C. [ 4 ]  He was admitted as an active member of the  State Bar of California  on January 26, 1990; he went on an inactive status on August 1, 1991, and remained an inactive member for the remainder of his career. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4341", "contents": "Stevens joined the United States Foreign Service in 1991. His early overseas assignments included: deputy principal officer and political section chief in  Jerusalem , political officer in  Damascus , consular/political officer in  Cairo , and consular/economic officer in  Riyadh . In Washington, Stevens served as director of the Office of Multilateral Nuclear and Security Affairs, Pearson Fellow with the  Senate Foreign Relations Committee  and Senator  Richard Lugar , special assistant to Undersecretary for Political Affairs, Iran desk officer, and staff assistant in the  Bureau of Near Eastern Affairs ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4342", "contents": "He had served in Libya twice previously: as Deputy Chief of Mission, 2007 to 2009, and as  Special Representative  to the  National Transitional Council , March 2011 to November 2011, during  Libyan revolution . He arrived in  Tripoli  in May 2012 as U.S. Ambassador to Libya. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4343", "contents": "Stevens spoke English, French, and some Arabic. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4344", "contents": "During the 2012 Benghazi attack, a fire was set against the wall of the main consulate building while three Americans were inside\u2014Stevens,  Sean Smith , and a security officer. [ 17 ]  According to U.S. officials, the security officer escaped; the staff found Smith dead. They were unable to locate Stevens before being driven from the building under large arms fire. [ 17 ]  Shortly after midnight, local civilians found Stevens and brought him to the Benghazi Medical Centre, in a state of cardiac arrest. [ 18 ]  Medical personnel tried to resuscitate him, but he was pronounced dead at about 2 a.m. local time on September 12, 2012. [ 17 ]  Later reports suggested that the attack was coordinated and planned, with any protests either coincidental or possibly diversionary. [ 19 ]   Libyan president  Muhammad Magariaf  blamed elements of  Ansar al-Sharia  for the killing, linking them to  Al-Qaeda in the Islamic Maghreb . Libyan officials suggested that it might have been a revenge attack mounted by loyalists (of deceased Libyan leader  Muammar Gaddafi ) who were defeated in the  Libyan Civil War  the previous year. [ 20 ] \nThe doctors who tended to Stevens said that no visible physical wounds were found on his body and that he died from  smoke inhalation , making  hypoxia  the cause of his death. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4345", "contents": "The surviving Americans were taken to a  safe house . A rescue squad consisting of eight former U.S. military was sent from Tripoli, the capital. They were ambushed and the safe house came under attack. Two more Americans died, including one sent from Tripoli; several were wounded. [ 17 ] [ 22 ] [ 23 ]  Later reports identified the victims as  Tyrone S. Woods  and  Glen A. Doherty , both former  Navy SEALs  working as security and intelligence contractors. [ 24 ] [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4346", "contents": "Stevens is buried in New Elm Ridge Cemetery (formerly known as Forester's Cemetery) in Grass Valley, California."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4347", "contents": "William Payne Stewart  (January 30, 1957 \u2013 October 25, 1999) was an American  professional golfer  who won 11  PGA Tour  events, including three  major championships , the last of which came just a few months before  his death in an airplane accident  at the age of 42."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4348", "contents": "Stewart gained his first major title at the  1989 PGA Championship . He won the  1991 U.S. Open  after a playoff against  Scott Simpson . At the  1999 U.S. Open  Stewart captured his third major title after holing a 15-foot (5\u00a0m) par putt on the final hole for a one-stroke victory."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4349", "contents": "Stewart was a popular golfer with spectators, who responded enthusiastically to his distinctive clothing. He was reputed to have the biggest wardrobe of all professional golfers and was a favorite of photographers because of his flamboyant attire of  ivy caps  and patterned pants, which were a cross between  plus fours  and  knickerbockers , a throwback to the once-commonplace golf \"uniform\". Stewart was also admired for having one of the most gracefully fluid and stylish golf swings of the modern era. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4350", "contents": "Stewart was born and raised in  Springfield, Missouri , and attended  Greenwood Laboratory School , a K-12 school, on the campus of  Missouri State University . He played collegiate golf at  Southern Methodist University  in  Dallas , Texas, where he was a member of  Phi Gamma Delta  and graduated in 1979."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4351", "contents": "Stewart failed to earn a  PGA Tour  card at  Qualifying School  in his graduation year, so he played on the Asia Golf Circuit for a couple of years. He won two tournaments in 1981, including the  Indonesia Open  in a playoff over three players. [ 3 ]  Later that year, he earned his PGA Tour card for 1982 and won his first title on the tour at that year's  Quad Cities Open . This win was especially memorable to him because it was the only time his father, Bill, saw him win. Stewart's father had played in the 1955  U.S. Open , and had introduced his son to the game. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4352", "contents": "In 1983, Stewart gained his second PGA Tour victory by winning the  Walt Disney World Golf Classic  by two strokes. At the 1985  Byron Nelson Golf Classic , Stewart came to the 72nd hole with a three-shot lead. Moments after  Bob Eastwood  birdied the final hole of regulation, Stewart took a double bogey to end the tournament tied for first. Stewart then made another double bogey on the first playoff hole, causing him to lose to Eastwood. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4353", "contents": "In  1985 , Stewart came close to winning  The Open Championship , when he finished one stroke behind the champion  Sandy Lyle ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4354", "contents": "Stewart briefly led the U.S. Open in  1986  during the back nine of the final round at  Shinnecock Hills . After birdieing the 11th and 12th, Stewart took a one-shot lead, but he then had bogeys at the 13th and 14th, finishing the tournament tied for sixth place, behind the winner  Raymond Floyd . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4355", "contents": "Stewart had four runner-up finishes on the PGA Tour in 1986. [ 7 ]  Despite not winning a tournament that year, he had the most top-10 finishes of any player on the PGA Tour in 1986, finishing inside the top-10 sixteen times. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4356", "contents": "Stewart won the  Hertz Bay Hill Classic  in  Orlando, Florida  in 1987, shooting a third round of 63 and a final round of 65 to beat South African  David Frost  by three shots. The tournament was a two-man duel in the final round, as Frost finished eight shots ahead of the third-place finisher  Dan Pohl . Stewart's victory was a memorable one to him as it came on his home course. His house was situated adjacent to the 12th tee of the Bay Hill Club course in Orlando, Florida. [ 9 ]  Stewart's cumulative tournament score of 264 is, to date, still a record for the lowest aggregate score over 72 holes in the event, which later became known as the \"Arnold Palmer Invitational\" held at the same Bay Hill venue."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4357", "contents": "After his 1987 victory at Bay Hill, Stewart donated his $108,000 prize money to a Florida hospital in memory of his father, who died of cancer in 1985. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4358", "contents": "Stewart had two runner-up finishes on the PGA Tour in 1988, at  The Honda Classic  and the  Provident Classic ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4359", "contents": "In April 1989, Stewart won the  MCI Heritage Golf Classic  by five strokes, with a then tournament-record score of 268, 16-under-par. [ 10 ]  His victory at the Heritage Classic was his 18th top-10 finish on the PGA Tour since his previous win at the Bay Hill Classic in March 1987. Stewart was gaining a reputation for being one of the most consistent players on the PGA Tour [ 10 ]  and one of the best players in the world not yet to have won a major championship at that point."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4360", "contents": "At  Kemper Lakes Golf Club , Stewart won the  PGA Championship  in  1989 , his first major title. At the start of the final round, Stewart was six shots behind the leader  Mike Reid . He made up five strokes in the final three holes to overtake Reid and win by a stroke. Stewart's back-nine of 31 included birdies on four of his last five holes. He was able to gain the lead over Reid, who bogeyed the 16th, double-bogeyed the 17th, and missed a seven-foot (2 m) birdie putt on the 18th, which would have forced a playoff. [ 11 ]  After the tournament, Stewart said: \"This is a dream I've been trying to realize for a long time.\" Reid shed tears and said: \"As disappointed as I am, I'm happy for Payne.\" [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4361", "contents": "The following  year , Stewart became the first player to win back-to-back titles at the  MCI Heritage Golf Classic  at  Harbour Town Golf Links , winning a playoff against  Larry Mize  and  Steve Jones  on the second extra hole with an 18-foot (5\u00a0m) birdie putt. This was his first playoff win on the PGA Tour, having lost all five of his playoffs in the 1980s. [ 13 ]  In May 1990, Stewart won his second tournament of the year at the  GTE Byron Nelson Golf Classic . As a result of this victory and runner-up finishes at the  Western Open  and  1990 Open Championship  Stewart reached his  Official World Golf Ranking  (OWGR) peak of number 3 in the summer of 1990. [ 14 ]  At the end of 1990, Stewart was ranked as the fifth-best golfer in the world on the OWGR. [ 15 ]  Overall, Stewart spent nearly 250 weeks within the top 10 of the OWGR between 1986, the year the OWGR began, and 1999, the year of his death. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4362", "contents": "Stewart's second major title came at the  1991 U.S. Open  after an 18-hole Monday playoff with  Scott Simpson  on a windblown  Hazeltine National Golf Club  course in Minnesota. Stewart was two shots behind Simpson going into the final three holes of the playoff. After the 16th hole, the match was squared, as Stewart holed a 20-foot (6\u00a0m) birdie putt and Simpson missed a 3-foot (1\u00a0m) par putt. Stewart's par on the 18th hole won the playoff by two strokes. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4363", "contents": "The following month, Stewart won the 1991  Heineken Dutch Open  by nine shots, which included a course record of 62 in the third round. [ 18 ]  Stewart won the  Hassan II Golf Trophy  in Morocco in 1992 and 1993."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4364", "contents": "In 1993 at  Royal St George's Golf Club  in England, Stewart's fourth round of 63 tied the record for the lowest individual round in The Open Championship. He was one of 10 players, until  Branden Grace  shot a 62 in 2017, to hold the record for shooting a 63 at the British Open. [ 19 ]  In 1995, Stewart gained his first U.S. PGA Tour win in four years by winning the  Shell Houston Open  in a playoff over  Scott Hoch , who lost a six-shot lead with seven holes to play. Hoch collapsed on the back-nine with three bogeys and a double-bogey on the 17th when his tee shot found water. Stewart won the playoff on the first extra hole. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4365", "contents": "In the  1998 U.S. Open  at  Olympic Club  in San Francisco, Stewart had a four-shot lead going into the final round, but lost to  Lee Janzen  by a stroke. [ 21 ]  Stewart missed a 25-foot birdie putt on the 18th hole of his final round, which would have forced a playoff with Janzen. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4366", "contents": "The following year at the 1999 U.S. Open at  Pinehurst Resort , Stewart won his last major title, memorably holing a 15-foot par putt that defeated  Phil Mickelson  by a stroke in the final round when  Tiger Woods  and  Vijay Singh  were also in contention for the trophy. Stewart credited his winning putt to being more at peace with himself after his strengthened religious belief. [ 21 ]  A statue of Stewart celebrates his winning putt behind the 18th green of the No. 2 course at Pinehurst Resort. [ 23 ] [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4367", "contents": "At the time of his death, Stewart was ranked third on the all-time money list and in the top 10 of the Official World Golf Ranking \u2013 he had been ranked in the top 10 for almost 250 weeks from 1986 to 1993, and again in 1999. [ 25 ]  At a time of international domination of the golf scene in the late 1980s and early 1990s, he was often the highest-ranked American player. At the time of his death, Stewart had won $12,673,193 in career earnings. He won over $2\u00a0million during the  1999 season  and finished seventh on the year's money list."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4368", "contents": "Stewart represented the United States on five  Ryder Cup  teams (1987, 1989, 1991, 1993, and 1999). He also played for the U.S. on three  World Cup  teams. His Ryder cup record was 8\u20139\u20132. Stewart was known for his patriotic passion for the Ryder Cup, once saying of his European opponents, \"On paper, they should be caddying for us.\" The United States team was 3\u20131\u20131 during the five times he played. [ 26 ]  He was disappointed to miss out in 1995 and 1997 when he failed to qualify automatically and was not chosen as a captain's pick. In the  1999 Ryder Cup , Stewart criticized the heckling of European player  Colin Montgomerie . With victory assured for the United States, Stewart conceded a putt (and his own singles match) to Montgomerie on the 18th hole. \"This game is about sportsmanship,\" Stewart said afterward. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4369", "contents": "Stewart was a golfing traditionalist, who once said: \"In the United States, all we do is play the ball in the air.\" [ 27 ]  He gained an affection for  links  golf, becoming a popular figure in Ireland after playing on Irish courses to warm up for The Open Championship. After he died in 1999, Waterville Golf Links in  County Kerry , Ireland, commissioned a bronze statue of Stewart to pay tribute to him and his affiliation with Waterville. [ 28 ]  Stewart historically played well in  The Open Championship , finishing runner-up in 1985 and 1990. In general, he was known to play well internationally, posting victories at the 1981  Indian Open , the 1981  Indonesia Open , and Japan Golf Tour's 1985  Jun Classic . He also played in international tournaments that were less obscure for American golfers, posting runners-up at the 1982  Australian Open , 1989  German Masters , and the 1993  Scottish Open . He also won the 1991  Dutch Open ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4370", "contents": "For a large part of his career, Stewart was known for his  National Football League  (NFL) sponsorship, whereby he wore the team colors of the geographically closest NFL franchise; [ 29 ]  the sponsorship ended in May 1995. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4371", "contents": "Stewart met Tracey Ferguson, sister of Australian golfer  Mike Ferguson , in  Kuala Lumpur  in 1980 while he was playing on the  Asia Golf Circuit , and they were married by November 1982. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4372", "contents": "Stewart was also a musician, and played harmonica in the  blues rock  group Jake Trout and the Flounders, which also included fellow golfers  Larry Rinker  and  Peter Jacobsen . [ 32 ]  The band released one album,  I Love to Play  in 1998. [ 32 ]  The music video for the title track, a golf-themed parody of  Randy Newman 's \" I Love L.A. \", earned rotation on  VH-1 . [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4373", "contents": "Stewart appeared on an episode of the American television sitcom  Home Improvement  titled \"Futile Attraction\", which aired on March 10, 1998, and featured Stewart as himself."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4374", "contents": "On October 25, 1999, Stewart  was killed in the crash  of a  Learjet  flying from his home in  Orlando, Florida , to  Texas  for the year-ending tournament, The Tour Championship, held at  Champions Golf Club  in  Houston .  National Transportation Safety Board  (NTSB) investigators concluded that the aircraft failed to pressurize and that all on board were incapacitated by  hypoxia  as the aircraft passed to the west of  Gainesville, Florida . The aircraft continued flying on autopilot until it ran out of fuel and crashed into a field near  Mina, South Dakota . [ 34 ] [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4375", "contents": "I didn't sleep at all. I tossed and turned all night, and I don't see how you couldn't. Anyone who knew Payne...it's a huge blow to all of us because he was a part of our lives. To have him gone, it's really difficult to refer to him right now in the past tense. That's the hardest thing for me right now when I talk about it...I just saw him the other day. It's hard to believe he's not going to be here."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4376", "contents": "At that week's tournament, The Tour Championship, Stewart's good friend,  Stuart Appleby , organized a tribute to his friend. With Stewart's wife's permission, he wore one of Payne's own signature outfits for the final round of the tournament on Sunday, and most of the rest of the golfers in the field wore \"short pants\" that day, as well. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4377", "contents": "The tournament had been delayed in order to allow those who would be competing in it to attend Stewart's memorial service at the First Baptist Church of Orlando on October 30. Speakers included Tracey Stewart and  Paul Azinger , both a fellow professional and one of Stewart's close friends, while attendees included Woods, Mickelson,  Jack Nicklaus ,  Greg Norman ,  Davis Love III ,  Hal Sutton ,  Justin Leonard  and  Fred Couples , along with MLB pitcher  Orel Hershiser , another friend of Stewart's. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4378", "contents": "One year after Stewart's death, his widow Tracey and their two children, and the family of Stewart's agent, Robert Fraley, who also died on that flight, brought a lawsuit against Learjet, flight operator SunJet Aviation, Inc., and aircraft owner JetShares One Inc.  They alleged that a cracked adapter resulted in an airflow valve detaching from the frame, causing a fatal loss of cabin pressure. They also claimed that the aircraft was severely out of maintenance because of SunJet's negligence. [ 39 ]  In April 2000 as part of a federal criminal investigation, the  Federal Bureau of Investigation  raided SunJet and seized its flight logbooks, effectively grounding all of its aircraft.  The investigation was dropped in 2002, but it was too late to save SunJet; unable to legally operate, it had filed for bankruptcy protection in June 2000. [ 40 ]  The case against Learjet went forward in state court in Orlando. In June 2005, jurors found that the aircraft's manufacturer had no liability in the deaths of Stewart and Fraley and that no negligence was found in the design or manufacture of the aircraft. [ 23 ] [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4379", "contents": "The segment of  Interstate 44  passing through  Springfield, Missouri , was designated the \"Payne Stewart Memorial Highway\" in his memory. Payne Stewart Drive in  Fullerton, California , and Payne Stewart Drive in  Surrey, British Columbia , Canada, leading into Northview golf course designed by  Arnold Palmer , were named after him.  Finally, Payne Stewart Drive in  Jacksonville, Florida , houses  The First Tee  along with a  Job Corps  center."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4380", "contents": "The communities of Mina and Aberdeen created their own memorial. Jon Hoffman, the owner of the property where the aircraft crashed, contacted Stewart's widow and several family members of other crash victims. All agreed that the memorial would be a rock from the crash site, engraved with the victims' names and a Bible passage. Hoffman fenced in about an acre (4,000 m 2 ) of the property surrounding the memorial. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4381", "contents": "In 2000, the PGA Tour established the  Payne Stewart Award , given each year to a player who shows respect for the traditions of the game, commitment to uphold the game's heritage of charitable support and professional and meticulous presentation of himself and the sport through his dress and conduct. [ 41 ]  At Pinehurst No. 2, a bronze statue of Stewart celebrating his winning putt in the 1999 U.S. Open there overlooks the 18th green. [ 23 ]  On the first day of the  2014 U.S. Open , the second time that Pinehurst No. 2 had hosted the tournament since 1999,  Rickie Fowler  wore plus fours and argyle socks in tribute to Stewart. [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4382", "contents": "Also, at  the 2000 U.S. Open  at  Pebble Beach , where Stewart would have been the defending champion, further tributes were paid. Firstly, on the eve of the tournament, there was another memorial at the 18th hole where speakers again included Tracey Stewart and Azinger. This time, the attendees included Stewart's old caddy Mike Hicks plus other professionals due to compete in the tournament such as Mickelson, Love,  David Duval ,  Tom Lehman ,  Lee Janzen  and  Sergio Garc\u00eda , and it concluded with shots being hit into Stillwater Cove in a golf version of a  21-gun salute . The next day, when Stewart's defending champion spot in the traditional initial pairings alongside the  Open Championship  winner ( Paul Lawrie ) and  U.S. Amateur  winner ( David Gossett ) was given to Nicklaus playing in his 44th consecutive and final U.S. Open, Nicklaus asked for a moment of silence before his opening tee shot. [ 43 ] [ 44 ]  Garc\u00eda also wore Stewart's trademark navy  plus fours  in his honor during his first round. [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4383", "contents": "In tribute to Stewart, as well as his southwestern Missouri roots, the Payne Stewart Golf Club was opened in  Branson, Missouri , in June 2009 with the approval of Stewart's widow. [ citation needed ]  Ground-breaking on the $31\u00a0million layout took place on July 24, 2006. The 7,319-yard, 18-hole course was designed by  Bobby Clampett  and Chuck Smith. Each hole on the course is named for some aspect or notable moment in Stewart's life. The fifth hole, for example, named \"Road Hole\", recounts the par Stewart made in the first round of the  1990 Open Championship  at  Old Course at St Andrews  when he was forced to knock his third shot against the wall behind the green at the Old Course's treacherous 17th. His ball finished just on the back fringe from where he chipped in. Later in 2020, Woods christened the first public course by him and his company TGR Design at Big Cedar Lodge near Branson as Payne's Valley in Stewart's honor. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4384", "contents": "On the 10th anniversary of Stewart's death in 2009,  Golf Channel  presented a special program to remember his life. It included recorded interviews with family, friends, and archived videos of his golf career."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4385", "contents": "The following is a list of courses for the design of which Stewart was at least in part responsible."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4386", "contents": "*Note: Tournament shortened to 54 holes due to weather."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4387", "contents": "PGA Tour playoff record (3\u20136)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4388", "contents": "European Tour playoff record (1\u20130)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4389", "contents": "*Note: The 1985 Gene Sarazen Jun Classic was shortened to 54 holes due to rain."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4390", "contents": "Asia Golf Circuit playoff record (1\u20130)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4391", "contents": "Other playoff record (1\u20132)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4392", "contents": "1 Defeated Simpson in an 18-hole playoff \u2013 Stewart 75 (+3), Simpson 77 (+5)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4393", "contents": "CUT = missed the half-way cut (3rd round cut in 1984 Open Championship) \n\"T\" = tied"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4394", "contents": "CUT = missed the halfway cut \n\"T\" indicates a tie for a place"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4395", "contents": "QF, R16, R32, R64 = Round in which player lost in match play \n\"T\" = Tied"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4396", "contents": "Professional"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4397", "contents": "Vladislav Nikolayevich Volkov  ( Russian :  \u0412\u043b\u0430\u0434\u0438\u0441\u043b\u0430\u0432 \u041d\u0438\u043a\u043e\u043b\u0430\u0435\u0432\u0438\u0447 \u0412\u043e\u043b\u043a\u043e\u0432 ; 23 November 1935\u00a0\u2013 30 June 1971) was a Soviet  cosmonaut  who flew on the  Soyuz 7  and  Soyuz 11  missions. The second mission  terminated fatally . [ 1 ] [ 2 ]  Volkov and the two other crew members were  asphyxiated  on reentry, the only three people to have died in outer space."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4398", "contents": "Volkov graduated from the  Moscow Aviation Institute  in 1959. [ 3 ]  As an aviation engineer at Korolyov Design Bureau, he was involved in the development of the Vostok and Voskhod spacecraft prior to his selection as a cosmonaut. He flew aboard Soyuz 7 in 1969."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4399", "contents": "Volkov, on his second space mission in 1971, was assigned to Soyuz 11 along with  Georgy Dobrovolsky  and  Viktor Patsayev . The three cosmonauts on this flight spent 23 days on  Salyut 1 , the world's first space station. After three relatively placid weeks in orbit, however, Soyuz 11 became the second Soviet  space flight  to terminate fatally, after  Soyuz 1 ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4400", "contents": "After a normal  re-entry , the Soyuz 11 capsule was opened and the corpses of the three crew members were found inside. [ 4 ]  It was discovered that a valve had opened just before leaving orbit that had allowed the capsule's atmosphere to  vent away into space , causing Volkov and his two flight companions to suffer fatal  hypoxia  as their cabin descended toward the Earth's atmosphere. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4401", "contents": "Vladislav Volkov was decorated twice as the  Hero of the Soviet Union  (first on 22 October 1969 and posthumously on 30 June 1971). He was also awarded the two  Orders of Lenin  and the title of  Pilot-Cosmonaut of the USSR . [ 1 ]  His ashes were interred in the  Kremlin Wall  on  Red Square  in Moscow. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4402", "contents": "The lunar crater  Volkov  and the minor planet  1790 Volkov  are named in his honor. A street in Moscow is named after him."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4403", "contents": "The \"Yeniseyles\" Soviet research/survey ship was renamed \"Kosmonavt Vladislav Volkov\" in his honor in 1974. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4404", "contents": "A tomato variety from Ukraine was named Cosmonaut Volkov in his memory by his friend the space scientist and gardener Mikhailovich Maslov. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4405", "contents": "Volkov is an  honorary citizen  of  Kaluga  and  Kirov . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4406", "contents": "1973 to 2015, the Pilotcosmonaut-Volkov-Award (later Volkov-Cup) was given for the best sports acrobatics since 2016 called Zolotov-Cup; while alive, Volkov became the first chairman of the Soviet Society of Sportsacrobatics in 1970. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4407", "contents": "In  Russia in Space , Brian Harvey described a fleet of communication vessels or \"comships\", used to track Soviet space missions.  The fleet included a ship known as the  Vladislav Volkov , built during the 1970s. Following the dissolution of the Soviet Union, several of the fleet's ships were either sold to other governments, or left idle in harbor. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4408", "contents": "An account of Volkov's life and space career appears in the 2003 book  Fallen Astronauts: Heroes Who Died Reaching for the Moon  by  Colin Burgess ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4409", "contents": "In the 1999 film  Virus , an alien intelligence infects the research vessel \"Akademic Vladislav Volkov\" 's computer system via a space transmission. The  USNS\u00a0 General Hoyt S. Vandenberg \u00a0(T-AGM-10)  was redecorated for the film."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4410", "contents": "Otto Zehm  (October \u00a0 31, 1969\u00a0\u2013 March \u00a0 20, 2006) was a man with a  developmental disability  from  Spokane, Washington , who died on March 20, 2006, during an altercation with  police officer  Karl F. Thompson Jr. [ 1 ]   Zehm committed no crime, and on May 30, 2006, the Spokane County Medical Examiner ruled the death a  homicide . [ 2 ] [ 3 ]  In 2012, the first of several officers on the scene at Zehm's death was convicted of excessive use of force and lying to investigators, and was sentenced to 51 months imprisonment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4411", "contents": "On March 18, 2006, Zehm, a white man\u2014who worked as a janitor and did not own a car\u2014went on foot to an  ATM  at his bank to withdraw money from his account. Two young women, who were in a car at the ATM when Zehm arrived, erroneously reported to police by phone that a man was attempting to steal money from the ATM. The women followed Zehm in their car while reporting additional information to the police dispatch by phone. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4412", "contents": "Zehm next entered the convenience store that he routinely visited to buy a soft drink and fast food. Video from the convenience store security cameras show that within sixteen seconds of the officer Thompson entering the store, the officer had run up to Zehm, whose back was initially turned to him, twice ordered him to \"drop the pop\", [ 5 ]  and batoned Zehm to the ground\u2014the first of at least seven baton strikes used on Zehm, including strikes to the head. [ 6 ]  Within another sixteen seconds Zehm had also been tasered. In addition to the multiple beatings and taserings, Zehm was improperly hog-tied by police and placed on his abdomen for more than sixteen minutes.  Furthermore, the police requested a  non-rebreather mask  from paramedics at the scene and strapped it to Zehm's face. The non-rebreather mask was not attached to oxygen. Zehm stopped breathing three minutes after the mask was placed on his face. When ruled a homicide by the county Medical Examiner on May 30, 2006, the cause of death was reported as \"lack of oxygen to the brain due to heart failure while being restrained on his stomach.\"  No illegal drugs or alcohol were found in Zehm's system."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4413", "contents": "Police alleged that Zehm had \"lunged\" at the original officer with a plastic soft drink bottle. However, the silent surveillance video of the incident (the full version of which was withheld by the police for three months\u2014they were initially altered by an unknown member of the  Spokane Police Department  to splice out scenes incriminating to Thomson [ 7 ] ) contradicted this police claim. Then-acting police chief Jim Nicks subsequently stated that he misspoke in alleging Zehm \"lunged\" at the officer. The video also did not provide support for the officer's claim that he paused and gave verbal orders to Zehm. Each frame showed the officer advancing at a brisk rate while Zehm, after seeing the officer advancing with his baton raised, only back-pedals slowly away. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4414", "contents": "In July 2006, then-Spokane mayor  Dennis Hession  ordered an independent review of Zehm's death, [ 9 ]  and in August 2006, the report was commissioned. [ 10 ]  Known as the Worley Report, after law enforcement consultant Michael Worley, [ 11 ]  the report was commissioned, [ 12 ] [ 13 ]  to look at the three matters\u2014the Zehm homicide, a Spokane Fire Department sex scandal, [ 14 ] [ 15 ]  and the Spokane City Citizens Review Commission.  Worley's findings were made public in a report released on October 26, 2007, but covered only the Fire Department sex scandal and the Citizens Advisory Commission. [ 16 ]   Worley submitted the incomplete report, for which the City of Spokane paid $8,800, pending the completion of other then-pending investigations of the Zehm death, including investigations by the Spokane County Prosecutor's Office, the Washington Association of Sheriffs and Police Chiefs (WASPC), [ 12 ] [ 13 ] [ 17 ]  and the FBI.  As of August 18, 2008, the FBI has not closed its investigation of the case and has made no public statements regarding the status of that investigation. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4415", "contents": "Three of the seven officers involved in the attack on Zehm received one day of administrative leave (paid).  Beyond that, no Spokane Police officer or administrator has been disciplined or suspended or fired as a result of the case.  However, one officer involved in the case, Spokane Police officer Jason Uberuaga, was subsequently fired for \" conduct unbecoming \" after being involved in an October 11, 2007, incident involving alcohol and allegations of sexual misconduct.  At the time of that incident, Uberuaga was a member of a federal law enforcement task force. [ 19 ]  Uberuaga was later reinstated with  10 + 1 \u2044 2  months back pay, following a union arbitrator's determination that firing was excessive punishment for the acts committed. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4416", "contents": "A second Spokane Police officer involved in the Zehm case is Dan Torok. [ 21 ]  In the Zehm case, Torok provided a written statement in which he stated, \"When my knee struck him, I heard him exhale and I was able to force his arm behind his back.\"  In addition to Torok's knee in his chest, Zehm was subjected to being hog-tied and placed on his chest for 16 minutes, as well as being subjected to a non-rebreather mask placed on his face without oxygen attached, thus limiting his ability to breathe. Zehm stopped breathing and was transported by para-medic to a Spokane area hospital where he was declared brain-dead and died two days later. Otto Zehm's last words were, \"All I wanted was a  Snickers Bar \"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4417", "contents": "Almost exactly a year after his involvement in Zehm's death, Officer Torok shot and killed a homeless man, Jerome Alford, on March 24, 2007. [ 22 ]  Following a Spokane area practice in which the Spokane Police and Spokane County Sheriff's Office investigate one another in officer involved deaths, the Spokane County Sheriff's Office was assigned to investigate the shooting of Alford by Torok. Spokane Chief of Police Anne E. Kirkpatrick ordered Torok to provide a written statement, known as a  Garrity letter , rather than submit to questioning by the Spokane County Sheriff's Office. Garrity letters are so infrequently used in the area that Spokane County Sheriff's personnel did not initially accept the letter from Torok. Final results of the Sheriff's investigation were never made public. [ 23 ]  Currently, Torok is a Spokane Police Department detective supervising assignments of child abuse cases, and also acting frequently as a spokesperson for the Spokane Police.  He is also a controversial participant in on-line blogging at Spokane's only daily newspaper, the  Spokesman-Review . In August 2007, he and a colleague, Sgt. Jim Faddis, were discovered blogging anonymously at a  Spokesman-Review  affiliated blog, Hard 7, until blog manager Frank Sennett discovered their identities and employment with the Spokane Police. [ 24 ]  Recently another  Spokesman-Review  blog, Community Comment, has given Torok and Faddis, a former internal affairs officer, semi-official status at Police Blotter, [ 25 ]  a periodic blog thread identified by a reproduction of the Spokane Police badge at the  Spokesman-Review's  online blog site."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4418", "contents": "The Zehm case provoked public outrage, including protests and public challenges to the Spokane Police by critics. [ 26 ]   On July 9, 2007, in the wake of another police scandal involving the arrest on July 4, 2007, of 17 people in Spokane's  Riverfront Park , a group of some 200 people gathered a block from Spokane's Public Safety Building demanding independent oversight of the Spokane Police Department. At the end of the rally, a group of people entered the street and marched to City Hall where they presented their concerns to the Spokane City Council."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4419", "contents": "The case also prompted intense scrutiny by the local media and calls for independent oversight.  A series of public meetings were held in the first half of 2007, including a three part series on Police Accountability at Gonzaga University.  Participants in the series included Breean Beggs of Spokane's Center for Justice, independent journalist Tim Connor, Spokane Police Chief Anne Kirkpatrick, Spokane City Councilwoman   Mary Verner , and others.  The series, sponsored by the  ACLU , the  League of Women Voters , and the Peace and Justice Action League (PJALS), culminated in a growing consensus that an appropriate step to address the concerns about police misconduct would be an independent  ombudsman  styled after the Boise (Idaho) Office of the Community Ombudsman [ 27 ]  headed by Pierce Murphy.  Murphy visited Spokane several times including to participate in one of the Police Accountability forums at Gonzaga.  Murphy also spoke prior to a Whitworth University theater production on Police Accountability and the death of Zehm.  The unique event\u2014 Crossing the Line: An Examination of Police, Power and People \u2014was held on May 16, 2008, at Spokane's CenterStage. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4420", "contents": "On June 22, 2009, a federal Grand Jury handed down an indictment on Spokane Police Officer Karl Thompson. Thompson is a veteran of the force and was the first of seven officers that responded to the Zip Trip.  The 2 counts are: unreasonable use of force and making a false entry into a record being investigated by a federal agency. Both counts are felonies and could hold a 20-year maximum sentence if Thompson is convicted on both charges. Standard sentencing ranges for these offenses would likely result in confinement in a federal institution for 2\u20134 years. The unreasonable use of force stems from the surveillance video that shows Thompson approaching Zehm from behind and striking him to the ground moments after Zehm turned and faced the officer without any indication of aggressiveness, followed by multiple vertical baton blows and an application of a drive-stun taser.  Zehm was not acting combatively at the time of the initial blow and only started fighting back after Thompson engaged Zehm with force.  Federal prosecutors confirmed that the unreasonable use of force charge against Thompson was due to the injuries Zehm suffered from the initial baton blows and not Zehm's death.  It is unclear at this time if more indictments will be handed down for Zehm's death or for his improper restraint for being hog-tied on his stomach with a non-rebreather mask."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4421", "contents": "Thompson's federal trial began on October 12, 2011, with jury selection. The trial was moved from Spokane to  Yakima, Washington  after defense attorneys raised concerns about the extent of local media coverage of the controversy. Judge Fred Van Sickle of US District Court in Yakima ruled to exclude residents of Spokane County from the jury pool in the interest of fairness. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4422", "contents": "On November 2, 2011, the jury found Thompson guilty on both counts; excessive use of force and lying to investigators about the confrontation. [ 30 ]  Over 50 police officers were in attendance when the verdict was announced and saluted Thompson in a show of solidarity. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4423", "contents": "Thompson's defense attorneys argued for a sentence of zero to 16 months, while federal prosecutors recommended a sentence of between 9 and 11 years. On November 15, 2012, Judge Van Sickle sentenced Thompson to 51 months in federal prison. [ 32 ]  Judge Van Sickle also ordered that Thompson be taken into custody immediately over the objections of Thompson's defense attorney, who wanted him to remain free while the verdict is appealed. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4424", "contents": "Washington State paid $541,180 in legal fees to the law firm defending Karl Thompson. Thompson was declared indigent in July 2009 following an uncontested divorce initiated by his then-wife, Diana J. Thompson. [ 34 ]  The terms of the divorce decree transferred the bulk of the family assets to Diana, including their $675,000 home, alimony in the amount $1,500 per month, and 50% of Thompson's pension. In addition, all community debts were assigned to Karl Thompson. Thompson continued to live with his ex-wife following the divorce, and shared joint assets and bank accounts in contravention of the divorce decree, until his sentencing and incarceration. Prosecutors have alleged the divorce was fraudulent, undertaken for the dual purposes of shielding assets from the civil suit filed by the Zehm family and forcing the State of Washington to pay for Thompson's legal defense costs. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4425", "contents": "Until his release from prison in July 2016, [ 36 ]  Thompson had been serving his sentence at the  Federal Correctional Institution, Safford , a low-security prison in Arizona. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4426", "contents": "On August 22, 2012, the civil case brought by the Estate of Otto Zehm was closed following mediation and settlement. [ 38 ]  The settlement included a $1.67 million payment to the family, and budgeting for specialized training for all Spokane Police Officers more than 1 year from retirement. The training will focus on police interaction with mentally ill detainees. The settlement also includes a budget for implementation of new rules regarding the use of force, and a permanent memorial to Otto Zehm. Attorneys for the Estate were Breean Beggs and Jeffry Finer; and for the City of Spokane, Nancy Isserlis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4427", "contents": "Branimir Nestorovi\u0107  ( Serbian Cyrillic :  \u0411\u0440\u0430\u043d\u0438\u043c\u0438\u0440 \u041d\u0435\u0441\u0442\u043e\u0440\u043e\u0432\u0438\u045b ; born 16 December 1954) is a Serbian politician, pulmonologist, conspiracy theorist, and retired university professor serving as the member of the  National Assembly  since 6 February 2024. [ 1 ] [ 2 ] [ 3 ]  He is one of the representatives of the  We\u2013The Voice from the People  organisation and was elected to the  National Assembly  and the  Belgrade City Assembly  in  2023 . [ 4 ] [ 5 ]  In his career, he was also a paediatrician, allergist, and a professor emeritus of the  Faculty of Medicine, University of Belgrade . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4428", "contents": "Nestorovi\u0107 was born on 16 December 1954 in  Belgrade ,  PR Serbia ,  FPR Yugoslavia . [ 7 ]  He graduated from the Natural-Mathematics Department of the Obrenovac Gymnasium. He completed his studies at the  Faculty of Medicine of the University of Belgrade  in 1979 and gained his doctorate at the same faculty in 1985 with a dissertation in the narrow scientific field of paediatrics and allergology titled  Pollen Allergy in Children. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4429", "contents": "Nestorovi\u0107 was the head of the Department of Pulmonology and Allergology at the  University Children's Hospital  in Belgrade. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4430", "contents": "In 1987, he was elected as an assistant at the Faculty of Medicine in Belgrade. He was re-elected in 1991, and was elected to the position of assistant professor in 1995. He became an associate professor in 2000 and was re-elected in 2009. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4431", "contents": "He holds the title of full professor in the field of paediatrics and has published paediatrics textbooks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4432", "contents": "He gained notoriety for downplaying the impact of the COVID-19 pandemic, and his support for the  anti-vaccination  and  alternative medicine  movements. [ 11 ]  As a member of the COVID-19 crisis team, appointed by the government of Serbia, he proclaimed COVID-19 as the \"funniest virus in the history of mankind\". [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4433", "contents": "Nestorovi\u0107 has endorsed many conspiracy theories, such as existence of a secret cure for cancer, usage of Tesla's  death ray  in Iraq and Serbia, and existence of \"time portals\" which send people to the future. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4434", "contents": "Nestorovi\u0107 was previously a member of the  Serbian Renewal Movement  and he took part in the protests against  Slobodan Milo\u0161evi\u0107  in the 1990s. [ 6 ]  In 1999, following the formation of  SPS -SPO coalition, Nestorovi\u0107 was the assistant to the minister of education. [ 6 ]  After the  overthrow of Slobodan Milo\u0161evi\u0107  in 2000, he became a member of the  Democratic Party . [ 6 ]  In 2022, he publicly endorsed the  Dveri \u2013 POKS  electoral list for the  2022 Serbian parliamentary election . [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4435", "contents": "In 2023, he was one of the founders of the  right-wing populist   We\u2013The Voice from the People  political organisation. He was also its ballot carrier in the  2023 parliamentary elections  and the  Belgrade City Assembly election . MI\u2014GIN passed the electoral census in both elections and Nestorovi\u0107 was elected to the  National Assembly  and the  Belgrade City Assembly . Following the preliminary results for the Belgrade City Assembly election, president  Aleksandar Vu\u010di\u0107  stated that Nestorovi\u0107's organisation will be the  kingmaker  for Belgrade's local government. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4436", "contents": "He was sworn in as MP in the National Assembly on 6 February 2024. Nestorovi\u0107 raised a controversy at the constitutive session of the National Assembly by comparing the  Serbia Against Violence  MP's to  Gypsies . He later apologized to the  Romani  community. [ 16 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4437", "contents": "Anton Hermann Victor Thomas Schr\u00f6tter , name sometimes referred to as  Hermann Schr\u00f6tter von Kristelli  (5 August 1870 \u2013 6 January 1928) was an Austrian  physiologist  and physician who was a native of  Vienna . He was the son of  laryngologist   Leopold von Schr\u00f6tter  (1837\u20131908), and grandson to  chemist   Anton Schr\u00f6tter von Kristelli  (1802\u20131875)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4438", "contents": "He studied medicine and  natural sciences  at the Universities of  Vienna  and  Strasbourg , earning his medical degree in 1894, and during the following year receiving his doctorate of philosophy. Afterwards he worked under  Carl Gussenbauer  (1842\u20131903) at the University Hospital in Vienna and was an assistant to his father at the clinic of  internal medicine . In the mid-1890s with physiologist  Nathan Zuntz  (1847\u20131920) and others, he began investigations involving physiological effects on the body associated with air pressure and altitude change. In 1896 made the first in a series of several high-altitude balloon ascents."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4439", "contents": "In 1910 Schr\u00f6tter accompanied scientists  Nathan Zuntz ,  Arnold Durig  (1872\u20131961) and  Joseph Barcroft  (1872\u20131947) on an expedition to  Tenerife , where he conducted research involving respiration and  oxygenation  at higher elevations. During the  Balkan Wars  of 1912-13, he worked with the  Red Cross  in  Montenegro , afterwards serving as a physician during  World War I  (including a stint as  Sanit\u00e4tschef  in  Jerusalem ). After the war he was director of  Malariaspitals  in  Wieselburg , and following his discharge from military service, he was in charge of the  Alland   Lungenheilanstalt  (lung hospital founded by his father in 1898). In the 1920s he made  balneological  studies of the  Dead Sea , and in 1925 was habilitated for  internal medicine  at the University of Vienna."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4440", "contents": "Schr\u00f6tter was a pioneer of  aviation  and  hyperbaric medicine , and made important contributions in the study of  decompression sickness . In 1906, Schr\u00f6tter suggested the use of oxygen with  recompression , but concerns over  oxygen toxicity  kept the suggestion from becoming the standard practice that it is today. [ 1 ]  He was interested in the physiological effects that divers experienced when ascending from ocean depths, as well as the effects that higher altitudes placed upon balloonists and mountain climbers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4441", "contents": "On 31 July 1901  meteorologists   Arthur Berson  (1859\u20131942) and  Reinhard S\u00fcring  (1866\u20131950) aboard the balloon  Preussen , and equipped with portable compressed oxygen containers, were able to reach 10,800 meters above sea level. However, at 10,000 meters the two scientists succumbed to unconsciousness, and from this experiment Schr\u00f6tter realized that even 100% oxygen would be an insufficient safeguard against  hypoxia  at very high altitudes. He recognized that special pressurized breathing equipment would be necessary to maintain sufficient blood oxygenation, and proposed using a pressurized sealed chamber for very high altitude balloon flights. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4442", "contents": "Schr\u00f6tter did extensive research involving  pulmonary tuberculosis , and was a pioneer of  bronchoscopy . In 1905 with  Adolf Loewy  (1862\u20131937), he was the first to use an  endobronchial   catheter  as an instrument for airway separation in humans."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4443", "contents": "Sze-Piao Yang  ( Chinese :  \u694a\u601d\u6a19 ;  pinyin :  Y\u00e1ng S\u012bbi\u0101o ; 4 June 1920 \u2013 26 May 2021), also spelled as  Sibiao Yang , was a  Taiwanese  physician and  pulmonologist  who focused on treating  tuberculosis  and related lung diseases. He acted as dean of the affiliated hospital of the  National Taiwan University Hospital  from 1978 to 1984. He then served concurrently as the dean of the National Taiwan University School of Medicine from 1983 to 1985, and also as president of the  Tzu Chi University of Science and Technology . [ 1 ]  He is referred to as the \"Father of Thoracic X-ray Interpretation in Taiwan\" due to his work in establishing the field of research involving X-rays in Taiwan. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4444", "contents": "Born in  Hsinchu  on 4 June 1920, [ 3 ]  Yang went on to attend and graduate from  National Taiwan University  with a  Bachelor of Science . Because of the rampant outbreaks of tuberculosis in his youth and contracting the disease during his schooling years, Yang's medical education and research ended up focusing on that and other lung-based diseases. He decided after recovering from his illness that he was only able to survive because of his access to medical care and the \"financially underprivileged\" wouldn't have the same level of healthcare accessibility, so he wanted to devote himself to such treatments [ 1 ] [ 4 ]  He then continued his education at the  Niigata Medical University , obtaining his  Ph.D. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4445", "contents": "After completing his degree at the National Taiwan University, Yang went on to become an  unpaid deputy  in the university's hospital at the Department of Internal Medicine. During the day, he assisted doctors with their procedures and worked on lab research during the night. However, because Taiwan was under Japanese rule at the time, it was difficult for Taiwanese medical workers to advance to full positions. It wasn't until he turned 25 and Taiwan gained independence after  WWII  that he was given the opportunity to become a professor at the university. After a number of promotions, he was also given a grant by the Ministry of Education to study medical techniques in the United States. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4446", "contents": "The earliest research Yang was involved in during the 1940s and 1950s was  thoracic medicine  and he was the first to conduct such research in Taiwan after his return to the country. His first major case occurred in 1951 while treating tuberculosis patients. A ship's captain had purportedly contracted the disease, but Yang's analysis of the  sputum  found that the man was instead infected with lung leeches, which can frequently be misdiagnosed as a variety of lung-based diseases. The cause of such infections usually results from eating raw  shellfish  and it led to Yang further investigating and writing a paper on how lung leech infections occur. His research was published both in the journal of the International Society of Thoracic Diseases in 1954 and then the  American Journal of Respiratory and Critical Care Medicine  in 1955. These were the first papers from Taiwan published in major international journals and resulted in his work being included in medical textbooks in Taiwan. [ 2 ]  Another incident in 1952 involving a trio of sick mine workers resulted in Yang being sent to  Jinguashi  to investigate and he was able to do a work environment study to determine that  pneumoconiosis  was the cause of the outbreak. [ 1 ]   This resulted in the first occupational disease research that was conducted in Taiwan. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4447", "contents": "Yang would go on to establish a Joint Thoracic Disease Symposium in the mid 1950's involving multiple hospitals and would treat the first person in Taiwan for lung cancer in 1957. [ 1 ]  Another medical conference was established by Yang in 1971 named  The Second Asia Pacific Conference on Thoracic Diseases  for an international attendance. After this, he would continue his medical work and eventually become  dean  of the school of medicine at the National Taiwan University and of the on-campus hospital in 1979. That same year, he joined the Sino-Saudi Medical Corps in order to expand Taiwan's medical outreach to other countries. [ 2 ]  Starting in 1984, he became the director of the  Tzu Chi  general hospital and was involved in the opening of the hospital in 1986. He also was the first principal of the Tzu Chi Nursing College (later renamed to the University of Science and Technology) and helped in its creation. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4448", "contents": "An area of research Yang became highly trained in was X-ray interpretations and even after his retirement from the hospital in 1985, he spent the next three decades until 2018 traveling once a week to the Hualien Tzu Chi Hospital to teach students how to read and interpret patient X-rays. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4449", "contents": "The 2018 Medical Contribution Award was given to Yang for his contributions to medical knowledge throughout his lifetime. A TV series also aired in 2019 titled \"Hundred Years Old Doctor\" that was based around events in his life. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4450", "contents": "During his early 20's working as a medical assistant in the National Taiwan University Hospital, Yang met the head nurse at the time, Chen Baoyu. Later, at the height of World War II, the Japanese commercial ship Takachihomaru was sunk by American battleships at the  Port of Keelung . His brother, sister-in-law, and their yet-to-be-born child died in the incident, and the grief this caused the family resulted in them ordering Yang to get married. This never occurred with Chen, however, due to him leaving for his research grant in the United States and this part of his life was dramatized in the theater play titled  Medical World Love . In the subsequent years, he was married to a different partner, but she died in the 1960s, and he later rekindled a relationship with Chen before marrying her in 1984. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4451", "contents": "Yang published a book about his life in early 2018 titled  A Hundred Years Old Physician Dedicates with Love  with the dedication that he would not retire until he reached 100 years old. [ 3 ]  In March 2018, Yang donated $60 million out of his life savings to the Tzu Chi general hospital. [ 7 ]  He died on 26 May 2021, aged 100. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4452", "contents": "Flight Transport, Air Ambulance"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4453", "contents": "A  respiratory therapist  is a specialized  healthcare practitioner  trained in  critical care  and cardio-pulmonary medicine in order to work therapeutically with people who have acute critical conditions,  cardiac  and  pulmonary disease . Respiratory therapists graduate from a college or university with a degree in respiratory therapy and have passed a national board certifying examination. The NBRC ( National Board for Respiratory Care ) is responsible for credentialing as a CRT ( certified respiratory therapist ), or RRT ( registered respiratory therapist ) in the United States. The CBRC ( Canadian Board for Respiratory Care ) is responsible for credentialing as an RRT in Canada."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4454", "contents": "The specialty certifications of respiratory therapy include: CPFT and RPFT (Certified or Registered Pulmonary Function Technologist), ACCS (Adult Critical Care Specialist), NPS (Neonatal/Pediatric Specialist), and SDS ( Sleep Disorder Specialist )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4455", "contents": "Respiratory therapists work in hospitals in the intensive care units (Adult, Pediatric, and Neonatal), on hospital floors, in emergency departments, in pulmonary functioning laboratories (PFTs), are able to intubate patients, work in sleep labs ( polysomnography ) (PSG) labs, and in home care specifically DME ( durable medical equipment ) and home oxygen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4456", "contents": "Respiratory therapists are specialists and educators in many areas including  cardiology ,  pulmonology , and sleep therapy. Respiratory therapists are clinicians trained in advanced  airway management ; establishing and maintaining the airway during management of trauma, and intensive care."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4457", "contents": "Respiratory therapists initiate and manage  life support  for people in intensive care units and emergency departments, stabilizing, treating and managing pre-hospital and hospital-to-hospital patient transport by air or ground ambulance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4458", "contents": "In the outpatient setting respiratory therapists work as educators in asthma clinics, ancillary clinical staff in pediatric clinics, and sleep-disorder diagnosticians in sleep-clinics, they also serve as clinical providers in cardiology clinics and cath-labs, as well as working in pulmonary rehabilitation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4459", "contents": "Respiratory therapy, done by respiratory therapists, is a large variety of treatments to help with breathing and support the heart's work. Giving oxygen and drugs to ease breathing are two examples. Respiratory therapists also do patient assessments."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4460", "contents": "Respiratory therapists educate, assist in diagnosis, and treat people who have heart and lung problems. Specialized in both cardiac and pulmonary care, respiratory therapists often collaborate with specialists in  pulmonology  and  anaesthesia  in various aspects of clinical care of patients. Respiratory therapists provide a vital role in both  medicine  and  nursing  such as the initiation and maintenance of mechanical ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4461", "contents": "Respiratory therapists are also primary clinicians in conducting tests to measure lung function and teaching people to manage  asthma ,  chronic obstructive pulmonary disorder  among other cardiac and lung functions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4462", "contents": "Internationally, respiratory therapists that provide  lung function testing  are termed respiratory scientists, but in North America, they may be a respiratory therapist."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4463", "contents": "Outside of clinics and hospitals, respiratory therapists often manage home oxygen needs of patients and their families, providing around the clock support for home ventilators and other equipment for conditions like  sleep apnea ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4464", "contents": "In the clinic or outpatient setting respiratory therapists assist with diagnosis and serve as an educator for patients with cardiac and respiratory illness. [ 1 ]  In the  United States , respiratory therapists with certification as  registered respiratory therapists  evaluate and treat patients with a great deal of autonomy under the direction of a  pulmonologist . [ 2 ]  In facilities that maintain critical care transport teams respiratory therapists are a preferred addition to all types of  surface  or  air transport . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4465", "contents": "In other settings respiratory therapists are found in schools as asthma educators, working with teachers and coaches about childhood symptoms of asthma and how to spot an emergency. In the United States, legislation has been unsuccessfully introduced several times to allow respiration therapists certified as asthma specialists with registered respiratory therapist certification to prescribe and manage previously diagnosed respiratory patients in physician clinics. [ 4 ] [ 5 ]  In sleep clinics, respiratory therapists work with physicians in the diagnosis of sleep-related illnesses. Respiratory therapists in the United States are migrating toward a role with autonomy similar to the   extension of the physician like the  physician assistant . [ 6 ]  Respiratory therapists are frequently utilized as complete cardiovascular specialists to place and manage arterial accesses along with peripherally-inserted central catheters. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4466", "contents": "In the  United States  and  Canada , respiratory therapists are healthcare practitioners who, after receiving their education, complete a credentialing process and become a certified respiratory therapists (CRT) or registered respiratory therapists (RRTs)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4467", "contents": "After satisfactorily completing the required examinations and being added to a registry, the practitioner is then eligible to apply for a license to practice in the region governed by their respective licensing body."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4468", "contents": "In the  United States , specialist respiratory therapists are clinicians who hold National Board for Respiratory Care specialty credentials, which may include neonatal/pediatric specialist (CRT-NPS or RRT-NPS), adult critical care specialist (RRT-ACCS), sleep disorder specialist (CRT-SDS or RRT-SDS), and pulmonary function technologist (CPFT or RPFT). The NBRC's RRT-ACCS examination is the newest NBRC examination: it was introduced in 2012."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4469", "contents": "In the  United States , one must obtain a degree in respiratory care and must then sit for the board exams to become a RRT. RRT is issued by the  National Board for Respiratory Care  after passing the Therapist Multiple-Choice Examination  NBRC-TMC  and Clinical Simulation Examination  NBRC-CSE  examinations. [ 8 ]  Eligibility for the NBRC-CSE examination is based on scoring high enough on the NBRC-TMC, and holding at least an  Associate of Science in Respiratory Care . Professional credentials denoted as a Certified Asthma Educator (AE-C) may also be earned by passing the National Asthma Educator Certification Board  [ 9 ] (NAECB) exam."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4470", "contents": "In some parts of Canada, one may practice as a provisional respiratory therapist after graduating, until writing and passing the CBRC exam. The RRT certification is granted by examination from the  Canadian Society of Respiratory Therapists ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4471", "contents": "The registered respiratory therapist is typically governed by their medical director for clinical services and their licensing body for laboratory, rehabilitation and home-health services. [ 10 ]  Trained in cardiology and pulmonology medicine. The registered respiratory therapist is prepared didactically and clinically to perform advanced procedures and emergency management. [ 11 ]  Actual scope of practice varies by region and institution. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4472", "contents": "Except for the United States and Canada, very few countries have a dedicated professional role for respiratory health. In these countries, respiratory care is provided by physiotherapists, nurses and physicians that have chosen to specialize in this field. In many countries this recognition is in a transition stage; as an example, in 2011, a journal from China claimed that hospitals in  Beijing, China  began a recruitment drive to acquire respiratory therapists for their intensive care units where previously nurses were the only clinician. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4473", "contents": "Upon graduation from an accredited school of respiratory therapy, the graduate is then eligible to write the national exam administered by the  Canadian Board for Respiratory Care ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4474", "contents": "Success on this examination will then allow the respiratory therapist to register with any licensing body in Canada. Alberta, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Quebec and Saskatchewan are the Canadian provinces with provincial licensing bodies; in these provinces, it is illegal to practice the profession of Respiratory Care without first being licensed as a full or provisional member with the provincial licensing body."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4475", "contents": "These provinces are so-called regulated provinces. In some provinces, one may work provisionally upon graduating, until writing and passing the exam. In all other jurisdictions, the licensing body for the profession of Respiratory Care is the  Canadian Society for Respiratory Therapy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4476", "contents": "Registration as a full member is optional for respiratory therapists living in regulated provinces, however, for respiratory therapists living in non-regulated provinces, registration as a full member with the CSRT is compulsory. Registration with the provincial regulatory body or the CSRT (in non-regulated provinces) confers upon the respiratory therapist the title of registered respiratory therapist (RRT). Canada and the United States recognize each of their cardio-pulmonary education structure as equal, however, a qualifying exam must be written in order to practice in either nation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4477", "contents": "There is pressure for the program to become a degree, like other therapies ( physical therapy ,  occupational therapy ) now require a master's degree or greater. However, in some places such as  Alberta , Canada the cardio-pulmonary course work is only offered at technical schools that are unable to grant a formal degree."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4478", "contents": "Respiratory therapy is a sub-specialty of  physical therapy  in France. [ 14 ]  Respiratory care as a specialty is regulated by the F\u00e9d\u00e9ration Fran\u00e7aise des Masseurs Kin\u00e9sith\u00e9rapeutes R\u00e9\u00e9ducateurs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4479", "contents": "The  German Respiratory Society [ 15 ]  first issued a resolution to develop the dedicated respiratory therapist (RT) role in 2004 as a means to increase the quality of patient care, delegate physician duties and respond to the observed increase in respiratory conditions and diseases. In 2006, a year-long pilot training program was offered to established nurses and physiotherapists. [ 16 ]  Researchers report that significant\nadditional work is necessary to define and position the role of the respiratory therapist within the current healthcare system. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4480", "contents": "In Italy, the title of the respiratory therapist can be acquired applying to the master's degree in respiratory therapy. [ 18 ]  It consists of frontal lessons and various internships throughout Italian hospitals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4481", "contents": "In  Philippines  respiratory therapists are clinicians who have been awarded at minimum a  Bachelor of Science in Respiratory Care  degree. [ 19 ]  Licenses to practice respiratory care are regulated by the Professional Regulatory Board of Respiratory therapy and Professional Regulation Commission which is established and legally maintained by the  Philippine Respiratory Therapy Act  (Republic Act No. 10024). [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4482", "contents": "In  United Arab Emirates  respiratory therapists must have been awarded a  Bachelor of Science in Respiratory Care . An additional two-years of experience is required for foreign applicants. Licenses are maintained and awarded by the  Dubai Health Authority . The  Dubai Health Authority  restricts respiratory therapists to working only in physical medicine and rehabilitation Centers, in hospitals, in surgical clinics with cardio-thoracic surgeons and with physicians in family/general practice or pulmonology. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4483", "contents": "Saudi Arabia utilizes respiratory therapists in a similar fashion to Canada and the U.S. Some respiratory therapists from North America travel to Saudi Arabia for temporary need."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4484", "contents": "In Singapore, a respiratory therapist is an allied health professional who plays an integral role in the care of critically ill patients in the Intensive Care Units, managing patients on invasive and non-invasive mechanical ventilation, and other respiratory supportive devices. Respiratory therapists are recognized domain experts pertaining to respiratory care and are responsible to facilitate learning and training for respiratory care topics (mechanical ventilation management, artificial airway management, lung protective strategies, diagnostic procedures, etc) for medical students, nursing students, and health care colleagues (nurses, physicians, allied health professions) in the hospitals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4485", "contents": "As part of their duties, some of the respiratory therapists are also routinely assigned to staff the emergency department, outpatient ambulatory clinics, diagnostic polysomnography laboratories, as well as the pulmonary function test laboratories to assist with the diagnostic procedures for patients."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4486", "contents": "All respiratory therapists in Singapore have a baccalaureate degree in respiratory therapy awarded by accredited institutions across the region and the United States and hold board certifications in their country of training.\nIn 2010, the Association of Respiratory Therapists Singapore (ARTS) was established as the national professional organization for respiratory therapists working in Singapore and is a recognized international affiliate of the American Association for Respiratory Therapists (AARC). In 2022, ARTS was also inducted as a council member into the International Council for Respiratory Therapists, with two established leaders serving as co-governors to represent the interests of respiratory therapists in Singapore."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4487", "contents": "As of 2024, services and care provided by respiratory therapists can be found in all public hospitals in the country and is continuing to grow at with demand."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4488", "contents": "In the United States, a respiratory therapist is a clinician who has at a minimum completed an  Associate of Science in Respiratory Care  degree along with a certification process. After satisfactorily completing required examinations either administered by the  National Board for Respiratory Care  or directly by the individual state licensing board (either the medical examiner's board or a special state respiratory care board), the practitioner is then eligible to apply for a license to practice in the region governed by their respective licensing body.."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4489", "contents": "There are two recognized governing bodies in the United States: the State Board of Respiratory Care in the state in which a respiratory therapist is licensed to practice and the  National Board for Respiratory Care  (NBRC), a non-profit organization which regulates two levels of certification along with some additional specialist certifications."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4490", "contents": "The  Certified Respiratory Therapist  (CRT) is the certification given after successfully passing the Therapist Multiple Choice  NBRC-TMC  exam; the  Registered Respiratory Therapist  (RRT) certification is given after first making the RRT cut-off score on the TMC exam, and passing the Clinical Simulation Exam  NBRC-CSE ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4491", "contents": "Most state boards of respiratory care require proof of the appropriate NBRC credential and award various license titles, including (but not limited to) respiratory care practitioner, licensed registered respiratory therapist, and licensed certified respiratory therapist."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4492", "contents": "There has been a substantial push to standardize the state licensure by the  American Association for Respiratory Care . [ 22 ]  The NBRC credential is renewed every 5 years for a fee in addition to fees assessed by the state boards of respiratory care."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4493", "contents": "Respiratory therapy in the UK is not a recognized specific profession, but a specialization route available to physicians, nurses, physiotherapists, and occupational therapists."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4494", "contents": "Common titles include cardio-respiratory  physiotherapist , clinical respiratory  physiologist  (as well as other healthcare scientists), respiratory  nurse  and cardio-respiratory  occupational therapist ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4495", "contents": "All UK trained  physiotherapists  receive advanced training in respiratory therapy theory and practice as a core component of their pre-registration physiotherapy degree program. Following qualification and a period of rotations throughout the core areas of physiotherapy practice, they may then follow a career pathway specializing in respiratory physiotherapy. Areas of practice include critical care, respiratory medicine, cystic fibrosis, asthma, hyperventilation syndrome, general and specialized surgery, non-invasive ventilation, ventilation weaning, cardiac and pulmonary rehab, respiratory therapy outpatient clinics and community respiratory therapy. The Association of Chartered Physiotherapists interested in respiratory care is the specialist interest group for UK physiotherapists working within the field of respiratory therapy. [ 23 ]  All physiotherapists working within the United Kingdom must be registered with the  Health and Care Professions Council , regardless of their area of clinical practice, in order to be allowed to work in both the public and private sectors. Respiratory physiotherapy postgraduate master's degree and PhD programs exist within the United Kingdom for suitably qualified and experienced therapists."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4496", "contents": "The main grouping of healthcare scientists working in areas similar to respiratory therapists are respiratory and sleep physiologists. [ 24 ]  They perform the majority of comprehensive pulmonary physiological assessments (including cardiopulmonary exercise tests) as well as sleep studies. They might also manage non-invasive ventilation services and undertake allergy testing. Similarly, critical care scientists are involved in many aspects of patient critical care care that respiratory therapists might, including the management and application of invasive ventilation technologies and other respiratory adjuncts as ell as point-of-care blood testing (including interpreting the results for other clinicians), but are also involved in other areas of critical care, such renal replacement therapy and non-respiratory related patient monitoring; Critical care scientists might also be involved in the provision of non-invasive ventilation services and pre-operative cardiopulmonary exercise testing. [ 25 ] [ 26 ] [ 27 ]  Other healthcare science groupings might also occasionally be involved in some of the physiological investigations mentioned above e.g. neurophysiologists might perform sleep studies to investigate neurological reasons for sleep disturbance, while cardiac scientist might perform cardiopulmonary exercise testing focused on the diagnosis of cardiac issues. Since the advent of modernising scientific careers, there have been a largely unitary model of accreditation pathway for Healthcare Scientists in the UK. [ 28 ]  The framework can be roughly divided into four stages: an associate/assistant stage (usually not holding any professional registration), a BSc-level practitioner stage eligible for voluntary registration (e.g.with the Registration Council for Clinical Physiologists or the Academy for Healthcare Science Healthcare Science Practitioner Register), an MSc-level Scientist stage where individuals are eligible for state registration as Clinical Scientists with the  Health and Care Professions Council , and a doctoral-level stage that in addition to registration with the  Health and Care Professions Council  involves registration on the Academy for Healthcare Science Higher Specialist Scientist Register. [ 28 ] [ 29 ] [ 30 ]  Those on the Higher Specialist Scientist Register are largely equivalent in seniority to medical consultants, though they cannot prescribe; in Respiratory Science this might e.g. involve the advising on the provision of non-invasive ventilation to complex patients. [ 31 ] [ 32 ] [ 33 ]  Healthcare Scientists are usually trained to work with all patient age groups."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4497", "contents": "In  Taiwan , the respiratory therapist is one of the allied health professionals who need minimum four-years Bachelor of Science in respiratory therapy (Care) for the license. According to the Health Professionals Act and Respiratory Therapist Act lawed in 2002, [ 34 ] [ 35 ]  respiratory therapists require \"Senior Professional and Technical Examinations\" by  the Ministry of Examination  to get the license. [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4498", "contents": "Most respiratory therapists in Taiwan participate in adult, neonatal and pediatric  ICU  care for artificial airway maintenance, invasive or non-invasive ventilation management, aerosol therapy, oxygen therapy, inhaled Nitric oxide therapy,  CPR , chest physiotherapy, artery blood gas analysis, pulmonary rehabilitation, and lung expansion therapy, etc."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4499", "contents": "Some respiratory therapists also will be available in  PFT (Pulmonary Function Testing)  room or RCC (Respiratory Care Center) and RCW (Respiratory Care Ward) built for focusing on difficult-weaning patients' ventilator weaning. [ 37 ]  Moreover, after 5 years of experience in hospital, respiratory therapists can set up a home respiratory care office by themselves."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4500", "contents": "Nowadays, there are five colleges with the Department of Respiratory Therapy including Chang Gung University, Taipei Medical University, Kao Hsiung Medical University, Chang Gung University of Science and Technology (ChiaYi Campus), and Fu Jen Catholic University. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4501", "contents": "Respiratory care in  Yemen  has started in 2005 and the profession has accredited by Yemeni Medical Council in 2020 as one of allied medical professions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4502", "contents": "Respiratory care professionals need to complete either minimum three years  Associate of Science in Respiratory Care  or four-years  Bachelor of Science in respiratory care  (BsRC) for the license called YRCLE. [ citation needed ]  there are currently 3 accredited programs in bachelor degree and one postgraduate program as  master of science in respiratory care  in Yemen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4503", "contents": "Yemen has joined  International Council For Respiratory care  in 2020 as the third Arabic country after  Saudi Arabia  &  UAE . It has currently full member of  International Council For Respiratory care  and Saleem N. Hamilah, BS, RCP, FNIV, MsRC is the official governor for Yemen. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4504", "contents": "The Respiratory Care Services Administration (RCSA) is a governmental administration at Yemen's Ministry of Public Health & Population established in July 2019. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4505", "contents": "The Yemeni Association for Respiratory Care (YARC) is a  non profit organization  and is the only professional organization supporting  Respiratory Care  in the Yemen. In addition to attempting to help respiratory therapists nationally and locally, the YARC is trying to promote the profession as a whole to increase interest and membership. The YARC established in 2017. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4506", "contents": "The traditional role of the operating room respiratory therapist has included providing technical support to the  anesthesiologist  for the proper use and maintenance of the  anesthetic  gas machine, in addition to also providing  airway management . In Ontario, Canada, this role in the operating room has evolved to include a more advanced and specialized role with increasing responsibilities to the respiratory therapist. This \"anesthesia assistant\" is a distinct occupation from the American \"anesthesiologist assistant\". These Canadian respiratory therapists are academically prepared to perform activities such as sedation by the administration of anesthetic gases and medications, insertion and management of vascular (arterial and venous) access and assessment of the depth of  anesthesia  under the guidance of an  anesthesiologist . [ 39 ]  This role is similar to the  nurse anesthetist , [ 40 ]  except that an anesthesia assistant must have an  anesthesiologist  supervising them and a  nurse anesthetist , does not. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4507", "contents": "Asthma  specialists work with clinics, hospitals and schools as an educator for teachers, parents, patients and practitioners on asthma and allergies. Respiratory therapists in the role as an asthma educator additionally help diagnose and treat asthma and other respiratory illness. [ 42 ]  Additionally, an asthma educator is the resource clinician in inpatient and outpatient environments for evaluating and advising physicians on treatment plans and helping facilitate patient understanding and compliance with the plan. [ 43 ]  In the United States, certified asthma educators (AE-C) are credentialed by the  National Asthma Education Certification Board  (NAECB). [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4508", "contents": "In Canada, the Canadian Network for Respiratory Care administers two certifications for the specialization as respiratory therapist asthma educator, the certified asthma educator (CAE) (preferred by practitioners with a pediatric focus) and the certified respiratory educator (CRE), which comprises the CAE program with additional training in  COPD . [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4509", "contents": "Respiratory therapists work with people who  cystic fibrosis  in clinics and hospitals [ 46 ]  by educating them about their disease and working with them on a treatment plan. While admitted to a hospital, patients with cystic fibrosis have their treatment schedule modified and maintained by respiratory therapists. Maintaining a healthy schedule for pharmacokinetic and physical therapeutic airway clearance typically more frequent than home treatment plans because admissions are usually due to an increased need for therapy during the stay."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4510", "contents": "Respiratory therapists are able to fulfill the role of perfusionist with appropriate training. The perfusionist is a highly trained member of the cardiothoracic surgical team (often time an RT with extra training) which consists of  cardiac surgeons ,  anesthesiologists ,  physician assistants ,  surgical technicians , other  respiratory therapists , and  nurses . The perfusionist's main responsibility is to support the physiological and metabolic needs of the cardiac surgical patient so that the  cardiac surgeon  may operate on a still, unbeating  heart . Perfusionist certifications are maintained and awarded by The  American Board of Cardiovascular Perfusion . [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4511", "contents": "Extracorporeal membrane oxygenation  (ECMO) is a modified  cardiopulmonary bypass  technique used for the treatment of life-threatening cardiac or respiratory failure. An ECMO Clinical Specialist is a technical specialist trained to manage the ECMO system including blood pump, tubing, artificial oxygenator, and related equipment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4512", "contents": "The ECMO Specialist is also responsible for the clinical needs of the patient on ECMO which may include bedside management of oxygenation and carbon dioxide removal, maintenance of normal acid-base balance, administration of medications, blood and blood products, and maintenance of appropriate anticoagulation therapies for the blood. [ 48 ] [ 49 ]  This ECMO Clinical Specialist may be the bedside critical care nurse specifically trained in ECMO patient and circuit management, [ 50 ]  or the ECMO system may be primarily managed by a  registered respiratory therapist , [ 51 ]  or physicians with training as ECMO clinical specialists. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4513", "contents": "Much like adult intensivist respiratory therapists, neonatal and pediatric specialists deal primarily with managing life support for the pediatric or neonatal patient. [ 52 ]  Pediatric respiratory therapists are trained extensively in antenatal and intrapartum patients and family. [ 52 ]  In the United States a specialist certification exists and is awarded by the  National Board for Respiratory Care . Available to respiratory therapists holding certification as a  certified respiratory therapist  or  registered respiratory therapist  however the registered respiratory therapist is preferred by most institutions. [ 52 ] [ 53 ] [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4514", "contents": "Respiratory therapists monitor, interpret and diagnose findings from a  sleep study , as well as the medical history and physical exam to make the diagnosis and decide on treatment related to sleep-disorders. A sleep study can also help diagnose  narcolepsy . [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4515", "contents": "In the United States a sleep disorder specialist can be a  registered respiratory therapist  with the sleep disorder specialist certification ( RRT-SDS ) who performs sleep disorders testing and therapeutic intervention along with a diagnosis of sleep-related disease such as  Obstructive Sleep Apnea  or  Central Apnea . In Canada, it is often an RT with additional training to become a Registered Polysomnography Technician (RPSGT)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4516", "contents": "Case management is a collaborative process that assesses, plans, implements, coordinates, monitors, and evaluates the options and services required to meet the client's health and human services needs. It is characterized by advocacy, communication, and resource management and promotes quality and cost-effective interventions and outcomes. Eligibility and certification is maintained by the Commission for Case Management Certification, a body certifying healthcare professionals in the United States. [ 56 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4517", "contents": "Respiratory therapists work with nurses, physicians, and paramedics in  emergency flight  and ground transport. [ 57 ] [ 58 ]  They are a vital practitioner delivering care inside helicopters, air ambulance or ground ambulance working to pick up a patient and move them to a facility that has what they need. In the United States certification for transport ( C-NPT ) is currently awarded by The National Certification Corporation. [ 59 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4518", "contents": "Respiratory therapists are sometimes referred to as respiratory scientists who are specialists in pulmonary function. [ 60 ]  Respiratory therapists work with  Pulmonologists  in both clinical and general research of the  respiratory system , ranging from the anatomy of the  respiratory epithelium  to the most effective treatment of  pulmonary hypertension  in pediatrics. Scientific research also takes place to look for causes and possible treatment in diseases such as  asthma  and  lung cancer . [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4519", "contents": "The  profession of respiratory care  was officially established in the United States  c. \u20091930 ; [ 22 ]  and respiratory research has officially existed since the early 1900s. [ 62 ]  During the early years, respiratory therapists were referred to as \"oxygen technicians\", and most of their activities involved moving cylinders of compressed gas and administering oxygen via nasal catheter or oxygen tent. [ 63 ]  Most oxygen technicians were trained on the job, although brief training programs began to appear in the late 1940s and 1950s. [ 64 ] [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4520", "contents": "Today the profession hardly resembles what it was in the 1940s. Respiratory therapists provide direct care, patient education, and care coordination. They are academically trained in respiratory nursing and respiratory medicine. They practice in acute care facilities, long-term acute care facilities, skilled nursing facilities, assisted-living centers, subacute care units, rehabilitation centers, diagnostics units, and in the home. [ 66 ]  Respiratory therapist training has also dramatically changed. Current accreditation standards require Respiratory therapists to have, at minimum, an  Associate of Science in Respiratory Care  degree from an accredited program. [ 67 ]  Legal requirements to practice respiratory therapy have also dramatically changed. 49 states now legally recognize respiratory therapists. [ 68 ]  Limited permits or state licenses are now required in all states except Alaska, which has no statutory authority over the practice of respiratory care. All states that have licensure requirements also require continuing education."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4521", "contents": "In 2007 the  American Association for Respiratory Care  (AARC) began developing recommendations for the promotion of the field of respiratory care in the United States [ 22 ]  in response to increased concern regarding licensure and credentialing issues as well as international recognition of those practicing in the United States. [ 6 ]  The task force decided to recommend that by 2015 the minimum education requirement for licensure and certification as a respiratory therapist be a  bachelor of science in respiratory therapy  (BSRT). [ 69 ]  The AARC task force also recommended the  American Respiratory Care Foundation  change its scholarship policies and only award assistance and grants to those working toward a bachelor's degree. The  Committee on Accreditation for Respiratory Care  (CoARC) was asked by the AARC task force to change its accreditation standards and no longer accredit associates level respiratory care programs. [ 69 ]  The CoARC replied by a press release rejecting the recommendation. [ 70 ]  In 2011 legislation introduced by the AARC will help improve the use of respiratory therapists in clinical applications by allowing them to manage patients with  asthma  and  COPD  seeing a clinic for routine checkups. [ 71 ]   Similar bills  have been introduced before and have died in committee. [ 4 ] [ 5 ] [ 72 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4522", "contents": "As of September 2009, there are 348  Registered Respiratory Therapist  (RRT) Programs currently accredited by the  COARC ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4523", "contents": "Acid\u2013base homeostasis  is the  homeostatic  regulation of the  pH  of the  body's   extracellular fluid  (ECF). [ 1 ]  The proper  balance  between the  acids  and  bases  (i.e. the pH) in the ECF is crucial for the normal  physiology  of the body\u2014and for  cellular   metabolism . [ 1 ]  The pH of the  intracellular fluid  and the extracellular fluid need to be maintained at a constant level. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4524", "contents": "The  three dimensional structures  of many extracellular proteins, such as the  plasma proteins  and  membrane proteins  of the body's  cells , are very sensitive to the extracellular pH. [ 3 ] [ 4 ]  Stringent mechanisms therefore exist to maintain the pH within very narrow limits. Outside the acceptable range of pH,  proteins  are  denatured  (i.e. their 3D structure is disrupted), causing  enzymes  and  ion channels  (among others) to malfunction."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4525", "contents": "An  acid\u2013base imbalance  is known as acidemia when the pH is acidic, or alkalemia when the pH is alkaline."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4526", "contents": "In humans and many other animals, acid\u2013base homeostasis is maintained by multiple mechanisms involved in three lines of defense: [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4527", "contents": "The second and third lines of defense operate by making changes to the buffers, each of which consists of two components: a weak acid and its  conjugate base . [ 5 ] [ 13 ]  It is the ratio concentration of the weak acid to its conjugate base that determines the pH of the solution. [ 14 ]  Thus, by manipulating firstly the concentration of the weak acid, and secondly that of its conjugate base, the pH of the  extracellular fluid  (ECF) can be adjusted very accurately to the correct value. The bicarbonate buffer, consisting of a mixture of carbonic acid (H 2 CO 3 ) and a bicarbonate ( HCO \u2212 3 ) salt in solution, is the most abundant buffer in the extracellular fluid, and it is also the buffer whose acid-to-base ratio can be changed very easily and rapidly. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4528", "contents": "The  pH  of the extracellular fluid, including the  blood plasma , is normally tightly regulated between 7.32 and 7.42 by the  chemical buffers , the  respiratory system , and the  renal system . [ 13 ] [ 16 ] [ 17 ] [ 18 ] [ 1 ]  The normal pH in the  fetus  differs from that in the adult. In the fetus, the pH in the  umbilical vein  pH is normally 7.25 to 7.45 and that in the  umbilical artery  is normally 7.18 to 7.38. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4529", "contents": "Aqueous   buffer solutions  will react with  strong acids  or  strong bases  by absorbing excess  H +  ions, or  OH \u2212  ions, replacing the strong acids and bases with  weak acids  and  weak bases . [ 13 ]  This has the effect of damping the effect of pH changes, or reducing the pH change that would otherwise have occurred. But buffers cannot correct abnormal pH levels in a solution, be that solution in a test tube or in the extracellular fluid. Buffers typically consist of a pair of compounds in solution, one of which is a weak acid and the other a weak base. [ 13 ]  The most abundant buffer in the ECF consists of a solution of carbonic acid (H 2 CO 3 ), and the bicarbonate ( HCO \u2212 3 ) salt of, usually, sodium (Na + ). [ 5 ]  Thus, when there is an excess of  OH \u2212  ions in the solution carbonic acid  partially  neutralizes them by forming H 2 O and bicarbonate ( HCO \u2212 3 ) ions. [ 5 ] [ 15 ]  Similarly an excess of H +  ions is  partially  neutralized by the bicarbonate component of the buffer solution to form carbonic acid (H 2 CO 3 ), which, because it is a weak acid, remains largely in the undissociated form, releasing far fewer H +  ions into the solution than the original strong acid would have done. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4530", "contents": "The pH of a buffer solution depends solely on the  ratio  of the  molar  concentrations of the weak acid to the weak base. The higher the concentration of the weak acid in the solution (compared to the weak base) the lower the resulting pH of the solution. Similarly, if the weak base predominates the higher the resulting pH. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4531", "contents": "This principle is exploited to  regulate  the pH of the extracellular fluids (rather than just  buffering  the pH). For the  carbonic acid-bicarbonate buffer , a molar ratio of weak acid to weak base of 1:20 produces a pH of 7.4; and vice versa\u2014when the pH of the extracellular fluids is 7.4 then the ratio of carbonic acid to bicarbonate ions in that fluid is 1:20. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4532", "contents": "The  Henderson\u2013Hasselbalch equation , when applied to the  carbonic acid-bicarbonate buffer system  in the extracellular fluids, states that: [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4533", "contents": "However, since the carbonic acid concentration is directly proportional to the  partial pressure  of carbon dioxide ( \n \n \n \n \n P \n \n \n \n \n C \n O \n \n \n \n 2 \n \n \n \n \n \n \n {\\displaystyle P_{{\\mathrm {CO} }_{2}}} \n \n ) in the extracellular fluid, the equation can be  rewritten as follows : [ 5 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4534", "contents": "The pH of the extracellular fluids can thus be controlled by the regulation of  \n \n \n \n \n P \n \n \n \n \n C \n O \n \n \n \n 2 \n \n \n \n \n \n \n {\\displaystyle P_{{\\mathrm {CO} }_{2}}} \n \n  and the other metabolic acids."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4535", "contents": "Homeostatic control  can change the  P CO 2  and hence the pH of the arterial plasma within a few seconds. [ 5 ]  The partial pressure of carbon dioxide in the arterial blood is monitored by the  central chemoreceptors  of the  medulla oblongata . [ 5 ] [ 20 ]  These chemoreceptors are sensitive to the levels of carbon dioxide and pH in the  cerebrospinal fluid . [ 14 ] [ 12 ] [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4536", "contents": "The central chemoreceptors send their information to the  respiratory centers  in the medulla oblongata and  pons  of the  brainstem . [ 12 ]  The respiratory centres then determine the average rate of ventilation of the  alveoli  of the  lungs , to keep the  P CO 2  in the arterial blood constant. The respiratory center does so via  motor neurons  which activate the  muscles of respiration  (in particular, the  diaphragm ). [ 5 ] [ 21 ]  A rise in the  P CO 2  in the arterial blood plasma above 5.3\u00a0kPa (40\u00a0mmHg) reflexly causes an increase in the rate and depth of  breathing . Normal breathing is resumed when the partial pressure of carbon dioxide has returned to 5.3\u00a0kPa. [ 8 ]  The converse happens if the partial pressure of carbon dioxide falls below the normal range. Breathing may be temporally halted, or slowed down to allow carbon dioxide to accumulate once more in the lungs and arterial blood. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4537", "contents": "The sensor for the plasma HCO \u2212 3  concentration is not known for certain. It is very probable that the  renal  tubular cells of the  distal convoluted tubules  are themselves sensitive to the pH of the plasma. The metabolism of these cells produces CO 2 , which is rapidly converted to H +  and HCO \u2212 3  through the action of  carbonic anhydrase . [ 5 ] [ 10 ] [ 11 ]  When the extracellular fluids tend towards acidity, the renal tubular cells secrete the H +  ions into the tubular fluid from where they exit the body via the urine. The HCO \u2212 3  ions are simultaneously secreted into the blood plasma, thus raising the bicarbonate ion concentration in the plasma, lowering the carbonic acid/bicarbonate ion ratio, and consequently raising the pH of the plasma. [ 5 ] [ 12 ]  The converse happens when the plasma pH rises above normal: bicarbonate ions are excreted into the urine, and hydrogen ions into the plasma. These combine with the bicarbonate ions in the plasma to form carbonic acid (H +  + HCO \u2212 3   \n \n \n \n \u21cc \n \n \n {\\displaystyle \\rightleftharpoons } \n \n  H 2 CO 3 ), thus raising the carbonic acid:bicarbonate ratio in the extracellular fluids, and returning its pH to normal. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4538", "contents": "In general, metabolism produces more waste acids than bases. [ 5 ]  Urine produced is generally acidic and is partially neutralized by the ammonia (NH 3 ) that is excreted into the urine when  glutamate  and  glutamine  (carriers of excess, no longer needed, amino groups) are  deaminated  by the  distal renal tubular epithelial  cells. [ 5 ] [ 11 ]  Thus some of the \"acid content\" of the urine resides in the resulting ammonium ion (NH 4 + ) content of the urine, though this has no effect on pH homeostasis of the extracellular fluids. [ 5 ] [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4539", "contents": "Acid\u2013base imbalance  occurs when a significant insult causes the blood pH to shift out of the normal range (7.32 to 7.42 [ 16 ] ). An abnormally low pH in the extracellular fluid is called an  acidemia  and an abnormally high pH is called an  alkalemia . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4540", "contents": "Acidemia  and  alkalemia  unambiguously refer to the actual change in the pH of the extracellular fluid (ECF). [ 24 ]  Two other similar sounding terms are  acidosis  and  alkalosis . They refer to the customary effect of a component, respiratory or metabolic.  Acidosis  would cause an  acidemia  on its own (i.e. if left \"uncompensated\" by an alkalosis). [ 24 ]  Similarly, an  alkalosis  would cause an  alkalemia  on its own. [ 24 ]  In medical terminology, the terms  acidosis  and  alkalosis  should always be qualified by an adjective to indicate the  etiology  of the disturbance:  respiratory  (indicating a change in the partial pressure of carbon dioxide), [ 25 ]  or  metabolic  (indicating a change in the Base Excess of the ECF). [ 9 ]  There are therefore four different acid-base problems:  metabolic acidosis ,  respiratory acidosis ,  metabolic alkalosis , and  respiratory alkalosis . [ 5 ]  One or a combination of these conditions may occur simultaneously. For instance, a  metabolic acidosis  (as in uncontrolled  diabetes mellitus ) is almost always partially compensated by a  respiratory alkalosis  (hyperventilation). Similarly, a  respiratory acidosis  can be completely or partially corrected by a  metabolic alkalosis . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4541", "contents": "Acid\u2013base imbalance  is an abnormality of the human body's normal  balance of acids and bases  that causes the  plasma   pH  to deviate out of the normal range (7.35 to 7.45). In the  fetus , the normal range differs based on which umbilical vessel is sampled ( umbilical vein  pH is normally 7.25 to 7.45;  umbilical artery  pH is normally 7.18 to 7.38). [ 1 ]  It can exist in varying levels of severity, some life-threatening."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4542", "contents": "An excess of acid is called  acidosis  or acidemia, while an excess in bases is called  alkalosis  or alkalemia. The process that causes the imbalance is classified based on the cause of the disturbance (respiratory or metabolic) and the direction of change in pH (acidosis or alkalosis). This yields the following four basic processes:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4543", "contents": "The presence of only one of the above derangements is called a  simple  acid\u2013base disorder. In a  mixed  disorder, more than one is occurring at the same time. [ 2 ]  Mixed disorders may feature an acidosis and alkosis at the same time that partially counteract each other, or there can be two different conditions affecting the pH in the same direction. The phrase \"mixed acidosis\", for example, refers to  metabolic acidosis  in conjunction with  respiratory acidosis . Any combination is possible, as metabolic acidosis and alkalosis can co exist together."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4544", "contents": "The traditional approach to the study of acid\u2013base physiology has been the  empirical  approach. The main variants are the  base excess  approach and the  bicarbonate  approach. The  quantitative  approach introduced by  Peter A Stewart  in 1978 [ 3 ]  is newer."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4545", "contents": "There are numerous reasons that each of the four processes can occur (detailed in each article). Generally speaking, sources of acid gain include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4546", "contents": "Sources of acid loss include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4547", "contents": "The body's  acid\u2013base balance  is tightly regulated. Several  buffering agents  exist which reversibly bind hydrogen ions and impede any change in pH.  Extracellular  buffers include  bicarbonate  and  ammonia , while  proteins  and  phosphate  act as  intracellular  buffers. The  bicarbonate buffering system  is especially key, as  carbon dioxide  (CO 2 ) can be shifted through  carbonic acid  (H 2 CO 3 ) to hydrogen ions and  bicarbonate  (HCO 3 \u2212 ) as shown below."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4548", "contents": "Acid\u2013base imbalances that overcome the buffer system can be compensated in the short term by changing the rate of  ventilation . This alters the concentration of  carbon dioxide  in the blood, shifting the above reaction according to  Le Chatelier's principle , which in turn alters the pH. For instance, if the blood pH drops too low ( acidemia ), the body will compensate by increasing breathing, expelling CO 2 , and shifting the reaction above to the right such that fewer hydrogen ions are free\u2013thus the pH will rise back to normal. For  alkalemia , the opposite occurs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4549", "contents": "The  kidneys  are slower to compensate, but  renal physiology  has several powerful mechanisms to control pH by the excretion of excess acid or base. In responses to acidosis,  tubular  cells reabsorb more bicarbonate from the tubular fluid,  collecting duct  cells secrete more hydrogen and generate more bicarbonate, and  ammoniagenesis  leads to increased formation of the NH 3  buffer. In responses to alkalosis, the kidney may excrete more bicarbonate by decreasing hydrogen ion secretion from the tubular epithelial cells, and lowering rates of  glutamine  metabolism and ammonia excretion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4550", "contents": "Airway clearance therapy  is treatment that uses a number of airway clearance techniques to clear the  respiratory airways  of  mucus  and other secretions. [ 1 ]  Several  respiratory diseases  cause the normal  mucociliary clearance mechanism  to become impaired resulting in a build-up of mucus which obstructs breathing, and also affects the  cough reflex . Mucus build-up can also cause infection, and inflammation, and repeated infections can result in damage to the airways, and the  lung tissue . [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4551", "contents": "All airway clearance therapy involves the techniques of  coughing , or huffing that need to be used in conjunction with another airway clearance technique. [ 3 ]   Respiratory therapists  make recommendations and give guidance for appropriate airway clearance therapies. They also give instruction in the use of various airway clearance techniques."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4552", "contents": "Airway clearance therapy uses different  airway clearance techniques  (ACTs) in a number of respiratory disorders including,  cystic fibrosis ,  bronchitis ,  bronchiectasis , and  chronic obstructive pulmonary disease  to maintain respiratory health, and prevent the damaging consequences of inflammation. [ 4 ] [ 1 ] [ 2 ]  Techniques used are breathing, manual, and mechanical. [ 5 ]  They all need to be used with either  coughing  or huffing which moves mucus from the large airways. [ 3 ]  To move mucus from the small airways an additional ACT needs to be employed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4553", "contents": "Breathing techniques include the active cycle of breathing which includes huffing; and autogenic drainage, a technique that requires concentrated effort. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4554", "contents": "Huffing  or a huff cough, is also called  forced expiration technique , and helps to move mucus away from the lung wall so that it can finally be  coughed out . Huffing needs to be carried out in a sitting position with the chin raised a little, and the mouth remaining open. A deep breath is taken to fill the lungs about 75 per cent, and held for two or three seconds. Breathing out is forceful and slow which helps to move the mucus from the smaller to the larger airways. A normal urge to cough at this point is repressed, and the breathing pattern is repeated a few times. A strong cough then follows to expel the mucus. [ 3 ]  Huffing forms part of the active cycle of breathing. Huffing as a clearance technique is different to the term of  huffing  used in substance  inhalation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4555", "contents": "The  active cycle of breathing technique  is carried out in three phases. Phase one is used to relax the airways; phase two involves moving the inhaled air to behind the mucus in order to clear it; phase three helps to clear the mucus out from the lungs. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4556", "contents": "Gentle effortless breathing, in through the nose, and out through the mouth is used in phase one to relax the airways. The shoulders and upper chest are kept relaxed. On breathing out, the  pursed lips method  is advised. Keeping the lips pursed (as in kissing somebody) when exhaling creates a back pressure that keeps the airways open for longer. One recommendation is for six breaths of control to take place before phase two of the cycle. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4557", "contents": "Phase two involves using exercises to expand the chest. Breathing is deep and may use a breath-hold of three seconds to move the air into the smaller airways, and reach behind the mucus. The out breath is unforced and may include some  percussive   clapping , or vibration. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4558", "contents": "Using huffing coughing, mucus is moved from the smaller airways to the larger airways, and huffing needs to be continued until all the mucus is expelled. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4559", "contents": "Autogenic drainage is a controlled airway clearance technique using different depths of inhalation, and different speeds of exhalation that enables mucus to be moved up the airway producing a voluntary cough. This method does not require any equipment, however, it is challenging to perform and appropriate training is required. [ 2 ]  Evidence supporting different techniques is limited. A review of the studies that have been conducted concluded that there is no strong evidence that autogenic drainage is better than other airway clearance techniques. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4560", "contents": "Chest physiotherapy  is a manual airway clearance therapy that uses  chest percussion  ( clapping , and vibration), and  postural drainage . [ 1 ] [ 7 ] [ 8 ]  However, they are labour-intensive, and time-consuming, and mechanical devices are often used instead. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4561", "contents": "Mechanical devices used include positive expiratory pressure (PEP),  intrapulmonary percussive ventilators ,  mechanical insufflation-exsufflation  known as a mechanically assisted cough, [ 1 ] [ 9 ]  and airway oscillatory devices. [ 10 ]  Several mechanical techniques are used to dislodge mucus and encourage its expectoration. Chest percussion can be administered as a manual technique but can also be performed using specific devices that use  chest wall oscillation  or intrapulmonary percussive ventilation. Intrapulmonary percussive ventilators (IPVs) are machines which deliver short bursts of air through a mouthpiece to help to clear mucus. The air is delivered at a rate of approximately 150 pulses per minute and may be used with  nebulized   medication . Chest wall oscillation is a passive system that is not dependent on effort from the user. It involves the use of a special vest that employs the use of a compressor to inflate and deflate the vest rhythmically at timed intervals, and thus imposes high frequency chest wall oscillations that are transferred to the lungs. These oscillations thin airway mucus, and facilitate its removal by coughing. Delivery of air to the vest can be controlled manually."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4562", "contents": "Other methods such as  biphasic cuirass ventilation , and associated clearance mode available in such devices, integrate a cough assistance phase, as well as a vibration phase for dislodging secretions. These are portable and adapted for home use. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4563", "contents": "Positive expiratory pressure physiotherapy consists of providing a back pressure to the airways during expiration. This effect is provided by devices that consist of a mask or a mouthpiece in which a resistance is applied only on the expiration phase. [ 12 ]  Operating principles of this technique seems to be the increase of gas pressure behind mucus through  collateral ventilation  along with a temporary increase in  functional residual capacity  preventing the early collapse of small airways during exhalation. [ 13 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4564", "contents": "The general term  nebulizer  refers to an apparatus that converts liquids into a fine mist. Nozzles also convert liquids into a fine mist, but do so by pressure through small holes. Nebulizers generally use gas flows to deliver the mist. The most common form of nebulizers are medical appliances such as  asthma inhalers  or paint spray cans.  Analytical nebulizers  are a special category in that their purpose is to deliver a fine mist to spectrometric instruments for elemental analysis. They are necessary parts of  inductively coupled plasma atomic emission spectroscopy  ( ICP-AES ),  inductively coupled plasma mass spectrometry  (ICP-MS), and  atomic absorption spectroscopy  (AAS)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4565", "contents": "Analytical nebulizers are used in trace element analysis. This type of work plays an important role in areas of pharmaceutical and clinical study, biological, environmental and agricultural assessment and petroleum testing. They also have nuclear applications."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4566", "contents": "Most analytical pneumatic nebulizers use the same essential principle ( induction ) to  atomize  the liquid: When gas at a higher pressure exits from a small hole (the orifice) into gas at a lower pressure, it forms a gas jet into the lower pressure zone, and pushes the lower pressure gas away from the orifice. This creates a current in the lower pressure gas zone, and draws some of the lower pressure gas into the higher pressure gas jet. At the orifice, the draw of the lower pressure gas creates considerable suction, the extent depending on the differential pressures, the size of the orifice, and the shape of the orifice and surrounding apparatus. In all pneumatic induction nebulizers, the suction near the orifice is utilized to draw the liquid into the gas jet. The liquid is broken into small droplets in the process."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4567", "contents": "Present induction pneumatic nebulizer designs fit into 5 categories: 1. Concentric: Liquid flow surrounded by a Gas flow or Gas flow surrounded by a Liquid flow; 2. Cross Flow: Gas flow at right angles to the Liquid flow; 3. Entrained: Gas and Liquid mixed in the system and emitted as a combined flow. 4. Babington and V Groove: Liquid is spread over a surface to decrease the surface tension, and passed over a gas orifice; 5. Parallel Path: Liquid is delivered beside a gas orifice and induction pulls the liquid into the gas stream."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4568", "contents": "Newer non-induction nebulizers include 3 more categories: 6. Enhanced Parallel Path: Liquid is delivered beside a gas orifice and drawn into the gas stream by surface tension along a spout; 7: Flow Blurring: liquid is injected by pressure into a gas stream; 8. Vibrating Mesh: liquid is pushed through tiny holes by a vibrating ultrasonic plate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4569", "contents": "Concentric nebulizers have a central capillary with the liquid and an outer capillary with the gas. The gas draws the liquid into the gas stream through induction, and the liquid is broken into a fine mist as it moves into the gas stream. In theory, the gas and liquid may be switched with the gas in the center and the liquid in the outer capillary, but generally they work better with the gas outside and the liquid inside. [ 1 ]  The first Canadian concentric patent was Canadian Patent #2405 of April 18, 1873. It was designed to deliver a better spray of oil into a burner. The design is larger but essentially the same as modern analytical nebulizers. The first one developed for spectrometers was a glass design developed by Dr. Meinhard of California in 1973. [ 2 ]  His design enabled early ICP users to have a consistent sample introduction nebulizer, but it plugged easily. Today many companies produce glass concentrics, and since 1997, Teflon concentrics have become available."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4570", "contents": "Cross flow nebulizers have a gas capillary set at right angles to the liquid capillary. The gas is blown across the liquid capillary and this produces a low pressure that draws the liquid into the gas stream. Generally the suction is similar to what is produced in a concentric nebulizer. The benefit of a cross flow is that the liquid capillary have a larger inside diameter allowing for more particles to pass through without plugging the nebulizer. The disadvantage is that the mist is usually not as fine or as consistent. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4571", "contents": "There are no analytical nebulizers at present using this technique, but some oil burners do. Mainly used in much older designs as newer concentrics and cross flows are much better and easier to make."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4572", "contents": "V Groove nebulizers are similar to a cross flow in that the liquid is delivered in a capillary at right angles to the gas capillary, but the liquid is poured down a vertically orientated groove that flows past a gas orifice. The gas pulls the liquid into the gas flow and forms a fine mist. These allow for very large ID liquid capillaries, but have no suction and require a pump to feed the liquid to the device. They must be correctly orientated or they do not allow the liquid to flow past the gas stream. And their mist usually produces larger droplets than with concentrics or cross flows."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4573", "contents": "This design was developed by John Burgener of Burgener Research Inc. Here, the gas stream and sample run through the nebulizer in parallel capillaries. At the tip of the nebulizer, the liquid is pulled into the gas stream and then dispersed into the chamber as a mist."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4574", "contents": "This design was developed by John Burgener of Burgener Research Inc. [ 4 ]  Here, the gas stream and sample run through the nebulizer in parallel capillaries. At the tip of the nebulizer, the liquid is pulled into the gas stream by surface tension along a spout dipping into the gas stream. This allows the gas to impact the liquid, and has the liquid interact in the center of the gas flow where the gas flow speed is highest, producing a better transfer of energy from the gas to the liquid, and producing a finer droplet size. The Burgener Mira Mist nebulizers are the main products using the Enhanced Parallel Path method."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4575", "contents": "This is a new type of nebulizer which does not use induction to mix the sample and gas. Instead, pneumatic atomization is employed here, which results in the micro-mixing of fluids using a reflux cell. [ 5 ]  This means that there is a turbulent mixing of the liquid and gas which results in great sensitivity and is very efficient. The OneNeb is the only example of this sort."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4576", "contents": "Since 2011, this variation on ultrasonic nebulizers has been available. There is a vibrating membrane which has micro holes in it. The sample enters through the back and is pushed through the holes as the membrane vibrates. This makes a fine mist with a droplet size proportional to the hole size. This method requires no gas flow, and is used in conjunction with a chamber. If the droplets are less than 5\u03bcm then they are too small to stick to the chamber walls and the chamber remains dry while 90\u2013100% of the sample makes it to the torch."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4577", "contents": "The early history of medical nebulizers can be read  here . The development of analytical nebulizers since the introduction of the ICP / ICP-MS is seen below: [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4578", "contents": "1970s Adjustable Cross flow (US patent #4,344,574) [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4579", "contents": "1974 Meinhard Concentric"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4580", "contents": "1978 V-groove (by Suddendorf and Boyer) (US Patent #4,206,160) [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4581", "contents": "1980 Pillar and Post (by Garbarino and Taylor)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4582", "contents": "1983 GMK Nebulizer: Glass Babington V-groove"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4583", "contents": "1983 Meinhard C-type nebulizer"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4584", "contents": "1983 Precision glassblowing (similar to Minehard A-type)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4585", "contents": "1983 Jarrell Ash (Thermo) Sapphire V-groove"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4586", "contents": "1983 Meddings' MAK: glass fixed cross flow"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4587", "contents": "1984 Meinhard K-type: recessed inner capillary"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4588", "contents": "1984 Glass Expansion begins making ICP glassware"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4589", "contents": "1985 Burgener-Legere \u2013 first commercial teflon nebulizer \u2013 V-groove \u2013 no adjustable parts"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4590", "contents": "1986 Direct injection micro nebulizer by Fassel, Rice & Lawrence (US patent #4,575,609) [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4591", "contents": "1986 Hildebrand Grid nebulizer"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4592", "contents": "Late 1980s Perkin Elmer Gem Tip cross flow"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4593", "contents": "1988 CETAC Ultrasonic Nebs"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4594", "contents": "1980s Cyclonic chambers"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4595", "contents": "1987 Glass Expansion's first neb \u2013 the VeeSpray (ceramic V-groove)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4596", "contents": "1989 Glass Expansion first concentric \u2013 the Conikal (machined instead of glass blown)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4597", "contents": "1989 Noordermeer Glass V Groove (US patent #4,880,164) [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4598", "contents": "1992 Glass Expansion \u2013 non salting Sea Spray"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4599", "contents": "1993 Modified Lichte Glass V-Groove"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4600", "contents": "1993 Burgener BTF \u2013 first Parallel Path Neb (US patent #5,411,208) [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4601", "contents": "1994\u20131995 Main Burgener Parallel Path Nebs \u2013 BTS 50, BTN & T2002"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4602", "contents": "Mid 1990s Perkin Elmer GemCone: Miniature V-Groove"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4603", "contents": "With the introduction of the ICP-MS to the laboratory, the creation of micro nebulizers became a priority in order to deliver smaller amounts of sample at lower flow rates."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4604", "contents": "1993 The Meinhard HEN (high efficiency nebulizer) was produced which handled very low flow rates but salted and plugged easily as a result. (25 times less sample than a standard Meinhard)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4605", "contents": "1997 Cetac Microconcentric Nebulizer \u2013 first Teflon concentric 50, 100, 200 or 400 \u03bcL/min"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4606", "contents": "1997 Meinhard Direct Injection HEN \u2013 (DIHEN) (US Patent #6,166,379) [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4607", "contents": "1999 Elemental Scientific \u2013 PFA Concentric Nebs 20, 50, 100 or 400 \u03bcL/min"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4608", "contents": "1999 Burgener Micro 1: Parallel Path"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4609", "contents": "2000 Burgener Micro 3: Parallel Path"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4610", "contents": "2001 Burgener Mira Mist: First Enhanced Parallel Path Nebulizer (US patent #6,634,572) [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4611", "contents": "2004 Epond Typhoon: Glass Concentric"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4612", "contents": "2005 Ingeniatrics OneNeb: Flow Blurring Technology"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4613", "contents": "2010 Epond Lucida: Teflon Micro Concentric"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4614", "contents": "2012 Burgener PFA 250: PFA Micro flow Enhanced Parallel Path Nebulizer"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4615", "contents": "2010 \u2013 2013 Meinhard and Glass Expansion: Significant improvements in attachments and designs of glass concentrics."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4616", "contents": "Artificial ventilation or respiration  is when a  machine assists in  a metabolic process to exchange gases in the body by pulmonary ventilation, external respiration, and internal respiration. [ 1 ]  A machine called a ventilator provides the person air manually by moving air in and out of the lungs when an individual is unable to breathe on their own. The ventilator prevents the accumulation of carbon dioxide so that the lungs don't collapse due to the low pressure. [ 2 ] [ 3 ]  The use of artificial ventilation can be traced back to the seventeenth century. There are three ways of exchanging gases in the body: manual methods, mechanical ventilation, and neurostimulation. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4617", "contents": "Here are some key words used throughout the article. The process of forcing air into and out of the lungs is known as ventilation. The process by which oxygen is taken in by the bloodstream is called oxygenation. Lung compliance is the capacity of the lungs to contract and expand. The obstruction of airflow via the respiratory tract is known as airway resistance. The amount of ventilated air that is not involved in gas exchange is known as dead-space ventilation. [ 5 ] [ tone ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4618", "contents": "Pulmonary ventilation is done by manual insufflation of the lungs either by the rescuer blowing into the patient's lungs ( mouth-to-mouth resuscitation ), or by using a mechanical device. Mouth-to-mouth resuscitation is also part of  cardiopulmonary resuscitation  (CPR) making it an essential skill for  first aid . In some situations, mouth to mouth is also performed separately, for instance in near- drowning  and  opiate  overdoses. [ 6 ]  The performance of mouth to mouth on its own is now limited in most protocols to  health professionals , whereas lay first aiders are advised to undertake full CPR in any case where the patient is not breathing. This method of insufflation has been proved more effective than methods which involve mechanical manipulation of the patient's chest or arms, such as the  Silvester method . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4619", "contents": "Mechanical ventilation is a method to mechanically assist or replace spontaneous  breathing . [ 8 ]  This involves the use of  ventilator  assisted by a  registered nurse ,  physician ,  physician assistant ,  respiratory therapist ,  paramedic , or other suitable person compressing a  bag valve mask . Mechanical ventilation is termed \"invasive\" if it involves any instrument penetrating through the mouth (such as an endo tracheal tube ) or the skin (such as a  tracheostomy  tube). [ 9 ]  There are two main  modes of mechanical ventilation  within the two divisions: positive pressure ventilation, where air (or another gas mix) is pushed into the  trachea , and negative pressure ventilation, where air is, in essence, sucked into the lungs. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4620", "contents": "Tracheal intubation  is often used for short-term  mechanical ventilation . It's when a tube is inserted through the nose (nasotracheal intubation) or mouth (orotracheal intubation) and advanced into the  trachea . In most cases tubes with inflatable cuffs are used for protection against leakage and aspiration. Intubation with a cuffed tube is thought to provide the best protection against aspiration. Downside of tracheal tubes is the pain and coughing that follows. Therefore, unless a patient is unconscious or anesthetized,  sedative  drugs are usually given to provide tolerance of the tube. Other disadvantages of tracheal intubation include damage to the mucosal lining of the  nasopharynx  or  oropharynx  and subglottic stenosis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4621", "contents": "In an emergency a  cricothyrotomy  can be used by health care professionals, where an airway is inserted through a surgical opening in the  cricothyroid membrane . This is similar to a  tracheostomy  but a  cricothyrotomy  is reserved for emergency access.  This is usually only used when there is a complete blockage of the  pharynx  or there is massive maxillofacial injury, preventing other adjuncts being used. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4622", "contents": "A rhythmic pacing of the diaphragm is caused with the help  of electrical impulses . [ 12 ] [ 13 ]  Diaphragm pacing is a technique used by persons with spinal cord injuries who are on a mechanical ventilator to aid with breathing, speaking, and overall quality of life. It may be possible to reduce reliance on a mechanical ventilator with diaphragm pacing. [ 14 ]  Historically, this has been accomplished through the electrical stimulation of a  phrenic nerve  by an implanted receiver/electrode, [ 15 ]  though today an alternative option of attaching  percutaneous  wires to the diaphragm exists. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4623", "contents": "The Greek physician  Galen  may have been the first to describe artificial ventilation: \"If you take a dead animal and blow air through its larynx through a reed, you will fill its bronchi and watch its lungs attain the greatest distention.\" [ 17 ]   Vesalius  too describes ventilation by inserting a reed or cane into the  trachea  of animals. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4624", "contents": "It wasn't until 1773, when an English physician  William Hawes  (1736\u20131808) began publicizing the power of artificial ventilation to resuscitate people who superficially appeared to have drowned. For a year he paid a reward out of his own pocket to any one bringing him a body rescued from the water within a reasonable time of immersion.  Thomas Cogan  who was another English physician had become interested in the same subject during a stay at  Amsterdam ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4625", "contents": "In the summer of 1774, Hawes and Cogan each brought fifteen friends to a meeting at the Chapter Coffee-house in  St Paul's  Churchyard, where they founded the  Royal Humane Society . Some methods and equipment were similar to methods used today, such as wooden pipes used in the victims nostrils to blow air into the lungs. Or the use of bellows with a flexible tube for blowing tobacco smoke through the anus to revive vestigial life in the victim's intestines, which was discontinued with the eventual further understanding of respiration. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4626", "contents": "The work of English physician and physiologist  Marshall Hall  in 1856 suggested against the use of any type of bellows/positive pressure ventilation. These views that were held for several decades. The introduction of a common method of external manual manipulation in 1858, was the \"Silvester Method\" invented by  Henry Robert Silvester . A method in which a patient is laid on their back and their arms are raised above their head to aid inhalation and then pressed against their chest to aid exhalation. In 1903, another manual technique, the \"prone pressure\" method, was introduced by Sir  Edward Sharpey Schafer . [ 20 ]  It involved placing the patient on his stomach and applying pressure to the lower part of the ribs. It was the standard method of artificial respiration taught in Red Cross and similar first aid manuals for decades, [ 21 ]  until mouth-to-mouth resuscitation became the preferred technique in mid-century. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4627", "contents": "The shortcomings of manual manipulation led doctors in the 1880s to come up with improved methods of mechanical ventilation, which included  Dr. George Edward Fell 's \"Fell method\" or \"Fell Motor.\" [ 23 ]  It consisted of a bellows and a breathing valve to pass air through a  tracheotomy . He collaboratied with Dr.  Joseph O'Dwyer  to invent the Fell-O'Dwyer apparatus, which is a bellows instrument for the insertion and extraction of a tube down the patients  trachea . [ 24 ] [ 25 ]  Such methods were still looked upon as harmful and were not adopted for many years."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4628", "contents": "In 2020, the supply of mechanical ventilation became a central question for public health officials due to \n 2019\u201320 coronavirus pandemic related shortages ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4629", "contents": "Media related to  Artificial respiration  at Wikimedia Commons"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4630", "contents": "An  Associate of Science in Respiratory Care  ( ASRC ) is an entry-level  tertiary education   respiratory therapy   degree .  In the  United States , this type of degree is usually awarded by  community colleges  or similar  respiratory schools . Some four year colleges also offer this degree. [ 1 ]    Students in the United States awarded an Associate of Science in Respiratory Care are qualified to sit for the  NBRC-ELE  and then the  NBRC-WRE  and  NBRC-CSE  then apply for state  licensure  as a  Registered Respiratory Therapist . [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4631", "contents": "Students awarded an Associate of Science in Respiratory Care are qualified to sit for the three credentialing examinations  NBRC-ELE ,  NBRC-WRE , and  NBRC-CSE  and apply for licensure as a  Registered Respiratory Therapist ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4632", "contents": "This article relating to  education  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4633", "contents": "Asthma camp  is a  summer camp  that is specialized for children with severe versions of  asthma . [ 1 ]   Typically categorized as a special needs summer camp.  The camp counselor role is fulfilled by  respiratory therapists  and  registered nurses  in order to provide a safe and positive experience for children who would otherwise not be able to go to a summer camp.  Asthma camps aim to provide a positive experience for children with asthma through activities like hiking, swimming, canoeing, rope games, arts and crafts, campfires and more all with special considerations and attention to asthma.  Children that attend asthma camps tend to have improved asthma self-management skills and an increase in overall quality of life. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4634", "contents": "Asthma camps are led by  respiratory therapists  and  nurses  who provide medical education, management and oversight for attendees. [ 3 ]   The camps should not have any element that can  trigger  asthma attacks such as pollen or animal dander; this is maintained by camp staff with medical oversight by the medically trained staff. [ 3 ]   Over half of cases in children in the United States occur in areas with air quality below EPA standards, therefore the best locations for these camps are in the top cities for raising a child with asthma. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4635", "contents": "Approximately 120 asthma camps presently serve nearly 10,000 children in the United States. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4636", "contents": "The  Bloxsom air lock  was an  incubator  used in the treatment of respiratory distress among newly born infants in the 1950s. The device attempted to mimic the rhythm of uterine contractions, which were thought to have a role in stimulating fetal breathing. The device was developed by Dr. Allan Bloxsom, a pediatrician at  St. Joseph Hospital  and  Baylor College of Medicine  in  Houston, Texas . At its peak, the device was utilized in more than 700 hospitals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4637", "contents": "In 1956, six years after its introduction, the Bloxsom air lock produced unfavorable results in a clinical trial. By that time physicians had also become leery of the link between high-concentration oxygen and  eye disease in premature babies , and the device fell out of favor. The Bloxsom air lock is sometimes cited as an example of technology that gained wide acceptance following inadequate evaluation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4638", "contents": "Allan Bloxsom was a pediatrician at St. Joseph Hospital and a faculty member at  Baylor College of Medicine . In the early 1940s, he noted that babies born by  cesarean section  required resuscitation at birth more often than those born by vaginal delivery. Writing a 1942 article for  The Journal of Pediatrics , Bloxsom hypothesized that the uterus played an important role in the initiation of breathing at birth. He thought that contractions of the uterus stimulated the fetal  respiratory center , possibly by \"the alternate forcing and drawing of blood from the fetal circulation by compressing the placenta.\" [ 1 ]  He also noted that uterine compression of the fetus, followed by the release of that pressure, might promote breathing in the baby born by vaginal delivery. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4639", "contents": "Bloxsom developed the air lock device based on his assumptions about the role of uterine contractions in establishing effective breathing at birth. The air lock was a sealed steel cylinder that delivered warmed and humidified 60% oxygen to newly born babies. The device has been compared to an  iron lung , but it did not utilize negative pressure. [ 2 ] [ 3 ]  The pressure inside the chamber alternated between 0.07 and 0.2 atmospheres above sea level. Rather than alternating the pressures at the rate of normal respirations as other devices did, the Bloxsom air lock cycled the pressure once per minute to mimic the rate of uterine contractions in late labor. [ 4 ]  Babies in distress were placed in the chamber immediately after delivery. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4640", "contents": "The device was rolled out in 1950. That year, Bloxsom presented a talk on the device at an  American Medical Association  conference. That led to the air lock being featured in  Newsweek , which referred to the device as the \"Plexiglass Mother\". A Houston company developed a Plexiglass model. In 1952,  U.S. Army  physicians shared their experience with the device, writing that the air lock was a valuable resuscitation device and that on occasion it appeared to be lifesaving. Though the apparatus was large and loud, one pediatrician pointed out that the infant was protected from \"meddlesome and unintelligent treatment\" while locked inside the chamber. [ 3 ]  The air lock, which sold for about $1,000 per unit, was used in more than 700 hospitals by the fall of 1952. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4641", "contents": "In a 1951 article in  The Medical Journal of Australia , pediatrician  Kate Isabel Campbell  advanced a theory that there was a link between oxygen administration and the occurrence of  retinopathy of prematurity  (ROP) in preterm infants. ROP had become an increasingly common cause of blindness among newborns. The next year, trials in Europe and the United States linked excessive oxygen and ROP more definitively, though an ideal level of oxygen administration was not clear and there was still no way to monitor an infant's  arterial oxygen levels . [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4642", "contents": "In 1953,  Virginia Apgar  and Joseph Kreiselman conducted a study in which they placed anesthesized dogs inside the chamber. They found that the device did not improve the exchange of carbon dioxide or oxygen in these dogs. Dr. Bloxsom and Sister Mary Angelique published a response to the criticism, pointing out that the device was never intended to help  apneic  dogs. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4643", "contents": "The next year, Bloxsom and Angelique published an article in the  American Journal of Obstetrics and Gynecology  on the 48-hour mortality rate among newborns at St. Joseph. Between 1949 and 1952, this rate had decreased from 63 per 10,000 infants to 37 per 10,000 infants. Bloxsom and Angelique cited the air lock device as a contributor to the improvement in outcomes. However, a 1956 study from  Johns Hopkins Hospital  failed to show a significant difference in outcomes between infants treated in the Bloxsom air lock versus those cared for in the Isolette brand of incubator. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4644", "contents": "Following the publication of the study at Johns Hopkins, and as physicians became aware of the link between high-concentration oxygen and eye disease in newborns, the device fell out of favor in the late 1950s. A small number of hospitals continued to utilize the device into the early 1970s. In 2001, Kending et al. wrote, \"The Bloxsom AL device experienced a precipitous birth, a rapid acceptance and proliferation of usage, a rapid death, and now extinction.\" [ 3 ]  The authors noted that the device was seen as a status symbol by many hospitals, which led these centers to utilize it before it had undergone enough evaluation. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4645", "contents": "The  Both respirator , also known as the  Both Portable Cabinet Respirator , was a  negative pressure ventilator  (more commonly known as an \"iron lung\") invented by  Edward Both  in 1937. Made from  plywood , the respirator was an affordable alternative to the more expensive designs that had been used prior to its development, and accordingly came into common usage in Australia. More widespread use emerged during the 1940s and 1950s, when the Both respirator was offered free of charge to  Commonwealth  hospitals by  William Morris ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4646", "contents": "In 1937, Australia faced a  poliomyelitis  (polio) epidemic. [ 1 ]  At the time, iron lungs provided one of the main methods of treating the \"paralytic breathing failures\" that were a complication of the illness. Although tank respirators had been developed earlier, the iron lung itself was still fairly new, having been designed by  Philip Drinker  and  Louis Agassiz Shaw  in 1928. [ 2 ]  Their design, which became known as a \"Drinker's\" or, due to its construction, an \"iron lung\", proved to be an effective means of prolonging the life of patients with poliomyelitis \u2013 although the first person to be treated in the ventilator died after two days from cardiac failure possibly related to  pneumonia , the second patient recovered after spending two weeks in the machine. [ 3 ]  However in Australia, the widespread use of the Drinkers was hampered by a number of factors, most notably cost, the heavy weight of the device, and the need to ship the device to the United States for servicing, and thus there were few of the devices in the country. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4647", "contents": "Adelaide inventor Edward Both was approached in the hope that he could provide an alternative to meet the demand brought on by the epidemic. Both ran Both Equipment Limited with his brother Donald, and had previously developed medical apparatus. It took a few weeks for the pair to create their own iron lung, which they named the \"Both portable cabinet respirator\". Unlike the Drinker's machine, the Both respirator was made from plywood (even though it continued to be referred to as an \"iron\" lung), and this both kept the price down and made it more portable. The Both device cost only \u00a3100, was portable due to its light weight and the addition of wheels, and was simple enough that hospitals could build their own in their workshops, and it soon proved to be a success. [ 1 ]  The portability also opened up other possibilities, and as a result people who needed extended assistance from the device were able to use one in their private residences: indeed, in 2003 there were still five privately owned Both respirators being used in residences within Victoria. [ 1 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4648", "contents": "In 1938, Edward Both traveled to England to sell an  electrocardiograph  which he had invented. [ 1 ]  While there, he heard over  BBC Radio  a request for an iron lung to help treat a young patient residing in a country hospital. [ 5 ]  Responding to the call, Both hired a workshop and assembled one of his designs within 24 hours, and the Both respirator was able to quickly gain the approval of the London County Council. Subsequently, he built more of the respirators during his stay, and one was sent to the Nuffield Department of Anaesthetics at the  Radcliffe Infirmary  where a short film was made of the device. This film was subsequently shown to  William Morris  (Lord Nuffield) by  Robert Macintosh , the department's Professor. Nuffield was the manufacturer of the  Morris motor car  as well as a philanthropist. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4649", "contents": "Nuffield was taken by the design, and in November of that year he offered to turn over part of his car factory for the manufacture of the Both respirators and to provide the respirators free of charge to any hospital in the  Commonwealth  that requested one. [ 1 ]  In spite of some initial opposition \u2013 Nuffield was criticized in the  British Medical Journal  by Frederick Menzies for using a design before the iron lung had been perfected, and for supplying it to hospitals which may lack the knowledge as to how to employ it [ 6 ]  \u2013 over 1,700 Both\u2013Nuffield respirators were distributed to hospitals. [ 1 ]  By the early 1950s there were over 700 Both\u2013Nuffield iron lungs in the United Kingdom, compared with only 50 Drinker's models. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4650", "contents": "Brittle asthma  is a type of  asthma  distinguishable from other forms by recurrent, severe attacks. [ 1 ] [ 2 ] [ 3 ]  There are two subtypes divided by symptoms: Type 1 and Type 2, [ 4 ]  depending on the stability of the patient's maximum speed of expiration, or peak expiratory flow rate (PEFR). Type 1 is characterized by a maintained wide PEF variability despite considerable medical therapy including a dose of inhaled steroids, and Type 2 is characterized by sudden acute attacks occurring in less than three hours without an obvious  trigger  on a background of well controlled asthma. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4651", "contents": "Brittle asthma is one of the \"unstable\" subtypes of \"difficult asthma\", a term used to characterize the less than 5% of asthma cases that do not respond to maximal inhaled treatment, including high doses of  corticosteroids  combined with additional therapies such as long-acting  beta-2 agonists . [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4652", "contents": "The 2005  Oxford Textbook of Medicine  distinguishes type 1 brittle asthma by \"persistent daily chaotic variability in peak flow (usually greater than 40 per cent diurnal variation in PEFR more than 50 per cent of the time)\", while type 2 is identified by \"sporadic sudden falls in PEFR against a background of usually well-controlled asthma with normal or near normal lung function\". [ 8 ]  In both types, patients are subject to recurrent, severe attacks. The cardinal symptoms of an asthma attack are shortness of breath ( dyspnea ),  wheezing , and chest tightness. [ 9 ]  Individuals with type 1 suffer chronic attacks in spite of ongoing medical therapy, while those with type 2 experience sudden, acute and even potentially life-threatening attacks even though otherwise their asthma seems well managed. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4653", "contents": "When first defined by  Margaret Turner-Warwick  in 1977, the term brittle asthma was used specifically to describe type 1, but as studies into the phenotype were conducted the second type was also distinguished. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4654", "contents": "In addition to any issues of  treatment compliance , and maximised  corticosteroids  (inhaled or oral) and  beta agonist ,  brittle asthma treatment also involves for type 1 additional subcutaneous injections of beta2 agonist and inhalation of  long acting beta-adrenoceptor agonist , [ 12 ]   whilst type 2 needs allergen avoidance and self-management approaches. [ 13 ]  Since catastrophic attacks are unpredictable in type 2, patients may display identification of the issue, such as a  MedicAlert  bracelet, and carry an  epinephrine autoinjector . [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4655", "contents": "The condition is rare. 1999's  Difficult Asthma  estimates a prevalence of approximately 0.05% brittle asthma sufferers among the asthmatic population. [ 14 ]  Though found in all ages, it is most commonly found in individuals between the ages of 18 and 55; it is present in both sexes, though type 1 has been diagnosed in three times as many women as men. [ 14 ]  Hospitalization is more frequent for type 1 than type 2. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4656", "contents": "Bronchial thermoplasty [ 1 ]  is a treatment for severe  asthma  approved by the  FDA  in 2010 involving the delivery of controlled, therapeutic  radiofrequency  energy to the airway wall, thus heating the tissue and reducing the amount of smooth muscle present in the airway wall. This reduces the capacity of the immune system to cause  bronchoconstriction  through  nitric oxide  signalling, which is the main root cause of asthma symptoms. [ 2 ]  Bronchial thermoplasty is normally used to treat patients with severe persistent asthma who do not respond well to typical pharmacotherapy regimens. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4657", "contents": "A full course of bronchial thermoplasty treatment [ 4 ]  includes three separate bronchoscopic procedures: one for the each lower lobe of the lung and another for both upper lobes. Each outpatient procedure is performed approximately three weeks apart."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4658", "contents": "Under sedation, a  catheter  inside a  bronchoscope  \u2013 a thin, flexible tube-like instrument introduced through the patient\u2019s nose or mouth and into their lungs \u2013 delivers thermal energy into the airways. The patient is monitored after the procedure and usually returns home the day of the procedure or early the following day. The catheter delivers a series of 10-second temperature controlled bursts of  radio frequency  energy which heat the lining of the lungs to 65 degrees Celsius (149\u00a0\u00b0F). It is this heat that destroys some of the muscle tissue which constricts during an asthma attack, reducing the number and severity of exacerbations."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4659", "contents": "Through a standard bronchoscopy procedure, a small flexible tube is advanced into the airway, via mouth or nose, to mildly heat the airway walls. This treatment has been shown to result in acute epithelial destruction with regeneration observed in the  epithelium ,  blood vessels ,  mucosa  and nerves; however, airway  smooth muscle  has demonstrated almost no capacity for  regeneration , and it is instead replaced with  connective tissue . The treatment has been shown in prospective studies to be safe and effective with duration up to five years. [ 5 ]  Bronchial thermoplasty is indicated for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well controlled with inhaled  corticosteroids  and long acting  beta agonists  as per guidelines of the  Global Initiative for Asthma  (GINA)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4660", "contents": "In a double-blind, randomized, sham-controlled clinical study of bronchial thermoplasty, [ 6 ]  adults with severe asthma treated with bronchial thermoplasty had improved asthma-related quality of life out to a year compared to the control (sham-treated) patients.  Additionally, when compared to control patients, patients treated with bronchial thermoplasty also experienced the following benefits, although none reached statistical significance:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4661", "contents": "In a clinical study, bronchial thermoplasty has been proven to provide long-term reduction in asthma induced breathing difficulty to at least 5 years and improve the quality of life for severe persistent asthma patients. [ 7 ]  Reduction in asthma attacks, ER visits, and hospitalizations for respiratory symptoms are maintained to at least 5 years. [ 8 ]  These benefits were observed during clinical studies where patients continued to take their standard maintenance asthma medications which included combinations of inhaled corticosteroids and long-acting bronchodilators."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4662", "contents": "In the period immediately following the bronchial thermoplasty procedure, there was an expected transient increase in the frequency and worsening of respiratory-related symptoms. Bronchial thermoplasty is not appropriate for patients who: [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4663", "contents": "Bronchial thermoplasty is irreversible; the smooth muscle tissue which is destroyed cannot be recovered."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4664", "contents": "Bronchial thermoplasty was first approved by FDA in April 2010. [ 10 ]  Bronchial thermoplasty is now being used as a treatment in many countries which include United Kingdom, [ 11 ]  India, [ 12 ]  and United States."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4665", "contents": "The  Byrdine F. Lewis College of Nursing and Health Professions  contains the  nursing school  and school of  allied health professions  at  Georgia State University ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4666", "contents": "The school is named after Byrdine F. Lewis, the mother of  Kenneth Lewis , a former CEO of  Bank of America  and an alumnus of Georgia State.  Ken's mother was a nurse, and he donated $2.5 million as an  endowment  in her honor. [ 1 ]  The school was originally part of the College of Health and Human Sciences, but was restructured to its current configuration. The School of Nursing's offices are located in the Urban Life Building, along with the  College of Law . On August 1, 2017, the institute was renamed from Byrdine F. Lewis School of Nursing and Health Professions to Byrdine F. Lewis College of Nursing and Health Professions"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4667", "contents": "The School of Nursing within the college offers degrees in  nursing  leading to eligibility to become a  registered nurse  or an  advanced practice registered nurse ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4668", "contents": "The school offers degrees in  clinical nutrition  leading to eligibility to become a  registered dietitian"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4669", "contents": "The school offers the  Doctor of physical therapy  degree."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4670", "contents": "The school offers a  Master of Occupational Therapy  degree."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4671", "contents": "The school offers degrees in  respiratory therapy  leading to eligibility to become a Certified Respiratory Therapist or Registered Respiratory Therapist"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4672", "contents": "33\u00b045\u203208\u2033N   84\u00b023\u203207\u2033W \ufeff / \ufeff 33.752103\u00b0N 84.385283\u00b0W \ufeff /  33.752103; -84.385283"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4673", "contents": "Certified in Neonatal Pediatric Transport  ( C-NPT ) is the designation in the USA for a  paramedic ,  physician ,  respiratory therapist ,  neonatal nurse ,  nurse practitioner ,  nurse  or  physician assistant  who has earned certification from the  National Certification Corporation  in  neonatal  and pediatric transport.  This certificate of added qualification was rolled out in 2009. [ 1 ]  National Certification Corporation utilizes applied measurement professionals to administer its tests."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4674", "contents": "The National Certification Corporation uses many sources for its test questions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4675", "contents": "In the United States,  Certified Pulmonary Function Technician  ( CPFT ) is a medical technician who is at least a  Certified Respiratory Therapist  and at most a  Registered Respiratory Therapist  that has successfully passed the national certification exam. [ 1 ]  A pulmonary function technician assists a  Registered Pulmonary Function Technician  with performing function tests on patients.  Tests are done both inpatient and outpatient and in specialty clinics such as asthma clinics and sleep centers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4676", "contents": "This job-, occupation-, or vocation-related article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4677", "contents": "A  Certified Respiratory Therapist  ( CRT ), formerly Certified Respiratory Therapy Technician (CRTT), is a therapist who has graduated from a respiratory therapy program at a university or college and has passed a national certification exam. [ 1 ]  A CRT or RRT is typically expected to adjust, modify or recommend therapeutic techniques within well-defined procedures based on a limited range of patient responses. In the healthcare setting, usually required supervision by a physician experienced in respiratory care."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4678", "contents": "From the 1980s through the 2000s, 49 states passed legislation relying on results from the certification examination as a central component in the regulation of respiratory therapists."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4679", "contents": "Changes in education requirements for the CRT vs the RRT have resulted in the CRT level practitioners having the same responsibilities and practice abilities, in most areas of the United States. However, the RRT credential is preferred in the vast majority of healthcare facilities in the United States.  The RRT is considered an advanced respiratory therapist, a CRT an entry level.  It is very difficult and almost unheard of for a Respiratory Care Department manager to achieve management level without being registered. Also, it is very difficult for a CRT to achieve supervisor status without first obtaining RRT status.  Even then, a bachelor's degree is highly preferred."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4680", "contents": "College of Respiratory Therapists of Ontario  ( CRTO ) regulates the profession of  respiratory care  by setting out requirements for entry to practise in  Ontario ,  Canada .  Authorized by the legislation \"Regulated Health Professionals Act\" in Ontario, the role of the College of Respiratory Therapists of Ontario is to regulate the practice of respiratory therapy and govern the registered respiratory therapists.  Respiratory therapy has been an established health care profession in Canada since 1964."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4681", "contents": "The College of Respiratory Therapists of Ontario approves members and applicants from schools accredited by the  Council on Accreditation for Respiratory Therapy Education  (CoARTE). Graduates from approved programs are eligible to register in the graduate class of registration, they are also eligible to write the  Canadian Board for Respiratory Care  (CBRC) examination."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4682", "contents": "The College of Respiratory Therapists of Ontario approves and regulates respiratory therapists in Ontario."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4683", "contents": "A  College of Respiratory Care  is a type of  educational institution , or part thereof, providing education and training to become a fully qualified  respiratory practitioner . [ 1 ]  The nature of  respiratory care education and respiratory practitioner qualifications varies considerably across the world. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4684", "contents": "In  Canada , \"College of Respiratory Therapy\" may refer to a provincial  professional association , such as the  College of Respiratory Therapists of Ontario ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4685", "contents": "Commission on Accreditation for Respiratory Care  ( CoARC ) is an American  nonprofit  accreditation organization dedicated to  respiratory care . [ 1 ] [ 2 ]   CoARC accredits degree-granting programs in respiratory care that have undergone a rigorous process of voluntary peer review and have met or exceeded the minimum accreditation Standards as set by the professional association in cooperation with CoARC. [ 2 ]  These programs are granted accreditation status by CoARC, which provides public recognition of such achievement. In 2009, there were over 300  accredited programs  in the United States. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4686", "contents": "Continuous mandatory ventilation  ( CMV ) is a  mode of mechanical ventilation  in which breaths are delivered based on set variables. Still used in the operating room, in previous nomenclature, CMV referred to \"controlled mechanical ventilation\" (\"control mode ventilation\"), a mode of ventilation characterized by a ventilator that makes no effort to sense patient breathing effort. In continuous mandatory ventilation, the ventilator can be triggered either by the patient or mechanically by the ventilator. The ventilator is set to deliver a breath according to parameters selected by the operator. \"Controlled mechanical ventilation\" is an outdated expansion for \"CMV\"; \"continuous mandatory ventilation\" is now accepted standard  nomenclature for mechanical ventilation . CMV today can assist or control itself dynamically, depending on the transient presence or absence of spontaneous breathing effort. Thus, today's CMV  would have been called ACV  (assist-control ventilation) in older nomenclature, and the original form of CMV is a thing of the past. But despite continual technological improvement over the past half century, CMV may still be uncomfortable for the patient."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4687", "contents": "Continuous mandatory ventilation is associated with profound diaphragm muscle dysfunction and atrophy.  [ 1 ]   CMV is no longer the preferred mode of mechanical ventilation.  [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4688", "contents": "Limits in VC-CMV may be set and pressure based.  The ventilator will attempt to deliver the set tidal volume by utilizing whatever pressure is required to reach its setting.  A pressure limit may be added to limit damage to the lungs ( barotrauma )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4689", "contents": "Expiration cycling can be set by time or the pressure limit.  Once the T i  (inspiratory time) is reached, or a pressure limit is reached, the ventilator will cycle into expiratory mode and allow passive exhalation until another breath is triggered."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4690", "contents": "Pressure control (PC) is a pressure-controlled mode of ventilation.  The ventilator delivers a flow to maintain the preset pressure at a preset  respiratory rate  over a preset inspiratory time.  [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4691", "contents": "The pressure is constant during the inspiratory time, and the flow is decelerating. If, for any reason, pressure decreases during inspiration, the flow from the ventilator will immediately increase to maintain the set inspiratory pressure.  [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4692", "contents": "Dual-control modes are  pressure-controlled  modes with an exhaled  tidal volume  target. They work on a breath-by-breath basis and provide pressure-limited, time-cycled breaths, increasing or decreasing the pressure of the next breath as necessary to achieve a user-selected desired tidal volume. They are known by various vendor-specific terms such as pressure-regulated volume control ( Siemens ), autoflow ( Dr\u00e4ger ), adaptive-pressure ventilation (Hamilton Medical), and volume-control plus ( Covidien ), among others."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4693", "contents": "Many terms have been developed to describe the same  modes of mechanical ventilation . The  nomenclature of mechanical ventilation  has become more standardized, and these terms are no longer preferred but may still be seen in older research.  [ 5 ]  There are many different names that were historically used to refer to CMV but now refer to Assist Control.  [ 5 ]  Names such as volume control ventilation and volume cycled ventilation in modern usage refer to the Assist Control mode."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4694", "contents": "Continuous spontaneous ventilation  is any  mode of mechanical ventilation  where every breath is spontaneous (i.e., patient triggered and patient cycled)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4695", "contents": "Spontaneous breathing is defined as the movement of gas in and out of the lungs that is produced in response to an individual's respiratory muscles. In a nutshell, spontaneous breathing is natural breathing. while at rest, a typical adult will take an average of 18 breaths per minute. Most people are unaware of their breathing patterns unless something interferes with the efficiency of this process. In extreme cases, mechanical ventilation is used when spontaneous breathing is inadequate or ceases entirely."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4696", "contents": "Some modes of mechanical ventilation require spontaneous ventilation, some of these include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4697", "contents": "Demand Valve Oxygen Therapy  (DVOT) is a way of delivering high flow  oxygen therapy   using a device that only delivers  oxygen  when the patient breathes in and shuts off when they breathe out. DVOT is commonly used to treat conditions such as  cluster headache , which affects up to four in 1000 people (0.4%), [ 1 ] [ 2 ] [ 3 ]  and is a recommended first aid procedure for several diving disorders. [ 4 ] [ 5 ]  It is also a recommended prophylactic for decompression sickness in the event of minor omitted decompression without symptoms. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4698", "contents": "High flow oxygen therapy, delivered at a rate of between 7 and 15 litres per minute, has been recognized as an effective treatment for cluster headache since 1981. [ 6 ]   Since then, several double-blind, randomized, placebo-controlled, crossover trials have provided further clinical evidence for its efficacy. [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4699", "contents": "When inhaled at 100% at the outset of a cluster headache attack, high flow oxygen therapy has been proven to abort episodes in up to 78% of patients. [ 7 ]   Inhaling 100% oxygen is recommended by the  European Federation of Neurological Societies  as the first choice for the treatment of cluster headache attacks. [ 9 ] [ 8 ]  The  British Thoracic Society  and  National Institute of Health and Care Excellence , among other organisations, endorse the therapy. [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4700", "contents": "A portable administration set will comprise a portable high-pressure oxygen cylinder containing sufficient gas for the expected treatment, with an oxygen service cylinder valve, an oxygen compatible first stage regulator with pressure gauge, intermediate pressure hose, and demand valve with mouthpiece."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4701", "contents": "Demand valves  have been proven to be particularly effective at delivering high flow oxygen therapy. [ 13 ]   Unlike conventional breathing systems, oxygen demand valves only deliver gas when the patient inhales and shut off the flow when they exhale. Exhaled gas is directed to the atmosphere through side vents. This means that almost 100 percent of the oxygen is inhaled, while the amount of exhaled carbon dioxide that the patient rebreathes is minimized."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4702", "contents": "Compared to other mask types, demand valves have been better at achieving pain relief at 15 minutes in the first cluster headache attack. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4703", "contents": "For diving first aid an  oxygen compatible  diving regulator may be used if a special purpose oxygen treatment demand valve is not available.  Technical divers  routinely use such equipment for in-water  decompression ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4704", "contents": "When used in  diving recompression chambers  and multi-place medical hyperbaric chambers, a  built-in breathing system  venting to the exterior is generally used to avoid buildup of oxygen partial pressure in the chamber to dangerous levels which would otherwise require more frequent venting."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4705", "contents": "High oxygen concentrations in the surroundings constitute a fire hazard. Oxygen therapy should be accompanied by good ventilation and avoidance of ignition sources, and where reasonably practicable, removal of combustible materials.  Oxygen firebreaks  are a requirement in some countries for patients using  oxygen therapy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4706", "contents": "Dual-control modes of ventilation  are auto-regulated  pressure-controlled   modes of mechanical ventilation  with a user-selected  tidal volume  target. The ventilator adjusts the pressure limit of the next breath as necessary according to the previous breath's measured exhaled tidal volume. Peak airway pressure varies from breath to breath according to changes in the patient's  airway resistance  and  lung compliance ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4707", "contents": "The pressure waveform is square, and the  flow waveform  is decelerating. This mode is a form of  continuous mandatory ventilation  as a minimum number of passive breaths will be time-triggered, and patient-initiated breaths are time-cycled and regulated according to operator-set tidal volume. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4708", "contents": "The first few breaths are delivered to the patient according to the ventilator manufacturer's particular algorithm for determining the patient's resistance and compliance. These are 'test breaths' that the ventilator can then use to calculate the optimal pressures for the next, regulated breaths. The pressure is constant during the set  inspiratory time  as with  pressure-controlled CMV . The ventilator will use the exhaled tidal volume measured at the end of that breath's expiratory phase to calculate the pressure of the next breath. If the exhaled tidal volume is lower than the software threshold, the next breath will be delivered at a higher pressure, and if the exhaled tidal volume is higher than the software threshold, the next breath will be delivered at a lower pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4709", "contents": "The theory is to ensure that the lowest inspiratory pressure necessary to achieve the desired tidal volume is used. As a safety feature, the ventilator will not increase the pressure beyond a predetermined high pressure limit. This is usually tied to (but not the same as) the operator-set high pressure alarm setting. If the ventilator delivers a breath at this high pressure limit and is still unable to achieve the operator-desired exhaled tidal volume, an alarm will sound to warn the operator that the volume target cannot be met."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4710", "contents": "Dynamic hyperinflation  is a phenomenon that occurs when a new breath begins before the lung has reached the static equilibrium volume. [ 1 ]  In simpler terms, this means that a new breath starts before the usual amount of air has been breathed out, leading to a build-up of air in the lungs, and causing breathing in and out to take place when the lung is nearly full."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4711", "contents": "Dynamic hyperinflation can occur in patients with  asthma  who are breathing spontaneously. It is a physiologic response to airflow obstruction and exists, to an extent, because increasing lung volume tends to increase airway caliber and can reduce the resistive work of breathing. However, in patients with severe asthma it becomes maladaptive, occurring at the expense of increased mechanical load and elastic work of breathing. [ 2 ]  Dynamic hyperinflation can cause alveolar overdistention resulting in hypoxemia, hypotension, or alveolar rupture. Dynamic hyperinflation increases the magnitude of the drop in airway pressure that the patient must generate to trigger a breath, thereby increasing the patient's workload."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4712", "contents": "Patients with  acute severe asthma  exacerbations are at risk for progressive air trapping and alveolar hyperinflation, which may lead to alveolar rupture and hemodynamic compromise. Airflow obstruction during expiration slows lung emptying and inspiration may be initiated before exhalation is complete. The phenomenon that occurs when a new breath begins before the lung has reached the static equilibrium volume is called dynamic hyperinflation. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4713", "contents": "Interventions to correct air-trapping include decreasing the respiratory rate (increasing expiratory time), increasing inspiratory flow rates (decreasing the inspiratory time) and lowering the  tidal volume . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4714", "contents": "In adults, it has been demonstrated that limiting minute ventilation is the key to avoiding dynamic hyperinflation; keeping the minute ventilation under 115/mL/kg is recommended [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4715", "contents": "Epinephrine , also known as  adrenaline , is a  medication  and  hormone . [ 10 ] [ 11 ]  As a medication, it is used to treat several conditions, including  anaphylaxis ,  cardiac arrest ,  asthma , and superficial bleeding. [ 8 ]   Inhaled  epinephrine may be used to improve the symptoms of  croup . [ 12 ]  It may also be used for  asthma  when other treatments are not effective. [ 8 ]  It is given  intravenously , by injection into a muscle, by inhalation, or by injection just under the skin. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4716", "contents": "Common side effects include shakiness,  anxiety , and sweating. [ 8 ]  A fast heart rate and high blood pressure may occur. [ 8 ]  Occasionally, it may result in an  abnormal heart rhythm . [ 8 ]  While the safety of its use during  pregnancy  and  breastfeeding  is unclear, the benefits to the mother must be taken into account. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4717", "contents": "Epinephrine is normally produced by both the  adrenal glands  and a small number of  neurons  in the brain, where it acts as a  neurotransmitter . [ 10 ] [ 13 ]  It plays an essential role in the  fight-or-flight response  by increasing blood flow to muscles, heart output,  pupil dilation , and  blood sugar . [ 14 ] [ 15 ]  Epinephrine does this through its effects on  alpha  and  beta receptors . [ 15 ]  It is found in many animals and some  single-celled organisms , [ 16 ] [ 17 ]  but the medication is produced synthetically and is not harvested from animals. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4718", "contents": "J\u014dkichi Takamine  first isolated epinephrine in 1901, and it came into medical use in 1905. [ 19 ] [ 20 ]  It is on the  World Health Organization's List of Essential Medicines . [ 21 ]  It is available as a  generic medication . [ 8 ]  In 2022, it was the 240th most commonly prescribed medication in the United States, with more than 1 \u00a0 million prescriptions. [ 22 ] [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4719", "contents": "The word  epinephrine  is formed from the Ancient Greek  \u1f10\u03c0\u03b9-  ( epi -, \"on\") and  \u03bd\u03b5\u03c6\u03c1\u03cc\u03c2  ( nephros , \" kidney \") because the adrenal glands, where it is produced, are located just above the kidneys. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4720", "contents": "Epinephrine is used to treat a number of conditions, including  cardiac arrest ,  anaphylaxis , and superficial bleeding. [ 25 ]  It has been used historically for  bronchospasm  and  low blood sugar , but newer treatments for these that are selective for  \u03b2 2  adrenoceptors , such as  salbutamol , are preferred. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4721", "contents": "While epinephrine is often used to treat  cardiac arrest , it has not been shown to improve long-term survival or mental function after recovery. [ 26 ] [ 27 ] [ 28 ]  It does, however, improve  return of spontaneous circulation . [ 28 ] [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4722", "contents": "Epinephrine is the only life-saving treatment for anaphylaxis. [ 30 ]  The commonly used  epinephrine autoinjector  delivers a 0.3\u00a0mg epinephrine injection (0.3 mL, 1:1000). [ citation needed ]  It is indicated in the emergency treatment of allergic reactions, including anaphylaxis to stings, contrast agents, medicines, or people with a history of anaphylactic reactions to known triggers. [ citation needed ]  A lower-strength product is available for children. [ 31 ] [ 32 ] [ 33 ] [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4723", "contents": "Intramuscular injection can be complicated in that the depth of subcutaneous fat varies and may result in  subcutaneous injection , or may be injected intravenously in error, or the wrong strength used. [ 35 ] [ 36 ]  Intramuscular injection gives a faster and higher  pharmacokinetic  profile compared to subcutaneous injection. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4724", "contents": "In August 2024, an epinephrine nasal spray (brand name Neffy) was approved in the United States for the emergency treatment of allergic reactions (type I), including those that are life-threatening (anaphylaxis), in people who weigh at least 30 kilograms (66\u00a0lb). [ 2 ] [ 30 ] [ 38 ]  It is the first nasal spray for the treatment of anaphylaxis approved by the US  Food and Drug Administration  (FDA). [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4725", "contents": "The approval of epinephrine nasal spray is based on four studies in 175 healthy adults, without anaphylaxis, that measured the epinephrine concentrations in the blood following administration of epinephrine nasal spray or approved epinephrine injection products. [ 30 ]  Results from these studies showed comparable epinephrine blood concentrations between epinephrine nasal spray and approved epinephrine injection products. [ 30 ]  Epinephrine nasal spray also demonstrated similar increases in blood pressure and heart rate as epinephrine injection products, two critical effects of epinephrine in the treatment of anaphylaxis. [ 30 ]  A study of epinephrine nasal spray in children weighing more than 66 pounds showed that epinephrine concentrations in children were similar to adults who received epinephrine nasal spray. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4726", "contents": "The most common side effects of epinephrine nasal spray include throat irritation, tingling nose (intranasal paresthesia), headache, nasal discomfort, feeling jittery, tingling sensation (paresthesia), fatigue, tremor, runny nose (rhinorrhea), itchiness inside the nose (nasal pruritus), sneezing, abdominal pain, gum (gingival) pain, numbness in the mouth (hypoesthesia oral), nasal congestion, dizziness, nausea and vomiting. [ 30 ]  The FDA granted the application of epinephrine nasal spray  fast track  designation and granted the approval of Neffy to ARS Pharmaceuticals. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4727", "contents": "Epinephrine is also used as a  bronchodilator  for  asthma  if specific \u03b2 2  agonists are unavailable or ineffective. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4728", "contents": "Because of the high intrinsic efficacy (receptor binding ability) of epinephrine, high drug concentrations cause adverse side effects when treating asthma. The value of using nebulized epinephrine in acute asthma is unclear. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4729", "contents": "Racemic epinephrine  has been used for the  treatment of croup . [ 41 ] [ 42 ]   Racemic  adrenaline is a 1:1 mixture of the two  enantiomers  of adrenaline. [ 43 ]  The  L -form is the active component. [ 43 ]  Racemic adrenaline works by stimulating the alpha-adrenergic receptors in the airway, with resultant mucosal vasoconstriction and decreased subglottic edema, and by stimulating the \u03b2 adrenergic receptors, with resultant relaxation of the bronchial smooth muscle. [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4730", "contents": "There is a lack of consensus as to whether inhaled nebulized epinephrine is beneficial in the treatment of  bronchiolitis , with most guidelines recommending against its use. [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4731", "contents": "When epinephrine is mixed with local anesthetics, such as  bupivacaine  or  lidocaine , and used for local anesthesia or intrathecal injection, it prolongs the numbing effect and motor block effect of the anesthetic by up to an hour. [ 45 ]  Epinephrine is frequently combined with local anesthetic and can cause panic attacks. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4732", "contents": "Epinephrine is mixed with  cocaine  to form  Moffett's solution , used in  nasal   surgery . [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4733", "contents": "Upper airway obstruction with edema and stridor can be treated with racemic epinephrine. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4734", "contents": "Adverse reactions to adrenaline include  palpitations ,  tachycardia ,  arrhythmia ,  anxiety ,  panic attack ,  headache ,  anorexia ,  tremor ,  hypertension , and acute  pulmonary edema . [ medical citation needed ]  The use of epinephrine based eye-drops, commonly used to treat glaucoma, may also lead to a buildup of adrenochrome pigments in the conjunctiva, iris, lens, and retina. [ medical citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4735", "contents": "Rarely, exposure to medically administered epinephrine may cause  Takotsubo cardiomyopathy . [ 49 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4736", "contents": "Use is contraindicated in people on nonselective  \u03b2-blockers  because severe hypertension and even  cerebral hemorrhage  may result. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4737", "contents": "Epinephrine acts by binding to a variety of  adrenergic receptors . Epinephrine is a nonselective  agonist  of all adrenergic receptors, including the major subtypes  \u03b1 1 ,  \u03b1 2 ,  \u03b2 1 ,  \u03b2 2 , and  \u03b2 3 . [ 50 ]  Epinephrine's binding to these receptors triggers several metabolic changes. Binding to \u03b1-adrenergic receptors inhibits  insulin  secretion by the  pancreas , stimulates  glycogenolysis  in the  liver  and  muscle , [ 51 ]  and stimulates  glycolysis  and inhibits insulin-mediated  glycogenesis  in muscle. [ 52 ] [ 53 ]  \u03b2 adrenergic receptor binding triggers  glucagon  secretion in the pancreas, increased  adrenocorticotropic hormone  (ACTH) secretion by the  pituitary gland , and increased  lipolysis  by  adipose tissue . Together, these effects increase  blood glucose  and  fatty acids , providing substrates for energy production within cells throughout the body. [ 53 ]  In the heart, the coronary arteries have a predominance of \u03b2 2  receptors, which cause  vasodilation  of the coronary arteries in the presence of epinephrine. [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4738", "contents": "Its actions increase peripheral resistance via  \u03b1 1  receptor -dependent  vasoconstriction  and increase  cardiac output  via its binding to \u03b2 1  receptors. The goal of reducing peripheral circulation is to increase coronary and cerebral perfusion pressures and therefore increase oxygen exchange at the cellular level. [ 55 ]  While epinephrine does increase aortic, cerebral, and carotid circulation pressure, it lowers carotid blood flow and  end-tidal CO 2  or E T CO 2  levels. It appears that epinephrine may improve macrocirculation at the expense of the capillary beds where perfusion takes place. [ 56 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4739", "contents": "Epinephrine, or adrenaline, also known as 3,4,\u03b2-trihydroxy- N -methylphenethylamine, is a  substituted phenethylamine  and  catecholamine . It is the  N - methylated   analogue  of  norepinephrine  (noradrenaline; 3,4,\u03b2-trihydroxyphenethylamine) and the  N -methylated and \u03b2- hydroxylated  analogue of  dopamine  (3,4-dihydroxyphenethylamine)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4740", "contents": "Extracts of the  adrenal gland  were first obtained by Polish physiologist  Napoleon Cybulski  in 1895. These extracts, which he called  nadnerczyna , contained adrenaline and other catecholamines. [ 57 ]  American ophthalmologist  William H. Bates  discovered adrenaline's usage for eye surgeries prior to 20 April 1896. [ 58 ]  Japanese chemist  J\u014dkichi Takamine  and his assistant Keizo Uenaka independently discovered adrenaline in 1900. [ 59 ] [ 60 ]  In 1901, Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen. [ 61 ]  Adrenaline was first synthesized in the laboratory by  Friedrich Stolz  and  Henry Drysdale Dakin , independently, in 1904. [ 60 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4741", "contents": "Epinephrine  is the  generic name  of the drug and its  INN Tooltip International Nonproprietary Name  and  USAN Tooltip United States Adopted Name , while  adrenaline  is its  BAN Tooltip British Approved Name . [ 62 ] [ 63 ] [ 64 ]  Epinephrine is sold under various brand names including Asthmanefrin, Micronefrin, Neffy, Nephron, VapoNefrin, and Primatene Mist, among others. [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4742", "contents": "In June 2024, the  Committee for Medicinal Products for Human Use  of the  European Medicines Agency  adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Eurneffy, intended for emergency treatment of allergic reactions (anaphylaxis) due to insect stings or bites, foods, medicinal products, and other allergens as well as idiopathic or exercise-induced anaphylaxis. [ 3 ] [ 65 ] [ 66 ]  The applicant for this medicinal product is ARS Pharmaceuticals IRL Limited. [ 3 ]  Eurneffy was approved for medical use in the European Union in August 2024. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4743", "contents": "Epinephrine is available in an  autoinjector  delivery system and a  nasal spray ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4744", "contents": "There is an epinephrine  metered-dose inhaler  sold  over the counter  in the United States to relieve  bronchial asthma . [ 67 ] [ 68 ]  It was introduced in 1963 by Armstrong Pharmaceuticals. [ 69 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4745", "contents": "A common concentration for epinephrine is 2.25%\u00a0w/v epinephrine in solution, which contains 22.5\u00a0mg/mL, while a 1% solution is typically used for aerosolization. [ 70 ] [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4746", "contents": "Exercise-induced bronchoconstriction  ( EIB ) occurs when the airways narrow as a result of exercise.  This condition has been referred to as  exercise-induced asthma  ( EIA ); however, this term is no longer preferred. [ 1 ]  While exercise does not cause  asthma , it is frequently an  asthma trigger . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4747", "contents": "It might be expected that people with EIB would present with  shortness of breath , and/or an  elevated respiratory rate  and  wheezing , consistent with an asthma attack.  However, many will present with decreased stamina, or difficulty in recovering from exertion compared to team members, or paroxysmal coughing from an irritable airway. [ 2 ]   Similarly, examination may reveal wheezing and  prolonged expiratory phase, or may be quite normal.  Consequently, a potential for under-diagnosis exists.  Measurement of airflow, such as  peak expiratory flow  rates, which can be done inexpensively on the track or sideline, may prove helpful. In athletes, symptoms of  bronchospasm  such as chest discomfort, breathlessness, and fatigue are often falsely attributed to the individual being out of shape, having asthma, or possessing a hyperreactive airway rather than EIB. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4748", "contents": "While the potential triggering events for EIB are well recognized, the underlying pathogenesis is poorly understood. [ 4 ]  It usually occurs after at least several minutes of vigorous,  aerobic  activity, which increases oxygen demand to the point where breathing through the nose ( nasal breathing ) must be supplemented by  mouth breathing .  The resultant inhalation of air that has not been warmed and humidified by the nasal passages seems to generate increased blood flow to the linings of the bronchial tree, resulting in  edema .  Constriction of these small airways then follows, worsening the degree of obstruction to airflow.  There is increasing evidence that the smooth muscle that lines the airways becomes progressively more sensitive to changes that occur as a result of injury to the airways from dehydration.  The chemical mediators that provoke the muscle spasm appear to arise from  mast cells . [ 4 ]  Mouth breathing as a result of decreased nasal breathing also increases lung surface exposure to irritants, pollutants, and allergens, causing  neutrophilic  inflammation in response to reactive oxygen species formation; research has found that individuals with genetically hindered  glutathione  counteraction of this  oxidative stress  are likely at a higher risk of developing EIB. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4749", "contents": "Exercise-induced  bronchoconstriction  can be difficult to diagnose clinically given the lack of specific symptoms [ 2 ]  and frequent misinterpretation as manifestations of vigorous exercise.  There are many mimics that present with similar symptoms, such as  vocal cord dysfunction ,  cardiac arrhythmias ,  cardiomyopathies , and  gastroesophageal reflux disease .  It is also important to distinguish those who have asthma with exercise worsening, and who consequently will have abnormal testing at rest, from true exercise-induced bronchoconstriction, where there will be normal baseline results.  Because of the wide differential diagnosis of exertional respiratory complaints, the diagnosis of exercise-induced bronchoconstriction based on history and self-reported symptoms alone has been shown to be inaccurate [ 6 ] [ 7 ]  and to result in an incorrect diagnosis more than 50% of the time. [ 8 ]  An important and often overlooked differential diagnosis is  exercise-induced laryngeal obstruction (EILO) . The latter can co-exist with EIB and is best differentiated using objective testing and continuous laryngoscopy during exercise (CLE) testing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4750", "contents": "Objective testing should begin with  spirometry  at rest. In true exercise-induced bronchoconstriction, the results should be within normal limits. Should resting values be abnormal, then asthma, or some other chronic lung condition, is present. There is, of course, no reason why asthma and exercise-induced bronchoconstriction should not co-exist but the distinction is important because without successful treatment of underlying asthma, treatment of an exercise component will likely be unsuccessful.  If baseline testing is normal, some form of exercise or pharmacologic stress will be required, either on the sideline or practice venue, or in the laboratory. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4751", "contents": "Treadmill or ergometer-based testing in lung function laboratories are effective methods for diagnosing exercise-induced bronchoconstriction, but may result in false negatives if the exercise stimulus is not intense enough."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4752", "contents": "Field-exercise challenge tests that involve the athlete performing the sport in which they are normally involved and assessing  FEV 1  after exercise are helpful if abnormal but have been shown to be less sensitive than eucapnic voluntary hyperventilation. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4753", "contents": "The  International Olympic Committee  recommends the  eucapnic voluntary hyperventilation  (EVH) challenge as the test to document exercise-induced asthma in  Olympic  athletes. [ 11 ]   In the EVH challenge, the patient voluntarily, without exercising, rapidly breathes dry air enriched with 5% CO 2  for six minutes.  The presence of the enriched CO 2  compensates for the CO 2  losses in the expired air, not matched by metabolic production, that occurs during hyperventilation, and so maintains CO 2  levels at normal. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4754", "contents": "Medication challenge tests, such as the  methacholine  challenge test, have a lower sensitivity for detection of exercise-induced bronchoconstriction in athletes and are also not a recommended first-line approach in the evaluation of exercise-induced asthma. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4755", "contents": "Mannitol  inhalation [ 14 ] [ 15 ]  has been recently approved for use in the United States."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4756", "contents": "A relatively recent review of the literature has concluded that there is currently insufficient available evidence to conclude that either mannitol inhalation or eucapnic voluntary hyperventilation are suitable alternatives to exercise challenge testing to detect exercise-induced bronchoconstriction and that additional research is required. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4757", "contents": "The best treatment is avoidance of conditions predisposing to attacks, when possible.  In athletes who wish to continue their sport or do so in adverse conditions, preventive measures include altered training techniques and medications."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4758", "contents": "Some take advantage of the  refractory period  by precipitating an attack by \"warming up,\" and then timing competition such that it occurs during the refractory period.  Step-wise training works in a similar fashion.  Warm up occurs in stages of increasing intensity, using the refractory period generated by each stage to reach a full workload. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4759", "contents": "There is no evidence supporting different treatment for EIB in asthmatic athletes and nonathletes. [ 18 ]  The most common medication used is a  beta agonist  taken about 20 minutes before exercise. [ 18 ]  Some physicians prescribe inhaled anti-inflammatory mists such as  corticosteroids  or  leukotriene antagonists , and  mast cell stabilizers  have also proven effective. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4760", "contents": "In May 2013, the  American Thoracic Society  issued the first treatment guidelines for EIB, recommending use of \"a short-acting \u03b22-agonist before exercise in all patients with EIB. For patients who continue to have symptoms of EIB despite the administration of a short-acting \u03b22-agonist before exercise, strong recommendations were made for a daily inhaled corticosteroid, a daily leukotriene receptor antagonist, or a mast cell stabilizing agent before exercise.\" [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4761", "contents": "There is conflicting information about the value of  theophylline  and other  methylxanthines  as prophylaxis against exercise-induced bronchoconstriction. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4762", "contents": "A  crossover study  compared oral  montelukast  with inhaled  salmeterol , both given two hours before exercise, showing that the drugs had similar benefit. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4763", "contents": "A  meta-analysis  of preliminary research indicated that  vitamin C  may be useful to relieve respiratory symptoms such as cough during exercise. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4764", "contents": "Olympic swimmers  Tom Dolan ,  Amy Van Dyken , and  Nancy Hogshead , Olympic track star  Jackie Joyner-Kersee , baseball Hall of Famer  Catfish Hunter , and American football player  Jerome Bettis  are among the many who have the condition. Tour de France winner  Chris Froome  reported that he suffers from the condition, after being spotted using a nasal inhaler during race. [ 23 ]  Other athletes with EIB include racing cyclist  Simon Yates , distance runner  Paula Radcliffe [ 24 ]  and cross-country skier  Marit Bj\u00f8rgen . [ 25 ]  Research by sports scientist John Dickinson found that 70 percent of UK-based members of the British swimming team had some form of asthma, as did a third of  Team Sky  cyclists, compared to a national asthma rate of eight to ten percent, [ 24 ]  whilst a study by the  United States Olympic Committee  in 2000 found that half of cross-country skiers had EIB. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4765", "contents": "In  medicine ,  exhaled nitric oxide  (eNO - now commonly known as FeNO) can be measured in a  breath test  for  asthma  and other  respiratory conditions  characterized by  airway   inflammation .  Nitric oxide  (NO) is a gaseous  molecule  produced by certain  cell  types in an inflammatory response. The fraction of exhaled NO (FE NO ) is a promising biomarker for the diagnosis, follow-up and as a guide to therapy in adults and children with asthma. The breath test has recently become available in many well-equipped hospitals in developed countries, although its exact role remains unclear."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4766", "contents": "In humans, nitric oxide is produced from  L-arginine  by three  enzymes  called  nitric oxide synthases  (NOS): inducible (iNOS), endothelial ( eNOS ), and neuronal (nNOS). The latter two are constantly active in  endothelial cells  and  neurons  respectively, whereas iNOS' action can be induced in states like inflammation (for example, by  cytokines ). In inflammation, several cells use iNOS to produce NO, including  eosinophils . As such, eNO (also known as FeNO \"fractional exhaled nitric oxide\") has been dubbed an  inflammometer . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4767", "contents": "Although iNOS is thought to be the main contributor to exhaled NO in asthmatics, [ 2 ] [ 3 ]  studies in mice also point to a role for nNOS. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4768", "contents": "It was initially thought that exhaled NO derived mostly from the sinuses, which contain high levels of NO. It has subsequently been shown that the lower airways contribute most of the exhaled NO, and that contamination from the sinuses is minimal. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4769", "contents": "Patients with  asthma  have higher eNO levels than other people. Their levels also rise together with other clinical and laboratory parameters of asthma (for example, the amount of  eosinophils  in their  sputum ). In conditions that trigger inflammation such as  upper respiratory tract infections  or the inhalation of  allergens  or  plicatic acid , eNO levels rise. [ 6 ] [ 7 ]  The eNO levels also tend to vary according to the results of lung function test results such as the degree of  bronchial hyperresponsiveness . Furthermore, drugs used to treat asthma (such as inhaled  glucocorticoids  or  leukotriene receptor antagonists ) also reduce eNO levels."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4770", "contents": "Clinical trials  have looked at whether tailoring asthma therapy based on eNO values is better than conventional care, in which therapy is gauged by symptoms and the results of lung function tests. [ 8 ] [ 9 ] [ 10 ]  To date, the results in both adults and children have been modest and this technique can not be universally recommended. [ 11 ] [ 12 ]  It has also been noted that factors other than inflammation can increase eNO levels, for example airway  acidity . [ 13 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4771", "contents": "The fraction of eNO has been found to be a better test to identify asthmatics than basic lung function testing (for airway obstruction). Its  specificity  is comparable to  bronchial challenge testing , although less  sensitive . [ 15 ] [ 16 ]  This means that a positive eNO test might be useful to rule in a diagnosis of asthma; however, a negative test might not be as useful to rule it out. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4772", "contents": "The role for eNO in other conditions is even less well established compared to asthma."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4773", "contents": "Since asthma can be a cause of  chronic coughing  (it may even be the sole manifestation, such as in  cough-variant asthma ), studies have looked at whether eNO can be used in the diagnosis of chronic cough. [ 18 ] [ 19 ] [ 20 ] [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4774", "contents": "Exhaled NO is minimally increased in chronic obstructive pulmonary disease, but levels may rise in sudden worsenings of the disease ( acute exacerbations ) or disease progression. Early findings indicate a possible role for eNO in predicting the response to inhaled glucocorticoids and the degree of airway obstruction reversibility."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4775", "contents": "Children with cystic fibrosis have been found to have low eNO levels. In subjects with  bronchiectasis  (a state of localized, irreversible dilatation of part of the  bronchial tree ) not due to cystic fibrosis, high levels have been found.  Sarcoidosis  could also feature increased eNO. Low levels have been found in  primary ciliary dyskinesia ,  bronchopulmonary dysplasia , and  pulmonary arterial hypertension . In the latter condition,  inhaled  NO is used as a diagnostic test of the response of the  pulmonary arteries  to  vasodilators  (agents that relax the blood vessels)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4776", "contents": "eNO has also been associated with wheeze, rhinitis and nasal allergy in primary school children. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4777", "contents": "Exposure to air pollution has been associated with decreased, [ 23 ]  and increased eNO levels. [ 24 ] [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4778", "contents": "The most widely used technique to measure eNO is with a  chemical reaction  that produces  light ; this is called a  chemiluminescence  reaction. The NO in the breath sample reacts with  ozone  to form  nitrogen dioxide  in an  excited state . When this returns to its ground state, it emits light in quantities that are  proportional  to the amount of exhaled NO."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4779", "contents": "The subject can exhale directly into a measurement device ('online' technique), or into a reservoir that can afterwards be connected to the analyser ('offline' technique). [ 27 ]  With the former technique, the early and later NO in the breath sample can be analysed separately. The test requires little coordination from the subject, and children older than 4 can be tested successfully. [ 28 ] [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4780", "contents": "The National Institute of Clinical Excellence (NICE) in the UK have published guidance on available measuring devices:  https://www.nice.org.uk/guidance/dg12"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4781", "contents": "The upper normal level of eNO in different studies ranges from 20 to 30  parts per billion . However, several major features influence the reference values. Men have higher eNO values than women. Smoking notoriously lowers eNO values, and even former smoking status can influence results. The levels are higher in people with an  atopic  constitution (a tendency towards  allergies ). [ 30 ]  The fraction of eNO is also flow-dependent (higher at lower flow rates and vice versa), so measurements are normally measured at 50 ml/s. Age or height could also considerably confound eNO values in children. [ 28 ]  The magnitude of these effects lies in the order of 10%, so even single cut-off values might be useful. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4782", "contents": "Until the 1980s, nitric oxide, a product of  fossil fuel  combustion, was thought only to play a role the detrimental effects of  air pollution  on the  respiratory tract . [ 17 ]  In 1987, experiments with  coronary arteries  showed that nitric oxide was the long sought  endothelium-derived relaxing factor . After scientists realised that NO played a biological role, its role as a  cell signalling  molecule and  neurotransmitter  became clear from abundant studies. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4783", "contents": "NO was first detected in exhaled breath samples in 1991. [ 32 ]  In 1992, NO was voted molecule of the year by the scientific journal  Science . [ 33 ]  In 1993, researchers from the  Karolinska Institute  in Sweden were the first to report increased eNO in asthmatics. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4784", "contents": "The first commercial FeNO testing device was developed in 1998 by the Swedish company Aerocrine AB, which is now a part of the  NIOX Group  of companies. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4785", "contents": "Today, NO is not only used in breath tests but also as a therapeutic agent for conditions such as  pulmonary arterial hypertension  and possibly for the  acute respiratory distress syndrome ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4786", "contents": "Fluticasone  is a  manufactured   glucocorticoid  used to treat  nasal congestion . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  Both the  esters ,  fluticasone propionate  (sold as Flovent) and  fluticasone furoate , are also used as  topical   anti-inflammatories  and inhaled  corticosteroids , and are used much more commonly in comparison. [ 3 ] [ 2 ] [ 4 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4787", "contents": "It is on the  World Health Organization's List of Essential Medicines . [ 7 ]  In 2022, it was the 25th most commonly prescribed medication in the United States, with more than 22 \u00a0 million prescriptions, [ 8 ] [ 9 ]  although it is also sold  over-the-counter  (OTC). [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4788", "contents": "This  pharmacology -related article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4789", "contents": "Fluticasone furoate/umeclidinium bromide/vilanterol , sold under the brand name  Trelegy Ellipta  among others, is a  fixed-dose combination  inhaled  medication  that is used for the maintenance treatment of  chronic obstructive pulmonary disease  (COPD). [ 6 ] [ 7 ]  The medications work in different ways:  fluticasone furoate  is an inhaled  corticosteroid  (ICS),  umeclidinium  is a long-acting  muscarinic antagonist  (LAMA), and  vilanterol  is a  long-acting beta-agonist  (LABA)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4790", "contents": "In 2022, it was the 144th most commonly prescribed medication in the United States, with more than 3 \u00a0 million prescriptions. [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4791", "contents": "The combination fluticasone furoate/umeclidinium bromide/vilanterol product is approved by the US  Food and Drug Administration  with an indication for the maintenance treatment of a chronic lung problem called  chronic obstructive pulmonary disease  (COPD) in adults who (1) have already tried  fluticasone furoate/vilanterol  (brand name Breo Ellipta) but are still experiencing symptoms of airway obstruction or who want to reduce the risk for COPD exacerbations and (2) are already receiving umeclidinium and fluticasone furoate/vilanterol and would like to consolidate their inhaler therapy into a single product. [ 4 ]  Similarly, in the European Union, FF/UMEC/VI is indicated for the maintenance treatment in adults with moderate to severe COPD who are not adequately treated by an inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA) combination or a LABA plus long-acting muscarinic antagonist (LAMA) combination. [ 5 ]  Because FF/UMEC/VI is for maintenance (chronic prophylaxis) treatment, it is not used when people are experiencing acute symptoms consistent with worsening airway obstruction (i.e.  COPD exacerbation  or an  asthma exacerbation ). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4792", "contents": "The 2018 National Institute for Health and Care Excellence (NICE) guidelines recommend consideration for ICS/LABA/LAMA triple therapy (like FF/UMEC/VI) provided that the person with COPD has received optimal non-pharmacologic management (e.g. smoking cessation), is experiencing acute COPD exacerbations (either 1 severe exacerbation leading to hospitalization or 2 moderate exacerbations within 1 year), and their COPD has worsened their quality of life. [ 10 ]  The 2020  Global Initiative for Chronic Obstructive Lung Disease  (GOLD) guidelines recommend consideration for triple therapy for people with COPD that\u2014despite ICS/LABA therapy\u2014are persistently breathless, cannot exercise due to their symptoms, or develop further exacerbations. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4793", "contents": "Fluticasone furoate/umeclidinium bromide/vilanterol is only available as an inhaler, which generally contains thirty doses (one-month supply) of medicated powder for inhalation (except in the case of, e.g.,  sample products  from the manufacturer or those produced specifically for hospitals [institutional formulations], which contain 14 doses). [ 4 ]  FF/UMEC/VI exists as a  dry-powder inhaler , which means that the force of the user's breath causes the medicated powder to leave the device and enter the lungs [ 4 ]  (unlike, e.g., a  metered-dose inhaler  which includes a propellant). [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4794", "contents": "Fluticasone furoate/umeclidinium bromide/vilanterol is contraindicated in people who are allergic to any of the individual medication components (i.e. an allergy to vilanterol precludes use of the combination product) or who are severely allergic to milk proteins. [ 4 ]  This is because each dose of FF/UMEC/VI is formulated with  lactose monohydrate  (a sugar found in milk), a portion of which contains detectable milk proteins. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4795", "contents": "The adverse effects of fluticasone furoate/umeclidinium bromide/vilanterol include those that are characteristic of its individual components. For example, there is a risk for  anticholinergic  side effects (e.g.  difficulty urinating ) due to umeclidinium. Effects on the  cardiovascular system , such as  increased pulse ,  elevated blood pressure , and  abnormal heart rhythms , can occur due to vilanterol. Fluticasone furoate, as an inhaled corticosteroid (ICS), can cause side effects that are characteristic of corticosteroids, such as decreased  bone mineral density ,  adrenal suppression  (decreased production of corticosteroids in the body), and a  weakened immune system . [ 4 ]  There is an elevated risk of  pneumonia  (a type of serious lung infection) with FF/UMEC/VI; in  clinical trials , there was a 1.53-fold higher risk of pneumonia in people that received FF/UMEC/VI or FF/VI instead of UMEC/VI (which does not include fluticasone furoate, an ICS). [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4796", "contents": "Fluticasone furoate/umeclidinium bromide/vilanterol may have  drug\u2013drug interactions  (DDIs) that are both  pharmacokinetic  (related to metabolism) and  pharmacodynamic  (related to the effect of medications) in nature. FF/UMEC/VI is susceptible to DDIs that would normally arise from any of the individual components of the medication. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4797", "contents": "All three components are substrates of the efflux transporter  p-glycoprotein  (p-gp), [ 4 ]  a protein that causes drugs to be transported out of cells. The presence of p-gp inhibiting drugs did not appear to effect the pharmacokinetics of vilanterol, though the  area under the curve  (a measure of systemic absorption) of umeclidinium increased 1.4-fold. The effect of p-gp inhibitors on fluticasone pharmacokinetics are unknown. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4798", "contents": "Fluticasone furoate  is metabolized by  cytochrome P450 3A4  (CYP3A4). [ 4 ]  Medications that are inhibitors of CYP3A4 (e.g.  ketoconazole ) may decrease fluticasone's metabolism in the body, causing levels to accumulate. The  bioavailability  (the amount of a medication that reaches the blood after administration) of fluticasone in the FF/UMEC/VI product is low (15.2%), [ 4 ]  decreasing the risk of acute toxicity in overdose/accumulation situations. However, if a person is exposed to high doses of fluticasone over time, it may increase their risk of experiencing  Cushing's syndrome [ 4 ]  (a syndrome that occurs due to high levels of  glucocorticoids , like fluticasone, and includes muscular weakness, weight gain, and  excessive hairiness ). In drug interaction studies of FF/UMEC/VI in the presence of the CYP3A4 inhibitor ketoconazole,  adrenal insufficiency  (as measured by serum  cortisol  levels was noted at 24 hours (27% decrease in cortisol). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4799", "contents": "Umeclidinium  is primarily metabolized by  CYP2D6 , in addition to a few  secondary metabolism  pathways (e.g.  glucuronidation ). [ 4 ]  At doses of umeclidinium that are above the recommended doses, no clinically significant differences in blood levels of umeclidinium was found after repeated dosing in people with impaired CYP2D6 function (compared to people with normal CYP2D6 function). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4800", "contents": "Vilanterol  is also a CYP3A4 substrate. [ 4 ]  Like fluticasone, CYP3A4 inhibitors may increase the levels of vilanterol in the body. [ 4 ]  In drug interaction studies of FF/UMEC/VI in the presence of the CYP3A4 inhibitor ketoconazole, side effects that are characteristic of vilanterol overdose were not observed (i.e.  elevated heart rate ). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4801", "contents": "Fluticasone furoate is a corticosteroid, a type of hormone that can suppress the function of the  immune system  (which fights off infections). [ 4 ]  This can increase the risk of infection, especially oral fungal infections when people do not rinse out their mouths with water after using fluticasone. [ 4 ]  Combining fluticasone with other steroids (e.g. oral  prednisone ) may theoretically increase the risk of infections. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4802", "contents": "Umeclidinium is a medication with  anticholinergic  properties. When combined with other medication that also antagonize cholinergic receptors, this may lead to a duplicate anticholinergic effect, increasing the risk for anticholinergic spectrum side effects (e.g.  dry mouth ,  constipation ). [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4803", "contents": "Vilanterol is a  beta 2 -adrenergic receptor agonist . When combined with medications that have the opposite effect (i.e.  beta blockers , like  carvedilol ), this may theoretically prevent vilanterol from working as intended. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4804", "contents": "Fluticasone furoate/umeclidinium bromide/vilanterol is a combination product made up of three medications: [ 4 ] [ 15 ] [ 16 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4805", "contents": "In the setting of chronic obstructive pulmonary disease (COPD), an inhaled corticosteroid (ICS) will reduce inflammation while a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) will cause  bronchodilation  (widening and opening of the  bronchi , the airways of the lungs). [ 4 ]  Because LABAs and LAMAs are \"long-acting\", they are not used for acute problems with breathing. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4806", "contents": "Fluticasone furoate, like  fluticasone propionate , is a synthetic corticosteroid that is derived from  fluticasone  (another synthetic corticosteroid). [ 17 ] [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4807", "contents": "Umeclidinium bromide is the  bromide  (Br \u22121 ) salt form of umeclidinium, which contains a  quaternary ammonium compound . [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4808", "contents": "Vilanterol is a 1,3- dichlorobenzene  derivative. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4809", "contents": "Fluticasone furoate/umeclidinium bromide/vilanterol was approved for medical use in the United States and in the European Union in 2017. [ 6 ] [ 15 ] [ 3 ] [ 16 ]  It was approved in the European Union with an additional indication in June 2019. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4810", "contents": "Due to the  COVID-19 pandemic , a meeting of the Pulmonary-Allergy Drugs Advisory Committee (PADAC) of the U.S.  Food and Drug Administration  (FDA) scheduled for April 2020, on the subject of FF/UMEC/VI was postponed indefinitely. [ 21 ]  The Advisory Committee had planned to discuss the manufacturer's claim that the medication reduces all-cause mortality in people with COPD. [ 21 ]  FF/UMEC/VI was one of many medications whose regulatory status was affected by the pandemic. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4811", "contents": "Fluticasone propionate , sold under the brand names  Flovent  and  Flonase  among others, is a  glucocorticoid   steroid  medication. [ 8 ]  When inhaled it is used for the long term management of  asthma  and  COPD . [ 8 ]  In the nose it is used for  hay fever  and  nasal polyps . [ 9 ] [ 10 ]  It can also be used for  mouth ulcers . [ 11 ]  It works by decreasing  inflammation ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4812", "contents": "Common side effects when inhaled include  upper respiratory tract infections ,  sinusitis ,  thrush , and  cough . [ 8 ]  Common side effects when used in the nose include  nosebleeding  and sore throat. [ 9 ]  Unlike  fluticasone furoate , which is approved in children as young as two years of age when used for allergies, fluticasone propionate is only approved for children four years and older. [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4813", "contents": "Fluticasone propionate was patented in 1980, and approved for medical use in 1990. [ 14 ]  It is available as a  generic medication . [ 10 ]  In 2022, fluticasone was the 25th most commonly prescribed medication in the United States, with more than 22 \u00a0 million prescriptions. [ 15 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4814", "contents": "Fluticasone propionate is used by powder or aerosol  inhalation  for the prophylaxis of asthma. [ 3 ] [ 8 ]  The  nasal spray  is used for prevention and treatment of  allergic rhinitis . [ 2 ]  Nasal drops are used in the treatment of  nasal polyps . The nasal spray can also be used in the mouth for  mouth ulcers . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4815", "contents": "Fluticasone propionate in a topical form can be used to treat skin conditions such as  eczema ,  psoriasis , and  rashes . [ 17 ] [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4816", "contents": "The nasal spray and oral inhaler formulation have fewer corticosteroid side effects than the tablet formulation because they limit systemic (blood) absorption. [ 2 ]  However, systemic absorption is not negligible even with correct administration. [ 2 ] [ specify ]  Using the spray or inhaler at higher than recommended doses or with other corticosteroids can increase the risk for serious, systemic corticosteroid induced side effects. [ 2 ] [ 3 ]  These side effects include weakened  immune system , increased risk of  systemic infections ,  osteoporosis , and elevated  pressure in the eyes . [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4817", "contents": "Common side effects may include nasal irritation (burning, stinging, bleeding), headache, upset stomach (nausea, vomiting), and diarrhea. Rare side effects include infection (evidenced by, for example, fever, sore throat, and cough),  vision problems ,  severe swelling , hoarse voice, and  difficulty breathing or swallowing . [ 20 ] [ 9 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4818", "contents": "Common side effects may include upper respiratory tract infection, throat irritation,  thrush , cough, and headache. Rare side effects include bruising, swelling of the face/neck, depression, tiredness, and shortness of breath. [ 21 ] [ 8 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4819", "contents": "Fluticasone propionate is a highly selective  agonist  at the  glucocorticoid receptor  with negligible activity at  androgen ,  estrogen , or  mineralocorticoid receptors , [ 4 ]  thereby producing  anti-inflammatory  and  vasoconstriction  effects. It has been shown to have a wide range of inhibitory effects on multiple cell types (e.g.  mast cell ,  eosinophil ,  neutrophil ,  macrophages , and  lymphocytes ) and mediators (e.g.  histamine ,  eicosanoids ,  leukotrienes , and  cytokines ) involved in  inflammation . Fluticasone propionate is stated to exert a topical effect on the lungs without significant systemic effects at usual doses, due to its low systemic  bioavailability . [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4820", "contents": "Fluticasone propionate is broken down by  CYP3A4  ( cytochrome P450  3A4), and has been shown to interact with strong CYP3A4 inhibitors such as  ritonavir  and  ketoconazole . [ 2 ] [ 3 ]  Coadministration of ritonavir and fluticasone may lead to increased levels of fluticasone in the body, which may lead to  Cushing's Syndrome  and  adrenal insufficiency . [ 22 ]   Ketoconazole , an  antifungal drug , has been shown to increase fluticasone concentration leading to systemic corticosteroid side effects. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4821", "contents": "In 2024,  GSK plc  removed Flovent from the market and replaced it with an authorized generic. [ 23 ] [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4822", "contents": "Heat and moisture exchangers  (HME) are devices used in  mechanically ventilated  patients intended to help prevent complications due to \"drying of the respiratory mucosa, such as mucus plugging and endotracheal tube (ETT) occlusion.\" [ 1 ]   HMEs are one type of commercial humidification system, which also include  non-heated-wire humidifiers  and  heated-wire humidifiers . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4823", "contents": "HMEs have been in clinical use for over 30 years. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4824", "contents": "An HME cassette plays a central part of lung rehabilitation after a total  laryngectomy . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4825", "contents": "Humidification and suctioning are necessary to manage secretions in patients on  mechanical ventilation .  According to Branson (2007), the optimal humidification level \"has been not well defined, but it is clear that in a patient with thick and copious secretions a heated humidifier is preferred to an HME\". [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4826", "contents": "In patients with  acute lung injury  and  acute respiratory distress syndrome  conventional humidifiers are preferred to HMEs for improved elimination of  carbon dioxide . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4827", "contents": "An HME has three purposes for patients with tracheostomies or laryngectomies:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4828", "contents": "In the lungs a temperature of 37\u00a0\u00b0C and 100% relative humidity (RH) is the ideal condition for the  ciliary  activity. If the conditions are too warm or cold, the cilia beat slower and at some point not at all. During normal nasal inspiration, air of 22\u00a0\u00b0C and 40% RH is conditioned into air of 32\u00a0\u00b0C and 99% RH at the level of the trachea. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4829", "contents": "The effect of the increased resistance (compared to  stoma  breathing without HME) in laryngectomy patients is poorly understood, but HMEs add a variable resistance to the airflow resistance, depending on the flow rate, though the outcomes of studies are not consistent. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4830", "contents": "HME cassettes with an electrostatic filter are designed to enhance the protection against airborne microbes to help to reduce the transfer of viruses and bacteria. Wearing an HME cassette does not compensate for the loss of upper airway filtration of smaller particles such as bacteria and viruses; the pores of the HME filter are larger than the diameter of the infectious particles. Only larger particles are filtered by the HME. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4831", "contents": "The basic components of heat and moisture exchangers are foam, paper, or a substance which acts as a condensation and absorption surface. The material is often impregnated with  hygroscopic  salts such as calcium chloride, to enhance the water-retaining capacity. HMEs used for laryngectomees are mostly hygroscopic. HMEs can vary in size but they are designed to fit all adhesives or other attachment devices within a certain product line. HME cassettes for  tracheotomy  patients vary in size and are usually a bit larger than for laryngectomy patients.  Air openings are at the side or at the front of the HME.  Some designs use crossbars to prevent clothing from blocking.  Usually a rim on the lid helps to find the correct finger position for occlusion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4832", "contents": "A hands-free HME enables laryngectomy patients with tracheoesophageal voice prostheses to speak without requiring finger occlusion. The device consists of a combination of HME and an automatic speaking valve. The valve closes automatically when exhaling air for speaking, enabling the pulmonary air to be diverted through the tracheoesophageal voice prosthesis into the esophagus. It reopens automatically when exhalation decreases. Besides that, the hands-free HME enables easy removal in case of coughing, or even an adjustable cough relief valve, to release the air that is built up during coughing. In some devices, speech membranes in different strengths can accommodate different speaking pressures."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4833", "contents": "HME devices with a lower airflow resistance make them suitable for physical exercise or when adapting to the breathing resistance for patients that have not used any stoma protection before and start using an HME or have not used an HME for a longer time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4834", "contents": "As antimicrobial filters, an HME is not considered to be an efficient barrier for microorganisms due to a relatively poor bacterial filtration capacity. Some HMEs provide an electrostatic filter for some protection from small particles and airborne microorganisms."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4835", "contents": "Heated humidified high-flow therapy , often simply called  high flow therapy  , is a type of respiratory support that delivers a flow of medical gas to a patient of up to 60 liters per minute and 100% oxygen through a large bore or high flow nasal cannula. Primarily studied in neonates, it has also been found effective in some adults to treat hypoxemia and work of breathing issues. The key components of it are a gas blender, heated humidifier, heated circuit, and cannula. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4836", "contents": "The development of heated humidified high flow started in 1999 with  Vapotherm  introducing the concept of high flow use with race horses. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4837", "contents": "High flow was approved by the U.S. Food and Drug Administration in the early 2000s and used as an alternative to  positive airway pressure  for treatment of  apnea of prematurity  in neonates. [ 3 ]  The term high flow is relative to the size of the patient which is why the flow rate used in children is done by weight as just a few liters can meet the inspiratory demands of a neonate unlike in adults [ 4 ]  It has since become popular for use in adults for respiratory failure [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4838", "contents": "The traditional low flow system used for medical gas delivery is the  Nasal cannula  which is limited to the delivery of 1\u20136 L/min of oxygen or up to 15 L/min in certain types. This is because even with quiet breathing, the inspiratory flow rate at the nares of an adult usually exceeds 30 L/min. Therefore, the oxygen provided is diluted with room air during inspiration. [ 6 ]  Being a high flow system means that it meets or exceeds the flow demands of the patient."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4839", "contents": "Since it is a high flow system, it is able to maintain the wearers fraction of inhaled oxygen (FiO2) at the set rate because they shouldn't be entraining ambient air. However, this may not be the case in patients who are poorly compliant with the therapy and are actively breathing through their mouth. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4840", "contents": "The flow can wash out some of the dead space in the upper airway. This can reduce slightly the amount of carbon dioxide rebreathed. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4841", "contents": "There is a correlation of the flow rate to mean airway pressure and in some subjects there has been an increase in lung volumes and decrease in respiratory rate. [ 8 ]  However, positive end expiratory pressure has only been measured at less 3 cmH2O meaning it is not able to provide close to what a closed ventilatory system could provide. [ 9 ]  In neonates it has been found, however, with a good fit and mouth closed, it can provide end expiratory pressure comparable to nasal continuous positive airway pressure. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4842", "contents": "The higher the flow, the more important proper humidification and heating of the flow becomes to prevent tissue irritation and mucous drying. It has been found that long term use of flows of 20-25 L/min can help reduce symptoms of  chronic obstructive pulmonary disease . This is because, heat and humidity help mucociliary clearance. [ 11 ] [ 12 ]  This is the reason why high-flow therapy is assumed to help with mucus clearance better than other less humidified methodologies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4843", "contents": "High-flow therapy is useful in patients that are spontaneously breathing but are in some type of respiratory failure. These are hypoxemic and certain cases of hypercapnic respiratory failure stemming from exacerbations of asthma and chronic obstructive pulmonary disease, bronchiolitis, pneumonia, and congestive heart failure are all possible situations where high-flow therapy may be indicated. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4844", "contents": "High-flow therapy has shown to be useful in  neonatal intensive care  settings for premature infants with  Infant respiratory distress syndrome , [ 14 ]  as it prevents many infants from needing more invasive ventilatory treatments."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4845", "contents": "Due to the decreased stress of effort needed to breathe, the neonatal body is able to spend more time utilizing metabolic efforts elsewhere, which causes decreased days on a  mechanical ventilator , faster weight gain, and overall decreased hospital stay entirely. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4846", "contents": "High-flow therapy has been successfully implemented in infants and older children. The cannula improves the respiratory distress, the oxygen saturation, and the patient's comfort. Its mechanism of action is the application of mild positive airway pressure and lung volume recruitment. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4847", "contents": "In high-flow therapy, clinicians can deliver higher FiO 2  than is possible with typical oxygen delivery therapy without the use of a  non-rebreather mask  or  tracheal intubation . [ 17 ]  Some patients requiring respiratory support for bronchospasm benefit using air delivered by high-flow therapy without additional oxygen. [ 18 ]   Patients can speak during use of high-flow therapy. As this is a non-invasive therapy, it avoids the risk of  ventilator-associated pneumonia ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4848", "contents": "Use of nasal high flow in acute hypoxemic respiratory failure does not affect mortality or length of stay either in hospital or in the intensive care unit. It can however reduce the need for tracheal intubation and escalation of oxygenation and respiratory support. [ 19 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4849", "contents": "Stable patients with hypercapnia on high-flow therapy have been found to have their carbon dioxide levels decrease similar amounts to noninvasive treatment, but evidence is still limited as to its efficacy and currently the practice guideline is still to use noninvasive ventilation for those with exacerbations of chronic obstructive pulmonary disease and acidosis. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4850", "contents": "Heated humidified high-flow therapy has been used in spontaneously breathing patients with during general anesthesia to facilitate surgery for airway obstruction. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4851", "contents": "High flow therapy is useful in the treatment of sleep apnea. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4852", "contents": "Heliox  is a  breathing gas  mixture of  helium  (He) and  oxygen  (O 2 ). It is used as a medical treatment for patients with difficulty breathing because this mixture generates less resistance than atmospheric air when passing through the airways of the lungs, and thus requires less effort by a patient to breathe in and out of the lungs. It is also used as a breathing gas for deep ambient pressure diving as it is not narcotic at high pressure, and for its low  work of breathing ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4853", "contents": "Heliox has been used medically since the 1930s, and although the medical community adopted it initially to alleviate symptoms of upper airway obstruction, its range of medical uses has since expanded greatly, mostly because of the low density of the gas. [ 1 ] [ 2 ]  Heliox is also used in  saturation diving  and sometimes during the deep phase of  technical dives . [ 3 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4854", "contents": "There is also some use of heliox in conditions of the medium airways ( croup , asthma and  chronic obstructive pulmonary disease ). A recent trial has suggested that lower fractions of helium (below 40%)\u00a0\u2013  thus allowing a higher fraction of oxygen\u00a0\u2013  might also have the same beneficial effect on upper airway obstruction. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4855", "contents": "Patients with these conditions may develop a range of symptoms including  dyspnea  (breathlessness), hypoxemia (below-normal oxygen content in the arterial blood) and eventually a weakening of the respiratory muscles due to  exhaustion , which can lead to respiratory failure and require intubation and mechanical ventilation. Heliox may reduce all these effects, making it easier for the patient to breathe. [ 7 ]  Heliox has also found utility in the weaning of patients off mechanical ventilation, and in the nebulization of inhalable drugs, particularly for the elderly. [ 8 ]  Research has also indicated advantages in using helium\u2013oxygen mixtures in delivery of  anaesthesia . [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4856", "contents": "In  medicine , heliox may refer to a mixture of 21% O 2  (the same as  air ) and 79% He, although other combinations are available (70/30 and 60/40)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4857", "contents": "Heliox generates less airway resistance than air and thereby requires less mechanical energy to ventilate the lungs. [ 10 ]  \" Work of breathing \" (WOB) is reduced by two mechanisms:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4858", "contents": "Heliox 20/80 diffuses 1.8 times faster than oxygen, and the flow of heliox 20/80 from an oxygen flowmeter is 1.8 times the normal flow for oxygen. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4859", "contents": "Heliox has a similar  viscosity  to air but a significantly lower  density  (0.5\u00a0g/L versus 1.25\u00a0g/L at  STP ). Flow of gas through the airway comprises laminar flow, transitional flow and turbulent flow. The tendency for each type of flow is described by the  Reynolds number . Heliox's low density produces a lower Reynolds number and hence higher probability of laminar flow for any given airway. Laminar flow tends to generate less resistance than turbulent flow."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4860", "contents": "In the small airways where flow is laminar, resistance is proportional to gas viscosity and is not related to density and so heliox has little effect. The  Hagen\u2013Poiseuille equation  describes laminar resistance. In the large airways where flow is turbulent, resistance is proportional to density, so heliox has a significant effect."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4861", "contents": "Heliox has been used medically since the early 1930s. It was the mainstay of treatment in acute  asthma  before the advent of  bronchodilators . Currently, heliox is mainly used in conditions of large airway narrowing (upper airway obstruction from tumors or foreign bodies and  vocal cord dysfunction )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4862", "contents": "Helium diluted breathing gases are used to eliminate or reduce the effects of  inert gas narcosis , and to reduce  work of breathing  due to increased gas density at depth. From the 1960s saturation diving physiology studies were conducted with helium from 45 to 610\u00a0m (148 to 2,001\u00a0ft) over several decades by a Hyperbaric Experimental Centre operated by the French company  COMEX  specializing in engineering and deep diving operations. [ 12 ]  Owing to the expense of helium, [ 13 ]  heliox is most likely to be used in deep  saturation diving . It is also sometimes used by  technical divers , particularly those using  rebreathers , which conserve the breathing gas at depth much better than  open circuit scuba . Use of heliox mixtures is known as heliox diving, a subs-category of mixed gas diving, also known simply as gas diving. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4863", "contents": "The proportion of oxygen in a diving mix depends on the maximum depth of the dive plan, but it is often  hypoxic  and may be less than 10%. Each mix is custom made using  gas blending  techniques, which often involve the use of  booster pumps  to achieve typical  diving cylinder  pressures of 200 to 300\u00a0 bar  (2,900 to 4,400\u00a0 psi ) from lower pressure banks of oxygen and helium cylinders."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4864", "contents": "Because  sound  travels faster in heliox than in air,  voice   formants  are raised, making divers' speech very high-pitched and hard to understand to people not used to it. [ 15 ]  Surface personnel often employ a piece of communications equipment called a \"helium de-scrambler\", which electronically lowers the pitch of the diver's voice as it is relayed through the communications gear, making it easier to understand."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4865", "contents": "Trimix  is a less expensive alternative to heliox for deep diving, which uses only enough helium to limit narcosis and gas density to tolerable levels for the planned depth. [ 16 ]  Trimix is often used in  technical diving , and is also sometimes used in  professional diving ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4866", "contents": "In 2015, the  United States Navy Experimental Diving Unit  showed that decompression from bounce dives using trimix is not more efficient  than dives on heliox. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4867", "contents": "The  helium dilution technique  is the way of measuring the  functional residual capacity  of the  lungs  (the volume left in the  lungs  after normal  expiration )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4868", "contents": "This technique is a closed-circuit system where a spirometer is filled with a mixture of  helium  (He) and oxygen. The amount of He in the spirometer is known at the beginning of the test (concentration \u00d7 volume = amount). The patient is then asked to breathe (normal breaths) in the mixture starting from FRC (functional residual capacity), which is the gas volume in the lung after a normal breath out. The spirometer measures helium concentration. The helium spreads into the lungs of the patient, and settles at a new concentration (C2). Because there is no leak of substances in the system, the amount of helium remains constant during the test, and the FRC is calculated by using the following equation:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4869", "contents": "C \n \n 1 \n \n \n \n V \n \n 1 \n \n \n = \n \n C \n \n 2 \n \n \n \n V \n \n 2 \n \n \n \n \n {\\displaystyle C_{1}V_{1}=C_{2}V_{2}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4870", "contents": "C \n \n 1 \n \n \n \n V \n \n 1 \n \n \n = \n \n C \n \n 2 \n \n \n ( \n \n V \n \n 1 \n \n \n + \n F \n R \n C \n ) \n \n \n {\\displaystyle C_{1}V_{1}=C_{2}(V_{1}+FRC)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4871", "contents": "F \n R \n C \n = \n \n \n \n C \n 1 \n V \n 1 \n \n \n C \n 2 \n \n \n \n \u2212 \n V \n 1 \n \n \n {\\displaystyle FRC={\\frac {C1V1}{C2}}-V1}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4872", "contents": "V2 = total gas volume (FRC + volume of spirometer)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4873", "contents": "V1 = volume of gas in spirometer"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4874", "contents": "C1 = initial (known) helium concentration"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4875", "contents": "C2 = final helium concentration (measured by the spirometer)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4876", "contents": "Note to measure FRC the patient is connected to the spirometer directly after a normal breath (when the lung volume equals FRC), if the patient is initially connected to the spirometer at a different lung volume (like TLC or RV) the measured volume will be the initial volume started from and not FRC. In patients with obstructive pulmonary diseases the measurements of the helium dilution technique are not reliable because of incomplete equilibration of the helium in all areas of the lungs. In such cases it is more accurate to use a body plethysmograph."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4877", "contents": "A simplified helium dilution technique may be used as an alternative to quantitative CT scans to assess end-expiratory lung volumes (EELV) among patients who are on  mechanical ventilation  with diagnosis of  ALI / ARDS  according to a  cross-sectional  study. [ 1 ]  The results show a good correlation [EELV(He)=208+0.858xEELV(CT),  r =0.941,  p  < 0.001] between the two methods, and the helium dilution technique offers the advantages of lower cost, decreased transportation of critically ill patients, and reduced radiation exposure. This study's results may have limited generalizability due to its specificity to the ALI/ARDS population and its small sample size (21 patients)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4878", "contents": "Hyperbaric medicine  is medical treatment in which an increase in barometric pressure over ambient pressure is employed increasing the  partial pressures  of all gases present in the ambient atmosphere. The immediate effects include reducing the size of  gas embolisms  and raising the partial pressures of all gases present according to  Henry's law .\nCurrently, there are two types of hyperbaric medicine depending on the gases compressed, hyperbaric air and hyperbaric oxygen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4879", "contents": "Hyperbaric air  ( HBA ), consists of compressed atmospheric air (79% nitrogen, 21% oxygen, and minor gases) and is FDA-approved for acute mountain sickness. The hyperbaric air environment is created by placing the patient in a  portable hyperbaric air chamber  and inflating that chamber up to 7.35  psi  gauge (1.5  atmospheres absolute ) using a foot-operated or electric air pump. Although the mechanisms of hyperbaric air are poorly understood it is thought that it relieves  hypoxemia  caused by the decreased partial pressure of oxygen resulting from high altitude by increasing the partial pressure of air (including oxygen and nitrogen) simulating a descent in altitude. [ 1 ] [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4880", "contents": "Hyperbaric oxygen therapy  ( HBOT ), the medical use of greater than 99%  oxygen  at an ambient pressure higher than  atmospheric pressure , and  therapeutic recompression  for  decompression illness , intended to reduce the injurious effects of systemic gas bubbles by physically reducing their size and providing improved conditions for elimination of bubbles and excess dissolved gas."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4881", "contents": "The equipment required for hyperbaric oxygen treatment consists of a  pressure vessel for human occupancy , which may be of rigid or flexible construction, and a means of a controlled atmosphere supply. Operation is performed to a predetermined schedule by trained personnel who monitor the patient and may adjust the schedule as required. HBOT found early use in the treatment of  decompression sickness , and has also shown great effectiveness in treating conditions such as  gas gangrene  and  carbon monoxide poisoning . More recent research has examined the possibility that it may also have value for other conditions such as cerebral palsy and multiple sclerosis, but no significant evidence has been found."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4882", "contents": "A pressure vessel for human occupancy (PVHO) is an enclosure that is intended to be occupied by one or more persons at a pressure which differs from ambient by at least 2 pounds per square inch (0.14\u00a0bar). All chambers used in the US made for hyperbaric medicine fall under the jurisdiction of the Federal Food and Drug Agency (FDA). The FDA requires hyperbaric chambers to comply with the  American Society of Mechanical Engineers  PVHO Codes [ 4 ]  and the National Fire Protection Association Standard 99, Health Care Facilities Code. [ 5 ]  Similar conditions apply in most other countries."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4883", "contents": "Hyperbaric medicine poses some inherent hazards that are mitigated by FDA-compliant equipment and trained personnel.  Serious injury can occur at pressures as low as 2 psig (13.8 kPa) if a person in the PVHO is rapidly decompressed. [ 6 ] [ 7 ]  If oxygen is used in the hyperbaric therapy, this can increase the fire hazard. This is why the FDA requires  hyperbaric chambers  to meet ASME PVHO and NFPA 99 standards or the local equivalent. All chambers that meet FDA standards must have an ASME data plate, and people seeking hyperbaric treatment should check to ensure the equipment and facilities are to proper standards."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4884", "contents": "Therapeutic recompression is usually also provided in a  hyperbaric chamber . It is the definitive treatment for  decompression sickness  and may also be used to treat  arterial gas embolism  caused by  pulmonary barotrauma  of ascent. In emergencies  divers  may sometimes be treated by  in-water recompression  (when a chamber is not available) if suitable  diving equipment  (to reasonably secure the airway) is available."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4885", "contents": "A number of  hyperbaric treatment schedules  have been published over the years for both therapeutic recompression and hyperbaric oxygen therapy for other conditions. Some of these use breathing gases other than air or pure oxygen, when the partial pressure of oxygen must be limited but the pressure required is relatively high.  Nitrox  and  Heliox  treatment schedules are available for these cases. Treatment gas may be the ambient chamber gas, or delivered via a  built-in breathing system ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4886", "contents": "Hyperbaric medicine includes hyperbaric oxygen treatment, which is the medical use of oxygen at greater than atmospheric pressure to increase the availability of oxygen in the body; [ 8 ]  and therapeutic recompression, which involves increasing the ambient pressure on a person, usually a diver, to treat  decompression sickness  or an  air embolism  by reducing the volume and more rapidly eliminating bubbles that have formed within the body. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4887", "contents": "In the United States the  Undersea and Hyperbaric Medical Society , known as UHMS, lists approvals for reimbursement for certain diagnoses in hospitals and clinics. The following  indications  have approved (for reimbursement) uses of hyperbaric oxygen therapy as defined by the UHMS Hyperbaric Oxygen Therapy Committee: [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4888", "contents": "There is no reliable evidence to support its use in  autism ,  cancer ,  diabetes ,  HIV/AIDS ,  Alzheimer's disease ,  asthma ,  Bell's palsy ,  cerebral palsy , depression, heart disease, migraines,  multiple sclerosis ,  Parkinson's disease , spinal cord injury, sports injuries, or stroke. [ 52 ] [ 53 ] [ 54 ]  Furthermore, there is evidence that potential side effects of hyperbaric medicine pose an unjustified risk in such cases. A  Cochrane review  published in 2016 reviewed a small set of  clinical trials  attempting to treat  autism spectrum disorders  with hyperbaric oxygen therapy. They noted a small sample size and large \"confidence intervals\" did not provide much evidence. No links between improvements in social abilities or cognitive function were noted. There are also ethical issues with further trials, as  the  eardrum  can be damaged during hyperbaric therapy. [ 55 ]  Despite the lack of evidence, in 2015, the number of people utilizing this therapy has continued to rise. [ 56 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4889", "contents": "There is also insufficient evidence to support its use in acute traumatic or surgical wounds. [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4890", "contents": "There is limited evidence that hyperbaric oxygen therapy improves hearing in patients with  sudden sensorineural hearing loss  who present within two weeks of hearing loss. There is some indication that HBOT might improve  tinnitus  presenting in the same time frame. [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4891", "contents": "HBOT in diabetic foot ulcers increased the rate of early ulcer healing but does not appear to provide any benefit in wound healing at long-term follow-up. In particular, there was no difference in major amputation rate. [ 59 ]  For venous, arterial and pressure ulcers, no evidence was apparent that HBOT provides a long-term improvement over standard treatment. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4892", "contents": "There is some evidence that HBOT is effective for late radiation tissue injury of bone and soft tissues of the head and neck. Some people with radiation injuries of the head, neck or bowel show an improvement in quality of life. Importantly, no such effect has been found in neurological tissues. The use of HBOT may be justified to selected patients and tissues, but further research is required to establish the best people to treat and timing of any HBO therapy. [ 60 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4893", "contents": "As of 2012, there was no sufficient evidence to support using hyperbaric oxygen therapy to treat people who have  traumatic brain injuries . [ 61 ]  In  acute   stroke , HBOT does not show benefit. [ 62 ] [ 54 ]  Small clinical trials, however, have shown benefits from HBOT for stroke survivors between 6\u00a0months to 3\u00a0years after the acute phase. [ 63 ] [ 64 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4894", "contents": "HBOT in  multiple sclerosis  has not shown benefit and routine use is not recommended. [ 53 ] [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4895", "contents": "A 2007 review of HBOT in  cerebral palsy  found no difference compared to the control group. [ 66 ] [ 67 ]   Neuropsychological  tests also showed no difference between HBOT and room air and based on caregiver report, those who received room air had significantly better mobility and social functioning. [ 66 ] [ 67 ]  Children receiving HBOT were reported to experience seizures and the need for  tympanostomy tubes  to equalize ear pressure, though the incidence was not clear. [ 66 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4896", "contents": "In  alternative medicine , hyperbaric medicine has been promoted as a treatment for cancer. However, a 2011 study by the  American Cancer Society  reported no evidence it is effective for this purpose. [ 68 ]  A 2012 review article in the journal,  Targeted Oncology,  reports that \"there is no evidence indicating that HBO neither acts as a stimulator of tumor growth nor as an enhancer of recurrence. On the other hand, there is evidence that implies that HBO might have tumor-inhibitory effects in certain cancer subtypes, and we thus strongly believe that we need to expand our knowledge on the effect and the mechanisms behind tumor oxygenation.\" [ 69 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4897", "contents": "Low-quality evidence suggests that hyperbaric oxygen therapy may reduce the pain associated with an acute migraine headache in some cases. [ 70 ]  It is not known which people would benefit from this treatment, and there is no evidence that hyperbaric medicine can prevent future migraines. [ 70 ]  More research is necessary to confirm the effectiveness of hyperbaric oxygen therapy for treating migraines. [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4898", "contents": "Patients who are having extreme difficulty breathing \u2013  acute respiratory distress syndrome  \u2013 are commonly given  oxygen  and there have been limited trials of hyperbaric equipment in such cases. Examples include treatment of the  Spanish flu [ 71 ]  and  COVID-19 . [ 72 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4899", "contents": "The toxicology of the treatment has been reviewed by Ustundag  et al. [ 73 ]  and its risk management is discussed by Christian R. Mortensen, in light of the fact that most hyperbaric facilities are managed by departments of anaesthesiology and some of their patients are critically ill. [ 74 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4900", "contents": "An absolute  contraindication  to hyperbaric oxygen therapy is untreated  pneumothorax . [ 75 ]  The reason is concern that it can progress to tension pneumothorax, especially during the decompression phase of therapy, although treatment on oxygen-based tables may avoid that progression. [ 76 ]  The COPD patient with a large  bleb  represents a relative contraindication for similar reasons. [ 77 ] [ page\u00a0needed ]  Also, the treatment may raise the issue of  occupational health and safety  (OHS), for chamber inside attendants, who should not be compressed if they are unable to  equalise  ears and  sinuses . [ 78 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4901", "contents": "The following are relative contraindications\u00a0\u2013  meaning that special consideration must be made by specialist physicians before HBO treatments begin:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4902", "contents": "Pregnancy is not a relative contraindication to hyperbaric oxygen treatments, [ 77 ] [ page\u00a0needed ]  although it may be for  underwater diving . In cases where a pregnant woman has carbon monoxide poisoning there is evidence that lower pressure (2.0 ATA) HBOT treatments are not harmful to the fetus, and that the risk involved is outweighed by the greater risk of the untreated effects of CO on the fetus (neurologic abnormalities or death.) [ 82 ] [ 83 ]  In pregnant patients, HBO therapy has been shown to be safe for the fetus when given at appropriate levels and \"doses\" (durations). In fact, pregnancy lowers the threshold for HBO treatment of carbon monoxide-exposed patients. This is due to the high affinity of fetal hemoglobin for CO. [ 77 ] [ page\u00a0needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4903", "contents": "The therapeutic consequences of HBOT and recompression result from multiple effects. [ 10 ] [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4904", "contents": "The increased overall pressure is of therapeutic value in the treatment of  decompression sickness  and  air embolism  as it provides a physical means of reducing the volume of inert gas bubbles within the body; [ 85 ]  Exposure to this increased pressure is maintained for a period long enough to ensure that most of the bubble gas is dissolved back into the tissues, removed by perfusion and eliminated in the lungs. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4905", "contents": "The improved concentration gradient for inert gas elimination ( oxygen window ) by using a high partial pressure of oxygen increases the rate of inert gas elimination in the treatment of decompression sickness. [ 86 ] [ 87 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4906", "contents": "For many other conditions, the therapeutic principle of HBOT lies in its ability to drastically increase  partial pressure  of oxygen in the tissues of the body. The oxygen partial pressures achievable using HBOT are much higher than those achievable while breathing pure oxygen under  normobaric  conditions (i.e. at normal atmospheric pressure). This effect is achieved by an increase in the oxygen transport capacity of the blood. At normal atmospheric pressure, oxygen transport is limited by the oxygen binding capacity of  hemoglobin  in  red blood cells  and very little oxygen is transported by  blood plasma . Because the hemoglobin of the red blood cells is almost saturated with oxygen at atmospheric pressure, this route of transport cannot be exploited any further. Oxygen transport by plasma, however, is significantly increased using HBOT because of the higher solubility of oxygen as pressure increases. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4907", "contents": "A study suggests that exposure to hyperbaric oxygen (HBOT) might also mobilize stem/progenitor cells from the bone marrow by a  nitric oxide -dependent mechanism. [ 88 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4908", "contents": "A more recent study suggests that stem cell mobilization, similar to that seen in the Thom study, is also invoked at relative normo-baric pressure with a significantly smaller increase in oxygen concentration. This study also found a significant decrease in the expression of the systemic inflammatory cytokine TNF-\u03b1 in venous blood. These results suggest that hyperbaria may not be required to invoke the transcriptional responses seen at higher partial pressures of oxygen and that the effect is due solely to oxygen. [ 89 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4909", "contents": "The traditional type of  hyperbaric chamber  used for therapeutic recompression and HBOT is a rigid shelled  pressure vessel . Such chambers can be run at absolute pressures typically about 6  bars  (87\u00a0 psi ), 600,000\u00a0 Pa  or more in special cases. [ 90 ]  Navies, professional diving organizations, hospitals, and dedicated recompression facilities typically operate these. They range in size from semi-portable, one-patient units to room-sized units that can treat eight or more patients. The larger units may be rated for lower pressures if they are not primarily intended for treatment of diving injuries. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4910", "contents": "A rigid chamber may consist of:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4911", "contents": "Flexible monoplace chambers are available ranging from collapsible flexible aramid fiber-reinforced chambers which can be disassembled for transport via truck or  SUV , with a maximum working pressure of 2 bar above ambient complete with BIBS allowing full oxygen treatment schedules. [ 92 ] [ 93 ] [ 94 ]  to portable, air inflated \"soft\" chambers that can operate at between 0.3 and 0.5 bars (4.4 and 7.3\u00a0psi) above atmospheric pressure with no supplemental oxygen, and longitudinal zipper closure. [ 95 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4912", "contents": "Acrylic windows with PVHO-1 defined standard geometries and design criteria are generally used. Shapes and sizes vary with chamber application and the requirements for the specific use. [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4913", "contents": "The geometries in general use include: [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4914", "contents": "Low pressure, small diameter chambers may use large cylindrical windows fitted inside the metal structure. In some cases the whole cylindrical pressure chamber has been made from an acrylic tube. [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4915", "contents": "The acrylic windows of a hyperbaric chamber have a limited lifespan, which can be expressed as the design life, which is the conservatively estimated life as calculated in the design process, typically about 10 years, and the service life, which is the actual time the window can be safely and legally used when well maintained, properly inspected, and repaired when necessary and possible and which can be as much as twice the design life. [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4916", "contents": "There are three grades of inspection required: [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4917", "contents": "The window is examined to detect crazing, cracks, blisters, discolouration, scratches or pits. [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4918", "contents": "The operating pressure depends on the application. Chambers used for clinical hyperbaric oxygen therapy commonly have a maximum allowable working pressure of 35 pounds per square inch (2.4\u00a0bar) with a maximum of about 150 pounds per square inch (10\u00a0bar) Chambers used for support of commercial or military diving operations and for research may have a maximum allowable working pressure of up to 1,000 pounds per square inch (69\u00a0bar). [ 96 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4919", "contents": "In the larger multiplace chambers, patients inside the chamber breathe from either \"oxygen hoods\" \u2013 flexible, transparent soft plastic hoods with a seal around the neck similar to a  space suit  helmet \u2013 or tightly fitting  oxygen masks , which supply pure oxygen and may be designed to directly exhaust the exhaled gas from the chamber. During treatment patients breathe 100% oxygen most of the time to maximise the effectiveness of their treatment, but have periodic \"air breaks\" during which they breathe chamber air (21% oxygen) to reduce the risk of  oxygen toxicity . The exhaled treatment gas must be removed from the chamber to prevent the buildup of oxygen, which could present a fire risk. Attendants may also breathe oxygen some of the time to reduce their risk of  decompression sickness  when they leave the chamber. The pressure inside the chamber is increased by opening valves allowing high-pressure air to enter from  storage cylinders , which are filled by an  air compressor . Chamber air oxygen content is kept between 19% and 23% to control fire risk (US Navy maximum 25%). [ 90 ]  If the chamber does not have a scrubber system to remove carbon dioxide from the chamber gas, the chamber must be isobarically ventilated to keep the CO 2  within acceptable limits. [ 90 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4920", "contents": "A soft chamber may be pressurized directly from a compressor. [ 95 ]  or from storage cylinders. [ 94 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4921", "contents": "Smaller \"monoplace\" chambers can only accommodate the patient, and no medical staff can enter. The chamber may be pressurised with pure oxygen or compressed air. If pure oxygen is used, no oxygen breathing mask or helmet is needed, but the cost of using pure oxygen is much higher than that of using compressed air. If compressed air is used, then an oxygen mask or hood is needed as in a multiplace chamber. Most monoplace chambers can be fitted with a demand breathing system for air breaks. In low pressure soft chambers, treatment schedules may not require air breaks, because the risk of oxygen toxicity is low due to the lower oxygen partial pressures used (usually 1.3 ATA), and short duration of treatment. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4922", "contents": "For alert, cooperative patients, air breaks provided by mask are more effective than changing the chamber gas because they provide a quicker gas change and a more reliable gas composition both during the break and treatment periods. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4923", "contents": "Initially, HBOT was developed as a treatment for  diving disorders  involving bubbles of gas in the tissues, such as decompression sickness and gas embolism, It is still considered the definitive treatment for these conditions. The chamber treats decompression sickness and gas embolism by increasing pressure, reducing the size of the gas bubbles and improving the transport of  blood  to downstream tissues. After elimination of bubbles, the pressure is gradually reduced back to atmospheric levels. [ 9 ]  Hyperbaric chambers are also used for animals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4924", "contents": "As of September 2023, a number of hyperbaric chambers in the US are turning divers with decompression sickness away, and only treating more profitable scheduled cases. The number of hyperbaric medical facilities in the US is estimated at about 1500, of which 67 are treating diving accidents, according to  Divers Alert Network . Many facilities only provide hyperbaric treatment for wound care for economic reasons. Emergency hyperbaric services are more expensive to train and staff, and liability is increased. [ 97 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4925", "contents": "Emergency HBOT for  decompression illness  follows treatment schedules laid out in treatment tables. Most cases employ a recompression to 2.8 bars (41\u00a0psi) absolute, the equivalent of 18 metres (60\u00a0ft) of water, for 4.5 to 5.5 hours with the casualty breathing pure oxygen, but taking air breaks every 20 minutes to reduce oxygen toxicity. For extremely serious cases resulting from very deep dives, the treatment may require a chamber capable of a maximum pressure of 8 bars (120\u00a0psi), the equivalent of 70 metres (230\u00a0ft) of water, and the ability to supply  heliox  as a breathing gas. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4926", "contents": "U.S. Navy  treatment charts are used in  Canada  and the United States to determine the duration, pressure, and  breathing gas  of the therapy. The most frequently used tables are Table 5 and Table 6. In the UK the  Royal Navy  62 and 67 tables are used."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4927", "contents": "The  Undersea and Hyperbaric Medical Society  (UHMS) publishes a report that compiles the latest research findings and contains information regarding the recommended duration and pressure of the longer-term conditions. [ 98 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4928", "contents": "There are several sizes of portable chambers, which are used for home treatment. These are usually referred to as \"mild personal hyperbaric chambers\", which is a reference to the lower pressure (compared to hard chambers) of soft-sided chambers. The American Medical Association is opposed to home use or any other use of hyperbaric chambers if it is not \"in facilities with appropriately trained staff including physician supervision and prescription and only when the intervention has scientific support or rationale\" due demonstrated hazard  [ 99 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4929", "contents": "In the US, these \"mild personal hyperbaric chambers\" are categorized by the FDA as CLASS II medical devices and requires a prescription in order to purchase one or take treatments. [ 100 ]  As with any hyperbaric chamber, the FDA require compliance with ASME and NFPA standards.  The most common option (but not approved by FDA) some patients choose is to acquire an oxygen concentrator which typically delivers 85\u201396% oxygen as the breathing gas."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4930", "contents": "Oxygen is never fed directly into soft chambers but is rather introduced via a line and mask directly to the patient. FDA approved oxygen concentrators for human consumption in confined areas used for HBOT are regularly monitored for purity (\u00b11%) and flow (10 to 15 liters per minute outflow pressure). An audible alarm will sound if the purity ever drops below 80%. Personal hyperbaric chambers use 120 volt or 220 volt outlets. The FDA warns against the use of oxygen concentrators or oxygen tanks with chambers that does not meet ASME and FDA standards, regardless of if the concentrators are FDA approved. [ 101 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4931", "contents": "There are risks associated with HBOT, similar to some diving disorders. Pressure changes can cause a \"squeeze\" or  barotrauma  in the tissues surrounding trapped air inside the body, such as the  lungs , [ 76 ]  behind the  eardrum , [ 102 ] [ 103 ]  inside  paranasal sinuses , [ 102 ]  or trapped underneath  dental fillings . [ 104 ]  Breathing high-pressure oxygen may cause  oxygen toxicity . [ 105 ]  Temporarily blurred vision can be caused by swelling of the  lens , which usually resolves in two to four weeks. [ 106 ] [ 107 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4932", "contents": "There are reports that cataracts may progress following HBOT, [ 108 ]  and rarely, may develop  de novo , but this may be unrecognized and under reported. The cause is not fully explained, but evidence suggests that lifetime exposure of the lens to high partial pressure oxygen may be a major factor. Oxidative damage to lens proteins is thought to be responsible. This may be an end-stage of the relatively well documented myopic shift detected in most hyperbaric patients after a course of multiple treatments. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4933", "contents": "Patients inside the chamber may notice discomfort inside their  ears  as a pressure difference develops between their middle ear and the chamber atmosphere. [ 109 ]  This can be relieved by  ear clearing  using the  Valsalva maneuver  or other techniques. Continued increase of pressure without equalizing may cause ear drums to rupture, resulting in severe pain. As the pressure in the chamber increases further, the air may become warm."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4934", "contents": "To reduce the pressure, a valve is opened to allow air out of the chamber. As the pressure falls, the patient's ears may \"squeak\" as the pressure inside the ear equalizes with the chamber. The temperature in the chamber will fall. The speed of pressurization and de-pressurization can be adjusted to each patient's needs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4935", "contents": "Oxygen toxicity  is a limitation on both maximum partial pressure of oxygen, and on length of each treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4936", "contents": "HBOT can accelerate the development of  cataracts  over multiple repetitive treatments, and can cause temporary relative myopia over the shorter term. [ 110 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4937", "contents": "The use of hyperbaric chambers for medical and therapeutic procedures is generally regulated. Authorities have warned of potential risks to patients receiving treatment in unlicensed facilities, notably in Israel, [ 111 ]  Canada, [ 112 ]  and the United States. [ 113 ]  In Italy, the use of hyperbaric chambers for therapy was severely restricted to limited medical settings after a serious fire which killed ten patients in 1997. [ 114 ] [ 115 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4938", "contents": "In some jurisdictions, the use and availability of HBOT is further restricted at the subnational level. In the U.S. state of North Carolina, several cities including Durham, Raleigh and Charlotte have ordered operators of mild hyperbaric oxygen therapy to close to protect public safety due to a risk of fire. [ 116 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4939", "contents": "Unlicensed and fraudulent operators have been subject to prosecution. In Australia, Oxymed Australia Pty Ltd and director Malcolm Hooper were ordered to pay AUS $3 million in fines after advertising hyperbaric therapy against the country's Therapeutic Goods Act. [ 117 ]  In Canada, certain soft-shelled hyperbaric chambers were removed from the market for a potential risk to patients. [ 118 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4940", "contents": "HBOT is recognized by  Medicare  in the  United States  as a reimbursable treatment for 14 UHMS \"approved\" conditions. A 1-hour HBOT session may cost between $300 and higher in private clinics, and over $2,000 in hospitals. U.S. physicians (M.D. or D.O.) may lawfully prescribe HBOT for \"off-label\" conditions such as  stroke , [ 119 ] [ 120 ]  and  migraine . [ 121 ] [ 122 ]  Such patients are treated in outpatient clinics. In the  United Kingdom  most chambers are financed by the  National Health Service , although some, such as those run by Multiple Sclerosis Therapy Centres, are non-profit. In Australia, HBOT is not covered by  Medicare  as a treatment for multiple sclerosis. [ 123 ]  China and Russia treat more than 80 maladies, conditions, and trauma with HBOT. [ 124 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4941", "contents": "Aspects under research include radiation-induced  hemorrhagic cystitis ; [ 125 ]  and  inflammatory bowel disease , [ 126 ]   rejuvenation . [ 127 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4942", "contents": "Some research found evidence that HBOT improves local tumor control, mortality, and local tumor recurrence for cancers of the head and neck. [ 128 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4943", "contents": "Some research also found evidence of an increase in stem progenitor cells [ 81 ]  and a decrease in inflammation. [ 89 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4944", "contents": "Tentative evidence shows a possible benefit in  cerebrovascular diseases . [ 129 ]  Rats subjected to HBOT after some time following the  acute  phase of experimentally-induced  stroke  showed reduced inflammation, increased  brain-derived neurotrophic factor , and evidence of  neurogenesis . [ 130 ]  Another rat study showed improved neurofunctional recovery as well as neurogenesis following the late-chronic phase of experimentally-induced stroke. [ 131 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4945", "contents": "The clinical experience and results so far published has promoted the use of HBOT therapy in patients with cerebrovascular injury and focal cerebrovascular injuries. [ 132 ]  However, the power of clinical research is limited because of the shortage of  randomized controlled trials . [ 129 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4946", "contents": "A 2010 review of studies of HBOT applied to wounds from radiation therapy reported that, while most studies suggest a beneficial effect, more experimental and clinical research is needed to validate its clinical use. [ 133 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4947", "contents": "Junod built a chamber in France in 1834 to treat pulmonary conditions at pressures between 2 and 4 atmospheres absolute. [ 134 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4948", "contents": "During the following century \"pneumatic centres\" were established in Europe and the USA which used hyperbaric air to treat a variety of conditions. [ 135 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4949", "contents": "Orval J Cunningham , a professor of anesthesia at the University of Kansas in the early 1900s observed that people with circulatory disorders did better at sea level than at altitude and this formed the basis for his use of hyperbaric air. In 1918, he successfully treated patients with the Spanish flu with hyperbaric air. In 1930 the American Medical Association forced him to stop hyperbaric treatment, since he did not provide acceptable evidence that the treatments were effective. [ 135 ] [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4950", "contents": "The English scientist  Joseph Priestley  discovered oxygen in 1775. Shortly after its discovery, there were reports of toxic effects of hyperbaric oxygen on the central nervous system and lungs, which delayed therapeutic applications until 1937, when  Behnke  and  Shaw  first used it in the treatment of decompression sickness. [ 135 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4951", "contents": "In 1955 and 1956 Churchill-Davidson, in the UK, used hyperbaric oxygen to enhance the  radiosensitivity  of tumours, while  Ite Boerema \u00a0[ nl ] , at the  University of Amsterdam , successfully used it in  cardiac surgery . [ 135 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4952", "contents": "In 1961  Willem Hendrik Brummelkamp \u00a0[ nl ]  et al. published on the use of hyperbaric oxygen in the treatment of clostridial  gas gangrene . [ 136 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4953", "contents": "In 1962 Smith and Sharp reported successful treatment of carbon monoxide poisoning with hyperbaric oxygen. [ 135 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4954", "contents": "The Undersea Medical Society (now Undersea and Hyperbaric Medical Society) formed a Committee on Hyperbaric Oxygenation which has become recognized as the authority on indications for hyperbaric oxygen treatment. [ 135 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4955", "contents": "Fires inside a hyperbaric chamber are extremely dangerous. A review article published in 1997 found 77 human fatalities in 35 different hyperbaric chamber fires that occurred from 1923 to 1996. [ 137 ]  Further studies indicate while the treatment is often considered safe, the use of hyperbaric equipment comes with risks to the operating personnel when improperly used. Proper equipment maintenance and safety procedures for the use  of pressure equipment is mandatory. [ 138 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4956", "contents": "Hyperbaric treatment schedules  or hyperbaric treatment tables, are planned sequences of events in chronological order for hyperbaric pressure exposures specifying the pressure profile over time and the breathing gas to be used during specified periods, for medical treatment. Hyperbaric therapy is based on exposure to pressures greater than normal atmospheric pressure, and in many cases the use of breathing gases with oxygen content greater than that of air."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4957", "contents": "A large number of hyperbaric treatment schedules are intended primarily for treatment of underwater divers and hyperbaric workers who present symptoms of  decompression illness  during or after a dive or hyperbaric shift, but  hyperbaric oxygen therapy  may also be used for other conditions."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4958", "contents": "Most hyperbaric treatment is done in  hyperbaric chambers  where environmental hazards can be controlled, but occasionally treatment is done in the field by  in-water recompression  when a suitable chamber cannot be reached in time. The risks of in-water recompression include maintaining gas supplies for multiple divers and people able to care for a sick patient in the water for an extended period of time. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4959", "contents": "Recompression of diving casualties presenting symptoms of decompression sickness has been the treatment of choice since the late 1800s. This acceptance was primarily based on clinical experience. [ 3 ] \n John Scott Haldane 's decompression procedures and the associated tables developed in the early 1900s greatly reduced the incidence of decompression sickness, but did not eliminate it entirely. It was, and remains, necessary to treat incidences of decompression sickness. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4960", "contents": "During the building of the  Brooklyn Bridge , workers with decompression sickness were recompressed in an iron chamber built for this purpose. They were recompressed to the same pressure they had been exposed to while working, and when the pain was relieved, decompressed slowly to atmospheric pressure. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4961", "contents": "Although recompression and slow decompression were the accepted treatment, there was not yet a standard for either the recompression pressure or the rate of decompression. This changed when the first standard table for recompression treatment with air was published in the US Navy Diving Manual in 1924. These tables were not entirely successful - there was a 50% relapse rate, and the treatment, though fairly effective for mild cases, was less effective in serious cases. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4962", "contents": "Field results showed that the 1944 oxygen treatment table was not yet satisfactory, so a series of tests were conducted by staff from the Navy Medical Research Institute and the Navy Experimental Diving Unit using human subjects to verify and modify the treatment tables. [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4963", "contents": "Tests were conducted using the 100-foot air-oxygen treatment table and the 100-foot air treatment table, which were found to be satisfactory. Other tables were extended until they produced satisfactory results. The resulting tables were used as the standard treatment for the next 20 years, and these tables and slight modifications were adopted by other navies and industry. Over time, evidence accumulated that the success of these table for severe decompression sickness was not very good. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4964", "contents": "These low success rates led to the development of the oxygen treatment table by Goodman and Workman in 1965, variations of which are still in general use as the definitive treatment for most cases of decompression sickness. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4965", "contents": "Treatment of DCS utilizing the US Navy Treatment Table 6 with oxygen at 18\u00a0m is a  standard of care . [ 3 ] [ 5 ] [ 6 ] [ 7 ]  Significant delay to treatment, difficult transport, and facilities with limited experience may lead one to consider on site treatment. [ 8 ]  Surface  oxygen for first aid  has been proven to improve the efficacy of recompression and decreased the number of recompression treatments required when administered within four hours post dive. [ 9 ]  IWR to 9\u00a0m breathing oxygen is one option that has shown success over the years. [ 2 ] [ 10 ] [ 11 ]  IWR is not without risk and should be undertaken with certain precautions. [ 1 ] [ 2 ] [ 12 ] [ 13 ]  IWR would only be suitable for an organised and disciplined group of divers with suitable equipment and practical training in the procedure. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4966", "contents": "Treatment of  decompression sickness ,  arterial gas embolism , and other medical applications."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4967", "contents": "The type of chamber which can be used depends on the maximum pressure required for the schedule, and what gases are used for treatment. Most treatment protocols for diving injuries require an attendant in the chamber, [ 6 ]  and a medical lock to transfer medical supplies into the chamber while under pressure. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4968", "contents": "Outside of the diving industry, most chambers are intended for a single occupant, and not all of them are fitted with built-in breathing systems (BIBS). This limits the schedules which can be safely used in them. Some schedules have been developed specifically for hyperbaric oxygen treatment in monoplace chambers, and some hyperbaric treatment schedules nominally intended for chambers with BIBS have been shown to be acceptable for use without air breaks if the preferred facilities are not available."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4969", "contents": "Originally therapeutic recompression was done using  air  as the only breathing gas, and this is reflected in several of the tables detailed below. However, work by Yarbrough and  Behnke [ 7 ]  showed that use of  oxygen  as a treatment gas is usually beneficial and this has become the standard of care for treatment of DCS. [ 3 ]  Pure oxygen can be used at pressures up to 60\u00a0 fsw  (18\u00a0 msw ) [ 6 ]  with acceptable risk of CNS  oxygen toxicity , which generally has acceptable consequences in the chamber environment when an inside tender is at hand. At greater pressures, treatment gas mixtures using  Nitrogen  or  Helium  as a diluent to limit  partial pressure  of oxygen to 3\u00a0ata (3 bar) or less are preferred to air as they are more effective both at elimination of inert gases and oxygenating injured tissues in comparison with air.  Nitrox  and  Heliox  mixtures are recommended by the US Navy for\ntreatment gases at pressures exceeding 60\u00a0fsw (18\u00a0msw), and Heliox is preferred at pressures exceeding 165\u00a0fsw (50\u00a0msw) to reduce  nitrogen narcosis . [ 6 ] \nHigh oxygen fraction gas mixtures may also be substituted for pure oxygen at pressures less than 60\u00a0fsw if the patient does not tolerate 100% oxygen. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4970", "contents": "Treatment gases are generally oxygen or oxygen rich mixtures which would constitute an unacceptable fire hazard if used as the chamber gas. Chamber oxygen concentration is limited due to fire hazard and the high risk of fatality or severe injury in the event of a chamber fire. US Navy specifications for oxygen content of chamber air allow a range from 19% to 25%. If the oxygen fraction rises above this limit the chamber must be ventilated with air to bring the concentration to an acceptable level. [ 6 ]  To minimize the requirement for venting, oxygen-rich treatment gases are usually provided to the patient by  built in breathing system  (BIBS) masks, which vent exhaled gas outside the chamber. BIBS masks are provided with straps to hold them in place over the mouth and nose, but are often held in place manually, so they will fall away if the user has an oxygen toxicity convulsion."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4971", "contents": "BIBS masks provide gas on demand (inhalation), much like a diving regulator, and use a similar system to control outflow to the normobaric environment. They are connected to supply lines plumbed through the pressure hull of the chamber, valved on both sides, and supplied from banks of storage cylinders, usually kept near the chamber. The BIBS system is normally used with medical oxygen, but can be connected to other breathing gases as required. Chamber gas oxygen content is usually monitored by bleeding chamber gas past an  electro-galvanic oxygen sensor  cell."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4972", "contents": "The commonly used units of pressure for hyperbaric treatment are metres of sea water (msw) and feet of sea water (fsw) which indicate the pressure of treatment in terms of the height of water column that would be supported in a  manometer . These units are also used for measuring the depth of a surface supplied diver using a  pneumofathometer  and directly relate the pressure to an equivalent depth. The  pressure gauges  used on diving chambers are often calibrated in both of these units. Elapsed time of treatment is usually recorded in minutes, or hours and minutes, and may be measured from the start of pressurisation, or from the time when treatment pressure is reached."}
+{"id": "WikiPedia_Pulmonology$$$corpus_4973", "contents": "The schedules listed here include both historical procedures and schedules currently in use. As a general rule, more recent tables from the same source have a greater success rate than the superseded schedules. Some of the older procedures are now considered to be dangerous. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4974", "contents": "Use: Treatment of decompression sickness where relief is obtained at or less than 66\u00a0fsw. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4975", "contents": "Use: Treatment of decompression sickness where relief is obtained at or less than 116 fsw. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4976", "contents": "Use: Treatment of decompression sickness where relief is obtained at or less than 166 fsw. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4977", "contents": "Use: Treatment of decompression sickness where relief is obtained at or less than 216\u00a0fsw. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4978", "contents": "Use: Treatment of decompression sickness where relief is obtained at or less than 266\u00a0fsw. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4979", "contents": "Use: Treatment of moderate to severe decompression sickness when oxygen is not available or the patient cannot tolerate the elevated oxygen partial pressure. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4980", "contents": "Use: Treatment of moderate to severe decompression sickness when oxygen is available. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4981", "contents": "Use: Treatment of mild decompression sickness when oxygen is not available or the patient cannot tolerate the elevated oxygen partial pressure. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4982", "contents": "Use: Treatment of mild decompression sickness. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4983", "contents": "Use: Treatment of pain only decompression sickness. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4984", "contents": "Table 1A is included in the US Navy Diving Manual Revision 6 and is authorized for use as a last resort when oxygen is not available. This table has been revised by decreasing the ascent rate from 1 minute between stops to 1\u00a0fsw per minute since the original was published in 1958. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4985", "contents": "Use: For treatment of pain only decompression sickness. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4986", "contents": "Use: Treatment of pain-only decompression sickness. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4987", "contents": "Table 2A is included in the US Navy Diving Manual Revision 6 and is authorized for use as a last resort when oxygen is not available. This table has been revised by decreasing the ascent rate from 1 minute between stops to 1\u00a0fsw per minute since the original was published in 1958. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4988", "contents": "Use: Treatment of pain only decompression sickness when oxygen cannot be used. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4989", "contents": "Table 3 is included in the US Navy Diving Manual Revision 6 and is authorized for use as a last resort when oxygen is not available. This table has been revised by decreasing the ascent rate from 1 minute between stops to 1\u00a0fsw per minute since the original was published in 1958. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4990", "contents": "Use: Treatment of serious symptoms when oxygen cannot be used and symptoms are relieved within 30 minutes at 165 feet. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4991", "contents": "This table is in the US Navy Diving Manual Revision 6 and is currently authorized for use. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4992", "contents": "Use: Treatment of serious symptoms when oxygen can be used and symptoms are not relieved within 30 minutes at 165\u00a0fsw (50\u00a0msw). [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4993", "contents": "Use: Treatment of pain-only decompression sickness when oxygen can be used and symptoms are relieved within 10 minutes at 60\u00a0ft. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4994", "contents": "Use: Treatment of gas embolism when oxygen can be used and symptoms are relieved within 15 minutes at 165\u00a0fsw (50\u00a0msw). [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4995", "contents": "Use: Treatment of pain-only decompression sickness when oxygen can be used and symptoms are not relieved within 10 minutes at 60\u00a0fsw (18\u00a0msw). [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4996", "contents": "The Catalina treatment table is a modification of Treatment Table 6. Oxygen cycles are 20 minutes, and air breaks 5 minutes. The full Catalina Table allows for up to 5 extensions at 60\u00a0fsw. [ 18 ] \nShorter versions include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4997", "contents": "Tenders breathe oxygen for 60 minutes at 30\u00a0fsw. Further treatments may follow after at least 12 hours on air at the surface. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4998", "contents": "Use: Treatment of gas embolism when oxygen can be used and symptoms moderate to a major extent within 30 minutes at 165\u00a0ft. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_4999", "contents": "At 50msw (absolute pressure 6 bar) an oxygen fraction of 50% will produce a partial pressure of 3 bar, This could be a  nitrox ,  heliox  or  trimix  blend with 50% oxygen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5000", "contents": "Use: Treatment of non-responding severe gas embolism or life-threatening decompression sickness. It is used when loss of life may result from decompression from 60\u00a0fsw. It is not used to treat residual symptoms that do not improve at 60\u00a0fsw, or to treat residual pain. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5001", "contents": "Use: Mainly for treating deep uncontrolled ascents when more than 60 minutes of decompression have been omitted. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5002", "contents": "Use: Hyperbaric oxygen treatment as prescribed by Diving Medical Officer for:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5003", "contents": "Use: For treatment of decompression sickness manifested as musculoskeletal pains only, during decompression from saturation. [ 3 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5004", "contents": "Use: For treatment of serious decompression sickness resulting from upward excursion. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5005", "contents": "Decompress after treatment according to normal saturation decompression schedule from the treatment depth. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5006", "contents": "Treatment of Tektite aquanauts after emergency surfacing. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5007", "contents": "Treatment of any decompression sickness symptoms. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5008", "contents": "Use: Treatment of pain-only decompression sickness when oxygen is not available and pain is relieved within 10 minutes at or less than 20\u00a0msw (667\u00a0fsw) [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5009", "contents": "Use: Treatment of pain-only decompression sickness when oxygen is not available and pain is  not  relieved within 10 minutes at or less than 20 msw (66 fsw) but does have relief within 10 minutes at 50 msw (165 fsw). [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5010", "contents": "Use: Treatment of joint pain plus a more serious symptom of decompression sickness when oxygen is not available and symptoms are relieved within 30 minutes at or less than 50 msw (164 fsw) [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5011", "contents": "Use: Treatment of joint pain plus a more serious symptom of decompression sickness when oxygen is available and symptoms are  not  relieved within 30 minutes at or less than 50 metres (164\u00a0ft) [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5012", "contents": "Use: Treatment of joint pain plus a more serious symptom of decompression sickness when oxygen is not available and symptoms are  not  relieved within 30 minutes at or less than 50msw (164 fsw) [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5013", "contents": "Use: Treatment of pain only decompression sickness when oxygen is available and pain is relieved within 10 minutes or at less than 18\u00a0msw (59\u00a0fsw), or for serious symptoms where a specialist medical officer is present. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5014", "contents": "Use: Treatment of pain only decompression sickness when oxygen is available and pain is not relieved within 10 minutes at 18\u00a0msw (59\u00a0fsw), or for serious symptoms where a specialist medical officer is present. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5015", "contents": "Use: Treatment of any decompression symptom if a specialist medical officer is present. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5016", "contents": "Use: Treatment of any decompression symptom if a specialist medical officer is present. Applicable for multiple recompression of submarine survivors. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5017", "contents": "Use: Treatment of decompression sickness occurring during decompression from a Heliox dive. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5018", "contents": "Use: Treatment of mild decompression sickness. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5019", "contents": "Use: Treatment of mild to moderate decompression sickness. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5020", "contents": "Use: Treatment of moderate to severe decompression sickness. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5021", "contents": "Use: Treatment of severe decompression sickness. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5022", "contents": "Use: Treatment of decompression sickness. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5023", "contents": "Use: Treatment of moderately severe decompression sickness. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5024", "contents": "Use: Treatment of mild decompression sickness after dives to less than 40 m depth. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5025", "contents": "Use: Treatment of mild decompression sickness after dives to more than 40\u00a0m depth. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5026", "contents": "Use: Treatment of moderately severe decompression sickness after dives to more than 40m depth or severe decompression sickness after dives shallower than 40m. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5027", "contents": "Use: Treatment of moderately severe and severe decompression sickness. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5028", "contents": "Use: Treatment of mild decompression sickness after dives to less than 40 m. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5029", "contents": "Use: Treatment of mild decompression sickness after dives to more than 40 m. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5030", "contents": "Use: Treatment of moderate or severe decompression sickness. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5031", "contents": "Use: Treatment of musculoskeletal decompression sickness following normal decompression if symptoms are relieved within 4 minutes or at less than 8\u00a0msw. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5032", "contents": "Use: Treatment of musculoskeletal decompression sickness following normal or shortened decompression if symptoms are not relieved within 4 minutes at 8\u00a0msw, but are relieved within 15 minutes at or less than 18\u00a0msw. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5033", "contents": "Use: Treatment of musculoskeletal decompression sickness following normal or shortened decompression if symptoms are not relieved within 15 minutes at 18\u00a0msw. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5034", "contents": "Use: Treatment of vestibular and general neurological decompression sickness following normal or shortened decompression. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5035", "contents": "Use: Treatment of musculoskeletal decompression sickness when signs of oxygen toxicity are present. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5036", "contents": "Use: Treatment of vestibular and general neurological decompression sickness when signs of oxygen toxicity are present. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5037", "contents": "Use: Treatment of light forms of decompression sickness when the symptoms are completely resolved when reaching a pressure of 29 msw (96 fsw). [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5038", "contents": "Use: Treatment of light forms of decompression sickness when the symptoms are completely resolved when reaching a pressure of 49 msw (160 fsw), or if there is a relapse after use of Regimen I. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5039", "contents": "Use: Treatment of moderately severe decompression sickness, or if there is a relapse after use of Regimen II. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5040", "contents": "Use: Treatment of severe decompression sickness, or if there is a relapse after use of Regimen III. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5041", "contents": "Use: Treatment of very severe decompression sickness, or if there is a relapse after use of Regimen IV. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5042", "contents": "Use: Treatment of mild decompression sickness where relief occurs within 30 minutes at 30 msw (98 fsw) [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5043", "contents": "Use: Treatment of mild decompression sickness where relief does not occur within 30 minutes at 30 msw (98 fsw) [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5044", "contents": "Use: Treatment of severe decompression sickness where relief does not occur within 30 minutes at 30 msw (98 fsw) [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5045", "contents": "(specifically for chambers without facility for air breaks)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5046", "contents": "100% oxygen for 30 minutes at 3.0 ATA followed by 60 minutes at 2.5 ATA. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5047", "contents": "Indication:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5048", "contents": "In-water recompression  ( IWR ) or  underwater oxygen treatment  is the emergency treatment of  decompression sickness  (DCS) by sending the  diver  back  underwater  to allow the gas bubbles in the tissues, which are causing the symptoms, to resolve. It is a risky procedure that should only ever be used when the time to  travel  to the nearest  recompression chamber  is too long to save the victim's life. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5049", "contents": "Carrying out in-water recompression when there is a nearby recompression chamber or without special equipment and training is never a favoured option. [ 1 ] [ 2 ]  The risk of the procedure comes from the fact that a diver with DCS is seriously ill and may become  paralysed ,  unconscious  or  stop breathing  whilst under water. Any one of these events is likely to result in the diver  drowning  or further injury to the diver during a subsequent rescue to the surface."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5050", "contents": "Six IWR treatment tables have been published in the  scientific literature . Each of these methods have several commonalities including the use of a full face mask, a tender to supervise the diver during treatment, a weighted recompression line and a means of communication. The history of the three older methods for providing oxygen at 9\u00a0m (30 fsw) was described in great detail by Drs.  Richard Pyle  and Youngblood. [ 2 ]  The fourth method for providing oxygen at 7.5\u00a0m (25 fsw) was described by Pyle at the 48th Annual UHMS Workshop on In-water Recompression in 1999. [ 1 ]  The Clipperton method involves recompression to 9\u00a0m (30\u00a0fsw) while the Clipperton(a)  rebreather  method involves a recompression to 30\u00a0m (98\u00a0fsw). [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5051", "contents": "Recommended equipment common to these tables includes: [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5052", "contents": "The Australian IWR Tables were developed by the  Royal Australian Navy  in the 1960s in response to their need for treatment in remote locations far away from recompression chambers. It was the shallow portion of the table developed for recompression chamber use. [ 13 ] [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5053", "contents": "Oxygen is breathed the entire portion of the treatment without any air breaks and is followed by alternating periods (12 hours) of oxygen and air breathing on the surface."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5054", "contents": "The Clipperton and Clipperton(a) methods were developed for use on a  scientific  mission to the  atoll of Clipperton , 1,300\u00a0km from the Mexican coast. [ 27 ]  The two versions are based on the equipment available for treatment with the Clipperton(a) table being designed for use with rebreathers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5055", "contents": "Both methods begin with 10 minutes of surface oxygen. For the Clipperton IWR table, oxygen is then breathed the entire portion of the treatment without any air breaks. For the Clipperton(a) IWR table, descent is made to the initial treatment depth maintaining a  partial pressure  of 1.4\u00a0ATA. Oxygen breathing on the surface for 6 hours post treatment and  intravenous  fluids are also administered following both treatment tables."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5056", "contents": "The Hawaiian IWR table was first described by Farm et al. while studying the diving habits of  Hawaii 's diving  fishermen . [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5057", "contents": "The initial portion of the treatment involves descent on air to the depth of relief plus 30\u00a0fsw or a maximum of 165\u00a0fsw for ten minutes. Ascent from initial treatment depth to 30\u00a0fsw occurs over 10 minutes. The diver then completes the treatment breathing oxygen and is followed by oxygen breathing on the surface for 30 minutes post treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5058", "contents": "The Hawaiian IWR Table with Pyle modifications can be found in the proceedings of the DAN 2008 Technical Diving Conference (In Press) or through download from DAN  here ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5059", "contents": "The Pyle IWR table was developed by  Dr. Richard Pyle  as a method for treating DCS in the field following scientific dives. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5060", "contents": "This method begins with a 10-minute surface oxygen evaluation period. Compression to 25\u00a0fsw on oxygen for another 10-minute evaluation period. The table is best described by the treatment  algorithm  ( Pyle IWR algorithm [usurped] ). This table does include alternating air breathing periods or \"air breaks\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5061", "contents": "The  US Navy  developed two IWR treatment tables. The table used depends on the symptoms diagnosed by the medical officer. [ 6 ] :\u200a20\u20114.4.2.2"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5062", "contents": "Oxygen is breathed the entire duration of the treatment without any air breaks and is followed by 3 hours of oxygen breathing on the surface.\nDiver descends to 30 feet accompanied by a standby diver, and remains there for 60 minutes for Type I symptoms and 90 minutes for Type II symptoms, after this ascends to 20 feet even if symptoms have not resolved, and decompresses for 60 minutes at 20 feet and 60 minutes at 10 feet. Oxygen is breathed for another 3 hours after surfacing. [ 6 ] :\u200a20\u20114.4.2.2"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5063", "contents": "Use: Emergency in-water recompression when no chamber is available. [ 20 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5064", "contents": "Although in-water recompression is regarded as risky, and to be avoided, there is increasing evidence that technical divers who surface and demonstrate mild DCS symptoms may often get back into the water and breathe pure oxygen at a depth 20 feet (6.1 meters) for a period of time to seek to alleviate the symptoms. This trend is noted in paragraph 3.6.5 of  DAN 's 2008 accident report. [ 29 ]   The report also notes that whilst the reported incidents showed very little success, \"[w]e must recognize that these calls were mostly because the attempted IWR failed. In case the IWR were successful, [the] diver would not have called to report the event. Thus we do not know how often IWR may have been used successfully.\" [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5065", "contents": "Used in commercial diving for: [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5066", "contents": "Depth limit 200 fsw for air."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5067", "contents": "Used for emergency recompression of technical divers in remote areas. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5068", "contents": "The certification agency  International Association of Nitrox and Technical Divers  (IANTD) have developed a training program for technical divers to run in water therapeutic recompression for suitably competent technical divers in remote locations, when conditions and equipment are suitable and the condition of the diver is assessed to require emergency treatment and the diver is likely to benefit sufficiently to justify the risk. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5069", "contents": "Most of the time on hyperbaric oxygen is at 25 fsw (7.5 msw) [ 31 ]  Oxygen is breathed, with air breaks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5070", "contents": "Mild total body hypothermia , induced by cooling a baby to 33-34\u00b0C for three days after birth, is nowadays a standardized treatment after moderate to severe  hypoxic ischemic encephalopathy  in full-term and near to fullterm neonates. [ 1 ] [ 2 ]  It has recently been proven to be the only medical intervention which reduces  brain damage , and improves an infant's chance of survival and reduced disability."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5071", "contents": "Hypoxic ischemic encephalopathy has many causes and is defined essentially as the reduction in the supply of blood or oxygen to a baby's brain before, during, or even after birth.  It is a major cause of death and disability, occurring in approximately 2\u20133 per 1000 births and causing around 20% of all cases of  cerebral palsy . A 2013 Cochrane review found that therapeutic hypothermia is useful in full term babies with encephalopathy. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5072", "contents": "Studies have been undertaken to determine the effects of  hypothermia  beyond early childhood. Participants in the  CoolCap ,  NICHD  and TOBY trials were entered into extended follow-up programmes. None of these programmes have sufficient power to make confident assessments of the long-term effect of hypothermia, however even these underpowered studies give important information on whether the therapeutic effects of cooling are sustained beyond the first two years after birth."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5073", "contents": "The most significant follow-up study published so far is the assessment of the NICHD trial participants at 6\u20137 years. [ 4 ]  Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the  control group , death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively ( P =0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). The CoolCap study gathered data using the WeeFim questionnaire at 7\u20138 years of age, but only collected information on 62 (32 cooled; 30 standard care) of 135 surviving children who had had neurodevelopmental assessment at 18 months. Disability status at 18 months was strongly associated with WeeFIM ratings (P < 0.001) suggesting that the therapeutic effect persisted, but there was no significant effect of treatment (P = 0.83). [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5074", "contents": "These results were not quite conclusive, as the effect in the NICHD trial appears to be on mortality rather than neurological function, but they gave considerable confidence that the therapeutic effects of hypothermia following birth asphyxia are sustained into later childhood, and when the Toby trial childhood follow up was published in the New England Journal of Medicine it confirmed the persistence of the effect  [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5075", "contents": "Hypothermic neural rescue therapy is an  evidence-based  clinical treatment which increases a severely injured full term infant's chance of surviving without brain damage detectable at 18 months by about 50%, an effect which seems to be sustained into later childhood."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5076", "contents": "At present data relate only to full term infants, and all human studies of hypothermia treatment have so far been restricted to infants >36 weeks out of an expected 40 weeks gestation.  There are both more potential side effects on the developing  premature  with  lung disease , and there is more evident protection by hypothermia when a greater volume of complex brain is actively developing. During mid gestation to late term the fetal brain is undergoing increasingly complex progressive growth of first the mid-brain and then development of the cortex and \"higher\" centers.  The effects of fetal asphyxia  on the developing brain in sheep are dependent on gestational age with near term fetuses showing both less tolerance of asphyxia and maximal damage in the rapidly expanding cortex; while fetuses prior to the last third of development experience more extended tolerance of asphyxia with maximal effects on the growing mid-brain. The fetal sheep asphyxia model also suggests a six-hour window post asphyxia in which hypothermia will have greatest benefit."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5077", "contents": "Since the prerequisites regarding immediate closeness after giving birth radically chances, researchers have become curious regarding parent's experiences and how to improve the nursing care around effects families. In interviews made by different researchers in different countries it has been clear the parents want clear communication with the NICU staff, but also in between the NICU staff and the obstetrics staff. [ 7 ]  They also described a strong wish touching and being really close to their baby but also actively participate in the baby's care  [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5078", "contents": "There remains much that is unknown. Recognition of infants with marginal external signs of  asphyctic  damage at birth, who still develop moderate hypoxic ischemic encephalopathy would be enhanced by finding more reliable bio-markers or physiologic tests accurately predicting the risk for progressive damage. These tests could also prevent unwarranted, expensive treatment of many infants. Long-term follow-up has yet to demonstrate show persisting benefit, but available data together with an imaging study nested in TOBY also found reduced brain tissue damage in cooled infants are encouraging. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5079", "contents": "The simplicity that attracted empiricists to cooling centuries ago now makes hypothermic neural rescue with accurate patient selection a potentially transforming therapy for low-resource environments where birth asphyxia remains a major cause of death and disability. Ironically this brings back the problem of cooling infants in an environment where modern resuscitation and intensive care are not available. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5080", "contents": "Much of what is known about the mechanisms of hypothermic neuroprotection is gathered from studies in mature and adult models. What follows uses some of these data while trying to focus on the immature brain."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5081", "contents": "Cerebral hypoxia - ischaemia  results in reduced cerebral  oxidative metabolism , cerebral  lactic acidosis  and cell membrane ionic transport failure; if prolonged there is  necrotic   cell death . [ 11 ] [ 12 ]  Although rapid recovery of cerebral energy metabolism occurs following successful resuscitation this is followed some hours later by a secondary fall in cerebral high energy phosphates accompanied by a rise in  intracellular pH , and the characteristic cerebral biochemical disturbance at this stage is a lactic alkalosis. [ 13 ]  In neonates, the severity of this secondary impairment in cerebral metabolism are associated with abnormal subsequent neurodevelopmental outcome and reduced head growth. [ 14 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5082", "contents": "Several adverse biological events contribute to this secondary deterioration, including: release of excitatory amino acids which activate  N-methyl-D-aspartate  (NMDA) and amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors on neurons (30,37) and oligodendroglial precursors, accumulation of excitatory neurotransmitters, generation of reactive oxygen radicals, intracellular calcium accumulation and mitochondrial dysfunction. [ 16 ]  Whilst necrotic cell death is prominent in the immediate and acute phases of severe cerebral insults, the predominant mode of death during the delayed phase of injury appears to be apoptosis. [ 17 ]  Neuroprotective mechanisms need to interact with these mechanisms to have beneficial effect."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5083", "contents": "Newborn hypoxic-ischaemic brain injury differs from injury in the adult brain in several ways:  NMDA receptor  toxicity is much higher in the immature brain. [ 18 ]  Apoptotic mechanisms including activation of caspases, translocation of  apoptosis -inducing factor and  cytochrome-c  release are much greater in the immature than the adult. [ 19 ] [ 20 ] [ 21 ]  The inflammatory activation is different with less contribution from  polymorphonuclear  cells [ 22 ]  and a more prominent role of  IL-18 [ 23 ]  whereas  IL-1 , which is critical in the adult brain, [ 24 ]  is less important. [ 25 ]  The  anti-oxidant  system is underdeveloped with reduced capacity to inactivate  hydrogen peroxide . [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5084", "contents": "Mild hypothermia helps prevent disruptions to cerebral metabolism both during and following cerebral insults. Hypothermia decreases the cerebral metabolic rate for glucose and oxygen and reduces the loss of high energy phosphates during hypoxia-ischaemia [ 27 ]  and during secondary cerebral energy failure, [ 28 ]  and reduces delayed cerebral lactic alkalosis. [ 29 ]  The simultaneous increase in cytotoxic oedema and loss of cerebral cortical activity that accompanies secondary energy failure is also prevented. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5085", "contents": "Hypothermia appears to have multiple effects at a cellular level following cerebral injury. Hypothermia reduces vasogenic oedema, haemorrhage and neutrophil infiltration after trauma. [ 31 ]  The release of excitatory neurotransmitters is reduced, limiting intracellular calcium accumulation. [ 32 ] [ 33 ] [ 34 ]  Free radical production is lessened, which protects cells and cellular organelles from oxidative damage during reperfusion. [ 35 ]  In addition mild hypothermia may reduce the activation of the cytokine and coagulation cascades through increased activation of suppressor signalling pathways, and by inhibiting release of platelet activating factor. [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5086", "contents": "Many of the effects induced by mild hypothermia may help to reduce the number of cells undergoing apoptosis. Experimental and clinical studies indicate that the number of apoptotic neurons is reduced caspase activity is lessened and cytochrome c translocation is diminished by mild hypothermia, [ 37 ] [ 38 ]   and there may be an increase in expression of the anti-apoptotic protein BCl-2. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5087", "contents": "Many physicians over the centuries have tried to resuscitate babies after birth by altering their body temperatures, essentially aiming to animate the infant by inducing the onset of breathing. [ 40 ]  Little thought was given to brain protection, because  cerebral hypoxia  during birth was not linked with later neurological problems until  William John Little  in 1861, [ 41 ]  and even then this was controversial;  Sigmund Freud , for example, famously disagreed, and when scientific studies of neonatal therapeutic hypothermia were begun in the 1950s researchers like Bjorn Westin still reported their work in terms of re-animation rather than neuroprotection. [ 42 ]  Investigators such as James Miller and Clement Smith carried out clinical observations and careful physiological experiments, [ 43 ] [ 44 ] [ 45 ] [ 46 ]  but although some babies were conscientiously followed up, they were not mainly concerned with long term neurological outcome."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5088", "contents": "However, by the 1960s physicians saw hypothermia after delivery as something to be avoided. The problem of infants who failed to breathe at birth had been solved by the invention of  mechanical ventilation , so any benefit cooling might have for re-animation was no longer needed, and an influential trial showed that keeping small and preterm infants warm increased survival. [ 47 ]  These results, together with observational [ 48 ]  and experimental [ 49 ]  data made it an article of medical faith for decades that babies should not be allowed to get cold."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5089", "contents": "Consequently, during the next two decades studies of neonatal hypothermia in Europe and the USA were sporadic and often unsuccessful. An interest in cooling for brain protection was beginning to emerge, but contemporary  neuroscience  provided few useful concepts to guide this research and little progress was made. [ 50 ] [ 51 ] [ 52 ] [ 53 ] [ 54 ] [ 55 ] [ 56 ]  Although across the Iron Curtain in the Soviet Union cooling was being applied empirically following birth asphyxia, [ 57 ]   the language barrier, cold war politics and the Russians' failure to carry out randomised controlled trials contributed to an almost total ignorance of this work in the West. Indeed, a group of Russian neonatologists who described hypothermic neural rescue during a visit to the Neonatal Unit in Bristol, UK, met with little interest. [ 58 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5090", "contents": "In the late 1980s the development of a new set of concepts and problems led to a re-examination. A new generation of neonatal researchers were influenced by the growing evidence that protecting the brain against the effects of oxygen deprivation during labour might be possible. These researchers were aware that cooling produced powerful  intra-ischaemic neuroprotection  during cardiac surgery but a new concept of hypothermic  post-insult neural rescue  developed. This shift in thinking was possible because of at least three major new ideas that were developing at the same time: delayed post-ischaemic cell death;  excitotoxicity ; and  apoptosis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5091", "contents": "The first paradigm shift that affected neonatal researchers in particular was the idea that if a baby was resuscitated after cerebral hypoxia-ischaemia there was a period of time before brain cells started to die. Osmund Reynolds at  University College London  used the newly developed technique of  Magnetic Resonance Spectroscopy  (MRS) to show that the infant brain metabolism is normal in the hours after birth asphyxia and deteriorated only after a distinct delay. [ 59 ]  Robert Vannucci confirmed the effect with painstaking biochemistry, [ 60 ]  and delayed injury was also reported in neuropathological studies. [ 61 ] [ 62 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5092", "contents": "Delayed brain injury (called 'secondary energy failure' by Reynolds) was a critical new idea. If brain cells remained normal for a time and the mechanism of the delayed death could be unravelled, it opened the possibility of therapeutic intervention in what had previously seemed an impossible situation. [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5093", "contents": "The new and transforming concept of  excitotoxicity  developed from the seminal experiments of  John Olney [ 64 ] [ 65 ]  and Brian Meldrum. [ 66 ]  They showed that at least some of the neural cell death caused by hypoxia-ischaemia is mediated by excess production of the excitatory neurotransmitter  glutamate , and that pharmacological blockade of the  N-methyl-D-aspartate receptor  could provide good protection against hypoxic damage. Olney and Meldrum had shifted the paradigm, allowing researchers to think of hypoxic-ischaemic damage as a treatable disease."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5094", "contents": "However, it was still a mystery how and why cells triggered by hypoxia-ischaemia should die hours or days later, particularly when it became clear that glutamate levels were not particularly high during secondary energy failure. The next critical idea came with the discovery of  programmed cell death , a novel form of cell suicide. Originally observed as a pathological appearance and named apoptosis (\"falling off\", as of leaves) in the 1970s, [ 67 ]  Horvitz, [ 68 ]  Raff [ 69 ]  and Evan [ 70 ]  provided a molecular understanding and showed that apoptosis could be triggered by cellular insults. The radical idea that hypoxia-ischaemia triggered a cell suicide programme which could explain the perplexing phenomenon of delayed cell death was soon supported by experimental [ 71 ] [ 72 ]  and human data, [ 73 ]  and many researchers believe this helps explain why neural rescue works in the newborn. However the picture is complex: both apoptosis and necrosis are present in variable proportions; [ 74 ]  and there seems to be prolonged neurodegeneration after an insult. [ 75 ]  Research into this problem continues."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5095", "contents": "These ideas flowed through the perinatal research community, producing a new belief that neural rescue after birth asphyxia should be possible. Amongst the first to have attempt neonatal neural rescue in animals were Ingmar Kjellmer and  Henrik Hagberg  in Gothenburg, [ 76 ] [ 77 ]  and Michael Johnston in Baltimore. [ 78 ]  The potential began to draw in other neonatal researchers from diverse fields to begin neuroprotection research, including those who came to form the informal neonatal hypothermia research group:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5096", "contents": "Peter Gluckman and Tania Gunn were endocrinologists in the  University of Auckland  New Zealand and interested in cooling for its effect on  thyroid  function; they had first cooled a  sheep   fetus  for  endocrine  studies in 1983. Denis Azzopardi, John Wyatt and  David Edwards , then young researchers working for Reynolds, were using Reynolds's sophisticated MRS approach to replicate secondary energy failure in newborn  piglets [ 28 ]  and immature  rats ; [ 79 ]  in Gluckman's laboratory Alistair Gunn and Chris Williams developed a simple and elegant biophysical method using cerebral impedance to do essentially the same thing in fetal sheep. [ 80 ]  Marianne Thoresen, who was working on cerebral perfusion, was prompted to think about neuroprotection by stories of children who fell through the Norwegian ice and suffering prolonged  drowning  in iced water but emerged with preserved cerebral function."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5097", "contents": "There were many potential therapies around which might achieve neural rescue, and most of these workers did not immediately move to hypothermia.  Magnesium  was an appealingly simple excitoxin  receptor antagonist  that protected  cells  in culture: the Reynolds group tested it in their piglet model without success. [ 81 ]  Gluckman and Gunn started by looking unsuccessfully at  flunarizine , a calcium entry inhibitor. [ 82 ]  Edwards picked on  nitric oxide synthase  inhibition which was also a failure. [ 83 ]  Gluckman had success with his innovative studies of  IGF-1 , but could not immediately translate this to clinical practice. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5098", "contents": "The  Hypoxic Training index  (HTi) provides an objective measure of the hypoxic stress delivered during the  Intermittent Hypoxic Training  (IHT) session, compared to simple recording the inhaled fraction of oxygen (FiO2).  HTi provides a figure (index) of dosage received by the individual at the end of the session. [ 1 ]  Knowledge of HTi can therefore be used to alter the training regime for different individuals, compensating for individual variability, and can be used in scientific studies to ensure that subject exposure was correctly controlled."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5099", "contents": "Tissue hypoxia develops only when arterial oxygen saturation ( SpO2 ) drops to 90% or below. This is due to the oxyhaemoglobin dissociation curve. Saturations above 90% produce very little effect or decrease of arterial oxygen partial pressure (PaO2). In order to obtain consistent and comparable values of HTi for different individuals the following conditions should be stipulated:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5100", "contents": "The resulting formula for calculating HTi is:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5101", "contents": "H \n T \n i \n = \n \n \n 1 \n 60 \n \n \n \n \u222b \n \n 0 \n \n \n t \n \n \n [ \n 90 \n \u2212 \n S \n p \n \n O \n \n 2 \n \n \n ( \n t \n ) \n ] \n d \n t \n \n \n {\\displaystyle HTi={\\frac {1}{60}}\\int \\limits _{0}^{t}[90-SpO_{2}(t)]dt}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5102", "contents": "where:  \n HTi  : Hypoxic Training index, \n t \u00a0: period of time, and  \n SpO2 (t) \u00a0:  SpO2 (%), arterial oxygen saturation value measured at one-second intervals."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5103", "contents": "This image shows a typical  SpO2  curve during a full biofeedback-controlled IHT session.  (FiO2 is altered automatically using biofeedback controlled  hypoxicator  to attain and sustain the desired SpO2 target value.)"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5104", "contents": "Advanced  biofeedback controlled hypoxicators  are capable of adjusting the oxygen concentration in the inhaled hypoxic air automatically.  This automatic biofeedback control allows targeting of the desired  SpO2 , compensating for individual variability. Software is also available [ 2 ]  to calculate HTi based on readings from a USB connected  Pulse Oximeter ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5105", "contents": "A  hypoxicator  is a  medical device  intended to provide a stimulus for the adaptation of an individual's cardiovascular system by means of breathing reduced oxygen  hypoxic air  and triggering mechanisms of compensation. The aim of  intermittent hypoxic training  or  hypoxic therapy  conducted with such a device is to obtain benefits in physical performance and wellbeing through improved oxygen metabolism."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5106", "contents": "There are several commercial systems available. Most of these systems have not been cleared for medical applications by the FDA and are used by athletes for altitude training."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5107", "contents": "Advanced hypoxicators have a built-in  pulse oximeter  used to monitor and in some cases control the temporary reduction of arterial  oxygen saturation  that results in physiological responses evident at both systemic and cellular levels even after only a few minutes of hypoxia. [ 1 ]   Hypoxic Training Index  (HTi) can be used to measure the delivered therapeutic dosage over the training session."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5108", "contents": "The underlying mechanisms of adaptation to mild, non-damaging, short-term (minutes) hypoxic stress (also called -  intermittent hypoxic training ) are complex and diverse, [ 2 ]  but are part of normal physiology and are opposite to patho-physiological effects of severe  sleep apnea   hypoxia . [ clarification needed ] [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5109", "contents": "There are a number of types of hypoxicators that can be distinguished by the method of producing hypoxic air and its delivery to the user's respiratory system. Commonly used are air separation systems employing  semi-permeable membrane  technology or  pressure swing adsorption  or (PSAS). There are also non-powered hand-held devices\u00a0\u2013  rebreathers-hypoxicators . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5110", "contents": "The term hypoxicator was suggested by Russian scientists in 1985 to describe a new class of devices for  Intermittent hypoxic training  (IHT)\u00a0\u2013 an emerging drug-free treatment for a wide range of degenerative disorders and for\nsimulated  altitude training  used to achieve greater endurance performance [ 3 ]  as well as offering pre-acclimatisation for mountaineers\u00a0\u2013 minimising the risk of succumbing to  acute mountain sickness  on a subsequent ascent."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5111", "contents": "The hypoxia challenge of IHT is normally delivered in an intermittent manner: 3-7 min of hypoxic air breathing alternated with 1-5 min of normoxic or hyperoxic air. The hypoxicator allows automated and pre-programmed delivery of the required hypoxic and hyperoxic or normoxic air and safety monitoring. The therapeutic range of arterial oxygen desaturation for IHT is SpO 2  =\n75% - 88% and must be selected based upon the recommendation of a medical specialist. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5112", "contents": "Studies have also shown that hypoxic air treatment may increase the recovery speed and endurance of spinal cord injuries. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5113", "contents": "There are no reported adverse effects associated with this kind of treatment. However, symptoms of over-training may appear as a result of abusing basic training protocols supplied by manufacturers. Products that do not offer effective and instant monitoring and control over the treatment sessions must be avoided. [ citation needed ]  Pulse oximeters should be used to monitor the level of arterial oxygen\nsaturation that is the basic measure of hypoxic training dosage. Good brands have pulse oximeters integrated into the system and the best hypoxicators are equipped with automated biofeedback hypoxic training control mechanisms. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5114", "contents": "This type of equipment has been validated as a cost-effective and safe method of assessing respiratory patients' response to the reduced levels of oxygen onboard commercial passenger flights. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5115", "contents": "An  incentive spirometer  is a handheld  medical device  used to help patients improve the functioning of their  lungs . By training patients to take slow and deep breaths, this simplified  spirometer  facilitates lung expansion and strengthening. Patients inhale through a mouthpiece, which causes a piston inside the device to rise. This visual feedback helps them monitor their inspiratory effort. Incentive spirometers are commonly used after surgery or certain illnesses to prevent pulmonary complications."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5116", "contents": "Incentive spirometer is indicated for patients who have had any surgery that might jeopardize respiratory function, particularly  surgery  to the lungs, [ 1 ]  but also to patients recovering from  cardiac  or other surgery involving extended time under  anesthesia  and prolonged in-bed recovery. Under general anesthesia and inactivity, a patient's breathing may slow, causing air sacs in their lungs to not fully inflate.  Atelectasis  can develop and, if unmanaged, lead to  pneumonia  and  postoperative fever . Pneumonia is a major lung complication associated with increased morbidity and mortality, length of hospital stay, and likelihood of hospital readmissions. [ 2 ]  In conjunction with breathing exercises and early mobility, incentive spirometry use is therefore beneficial for patients recovering from pneumonia or rib damage to help minimize the chance of fluid build-up in the lungs. Because of its role in pulmonary rehabilitation and inspiratory muscle training, this device may theoretically benefit patients with  COVID-19 . [ 3 ]  It may be used as well by wind instrument players who want to improve their air flow. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5117", "contents": "Incentive spirometer is indicated for the following reasons: [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5118", "contents": "While there are no absolute contraindications for spirometry use, inspiratory muscle training can worsen some existing medical conditions, including the following: [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5119", "contents": "Patient starts in a seated upright position. Patient exhales completely before using device. The patient then places the mouthpiece into their mouth and seals their lips tightly around it. The patient breathes in from the device as slowly and as deeply as possible, then holds that breath in for 2\u20136 seconds. This provides back pressure that pops open  alveoli . It has the same effect as that which occurs during yawning. An indicator piston driven by the patient's breathing provides a gauge of how well the patient's lungs (or lung if singular) are functioning, by indicating sustained inhalation vacuum. While the patient is holding their breath, the indicator piston will slowly return to the bottom of the column. Patient then removes the mouthpiece from their mouth and exhales normally. Coughing can be expected to clear the airway and lungs of mucus. Patients are encouraged to rest if they begin feeling dizzy. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5120", "contents": "Generally, patients are encouraged to do many repetitions a day while measuring progress by way of advancing the movable gauge along the central column of the device as they improve. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5121", "contents": "Traditional incentive spirometers can be more challenging for children due to compliance and submaximal effort. [ 9 ]  Age-appropriate devices including whistles,  pinwheels , and bubble wands should be considered. [ 10 ]  These toys and activities reinforce proper breathing mechanics by stimulating deep inhalation and prolonged exhalation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5122", "contents": "An  inhaler  ( puffer ,  asthma pump  or  allergy spray ) is a medical device used for delivering medicines into the  lungs  through the work of a person's breathing. This allows medicines to be delivered to and absorbed in the lungs, which provides the ability for targeted medical treatment to this specific region of the body, as well as a reduction in the side effects of oral medications. There are a wide variety of inhalers, and they are commonly used to treat numerous medical conditions with  asthma  and  chronic obstructive pulmonary disease  (COPD) being among the most notable. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5123", "contents": "Some of the common types of inhalers include  metered-dose inhalers ,  dry powder inhalers , soft mist inhalers, and  nebulizers . Each device has advantages and disadvantages and can be selected based on individually specific patient needs, as well as age, pathological conditions, coordination, and lung function. [ 2 ]  Proper education on inhaler use is important to ensure that inhaled medication creates its proper effects in the lungs. [ 3 ]  Using a spacer can ensure that more medicine reaches the lungs, [ 4 ] [ 5 ]  thus providing the most optimal treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5124", "contents": "Inhalers are designed to deliver medication directly to the lungs through a person's own breathing. This may benefit a patient by providing medicines directly to areas of disease, allowing medication to take a greater effect on its intended target, and limit side effects of medications when administered locally. [ 1 ]  Inhalers are used in a variety of different medical conditions with  diseases of the lungs  and  respiratory system  being among the most common. Individuals with these diseases/conditions need medications designed to decrease airway inflammation and obstruction to allow for easier and comfortable breathing. [ 6 ]  Antibiotic medications have even been developed for inhalers to allow for direct delivery to areas of infection within the lungs. [ 7 ]  Two of the most common conditions that warrant inhaler therapy are  asthma  and  chronic obstructive pulmonary disease . [ 6 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5125", "contents": "Asthma  is a condition of intermittent  airway obstruction  due to  inflammatory  processes in the lungs. Inhaled medications are used to calm down the inflammation present in the lungs and allow for relief of the airway obstruction. Common inhaled medications used for treatment of asthma include long term inhalational steroidal  anti-inflammatory drugs  (most commonly  inhaled corticosteroids , also called ICS) and fast-relieving bronchodilators such as  salbutamol  (known commonly as \"Ventolin\") and  salmeterol . These medications allow for patients to have relief of airway obstruction symptoms and reduced inflammation. [ 6 ]  If some people are unable to use inhalers,  non-steroidal anti-inflammatory drugs  (NSAIDs) may be used, but with caution since they may cause immunological  hypersensitivity  to NSAIDs, resulting in respiratory-related symptoms such as  bronchospasms , acute  asthma exacerbation , and severe asthma morbidity. [ 9 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5126", "contents": "COPD is an obstructive lung disease due to long-term damage to the airways of the lungs. The long-term damage leads to the inability of the airways to open properly, causing  airway obstruction . Inhaled medications allow patients to see improvement in symptoms and better function of daily living. Some commonly used inhaled medications in patient's with COPD are  ipratroprium ,  salmeterol , and  corticosteroids . [ 8 ]  Inhalers that combine two or three different medications including inhaled corticosteroids, long-active muscarinic medications (LAMA) and long acting beta2 agonists (LABA) for treating COPD may be associated with improvements in some quality of life variables and small improvements in lung function and respiratory symptoms, however, may also be associated with an increase in the risk of pneumonia. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5127", "contents": "The most common type of inhaler is the pressurized  metered-dose inhaler  (MDI) which is made up of 3 standard components- a metal canister, plastic actuator, and a metering valve. The medication is typically stored in solution in a pressurized canister that contains a propellant or suspension. The MDI canister is attached to a plastic, hand-operated actuator. On activation, the metered-dose inhaler releases a fixed dose of medication in  aerosol  form through the actuator and into a patient's lungs. [ 12 ]   These devices require significant coordination as a person must discharge the medication at or near the same time that they inhale in order for the medication to be effective. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5128", "contents": "Dry powder inhalers  release a metered or device-measured dose of powdered medication that is inhaled through a DPI device. This device usually contains a chamber in which the powdered medication is deposited prior to each dosage. [ 3 ]  The powder can then be inhaled with a quick breath. [ 1 ]   This allows for medication to be delivered to the lungs without the need for use of propellant/suspension. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5129", "contents": "Soft mist inhalers release a light mist containing medication without the need for a propellant/suspension. Upon pressing a button, the inhaler creates a mist of medication, allowing for inhalation into the lungs. SMIs suspend inhaled medications for roughly 1.2 seconds, which is longer than the average MDI inhaler suspension time period.  This requires less coordination when using and may be helpful for young patients or patients that find the MDI inhalers difficult to use. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5130", "contents": "Nebulizers  are designed to deliver medications over an extended period of time over multiple breaths through a mouthpiece or face mask.  They generate a continuous mist with aerosolized medication, allowing a patient to breathe normally and receive medications. [ 13 ]   They are commonly used in infants and toddlers requiring inhaled medications or in patients in the hospital who require inhaled medications. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5131", "contents": "The smart-inhaler is an inhaler that will automatically update an app with information that includes the time of day, air quality, and how many times it has been used through sensor technology on the device. [ 14 ]  The first smart-inhaler was approved in 2019 by the FDA, its purpose is to track patient use of the device and some other circumstantial factors that could affect the effectiveness of the dosage. [ 14 ]  This information is sent via Bluetooth to a mobile device app, and is later shared with their physician to determine what kind of things can trigger issues with asthma and other problems. [ 14 ]  This technology presents a great way to cut down on medical costs associated with asthma and also help patients better manage their condition with fewer emergencies."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5132", "contents": "The Teva ProAir Digihaler was the first FDA approved smart inhaler. [ 15 ]  It shows how effective the device is at aiding patients in using the proper dose amount for their asthma. In a study published by the European Respiratory Journal, the ProAir Digihaler accurately identified when patients were using their inhalers and whether they were effectively administering the dose in a 370 patient trial with the device. [ 15 ]  This study further gives an overview on the technology regarding applications and devices that help aid in the tracking and medication management for asthma and other lung conditions. Another study showed that smart inhalers accurately recorded all doses administered by patients with their technology, which signifies their importance in providing accurate dosage information to patients and their physicians. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5133", "contents": "In 2009, the FDA banned the use of inhalers that use  chlorofluorocarbons  (CFC) as  propellants . In their place, inhalers now use  hydrofluoroalkane  (HFA). HFA is not environmentally inert as it is a  greenhouse gas  but it does not affect the  ozone layer . [ 17 ]  While some people with asthma and advocacy groups contend that HFA inhalers are not as effective, [ 18 ]  published clinical studies indicate CFC and HFA inhalers are equally effective in controlling asthma. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5134", "contents": "While the impact of CFCs from inhalers on the ozone layer had been minuscule (dwarfed by industrial processes using CFCs), the FDA in its interpretation of the  Montreal Protocol  mandated the switch in propellants. [ 17 ]  Patients expressed concern about the high price of the HFA inhalers as there were initially no generic versions, whereas generic CFC inhalers had been available. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5135", "contents": "It is important to use proper techniques when administering medications through inhalers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5136", "contents": "Proper use of inhalers often involves initial  deep breathing  (which involves mostly the  diaphragm 's movements), and then rapid breathing [ 20 ]  (which involves most of the muscles of respiration, such as external and internal  intercostal muscles [ 21 ] ) during intake of one or more puffs from the inhalers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5137", "contents": "Improper use of inhalers is very common, can lead to distribution of the medicine into the mouth or throat where it cannot create its desired effect and may cause harm. [ 1 ] [ 22 ] [ 23 ]  Education on the correct use of inhalers for delivery of medications is a commonly cited topic in medical studies and a great deal of thought has been put into how best to help people learn to use their inhalers effectively. [ 24 ] [ 3 ]  Below is a description of proper inhaler technique for each different type of inhaler as well as a helpful video explaining what the text states."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5138", "contents": "Spacer is placed at the mouthpiece of a meter-dosed inhaler while keeping mouth at the end of the spacer. After pressing the canister of the inhaler, the medicine will linger inside the spacer, allowing for the user of the inhaler to directly absorb medicine into their lungs. [ 25 ]  Deep breathing is done to be ready for the delivery of the medicine to the lungs; this minimizes need for coordination of breathing with inhaler activation. [ 1 ]  Cleanage of the spacer regularly with warm soapy water is recommended. [ 25 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5139", "contents": "If inhaler is used everyday, the inhaler usually has to be primed the first time using a new cartridge, but it may need to be primed again if it has not been used in multiple days. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5140", "contents": "If using inhaled corticosteroids, one should wash the mouth out directly after use of an inhaler. This helps to prevent  mouth infections  that can occur due to  immunosuppressant  effects of corticosteroids. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5141", "contents": "In the United States, pharmaceutical manufacturers use legal and regulatory strategies to keep inhaler prices artificially high. There has been little innovation in inhaler technology for decades \u2014 the most recent drug to be approved by the FDA for treating asthma or COPD via a novel  target of action  was  Ipratropium bromide  in 1986. Since then, manufacturers have used small changes to drug delivery mechanisms, or have switched active ingredients from one inhaler device to another (a strategy known as a \" device hop \") to keep patents active. This has the effect of limiting competition, keeping inhalers expensive. [ 26 ]  Because of high prices, patients sometimes skip doses or give up using their inhalers."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5142", "contents": "The idea of directly delivering medication into the lungs was based on ancient traditional cures that involved the use of aromatic and medicinal vapors. These did not involve any special devices beyond the apparatus used for burning or heating to produce fumes. Early inhalation devices included one devised by John Mudge in 1778. It had a pewter mug with a hole allowing attachment of a flexible tube. Mudge used it for the treatment of coughs using opium. These devices evolved with modifications by Wolfe, Mackenzie (1872) and better mouth attachments such as by Beigel in 1866. Many of these early inhalers needed heat to vaporize the active chemical ingredient. The benefits of forced expiration and inspiration to treat asthma were noted by J. S. Monell in 1865. Chemicals used in inhalers included ammonia, chlorine, iodine, tar, balsams, turpentine camphor and numerous others in combinations. [ 27 ]   Julius Mount Bleyer  used a variation in 1890 in New York. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5143", "contents": "In 1968, Robert Wexler of  Abbott Laboratories  developed the Analgizer, a disposable inhaler that allowed the self-administration of  methoxyflurane   vapor  in air for  analgesia . [ 29 ]  The Analgizer consisted of a  polyethylene  cylinder 5\u00a0inches long and 1\u00a0inch in diameter with a 1\u00a0inch long mouthpiece. The device contained a rolled  wick  of  polypropylene   felt  which held 15\u00a0 milliliters  of methoxyflurane."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5144", "contents": "Because of the simplicity of the Analgizer and the  pharmacological  characteristics of methoxyflurane, it was easy for patients to self-administer the drug and rapidly achieve a level of  conscious analgesia  which could be maintained and adjusted as necessary over a period of time lasting from a few minutes to several hours. The 15\u00a0milliliter supply of methoxyflurane would typically last for two to three hours, during which time the user would often be partly  amnesic  to the sense of pain; the device could be refilled if necessary. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5145", "contents": "The Analgizer was found to be safe, effective, and simple to administer in  obstetric  patients during childbirth, as well as for patients with  bone fractures  and  joint dislocations , [ 30 ]  and for dressing changes on  burn  patients. [ 31 ]  When used for labor analgesia, the Analgizer allows labor to progress normally and with no apparent  adverse effect  on  Apgar scores . [ 30 ]  All  vital signs  remain normal in obstetric patients, newborns, and injured patients. [ 30 ]  The Analgizer was widely utilized for analgesia and  sedation  until the early 1970s, in a manner that foreshadowed the  patient-controlled analgesia   infusion pumps  of today. [ 32 ] [ 33 ] [ 34 ] [ 35 ]  The Analgizer inhaler was withdrawn in 1974, but use of methoxyflurane as a sedative and analgesic continues in Australia and New Zealand in the form of the  Penthrox inhaler . [ 36 ] [ 37 ] [ 38 ] [ 39 ] [ 40 ] [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5146", "contents": "Intermittent hypoxic training (IHT) , also known as  intermittent hypoxic therapy , is a technique aimed at improving human performance by way of adaptation to reduced oxygen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5147", "contents": "An IHT session consists of an interval of several minutes breathing  hypoxic  (low oxygen) air, alternated with intervals breathing ambient (normoxic) or hyperoxic air. The procedure may be repeated several times in variable-length sessions per day, depending on a physician's prescription or a manufacturer's protocol. [ 1 ]  \nStandard practice is for the patient to remain stationary while breathing hypoxic air via a  hand-held mask . The therapy is delivered using a  hypoxicator  during the day time, allowing the dosage to be monitored.  Biofeedback  can be delivered using a  pulse oximeter ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5148", "contents": "A number of effects are reported. [ 2 ] [ 3 ] [ clarification needed ]  It is important to differentiate between physiological adaptations to mild hypoxia and re-oxygenation episodes (i.e., the IHT protocol) and frequent nocturnal suffocation awakenings produced by  sleep apnea , which might result in various pathologies. [ 4 ] [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5149", "contents": "IHT has been used to try to improve performance in sports. [ 5 ]  and has been used in a number of health conditions. [ 6 ] [ clarification needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5150", "contents": "Intermittent Mandatory Ventilation  ( IMV ) refers to any  mode of mechanical ventilation  where a regular series of breaths are scheduled but the ventilator senses patient effort and reschedules mandatory breaths based on the calculated need of the patient.  Similar to  continuous mandatory ventilation  in parameters set for the patients pressures and volumes but distinct in its ability to support a patient by either supporting their own effort or providing support when patient effort is not sensed.  IMV is frequently paired with additional strategies to improve weaning from ventilator support or to improve cardiovascular stability in patients who may need full  life support ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5151", "contents": "To help illustrate the use of the different types of ventilation, it is helpful to think of a continuum of the common ventilator settings; assist control or continuous mechanical ventilation (AC/CMV), to SIMV, to pressure support (PS).  The lungs require a certain amount of oxygen to fill them, the volume, and a certain amount of force to get the oxygen into the lungs, the pressure.  In assist control, one of those two variables will be controlled by the ventilator, either pressure or volume.  Typically, in AC/CMV, it is volume."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5152", "contents": "In AC/CMV, the ventilator will deliver a set volume whenever the patient triggers a breath.  In contrast, pressure support delivers a set pressure for every triggered breath, rather than a set volume.  SIMV works in between AC and PS; it will deliver a set volume, only when the patient reaches the breath threshold, instead of just triggering a breath.  If the patient does not reach the threshold, then no volume will be delivered, and the patient will be responsible for whatever volume they get into their lungs. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5153", "contents": "Synchronized Intermittent Mechanical Ventilation is a variation of IMV, in which the ventilator breaths are synchronized with patient inspiratory effort. [ 2 ] [ 3 ]   SIMV, with and without  pressure support  has not been shown to have any advantages over  continuous mandatory ventilation  (CMV) in terms of mortality [ 4 ]   or weaning success, [ 5 ]   and has been shown to result in longer weaning times when compared to t-piece trials or gradual reductions in  pressure support . [ 6 ] [ 7 ] [ 8 ]  Some studies have shown an increase in patient work of breathing when switched from CMV to SIMV, [ 9 ] [ 10 ]  and others [ 11 ]  have demonstrated potential detrimental effects of SIMV on respiratory muscles and respiratory drive."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5154", "contents": "Mandatory minute ventilation is a mode which requires the operator to determine what the appropriate minute ventilation for the patient should be, and the ventilator then monitors the patient's ability to generate this volume every 7.5 seconds. If the calculation suggests the volume target will not be met, SIMV breaths are delivered at the targeted volume to achieve the desired minute ventilation. [ 12 ]   Allows spontaneous breathing with automatic adjustments of mandatory ventilation to the meet the patient\u2019s preset minimum minute volume requirement. If the patient maintains the minute volume settings for VT x f, no mandatory breaths are delivered. If the patient's minute volume is insufficient, mandatory delivery of the preset tidal volume will occur until the minute volume is achieved.  The method for monitoring whether or not the patient is meeting the required minute ventilation (V E ) is different per ventilator brand and model, but generally there is a window of time being monitored and a smaller window being checked against that larger window (i.e., in the Dr\u00e4ger Evita\u00ae line of mechanical ventilators there is a moving 20-second window and every 7 seconds the current tidal volume and rate are measured against to make a decision for if a mechanical breath is needed to maintain the minute ventilation).  MMV is the most optimal mode for weaning in neonatal and pediatric populations and has been shown to reduce long term complications related to mechanical ventilation. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5155", "contents": "Proportional assist ventilation is a mode in which the ventilator guarantees the percentage of work regardless of changes in  pulmonary compliance  and resistance. [ 13 ]  The ventilator varies the tidal volume and pressure based on the patients work of breathing, the amount it delivers is proportional to the percentage of assistance it is set to give."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5156", "contents": "Adaptive Support Ventilation is a positive pressure  mode of mechanical ventilation  that is closed-loop controlled. In this mode, the clinician enters patient ideal body weight and desired level of ventilation in percent of predicted alveolar ventilation and the ventilator then applies inspiratory pressures at a rate which leads to minimal work of breathing. The equation used to calculate this minimal work was derived from the work of Otis et.al.  [ 14 ]  and published and discussed in Grodins and Yamashiro as early as 1977. [ 15 ]  In the ASV mode, every breath is synchronized with patient effort if such an effort exists, and otherwise, full mechanical ventilation is provided to the patient. Since the first implementation, ASV has undergone a number of refinements and is available on different ventilator brands under different names."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5157", "contents": "The invention of ASV is claimed by two competing groups, [ 16 ]  published as scientific article by one group [ 17 ]  and disclosed as one of the embodiments of US Patent No. 4986268. [ 18 ]  In this invention, the control algorithm computes the optimal rate of respiration to minimize the work rate of breathing. The rationale is to make the patient's breathing pattern comfortable and natural within safe limits, and thereby stimulate spontaneous breathing and reduce the weaning time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5158", "contents": "Intermittent positive pressure breathing  ( IPPB ) is a  respiratory therapy  treatment for people who are  hypoventilating .  While not a preferred method due to cost, [ 1 ]  IPPB is used to expand the lungs, deliver aerosol medications, and in some circumstances  ventilate  the patient. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5159", "contents": "IPPB may be indicated for patients who are at risk for developing  atelectasis  and who are unable or unwilling to breathe deeply without assistance. [ 3 ]  In patients with severe lung hyperinflation, IPPB may decrease  dyspnea  and discomfort during nebulized therapy. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5160", "contents": "Most contraindications are relative, such as nausea,  hemodynamic  instability, [ 5 ]   tracheal   fistula ,  singulation  and  hemoptysis . [ 6 ]  Untreated  tension pneumothorax  is an absolute contraindication. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5161", "contents": "IMPLEMENTATION"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5162", "contents": "When treating atelectasis -"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5163", "contents": "2. Tidal volumes(VT) must be measured"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5164", "contents": "3. VT goals must be set"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5165", "contents": "4. VT goal of 10-15mL/kg ofbody weight"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5166", "contents": "5. Pressure can be increased to reach VT goal if tolerated by patient."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5167", "contents": "When treating atelectasis, IPPB is only useful in the treatment of atelectasis if the volume delivered exceeds those volumes achieved by the patient's spontaneous efforts."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5168", "contents": "Inverse ratio ventilation  ( IRV ) is not necessarily a  mode of mechanical ventilation  though it may be referred to as such.  IRV is a strategy (method or style) of ventilating the lungs in such a way that the amount of time the lungs are in inhalation is greater than the amount of time they are in exhalation, allowing for a constant inflation of the lungs, ensuring they remain \"recruited\" (meaning they participate in gas exchange and are not allowed to deflate to get stuck together or tighten up).  The primary goal for IRV is improved oxygenation by forcing inspiratory time to be greater than expiratory time (example: inhale is 3 seconds and exhalation is 1 second, a 3:1 I:E ratio) increasing the mean airway pressure and potentially improving oxygenation. Normal I:E ratio is 5:6, so forcing the I:E to be 2:1, 3:1, 4:1, (or even as high as 20:1) is the source of the term for the strategy."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5169", "contents": "IRV has not often been shown to improve important clinical outcomes, such as mortality, duration of mechanical ventilation, or duration of ICU stay. This may be due to the fact that IRV is not considered as a mode early enough once ARDS is diagnosed. The preponderance of evidence suggests that IRV improves oxygenation, although the evidence is weak and characterized by low quality, conflicting studies. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5170", "contents": "IRV can be performed during  pressure-controlled ventilation  (PC-IRV) or  volume-controlled ventilation (VC-IRV). Neither is clearly superior to the other. In a multicenter, randomized trial that compared PC-IRV to VC-IRV in patients with  acute respiratory distress syndrome , the type of IRV did not affect mortality. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5171", "contents": "The shorter expiratory time during IRV increases the risk of auto-PEEP and its associated development of problems (e.g.  pulmonary barotrauma ,  hypotension ). [ 10 ]  IRV also appears to increase the risk of pulmonary barotrauma independent of auto-PEEP. In a study of 14 patients undergoing mechanical ventilation with PC-IRV, the incidence of pneumothorax was 29 percent despite the lack of measurable auto-PEEP. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5172", "contents": "The most popular mode that utilizes IRV is the  airway pressure release ventilation  mode, also known by the brand name \"BiVent\".  This employs an extremely high inverse ratio in a continuous pressure system similar to  biphasic positive airway pressure  but with several additional variables."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5173", "contents": "An  iron lung  is a type of  negative pressure ventilator , a  mechanical respirator  which encloses most of a person's body and varies the air pressure in the enclosed space to stimulate breathing. [ 1 ] [ 2 ]  It assists breathing when  muscle  control is lost, or the work of breathing exceeds the person's ability. [ 1 ]  Need for this treatment may result from diseases including  polio  and  botulism  and certain poisons (for example,  barbiturates  and  tubocurarine )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5174", "contents": "The use of iron lungs is largely obsolete in modern medicine as more modern breathing therapies have been developed [ 3 ]  and due to the  eradication of polio  in most of the world. [ 4 ]  In 2020 however, the  COVID-19 pandemic  revived some interest in them as a cheap, readily-producible substitute for  positive-pressure ventilators , which were feared to be outnumbered by patients potentially needing temporary artificially assisted respiration. [ 5 ] [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5175", "contents": "The iron lung is a large horizontal cylinder designed to stimulate breathing in patients who have lost control of their respiratory muscles. The patient's head is exposed outside the cylinder, while the body is sealed inside. Air pressure inside the cylinder is cycled to facilitate inhalation and exhalation. Devices like the Drinker, Emerson, and  Both  respirators are examples of iron lungs, which can be manually or mechanically powered. Smaller versions, like the cuirass ventilator and jacket ventilator, enclose only the patient's torso. Breathing in humans occurs through negative pressure, where the rib cage expands and the  diaphragm  contracts, causing air to flow in and out of the lungs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5176", "contents": "The concept of external negative pressure ventilation was introduced by  John Mayow  in 1670. The first widely used device was the iron lung, developed by  Philip Drinker  and  Louis Shaw  in 1928. Initially used for  coal gas  poisoning treatment, the iron lung gained fame for treating respiratory failure caused by polio in the mid-20th century.  John Haven Emerson  introduced an improved and more affordable version in 1931. The Both respirator, a cheaper and lighter alternative to the Drinker model, was invented in Australia in 1937. British philanthropist  William Morris  financed the production of the Both\u2013Nuffield respirators, donating them to hospitals throughout Britain and the British Empire. During the polio outbreaks of the 1940s and 1950s, iron lungs filled hospital wards, assisting patients with paralyzed diaphragms in their recovery."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5177", "contents": "Polio vaccination  programs and the development of modern ventilators have nearly eradicated the use of iron lungs in the developed world.  Positive pressure ventilation  systems, which blow air into the patient's lungs via intubation, have become more common than negative pressure systems like iron lungs. However, negative pressure ventilation is more similar to normal physiological breathing and may be preferable in rare conditions. As of 2024 [update] , after the death of  Paul Alexander , only one patient in the U.S.,  Martha Lillard , is still using an iron lung. In response to the COVID-19 pandemic and the shortage of modern ventilators, some enterprises developed prototypes of new, easily producible versions of the iron lung."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5178", "contents": "The iron lung is typically a large horizontal cylinder in which a person is laid, with their head protruding from a hole in the end of the cylinder, so that their full head (down to their voice box) is outside the cylinder, exposed to ambient air, and the rest of their body sealed inside the cylinder, where air pressure is continuously cycled up and down to stimulate breathing. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5179", "contents": "To cause the patient to inhale, air is pumped out of the cylinder, causing a slight vacuum, which causes the patient's chest and abdomen to expand (drawing air from outside the cylinder, through the patient's exposed nose or mouth, into their lungs). Then, for the patient to exhale, the air inside the cylinder is compressed slightly (or allowed to equalize to ambient room pressure), causing the patient's chest and abdomen to partially collapse, forcing air out of the lungs, as the patient exhales the breath through their exposed mouth and nose, outside the cylinder. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5180", "contents": "Examples of the device include the Drinker respirator, the Emerson respirator, and the Both respirator. Iron lungs can be either manually or mechanically powered, but are normally powered by an electric motor linked to a flexible pumping diaphragm (commonly opposite the end of the cylinder from the patient's head). [ 9 ]  Larger \"room-sized\" iron lungs were also developed, allowing for simultaneous ventilation of several patients (each with their heads protruding from sealed openings in the outer wall), with sufficient space inside for a  nurse  or a  respiratory therapist  to be inside the sealed room, attending the patients. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5181", "contents": "Smaller, single-patient versions of the iron lung include the so-called  cuirass ventilator  (named for the  cuirass , a torso-covering  body armor ). The cuirass ventilator encloses only the patient's torso, or chest and abdomen, but otherwise operates essentially the same as the original, full-sized iron lung. A lightweight variation on the cuirass ventilator is the  jacket ventilator  or  poncho  or  raincoat  ventilator, which uses a flexible, impermeable material (such as plastic or rubber) stretched over a metal or plastic frame over the patient's torso. [ 5 ] [ 10 ] [ 11 ] [ excessive citations ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5182", "contents": "Humans, like most mammals, breathe by  negative pressure  breathing: [ 12 ]  the rib cage expands and the  diaphragm  contracts, expanding the  chest cavity . This causes the pressure in the chest cavity to decrease, and the  lungs  expand to fill the space. This, in turn, causes the pressure of the air inside the lungs to decrease (it becomes negative, relative to the atmosphere), and air flows into the lungs from the atmosphere:  inhalation . When the diaphragm relaxes, the reverse happens and the person  exhales . If a person loses part or all of the ability to control the muscles involved, breathing becomes difficult or impossible."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5183", "contents": "In 1670, English scientist John Mayow came up with the idea of external negative pressure ventilation. Mayow built a model consisting of bellows and a  bladder  to pull in and expel air. [ 13 ]  The first negative pressure ventilator was described by British physician John Dalziel in 1832. Successful use of similar devices was described a few years later. Early prototypes included a hand-operated bellows-driven \"Spirophore\" designed by Dr Woillez of  Paris  (1876), [ 14 ]  and an airtight wooden box designed specifically for the treatment of polio by Dr Stueart of South Africa (1918). Stueart's box was sealed at the waist and shoulders with clay and powered by motor-driven bellows. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5184", "contents": "The first of these devices to be widely used however was developed in 1928 by Phillip Drinker and Louis Shaw of the United States. [ 16 ]  The iron lung, often referred to in the early days as the \"Drinker respirator\", was invented by Philip Drinker (1894\u20131972) and Louis Agassiz Shaw Jr., professors of  industrial hygiene  at the  Harvard School of Public Health . [ 17 ] [ 18 ] [ 19 ] [ excessive citations ]  The machine was powered by an electric motor with air pumps from two vacuum cleaners. The air pumps changed the pressure inside a rectangular, airtight metal box, pulling air in and out of the lungs. [ 20 ] \nThe first clinical use of the Drinker respirator on a human was on October 12, 1928, at the  Boston Children's Hospital  in the US. [ 18 ] [ 21 ]  The subject was an eight-year-old girl who was nearly dead as a result of  respiratory failure  due to polio. [ 19 ]  Her dramatic recovery within less than a minute of being placed in the chamber helped popularize the new device. [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5185", "contents": "Boston manufacturer Warren E. Collins began production of the iron lung that year. [ 23 ] [ 24 ]  Although it was initially developed for the treatment of victims of coal gas poisoning, it was most famously used in the mid-20th century for the treatment of respiratory failure caused by polio. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5186", "contents": "Danish physiologist  August Krogh , upon returning to  Copenhagen  in 1931 from a visit to New York where he saw the Drinker machine in use, constructed the first Danish respirator designed for clinical purposes. Krogh's device differed from Drinker's in that its motor was powered by water from the city pipelines. Krogh also made an infant respirator version. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5187", "contents": "In 1931, John Haven Emerson (1906\u20131997) introduced an improved and less expensive iron lung. [ 26 ] [ 27 ]  The Emerson iron lung had a bed that could slide in and out of the cylinder as needed, and the tank had portal windows which allowed attendants to reach in and adjust limbs, sheets, or hot packs. [ 20 ]  Drinker and  Harvard University  sued Emerson, claiming he had infringed on  patent rights . Emerson defended himself by making the case that such lifesaving devices should be freely available to all. [ 20 ]  Emerson also demonstrated that every aspect of Drinker's patents had been published or used by others at earlier times. Since an invention must be novel to be patentable, prior publication/use of the invention meant it was not novel and therefore unpatentable. Emerson won the case, and Drinker's patents were declared invalid. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5188", "contents": "The United Kingdom's first iron lung was designed in 1934 by Robert Henderson, an  Aberdeen  doctor. Henderson had seen a demonstration of the Drinker respirator in the early 1930s and built a device of his own upon his return to Scotland. Four weeks after its construction, the Henderson respirator was used to save the life of a 10-year-old boy from  New Deer ,  Aberdeenshire  who had poliomyelitis. Despite this success, Henderson was reprimanded for secretly using hospital facilities to build the machine. [ 28 ] [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5189", "contents": "The Both respirator, a negative pressure ventilator, was invented in 1937 when Australia's epidemic of poliomyelitis created an immediate need for more ventilating machines to compensate for respiratory paralysis. Although the Drinker model was effective and saved lives, its widespread use was hindered by the fact that the machines were very large, heavy (about 750\u00a0lbs or 340\u00a0kg), bulky, and expensive. An adult machine cost about $2,000 in the US in 1930 (equivalent to $36,000 in 2023), and about \u00a31,500 sterling in Europe in the mid-1950s (equivalent to $50,000 in 2023). The cost of one delivered to  Melbourne  in 1936 was AU\u00a32,000 (equivalent to $216,000 in 2022). Consequently, there were few of the Drinker devices in Australia and Europe. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5190", "contents": "The  South Australia Health Department  asked Adelaide brothers Edward and Don Both to create an inexpensive \"iron lung\". [ 31 ]  Biomedical engineer  Edward Both  designed and developed a cabinet respirator made of plywood that worked similarly to the Drinker device, with the addition of a bi-valved design which allowed temporary access to the patient's body. [ 30 ]  Far cheaper to make (only \u00a3100) than the Drinker machine, the Both Respirator also weighed less and could be constructed and transported more quickly. [ 30 ] [ 32 ]  Such was the demand for the machines that they were often used by patients within an hour of production. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5191", "contents": "Visiting London in 1938 during another polio epidemic, Both produced additional respirators there which attracted the attention of William Morris (Lord Nuffield), a British motor manufacturer and philanthropist. Nuffield, intrigued by the design, financed the production of approximately 1700 machines at his  car factory  in  Cowley  and donated them to hospitals throughout all parts of Britain and the British Empire. [ 33 ]  Soon, the Both\u2013Nuffield respirators were able to be produced by the thousand at about one-thirteenth the cost of the American design. [ 31 ]  By the early 1950s, there were over 700 Both-Nuffield iron lungs in the United Kingdom, but only 50 Drinker devices. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5192", "contents": "Rows of iron lungs filled hospital wards at the height of the polio outbreaks of the 1940s and 1950s, helping children, and some adults, with bulbar polio and bulbospinal polio. A polio patient with a paralyzed diaphragm would typically spend two weeks inside an iron lung while recovering. [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5193", "contents": "Polio vaccination programs have virtually  eradicated  new cases of poliomyelitis in the developed world. Because of this, the development of modern  ventilators , and widespread use of  tracheal intubation  and  tracheotomy , the iron lung has mostly disappeared from modern medicine. In 1959, 1,200 people were using tank respirators in the United States, but by 2004 that number had decreased to just 39. [ 36 ]  By 2014, only 10 people were left with an iron lung. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5194", "contents": "Positive pressure ventilation  systems are now more common than negative pressure systems. Positive pressure ventilators work by blowing air into the patient's lungs via  intubation  through the airway; they were used for the first time in  Blegdams Hospital , Copenhagen, Denmark, during a polio outbreak in 1952. [ 39 ] [ 40 ]  It proved a success and by 1953 it had superseded the iron lung throughout Europe. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5195", "contents": "The positive pressure ventilator has the asset that the patient's airways can be cleared and the patient can be in a semi-seated position in the acute phase of polio. The fatality rate on using iron lungs on respiratory paralysis patients could be as high as 80% to 90%, most patients either drowning in their own saliva as their swallowing muscles had been paralyzed, or from organ shutdown due to  acidosis  due to accumulated  carbon dioxide  in bloodstream due to clogged airways. By using the positive pressure ventilators instead of iron lungs, the Copenhagen hospital team was able to decrease the fatality rate eventually down to 11%. [ 42 ]  The first patient treated this way was a 12-year-old girl named Vivi Ebert, who had bulbar polio."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5196", "contents": "The iron lung now has a marginal place in modern  respiratory therapy . Most patients with paralysis of the breathing muscles use modern  mechanical ventilators  that push air into the airway with positive pressure. These are generally efficacious and have the advantage of not restricting patients' movements or caregivers' ability to examine the patients as significantly as an iron lung does. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5197", "contents": "Despite the advantages of positive ventilation systems, negative pressure ventilation is a truer approximation of normal physiological breathing and results in a more normal distribution of air in the lungs. It may also be preferable in certain rare conditions, [ 1 ]  such as  central hypoventilation syndrome , in which failure of the medullary respiratory centers at the base of the brain results in patients having no  autonomic control  of breathing. At least one reported polio patient,  Dianne Odell , had a spinal deformity that caused the use of mechanical ventilators to be  contraindicated . [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5198", "contents": "At least a few patients today still use the older machines, often in their homes, despite the occasional difficulty of finding replacement parts. [ 44 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5199", "contents": "Joan Headley of  Post-Polio Health International  said that as of May 28, 2008, about 30 patients in the US were still using an iron lung. [ 45 ]  That figure may be inaccurately low;  Houston  alone had 19 iron lung patients living at home in 2008. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5200", "contents": "Martha Mason  of  Lattimore ,  North Carolina , died on May 4, 2009, after spending 61 of her 72 years in an iron lung. [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5201", "contents": "On October 30, 2009,  June Middleton  of Melbourne, Australia, who had been entered in the  Guinness Book of Records  as the person who spent the longest time in an iron lung, died aged 83, having spent more than 60 years in her iron lung. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5202", "contents": "In 2013, the  Post-Polio Health International  (PHI) organizations estimated that only six to eight iron lung users were in the United States; as of 2017, its executive director knew of none. Press reports then emerged, however, of at least three (perhaps the last three) [ 49 ]  users of such devices, [ 50 ]  sparking interest amongst those in the  makerspace  community such as  Naomi Wu [ 51 ]  in the manufacture of the obsolete components, particularly the gaskets. [ 52 ] [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5203", "contents": "In 2021, the  National Public Radio  programs  Radio Diaries  and  All Things Considered  gave a report on Martha Lillard, one of the last remaining Americans depending on the daily use of an iron lung, which she had been using since 1953. In her audio interview, she reported that she was having problems obtaining replacement parts to keep her machine working properly. [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5204", "contents": "On March 11, 2024,  Paul Alexander  of Dallas, Texas, United States, died at the age of 78. He had been confined to an iron lung for 72 years from the age of six, longer than anyone, and was the last man living in an iron lung. With his death,  Martha Lillard  is the only person in the U.S. known to use an iron lung. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5205", "contents": "In early 2020, reacting to the COVID-19 pandemic, to address the urgent global shortage of modern ventilators (needed for patients with advanced, severe  COVID-19 ), some enterprises developed prototypes of new, readily-producible versions of the iron lung. These developments included:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5206", "contents": "A  liquid ventilator  is similar to a  medical ventilator  except that it should be able to ensure reliable total  liquid ventilation  with a  breatheable liquid  (a  perfluorocarbon ). [ 1 ] [ 2 ]  Liquid ventilators are prototypes that may have been used for  animal experimentations  but experts recommend continued development of a liquid ventilator toward clinical applications. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5207", "contents": "In total  liquid ventilation  (TLV), the lungs are completely filled with a  perfluorocarbon  (PFC) liquid while the liquid ventilator renews the tidal volume of PFC. The liquid ventilator operates in mandatory mode: it must force the PFC in and out of the lungs with a pumping system."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5208", "contents": "The pumping system is either a  peristaltic pump  (in the simplest liquid ventilators) or two  piston pumps  (in the most advanced liquid ventilators)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5209", "contents": "Because of the PFC  viscosity , the  head loss  in the airways requires a low negative driving pressure during the expiration phase that can collapse the airways. This is the choked flow phenomenon in TLV [ 4 ] [ 5 ]  which compromises the minute ventilation and consequently the gas exchanges. [ 6 ]  To address this limitation, liquid ventilator integrates a control of the pumping system. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5210", "contents": "The introduction of computers in liquid ventilators to control the pumping system provides different control modes, monitoring and valuable data for decision making. [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5211", "contents": "The liquid ventilator is always  volume-controlled  because the specified  tidal volume  of PFC must be accurately delivered and retrieved. It is also  pressure-limited  because it must stop the expiratory or inspiratory phase when a too low, or a too large, driving pressure is detected. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5212", "contents": "However, during the expiratory phase, the expiratory flow can be commanded by an  open-loop controller  or a  closed-loop controller :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5213", "contents": "Also, during the inspiratory phase, the volume-controlled mode is realized by open-loop or closed loop control of the PFC flow."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5214", "contents": "The liquid ventilator removes  Carbon dioxide  (CO 2 ) from the PFC by saturating it with  oxygen  (O 2 ) and medical  air . This procedure can be performed with either a membrane oxygenator (a technology used in  extracorporeal  oxygenators) or a bubble oxygenator. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5215", "contents": "The liquid ventilator heats the PFC to body temperature. This is performed with a  heat exchanger  connected to the oxygenator or with dedicated heaters integrated in the oxygenator. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5216", "contents": "The oxygenator and the heater produce PFC vapor which is recuperated with a  condenser  in order to limit the evaporation loss (the PFC is a  greenhouse gas )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5217", "contents": "An example of a liquid ventilator is the Inolivent-4. It is composed of two independent piston pumps and integrated unit allowing for oxygenation of PFC, temperature control, and recovery of evaporated PFC. [ 13 ]  This liquid ventilator also includes volume and pressure control strategies to optimize the ventilatory cycle: it performs a  pressure-regulated volume-controlled  ventilation mode. [ 12 ]  It is designed for experimental research on animal models weighing between 0.5\u00a0kg to 9\u00a0kg."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5218", "contents": "A typical cycle is composed of four steps\u00a0:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5219", "contents": "Studies have shown both the efficacy and safety of liquid ventilation in normal, mature and immature newborn lungs. Overall, liquid ventilation improves gas exchange and lung  compliance  and prevents the lungs against ventilation-induced lung injury. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5220", "contents": "Studies suggest clear benefits of liquid ventilation in  acute respiratory distress syndrome  (ARDS). [ 14 ]  For example, total liquid ventilation could be used for  newborns  with severe neonatal respiratory distress syndrome [ 15 ]  in which conventional treatment has failed. Typical cases are late  preterm  newborns who have an increased risk of  intracranial hemorrhage  and for whom their small vessel size poses technical limitations for  Extracorporeal membrane oxygenation  (ECMO)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5221", "contents": "Liquid ventilator can perform therapeutic  lung lavage , the washout of endogenous and exogenous debris from the lungs, without suspension of ventilation support (without  apnea ). For example, literature data suggest a radical change in the treatment of  meconium aspiration syndrome  (MAS) by considering the use of a liquid ventilator. The demonstration of its efficacy was performed in the neonatal lamb.. [ 16 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5222", "contents": "The liquid ventilator with advanced control temperature of PFC allows the rapid cooling of the body. Consequently,  therapeutic hypothermia  is an expected clinical application. For example, studies present that rapid cooling instituted by TLV can improve cardiac and mitochondrial function  [ 18 ]  or can induce favorable neurological and cardiac outcomes after cardiac arrest in rabbits. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5223", "contents": "Modes of  mechanical ventilation  has only had an established  nomenclature  since 2008. [ 1 ]   It is suggested that the modes categorized under the following sections be referred to as their section header instead of their individual name, which is often a brand name instead of the preferred nomenclature. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5224", "contents": "Strategies are not  modes of mechanical ventilation  but are instead strategies for using modes."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5225", "contents": "Famous people in healthcare  are famous for many different reasons. For physicians see:  List of physicians ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5226", "contents": "This is a list of notable  ventilator  manufacturers and businesses that manufacture ventilator components for the healthcare industry."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5227", "contents": "The  Master of Science in Respiratory Care  ( MSRC ) is an advanced level  postgraduate degree  for  respiratory therapists . [ 1 ]   Few colleges and Universities currently offer this degree though an emphasis on its importance to respiratory care and research in pulmonary medicine is growing by both nursing groups and medical colleges."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5228", "contents": "Mechanical ventilation  or  assisted ventilation  is the  medical  term for using a  ventilator machine  to fully or partially provide  artificial ventilation . Mechanical ventilation helps move air into and out of the lungs, with the main goal of helping the delivery of oxygen and removal of carbon dioxide. Mechanical ventilation is used for many reasons, including to protect the airway due to mechanical or neurologic cause, to ensure adequate oxygenation, or to remove excess carbon dioxide from the lungs. Various healthcare providers are involved with the use of mechanical ventilation and people who require ventilators are typically monitored in an  intensive care unit ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5229", "contents": "Mechanical ventilation is termed invasive if it involves an instrument to create an airway that is placed inside the  trachea . This is done through an  endotracheal tube  or nasotracheal tube. [ 1 ]  For  non-invasive ventilation  in people who are conscious, face or nasal masks are used. The two main types of mechanical ventilation include  positive pressure ventilation  where air is pushed into the lungs through the airways, and  negative pressure ventilation  where air is pulled into the lungs. There are many specific  modes of mechanical ventilation , and their nomenclature has been revised over the decades as the technology has continually developed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5230", "contents": "The Greek physician  Galen  may have been the first to describe mechanical ventilation: \"If you take a dead animal and blow air through its larynx [through a reed], you will fill its bronchi and watch its lungs attain the greatest distention.\" In the 1600s,  Robert Hooke  conducted experiments on dogs to demonstrate this concept.  Vesalius  too describes ventilation by inserting a reed or cane into the  trachea  of animals. [ 2 ]  These experiments predate the discovery of oxygen and its role in respiration. In 1908,  George Poe  demonstrated his mechanical respirator by  asphyxiating  dogs and seemingly bringing them back to life. These experiments all demonstrate positive pressure ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5231", "contents": "To achieve negative pressure ventilation, there must be a sub-atmospheric pressure to draw air into the lungs. This was first achieved in the late 19th century when John Dalziel and Alfred Jones independently developed tank ventilators, in which ventilation was achieved by placing a patient inside a box that enclosed the body in a box with sub-atmospheric pressures. [ 3 ]  This machine came to be known colloquially as the  Iron lung , which went through many iterations of development. The use of the iron lung became widespread during the  polio epidemic  of the 1900s."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5232", "contents": "Early ventilators were control style with no support breaths integrated into them and were limited to an inspiration to expiration ration of 1:1. In the 1970s,  intermittent mandatory ventilation  was introduced as well as synchronized intermittent mandatory ventilation. These styles of ventilation had control breaths that patients could breathe between. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5233", "contents": "Mechanical ventilation is indicated when a patient's spontaneous  breathing  is inadequate to maintain life. It may be indicated in anticipation of imminent respiratory failure, acute respiratory failure, acute hypoxemia, or prophylactically. Because mechanical ventilation serves only to provide assistance for breathing and does not cure a disease, the patient's underlying condition should be identified and treated in order to liberate them from the ventilator."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5234", "contents": "Common specific medical indications for mechanical ventilation include: [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5235", "contents": "Mechanical ventilation is typically used as a short-term measure. It may, however, be used at home or in a nursing or rehabilitation institution for patients that have chronic illnesses that require long-term ventilatory assistance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5236", "contents": "Mechanical ventilation is often a life-saving intervention, but carries potential complications. A common complication of positive pressure ventilation stemming directly from the ventilator settings include volutrauma and  barotrauma . [ 11 ] [ 12 ]  Others include  pneumothorax ,  subcutaneous emphysema ,  pneumomediastinum , and  pneumoperitoneum . [ 12 ] [ 13 ]  Another well-documented complication is  ventilator-associated lung injury  which presents as acute respiratory distress syndrome. [ 14 ] [ 15 ] [ 16 ]  Other complications include diaphragm atrophy, [ 17 ] [ 18 ] [ 19 ]  decreased cardiac output, [ 20 ]  and oxygen toxicity. One of the primary complications that presents in patients mechanically ventilated is acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). ALI/ARDS are recognized as significant contributors to patient morbidity and mortality. [ 21 ] [ 22 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5237", "contents": "In many healthcare systems, prolonged ventilation as part of  intensive care  is a limited resource. For this reason, decisions to commence and remove ventilation may raise ethical debate and often involve legal orders such as  do-not-resuscitate  orders. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5238", "contents": "Mechanical ventilation is often associated with many painful procedures and the ventilation itself can be uncomfortable. For infants who require opioids for pain, the potential side effects of opioids include problems with feeding, gastric and  intestinal mobility  problems, the potential for  opioid dependence , and opioid tolerance. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5239", "contents": "Timing of withdrawal from mechanical ventilation\u2014also known as weaning\u2014is an important consideration. People who require mechanical ventilation should have their ventilation considered for withdrawal if they are able to support their own ventilation and oxygenation, and this should be assessed continuously. [ 25 ] [ 5 ]  There are several objective parameters to look for when considering withdrawal, but there are no specific criteria that generalizes to all patients."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5240", "contents": "The  Rapid Shallow Breathing Index  (RSBI, the ratio of respiratory frequency to tidal volume (f/VT), previously referred to as the \"Yang Tobin Index\" or \"Tobin Index\" after Dr. Karl Yang and Prof.  Martin J. Tobin  of  Loyola University Medical Center ) is one of the best studied and most commonly used weaning predictors, with no other predictor having been shown to be superior. It was described in a prospective cohort study of mechanically ventilated patients which found that a RSBI > 105 breaths/min/L was associated with weaning failure, while a RSBI < 105 breaths/min/L. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5241", "contents": "Spontaneous breathing trials are conducted to assess the likelihood of a patient being able to maintain stability and breath on their own without the ventilator. This is done by changing the mode to one where they have to trigger breaths and ventilatory support is only given to compensate for the added resistance of the endotracheal tube. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5242", "contents": "A cuff leak test is done to detect if there is airway edema to show the chances of post-extubation stridor. This is done by deflating to the cuff to check if air begins leaking around the endotracheal tube. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5243", "contents": "The function of the lungs is to provide gas exchange via oxygenation and ventilation. This phenomenon of  respiration  involves the physiologic concepts of air flow, tidal volume, compliance, resistance, and  dead space . [ 6 ] [ 28 ]  Other relevant concepts include alveolar ventilation, arterial PaCO2, alveolar volume, and  FiO2 . Alveolar ventilation is the amount of gas per unit of time that reaches the alveoli and becomes involved in gas exchange. [ 29 ]  PaCO2 is the partial pressure of carbon dioxide of arterial blood, which determines how well carbon dioxide is able to move out of the body. [ 30 ]  Alveolar volume is the volume of air entering and leaving the alveoli per minute. [ 31 ]  Mechanical dead space is another important parameter in ventilator design and function, and is defined as the volume of gas breathed again as the result of use in a mechanical device."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5244", "contents": "Due to the anatomy of the human  pharynx ,  larynx , and  esophagus  and the circumstances for which ventilation is needed, additional measures are required to secure the  airway  during positive-pressure ventilation in order to allow unimpeded passage of air into the trachea and avoid air passing into the esophagus and stomach. The common method is by  insertion of a tube into the trachea . Intubation, which provides a clear route for the air  can be either an  endotracheal tube , inserted through the natural openings of mouth or nose, or a  tracheostomy  inserted through an artificial opening in the neck. In other circumstances simple  airway maneuvers , an  oropharyngeal airway  or  laryngeal mask airway  may be employed. If  non-invasive ventilation  or  negative-pressure ventilation  is used, then an  airway adjunct  is not needed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5245", "contents": "Pain medicine such as  opioids  are sometimes used in adults and infants who require mechanical ventilation. For preterm or full term infants who require mechanical ventilation, there is no strong evidence to prescribe opioids or sedation routinely for these procedures, however, some select infants requiring mechanical ventilation may require pain medicine such as opioids. It is not clear if  clonidine  is safe or effective to be used as a  sedative  for preterm and full term infants who require mechanical ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5246", "contents": "When 100% oxygen (1.00 Fi O 2 ) is used initially for an adult, it is easy to calculate the next Fi O 2  to be used, and easy to estimate the shunt fraction. [ 32 ]  The estimated shunt fraction refers to the amount of oxygen not being absorbed into the circulation. [ 32 ]  In normal physiology, gas exchange of oxygen and carbon dioxide occurs at the level of the  alveoli  in the lungs. The existence of a shunt refers to any process that hinders this gas exchange, leading to wasted oxygen inspired and the flow of un-oxygenated blood back to the left heart, which ultimately supplies the rest of the body with de-oxygenated blood. [ 32 ]  When using 100% oxygen, the degree of shunting is estimated as 700 mmHg - measured Pa O 2 . For each difference of 100 mmHg, the shunt is 5%. [ 32 ]  A shunt of more than 25% should prompt a search for the cause of this hypoxemia, such as mainstem intubation or  pneumothorax , and should be treated accordingly. If such complications are not present, other causes must be sought after, and  positive end-expiratory pressure  (PEEP) should be used to treat this intrapulmonary shunt. [ 32 ]  Other such causes of a shunt include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5247", "contents": "Mechanical ventilation utilizes several separate systems for ventilation, referred to as the mode. Modes come in many different delivery concepts, but all conventional positive pressure ventilators modes fall into one of two categories:volume-cycled or pressure-cycled. [ 33 ] [ 25 ]  A relatively new ventilation mode is flow-controlled ventilation (FCV). [ 34 ]  FCV  is a fully dynamic mode without   significant periods of 'no flow'. It is based on creating a stable gas flow into or out of the patient's lungs to generate an inspiration or expiration, respectively. This results in linear increases and decreases in intratracheal pressure. In contrast the conventional modes of ventilation, there are no abrupt drop intrathoracic pressure drops, because of the controlled expiration. [ 35 ]  Further, this mode allows to use thin endotracheal tubes (~2 \u2013 10\u00a0mm inner diameter) to ventilate a patient as expiration is actively supported. [ 36 ]  In general, the selection of which mode of mechanical ventilation to use for a given patient is based on the familiarity of  clinicians  with modes and the equipment availability at a particular institution. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5248", "contents": "The design of the modern positive-pressure ventilators were based mainly on technical developments by the military during World War II to supply oxygen to fighter pilots in high altitude. Such ventilators replaced the iron lungs as safe endotracheal tubes with high-volume/low-pressure cuffs were developed. The popularity of positive-pressure ventilators rose during the polio epidemic in the 1950s in Scandinavia [ 38 ] [ 39 ]  and the United States and was the beginning of modern ventilation therapy. Positive pressure through manual supply of 50% oxygen through a  tracheostomy  tube led to a reduced mortality rate among patients with polio and respiratory paralysis. However, because of the sheer amount of man-power required for such manual intervention, mechanical positive-pressure ventilators became increasingly popular. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5249", "contents": "Positive-pressure ventilators work by increasing the patient's airway pressure through an endotracheal or tracheostomy tube. The positive pressure allows air to flow into the airway until the ventilator breath is terminated. Then, the airway pressure drops to zero, and the elastic recoil of the chest wall and lungs push the  tidal volume  \u2014 the breath-out through passive exhalation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5250", "contents": "Negative pressure mechanical ventilators are produced in small, field-type and larger formats. [ 40 ]  The prominent design of the smaller devices is known as the  cuirass , a shell-like unit used to create negative pressure only to the chest using a combination of a fitting shell and a soft bladder. In recent years this device has been manufactured using various-sized  polycarbonate  shells with multiple seals, and a high-pressure oscillation pump in order to carry out  biphasic cuirass ventilation . [ 41 ]  Its main use has been in patients with neuromuscular disorders that have some residual muscular function. [ 42 ]  The latter, larger formats are in use, notably with the polio wing hospitals in  England  such as  St Thomas' Hospital  in London and the  John Radcliffe  in  Oxford . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5251", "contents": "The larger units have their origin in the  iron lung , also known as the Drinker and Shaw tank, which was developed in 1928 by J.H Emerson Company and was one of the first negative-pressure machines used for long-term ventilation. [ 4 ] [ 41 ]  It was refined and used in the 20th century largely as a result of the  polio   epidemic  that struck the world in the 1940s. The machine is, in effect, a large elongated  tank , which encases the patient up to the neck. [ 3 ]  The neck is sealed with a rubber  gasket  so that the patient's face (and airway) are exposed to the room air. While the exchange of  oxygen  and  carbon dioxide  between the bloodstream and the pulmonary airspace works by  diffusion  and requires no external work, air must be moved into and out of the  lungs  to make it available to the  gas exchange  process. In spontaneous breathing, a negative pressure is created in the  pleural cavity  by the muscles of respiration, and the resulting gradient between the  atmospheric pressure  and the pressure inside the  thorax  generates a flow of air. In the iron lung by means of a pump, the air is withdrawn mechanically to produce a vacuum inside the tank, thus creating negative pressure. [ 41 ]  This negative pressure leads to expansion of the chest, which causes a decrease in intrapulmonary pressure, and increases flow of ambient air into the lungs. As the vacuum is released, the pressure inside the tank equalizes to that of the ambient pressure, and the elastic recoil of the chest and lungs leads to passive exhalation. However, when the vacuum is created, the abdomen also expands along with the lung, cutting off venous flow back to the heart, leading to pooling of venous blood in the lower extremities. The patients can talk and eat normally, and can see the world through a well-placed series of mirrors. Some could remain in these iron lungs for years at a time quite successfully. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5252", "contents": "Some of the problems with the full body design were such as being unable to control the inspiratory to expiratory ratio and the flow rate. This design also caused blood pooling in the legs. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5253", "contents": "Another type is the  intermittent abdominal pressure ventilator  that applies pressure externally via an inflated bladder, forcing exhalation, sometimes termed  exsufflation . The first such apparatus was the  Bragg-Paul Pulsator . [ 43 ] [ 44 ]  The name of one such device, the Pneumobelt made by  Puritan Bennett  has to a degree become a  generic name  for the type. [ 44 ] [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5254", "contents": "The most commonly used high frequency ventilator and only one approved in the United States is the 3100A from Vyaire Medical. It works by using very small tidal volumes by setting amplitude and a high rate set in hertz. This type of ventilation is primarily used in neonates and pediatric patients who are failing conventional ventilation. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5255", "contents": "The first type of high frequency ventilator made for neonates and the only jet type is made by Bunnell Incorporated. It works in conjunction with a separate CMV ventilator to add pulses of air to the control breaths and PEEP. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5256", "contents": "One of the main reasons why a patient is admitted to an ICU is for delivery of mechanical ventilation. Monitoring a patient in mechanical ventilation has many clinical applications: Enhance understanding of pathophysiology, aid with diagnosis, guide patient management, avoid complications, and assess trends."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5257", "contents": "In ventilated patients, pulse oximetry is commonly used when titrating FIO2. A reliable target of Spo2 is greater than 95%. [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5258", "contents": "The total PEEP in the patient can be determined by doing an expiratory hold on the ventilator. If this is higher than the set PEEP, this indicates air trapping."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5259", "contents": "The plateau pressure can be found by doing an inspiratory hold. This shows the actual pressure the patient's lungs are experiencing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5260", "contents": "Loops can be used to see what is occurring in the patient's lungs. These include flow-volume and pressure-volume loops. They can show changes in compliance and resistance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5261", "contents": "Functional Residual Capacity  can be determined when using the GE Carestation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5262", "contents": "Modern ventilators have advanced monitoring tools. There are also monitors that work independently of the ventilator which allow for measuring patients after the ventilator has been removed, such as a  Tracheal tube test ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5263", "contents": "Ventilators come in many different styles and method of giving a breath to sustain life. [ 6 ]   There are manual ventilators such as  bag valve masks  and anesthesia bags that require the users to hold the ventilator to the face or to an  artificial airway  and maintain breaths with their hands.  Mechanical ventilators are ventilators not requiring operator effort and are typically computer-controlled or pneumatic-controlled. [ 25 ]  Mechanical ventilators typically require power by a battery or a wall outlet (DC or AC) though some ventilators work on a pneumatic system not requiring power. There are a variety of technologies available for ventilation, falling into two main (and then lesser categories), the two being the older technology of negative-pressure mechanisms, and the more common positive-pressure types."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5264", "contents": "Common positive-pressure mechanical ventilators include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5265", "contents": "The trigger, either flow or pressure, is what causes a breath to be delivered by a mechanical ventilator. Breaths may be triggered by a patient taking their own breath, a ventilator operator pressing a manual breath button, or based on the set respiratory rate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5266", "contents": "The cycle is what causes the breath to transition from the inspiratory phase to the exhalation phase.  Breaths may be cycled by a mechanical ventilator when a set time has been reached, or when a preset flow or percentage of the maximum flow delivered during a breath is reached depending on the breath type and the settings. Breaths can also be cycled when an alarm condition such as a high pressure limit has been reached."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5267", "contents": "Limit is how the breath is controlled. Breaths may be limited to a set maximum pressure or volume."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5268", "contents": "Exhalation in mechanical ventilation is almost always completely passive. The ventilator's expiratory valve is opened, and expiratory flow is allowed until the baseline pressure ( PEEP ) is reached. Expiratory flow is determined by patient factors such as compliance and resistance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5269", "contents": "There are various procedures and mechanical devices that provide protection against airway collapse, air leakage, and  aspiration :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5270", "contents": "A  nasopharyngeal swab  is a device used for collecting a sample of  nasal secretions  from the back of the  nose  and  throat . [ 1 ] [ 2 ]  The sample is then analyzed for the presence of organisms or other clinical markers for disease. This diagnostic method is commonly used in suspected cases of  whooping cough ,  diphtheria ,  influenza , and various types of diseases caused by the  coronavirus  family of viruses, including  SARS ,  MERS , and  COVID-19 . [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5271", "contents": "To collect the sample, the swab is inserted in the  nostril  and gently moved forward into the  nasopharynx , a region of the pharynx that covers the roof of the mouth. [ 9 ]  The swab is then rotated for a specified period of time to collect secretions, then the swab is removed and placed into a sterile  viral transport media , which preserves the sample for the subsequent analysis. [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5272", "contents": "Similar in concept to the  cotton swab , a swab used for nasopharyngeal collection constitutes a narrow stick made of a short plastic rod that is covered, at one tip, with  adsorbing  material such as cotton, polyester, or flocked nylon. (Some swab handles have been made of  nichrome  or stainless steel wire. [ 3 ] [ 10 ] ) The swab material used for a particular diagnostic application may vary based on the test type. Some research has shown that  flocked  swabs collect a larger volume of the sample material, when compared to fiber swabs. [ 7 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5273", "contents": "Slightly different but related is nasopharyngeal aspiration. Rather than depending on a physical swab to catch material from the nasopharynx, aspiration uses a  catheter  that is attached to a syringe. As with the swab method, the catheter is placed into the nostril and gently advanced to the nasopharynx, where approximately one to three milliliters of saline are introduced, followed by immediate re-aspiration of the saline\u2014along with cells and secretions\u2014back into the syringe. [ 7 ]  This aspiration method is often used when 1. the patient is an infant or elderly and 2. when the method is indicated as effective for a test type. [ 6 ] [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5274", "contents": "In  medicine , a  nebulizer  ( American English ) [ 1 ]  or  nebuliser  ( British English ) [ 2 ]  is a  drug delivery device  used to administer medication in the form of a mist inhaled into the lungs. Nebulizers are commonly used for the treatment of  asthma ,  cystic fibrosis ,  COPD  and other  respiratory diseases  or disorders. They use  oxygen ,  compressed air  or  ultrasonic  power to break up solutions and suspensions into small  aerosol  droplets that are inhaled from the mouthpiece of the device. An aerosol is a mixture of gas and solid or liquid particles."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5275", "contents": "Various asthma guidelines, such as the Global Initiative for Asthma Guidelines [GINA], the British Guidelines on the management of Asthma, The Canadian Pediatric Asthma Consensus Guidelines, and United States Guidelines for Diagnosis and Treatment of Asthma each recommend  metered dose inhalers  in place of nebulizer-delivered therapies. [ 3 ] \nThe European Respiratory Society acknowledge that although nebulizers are used in hospitals and at home they suggest much of this use may not be evidence-based. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5276", "contents": "Recent evidence shows that nebulizers are no more effective than  metered-dose inhalers  (MDIs) with spacers. [ 5 ]   An MDI with a spacer may offer advantages to children who have acute asthma. [ 3 ] [ 6 ] [ 5 ]  Those findings refer specifically to the treatment of asthma and not to the efficacy of nebulisers generally, as for COPD for example. [ 5 ]  For COPD, especially when assessing exacerbations or lung attacks, there is no evidence to indicate that MDI (with a spacer) delivered medicine is more effective than administration of the same medicine with a nebulizer. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5277", "contents": "The  European Respiratory Society  highlighted a risk relating to droplet size reproducibility caused by selling nebulizer devices separately from nebulized solution. They found this practice could vary droplet size 10-fold or more by changing from an inefficient nebulizer system to a highly efficient one. [ 4 ] [ 5 ] \nTwo advantages attributed to nebulizers, compared to MDIs with spacers (inhalers), are their ability to deliver larger dosages at a faster rate, especially in acute asthma; however, recent data suggests actual lung deposition rates are the same. In addition, another trial found that a MDI (with spacer) had a lower required dose for clinical result compared to a nebulizer. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5278", "contents": "Beyond use in chronic lung disease, nebulizers may also be used to treat acute issues like the inhalation of toxic substances. One such example is the treatment of inhalation of toxic  hydrofluoric acid  (HF) vapors. [ 8 ]   Calcium gluconate  is a first-line treatment for HF exposure to the skin. By using a nebulizer, calcium gluconate is delivered to the lungs as an aerosol to counteract the toxicity of inhaled HF vapors."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5279", "contents": "The lung deposition characteristics and efficacy of an aerosol depend largely on the particle or droplet size. Generally, the smaller the particle the greater its chance of peripheral penetration and retention. However, for very fine particles below 0.5\u00a0\u03bcm in diameter there is a chance of avoiding deposition altogether and being exhaled. In 1966 the Task Group on Lung Dynamics, concerned mainly with the hazards of inhalation of environmental toxins, proposed a model for deposition of particles in the lung. This suggested that particles of more than 10\u00a0\u03bcm in diameter are most likely to deposit in the mouth and throat, for those of 5\u201310\u00a0\u03bcm diameter a transition from mouth to airway deposition occurs, and particles smaller than 5\u00a0\u03bcm in diameter deposit more frequently in the lower airways and are appropriate for pharmaceutical aerosols. [ 9 ] \nNebulizing processes have been modeled using  computational fluid dynamics . [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5280", "contents": "The most commonly used nebulizers are jet nebulizers, which are also called \"atomizers\". [ 11 ]  Jet nebulizers are connected by tubing to a supply of compressed gas, usually  compressed air  or  oxygen  to flow at high velocity through a liquid medicine to turn it into an  aerosol  that is inhaled by the patient. Currently there seems to be a tendency among physicians to prefer prescription of a  pressurized Metered Dose Inhaler  (pMDI) for their patients, instead of a jet nebulizer that generates a lot more noise (often 60\u00a0dB during use) and is less portable due to a greater weight. However, jet nebulizers are commonly used in hospitals for patients who have difficulty using inhalers, such as in serious cases of respiratory disease, or severe asthma attacks. [ 12 ]  The main advantage of the jet nebulizer is related to its low operational cost. If the patient needs to inhale medicine on a daily basis the use of a pMDI can be rather expensive. Today several manufacturers have also managed to lower the weight of the jet nebulizer to just over half a kilogram (just under one and a half pounds), and therefore started to label it as a portable device. Compared to all the competing inhalers and nebulizers, the noise and heavy weight is still the biggest draw back of the jet nebulizer. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5281", "contents": "The medical company  Boehringer Ingelheim  also invented a device named  Respimat  Soft Mist Inhaler in 1997. This new technology provides a metered dose to the user, as the liquid bottom of the inhaler is rotated clockwise 180 degrees by hand, adding a buildup tension into a spring around the flexible liquid container. When the user activates the bottom of the inhaler, the energy from the spring is released and imposes pressure on the flexible liquid container, causing liquid to spray out of 2 nozzles, thus forming a soft mist to be inhaled. The device features no gas propellant and no need for battery/power to operate. The average droplet size in the mist was measured to 5.8 micrometers, which could indicate some potential efficiency problems for the inhaled medicine to reach the lungs. Subsequent trials have proven this was not the case. Due to the very low velocity of the mist, the Soft Mist Inhaler in fact has a higher efficiency compared to a conventional pMDI. [ 14 ]  In 2000, arguments were launched towards the European Respiratory Society (ERS) to clarify/expand their definition of a nebulizer, as the new Soft Mist Inhaler in technical terms both could be classified as a \"hand driven nebulizer\" and a \"hand driven pMDI\". [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5282", "contents": "Ultrasonic wave nebulizers were invented in 1965 [ 16 ]  as a new type of portable nebulizer. The technology inside an ultrasonic wave nebulizer is to have an  electronic oscillator  generate a high frequency  ultrasonic wave , which causes the mechanical vibration of a  piezoelectric  element. This vibrating element is in contact with a liquid reservoir and its high frequency vibration is sufficient to produce a vapor mist [ 17 ]  via  ultrasonic atomization . As they create aerosols from ultrasonic vibration instead of using a heavy air compressor, they only have a weight around 170 grams (6.0\u00a0oz). Another advantage is that the ultrasonic vibration is almost silent. Examples of these more modern type of nebulizers are:  Omron  NE-U17 and Beurer Nebulizer IH30. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5283", "contents": "A new significant innovation was made in the nebulizer market around 2005, with creation of the ultrasonic Vibrating Mesh Technology (VMT). With this technology a mesh/membrane with 1000\u20137000 laser drilled holes vibrates at the top of the liquid reservoir, and thereby pressures out a mist of very fine droplets through the holes. This technology is more efficient than having a vibrating piezoelectric element at the bottom of the liquid reservoir, and thereby shorter treatment times are also achieved. The old problems found with the ultrasonic wave nebulizer, having too much liquid waste and undesired heating of the medical liquid, have also been solved by the new vibrating mesh nebulizers. Available VMT nebulizers include: Pari eFlow, [ 19 ]   Respironics  i-Neb, [ 20 ]  Beurer Nebulizer IH50, [ 21 ]  and Aerogen Aeroneb. [ 22 ]  As the price of the ultrasonic VMT nebulizers is higher than models using previous technologies, most manufacturers continue to also sell the classic jet nebulizers. [ 23 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5284", "contents": "Nebulizers accept their medicine in the form of a liquid solution, which is often loaded into the device upon use.  Corticosteroids  and  bronchodilators  such as  salbutamol  ( albuterol   USAN ) are often used, and sometimes in combination with  ipratropium . The reason these pharmaceuticals are inhaled instead of ingested is in order to target their effect to the  respiratory tract , which speeds onset of action of the medicine and reduces side effects, compared to other alternative intake routes. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5285", "contents": "Usually, the aerosolized medicine is inhaled through a tube-like mouthpiece, similar to that of an  inhaler . The mouthpiece, however, is sometimes replaced with a face mask, similar to that used for inhaled  anesthesia , for ease of use with young children or the elderly. Pediatric masks are often shaped like animals such as fish, dogs or dragons to make children less resistant to nebulizer treatments. Many nebulizer manufacturers also offer pacifier attachments for infants and toddlers. But mouthpieces are preferable if patients are able to use them since face-masks result in reduced lung delivery because of aerosol losses in the nose. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5286", "contents": "After use with corticosteroid, it is theoretically possible for patients to develop a  yeast infection  in the mouth ( thrush ) or hoarseness of voice ( dysphonia ), although these conditions are clinically very rare. To avoid these adverse effects, some clinicians suggest that the person who used the nebulizer should rinse his or her mouth. This is not true for bronchodilators; however, patients may still wish to rinse their mouths due to the unpleasant taste of some bronchodilating drugs."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5287", "contents": "The first \"powered\" or pressurized inhaler was invented in France by Sales-Girons in 1858. [ 24 ]  This device used pressure to atomize the liquid medication. The pump handle is operated like a bicycle pump. When the pump is pulled up, it draws liquid from the reservoir, and upon the force of the user's hand, the liquid is pressurized through an atomizer, to be sprayed out for inhalation near the user's mouth. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5288", "contents": "In 1864, the first steam-driven nebulizer was invented in Germany. This inhaler, known as \"Siegle's steam spray inhaler\", used the  Venturi principle  to atomize liquid medication, and this was the very beginning of nebulizer therapy. The importance of droplet size was not yet understood, so the efficacy of this first device was unfortunately mediocre for many of the medical compounds. The Siegle steam spray inhaler consisted of a spirit burner, which boiled water in the reservoir into steam that could then flow across the top and into a tube suspended in the pharmaceutical solution. The passage of steam drew the medicine into the vapor, and the patient inhaled this vapor through a mouthpiece made of glass. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5289", "contents": "The first pneumatic nebulizer fed from an electrically driven gas (air) compressor was invented in the 1930s and called a Pneumostat. With this device, a medical liquid (typically  epinephrine chloride , used as a bronchial muscle relaxant to reverse constriction). [ 28 ]  As an alternative to the expensive electrical nebulizer, many people in the 1930s continued to use the much more simple and cheap hand-driven nebulizer, known as the Parke-Davis Glaseptic. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5290", "contents": "In 1956, a technology competing against the nebulizer was launched by Riker Laboratories ( 3M ), in the form of pressurized  metered-dose inhalers , with Medihaler-iso ( isoprenaline ) and Medihaler-epi ( epinephrine ) as the two first products. [ 30 ]  In these devices, the drug is cold-fill and delivered in exact doses through some special metering valves, driven by a gas propellant technology (i.e.  Freon  or a less environmentally damaging HFA). [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5291", "contents": "In 1964, a new type of electronic nebulizer was introduced: the \"ultrasonic wave nebulizer\". [ 31 ]  Today the nebulizing technology is not only used for medical purposes. Ultrasonic wave nebulizers are also used in  humidifiers , to spray out water aerosols to moisten dry air in buildings. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5292", "contents": "Some of the first models of  electronic cigarettes  featured an ultrasonic wave nebulizer (having a  piezoelectric  element vibrating and creating high-frequency  ultrasound  waves, to cause vibration and atomization of liquid  nicotine ) in combination with a  vapouriser  (built as a  spray nozzle  with an electric  heating element ). [ 32 ]  The most common type of electronic cigarettes currently sold, however, omit the ultrasonic wave nebulizer, as it was not found to be efficient enough for this kind of device. Instead, the electronic cigarettes now use an electric vaporizer, either in direct contact with the absorbent material in the \"impregnated atomizer,\" or in combination with the nebulization technology related to a \"spraying jet atomizer\" (in the form of liquid droplets being out-sprayed by a high-speed air stream, that passes through some small venturi injection channels, drilled in a material absorbed with nicotine liquid). [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5293", "contents": "A  negative pressure ventilator  ( NPV ) is a type of  mechanical ventilator  that stimulates an ill person's  breathing  by periodically applying negative air pressure to their body to expand and contract the chest cavity. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5294", "contents": "In most NPVs (such as the  iron lung  in the diagram), the negative pressure is applied to the patient's torso, or entire body below the neck, to cause their chest to expand, expanding their lungs, drawing air into the patient's lungs through their  airway , assisting (or forcing) inhalation. When negative pressure is released, the chest naturally contracts, compressing the lungs, causing exhalation. In some cases, positive external pressure may be applied to the torso to further stimulate exhalation. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5295", "contents": "Another form of NPV device (such as the  Pulmotor ) is placed at the patient's airway, and alternates negative pressure with  positive pressure  to pump air into their lungs (inhale under positive pressure), then suck it back out (exhale under negative pressure). [ 2 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5296", "contents": "Negative pressure ventilators, while widely used in the early-to-mid 20th century (particularly for victims of the  polio epidemics ), are now largely replaced by  positive-pressure airway ventilators , which force air (or oxygen) directly into the patient's airway. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  However, researchers and clinicians still find some uses for NPVs, owing to their specific advantages. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5297", "contents": "Research and developments in artificial ventilation, both negative-pressure and  positive-pressure, result in evolving assessments of the benefits and hazards of negative-pressure ventilators (NPVs).  Different researchers and clinicians have made varying assessments, over time, about the primary positive and negative aspects of NPVs. A sampling includes:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5298", "contents": "Generally, NPVs are best with patients who have neuromuscular diseases, but normal  lung compliance  (a measure of the lungs' ability to expand and contract). [ 2 ]  They are effective for various conditions, especially neuromuscular and skeletal disorders, particularly for long-term night-time ventilation. [ 1 ]  They are effective in patients who have severe  respiratory acidosis , impaired consciousness, are unable to tolerate a facial mask (due to facial deformity, or  claustrophobia , or excess airway secretions), and in children. [ 11 ]  Continuous external negative pressure ventilation (CENPV) was found in a 2015 study to \"[improve] oxygenation under [a greater number of] physiological conditions\", concurrent with lower \"airway,\" \"transpulmonary,\" and \"intra-abdominal\" pressures, than experienced with continuous  positive pressure ventilation  (CPPV), in study of  adult respiratory distress syndrome  (ARDS) patients, possibly reducing high ARDS mortality. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5299", "contents": "NPVs do not work well if patient's lung compliance is decreased, or their lung resistance is increased. [ 2 ]  They result in a greater vulnerability of the airway to  aspiration , such as inhalation of  vomit  or swallowed liquids, than with intermittent positive pressure ventilation. [ 1 ]  They exacerbate obstructive  sleep apnea . The device is not portable and its installation may be difficult. Patients must sleep in a supine position. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5300", "contents": "There are several types of NPVs, including: [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5301", "contents": "The  iron lung , also known as the tank ventilator, Drinker tank or Emerson tank, was the first common pure-NPV device when it was developed in the 1920s by Drinker, Shaw and Mason. It is a large, sealed horizontal cylinder (or \"tank\") in which the patient lies, with their head protruding from a sealed opening at one end of the tank. An air pump or a flexible  diaphragm  (usually motor-driven) varies the air pressure inside the tank, in continuous alternations, lowering and raising the air pressure in the cylinder. This causes the patient's chest to rise and fall, stimulating inhalation and exhalation through the patient's nose and mouth (which are outside the cylinder, exposed to ambient air pressure). [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5302", "contents": "The cuirass ventilator, also known as the chest shell, turtle shell or tortoise shell, is a more compact variation of the iron lung which only encloses the patient's torso and is sealed around their neck and waist, and depressurized and repressurized by an external pump or portable ventilator. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5303", "contents": "The exovent is a modern device similar to the cuirass ventilator, but developed in 2020, in response to the  COVID-19 pandemic . [ 14 ] [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5304", "contents": "The jacket ventilator, also known as a poncho or raincoat ventilator, is a lighter version of the iron lung or the cuirass ventilator, constructed of an airtight material (such as plastic or rubber) arranged over a light metal or plastic frame, or screen, and depressurized and repressurized by a portable ventilator. [ 1 ] [ 2 ] [ 12 ] [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5305", "contents": "The Pulmotor is a device developed in the early 1900s which was the forerunner of modern  mechanical ventilators . It used pressure from a tank of compressed oxygen to operate a valve system that alternately forced air into and out of a person's airway, using alternating positive and negative air pressure. Although portable, and able to be used by lay persons and non-medical emergency responders, some medical personnel criticized it as dangerous (in part due to the risks of barotrauma or vomiting) and inefficient. [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5306", "contents": "Neurally adjusted ventilatory assist (NAVA)  is a  mode of mechanical ventilation . NAVA delivers assistance in proportion to and in synchrony with the patient's  respiratory efforts , as reflected by an electrical signal. This signal represents the electrical activity of the  diaphragm , the body's principal breathing muscle. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5307", "contents": "The act of taking a breath is controlled by the respiratory center of the brain, which decides the characteristics of each breath, timing and size. The respiratory center sends a signal along the phrenic nerve, excites the diaphragm muscle cells, leading to muscle contraction and descent of the diaphragm dome. As a result, the pressure in the airway drops, causing an inflow of air into the lungs. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5308", "contents": "With NAVA, the electrical activity of the diaphragm (Edi) is captured, fed to the ventilator and used to assist the patient's breathing in synchrony with and in proportion to the patients own efforts, regardless of patient category or size. As the work of the ventilator and the diaphragm is controlled by the same signal, coupling between the diaphragm and the SERVO-i ventilator is synchronized simultaneously. [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5309", "contents": "Nitrogen washout  (or  Fowler's method ) is a test for measuring anatomic  dead space  in the lung during a  respiratory cycle , as well as some parameters related to the closure of airways."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5310", "contents": "A nitrogen washout can be performed with a single nitrogen breath, or multiple ones. \nBoth tests use similar tools, both can estimate  functional residual capacity  and the degree of nonuniformity of gas distribution in the lungs, but the multiple-breath test more accurately measures\nabsolute  lung volumes . [ 1 ]  The following describes a single-breath nitrogen test:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5311", "contents": "A subject takes a breath of 100% oxygen and exhales through a one-way valve measuring nitrogen content and volume. A plot of the nitrogen concentration (as a\u00a0% of total gas) vs. expired volume is obtained by increasing the nitrogen concentration from zero to the percentage of nitrogen in the  alveoli . The nitrogen concentration is initially zero because the subject is exhaling the dead space oxygen they just breathed in (does not participate in alveolar exchange), and climbs as alveolar air mixes with the dead space air. The dead space can be determined from this curve by drawing a vertical line down the curve such that the areas below the curve (left of the line) and above the curve (right of the line) are equal."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5312", "contents": "Most people with a normal distribution of airways resistances will reduce their expired end-tidal nitrogen concentrations to less than 2.5% within seven minutes.  Individuals with high resistance in their airways can take longer than seven minutes to remove all the nitrogen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5313", "contents": "A nitrogen washout can obtain the following parameters:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5314", "contents": "Also, from those values, additional parameters can be calculated:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5315", "contents": "Both of the above should be less than 125% of population average. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5316", "contents": "Obstructive lung disease  is a  category of  respiratory disease  characterized by  airway obstruction . Many obstructive diseases of the  lung  result from narrowing (obstruction) of the smaller bronchi and larger bronchioles, often because of excessive contraction of the smooth muscle itself. It is generally characterized by inflamed and easily collapsible airways, obstruction to airflow, problems exhaling, and frequent medical clinic visits and hospitalizations. Types of obstructive lung disease include  asthma ,  bronchiectasis ,  bronchitis  and  chronic obstructive pulmonary disease  (COPD).  Although COPD shares similar characteristics with all other obstructive lung diseases, such as the signs of  coughing  and  wheezing , they are distinct conditions in terms of disease onset, frequency of symptoms, and reversibility of airway obstruction. [ 1 ]   Cystic fibrosis  is also sometimes included in obstructive pulmonary disease. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5317", "contents": "Asthma is an obstructive lung disease where the  bronchial  tubes (airways) are extra sensitive ( hyperresponsive ). The airways become inflamed and produce excess mucus and the muscles around the airways tighten making the airways narrower. Asthma is usually triggered by breathing in things in the air such as dust or pollen that produce an allergic reaction. It may be triggered by other things such as an  upper respiratory tract infection , cold air, exercise, or smoke. Asthma is a common condition and affects over 300 million people around the world. [ 3 ] \nAsthma causes recurring episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5318", "contents": "A  peak flow meter  can record variations in the severity of asthma over time.  Spirometry , a measurement of lung function, can provide an assessment of the severity, reversibility, and variability of airflow limitation, and help confirm the diagnosis of asthma. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5319", "contents": "Bronchiectasis refers to the abnormal, irreversible dilatation of the bronchi caused by destructive and inflammatory changes in the airway walls.  Bronchiectasis has three major anatomical patterns: cylindrical bronchiectasis, varicose bronchiectasis and cystic bronchiectasis. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5320", "contents": "Chronic obstructive pulmonary disease  (COPD), previously known as chronic obstructive airways disease (COAD) or chronic airflow limitation (CAL), is a group of illnesses characterised by airflow limitation that is not fully reversible. The flow of air into and out of the lungs is impaired. [ 6 ]  This can be measured with breathing devices such as a  peak flow meter  or by  spirometry . Most people with COPD have characteristics of  emphysema  and  chronic bronchitis  to varying degrees.  Asthma  being a reversible obstruction of airways is often considered separately, but many COPD patients also have some degree of reversibility in their airways. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5321", "contents": "In COPD, there is an increase in  airway resistance , shown by a decrease in the forced expiratory volume in 1 second (FEV1) measured by  spirometry .  COPD is defined as a forced expiratory volume in 1 second divided by the forced vital capacity  (FEV1/FVC) that is less than 0.7 (or 70%). [ 8 ]  The residual volume, the volume of air left in the lungs following full expiration, is often increased in COPD, as is the total lung capacity, while the vital capacity remains relatively normal. The increased total lung capacity (hyperinflation) can result in the clinical feature of a  barrel chest  \u2013 a chest with a large front-to-back diameter that occurs in some individuals with  emphysematous COPD . Hyperinflation can also be seen on a  chest X-ray  as a flattening of the  diaphragm . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5322", "contents": "The most common cause of COPD is cigarette  smoking . COPD is a gradually progressive condition and usually only develops after about 20  pack-years  of smoking. COPD may also be caused by breathing in other particles and gases. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5323", "contents": "The diagnosis of COPD is established through  spirometry  although other pulmonary function tests can be helpful.  A chest X-ray is often ordered to look for hyperinflation and rule out other lung conditions but the lung damage of COPD is not always visible on a chest x-ray. Emphysema, for example, can only be seen on  CT scan ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5324", "contents": "The main form of long term management involves the use of  inhaled bronchodilators  (specifically  beta agonists  and  anticholinergics ) and inhaled  corticosteroids . Many patients eventually require  oxygen supplementation  at home. In severe cases that are difficult to control, chronic treatment with oral  corticosteroids  may be necessary, although this is fraught with significant side effects."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5325", "contents": "COPD is generally irreversible although lung function can partially recover if the patient stops smoking. Smoking cessation is an essential aspect of treatment. [ 9 ]  Pulmonary rehabilitation programmes involve intensive exercise training combined with education and are effective in improving shortness of breath. Severe emphysema has been treated with  lung volume reduction surgery , with in carefully chosen cases.  Lung transplantation  is also performed for severe COPD in carefully chosen cases. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5326", "contents": "Alpha 1-antitrypsin deficiency  is a fairly rare genetic condition that results in COPD (particularly emphysema) due to a lack of the antitrypsin protein which protects the fragile alveolar walls from protease enzymes released by  inflammatory processes . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5327", "contents": "Diagnosis of obstructive disease requires several factors depending on the exact disease being diagnosed.  However one commonality between them is an  FEV1/FVC ratio  less than 0.7, i.e. the inability to exhale 70% of their breath within one second. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5328", "contents": "Following is an overview of the main obstructive lung diseases. Chronic obstructive pulmonary disease is mainly a combination of chronic bronchitis and emphysema, but may be more or less overlapping with all conditions. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5329", "contents": "An  open source ventilator  is a disaster-situation  ventilator  made using a freely licensed ( open-source ) design, and ideally, freely available components and parts ( open source hardware ). Designs, components, and parts may be anywhere from completely  reverse-engineered  or completely new creations, components may be  adaptations  of various inexpensive existing products, and special hard-to-find and/or expensive parts may be  3D-printed  instead of purchased. [ 2 ] [ 3 ]  As of early 2020, the levels of documentation and testing of open source ventilators was well below scientific and medical-grade standards. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5330", "contents": "One small, early prototype effort was the Pandemic Ventilator created in 2008 during the  resurgence of H5N1  avian influenza that began in 2003, so named \"because it is meant to be used as a ventilator of last resort during a possible avian (bird) flu pandemic.\" [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5331", "contents": "The policy of using both  free and open source software  (FOSS) and  open source hardware  theoretically allows community-wide  peer-review  and correction of bugs and faults in open source ventilators, which is not available in closed source hardware development. In early 2020 during the  COVID-19  pandemic, a review of open source ventilators stated that \"the tested and peer-reviewed systems lacked complete documentation and the open systems that were documented were either at the very early stages of design ... and were essentially only basically tested ...\" The author speculated that the pandemic would motivate development that would significantly improve the open source ventilators, and that much work, policies, regulations, and funding would be needed for the open source ventilators to achieve medical-grade standards. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5332", "contents": "A number of features are required for an invasive mechanical ventilator to be safely used on a patient: [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5333", "contents": "The requirements for  non-invasive ventilation  are less strict."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5334", "contents": "On March 16, 2020, [ 10 ]  the  Open Source Ventilator Ireland  (OSV) group was formed [ 11 ]   [ 12 ] [ 13 ]  initially with the goal of building a focus team in Ireland to begin development on what was termed the \u201cField Emergency Ventilator (FEV)\u201d. Inspired by the initial efforts of the  Open Source Medical Supplies  (OSCMS), [ 14 ]  which initially focused on developing open ventilators but quickly refocusing mainly on the local production of Personal Protective Experiment (PPE). [ 15 ]  OSV Ireland partnered with the OpenLung team [ 16 ] [ 17 ]  in Canada, who were developing and publishing open source designs via GitLab. [ 18 ]  The group quickly grew amassing volunteer engineers, designers and medical professionals with the goal of developing new, low resource medical interventions to support a perceived lack of mechanical ventilation equipment globally. The well-known Bag Valve Mask (BVM) quickly became the core functional component of their design, [ 19 ]  with the goal of utilizing 3D printed and traditionally manufactured components for localized assembly of the systems to maximise potential manufacturing capabilities around the globe. The  Open Source Ventilator Ireland  (OSV) group evolved into  TeamOSV , to fully incorporate both ventilator and other covid related medical equipment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5335", "contents": "The FOSS Initiative OpenVentilator.io project began on March 19, after two weeks of research. [ 20 ]  Jeremias Almadas  [ 21 ]  had posted some drafts he made on the Open Source COVID-19 Medical Supplies forum. [ 22 ]  Marcos Mendez contacted him to join efforts to develop a solution that could be reproduced on a very high scale. [ 23 ]  This project later became the \"OpenVentilator Spartan Model\".  [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5336", "contents": "With the COVID-19 pandemic a new challenge had just arisen, this was no longer to manufacture ventilator, after all, these are manufactured since biblical times, [ 24 ]  including since the 1960s models like the Bird MK VII  [ 25 ]  were already consolidated with an enviable engineering that is very simple."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5337", "contents": "The challenge now was to design an item that solves a problem on a global scale. Manufactured on a very large scale and with parts found in small towns and villages. These were the premises assumed by some projects like OpenVentilator.io. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5338", "contents": "On March 18,  Medtronic  had opened its code and files for manufacturing its main pulmonary ventilation equipment. [ 26 ]  The issue was on a scale that Medtronic would not be able to fulfill at the global level, nor at the regional level. The same was already happening with Philips, GE and Drager, world leaders in the manufacture of this type of equipment. It would not make sense to reinvent something that had already been studied for 100 years. The problem was also not an engineering problem, but a logistical and scale problem so that these projects that were to emerge were applicable and achievable. Manufacturing should be decentralized, focused on the regional resources of each individual on planet earth. Nine out of ten Brazilian cities do not even have an ICU bed, let alone an electronics store and or an Ambu factory. The African situation had already been proclaimed a catastrophe. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5339", "contents": "Several projects are beginning to emerge in this area, many of them with an engineering approach, many others following strict validations with the regulations. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5340", "contents": "There are few projects that have an [analysis of complex thinking [ 28 ] [ circular reference ]  within the global economic-political stagnation. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5341", "contents": "A major worldwide design effort began during the  COVID-19 pandemic  after a  Hackaday  project was started, in order to respond to  expected ventilator shortages  causing higher mortality among severe patients. This project aims to build a  continuous positive airway pressure  device. [ 30 ] [ non-primary source needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5342", "contents": "On March 19, the MakAir open source ventilator project [ 31 ]  was started by a team of software engineers in France, using  3D printing  to quickly iterate on a prototype, with the goal of letting an established manufacturer produce the final ventilators for a cost nearing \u20ac2,000. The team built a working prototype in one month, [ 32 ]  at the end of which a successful 12 hour ventilation test on a pig was performed. The project received official support [ 33 ]  from the  French Army 's investment branch, Agence Innovation D\u00e9fense of  Direction g\u00e9n\u00e9rale de l'armement , granting the project \u20ac426,000 to help fund clinical trials.  Groupe SEB  agreed [ 34 ]  to manufacture the MakAir ventilator in their facilities in Vernon, France. As of December 2020, the MakAir ventilator project is still active on the engineering side, with full support for both pressure and volume controlled ventilation modes, and on the medical side with ongoing clinical trials at CHU Nantes [ 35 ]  on human patients."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5343", "contents": "On March 20, 2020,  Irish Health Services [ 36 ]  began reviewing the designs from the Open Source Ventilator Ireland project. [ 37 ]  A prototype is being designed and tested in Colombia. [ 38 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5344", "contents": "The  University of Minnesota Bakken Medical Device Center  initiated a collaboration with various companies to bring a ventilator alternative to the market that works as a one-armed  robot  and replaces the need for manual ventilation in emergency situations. The  Coventor  device was developed in a very short time and approved on April 15, 2020, by the  FDA , only 30 days after conception. The mechanical ventilator is designed for use by trained medical professionals in  intensive care units  and easy to operate. It has a compact design and is relatively inexpensive to manufacture and distribute. The cost is only about 4% of a normal ventilator. In addition, this device does not require pressurized oxygen or air supply, as is normally the case. A first series is manufactured by  Boston Scientific . The plans are to be freely available online to the general public without royalties. [ 40 ] [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5345", "contents": "The Polish company Urbicum reports successful testing [ 42 ]  of a 3D-printed, open source prototype device called VentilAid. The makers describe it as a last resort device when professional equipment is missing. The design is publicly available. [ 43 ]  The first Ventilaid prototype requires compressed air to run. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5346", "contents": "On March 21, 2020, the  New England Complex Systems Institute  (NECSI) began maintaining a strategic list of open source designs being worked on. [ 44 ] [ 45 ]  The NECSI project considers manufacturing capability, medical safety and need for treating patients in various conditions, speed dealing with legal and political issues, logistics and supply. [ 46 ]  NECSI is staffed with scientists from Harvard, MIT, and others who have an understanding of pandemics, medicine, systems, risk, and data collection. [ 46 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5347", "contents": "Massachusetts Institute of Technology  began an emergency project to design a low-cost ventilator that uses a  bag valve mask  as the main component. [ 39 ]  Other groups and companies, such as  Monolithic Power Systems , also developed designs based on this concept. [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5348", "contents": "The Oxysphere project develops open blueprints for a positive pressure ventilation hood. [ 48 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5349", "contents": "On April 23, 2020,  NASA  reported building, in 37 days, a successful  COVID-19 ventilator  (named  VITAL  (\"Ventilator Intervention Technology Accessible Locally\") which is currently undergoing further testing. NASA is seeking fast-track approval by the  United States Food and Drug Administration  for the new ventilator. [ 49 ] [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5350", "contents": "On May 29, 2020,  NASA  revealed the \"Eight US Manufacturers Selected to Make NASA COVID-19 Ventilator.\" [ 51 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5351", "contents": "The U.S. companies selected for licenses are:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5352", "contents": "Israeli engineers created an open source ventilator  [ 52 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5353", "contents": "On March 24, 2020, the  U.S. Secretary of Health and Human Services  (HHS) enacted  Emergency Use Authorizations [ 53 ]  to allow the use of additional devices, including: \"Ventilators, positive pressure breathing devices modified for use as ventilators (collectively referred to as 'ventilators'), ventilator tubing connectors, and ventilator accessories.\" This was done in accordance with its February 4 declaration [ 54 ]  for medical countermeasures against the  coronavirus disease 2019 , and the equipment is subject to the  FDA 's \"criteria for safety, performance and labeling.\""}
+{"id": "WikiPedia_Pulmonology$$$corpus_5354", "contents": "An  oxygen firebreak , also known as a fire stop valve or fire safety valve, is a  thermal fuse  designed to extinguish a fire in the delivery tube being used by a patient on  oxygen therapy  and stop the flow of oxygen if the tube is accidentally ignited. Oxygen firebreaks are fitted into the oxygen delivery tubing close to the patient, typically around the patient's  sternum  where the two nasal  cannula  tubes join and connect to the delivery tubing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5355", "contents": "Oxygen  is not flammable, but when it is present in increased concentrations it will enable fires to start much more easily. Once a fire has started, if supplemental oxygen is present it will burn more fiercely, based on the principle of the  fire triangle . Materials that do not burn in ambient air may burn when there is a greater concentration of oxygen present than there is in air."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5356", "contents": "Most home oxygen fires are caused by patients smoking whilst using medical oxygen. Other sources of naked flames, such as gas flames and birthday candles, can also pose a risk. [ 1 ]  Despite the inherent dangers, researchers estimate that between 10 and 50 per cent of home oxygen patients continue to smoke. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5357", "contents": "Once a fire has started in the patient's nasal cannula it will track back towards the oxygen source and if not stopped may lead to a 'whole house' fire. Whole house fires are directly correlated with single or even multiple deaths. According to the US  National Fire Protection Association  (NFPA), 25% of oxygen fires get beyond the immediate surrounding area to become 'whole house' fires. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5358", "contents": "While an oxygen firebreak / thermal fuse cannot stop the initial ignition, it can limit the potential for whole house fires, more serious injury and death. Firebreaks / thermal fuses can also buy more time for a patient and other individuals in the building to escape, and limit the material cost of fire damage."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5359", "contents": "A study,  The prevalence and impact of home oxygen fires in the USA , published in September 2019, analysed media reports of home oxygen fire incidents between December 2017 and August 2019. The report found 311 incidents, resulting in 164 deaths, equivalent to one patient death every four days. It also found that a third of reported incidents referenced exploding cylinders, posing a significant risk to third parties, including emergency services. The estimates that there are between 100 and 150 deaths every year from home oxygen fires in the US, describing it as a 'material health issue'."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5360", "contents": "Further research published in November 2021 confirmed that home oxygen fires remain a material public health challenge. The study,  Firebreaks: a risk-based approach to safer home oxygen delivery  examined media reports of home oxygen fire incidents between August 2019 and July 2021. 256 incidents and 152 deaths were recorded in this 23-month period, equating to a death every four days, consistent with the previous research. Over the total study period of 3.5 years, there were 567 fires involving home oxygen and 316 deaths, including two firefighters who lost their lives. The new report also examines the significant impact of burns resulting from home oxygen fires, drawing on a study by Wake Forest Baptist Medical Center in 2020 which found home oxygen fires cause at least 1,000 burn injuries per year."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5361", "contents": "In 2008 the  NFPA  published a  report  suggesting that there are 46 deaths each year in the US from 182 fires. The report also stated that US hospital emergency rooms deal with an average 1,190 cases of burns each year as a result of home oxygen fires. However, the NFPA describes these statistics as \"likely underestimates\". [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5362", "contents": "Further analysis by Marty Ahrens on behalf of the NFPA in 2017 recorded a likely average annual death rate for home fires involving oxygen administration equipment of 70 people (or 3% or all home fire deaths), based upon figures between 2011 and 2015. The  report  also suggested that these fires or burns are becoming more common. [ 4 ]  In 2019 the NFPA also reported that \"medicinal oxygen was involved in 13% of the home smoking material fire deaths\". [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5363", "contents": "The  United States Fire Administration  (USFA) said in a 2015 report that \"While no one factor is solely responsible for the increased fire risk to older adults receiving home health care, smoking in the presence of oxygen is recognized as one important problem.\" [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5364", "contents": "A study of home oxygen therapy patients in the  Veterans Health Administration  between 2009 and 2015 examined 123 cases of reported adverse events related to flash burns. It found that 100 cases (81%) resulted in injury, and 23 (19%) resulted in death. Although 89% of veterans claimed to have quit smoking, 92% of burns occurred as a result of smoking. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5365", "contents": "In July 2022, the International Association of Fire Chiefs (IAFC) adopted a position statement on home oxygen fire safety that recommended the use of firebreaks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5366", "contents": "Not all European countries monitor data on the number of fires that occur as a result of home oxygen. Despite a European Union  Medical Device Directive  requiring incidents to be reported to national vigilance authorities, there is often inadequate coordination to publish the information centrally. [ 1 ]   According to the German Federal Institute for Drugs and Medical Devices ( Bundesinstitut fur Arzneimittel und Medizinprodukte, BfArM ) it is likely that such incidents are grossly under-reported. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5367", "contents": "Data from the  European Industrial Gases Association (EIGA) , reports home oxygen fires caused 15 fatalities between 2013 and 2017 across 16 countries, suggesting significant under-reporting of the issue. By contrast, a  white paper report , published by BPR Medical in April 2022, found that 23 deaths from home oxygen fire incidents in France and Italy, had been reported by the media between 2017 and 2021."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5368", "contents": "In England and Wales, central reporting of adverse incidents is a requirement of the  NHS Service Specification for Home Oxygen . After firebreaks became mandatory in 2006, the average number of deaths by fire was 0.36 per thousand patients per year. In the US, where firebreaks were not required, almost twice as many patients (0.62 patients per thousand) died. [ 1 ]  A Freedom of Information request in 2018 revealed that only one fatality relating to home oxygen fires was recorded in the five-year period between 2013 and 2017. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5369", "contents": "In 2018, a  freedom of information  request to all  clinical commissioning groups  in England (where firebreaks are mandatory) revealed that during the five years between 2013 and 2017 inclusive, 63 serious incidents involving oxygen fires were recorded and just one fatality. 73% of CCGs, representing 71% of patients in England, responded to the request. When the results are extrapolated to cover the whole patient population of 81,000, the figures are 89 incidents and 1.4 deaths. [ 7 ]  The fatality rate is significantly lower than any other previous study in the UK or internationally, and significantly lower than rates in the US or Japan where, compared with the equivalent patient population, they were 27 and 14 respectively. [ 8 ]  The white paper report suggests that the mandatory introduction of firebreaks, in conjunction with a \"multidisciplinary approach to patient education\", as well as risk assessments, is responsible for the low level of fatalities. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5370", "contents": "Some of the incidents involving deaths and injuries to patients, their relatives, fellow residents, as well as firefighters include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5371", "contents": "Collelongo (L'Aquila), Italy. April 15, 2021"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5372", "contents": "Bradford County, Pennsylvania, US. March 23, 2021"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5373", "contents": "Vancouver, Washington, US. March 9, 2021"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5374", "contents": "Nottingham, Maryland, US. December 3, 2020"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5375", "contents": "Wellington, Kansas, US. September 22, 2020"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5376", "contents": "Giromagny, France. March 8, 2020"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5377", "contents": "Saint-Nazaire, France. January 12, 2020"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5378", "contents": "Richmond, Indiana, US. November 19, 2018"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5379", "contents": "Tilford, South Dakota, US. September 7, 2018"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5380", "contents": "Fayetteville, Arkansas, US. July 14, 2018"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5381", "contents": "Marion County, Indianapolis, US. May 19, 2018"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5382", "contents": "Rathcobican, County Offaly, Ireland. June 22, 2017"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5383", "contents": "San Remo, Italy. March 23, 2017"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5384", "contents": "Pont-Sainte-Maxence, Oise, France. March 11, 2017"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5385", "contents": "Pau, France. February 19, 2017"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5386", "contents": "Winchester, Kentucky, US. March 11, 2016"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5387", "contents": "Knox County, Tennessee, US. February, 2012"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5388", "contents": "Before placing a new concentrator on the market, all oxygen concentrator manufacturers need to make a  510(k) premarket submission  to the  US Food and Drug Administration (FDA) ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5389", "contents": "If the manufacturer chose to apply  ISO 80601-2-69:2014  to demonstrate the safety of the new device, the fire safety elements of the standard, including 'a means to extinguish a tubing fire and isolate the oxygen flow' are a requirement. Approval to market the product would then be based upon compliance to the standard."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5390", "contents": "In March, 2018, the  US Veterans Health Administration  issued a  Patient Safety Alert  mandating the use of thermal fuses in all its patients' home oxygen installations, unless there is a clinical reason for not doing so. The Patient Safety Alert applies to all patients, not just those deemed to be at 'high risk'. It requires two thermal fuses to be fitted per patient installation, and any unidirectional thermal fuses must be replaced with bidirectional versions at the next scheduled visit (unless the unidirectional thermal fuse is designed so it cannot be fitted in the wrong direction)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5391", "contents": "In January 2020, in coordination with Fire Departments around the state and other agencies, the  Wyoming State Fire Marshals Office  launched the statewide community risk 307 CRR initiative. [ 26 ]  This aims to \"to reach users of home medical oxygen, place safety devices on their units, and provide a home-risk checkup for the residents when possible\". [ 27 ]  The initiative follows Wyoming fire data which revealed that more than fifty percent of the deaths in residential structure fires throughout the state have been in homes with medical oxygen. The goal of the initiative is to reduce fire deaths and injuries by 2024 by installing inline oxygen firebreaks in 100% of home using medical oxygen across the State."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5392", "contents": "In March 2022, the  American Burn Association  (ABA) agreed a  position statement  on home oxygen burn prevention supporting the use of bidirectional thermal fuses in oxygen tubing. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5393", "contents": "In July 2022, the  International Association of Fire Chiefs  (IAFC) adopted a  position statement  on home oxygen fire safety that recommended the use of firebreaks."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5394", "contents": "In November 2023, Iowa has become the first US State to fund bidirectional thermal fuses through the Iowa Medicaid system. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5395", "contents": "In the  European Union  the fitting of firebreaks is a legal requirement for all home oxygen installations. [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5396", "contents": "All economic operators in the EU, including home oxygen service providers, must comply with the  Medical Device Directive (93/42/EEC)  or the  Medical Device Regulation (2017/745) ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5397", "contents": "The instructions for use for an  oxygen concentrator  placed on the EU single market must include an instruction to the effect that a firebreak shall be fitted close to the patient to stop the flow of oxygen in the event of a fire. By including this statement the  oxygen concentrator  manufacturer is complying with the harmonised EN ISO type standard for oxygen concentrators  EN ISO 8359:2009+A1:2012 , which provides the manufacturer with an immediate  presumption of conformity  to the Essential Requirements of the  Medical Devices Directive  and allows them to properly apply the  CE mark .  Since January 2015 all instructions for use provided with oxygen concentrators placed on the European market will include this statement."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5398", "contents": "The applied  CE mark  is reliant on the home oxygen service provider following this instruction and fitting a firebreak. If the firebreak is not fitted, then the Essential Requirements for performance and safety are not met and the CE mark is no longer valid.  It also means that the home oxygen service provider's status, within the framework under which the single market for medical devices operates, changes from 'distributor' to 'manufacturer'. This has significant regulatory implications."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5399", "contents": "The EU  Medical Devices Directive  also requires that economic operators adopt solutions that 'reduce risk as far as possible' in line with the 'state of the art'. The fitting of firebreaks is therefore a requirement irrespective of the oxygen source, including  oxygen concentrators ,  liquid oxygen   dewars  or  gas cylinders . [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5400", "contents": "Statistics from the  European Industrial Gases Association (EIGA)  suggest that home oxygen fires caused 15 deaths between 2013 and 2017 in 16 EU countries. However media analysis across another five-year period (2017\u20132021), published in a  white paper  by BPR Medical, [ 32 ]  identified 23 deaths in France and Italy alone."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5401", "contents": "The report calls for Competent Authorities in Europe to address home oxygen fire reporting procedures and the implementation of existing patient safety regulations."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5402", "contents": "An additional legal requirement applies in the UK, where the fitting of firebreaks has been mandatory under the service specification of the  home oxygen service [ 33 ]  since 2006. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5403", "contents": "In 2011, the German  Federal Institute for Drugs and Medical Devices  recommended 'corrective actions to prevent fires in oxygen concentrators'. It issued a notice stating that from July 1, 2012, all devices should be equipped with installations for stopping encroachment of the fire into the device, and interruption of the delivery of oxygen in the accessory as close to the patient as possible, in case of ignition. Manufacturers were also required to offer retrospective refitting for devices placed on the market before July 1, 2012. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5404", "contents": "The World Health Organization recommends 'firebreak connectors to stop the oxygen flow in the event of fire' in all oxygen concentrators. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5405", "contents": "Three main standards cover the use of oxygen firebreaks / thermal fuses:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5406", "contents": "The safety requirements for oxygen concentrators are governed by the amended standard  ISO 8359:1996+A1:2012 . The US FDA recognized the standard from January 2014. In January 2015, it was superseded by  ISO 80601-2-69:2014 .  Health Canada , which is responsible for national public health, still recognizes the standard."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5407", "contents": "All of the 28  CEN (European Committee for Standardization)  national standardization bodies (NSBs) have published  EN ISO 8359:2009+A1:2012  as national standards. In Europe EN ISO 8359:2009+A1:2012 has harmonized standard status, which triggers ' presumption of conformity '."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5408", "contents": "Included in  ISO 80601-2-69:2014  are specific requirements that serve to mitigate the risk of fire related to oxygen therapy. The requirements state that the following should be provided:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5409", "contents": "An  oxygen mask  is a mask that provides a method to transfer  breathing oxygen gas  from a storage tank to the  lungs . Oxygen masks may cover only the nose and mouth (oral nasal mask) or the entire face (full-face mask). They may be made of  plastic ,  silicone , or  rubber .\nIn certain circumstances, oxygen may be delivered via a  nasal cannula  instead of a mask."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5410", "contents": "Medical plastic oxygen masks are used primarily by medical care providers for  oxygen therapy  because they are disposable and so reduce cleaning costs and infection risks. Mask design can determine accuracy of oxygen delivered with many various medical situations requiring treatment with oxygen."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5411", "contents": "Oxygen is naturally occurring in room air at 21% and higher percentages are often essential in medical treatment. Oxygen in these higher percentages is classified as a drug with too much oxygen being potentially harmful to a patient's health, resulting in oxygen dependence over time, and in extreme circumstances patient blindness. For these reasons oxygen therapy is closely monitored. Masks are light in weight and attached using an elasticated headband or ear loops. They are transparent for allowing the face to be visible for patient assessment by healthcare providers, and reducing a sensation of claustrophobia experienced by some patients when wearing an oxygen mask. The vast majority of patients having an operation will at some stage wear an oxygen mask; they may alternatively wear a nasal cannula but oxygen delivered in this way is less accurate and restricted in concentration."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5412", "contents": "The global disposable oxygen masks market, according to Altus Market Research, has the potential to grow by US$1.1 billion between 2019 and 2023. The market's growth pace will also pick up speed throughout this time. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5413", "contents": "Silicone and rubber oxygen masks are heavier than plastic masks. They are designed to provide a good seal for long-duration use by  aviators , medical research subjects, and  hyperbaric chamber  and other patients who require administration of pure oxygen, such as  carbon monoxide poisoning  and  decompression sickness  victims. Dr.  Arthur H. Bulbulian  pioneered the first modern viable oxygen mask, worn by World War II pilots and used by hospitals. [ 2 ]   Valves  inside these tight-fitting masks control the flow of gases into and out of the masks, so that rebreathing of exhaled gas is minimised."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5414", "contents": "Hoses or tubing connect an oxygen mask to the oxygen supply. Hoses are larger in diameter than tubing and can allow greater oxygen flow. When a hose is used it may have a ribbed or corrugated design to allow bending of the hose while preventing twisting and cutting off the oxygen flow. The quantity of oxygen delivered from the storage tank to the oxygen mask is controlled by a valve called a  regulator . Some types of oxygen masks have a breathing bag made of plastic or rubber attached to the mask or oxygen supply hose to store a supply of oxygen to allow deep breathing without waste of oxygen with use of simple fixed flow regulators."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5415", "contents": "An early 1919 high-altitude oxygen system used a vacuum flask of liquid oxygen to supply two people for one hour at 15,000\u00a0ft (4,600\u00a0m). The liquid passed through several warming stages before use, as expansion when it evaporated, and absorbed  latent heat of vaporization , would make the gasified oxygen so cold that it could cause instant  frostbite  of the lungs. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5416", "contents": "The first successful creation for the oxygen mask was by Armenian born  Dr. Arthur Bulbulian , in the field of facial prosthetics, in 1941. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5417", "contents": "Many designs of aviator's oxygen masks contain a microphone to transmit speech to other crew members and to the aircraft's radio. Military aviators' oxygen masks have face pieces that partially cover the sides of the face and protect the face against flash burns, flying particles, and effects of a high speed air stream hitting the face during emergency evacuation from the aircraft by  ejection seat  or  parachute . They are often part of a  pressure suit  or intended for use with a  flight helmet ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5418", "contents": "Three main kinds of oxygen masks are used by  pilots  and crews who fly at high altitudes: continuous flow, diluter demand, and pressure demand. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5419", "contents": "In a  continuous-flow system , oxygen is provided to the user continuously. It does not matter if the user is exhaling or inhaling as oxygen is flowing from the time the system is activated. Below the oxygen mask is a rebreather bag that collects oxygen during exhalation and as a result allows a higher flow rate during the inhalation cycle. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5420", "contents": "Diluter-demand  and  pressure-demand  masks supply oxygen only when the user inhales. [ 6 ]  They each require a good seal between the mask and the user's face."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5421", "contents": "In a  diluter-demand system,  as the altitude increases (ambient pressure, and therefore the partial pressure of ambient oxygen, decreases), the oxygen flow increases such that the partial pressure of oxygen is roughly constant. Diluter-demand oxygen systems can be used up to 40,000\u00a0ft (12,000\u00a0m). [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5422", "contents": "In a  pressure-demand system , oxygen in the mask is above ambient pressure, permitting breathing above 40,000 feet (12,000\u00a0m). [ 5 ]  Because the pressure inside the mask is greater than the pressure around the user's torso, inhalation is easy, but exhalation requires more effort. Aviators are trained in pressure-demand breathing in  altitude chambers . Because they seal tightly, pressure-demand-type oxygen masks are also used in hyperbaric oxygen chambers and for oxygen breathing research projects with standard oxygen regulators. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5423", "contents": "Supplemental oxygen is needed for flying more than 30 minutes at cabin pressure altitudes of 12,500 feet (3,800\u00a0m) or higher, pilots must use oxygen at all times above 14,000 feet (4,300\u00a0m) and each occupant must be provided supplemental oxygen above 15,000 feet (4,600\u00a0m). [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5424", "contents": "Most  commercial aircraft  are fitted with oxygen masks for use when cabin pressurization fails. [ 8 ] [ 9 ]  In general, commercial aircraft are  pressurized  so that the cabin air is at a pressure equivalent to no more than 8,000 feet (2,400\u00a0m) altitude (usually somewhat lower altitude), where one can breathe normally without an oxygen mask. If the oxygen pressure in the cabin drops below a safe level, risking  hypoxia , compartments containing the oxygen masks will open automatically, either above or in front of the passenger and crew seats, and in the lavatories."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5425", "contents": "In the early years of commercial flight, before  pressurized cabins  were invented, airliner passengers sometimes had to wear oxygen masks during routine flights."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5426", "contents": "Firefighters  and  emergency service  workers use full face masks that provide breathing air as well as eye and face protection. [ 10 ]  These masks are typically attached to a tank carried upon the back of the wearer and are called  self-contained breathing apparatuses  (SCBA). [ 11 ]  Open circuit SCBAs do not normally supply oxygen, as it is not necessary and constitutes an easily avoidable fire hazard. Rebreather SCBAs usually supply oxygen as this is the lightest and most compact option, and uses a simpler mechanism than other types of rebreather."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5427", "contents": "Specialized full-face masks that supply oxygen or other  breathing gases  are used by  astronauts  to remove nitrogen from their blood before  space walks  (EVA). [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5428", "contents": "Specialized snout masks which supply oxygen to revive family  pets  have been donated to  fire departments . [ 12 ] [ 13 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5429", "contents": "Divers only use pure oxygen for  accelerated decompression , or from oxygen  rebreathers  at shallow depths where the risk of acute  oxygen toxicity  is acceptable. Oxygen supply during in-water decompression is via rebreather,  open circuit diving regulator ,  full-face mask  or  diving helmet  which has been prepared for  oxygen service . [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5430", "contents": "Oxygen supply to divers in  decompression chambers  is preferably through a built-in breathing system, which uses an oxygen mask plumbed into supply and exhaust hoses which supply oxygen from outside the chamber, and discharge the exhaled oxygen-rich gas outside the chamber, using a system equivalent to two  demand valves , one upstream of the diver, to supply oxygen on demand, and the other downstream, to exhaust exhaled gas on demand, so that the oxygen partial pressure in the chamber is limited to relatively safe levels. If oxygen masks are used that discharge into the chamber, the chamber air must be replaced frequently to keep the oxygen level within safe operating limits. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5431", "contents": "Anesthesia masks are face masks that are designed to administer  anesthetic  gases to a patient through inhalation. Anesthesia masks are either made of anti-static silicone or rubber, as a static electricity spark may ignite some anesthetic gases. They are either black rubber or clear silicone. Anesthesia masks fit over the mouth and nose and have a double hose system. One hose carries inhaled anesthetic gas to the mask and the other brings exhaled anesthetic gas back to the machine. Anesthesia masks have 4 point head strap harnesses to securely fit on the head to hold the mask in place as the anaesthetist controls the gases and oxygen inhaled."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5432", "contents": "Oxygen masks are used by  climbers  of high peaks such as  Mount Everest . [ 17 ]  Because of the severe cold and harsh conditions oxygen masks for use at extreme altitude must be robust and effective. The oxygen storage tanks used with the masks (called oxygen bottles) are made of lightweight, high-strength metals and are covered in high-strength fiber such as  kevlar . These special oxygen bottles are filled with oxygen at a very high pressure which provides a longer time duration of oxygen for breathing than standard pressure oxygen bottles. These systems are generally only used above 7,000 metres (23,000\u00a0ft)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5433", "contents": "In recent years oxygen mask systems for high-altitude climbing which pump oxygen constantly have been increasingly replaced by systems supplying oxygen on demand via  nasal cannulas . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5434", "contents": "Oxygen helmets are used in  hyperbaric oxygen  chambers for oxygen administration. [ 2 ]  They are transparent, lightweight plastic helmets with a seal that goes around the wearer's neck that looks like a  space suit   helmet . They offer a good visual field. Light weight plastic hoses provide oxygen to the helmet and remove exhaled gas to the outside of the chamber. Oxygen helmets are often preferred for oxygen administration in hyperbaric oxygen chambers for children and patients that are uncomfortable wearing an oxygen mask. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5435", "contents": "Medical oxygen masks are held in place by medical personnel or the user by hand, or they may be fitted with a lightweight elastic headband so the mask can be removed quickly. Full-face masks are secured by several straps. Tightly fitting oxygen masks are secured at four points by two head straps. Aviators' masks are often equipped with \"quick don\" harnesses that allow those in pressurized aircraft to rapidly don the masks in emergencies. Military aviators' oxygen masks are secured to flight helmets with quick-release systems."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5436", "contents": "An  oxygen tent  consists of a canopy placed over the head and shoulders, or over the entire body of a patient to provide  oxygen  at a higher level than normal. Some devices cover only a part of the face. Oxygen tents are sometimes confused with  altitude tents  as used by athletes and those looking to acclimatize to a higher altitude, but those contain a reduced oxygen content."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5437", "contents": "This form of  treatment  is often prescribed in conditions where people have difficulty in breathing. An oxygen tent can be used in either a  hospital  setting or outside a health-care facility, and can be recommended for short- or long-term therapy."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5438", "contents": "Typically the tent is made of transparent plastic material. It can envelop the patient's bed with the end sections held in place by a mattress to ensure that the tent is airtight. The enclosure often has a side opening with a zipper."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5439", "contents": "Oxygen therapy often benefits patients by providing more oxygen to their  lungs  and consequently to their  tissues . Typically, the treatment raises the amount of oxygen in the  blood , decreases load on the  heart , and facilitates breathing. It can ease symptoms such as cough and dried up secretions that occur in respiratory conditions. Oxygen therapy might be advised for lung diseases, heart conditions,  carbon monoxide poisoning , and could be administered to patients in case of surgery. [ citation needed ]  A person with  viral  or  bacterial meningitis  who develops breathing difficulty might be kept in an oxygen tent."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5440", "contents": "Raised levels of oxygen increase fire risk, both of ignition and of spreading rate and damage. Many materials that will not burn in air will ignite and burn in a high oxygen atmosphere. Extinguishing a fire is more difficult in a high oxygen environment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5441", "contents": "Certain precautions are usually recommended when using an oxygen tent. One of the measures is to avoid opening the tent very often. If the tent is opened to attend to the patient, the edges need to be tucked back to prevent oxygen from seeping out. In general, it is advisable not to smoke or have any flammable material within the vicinity of any oxygen apparatus. [ 1 ]  Using an electrical device inside an oxygen tent also could be hazardous."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5442", "contents": "Oxygen therapy , also referred to as  supplemental oxygen , is the use of  oxygen  as  medical treatment . [ 1 ]   Supplemental oxygen  can also refer to the use of oxygen enriched air at altitude. Acute indications for  therapy  include  hypoxemia  (low blood oxygen levels),  carbon monoxide toxicity  and  cluster headache . It may also be prophylactically given to maintain blood oxygen levels during the induction of  anesthesia . [ 2 ]  Oxygen therapy is often useful in chronic hypoxemia caused by conditions such as severe  COPD  or  cystic fibrosis . [ 3 ] [ 1 ]  Oxygen can be delivered via  nasal cannula ,  face mask , or  endotracheal intubation   at normal atmospheric pressure, or in a  hyperbaric chamber . [ 4 ] [ 5 ]  It can also be given through bypassing the airway, such as in  ECMO  therapy."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5443", "contents": "Oxygen is required for normal  cellular metabolism . [ 6 ]  However, excessively high concentrations can result in  oxygen toxicity , leading to lung damage and  respiratory failure . [ 2 ] [ 7 ]  Higher oxygen concentrations can also increase the risk of airway fires, particularly while smoking. [ 1 ]  Oxygen therapy can also dry out the nasal mucosa without humidification. [ 1 ]  In most conditions, an oxygen saturation of 94\u201396% is adequate, while in those at risk of  carbon dioxide retention , saturations of 88\u201392% are preferred. [ 1 ] [ 8 ]  In cases of carbon monoxide toxicity or  cardiac arrest , saturations should be as high as possible. [ 1 ] [ 8 ]  While  air  is typically 21% oxygen by volume, oxygen therapy can increase O 2  content of air up to 100%. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5444", "contents": "The medical use of oxygen first became common around 1917, and is the most common hospital treatment in the developed world. [ 1 ] [ 9 ] [ 10 ] [ 11 ]  It is currently on the  World Health Organization's List of Essential Medicines . [ 11 ]  Home oxygen can be provided either by  oxygen tanks  or  oxygen concentrator . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5445", "contents": "Oxygen is widely used by hospitals,  EMS , and  first-aid  providers in a variety of conditions and settings. A few indications frequently requiring high-flow oxygen include  resuscitation ,  major trauma ,  anaphylaxis , major  bleeding ,  shock , active  convulsions , and  hypothermia . [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5446", "contents": "In context of acute hypoxemia, oxygen therapy should be titrated to a target level based on  pulse oximetry  (94\u201396% in most patients, or 88\u201392% in people with COPD). [ 12 ] [ 8 ]   This can be performed by increasing oxygen delivery, described as F I O 2 (fraction of inspired oxygen). In 2018, the  British Medical Journal  recommended that oxygen therapy be stopped for saturations greater than 96% and not started for saturations above 90 to 93%. [ 14 ]  This may be due to an association between excessive oxygenation in the acutely ill and increased mortality. [ 8 ]  Exceptions to these recommendations include  carbon monoxide poisoning ,  cluster headaches ,  sickle cell crisis , and  pneumothorax . [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5447", "contents": "Oxygen therapy has also been used as emergency treatment for  decompression sickness  for years. [ 15 ]  Recompression in a  hyperbaric chamber  with 100% oxygen is the standard treatment for  decompression illness . [ 15 ] [ 16 ] [ 17 ]  The success of recompression therapy is greatest if given within four hours after resurfacing, with earlier treatment associated with a decreased number of recompression treatments required for resolution. [ 18 ]  It has been suggested in literature that  heliox  may be a better alternative to oxygen therapy. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5448", "contents": "In the context of stroke, oxygen therapy may be beneficial as long as hyperoxic environments are avoided. [ 20 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5449", "contents": "People receiving outpatient oxygen therapy for hypoxemia following acute illness or hospitalization should be re-assessed by a physician prior to prescription renewal to gauge the necessity of ongoing oxygen therapy. [ 21 ]  If the initial hypoxemia has resolved, additional treatment may be an unnecessary use of resources. [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5450", "contents": "Common conditions which may require a baseline of supplementary oxygen include  chronic obstructive pulmonary disease  (COPD),  chronic bronchitis , and  emphysema . Patients may also require additional oxygen during acute exacerbations. Oxygen may also be prescribed for  breathlessness , end-stage cardiac failure, respiratory failure, advanced cancer, or neurodegenerative disease in spite of relatively normal blood oxygen levels. Physiologically, it may be indicated in people with arterial oxygen partial pressure Pa O 2  \u2264 55mmHg (7.3kPa) or arterial oxygen saturation Sa O 2  \u2264 88%. [ 22 ] [ 23 ] [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5451", "contents": "Careful titration of oxygen therapy should be considered in patients with chronic conditions predisposing them to carbon dioxide retention (e.g., COPD, emphysema). In these instances, oxygen therapy may decrease respiratory drive, leading to accumulation of carbon dioxide (hypercapnia),  acidemia , and increased mortality secondary to respiratory failure. [ 25 ]  Improved outcomes have been observed with titrated oxygen treatment largely due to gradual improvement of the  ventilation/perfusion ratio . [ 26 ]  The risks associated with loss of respiratory drive are far outweighed by the risks of withholding emergency oxygen, so emergency administration of oxygen is never contraindicated. Transfer from the field to definitive care with titrated oxygen typically occurs long before significant reductions to the respiratory drive are observed. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5452", "contents": "There are certain situations in which oxygen therapy has been shown to negatively impact a person's condition. [ 27 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5453", "contents": "In some instances, oxygen delivery can lead to particular complications in population subsets."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5454", "contents": "Some practitioners of  alternative medicine  have promoted \"oxygen therapy\" as a cure for many human ailments including  AIDS ,  Alzheimer's disease  and  cancer . According to the  American Cancer Society , \"available scientific evidence does not support claims that putting oxygen-releasing chemicals into a person's body is effective in treating cancer\", and some of these treatments can be dangerous. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5455", "contents": "Oxygen supplementation has a variety of physiologic effects on the human body. Whether or not these effects are adverse to a patient is dependent upon clinical context. Cases in which an excess amount of oxygen is available to organs is known as  hyperoxia . [ 35 ]  While the following effects may observed with noninvasive high-dose oxygen therapy (i.e., not  ECMO ), delivery of oxygen at higher pressures is associated with exacerbation of the following associated effects. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5456", "contents": "It has been hypothesized that oxygen therapy may promote accelerated development of  atelectasis  (partial or complete lung collapse), as well as denitrogenation of gas cavities (e.g.,  pneumothorax ,  pneumocephalus ). [ 36 ] [ 37 ]  This concept is based on the idea that oxygen is more quickly absorbed compared to nitrogen within the body, leading oxygen-rich areas that are poorly ventilated to be rapidly absorbed, leading to atelectasis. [ 36 ]  It is thought that higher  fractions of inhaled oxygen  ( F I O 2 ) are associated with increasing rates of atelectasis in the clinical scenario. [ 38 ]  In clinically healthy adults, it is believed that absorption atelectasis typically does not have any significant implications when managed properly. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5457", "contents": "In regard to the airway, both  tracheobronchitis  and  mucositis  have been observed with high levels of oxygen delivery (typically >40% O2). [ 40 ]  Within the lungs, these elevated concentrations of oxygen have been associated with increased alveolar toxicity (coined the  Lorrain-Smith effect ). [ 35 ]  Mucosal damage is observed to increase with elevated atmospheric pressure and oxygen concentrations, which may result in the development of  ARDS  and possibly death. [ 41 ] [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5458", "contents": "Decreased cerebral blood flow and  intracranial pressure  (ICP) have been reported in hyperoxic conditions, with mixed results regarding impact on cognition. [ 43 ] [ 44 ] [ 45 ] [ 46 ]  Hyperoxia as also been associated with  seizures ,  cataract  formation, and reversible  myopia . [ 47 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5459", "contents": "Among CO 2  retainers, excess exposure to oxygen in context of the  Haldane effect  causes decreased binding of  deoxyhemoglobin  to CO 2  in the blood. [ 48 ]  This unloading of CO 2  may contribute to the development of  acid-base disorders  due to the associated increase in  PaCO2  ( hypercapnea ).  Patients with underlying lung disease such as  COPD may not be able to adequately clear the additional CO 2  produced by this effect, worsening their condition. [ 49 ]  In addition, oxygen therapy has also been shown to decrease respiratory drive, further contributing to possible hypercapnea. [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5460", "contents": "Hyperoxic environments have been observed to decrease  granulocyte  rolling and  diapedesis  in specific circumstances in humans. [ 50 ]  In regard to anaerobic infections, cases of  necrotizing fasciitis  have been observed to require fewer debridement operations and have improvement in regard to mortality in patients treated with hyperbaric oxygen therapy. [ 51 ]  This may stem from oxygen intolerance of otherwise anaerobic microorganisms. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5461", "contents": "Sustained exposure to oxygen may overwhelm the body's capacity to deal with  oxidative stress . [ 52 ]  \u00a0Rates of oxidative stress appears to be influenced by both oxygen concentration and length of exposure, with general toxicity observed to occur within hours in certain hyperoxic conditions. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5462", "contents": "Hyperoxia is observed to result in a serum reduction in  erythropoietin , resulting in reduced stimulus for  erythropoiesis . [ 54 ]  Hyperoxia at normobaric environments does not appear to be able to halt erythropoiesis completely. [ 54 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5463", "contents": "Within the lungs, hypoxia is observed to be a potent pulmonary  vasoconstrictor , due to inhibition of an outward potassium current and activation of inward sodium current leading to pulmonary vascular muscular contraction. [ 55 ]  However, the effects of hyperoxia do not seem to have a particularly strong vasodilatory effect from the few studies that have been performed on patients with  pulmonary hypertension . [ 56 ] [ 57 ]  As a result, an effect appears to be present but minor. [ 56 ] [ 57 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5464", "contents": "In the systemic vasculature, oxygen serves as a vasoconstrictor, leading to mildly increased blood pressure and decreased cardiac output and heart rate. Hyperbaric conditions do not seem to have a significant impact on these overall physiologic effects. [ 58 ] [ 46 ]  Clinically, this may lead to increased  left-to-right shunting  in certain patient populations, such as those with  atrial septal defect . While the mechanism of the vasoconstriction is unknown, one proposed theory is that increased  reactive oxygen species  from oxygen therapy accelerates the degradation of endothelial  nitric oxide , a vasodilator. [ 59 ] [ 46 ]  These vasoconstrictive effects are thought to be the underlying mechanism helping to abort cluster headaches. [ 60 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5465", "contents": "Dissolved oxygen in hyperoxic conditions may make also a significant contribution to total gas transport. [ 61 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5466", "contents": "Oxygen can be separated by a number of methods (e.g.,  chemical reaction ,  fractional distillation ) to enable immediate or future use. The main methods utilized for oxygen therapy include:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5467", "contents": "Highly concentrated sources of oxygen also increase risk for rapid combustion. Oxygen itself is not flammable, but the addition of concentrated oxygen to a fire greatly increases its intensity, and can aid the combustion of materials that are relatively inert under normal conditions. Fire and  explosion  hazards exist when concentrated oxidants and  fuels  are brought together in close proximity, although an ignition event (e.g., heat or spark) is needed to trigger combustion. [ 65 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5468", "contents": "Concentrated oxygen will allow combustion to proceed rapidly and energetically. [ 65 ]  Steel pipes and storage vessels used to store and transmit both gaseous and  liquid oxygen  will act as a fuel; and therefore the design and manufacture of oxygen systems requires special training to ensure that ignition sources are minimized. [ 65 ]  Highly concentrated oxygen in a high-pressure environment can spontaneously ignite hydrocarbons such as oil and grease, resulting in a fire or explosion. The heat caused by rapid pressurization serves as the ignition source. For this reason, storage vessels, regulators, piping and any other equipment used with highly concentrated oxygen must be \"oxygen-clean\" prior to use to ensure the absence of potential fuels. This does not only apply to pure oxygen; any concentration significantly higher than atmospheric (approximately 21%) carries a potential ignition risk. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5469", "contents": "Some hospitals have instituted \"no-smoking\" policies which can help keep ignition sources away from medically piped oxygen. These policies do not eliminate the risk of injury among patients with portable oxygen systems, especially among smokers. [ 66 ]  Other potential sources of ignition include candles, aromatherapy, medical equipment, cooking, and deliberate vandalism. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5470", "contents": "Various devices are used for oxygen administration. In most cases, the oxygen will first pass through a  pressure regulator , used to control the high pressure of oxygen delivered from a cylinder (or other source) to a lower pressure. This lower pressure is then controlled by a  flowmeter  (which may be preset or selectable) which controls the flow at a measured rate (e.g., litres per minute [LPM]). The typical flowmeter range for medical oxygen is between 0 and 15 LPM with some units capable of obtaining up to 25 LPM. Many wall flowmeters using a  Thorpe tube  design are able to be dialed to \"flush\" oxygen which is beneficial in emergency situations. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5471", "contents": "Many people only require slight increases in inhaled oxygen, rather than pure or near-pure oxygen. [ 67 ]  These requirements can be met through a number of devices dependent on situation, flow requirements, and personal preference."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5472", "contents": "A  nasal cannula  (NC) is a thin tube with two small nozzles inserted into a person's nostrils. It can provide oxygen at low flow rates, 1\u20136 litres per minute (LPM), delivering an oxygen concentration of 24\u201340%. [ 68 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5473", "contents": "There are also a number of face mask options, such as the  simple face mask , often used at between 5 and 10 LPM, capable of delivering oxygen concentrations between 35% and 55%. [ 68 ]  This is closely related to the more controlled  air-entrainment masks , also known as Venturi masks, which can accurately deliver a predetermined oxygen concentration from 24 to 50%. [ 68 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5474", "contents": "In some instances, a partial rebreathing mask can be used, which is based on a simple mask, but features a reservoir bag, which can provide oxygen concentrations of 40\u201370% at 5\u201315 LPM. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5475", "contents": "Demand oxygen delivery systems (DODS) or oxygen resuscitators deliver oxygen only when the person inhales or the caregiver presses a button on the mask (e.g., nonbreathing patient). [ 69 ]  These systems greatly conserve oxygen compared to steady-flow masks, and are useful in emergency situations when a limited supply of oxygen is available and there is a delay in transporting the person to higher care. [ 69 ]  Due to utilization of a variety of methods for oxygenation requirements performance differences arise. [ 70 ]  They are very useful in  CPR , as the caregiver can deliver rescue breaths composed of 100% oxygen with the press of a button. Care must be taken not to over-inflate the person's lungs, for which some systems employ safety valves. These systems may not be appropriate for people who are unconscious or in respiratory distress because of the required respiratory effort. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5476", "contents": "For patients requiring high concentrations of oxygen, a number of devices are available. The most commonly utilized device is the  non-rebreather mask  (or reservoir mask). Non-rebreather masks draw oxygen from attached reservoir bags with one-way valves that direct exhaled air out of the mask. If flow rate is not sufficient (~10L/min), the bag may collapse on inspiration. [ 68 ]  This type of mask is indicated for acute medical emergencies. The delivered F I O 2  (Inhalation volumetric fraction of molecular oxygen) of this system is 60\u201380%, depending on oxygen flow and breathing pattern. [ 71 ] [ 72 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5477", "contents": "Another type of device is a humidified high flow  nasal cannula  which enables flows exceeding a person's peak inspiratory flow demand to be delivered via nasal cannula, thus providing F I O 2  of up to 100%  because there is no entrainment of room air. [ 73 ]   This also allows the person to continue to talk, eat, and drink while still receiving therapy. [ 74 ]  This type of delivery method is associated with greater overall comfort, improved oxygenation, respiratory rates and reduced sputumstatis compared with face mask oxygen. [ 75 ] [ 76 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5478", "contents": "In specialist applications such as aviation, tight-fitting masks can be used. These masks also have applications in  anaesthesia ,  carbon monoxide poisoning  treatment and in  hyperbaric oxygen therapy . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5479", "contents": "Patients who are unable to breathe on their own will require positive pressure to move oxygen into their lungs for gaseous exchange to take place. Systems for delivery vary in complexity and cost, starting with a basic  pocket mask  adjunct which can be used to manually deliver  artificial respiration  with supplemental oxygen delivered through a mask port."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5480", "contents": "Many  emergency medical service  members,  first aid  personnel, and hospital staff may use a  bag-valve-mask  (BVM), which is a malleable bag attached to a face mask (or invasive airway such as an  endotracheal tube  or  laryngeal mask airway ), usually with a reservoir bag attached, which is manually manipulated by the healthcare professional to push oxygen (or air) into the lungs. This is the only procedure allowed for initial treatment of  cyanide poisoning  in the  UK  workplace. [ 77 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5481", "contents": "Automated versions of the BVM system, known as a  resuscitator  or pneupac can also deliver measured and timed doses of oxygen directly to people through a facemask or airway. These systems are related to the  anaesthetic machines  used in operations under  general anaesthesia  that allow a variable amount of oxygen to be delivered, along with other gases including air,  nitrous oxide  and  inhalational anaesthetics ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5482", "contents": "Oxygen and other compressed gases are used in conjunction with a  nebulizer  to allow delivery of medications to the upper and/or lower airways. Nebulizers use compressed gas to propel liquid medication into therapeutically sized aerosol droplets for deposition to the appropriate portion of the airway. A typical compressed gas flow rate of 8\u201310 L/min is used to  nebulize  medications, saline, sterile water, or a combination these treatments into a therapeutic aerosol for inhalation. In the clinical setting, room air (ambient mix of several gasses),  molecular oxygen , and  Heliox [ citation needed ]  are the most common gases used to nebulize a  bolus  treatment or a continuous volume of therapeutic aerosols."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5483", "contents": "Filtered oxygen masks have the ability to prevent exhaled particles from being released into the surrounding environment. These masks are normally of a closed design such that leaks are minimized and breathing of room air is controlled through a series of one-way valves. Filtration of exhaled breaths is accomplished either by placing a filter on the exhalation port or through an integral filter that is part of the mask itself. These masks first became popular in the Toronto (Canada) healthcare community during the 2003 SARS Crisis. SARS was identified as being respiratory based, and it was determined that conventional oxygen therapy devices were not designed for the containment of exhaled particles. [ 78 ] [ 79 ] [ 80 ]   In 2003, the HiOx 80  oxygen mask was released for sale. The HiOx 80  mask is a closed design mask that allows a filter to be placed on the exhalation port. Several new designs have emerged in the global healthcare community for the containment and filtration of potentially infectious particles. Other designs include the ISO- O 2  oxygen mask, the Flo 2 Max oxygen mask, and the O-Mask."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5484", "contents": "Typical oxygen masks allow a person to breathe in a mixture of room air and therapeutic oxygen. However, as filtered oxygen masks use a closed design that minimizes or eliminates the person's contact with and ability to inhale room air, delivered oxygen concentrations in such devices have been found to be elevated, approaching 99% using adequate oxygen flows. [ citation needed ]  Because all exhaled particles are contained within the mask,  nebulized  medications are also prevented from releasing into the surrounding atmosphere, decreasing the occupational exposure to healthcare staff and other people. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5485", "contents": "In the United States, most airlines restrict the devices allowed on board an aircraft. As a result, passengers are restricted in what devices they can use. Some airlines will provide cylinders for passengers with an associated fee. Other airlines allow passengers to carry on approved portable concentrators. However, the lists of approved devices varies by airline so passengers may need to check with any airline they are planning to fly on. Passengers are generally not allowed to carry on personal cylinders. In all cases, passengers need to notify the airline in advance of their equipment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5486", "contents": "Effective May 13, 2009, the Department of Transportation and FAA ruled that a select number of portable oxygen concentrators are approved for use on all commercial flights. [ 81 ]  FAA regulations require larger airplanes to carry D-cylinders of oxygen for use in case of an emergency."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5487", "contents": "Since the 1980s, devices have been available which conserve stored oxygen by delivering it during the portion of the breathing cycle when it is more effectively used. This has the effect of stored oxygen lasting longer, or a smaller, and therefore lighter, portable oxygen delivery system being practicable. This class of device can also be used with portable oxygen concentrators, making them more efficient. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5488", "contents": "The delivery of supplemental oxygen is most effective if it is made at a point in the breathing cycle when it will be inhaled to the alveoli, where gas transfer occurs. oxygen delivered later in the cycle will be inhaled into  physiological dead space , wher it serves no useful purpose as it cannot diffuse into the blood. Oxygen delivered during stages of the breathing cycle in which it is not inhaled is also wasted. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5489", "contents": "A continuous constant flow rate uses a simple regulator, but is inefficient as a high percentage of the delivered gas does not reach the alveoli, and over half is not inhaled at all. A system which accumulates free-flow oxygen during resting and exhalation stages, (reservoir cannulas) makes a larger part of the oxygen available for inhalation, and it will be selectively inhaled during the initial part of inhalation, which reaches furthest into the lungs. A similar function is provided by a mechanical demand regulator which provides gas only during inhalation, but requires some physical effort by the user, and also ventilates dead space with oxygen. A third class of system (pulse dose oxygen conserving device, or demand pulse devices) senses the start of inhalation and provides a metered bolus, which if correctly matched to requirements, will be sufficient and effectively inhaled into the alveoli.Such systems can be pneumatically or electrically controlled. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5490", "contents": "Adaptive demand systems [ 82 ] \nA development in pulse demand delivery are devices that automatically adjust the volume of the pulsed bolus to suit the activity level of the user. This adaptive response in intended to reduce desaturation responses caused by exercise rate variation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5491", "contents": "Pulsed delivery devices are available as stand alone modules or integrated into a system specifically designed to use compressed gas, liquid oxygen or oxygen concentrator sources. Integrated design usually allows optimisation of the system for the source type at the cost of versatility. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5492", "contents": "Transtracheal oxygen catheters are inserted directly into the trachea through a small opening in the front of the neck for that purpose. The opening is directed downward, towards the bifurcation of the bronchi. Oxygen introduced through the catheter bypasses the dead spaces of the nose, pharynx and upper trachea during inhalation, and during continuous flow, will accumulate in the anatomic dead space at the end of exhalation and be available for immediate inhalation to the alveoli on the following inhalation. This reduces wastage and provides efficiency roughly three times greater than with external continuous flow. This is roughly equivalent to a  reservoir cannula . Transtracheal catheters have been found to be effective during rest, exercise and sleep. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5493", "contents": "The  peak expiratory flow  ( PEF ), also called  peak expiratory flow rate  ( PEFR ) and  peak flow measurement , [ 1 ]  is a person's maximum speed of  expiration , as measured with a  peak flow meter , a small, hand-held device used to monitor a person's ability to breathe out air. It measures the airflow through the  bronchi  and thus the degree of obstruction in the airways. Peak expiratory flow is typically measured in units of liters per minute (L/min)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5494", "contents": "Peak flow readings are higher when patients are well, and lower when the airways are constricted. From changes in recorded values, patients and doctors may determine lung functionality, the severity of asthma symptoms, and treatment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5495", "contents": "Measurement of PEFR requires training to correctly use a meter and the normal expected value depends on the patient's sex, age, and height. It is classically reduced in obstructive lung disorders such as  asthma ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5496", "contents": "Due to the wide range of 'normal' values and the high degree of variability, peak flow is not the recommended test to identify asthma. However, it can be useful in some circumstances."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5497", "contents": "A small portion of people with  asthma  may benefit from regular peak flow monitoring. When monitoring is recommended, it is usually done in addition to reviewing asthma symptoms and frequency of reliever medication use. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5498", "contents": "When peak flow is being monitored regularly, the results may be recorded on a peak flow chart."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5499", "contents": "It is important to use the same peak flow meter every time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5500", "contents": "To interpret the significance of peak expiratory flow measurements, a comparison is made to reference (normal, predicted) values based on measurements taken from the general population. Various reference values have been published in the literature and vary by population, ethnic group, age, sex, height and weight of the patient. For this reason, tables or charts are used to determine the normal value for a particular individual. More recently,  medical calculators  have been developed to calculate predicted values for peak expiratory flow. There are a number of non-equivalent scales used in the interpretation of peak expiratory flow. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5501", "contents": "Some examples of Reference Values are given below. There is a wide natural variation in results from healthy test subjects."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5502", "contents": "In 2004 the  UK  switched from the original Wright scale to the newer, more accurate European scale. Wright values may be converted to the EU scale using the following formula: [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5503", "contents": "The reverse calculation is:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5504", "contents": "Where  \n \n \n \n W \n \n \n {\\displaystyle W} \n \n  is the value in the Wright scale."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5505", "contents": "These formulas have also been trended over time in both rural and metropolitan areas both as air quality studies and as studies on asthma due to the Peak Flow measurement's accuracy as a predictor of mortality and poor prognosis. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5506", "contents": "Measurements may be based on 1 second or less but are usually reported as a volume per minute. Electronic devices will sample the flow and multiply the sample volume(Litres) by 60, divided by the sample time(seconds) for a result measured in L/minute\u00a0:  \n \n \n \n \n \n \n \n sample volume \n \n \u00d7 \n 60 \n \n sample time \n \n \n \n \n {\\displaystyle {\\frac {{\\text{sample volume}}\\times 60}{\\text{sample time}}}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5507", "contents": "The highest of three readings is used as the recorded value of the Peak Expiratory Flow Rate. It may be plotted out on  graph paper  charts together with a record of symptoms or using peak flow charting software. This allows patients to self-monitor and pass information back to their doctor or nurse. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5508", "contents": "Peak flow readings are often classified into 3 zones of measurement according to the  American Lung Association ; [ 12 ]  green, yellow, and red. Doctors and health practitioners can develop an  asthma  management plan based on the green-yellow-red zones."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5509", "contents": "The measurement of peak expiratory flow was pioneered by  Martin Wright , who produced the first meter specifically designed to measure this index of lung function. Since the original design of instrument was introduced in the late 1950s, and the subsequent development of a more portable, lower cost version (the \"Mini-Wright\" peak flow meter), other designs and copies have become available across the world. [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5510", "contents": "Percutaneous transtracheal ventilation  is a form of  conventional ventilation [ 1 ] [ 2 ] [ 3 ]  by which oxygen is delivered to the lungs using a high pressure gas source through an  over-the-needle  catheter inserted through the skin into the trachea."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5511", "contents": "Percutaneous transtracheal ventilation may be mistaken for  transtracheal jet ventilation , which is not considered conventional ventilation and refers to  high-frequency ventilation ; a low  tidal volume  ventilation and needs specialized ventilators only available in critical care units."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5512", "contents": "A  polysomnographic technologist  (formerly called a  polysomnographic technician ) performs overnight, daytime, or home sleep studies,  polysomnograms , on people with suspected  sleep disorders . In the United States and worldwide, the process for becoming a polysomnography technician or technologist is primarily either on-the-job or certificate based. [ 1 ]  There are associate level programs offered by  for-profit schools  that award a degree in polysomnography technology in the United States, though not necessary to attain employment with the same title. [ 2 ]  After an education program or adequate on-the-job training is complete, the student is eligible for credentialing by the  Board of Registered Polysomnographic Technologists  (BRPT), a non-profit credentialing agency based in the United States but serving polysomnographers worldwide. The BRPT maintains credentialing for over 35 countries including  Canada  and the  United States  as well as over 17,000 individuals working in the industry. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5513", "contents": "Registered Polysomnographic Technologist (RPSGT) is a certification awarded by the Board of Registered Polysomnographic Technologists in the US. The RPSGT credential certifies its holder is regarded by the BRPT as fully competent to work in the field of  sleep studies . Most RPSGTs conduct sleep studies on patients. Some RPSGTs score sleep studies. Basically scoring a study means summarizing it, so it can be used by others involved in the  sleep medicine  field. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5514", "contents": "The RPSGT candidate may qualify for the credentialing examination by a variety of paths. Depending on the qualifying path taken, one must work for a minimum of six to eighteen months full-time in  polysomnography  to be eligible for the examination. As of December 2014 the BRPT listed over 21,000 holders of the RPSGT credential. The credential is valid for five years. To renew it, the holder must earn 50 continuing education credits (CECs) or retake the credentialing exam. Two major sources in the US for obtaining CECs are the  American Association of Sleep Technologists  (AAST) and the  American Association for Respiratory Care  (AARC). [ 4 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5515", "contents": "In the US, certification is awarded by the Board of Registered Polysomnographic Technologists (BRPT). The CPSGT is considered a transitional certification. It is valid for only three years. By that time the CPSGT holder must earn the RPSGT certification, as the CPSGT cannot be renewed. To become a CPSGT, one must pass an examination. To be eligible for the exam, one must have worked full-time for three months in polysomnography and have taken the AASM A-STEP Self-Learning Modules. The AASM is the  American Academy of Sleep Medicine . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5516", "contents": "To maintain the CPSGT, the holder must earn ten continuing education credits (CECs) per year. Major sources for obtaining CECs are the American Association of Sleep Technologists and the American Association for Respiratory Care. [ 4 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5517", "contents": "Registered sleep technologists (RST) are sleep specialists who have been granted the certification by the  American Board of Sleep Medicine ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5518", "contents": "The  National Board for Respiratory Care  (NBRC) developed the Sleep Disorders Specialist (SDS) credential in 2007. The NBRC initiated this credential, in spite of the fact that the Registered Polysomnographic Technologist (RPSGT) credential was widely accepted in the field of sleep medicine. This initially caused conflict amongst various organizations in the sleep field. To earn the SDS credential, the applicant must first be a  Certified Respiratory Therapist  (CRT) or a  Registered Respiratory Therapist  (RRT). The CRT applicant must have six months experience in sleep studies and the RRT applicant must have three months in sleep studies. Both the CRT and RRT applicants must pass an examination. The holder of the SDS credential then appends this abbreviation to his CRT or RRT credential, thus becoming a CRT-SDS or RRT-SDS. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5519", "contents": "Positive end-expiratory pressure  ( PEEP ) is the pressure in the lungs ( alveolar pressure ) above  atmospheric pressure  (the pressure outside of the body) that exists at the end of  expiration . [ 1 ]  The two types of PEEP are extrinsic PEEP (PEEP applied by a ventilator) and intrinsic PEEP (PEEP caused by an incomplete exhalation). Pressure that is applied or increased during an inspiration is termed  pressure support . PEEP is a therapeutic parameter set in the ventilator (extrinsic PEEP), or a complication of mechanical ventilation with air trapping (auto-PEEP). [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5520", "contents": "Auto-PEEP is an incomplete expiration prior to the initiation of the next breath causes progressive air trapping ( hyperinflation ). This accumulation of air increases alveolar pressure at the end of expiration, which is referred to as auto-PEEP."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5521", "contents": "Auto-PEEP develops commonly in high minute ventilation ( hyperventilation ), expiratory flow limitation (obstructed airway) and expiratory resistance (narrow airway)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5522", "contents": "Once auto-PEEP is identified, steps should be taken to stop or reduce the pressure build-up. [ 3 ]  When auto-PEEP persists despite management of its underlying cause, applied PEEP may be helpful if the patient has an expiratory flow limitation (obstruction). [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5523", "contents": "Applied PEEP is usually one of the first  ventilator settings  chosen when  mechanical ventilation  is initiated. It is set directly on the  ventilator ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5524", "contents": "A small amount of applied PEEP (4 to 5 cmH 2 O) is used in most mechanically ventilated patients to mitigate end-expiratory alveolar collapse. [ 6 ]  A higher level of applied PEEP (>5 cmH 2 O) is sometimes used to improve hypoxemia or reduce  ventilator-associated lung injury  in patients with acute lung injury,  acute respiratory distress syndrome , or other types of hypoxemic respiratory failure. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5525", "contents": "Positive end-expiratory pressure can contribute to:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5526", "contents": "John Scott Inkster , an English  anaesthetist  and physician, is credited with discovering PEEP. [ 11 ] \nWhen his discovery was published in the proceedings of the World Congress of Anaesthesia in 1968, Inkster called it Residual Positive Pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5527", "contents": "Pressure-controlled ventilation  may refer to:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5528", "contents": "Pulmonary function testing  ( PFT )  is a complete evaluation of the  respiratory system  including patient history, physical examinations, and tests of pulmonary function. The primary purpose of pulmonary function testing is to identify the severity of pulmonary impairment. [ 1 ]   Pulmonary function testing has diagnostic and therapeutic roles and helps clinicians answer some general questions about patients with lung disease. PFTs are normally performed by a pulmonary function technologist, respiratory therapist, respiratory physiologist, physiotherapist,  pulmonologist , or general practitioner."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5529", "contents": "Pulmonary function testing is a diagnostic and management tool used for a variety of reasons, such as:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5530", "contents": "Pulmonary function testing in patients with neuromuscular disorders helps to evaluate the respiratory status of patients at the time of diagnosis, monitor their progress and course, evaluate them for possible surgery, and gives an overall idea of the prognosis. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5531", "contents": "Duchenne muscular dystrophy  is associated with gradual loss of muscle function over time. Involvement of respiratory muscles results in poor ability to cough and decreased ability to breathe well and leads to  collapse of part or all of the lung  leading to impaired gas exchange and an overall insufficiency in lung strength. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5532", "contents": "Spirometry includes tests of pulmonary mechanics \u2013 measurements of FVC, FEV 1 , FEF values, forced inspiratory flow rates (FIFs), and MVV.  Measuring pulmonary mechanics assesses the ability of the lungs to move huge volumes of air quickly through the airways to identify airway obstruction. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5533", "contents": "The measurements taken by the spirometry device are used to generate a pneumotachograph that can help to assess lung conditions such as: asthma, pulmonary fibrosis, cystic fibrosis, and chronic obstructive pulmonary disease.   Physicians  may also use the test results to diagnose bronchial hyperresponsiveness to exercise, cold air, or pharmaceutical agents. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5534", "contents": "The  helium dilution technique  for measuring lung volumes uses a closed, rebreathing circuit. [ 6 ]   This technique is based on the assumptions that a known volume and concentration of helium in air begin in the closed  spirometer , that the patient has no helium in their lungs, and that an equilibration of helium can occur between the spirometer and the lungs. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5535", "contents": "The  nitrogen washout  technique uses a non-rebreathing open circuit. The technique is based on the assumptions that the nitrogen concentration in the lungs is 78% and in equilibrium with the atmosphere, that the patient inhales 100% oxygen and that the oxygen replaces all of the nitrogen in the lungs. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5536", "contents": "The plethysmography technique applies  Boyle's law  and uses measurements of volume and pressure changes to determine total lung volume, assuming temperature is constant. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5537", "contents": "There are four lung volumes and four lung capacities.  A lung's capacity consists of two or more lung volumes.  The lung volumes are  tidal volume  (V T ),  inspiratory reserve volume  (IRV),  expiratory reserve volume  (ERV), and  residual volume  (RV).  The four lung capacities are  total lung capacity  (TLC), inspiratory capacity (IC),  functional residual capacity  (FRC) and  vital capacity  (VC)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5538", "contents": "Measurement of maximal inspiratory and expiratory pressures is indicated whenever there is an unexplained decrease in vital capacity or respiratory muscle weakness is suspected clinically.  Maximal inspiratory pressure (MIP) is the maximal pressure that can be produced by the patient trying to inhale through a blocked mouthpiece.  Maximal expiratory pressure (MEP) is the maximal pressure measured during forced expiration (with cheeks bulging) through a blocked mouthpiece after a full inhalation. Repeated measurements of MIP and MEP are useful in following the course of patients with  neuromuscular  disorders. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5539", "contents": "Measurement of the single-breath diffusing capacity for  carbon monoxide  (DLCO) is a fast and safe tool in the evaluation of both restrictive and  obstructive lung disease . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5540", "contents": "When a patient has an obstructive defect, a bronchodilator test is given to evaluate if airway constriction is reversible with a short acting beta-agonist. This is defined as an increase of \u226512% and \u2265200 mL in the FEV1 or FVC. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5541", "contents": "The six-minute walk test is a good index of physical function and therapeutic response in patients with a chronic  lung disease , such as  COPD  or  idiopathic pulmonary fibrosis . [ 10 ] [ 11 ] [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5542", "contents": "Arterial blood gases  (ABGs) are a helpful measurement in pulmonary function testing in selected patients. The primary role of measuring ABGs in individuals that are healthy and stable is to confirm hypoventilation when it is suspected on the basis of medical history, such as respiratory muscle weakness or advanced  COPD . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5543", "contents": "ABGs also provide a more detailed assessment of the severity of hypoxemia in patients who have low normal oxyhemoglobin saturation. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5544", "contents": "Pulmonary function testing is a safe procedure; however, there is cause for concern regarding untoward reactions and the value of the test data should be weighed against potential hazards. Some complications include dizziness, shortness of breath, coughing, pneumothorax, and inducing an asthma attack. [ 13 ] [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5545", "contents": "There are some indications against a pulmonary function test being done. These include a recent heart attack, stroke, head injury, an aneurysm, or confusion. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5546", "contents": "Subjects have measurements of height and weight taken before spirometry to determine what their predicted values should be. Additionally, a history of smoking, recent illness, and medications is taken. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5547", "contents": "In order for the forced vital capacity to be considered accurate it has to be conducted three times where the peak is sharp in the flow-volume curve and the exhalation time is longer than 6 seconds."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5548", "contents": "Repeatability of the PFT is determined by comparing the values of forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1). The difference between the highest values of two FVCs need to be within 5% or 150 mL. When the FVC is less than 1.0 L, the difference between the highest two values must be within 100 mL. Lastly, the difference between the two highest values of FEV1 should also be within 150 mL. The highest FVC and FEV1 may be used from each different test. Until the results of three tests meet the criteria of reproducibility, the test can be repeated up to eight times. If it is still not possible to get accurate results, the best three tests are used. [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5549", "contents": "Changes in lung volumes and capacities from normal are generally consistent with the pattern of lung impairment."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5550", "contents": "Spirometry is required for a diagnosis of COPD. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5551", "contents": "Professional societies such as the  American Thoracic Society  and the  European Respiratory Society  have published guidelines regarding the conduct and interpretation of pulmonary function testing to ensure standardization and uniformity in performance of tests. The interpretation of tests depends on comparing the patients values to published normals from previous studies. Deviation from guidelines can result in false-positive or false negative test results, even though only a small minority of pulmonary function laboratories followed published guidelines for spirometry, lung volumes and diffusing capacity in 2012. [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5552", "contents": "The  Global Initiative for Chronic Obstructive Lung Disease  provides guidelines for the diagnosis, severity, and management of  COPD . [ 20 ]  To determine obstruction in a patient's lungs, the post-bronchodilator FEV1/FVC needs to be <0.7. [ 17 ]  Then, the FEV1 percentage of predicted result is used to determine the degree of obstruction where the lower the percent the worse the obstruction. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5553", "contents": "Several calculations are needed for what a normal maximum inspiratory (MIP) and expiratory pressure (MEP) is. For males this found by:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5554", "contents": "M \n I \n P \n = \n 120 \n \u2212 \n ( \n 0.41 \n \u00d7 \n a \n g \n e \n ) \n \n \n {\\displaystyle MIP=120-(0.41\\times age)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5555", "contents": "and"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5556", "contents": "M \n E \n P \n = \n 174 \n \u2212 \n ( \n 0.83 \n \u00d7 \n a \n g \n e \n ) \n \n \n {\\displaystyle MEP=174-(0.83\\times age)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5557", "contents": "To find the lower limit of what is acceptable in males the equations are:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5558", "contents": "M \n I \n \n P \n \n L \n L \n N \n \n \n = \n 62 \n \u2212 \n ( \n 0.15 \n \u00d7 \n a \n g \n e \n ) \n \n \n {\\displaystyle MIP_{LLN}=62-(0.15\\times age)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5559", "contents": "M \n E \n \n P \n \n L \n L \n N \n \n \n = \n 117 \n \u2212 \n ( \n 0.83 \n \u00d7 \n a \n g \n e \n ) \n \n \n {\\displaystyle MEP_{LLN}=117-(0.83\\times age)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5560", "contents": "For females, the equations are slightly different. For the normal values this is used:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5561", "contents": "M \n I \n P \n = \n 108 \n \u2212 \n ( \n 0.61 \n \u00d7 \n a \n g \n e \n ) \n \n \n {\\displaystyle MIP=108-(0.61\\times age)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5562", "contents": "M \n E \n P \n = \n 131 \n \u2212 \n ( \n 0.86 \n \u00d7 \n a \n g \n e \n ) \n \n \n {\\displaystyle MEP=131-(0.86\\times age)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5563", "contents": "For find the lower limit of what it should be without impairment this form of the equations is used:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5564", "contents": "M \n I \n \n P \n \n L \n L \n N \n \n \n = \n 62 \n \u2212 \n ( \n 0.50 \n \u00d7 \n a \n g \n e \n ) \n \n \n {\\displaystyle MIP_{LLN}=62-(0.50\\times age)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5565", "contents": "M \n E \n \n P \n \n L \n L \n N \n \n \n = \n 95 \n \u2212 \n ( \n 0.57 \n \u00d7 \n a \n g \n e \n ) \n \n \n {\\displaystyle MEP_{LLN}=95-(0.57\\times age)}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5566", "contents": "Pulmonary hygiene , also referred to as  pulmonary toilet , [ 1 ]  is a set of methods used to clear  mucus  and  secretions  from the  airways .  The word  pulmonary  refers to the  lungs .  The word  toilet , related to the French  toilette , refers to body care and  hygiene ; this root is used in words such as  toiletry  that also relate to cleansing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5567", "contents": "Respiratory health (pulmonary hygiene) depends on consistent clearance of airway secretions. Normal airway clearance is accomplished by two important mechanisms: the  mucociliary clearance  system and the ability to cough. Impaired mucociliary clearance is linked to poor lung function in a broad range of diseases and disabilities. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5568", "contents": "Pulmonary hygiene prevents  atelectasis  (the collapse of the  alveoli  of the lungs) and rids the respiratory system of secretions, [ 3 ]  which could cause  respiratory infections .  It can also decrease  pulmonary shunting , increase the  functional reserve capacity  of the lungs, and prevent respiratory infection after  chest trauma . [ 4 ]   Methods include using suction to remove fluids and placing the patient in a position that allows secretions to drain by gravity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5569", "contents": "Methods used for pulmonary hygiene include  suctioning  of the airways,  chest physiotherapy ,  blow bottles , [ 3 ]  and nasotracheal suction. [ 5 ]   Bronchoscopy , in which a tube is inserted into the airways so that an examiner can view them, can be used therapeutically as part of pulmonary hygiene. [ 4 ]   Incentive spirometry  and use of  analgesics  (pain medications) that do not inhibit breathing are also parts of pulmonary toilet. [ 6 ]   Coughing  is also important for ridding the airways of secretions, so healthcare providers are careful not to  oversedate  patients, because that could inhibit coughing. [ 7 ]   Tracheotomy  facilitates pulmonary toilet. [ 8 ]  Percussion, another method, loosens secretions and allows the  cilia  of the airways to remove material.  Positioning is another method for promoting drainage of secretions; sometimes patients are placed in a  prone position  to aid in this purpose. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5570", "contents": "The most common treatment of  atelectasis  in the hospital setting is manual chest physiotherapy [ 9 ]  though there is limited evidence of its efficacy. [ 10 ] [ 11 ]   Chest percussion and  postural drainage  are used in  bronchiectasis  and lung  abscess .  The patient's body is positioned so that the  trachea  is inclined downward and below the affected chest area. [ 12 ]  Postural drainage is essential in treating bronchiectasis.  Patients must receive  physiotherapy  to learn to tip themselves into a position in which the lobe to be drained is uppermost at least three times daily for up to 30 minutes during each session."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5571", "contents": "The treatment is often used in conjunction with a technique for loosening secretions in the chest cavity called chest percussion. Chest percussion is performed by clapping the back or chest with a cupped hand. Alternatively, a mechanical vibrator may be used in some cases to facilitate loosening of secretions. [ 13 ]  There are drainage positions for all segments of the lung. These positions are modified depending on the patient's condition and the location of the area in most need of therapy."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5572", "contents": "Intermittent positive pressure breathing (IPPB) physiotherapy has long been used in the intensive care setting in non-intubated patients. Although widely accepted, few studies have validated its efficacy.  In a Respiratory Care Clinical Practice Guideline, [ 14 ]  IPPB is suggested for patients who have impaired airway clearance, and for delivery of aerosolized medications to patients with neuromuscular weakness who are incapable of inhaling deeply. IPPB physiotherapy should be used with caution in patients with severe, uncontrolled bronchospasm or severe airway obstruction"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5573", "contents": "People with neuromuscular weakness and atelectasis benefit from mechanical insufflation-exsufflation. [ 15 ]  Mechanically-assisted coughing greatly improves secretion clearance in the setting of respiratory infection in the patient with neuromuscular disease and should be first-line therapy for this patient population. [ 16 ]  Mechanical insufflation-exsufflation physiotherapy is greatly aided by simultaneous manual augmentation of cough with either a thoracic squeeze or  abdominal thrust  during the expiratory phase (exhale). An American Thoracic Society consensus statement in 2004 supported the use of mechanical insufflation-exsufflation physiotherapy for patients with  Duchenne muscular dystrophy . [ 17 ]  The use of this technique for children with neuromuscular disease has gained widespread acceptance in the United States and internationally. [ 18 ] [ 19 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5574", "contents": "Pulmonary bronchial hygiene is used for preventing infections such as  pneumonia .  It is also used in the management of conditions such as pneumonia and  cystic fibrosis . [ 6 ]   For people with chronic  lung diseases , bronchial hygiene  is used to prevent infections and  lung abscesses . [ 20 ]   Bronchial hygiene is also used to prevent  acute respiratory distress syndrome  after chest trauma. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5575", "contents": "The need for bronchial hygiene is indicated in cases of  COPD ,  pneumonia  and  cystic fibrosis  as both interventional and prophylactic.  Prophylactic indications also include pre and post thoracic surgery to prevent atelectasis and respiratory infections."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5576", "contents": "The decision to use postural drainage therapy requires assessment of potential benefits versus potential risks. Therapy should be provided for no longer than necessary to obtain the desired therapeutic results.  Some of the contraindications include an increased intracranial pressure (>20\u00a0mmHg), any spinal injury acute or otherwise, active  hemoptysis ,  pulmonary embolism , pulmonary edema with  congestive heart failure  and an open or healing wound in the area where chest physiotherapy is otherwise indicated."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5577", "contents": "Medication contraindications vary depending on the medication being delivered."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5578", "contents": "Pulmonary rehabilitation , also known as  respiratory rehabilitation , is an important part of the management and health maintenance of people with chronic respiratory disease who remain symptomatic or continue to have decreased function despite standard medical treatment. It is a broad therapeutic concept. It is defined by the American Thoracic Society and the European Respiratory Society as an evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. [ 2 ]   In general, pulmonary rehabilitation refers to a series of services that are administered to patients of  respiratory disease  and their families, typically to attempt to improve the quality of life for the patient. [ 3 ]  Pulmonary rehabilitation may be carried out in a variety of settings, depending on the patient's needs, and may or may not include  pharmacologic  intervention. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5579", "contents": "The NICE clinical guideline on  chronic obstructive pulmonary disease  states that \u201cpulmonary rehabilitation should be offered to all patients who consider themselves functionally disabled by COPD (usually MRC [Medical Research Council] grade 3 and above)\u201d. [ 5 ]  It is indicated not only in patients with COPD, but also for the following conditions:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5580", "contents": "Pulmonary rehabilitation is generally specific to the individual patient, with the objective of meeting the needs of the patient. It is a broad program and may benefit patients with lung diseases such as chronic obstructive pulmonary disease (COPD), sarcoidosis, idiopathic pulmonary fibrosis (IPF) and cystic fibrosis, among others. Although the process is focused primarily on the rehabilitation of the patient, the family is also involved. The process typically does not begin until a medical examination of the patient has been performed by a licensed physician. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5581", "contents": "The setting of pulmonary rehabilitation varies by patient; settings may include  inpatient care ,  outpatient care , the office of a  physician , or the patient's home. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5582", "contents": "Although there are no universally accepted  procedure codes  for pulmonary rehabilitation, providers usually use codes for general  therapeutic processes . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5583", "contents": "The goal of pulmonary rehabilitation is to help improve the well-being and quality of life of the patient and their families. Accordingly, programs typically focus on several aspects of the patient's recovery and can include medication management, exercise training, breathing retraining, education about the patient's lung disease and how to manage it, nutrition counseling, and emotional support."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5584", "contents": "Medications may be used in the process of pulmonary rehabilitation including:  anti-inflammatory agents  (inhaled steroids),  bronchodilators ,  long-acting bronchodilators ,  beta-2 agonists ,  anticholinergic agents ,  oral steroids ,  antibiotics ,  mucolytic agents ,  oxygen therapy , or  preventive healthcare  (i.e.,  vaccination )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5585", "contents": "Exercise is the cornerstone of pulmonary rehabilitation programs. Although exercise training does not  directly  improve lung function, it causes several physiological adaptations to exercise that can improve physical condition. There are three basic types of exercises to be considered. Aerobic exercise tends to improve the body's ability to use oxygen by decreasing heart rate and blood pressure. Strengthening or resistance exercises can help build strength in the respiratory muscles. Stretching and flexibility exercises like yoga and Pilates can enhance breathing coordination. As exercise can trigger shortness of breath, it is important to build up the level of exercise gradually under the supervision of health care professionals (e.g., respiratory therapist, physiotherapist, exercise physiologist). Additionally,  pursed lip breathing  can be used to increase oxygen level in the patient's body. Breathing games can be used to motivate patients to learn the pursed lip breathing technique."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5586", "contents": "Clinical practice guidelines  have been issued by various regulatory authorities."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5587", "contents": "The exclusion criteria for pulmonary rehabilitation consists of the following:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5588", "contents": "The clinical improvement in outcomes due to pulmonary rehabilitation is measurable through:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5589", "contents": "A  pulmonary scientist  is a  health care  occupation in the field of diagnostic studies related specifically to  pulmonary function , the term  respiratory scientist  may also refer to a  pulmonologist  who holds a  medical degree  and a  doctoral degree  ( MD-PhD ). [ 1 ]   Internationally pulmonary scientists have many different titles, such as: pulmonary function technologist, respiratory scientist, pulmonary scientist, cardiopulmonary specialist and in some places  registered respiratory therapists  are also used in the role of pulmonary scientists.  A physician in respiratory science is generally referred to as a physician in their title (i.e. Respiratory Physician-Scientist). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5590", "contents": "Respiratory science is a diminishing field of study and research even though the increase in respiratory related disease is increasing. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5591", "contents": "In Australia there is no register or licensure for Respiratory Care; there is, however, the Certified Respiratory Function Scientist (CRFS) credential.  Australian respiratory therapy is done by physiotherapists who have further specialized in cardiopulmonary therapeutics and the scope not covered by physiotherapists are managed by specialized respiratory nurses.  The term Respiratory Scientist is used to describe the profession which is limited to  pulmonary function testing .  Though there is no official credentialing required, university degrees are required to practice."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5592", "contents": "The Respiratory Scientist is involved in all aspects of respiratory function assessment including patient testing, interpretation of test results, maintenance of equipment, development and evaluation of new methods and quality assurance. The Respiratory Scientist may work unsupervised in core areas and provide training to trainee scientists in these areas under the direction of a senior Respiratory Scientist.  Minimum education requirements for the CRFS credential is a  BSc  in Respiratory Physiology and Science but more likely a Masters or PhD in  Respiratory Science .  Australian credentialing is maintained by the  Australian & New Zealand Society of Respiratory Science .  Additionally, Respiratory Scientists in Australia act as consult clinicians for  pharmacists  in rural areas to improve respiratory function testing access. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5593", "contents": "In  Ireland  respiratory care practitioners are called Respiratory Scientists.  Their role is primarily that of the RRT-Sleep Disorders Specialist and the Registered Pulmonary Function Technologist.  The representative body is the  Irish Association of Respiratory Scientists ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5594", "contents": "The registered pulmonary function technologist in the  United States  is an advanced credential awarded by the  National Board for Respiratory Care .  Primarily the RPFT performs the technical function of  pulmonary function testing ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5595", "contents": "The certified pulmonary function technologist in the United States is an entry-level credential awarded by the National Board for Respiratory Care.  Much like the registered technologist/technician the CPFT performs pulmonary function testing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5596", "contents": "Pursed-lip breathing  ( PLB ) is a breathing technique that consists of  exhaling  through tightly pressed (pursed)  lips  and inhaling through the  nose  with the  mouth  closed."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5597", "contents": "Pursed-lip breathing can help to ease  shortness of breath  in people with a variety of lung problems. It can be used effectively during  asthma attacks  to slow breathing and reduce the work of breathing. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5598", "contents": "Physicians ,  nurses ,  physical therapists ,  occupational therapists , and  respiratory therapists  teach this technique to their patients to ease  shortness of breath  and to promote deep breathing, also referred to as abdominal or  diaphragmatic breathing . The purpose of PLB is to create back-pressure inside airways to splint them open; moving air thus takes less work. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5599", "contents": "Breathing through pursed lips on both exhalation and inhalation is one of the signs that health workers use to detect possible chronic obstructive pulmonary disease ( COPD ) in patients. COPD Canada suggests that using PLB has positive effects in treating stress- and anxiety-related disorders. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5600", "contents": "Pursed-lip breathing increases positive pressure generated in the conducting branches of the  lungs . [ 4 ]  This can hold open bronchioles in patients with high lung compliance, such as those with emphysema. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5601", "contents": "Pursed-lip breathing also accesses the  parasympathetic nervous system , which reduces stress during episodes of shortness of breath. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5602", "contents": "The  rapid shallow breathing index  (RSBI) or  Yang Tobin index  is a tool that is used in the weaning of  mechanical ventilation  on  intensive care units . The RSBI is defined as the ratio of  respiratory frequency  to  tidal volume  (f/VT). People on a ventilator who cannot tolerate independent breathing tend to breathe rapidly (high frequency) and shallowly (low tidal volume), and will therefore have a high RSBI. [ 1 ]   The index was introduced in 1991 by Karl Yang and  Martin J. Tobin ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5603", "contents": "R \n S \n B \n I \n = \n \n \n f \n \n V \n \n T \n \n \n \n \n \n \n {\\displaystyle RSBI={\\frac {f}{V_{T}}}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5604", "contents": "Measurement is done with a handheld  spirometer  attached to the  endotracheal tube  while a patient breathes room air for one minute without any ventilator assistance. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5605", "contents": "As an example, a patient who has a respiratory rate of 25 breaths/min and an average tidal volume of 250 mL/breath has an RSBI = (25 breaths/min)/(0.25 L) = 100 breaths/min/L."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5606", "contents": "In contrast, the 'average' patient breathing 12 breaths/min, with a tidal volume of 420 mL/breath (70kg x 6 mL/kg) would have an RSBI = (12 breaths/min)/(.420 L) = 28 breaths/min/L."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5607", "contents": "The higher the RSBI, the more distressed the patient is generally considered to be."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5608", "contents": "The concept was introduced in a 1991 paper by physicians Karl Yang and  Martin J. Tobin  from the  University of Texas Health Science Center at Houston  and  Stritch School of Medicine  at  Loyola University  in Chicago. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5609", "contents": "A RSBI score of less than 65 [ 3 ]  indicating a relatively low respiratory rate compared to tidal volume is generally considered as an indication of weaning readiness.\nA patient with a rapid shallow breathing index (RSBI) of less than 105 has an approximately 80% chance of being successfully extubated, whereas an RSBI of greater than 105 virtually guarantees weaning failure. [ 4 ] \nOther criteria that have been suggested for a successful weaning trial include the ability to (1) tolerate a  Spontaneous breathing trial  for 30 minutes (in most patients, SBT failure will occur within approximately 20 minutes), (2) maintain a respiration rate of less than 35/min, and (3) keep an oxygen saturation of 90% without arrhythmias; sudden increases in heart rate and blood pressure; or development of respiratory distress, diaphoresis, or anxiety. Once the SBT is tolerated, the ability to clear secretions, a decreasing secretion burden, and a patent upper airway are other criteria that should be met to increase extubation success.\nPatients should be assessed daily for their readiness to be weaned from mechanical ventilation by withdrawing sedation and performing a spontaneous breathing trial."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5610", "contents": "A  Respiratory Care Act  is a common term for a law enacted allowing for the practice of Respiratory Care in a given state, province, region or nation. [ 1 ]   The name of the law may differ slightly but typically Respiratory Care is the identifier title. [ 2 ] [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5611", "contents": "A board of respiratory care is typically a division of that states Department of Health, much like a Board of Nursing or Board of Medicine.  Granting licenses to applicants and reviewing policy related to practice and care.  [ 5 ] [ 6 ] [ 7 ] [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5612", "contents": "Medicare Respiratory Therapy Initiative Act - Amends title XVIII (Medicare) of the  Social Security Act  to cover the services of a qualified  respiratory practitioner  performed under the general supervision of a  physician . [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5613", "contents": "The  Respiratory Therapy Society of Ontario  is a non-profit organization of  respiratory therapists  and other healthcare professionals devoted to the promotion of  Respiratory Therapy  in the province of  Ontario ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5614", "contents": "Restrictive lung diseases   are a category of  extrapulmonary ,  pleural , or parenchymal  respiratory diseases  that restrict lung expansion, [ 2 ]  resulting in a decreased  lung volume , an increased work of  breathing , and inadequate  ventilation  and/or  oxygenation . Pulmonary function test demonstrates a decrease in the forced vital capacity."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5615", "contents": "Due to the chronic nature of this disease, the leading symptom of restrictive lung disease is progressive exertional dyspnea. [ 3 ] \u00a0 For acute on chronic cases,  shortness of breath ,  cough , and  respiratory failure  are some of the more common signs. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5616", "contents": "Restrictive lung diseases may be due to specific causes which can be intrinsic to the  parenchyma  of the lung, or extrinsic to it. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5617", "contents": "Many cases of restrictive lung disease are  idiopathic  (have no known cause). Still, there is generally  pulmonary fibrosis . [ 5 ]  Examples are:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5618", "contents": "Conditions specifically affecting the interstitium are called  interstitial lung diseases ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5619", "contents": "In normal respiratory function, the air flows in through the upper airway, down through the bronchi and into the lung parenchyma (the bronchioles down to the alveoli) where gas exchange of carbon dioxide and oxygen occurs. [ 7 ]  During inspiration, the lungs expand to allow airflow into the lungs and thereby increasing total volume. After inspiration follows expiration during which the lungs recoil and push air back out of the pulmonary pathway.\u00a0 Lung compliance  is the difference of volume during inspiration and expiration. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5620", "contents": "Restrictive lung disease is characterized by reduced lung volumes, and therefore reduced lung compliance, either due to an intrinsic reason, for example a change in the lung parenchyma, or due to an extrinsic reason, for example diseases of the chest wall, pleura, or respiratory muscles. [ 3 ]  Generally, intrinsic causes are from lung parenchyma diseases that cause inflammation or scarring of the lung tissue, such as interstitial lung disease or  pulmonary fibrosis , or from having the alveoli air spaces filled with external material such as debris or exudate in pneumonitis. [ 3 ]  As some diseases of the lung parenchyma progress, the normal lung tissue can be gradually replaced with scar tissue that is interspersed with pockets of air. [ 5 ]  This can lead to parts of the lung having a honeycomb-like appearance. The extrinsic causes result in lung restriction, impaired ventilatory function, and even respiratory failure due to the diseases that effect the lungs ability to create a change in lung volumes during respiration due to the diseases of the systems stated above. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5621", "contents": "In restrictive lung disease, both forced expiratory volume in one second ( FEV1 ) and  forced vital capacity  (FVC) are reduced, however, the decline in FVC is more than that of FEV1, resulting in a higher than 80%  FEV1/FVC ratio .\nIn  obstructive lung disease  however, the FEV1/FVC is less than 0.7, indicating that FEV1 is significantly reduced when compared to the total expired volume. This indicates that the FVC is also reduced, but not by the same ratio as FEV1. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5622", "contents": "One definition requires a  total lung capacity  which is 80% or less of the expected value. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5623", "contents": "Medical treatment for restrictive lung disease is normally limited to supportive care since both the intrinsic and extrinsic causes can have irreversible effects on lung compliance. [ 10 ]  The supportive therapies focus on maximizing pulmonary function and preserving activity tolerance through oxygen therapy, bronchodilators, inhaled beta-adrenergic agonists, and diuretics. [ 10 ]  Because there is no effective treatment for restrictive lung disease, prevention is key. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5624", "contents": "A  Sleep disorder specialist  ( SDS ) is a  Registered Respiratory Therapist  (RRT-SDS) that has successfully passed the certification examination  NBRC-SDS . [ 1 ]   The respiratory therapist may also be a  Certified Respiratory Therapist  (CRT-SDS) under certain conditions. [ 2 ]   The sleep disorder specialist scores and performs  polysomnography  and also assists in diagnosing and preparing a treatment plan for the condition.  Some of the conditions the sleep disorder specialist helps evaluate and treat are;  insomnia ,  sleep apnea ,  restless legs syndrome , and  narcolepsy ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5625", "contents": "Surfactant therapy  is the medical administration of pulmonary surfactant that is derived from outside of the body. Pulmonary surfactant is a soap-like chemical synthesized by type II alveolar pneumocytes and is of various lipids (80% phospholipids, 5-10% cholesterol, and \u223c10% surfactant-associated proteins). This biological fluid reduces surface tension and lines the aqueous layer covering the alveolar surface of the lung. For more details, see  Pulmonary surfactant .  [ 1 ] [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5626", "contents": "Surfactant therapy, or surfactant replacement therapy, is used in situations where there is not sufficient fluid covering the lung. The most common use is in premature neonates or babies born with  respiratory distress syndrome . Conditions  adult respiratory distress syndrome  or  Hyaline Membrane Disease  are also sometimes treated with exogenously derived surfactant. One of the more common uses of surfactant therapy is to treat alveolar surfactant deficiency in premature newborns. Most commonly, treatment is composed of multiple doses of 100 mg/kg of exogenous surfactant.  [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5627", "contents": "Poractant alfa ,  Calfactant , and  Beractant  are types of natural surfactants commercially available in the  United States .  Although data is sometimes conflicting, it appears that there are no significant differences among the available preparations. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5628", "contents": "The LISA (Less Invasive Surfactant Administration) method is much more effective in situations where the preterm infant is already breathing, and it has become a standard procedure in German hospitals. [ 4 ]  Intubation via mechanical ventilation is less effective than the LISA method within the first 72 hours of birth. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5629", "contents": "Exogenous surfactant replacement therapy is effective in reducing  IRDS  mortality and morbidity in preterm infants. [ 6 ] [ 7 ] [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5630", "contents": "Surfactant therapy is not used to treat adults with  adult respiratory distress syndrome  because the evidence regarding its effect on patient-important outcomes is inconsistent."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5631", "contents": "A  Thorpe tube flowmeter , a type of  variable-area flowmeter , or a  rotameter , is an instrument used to directly measure the flow rate of a gas in medical instruments. It consists of a connection to a gas source, a  needle valve  opened and closed by turning an attached dial for control of flow rate, a float resting in a clear tapered tube, and an outlet port. It is primarily used in health care institutions during delivery of medical gases, often in conjunction with other devices such as  pressure gauges  or  pressure reducing valves ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5632", "contents": "When a driving pressure is applied to the inlet of a Thorpe tube flowmeter, the ball rises in the tapered tube until the flow rate creates an applied pressure on the ball equal to its weight. The tube's shape, that of a slender cone, decreases the pressure behind the ball as it rises. A cylindrical tube would not permit driving pressure to decrease with flow rate, resulting in the ball rising to the top of the tube, and allowing for no variance in readings. The flow rate of a specific gas necessary to cause the float to rise to a given height is precalculated in order to calibrate a tube."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5633", "contents": "A variety of float shapes may be seen with older Thorpe tube flowmeters, and all floats should be read from the top of the float, except for the ball float, which is read from its center.  Floats should rotate in the airstream, and the absence of rotation may indicate faulty readings resulting from the float catching on the tube."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5634", "contents": "The needle valve may be located proximal or distal to the inlet port; these two types of flowmeter are respectively called 'non-compensated' or 'compensated'.  The original Thorpe tube flowmeter is the non-compensated type: it works with a fixed orifice and variable pressure. The non-compensated type is more accurate for low flow rates, such as are used in neonatal units, laboratory experiments, or  anaesthetic machines . Compensated flowmeters work with a variable orifice and fixed pressure.  They  read back pressure, and take into account resistance changes downstream from the needle valve.  If pressure exceeds 50 psig downstream, flow ceases."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5635", "contents": "The types can be distinguished by their response when gas starts to flow. In compensated flowmeters, the ball will initially jump as the gas flows through the tube before being released through the needle valve just before the outlet. No result will be observed in the non-compensated flow meter, as the gas will release before reaching the tapered tube containing the float."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5636", "contents": "Although Thorpe tube flowmeters are very similar in design and function to  rotameters , the latter are more accurate.  As a result, Thorpe tube flowmeters are often checked against rotameters to ensure their accuracy. Rotameters are also used on  anaesthesia  machines, where precise measurement of gas delivery is crucial to the wellbeing of the patient."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5637", "contents": "Thorpe tube flowmeters are designed for use only on systems not supplying more than 50 PSI ( about 3 bar). The flowmeters will be labelled for the gas they are specific to.  Additional color-coding may be used, for example, O 2  flowmeters may have white and green labels, since white and green are respectively the Canadian and American colours identifying this gas. The flowmeter will have a safety  Relief valve  to relieve excess pressure."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5638", "contents": "Inaccurate flow readings may occur if the device is damaged, or contaminated with water or debris. Flowmeters are only calibrated for a specified gas and will not directly read accurately on gases of different density. Changes in pressure or temperature will also affect the accuracy, and may be significant in  air transport , or cities at high altitudes. Flowmeters are only calibrated in the vertical position, and for flow rates less than 15 litres per minute."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5639", "contents": "Tracheal intubation , usually simply referred to as  intubation , is the placement of a flexible plastic  tube  into the  trachea  (windpipe) to maintain an open  airway  or to serve as a conduit through which to administer certain drugs. It is frequently performed in critically injured, ill, or anesthetized patients to facilitate  ventilation  of the lungs, including  mechanical ventilation , and to prevent the possibility of  asphyxiation  or airway obstruction."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5640", "contents": "The most widely used route is orotracheal, in which an  endotracheal tube  is passed through the mouth and  vocal apparatus  into the trachea. In a nasotracheal procedure, an endotracheal tube is passed through the nose and vocal apparatus into the trachea. Other methods of intubation involve surgery and include the  cricothyrotomy  (used almost exclusively in emergency circumstances) and the  tracheotomy , used primarily in situations where a prolonged need for airway support is anticipated."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5641", "contents": "Because it is an  invasive  and uncomfortable  medical procedure , intubation is usually performed after administration of  general anesthesia  and a  neuromuscular-blocking drug . It can, however, be performed in the awake patient with  local  or  topical anesthesia  or in an emergency without any anesthesia at all. Intubation is normally facilitated by using a conventional  laryngoscope ,  flexible fiberoptic bronchoscope , or  video laryngoscope  to identify the  vocal cords  and pass the tube between them into the  trachea  instead of into the esophagus. Other devices and techniques may be used alternatively."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5642", "contents": "After the trachea has been intubated, a balloon cuff is typically inflated just above the far end of the tube to help secure it in place, to prevent leakage of respiratory gases, and to protect the  tracheobronchial tree  from  receiving undesirable material  such as stomach acid. The tube is then secured to the face or neck and connected to a T-piece, anesthesia breathing circuit,  bag valve mask  device, or a  mechanical ventilator . Once there is no longer a need for ventilatory assistance or protection of the airway, the tracheal tube is removed; this is referred to as extubation of the trachea (or decannulation, in the case of a surgical airway such as a cricothyrotomy or a tracheotomy)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5643", "contents": "For centuries,  tracheotomy  was considered the only reliable method for intubation of the trachea. However, because only a minority of patients survived the operation, physicians undertook tracheotomy only as a last resort, on patients who were nearly dead. It was not until the late 19th century, however, that advances in understanding of  anatomy  and  physiology , as well an appreciation of the  germ theory of disease , had improved the outcome of this operation to the point that it could be considered an acceptable treatment option. Also at that time, advances in  endoscopic  instrumentation had improved to such a degree that direct laryngoscopy had become a viable means to secure the airway by the non-surgical orotracheal route. By the mid-20th century, the tracheotomy as well as endoscopy and non-surgical tracheal intubation had evolved from rarely employed procedures to becoming essential components of the practices of  anesthesiology ,  critical care medicine ,  emergency medicine , and  laryngology ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5644", "contents": "Tracheal intubation can be associated with  complications  such as broken teeth or lacerations of the  tissues  of the  upper airway . It can also be associated with potentially fatal complications such as  pulmonary aspiration  of stomach contents which can result in a severe and sometimes fatal chemical  aspiration pneumonitis , or unrecognized intubation of the  esophagus  which can lead to potentially fatal  anoxia . Because of this, the potential for difficulty or complications due to the presence of unusual airway anatomy or other uncontrolled variables is carefully evaluated before undertaking tracheal intubation. Alternative strategies for securing the airway must always be readily available."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5645", "contents": "Tracheal intubation is  indicated  in a variety of situations when illness or a medical procedure prevents a person from maintaining a clear airway, breathing, and  oxygenating  the blood. In these circumstances,  oxygen supplementation  using a  simple face mask  is inadequate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5646", "contents": "Perhaps the most common indication for tracheal intubation is for the placement of a conduit through which  nitrous oxide  or  volatile anesthetics  may be administered.  General anesthetic agents ,  opioids , and neuromuscular-blocking drugs may  diminish  or even  abolish  the  respiratory drive . Although it is not the only means to maintain a patent airway during general anesthesia, intubation of the trachea provides the most reliable means of oxygenation and  ventilation [ 1 ]  and the greatest degree of protection against regurgitation and pulmonary aspiration. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5647", "contents": "Damage to the brain (such as from a massive  stroke ,  non-penetrating head injury ,  intoxication  or  poisoning ) may result in a  depressed level of consciousness . When this becomes severe to the point of  stupor  or  coma  (defined as a score on the  Glasgow Coma Scale  of less than 8), [ 3 ]  dynamic collapse of the extrinsic  muscles of the airway  can obstruct the airway, impeding the free flow of air into the lungs. Furthermore, protective airway reflexes such as  coughing  and  swallowing  may be diminished or absent. Tracheal intubation is often required to restore patency (the relative absence of blockage) of the airway and protect the tracheobronchial tree from pulmonary aspiration of gastric contents. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5648", "contents": "Intubation may be necessary for a patient with  decreased oxygen content  and  oxygen saturation  of the blood caused when their breathing is inadequate ( hypoventilation ), suspended ( apnea ), or when the lungs are unable to sufficiently  transfer gasses to the blood . [ 5 ]  Such patients, who may be awake and alert, are typically critically ill with a multisystem disease or  multiple severe injuries . [ 1 ]  Examples of such conditions include  cervical spine injury ,  multiple rib fractures , severe  pneumonia ,  acute respiratory distress syndrome  (ARDS), or near- drowning . Specifically, intubation is considered if the  arterial   partial pressure  of oxygen (PaO 2 ) is less than 60\u00a0 millimeters of mercury  (mm Hg) while breathing an inspired O 2  concentration ( FIO 2 ) of 50% or greater. In patients with  elevated arterial carbon dioxide , an arterial partial pressure of CO 2  (PaCO 2 ) greater than 45\u00a0mm Hg in the setting of  acidemia  would prompt intubation, especially if a series of measurements demonstrate a worsening  respiratory acidosis . Regardless of the laboratory values, these guidelines are always interpreted in the clinical context. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5649", "contents": "Actual or impending airway obstruction is a common indication for intubation of the trachea. Life-threatening airway obstruction may occur when a  foreign body  becomes lodged in the airway; this is especially common in infants and toddlers. Severe  blunt  or  penetrating  injury to the face or neck may be accompanied by  swelling  and an expanding  hematoma , or injury to the  larynx, trachea or bronchi . Airway obstruction is also common in people who have suffered  smoke inhalation  or burns within or near the airway or  epiglottitis . Sustained  generalized seizure activity  and  angioedema  are other common causes of life-threatening airway obstruction which may require tracheal intubation to secure the airway. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5650", "contents": "Diagnostic or therapeutic manipulation of the airway (such as bronchoscopy,  laser therapy  or  stenting  of the  bronchi ) may intermittently interfere with the ability to breathe; intubation may be necessary in such situations. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5651", "contents": "Syndromes such as  respiratory distress syndrome ,  congenital heart disease ,  pneumothorax , and  shock  may lead to breathing problems in newborn infants that require endotracheal intubation and mechanically assisted breathing ( mechanical ventilation ). [ 7 ]  Newborn infants may also require endotracheal intubation during surgery while under  general anaesthesia . [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5652", "contents": "The vast majority of tracheal intubations involve the use of a  viewing instrument  of one type or another. The modern conventional laryngoscope consists of a handle containing batteries that power a light and a set of interchangeable  blades , which are either straight or curved. This device is designed to allow the laryngoscopist to directly view the larynx. Due to the widespread availability of such devices, the technique of blind intubation [ 8 ]  of the trachea is rarely practiced today, although it may still be useful in certain emergency situations, such as natural or man-made disasters. [ 9 ]  In the prehospital emergency setting, digital intubation may be necessitated if the patient is in a position that makes direct laryngoscopy impossible. For example, digital intubation may be used by a paramedic if the patient is entrapped in an inverted position in a vehicle after a motor vehicle collision with a prolonged extrication time."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5653", "contents": "The decision to use a straight or curved laryngoscope blade depends partly on the specific anatomical features of the airway, and partly on the personal experience and preference of the laryngoscopist. The Miller blade, characterized by its straight, elongated shape with a curved tip, is frequently employed in patients with challenging airway anatomy, such as those with limited mouth opening or a high larynx. Its design allows for direct visualization of the epiglottis, facilitating precise glottic exposure. [ 10 ] \nConversely, the Macintosh blade, with its curved configuration reminiscent of the letters \"C\" or \"J,\" is favored in routine intubations for patients with normal airway anatomy. Its curved design enables indirect laryngoscopy, providing enhanced visualization of the vocal cords and glottis in most adult patients. [ 11 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5654", "contents": "The choice between the Miller and Macintosh blades is influenced by specific anatomical considerations and the preferences of the laryngoscopist. While the Macintosh blade is the most commonly utilized curved laryngoscope blade, the Miller blade is the preferred option for straight blade intubation. Both blades are available in various sizes, ranging from size 0 (infant) to size 4 (large adult), catering to patients of different ages and anatomies. Additionally, there exists a myriad of specialty blades with unique features, including mirrors for enhanced visualization and ports for oxygen administration, primarily utilized by anesthetists and otolaryngologists in operating room settings. [ 12 ] [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5655", "contents": "Fiberoptic  laryngoscopes have become increasingly available since the 1990s. In contrast to the conventional laryngoscope, these devices allow the laryngoscopist to indirectly view the larynx. This provides a significant advantage in situations where the operator needs to see around an acute bend in order to visualize the glottis, and deal with otherwise difficult intubations.  Video laryngoscopes  are specialized fiberoptic laryngoscopes that use a  digital   video camera sensor  to allow the operator to view the glottis and larynx on a video monitor. [ 13 ] [ 14 ]  Other \"noninvasive\" devices which can be employed to assist in tracheal intubation are the  laryngeal mask airway [ 15 ]  (used as a conduit for endotracheal tube placement) and the  Airtraq . [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5656", "contents": "An intubating stylet is a malleable metal wire designed to be inserted into the endotracheal tube to make the tube conform better to the upper airway anatomy of the specific individual. This aid is commonly used with a difficult laryngoscopy. Just as with laryngoscope blades, there are also several types of available stylets, [ 17 ]  such as the Verathon Stylet, which is specifically designed to follow the 60\u00b0 blade angle of the GlideScope video laryngoscope. [ 18 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5657", "contents": "The Eschmann tracheal tube introducer (also referred to as a \"gum elastic bougie\") is specialized type of stylet used to facilitate difficult intubation. [ 19 ]  This flexible device is 60\u00a0cm (24\u00a0in) in length, 15  French  (5\u00a0mm diameter) with a small \"hockey-stick\" angle at the far end. Unlike a traditional intubating stylet, the Eschmann tracheal tube introducer is typically inserted directly into the trachea and then used as a guide over which the endotracheal tube can be passed (in a manner analogous to the  Seldinger technique ). As the Eschmann tracheal tube introducer is considerably less rigid than a conventional stylet, this technique is considered to be a relatively atraumatic means of tracheal intubation. [ 20 ] [ 21 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5658", "contents": "The tracheal tube exchanger is a hollow  catheter , 56 to 81\u00a0cm (22.0 to 31.9\u00a0in) in length, that can be used for removal and replacement of tracheal tubes without the need for laryngoscopy. [ 22 ]  The Cook Airway Exchange Catheter (CAEC) is another example of this type of catheter; this device has a central  lumen  (hollow channel) through which  oxygen can be administered . [ 23 ]  Airway exchange catheters are long hollow catheters which often have connectors for jet ventilation, manual ventilation, or oxygen insufflation.\u00a0It is also possible to connect the catheter to a capnograph to perform respiratory monitoring."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5659", "contents": "The lighted stylet is a device that employs the principle of  transillumination  to facilitate blind orotracheal intubation (an intubation technique in which the laryngoscopist does not view the glottis). [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5660", "contents": "A tracheal tube is a catheter that is inserted into the trachea for the primary purpose of establishing and maintaining a patent (open and unobstructed) airway. Tracheal tubes are frequently used for  airway management  in the settings of general anesthesia, critical care, mechanical ventilation, and emergency medicine. Many different types of tracheal tubes are available, suited for different specific applications. An endotracheal tube is a specific type of tracheal tube that is nearly always inserted through the mouth (orotracheal) or nose (nasotracheal). It is a  breathing  conduit designed to be placed into the airway of critically injured, ill or anesthetized patients in order to perform mechanical  positive pressure ventilation  of the lungs and to prevent the possibility of aspiration or airway obstruction. [ 25 ]  The endotracheal tube has a fitting designed to be connected to a source of pressurized gas such as oxygen. At the other end is an orifice through which such gases are directed into the lungs and may also include a balloon (referred to as a cuff). The tip of the endotracheal tube is positioned above the  carina  (before the trachea divides to each lung) and sealed within the trachea so that the lungs can be ventilated equally. [ 25 ]  A tracheostomy tube is another type of tracheal tube; this 50\u201375-millimetre-long (2.0\u20133.0\u00a0in) curved metal or plastic tube is inserted into a tracheostomy  stoma  or a cricothyrotomy incision. [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5661", "contents": "Tracheal tubes can be used to ensure the adequate  exchange  of oxygen and  carbon dioxide , to deliver oxygen in higher concentrations than found in air, or to administer other gases such as  helium , [ 27 ]   nitric oxide , [ 28 ]  nitrous oxide,  xenon , [ 29 ]  or certain volatile anesthetic agents such as  desflurane ,  isoflurane , or  sevoflurane . They may also be used as a route for administration of certain medications such as  bronchodilators ,  inhaled corticosteroids , and drugs used in treating  cardiac arrest  such as  atropine ,  epinephrine ,  lidocaine  and  vasopressin . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5662", "contents": "Originally made from  latex rubber , [ 30 ]  most modern endotracheal tubes today are constructed of  polyvinyl chloride . Tubes constructed of  silicone rubber , wire-reinforced silicone rubber or  stainless steel  are also available for special applications. For human use, tubes range in size from 2 to 10.5\u00a0mm (0.1 to 0.4\u00a0in) in internal diameter. The size is chosen based on the patient's body size, with the smaller sizes being used for infants and children. Most endotracheal tubes have an inflatable cuff to seal the tracheobronchial tree against leakage of respiratory gases and pulmonary aspiration of gastric contents, blood, secretions, and other fluids. Uncuffed tubes are also available, though their use is limited mostly to children (in small children, the  cricoid cartilage  is the narrowest portion of the airway and usually provides an adequate seal for mechanical ventilation). [ 13 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5663", "contents": "In addition to cuffed or uncuffed, preformed endotracheal tubes are also available. The oral and nasal RAE tubes (named after the inventors Ring, Adair and Elwyn) are the most widely used of the preformed tubes. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5664", "contents": "There are a number of different types of  double-lumen endo-bronchial tubes  that have endobronchial as well as endotracheal channels (Carlens, White and Robertshaw tubes). These tubes are typically  coaxial , with two separate channels and two separate openings. They incorporate an endotracheal lumen which terminates in the trachea and an endobronchial lumen, the distal tip of which is positioned 1\u20132\u00a0cm into the right or left mainstem bronchus. There is also the Univent tube, which has a single tracheal lumen and an integrated  endobronchial blocker . These tubes enable one to ventilate both lungs, or either lung independently. Single-lung ventilation (allowing the lung on the operative side to collapse) can be useful during  thoracic surgery , as it can facilitate the surgeon's view and access to other relevant structures within the  thoracic cavity . [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5665", "contents": "The \"armored\" endotracheal tubes are cuffed, wire-reinforced silicone rubber tubes. They are much more flexible than polyvinyl chloride tubes, yet they are difficult to compress or kink. This can make them useful for situations in which the trachea is anticipated to remain intubated for a prolonged duration, or if the neck is to remain flexed during surgery. Most armored tubes have a Magill curve, but preformed armored RAE tubes are also available. Another type of endotracheal tube has four small openings just above the inflatable cuff, which can be used for suction of the trachea or administration of intratracheal medications if necessary. Other tubes (such as the Bivona Fome-Cuf tube) are designed specifically for use in laser surgery in and around the airway. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5666", "contents": "No single method for confirming tracheal tube placement has been shown to be 100% reliable. Accordingly, the use of multiple methods for confirmation of correct tube placement is now widely considered to be the  standard of care . [ 34 ]  Such methods include direct visualization as the tip of the tube passes through the glottis, or indirect visualization of the tracheal tube within the trachea using a device such as a bronchoscope. With a properly positioned tracheal tube, equal bilateral  breath sounds  will be heard upon  listening to  the chest with a stethoscope, and no sound upon listening to the area  over the stomach . Equal bilateral rise and fall of the chest wall will be evident with ventilatory excursions. A small amount of  water vapor  will also be evident within the lumen of the tube with each exhalation and there will be no gastric contents in the tracheal tube at any time. [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5667", "contents": "Ideally, at least one of the methods utilized for confirming tracheal tube placement will be a  measuring instrument . Waveform  capnography  has emerged as the  gold standard  for the confirmation of tube placement within the trachea. Other methods relying on instruments include the use of a  colorimetric  end-tidal carbon dioxide detector, a self-inflating esophageal bulb, or an esophageal detection device. [ 35 ]  The distal tip of a properly positioned tracheal tube will be located in the mid-trachea, roughly 2\u00a0cm (1\u00a0in) above the bifurcation of the carina; this can be confirmed by  chest x-ray . If it is inserted too far into the trachea (beyond the carina), the tip of the tracheal tube is likely to be within the  right main bronchus \u2014a situation often referred to as a \"right mainstem intubation\". In this situation, the left lung may be unable to participate in ventilation, which can lead to  decreased oxygen content  due to  ventilation/perfusion mismatch . [ 36 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5668", "contents": "Tracheal intubation in the emergency setting can be difficult with the fiberoptic bronchoscope due to blood, vomit, or  secretions  in the airway and poor patient cooperation. Because of this, patients with massive facial injury, complete upper airway obstruction, severely diminished ventilation, or profuse upper airway bleeding are poor candidates for fiberoptic intubation. [ 37 ]  Fiberoptic intubation under general anesthesia typically requires two skilled individuals. [ 38 ]  Success rates of only 83\u201387% have been reported using fiberoptic techniques in the emergency department, with significant  nasal bleeding  occurring in up to 22% of patients. [ 39 ] [ 40 ]  These drawbacks limit the use of fiberoptic bronchoscopy somewhat in urgent and emergency situations. [ 41 ] [ 42 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5669", "contents": "Personnel experienced in direct laryngoscopy are not always immediately available in certain settings that require emergency tracheal intubation. For this reason, specialized devices have been designed to act as bridges to a definitive airway. Such devices include the laryngeal mask airway, cuffed  oropharyngeal  airway and the esophageal-tracheal combitube ( Combitube ). [ 43 ] [ 44 ]  Other devices such as rigid stylets, the lightwand (a blind technique) and indirect fiberoptic rigid stylets, such as the Bullard scope, Upsher scope and the WuScope can also be used as alternatives to direct laryngoscopy. Each of these devices have its own unique set of benefits and drawbacks, and none of them is effective under all circumstances. [ 17 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5670", "contents": "Rapid sequence induction and intubation (RSI) is a particular method of induction of general anesthesia, commonly employed in emergency operations and other situations where patients are assumed to have a full stomach. The objective of RSI is to minimize the possibility of  regurgitation  and pulmonary aspiration of gastric contents during the induction of general anesthesia and subsequent tracheal intubation. [ 34 ]  RSI traditionally involves preoxygenating the lungs with a tightly fitting oxygen mask, followed by the sequential administration of an intravenous  sleep-inducing  agent and a rapidly acting neuromuscular-blocking drug, such as  rocuronium ,  succinylcholine , or  cisatracurium besilate , before intubation of the trachea. [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5671", "contents": "One important difference between RSI and routine tracheal intubation is that the practitioner does not manually assist the ventilation of the lungs after the onset of general anesthesia and  cessation of breathing , until the trachea has been intubated and the cuff has been inflated. Another key feature of RSI is the application of manual ' cricoid pressure ' to the cricoid cartilage, often referred to as the \"Sellick maneuver\", prior to instrumentation of the airway and intubation of the trachea. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5672", "contents": "Named for British anesthetist Brian Arthur Sellick (1918\u20131996) who first described the procedure in 1961, [ 46 ]  the goal of cricoid pressure is to minimize the possibility of regurgitation and pulmonary aspiration of gastric contents. Cricoid pressure has been widely used during RSI for nearly fifty years, despite a lack of compelling evidence to support this practice. [ 47 ]  The initial article by Sellick was based on a small sample size at a time when high  tidal volumes ,  head-down positioning  and  barbiturate  anesthesia were the rule. [ 48 ]  Beginning around 2000, a significant body of evidence has accumulated which questions the effectiveness of cricoid pressure. The application of cricoid pressure may in fact displace the esophagus laterally [ 49 ]  instead of compressing it as described by Sellick. Cricoid pressure may also compress the glottis, which can obstruct the view of the laryngoscopist and actually cause a delay in securing the airway. [ 50 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5673", "contents": "Cricoid pressure is often confused with the \"BURP\" (Backwards Upwards Rightwards Pressure) maneuver. [ 51 ]  While both of these involve digital pressure to the anterior aspect (front) of the laryngeal apparatus, the purpose of the latter is to improve the view of the glottis during laryngoscopy and tracheal intubation, rather than to prevent regurgitation. [ 52 ]  Both cricoid pressure and the BURP maneuver have the potential to worsen laryngoscopy. [ 53 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5674", "contents": "RSI may also be used in prehospital emergency situations when a patient is conscious but respiratory failure is imminent (such as in extreme trauma). This procedure is commonly performed by flight paramedics. Flight paramedics often use RSI to intubate before transport because intubation in a moving fixed-wing or rotary-wing aircraft is extremely difficult to perform due to environmental factors. The patient will be paralyzed and intubated on the ground before transport by aircraft."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5675", "contents": "A cricothyrotomy is an incision made through the skin and  cricothyroid membrane  to establish a patent airway during certain life-threatening situations, such as airway obstruction by a foreign body, angioedema, or massive facial trauma. [ 54 ]  A cricothyrotomy is nearly always performed as a last resort in cases where orotracheal and nasotracheal intubation are impossible or contraindicated. Cricothyrotomy is easier and quicker to perform than tracheotomy, does not require manipulation of the cervical spine and is associated with fewer complications. [ 55 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5676", "contents": "The easiest method to perform this technique is the needle cricothyrotomy (also referred to as a  percutaneous  dilational cricothyrotomy), in which a large-bore (12\u201314  gauge )  intravenous catheter  is used to puncture the cricothyroid membrane. [ 56 ]  Oxygen can then be administered through this catheter via  jet insufflation . However, while needle cricothyrotomy may be life-saving in extreme circumstances, this technique is only intended to be a temporizing measure until a definitive airway can be established. [ 57 ]  While needle cricothyrotomy can provide adequate oxygenation, the small diameter of the cricothyrotomy catheter is insufficient for elimination of carbon dioxide (ventilation). After one hour of  apneic oxygenation  through a needle cricothyrotomy, one can expect a  PaCO 2  of greater than 250\u00a0mm Hg and an arterial  pH  of less than 6.72, despite an oxygen saturation of 98% or greater. [ 58 ]  A more definitive airway can be established by performing a surgical cricothyrotomy, in which a 5 to 6\u00a0mm (0.20 to 0.24\u00a0in) endotracheal tube or tracheostomy tube can be inserted through a larger incision. [ 59 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5677", "contents": "Several manufacturers market prepackaged cricothyrotomy kits, which enable one to use either a wire-guided percutaneous dilational (Seldinger) technique, or the classic surgical technique to insert a polyvinylchloride catheter through the cricothyroid membrane. The kits may be stocked in hospital emergency departments and operating suites, as well as ambulances and other selected  pre-hospital  settings. [ 60 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5678", "contents": "Tracheotomy consists of making an incision on the front of the neck and opening a direct airway through an incision in the trachea. The resulting  opening  can serve independently as an airway or as a site for a tracheostomy tube to be inserted; this tube allows a person to breathe without the use of his nose or mouth. The opening may be made by a scalpel or a needle (referred to as surgical [ 59 ]  and percutaneous [ 61 ]  techniques respectively) and both techniques are widely used in current practice. In order to limit the risk of damage to the  recurrent laryngeal nerves  (the nerves that control the  voice box ), the tracheotomy is performed as high in the trachea as possible. If only one of these nerves is damaged, the patient's voice may be impaired ( dysphonia ); if both of the nerves are damaged, the patient will be unable to speak ( aphonia ). In the acute setting, indications for tracheotomy are similar to those for cricothyrotomy. In the chronic setting, indications for tracheotomy include the need for long-term mechanical ventilation and removal of tracheal secretions (e.g., comatose patients, or extensive surgery involving the head and neck). [ 62 ] [ 63 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5679", "contents": "There are significant differences in airway anatomy and respiratory physiology between children and adults, and these are taken into careful consideration before performing tracheal intubation of any  pediatric  patient. The differences, which are quite significant in infants, gradually disappear as the human body approaches a mature age and  body mass index . [ 64 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5680", "contents": "For infants and young children, orotracheal intubation is easier than the nasotracheal route. Nasotracheal intubation carries a risk of dislodgement of  adenoids  and nasal bleeding. Despite the greater difficulty, nasotracheal intubation route is preferable to orotracheal intubation in children undergoing intensive care and requiring prolonged intubation because this route allows a more secure fixation of the tube. As with adults, there are a number of devices specially designed for assistance with difficult tracheal intubation in children. [ 65 ] [ 66 ] [ 67 ] [ 68 ]  Confirmation of proper position of the tracheal tube is accomplished as with adult patients. [ 69 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5681", "contents": "Because the airway of a child is narrow, a small amount of glottic or tracheal  swelling  can produce critical obstruction. Inserting a tube that is too large relative to the diameter of the trachea can cause swelling. Conversely, inserting a tube that is too small can result in inability to achieve effective positive pressure ventilation due to retrograde escape of gas through the glottis and out the mouth and nose (often referred to as a \"leak\" around the tube). An excessive leak can usually be corrected by inserting a larger tube or a cuffed tube. [ 70 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5682", "contents": "The tip of a correctly positioned tracheal tube will be in the mid-trachea, between the  collarbones  on an  anteroposterior  chest radiograph. The correct diameter of the tube is that which results in a small leak at a pressure of about 25\u00a0cm (10\u00a0in) of water. The appropriate inner diameter for the endotracheal tube is estimated to be roughly the same diameter as the child's little finger. The appropriate length for the endotracheal tube can be estimated by doubling the distance from the corner of the child's mouth to the  ear canal . For  premature infants  2.5\u00a0mm (0.1\u00a0in) internal diameter is an appropriate size for the tracheal tube. For infants of normal  gestational age , 3\u00a0mm (0.12\u00a0in) internal diameter is an appropriate size. For normally nourished children 1\u00a0year of age and older, two formulae are used to estimate the appropriate diameter and depth for tracheal intubation. The internal diameter of the tube in mm is (patient's age in years + 16) / 4, while the appropriate depth of insertion in cm is 12 + (patient's age in years / 2). [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5683", "contents": "Endotrachael suctioning is often used during intubation in newborn infants to reduce the risk of a blocked tube due to secretions, a collapsed lung, and to reduce pain. [ 7 ]  Suctioning is sometimes used at specifically scheduled intervals, \"as needed\", and less frequently. Further research is necessary to determine the most effective suctioning schedule or frequency of suctioning in intubated infants. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5684", "contents": "In newborns free flow  oxygen  used to be recommended during intubation however as there is no evidence of benefit the 2011  NRP guidelines  no longer do. [ 71 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5685", "contents": "Tracheal intubation is not a simple procedure and the consequences of failure are grave. Therefore, the patient is carefully evaluated for potential difficulty or complications beforehand. This involves taking the  medical history  of the patient and performing a  physical examination , the results of which can be scored against one of several classification systems. The proposed surgical procedure (e.g., surgery involving the head and neck, or  bariatric surgery ) may lead one to anticipate difficulties with intubation. [ 34 ]  Many individuals have unusual airway anatomy, such as those who have limited movement of their neck or jaw, or those who have tumors, deep swelling  due to injury  or  to allergy , developmental abnormalities of the jaw, or excess fatty tissue of the face and neck. Using conventional laryngoscopic techniques, intubation of the trachea can be difficult or even impossible in such patients. This is why all persons performing tracheal intubation must be familiar with alternative techniques of securing the airway. Use of the flexible fiberoptic bronchoscope and similar devices has become among the preferred techniques in the management of such cases. However, these devices require a different skill set than that employed for conventional laryngoscopy and are expensive to purchase, maintain and repair. [ 72 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5686", "contents": "When taking the patient's medical history, the subject is questioned about any significant  signs  or  symptoms , such as  difficulty in speaking  or  difficulty in breathing . These may suggest obstructing  lesions  in various locations within the upper airway,  larynx , or tracheobronchial tree. A history of previous surgery (e.g., previous  cervical fusion ), injury,  radiation therapy , or  tumors  involving the head, neck and  upper chest  can also provide clues to a potentially difficult intubation. Previous experiences with tracheal intubation, especially difficult intubation, intubation for prolonged duration (e.g., intensive care unit) or prior tracheotomy are also noted. [ 34 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5687", "contents": "A detailed  physical examination  of the airway is important, particularly: [ 73 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5688", "contents": "Many classification systems have been developed in an effort to predict difficulty of tracheal intubation, including the  Cormack-Lehane classification system , [ 74 ]  the Intubation Difficulty Scale (IDS), [ 75 ]  and the  Mallampati score . [ 76 ]  The Mallampati score is drawn from the observation that the size of the  base of the tongue  influences the difficulty of intubation. It is determined by looking at the anatomy of the mouth, and in particular the visibility of the base of  palatine uvula ,  faucial pillars  and the  soft palate . Although such medical scoring systems may aid in the evaluation of patients, no single score or combination of scores can be trusted to specifically detect all and only those patients who are difficult to intubate. [ 77 ] [ 78 ]  Furthermore, one study of experienced anesthesiologists, on the widely used Cormack\u2013Lehane classification system, found they did not score the same patients consistently over time, and that only 25% could correctly define all four grades of the widely used Cormack\u2013Lehane classification system. [ 79 ]  Under certain emergency circumstances (e.g., severe head trauma or suspected cervical spine injury), it may be impossible to fully utilize these the physical examination and the various classification systems to predict the difficulty of tracheal intubation. [ 80 ]  A Cochrane systematic review examined the sensitivity and specificity of various bedside tests commonly used for predicting difficulty in airway management. [ 81 ]  In such cases, alternative techniques of securing the airway must be readily available. [ 82 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5689", "contents": "Tracheal intubation is generally considered the best method for airway management under a wide variety of circumstances, as it provides the most reliable means of oxygenation and ventilation and the greatest degree of protection against regurgitation and pulmonary aspiration. [ 2 ]  However, tracheal intubation requires a great deal of clinical experience to master [ 83 ]  and serious complications may result even when properly performed. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5690", "contents": "Four anatomic features must be present for orotracheal intubation to be straightforward: adequate mouth opening (full range of motion of the temporomandibular joint), sufficient pharyngeal space (determined by examining the  back of the mouth ), sufficient submandibular space (distance between the thyroid cartilage and the chin, the space into which the tongue must be displaced in order for the larygoscopist to view the glottis), and adequate extension of the cervical spine at the atlanto-occipital joint. If any of these variables is in any way compromised, intubation should be expected to be difficult. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5691", "contents": "Minor complications are common after laryngoscopy and insertion of an orotracheal tube. These are typically of short duration, such as sore throat, lacerations of the lips or  gums  or other structures within the upper airway, chipped, fractured or dislodged teeth, and nasal injury. Other complications which are common but potentially more serious include  accelerated  or  irregular  heartbeat,  high blood pressure , elevated  intracranial  and  introcular  pressure, and  bronchospasm . [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5692", "contents": "More serious complications include  laryngospasm ,  perforation of the trachea  or  esophagus , pulmonary aspiration of gastric contents or other foreign bodies, fracture or dislocation of the cervical spine,  temporomandibular joint  or  arytenoid cartilages , decreased oxygen content,  elevated arterial carbon dioxide , and  vocal cord weakness . [ 84 ]  In addition to these complications, tracheal intubation via the nasal route carries a risk of dislodgement of adenoids and potentially severe nasal bleeding. [ 39 ] [ 40 ]  Newer technologies such as flexible fiberoptic laryngoscopy have fared better in reducing the incidence of some of these complications, though the most frequent cause of intubation trauma remains a lack of skill on the part of the laryngoscopist. [ 84 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5693", "contents": "Complications may also be severe and long-lasting or permanent, such as vocal cord damage, esophageal perforation and  retropharyngeal abscess , bronchial intubation, or nerve injury. They may even be immediately life-threatening, such as laryngospasm and negative pressure  pulmonary edema  (fluid in the lungs), aspiration, unrecognized esophageal intubation, or accidental disconnection or dislodgement of the tracheal tube. [ 84 ]  Potentially fatal complications more often associated with prolonged intubation or tracheotomy include abnormal communication between the trachea and nearby structures such as the  innominate artery  (tracheoinnominate  fistula ) or esophagus ( tracheoesophageal fistula ). Other significant complications include airway obstruction due to  loss of tracheal rigidity ,  ventilator-associated pneumonia  and  narrowing  of the glottis or trachea. [ 33 ]  The cuff pressure is monitored carefully in order to avoid complications from over-inflation, many of which can be traced to excessive cuff pressure  restricting the blood supply to  the tracheal mucosa. [ 85 ] [ 86 ]  A 2000 Spanish study of bedside percutaneous tracheotomy reported overall complication rates of 10\u201315% and procedural mortality of 0%, [ 61 ]  which is comparable to those of other series reported in the literature from the Netherlands [ 87 ]  and the United States. [ 88 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5694", "contents": "Inability to secure the airway, with subsequent failure of oxygenation and ventilation is a life-threatening complication which if not immediately corrected leads to  decreased oxygen content , brain damage,  cardiovascular collapse , and death. [ 84 ]  When performed improperly, the associated complications (e.g., unrecognized esophageal intubation) may be rapidly fatal. [ 89 ]  Without adequate training and experience, the incidence of such complications is high. [ 2 ]  The case of Andrew Davis Hughes, from Emerald Isle, NC is a widely known case in which the patient was improperly intubated and, due to the lack of oxygen, sustained severe brain damage and died. For example, among  paramedics  in several United States urban communities, unrecognized esophageal or  hypopharyngeal  intubation has been reported to be 6% [ 90 ] [ 91 ]  to 25%. [ 89 ]  Although not common, where basic  emergency medical technicians  are permitted to intubate, reported success rates are as low as 51%. [ 92 ]  In one study, nearly half of patients with misplaced tracheal tubes died in the emergency room. [ 89 ]  Because of this, the  American Heart Association 's  Guidelines for Cardiopulmonary Resuscitation  have de-emphasized the role of tracheal intubation in favor of other airway management techniques such as bag-valve-mask ventilation, the laryngeal mask airway and the Combitube. [ 2 ]   Higher quality studies demonstrate favorable evidence for this shift, as they have shown no survival or neurological benefit with endotracheal intubation over supraglottic airway devices (Laryngeal mask or Combitube). [ 93 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5695", "contents": "One complication\u2014unintentional and unrecognized intubation of the esophagus\u2014is both common (as frequent as 25% in the hands of inexperienced personnel) [ 89 ]  and likely to result in a deleterious or even fatal outcome. In such cases, oxygen is inadvertently administered to the stomach, from where it cannot be taken up by the  circulatory system , instead of the lungs. If this situation is not immediately identified and corrected, death will ensue from cerebral and cardiac anoxia."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5696", "contents": "Of 4,460 claims in the  American Society of Anesthesiologists  (ASA) Closed Claims Project database, 266 (approximately 6%) were for airway injury. Of these 266 cases, 87% of the injuries were temporary, 5% were permanent or disabling, and 8% resulted in death. Difficult intubation, age older than 60 years, and female gender were associated with claims for perforation of the esophagus or pharynx. Early signs of perforation were present in only 51% of perforation claims, whereas late  sequelae  occurred in 65%. [ 94 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5697", "contents": "During the  SARS  and  COVID-19 pandemics , tracheal intubation has been used with a  ventilator  in severe cases where the patient struggles to breathe. Performing the procedure carries a risk of the caregiver becoming infected. [ 95 ] [ 96 ] [ 97 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5698", "contents": "Although it offers the greatest degree of protection against regurgitation and pulmonary aspiration, tracheal intubation is not the only means to maintain a patent airway. Alternative techniques for airway management and delivery of oxygen, volatile anesthetics or other  breathing gases  include the  laryngeal mask airway , i-gel, cuffed oropharyngeal airway,  continuous positive airway pressure  (CPAP mask), nasal  BiPAP  mask, simple face mask, and nasal cannula. [ 98 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5699", "contents": "General anesthesia is often administered without tracheal intubation in selected cases where the procedure is brief in duration, or procedures where the depth of anesthesia is not sufficient to cause significant compromise in ventilatory function. Even for longer duration or more invasive procedures, a general anesthetic may be administered without intubating the trachea, provided that patients are carefully selected, and the  risk-benefit ratio  is favorable (i.e., the risks associated with an unprotected airway are believed to be less than the risks of intubating the trachea). [ 98 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5700", "contents": "Airway management can be classified into closed or open techniques depending on the system of ventilation used. Tracheal intubation is a typical example of a closed technique as ventilation occurs using a closed circuit. Several open techniques exist, such as spontaneous ventilation, apnoeic ventilation or jet ventilation. Each has its own specific advantages and disadvantages which determine when it should be used."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5701", "contents": "Spontaneous ventilation has been traditionally performed with an inhalational agent (i.e. gas induction or inhalational induction using halothane or sevoflurane) however it can also be performed using intravenous anaesthesia (e.g. propofol, ketamine or dexmedetomidine). SponTaneous Respiration using IntraVEnous anaesthesia and High-flow nasal oxygen (STRIVE Hi) is an open airway technique that uses an upwards titration of propofol which maintains ventilation at deep levels of anaesthesia. It has been used in airway surgery as an alternative to tracheal intubation. [ 99 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5702", "contents": "The earliest known depiction of a tracheotomy is found on two Egyptian tablets dating back to around 3600 BC. [ 100 ]  The 110-page  Ebers Papyrus , an  Egyptian medical papyrus  which dates to roughly 1550 BC, also makes reference to the tracheotomy. [ 101 ]  Tracheotomy was described in the  Rigveda , a  Sanskrit  text of  ayurvedic medicine  written around 2000 BC in  ancient India . [ 102 ]  The  Sushruta Samhita  from around 400 BC is another text from the Indian subcontinent on ayurvedic medicine and surgery that mentions tracheotomy. [ 103 ]   Asclepiades of Bithynia  ( c. \u2009124 \u201340 BC) is often credited as being the first physician to perform a non-emergency tracheotomy. [ 104 ]   Galen  of  Pergamon  (AD 129\u2013199) clarified the anatomy of the trachea and was the first to demonstrate that the larynx generates the voice. [ 105 ]  In one of his experiments, Galen used bellows to inflate the lungs of a dead animal. [ 106 ]   Ibn S\u012bn\u0101  (980\u20131037) described the use of tracheal intubation to facilitate breathing in 1025 in his 14-volume medical encyclopedia,  The Canon of Medicine . [ 107 ]  In the 12th century medical textbook  Al-Taisir ,  Ibn Zuhr  (1092\u20131162)\u2014also known as Avenzoar\u2014of  Al-Andalus   provided a correct description of the tracheotomy operation. [ 108 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5703", "contents": "The first detailed descriptions of tracheal intubation and subsequent  artificial respiration  of animals were from  Andreas Vesalius  (1514\u20131564) of Brussels. In his landmark book published in 1543,  De humani corporis fabrica , he described an experiment in which he passed a  reed  into the trachea of a dying animal whose thorax had been opened and maintained ventilation by blowing into the reed intermittently. [ 106 ]   Antonio Musa Brassavola  (1490\u20131554) of  Ferrara  successfully treated a patient with  peritonsillar abscess  by tracheotomy. Brassavola published his account in 1546; this operation has been identified as the first recorded successful tracheotomy, despite the many previous references to this operation. [ 109 ]  Towards the end of the 16th century,  Hieronymus Fabricius  (1533\u20131619) described a useful technique for tracheotomy in his writings, although he had never actually performed the operation himself. In 1620 the French surgeon  Nicholas Habicot  (1550\u20131624) published a report of four successful tracheotomies. [ 110 ]  In 1714, anatomist Georg Detharding (1671\u20131747) of the  University of Rostock  performed a tracheotomy on a drowning victim. [ 111 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5704", "contents": "Despite the many recorded instances of its use since  antiquity , it was not until the early 19th century that the tracheotomy finally began to be recognized as a legitimate means of treating severe airway obstruction. In 1852, French physician  Armand Trousseau  (1801\u20131867) presented a series of 169 tracheotomies to the  Acad\u00e9mie Imp\u00e9riale de M\u00e9decine . 158 of these were performed for the treatment of  croup , and 11 were performed for \"chronic maladies of the larynx\". [ 112 ]  Between 1830 and 1855, more than 350 tracheotomies were performed in Paris, most of them at the  H\u00f4pital des Enfants Malades , a  public hospital , with an overall survival rate of only 20\u201325%. This compares with 58% of the 24 patients in Trousseau's private practice, who fared better due to greater postoperative care. [ 113 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5705", "contents": "In 1871, the German surgeon  Friedrich Trendelenburg  (1844\u20131924) published a paper describing the first successful elective human tracheotomy to be performed for the purpose of administration of general anesthesia. [ 114 ]  In 1888, Sir  Morell Mackenzie  (1837\u20131892) published a book discussing the indications for tracheotomy. [ 115 ]  In the early 20th century, tracheotomy became a life-saving treatment for patients affected with paralytic  poliomyelitis  who required mechanical ventilation. In 1909, Philadelphia laryngologist  Chevalier Jackson  (1865\u20131958) described a technique for tracheotomy that is used to this day. [ 116 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5706", "contents": "In 1854, a Spanish  singing teacher  named  Manuel Garc\u00eda  (1805\u20131906) became the first man to view the functioning glottis in a living human. [ 117 ]  In 1858, French pediatrician  Eug\u00e8ne Bouchut  (1818\u20131891) developed a new technique for non-surgical orotracheal intubation to bypass laryngeal obstruction resulting from a  diphtheria -related pseudomembrane. [ 118 ]  In 1880, Scottish surgeon  William Macewen  (1848\u20131924) reported on his use of orotracheal intubation as an alternative to tracheotomy to allow a patient with glottic edema to breathe, as well as in the setting of general anesthesia with  chloroform . [ 119 ]  In 1895,  Alfred Kirstein  (1863\u20131922) of Berlin first described direct visualization of the vocal cords, using an esophagoscope he had modified for this purpose; he called this device an autoscope. [ 120 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5707", "contents": "In 1913, Chevalier Jackson was the first to report a high rate of success for the use of direct laryngoscopy as a means to intubate the trachea. [ 121 ]  Jackson introduced a new laryngoscope blade that incorporated a component that the operator could slide out to allow room for passage of an endotracheal tube or bronchoscope. [ 122 ]  Also in 1913, New York surgeon  Henry H. Janeway  (1873\u20131921) published results he had achieved using a laryngoscope he had recently developed. [ 123 ]  Another pioneer in this field was Sir  Ivan Whiteside Magill  (1888\u20131986), who developed the technique of awake blind nasotracheal intubation, [ 124 ] [ 125 ]  the Magill forceps, [ 126 ]  the Magill laryngoscope blade, [ 127 ]  and several apparati for the administration of volatile anesthetic agents. [ 128 ] [ 129 ] [ 130 ]  The Magill curve of an endotracheal tube is also named for Magill. Sir  Robert Macintosh  (1897\u20131989) introduced a curved laryngoscope blade in 1943; [ 131 ]  the Macintosh blade remains to this day the most widely used laryngoscope blade for orotracheal intubation. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5708", "contents": "Between 1945 and 1952,  optical engineers  built upon the earlier work of  Rudolph Schindler  (1888\u20131968), developing the first gastrocamera. [ 132 ]  In 1964,  optical fiber  technology was applied to one of these early gastrocameras to produce the first flexible fiberoptic endoscope. [ 133 ]  Initially used in  upper GI endoscopy , this device was first used for laryngoscopy and tracheal intubation by Peter Murphy, an English anesthetist, in 1967. [ 134 ]  The concept of using a stylet for replacing or exchanging orotracheal tubes was introduced by Finucane and Kupshik in 1978, using a  central venous catheter . [ 135 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5709", "contents": "By the mid-1980s, the flexible fiberoptic bronchoscope had become an indispensable instrument within the pulmonology and anesthesia communities. [ 13 ]  The  digital revolution  of the 21st century has brought newer technology to the art and science of tracheal intubation. Several manufacturers have developed video laryngoscopes which employ  digital technology  such as the  CMOS   active pixel sensor  (CMOS APS) to generate a view of the glottis so that the trachea may be intubated. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5710", "contents": "A  ventilator  is a type of  breathing apparatus , a class of  medical technology  that provides  mechanical ventilation  by moving breathable air into and out of the  lungs , to deliver breaths to a patient who is physically unable to breathe, or breathing insufficiently. Ventilators may be  computerized   microprocessor-controlled  machines, but patients can also be ventilated with a simple, hand-operated  bag valve mask .  Ventilators are chiefly used in  intensive-care medicine ,  home care , and  emergency medicine  (as standalone units) and in  anesthesiology  (as a component of an  anesthesia machine )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5711", "contents": "Ventilators are sometimes called \"respirators\", a term commonly used for them in the 1950s (particularly the  \"Bird respirator\" ). However, contemporary medical terminology uses the word \" respirator \" to refer to a face-mask that protects wearers against hazardous airborne substances. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5712", "contents": "In its simplest form, a modern  positive pressure ventilator , consists of a compressible  air  reservoir or turbine, air and  oxygen  supplies, a set of valves and tubes, and a disposable or reusable \"patient circuit\". The air reservoir is pneumatically compressed several times a minute to deliver room-air, or in most cases, an air/oxygen mixture to the patient. If a turbine is used, the turbine pushes air through the ventilator, with a flow valve adjusting pressure to meet patient-specific parameters. When over pressure is released, the patient will exhale passively due to the  lungs ' elasticity, the exhaled air being released usually through a  one-way valve  within the patient circuit called the patient manifold."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5713", "contents": "Ventilators may also be equipped with monitoring and alarm systems for patient-related parameters (e.g., pressure, volume, and flow) and ventilator function (e.g., air leakage, power failure, mechanical failure), backup batteries, oxygen tanks, and remote control. The pneumatic system is nowadays often replaced by a computer-controlled  turbopump ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5714", "contents": "Modern ventilators are electronically controlled by a small  embedded system  to allow exact adaptation of pressure and flow characteristics to an individual patient's needs. Fine-tuned ventilator settings also serve to make ventilation more tolerable and comfortable for the patient. In Canada and the United States,  respiratory therapists  are responsible for tuning these settings, while biomedical technologists are responsible for the maintenance.  In the United Kingdom and Europe the management of the patient's interaction with the ventilator is done by  critical care  nurses."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5715", "contents": "The patient circuit usually consists of a set of three durable, yet lightweight plastic tubes, separated by function (e.g. inhaled air, patient pressure, exhaled air). Determined by the type of ventilation needed, the patient-end of the circuit may be either noninvasive or invasive."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5716", "contents": "Noninvasive methods, such as  continuous positive airway pressure (CPAP)  and  non-invasive ventilation , which are adequate for patients who require a ventilator only while sleeping and resting, mainly employ a nasal mask. Invasive methods require  intubation , which for long-term ventilator dependence will normally be a  tracheotomy  cannula, as this is much more comfortable and practical for long-term care than is larynx or nasal intubation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5717", "contents": "As failure may result in death, mechanical ventilation systems are classified as  safety-critical systems , and precautions must be taken to ensure that they are highly reliable, including their  power supply . Ventilatory failure is the inability to sustain a sufficient rate of CO 2  elimination to maintain a stable pH without mechanical assistance, muscle fatigue, or intolerable dyspnea. [ 2 ]  Mechanical ventilators are therefore carefully designed so that no  single point of failure  can endanger the patient. They may have manual backup mechanisms to enable hand-driven respiration in the absence of power (such as the mechanical ventilator integrated into an  anaesthetic machine ). They may also have safety valves, which open to atmosphere in the absence of power to act as an anti-suffocation valve for spontaneous breathing of the patient. Some systems are also equipped with compressed-gas tanks, air compressors or backup batteries to provide ventilation in case of power failure or defective gas supplies, and methods to operate or call for help if their mechanisms or software fail. [ 3 ]   Power failures , such as during a natural disaster, can create a life-threatening emergency for people using ventilators in a home care setting. [ 4 ]   Battery power may be sufficient for a brief loss of electricity, but longer power outages may require going to a hospital. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5718", "contents": "The history of mechanical ventilation begins with various versions of what was eventually called the  iron lung , a form of noninvasive negative-pressure ventilator widely used during the  polio  epidemics of the twentieth century after the introduction of the \"Drinker respirator\" in 1928, improvements introduced by  John Haven Emerson  in 1931, [ 5 ]  and the  Both respirator  in 1937. Other forms of noninvasive ventilators, also used widely for polio patients, include  Biphasic Cuirass Ventilation , the rocking bed, and rather primitive positive pressure machines. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5719", "contents": "In 1949, John Haven Emerson developed a mechanical assister for anaesthesia with the cooperation of the anaesthesia department at  Harvard University . Mechanical ventilators began to be used increasingly in anaesthesia and intensive care during the 1950s. Their development was stimulated both by the need to treat polio patients and the increasing use of  muscle relaxants  during anaesthesia. Relaxant drugs paralyse the patient and improve operating conditions for the surgeon but also paralyse the respiratory muscles. In 1953  Bj\u00f8rn Aage Ibsen  set up what became the world's first Medical/Surgical ICU utilizing muscle relaxants and controlled ventilation. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5720", "contents": "In the United Kingdom, the East Radcliffe and Beaver models were early examples. The former used a  Sturmey-Archer  bicycle  hub gear  to provide a range of speeds, and the latter an automotive  windscreen wiper  motor to drive the bellows used to inflate the lungs. [ 7 ]  Electric motors were, however, a problem in the operating theatres of that time, as their use caused an explosion hazard in the presence of flammable anaesthetics such as  ether  and  cyclopropane . In 1952, Roger Manley of the  Westminster Hospital , London, developed a ventilator which was entirely gas-driven and became the most popular model used in Europe. It was an elegant design, and became a great favourite with European anaesthetists for four decades, prior to the introduction of models controlled by electronics. It was independent of electrical power and caused no explosion hazard. The original Mark I unit was developed to become the Manley Mark II in collaboration with the Blease company, which manufactured many thousands of these units. Its principle of operation was very simple, an incoming gas flow was used to lift a weighted bellows unit, which fell intermittently under gravity, forcing breathing gases into the patient's lungs. The inflation pressure could be varied by sliding the movable weight on top of the bellows. The volume of gas delivered was adjustable using a curved slider, which restricted bellows excursion. Residual pressure after the completion of expiration was also configurable, using a small weighted arm visible to the lower right of the front panel. This was a robust unit and its availability encouraged the introduction of positive pressure ventilation techniques into mainstream European anesthetic practice."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5721", "contents": "The 1955 release of  Forrest Bird 's \"Bird Universal Medical Respirator\" in the United States changed the way mechanical ventilation was performed, with the small green box becoming a familiar piece of medical equipment. [ 8 ]  The unit was sold as the Bird Mark 7 Respirator and informally called the \"Bird\". It was a  pneumatic  device and therefore required no  electrical power  source to operate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5722", "contents": "In 1965, the Army Emergency Respirator was developed in collaboration with the Harry Diamond Laboratories (now part of the  U.S. Army Research Laboratory ) and  Walter Reed Army Institute of Research . Its design incorporated the principle of fluid amplification in order to govern pneumatic functions. Fluid amplification allowed the respirator to be manufactured entirely without moving parts, yet capable of complex resuscitative functions. [ 9 ]  Elimination of moving parts increased performance reliability and minimized maintenance. [ 10 ]  The mask is composed of a  poly(methyl methacrylate)  (commercially known as  Lucite ) block, about the size of a pack of cards, with machined channels and a cemented or screwed-in cover plate. [ 11 ]  The reduction of moving parts cut manufacturing costs and increased durability. [ 10 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5723", "contents": "The bistable fluid amplifier design allowed the respirator to function as both a respiratory assistor and controller. It could functionally transition between assistor and controller automatically, based on the patient's needs. [ 11 ] [ 10 ]  The dynamic pressure and turbulent jet flow of gas from inhalation to exhalation allowed the respirator to synchronize with the breathing of the patient. [ 12 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5724", "contents": "Intensive care environments around the world revolutionized in 1971 by the introduction of the first SERVO 900 ventilator (Elema-Sch\u00f6nander), constructed by  Bj\u00f6rn Jonson . It was a small, silent and effective electronic ventilator, with the famous SERVO feedback system controlling what had been set and regulating delivery. For the first time, the machine could deliver the set volume in volume control ventilation."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5725", "contents": "Microprocessor control  led to the third generation of  intensive care unit  (ICU) ventilators, starting with the  Dr\u00e4ger  EV-A [ 13 ]  in 1982 in Germany which allowed monitoring the patient's  breathing curve  on an  LCD monitor . One year later followed  Puritan Bennett  7200 and Bear 1000, SERVO 300 and Hamilton Veolar over the next decade.  Microprocessors  enable customized gas delivery and monitoring, and mechanisms for gas delivery that are much more responsive to patient needs than previous generations of mechanical ventilators. [ 14 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5726", "contents": "An  open-source  ventilator is a disaster-situation ventilator made using a freely-licensed design, and ideally, freely-available components and parts. Designs, components, and parts may be anywhere from completely reverse-engineered to completely new creations, components may be  adaptations  of various inexpensive existing products, and special hard-to-find and/or expensive parts may be 3D printed instead of sourced. [ 15 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5727", "contents": "During the 2019\u20132020  COVID-19 pandemic , various kinds of ventilators have been considered. Deaths caused by  COVID-19  have occurred when the most severely infected experience  acute respiratory distress syndrome , a widespread inflammation in the lungs that impairs the lungs' ability to absorb oxygen and expel carbon dioxide. These patients require a capable ventilator to continue breathing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5728", "contents": "Among ventilators that might be brought into use for treating people with COVID-19, there have been many concerns. These include current availability, [ 17 ] [ 18 ]  the challenge of making more and lower cost ventilators, effectiveness, [ 19 ]   functional design , safety, [ 20 ] [ 21 ]  portability, [ 22 ]  suitability for infants, [ 23 ]  assignment to treat other illnesses, and operator training. [ 24 ]  Deploying the best possible mix of ventilators can save the most lives."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5729", "contents": "Although not formally open-sourced, the Ventec V+ Pro ventilator was developed in April 2020 as a shared effort between  Ventec Life Systems  and  General Motors , to provide a rapid supply of 30,000 ventilators capable of treating COVID-19 patients. [ 25 ] [ 26 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5730", "contents": "A major worldwide design effort began during the  2019-2020 coronavirus pandemic  after a  Hackaday  project was started, [ 27 ] [ non-primary source needed ]  in order to respond to  expected ventilator shortages  causing higher mortality rate among severe patients."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5731", "contents": "On March 20, 2020, the  Irish Health Service [ 28 ]  began reviewing designs. [ 29 ]  A prototype is being designed and tested in  Colombia . [ 30 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5732", "contents": "The Polish company Urbicum reports successful testing [ 31 ]  of a 3D-printed open-source prototype device called VentilAid. The makers describe it as a last resort device when professional equipment is missing. The design is publicly available. [ 32 ]  The first Ventilaid prototype requires compressed air to run."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5733", "contents": "On March 21, 2020, the  New England Complex Systems Institute  (NECSI) began maintaining a strategic list of open source designs being worked on. [ 33 ] [ 34 ]  The NECSI project considers manufacturing capability, medical safety and need for treating patients in various conditions, speed dealing with legal and political issues, logistics and supply. [ 35 ]  NECSI is staffed with scientists from Harvard and MIT and others who have an understanding of pandemics, medicine, systems, risk, and data collection. [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5734", "contents": "The  University of Minnesota Bakken Medical Device Center  initiated a collaboration with various companies to bring a ventilator alternative to the market that works as a one-armed  robot  and replaces the need for manual ventilation in emergency situations. The  Coventor  device was developed in a very short time and approved on April 15, 2020, by the  FDA , only 30 days after conception. The mechanical ventilator is designed for use by trained medical professionals in  intensive care units  and easy to operate. It has a compact design and is relatively inexpensive to manufacture and distribute. The cost is only about 4% of a normal ventilator. In addition, this device does not require pressurized oxygen or air supply, as is normally the case. A first series is manufactured by  Boston Scientific . The plans are to be freely available online to the general public without royalties. [ 36 ] [ 37 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5735", "contents": "The  COVID-19 pandemic  has led to  shortages of essential goods and services  - from hand sanitizers to masks to beds to ventilators. [ citation needed ]  Countries around the world have experienced shortages of ventilators. [ 38 ]  Furthermore, fifty-four governments, including many in Europe and Asia, imposed restrictions on medical supply exports in response to the coronavirus pandemic. [ 39 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5736", "contents": "The capacities to produce and distribute  invasive  and  non-invasive ventilators  vary by country. In the initial phase of the pandemic, China ramped up its production of ventilators, secured large amounts of donations from private firms, and dramatically increased imports of medical devices worldwide. As a result, the country accumulated a reservoir of ventilators throughout the pandemic in Wuhan. Western Europe and the United States, which outrank China in their production capacities, suffered a shortage of supplies due to the sudden and scattered outbreaks throughout the North American and European continents. Finally,  Central Asia ,  Africa , and  Latin America , which depend almost entirely on importing ventilators, suffered severe shortages of supplies. [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5737", "contents": "Healthcare policy-makers have met serious challenges to estimate the number of ventilators needed and used during the pandemic. When data is often not available for ventilators specifically, estimates are sometimes made based on the number of  intensive care unit  beds available, which often contain ventilators. [ 40 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5738", "contents": "In 2006, president  George W. Bush  signed the  Pandemic and All-Hazards Preparedness Act , which created the  Biomedical Advanced Research and Development Authority  (BARDA) within the  United States Department of Health and Human Services . In preparation for a possible epidemic of respiratory disease, the newly created office awarded a $6 million contract to  Newport Medical Instruments , a small company in California, to make 40,000 ventilators for under $3,000 apiece. In 2011, Newport sent three prototypes to the  Centers for Disease Control . In 2012,  Covidien , a $12 billion/year medical device manufacturer, which manufactured more expensive competing ventilators, bought Newport for $100 million. Covidien delayed and in 2014 cancelled the contract."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5739", "contents": "BARDA started over again with a new company,  Philips , and in July 2019, the  FDA  approved the Philips ventilator, and the government ordered 10,000 ventilators for delivery in mid-2020. [ 41 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5740", "contents": "On April 23, 2020,  NASA  reported building, in 37 days, a successful COVID-19 ventilator, named VITAL (\"Ventilator Intervention Technology Accessible Locally\"). On April 30, NASA reported receiving fast-track approval for emergency use by the  United States Food and Drug Administration  for the new ventilator. [ 42 ] [ 43 ] [ 44 ]  On May 29, NASA reported that eight manufacturers were selected to manufacture the new ventilator. [ 45 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5741", "contents": "On April 7, 2020, Prime Minister Justin Trudeau announced that the Canadian Federal Government would be sourcing thousands of 'Made in Canada' ventilators. A number of organisations responded from across the country. [ 46 ]  They delivered a large quantity of ventilators to the National Emergency Strategic Stockpile. From west to east, the companies include Canadian Emergency Ventilators Inc, Bayliss Medical Inc, Thornhill Medical, Vexos Inc, and CAE Inc."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5742", "contents": "Pulmonology\nPaediatric Critical Care Medicine"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5743", "contents": "Ventilator-associated pneumonia  ( VAP ) is a type of lung infection that occurs in people who are on  mechanical ventilation  breathing machines in hospitals.  As such, VAP typically affects critically ill persons that are in an  intensive care unit  (ICU) and have been on a mechanical ventilator for at least 48 hours. [ 1 ] [ 2 ]  VAP is a major source of increased illness and death. Persons with VAP have increased lengths of ICU hospitalization and have up to a 20\u201330% death rate. [ 3 ]   The diagnosis of VAP varies among hospitals and providers but usually requires a new infiltrate on chest x-ray plus two or more other factors. These factors include temperatures of >38\u00a0\u00b0C or <36\u00a0\u00b0C, a white blood cell count of >12 \u00d7 10 9 /ml, purulent secretions from the airways in the lung, and/or reduction in gas exchange. [ 2 ] [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5744", "contents": "A different less studied infection found in mechanically ventilated people is  ventilator-associated tracheobronchitis  (VAT). [ 5 ]  As with VAP, tracheobronchial infection can colonise the trachea and travel to the bronchi. VAT may be a risk factor for VAP. [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5745", "contents": "People who are on mechanical ventilation are often sedated and are rarely able to communicate due to which many of the typical symptoms of pneumonia will either be absent or unable to be obtained. The most important signs are  fever  or  low body temperature , new  purulent   sputum , and  hypoxemia  (decreasing amounts of oxygen in the blood). However, these symptoms may be similar for tracheobronchitis."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5746", "contents": "Risk factors for VAP include underlying heart or lung disease, neurologic disease, and trauma, as well as modifiable risk factors such as whether the head of the bed is flat (increased risk) or raised, whether the patient had an  aspiration event  before intubation, and prior antibiotic exposure. [ 3 ]  As a result of intubation many of the body's defenses against infections are reduced or impaired; this can result in an ability for microorganisms to enter and cause infection. [ 6 ] [ 1 ]  Patients who are in the ICU for head trauma or other severe neurologic illness, as well as patients who are in the ICU for blunt or penetrating trauma, are at especially high risk of developing VAP. [ 2 ]  Further, patients hospitalized for blunt trauma are at a higher risk of developing VAP compared to patients with penetrating trauma. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5747", "contents": "Ventilator-associated tracheobronchitis may be a risk factor for VAP, though not all cases of VAT progress to VAP. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5748", "contents": "Recent studies have also linked the overall oral health of a patient to the potential development of VAP; suggesting that bacteria found in plaque can \"migrate to the respiratory system.\" [ 8 ] [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5749", "contents": "The microbiologic  flora  responsible for VAP is different from that of the more common  community-acquired pneumonia  (CAP). In particular, viruses and fungi are uncommon causes in people who do not have underlying  immune deficiencies . Though any microorganism that causes CAP can cause VAP, there are several bacteria which are particularly important causes of VAP because of their resistance to commonly used antibiotics. These bacteria are referred to as  multidrug resistant  (MDR)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5750", "contents": "It is thought by many, that VAP primarily occurs because the endotracheal or tracheostomy tube allows free passage of bacteria into the lower segments of the lung in a person who often has underlying lung or immune problems. Bacteria travel in small  droplets  both through the endotracheal tube and around the cuff. Often, bacteria colonize the endotracheal or tracheostomy tube and are  embolized  into the lungs with each breath. Bacteria may also be brought down into the lungs with procedures such as deep suctioning or  bronchoscopy . Another possibility is that the bacteria already exist in the mucus lining the bronchial tree, and are just kept in check by the body's first line of defenses. Ciliary action of the cells lining the trachea drive the mucus superiorly, leading to a build-up of fluids around the inflated cuff where there is little to no airway clearance. The bacteria can then colonize easily without disturbance and then rise in numbers enough to become infective. The droplets that are driven into the airstream and into the lung fields are lofted by way of Bernoulli's principle. There is also a condition called oxidative damage that occurs when concentrations of pure oxygen come into prolonged contact with cells and this damages the cilia of the cells, thus inhibiting their action as part of the body's first line of defense."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5751", "contents": "Whether bacteria also travel from the  sinuses  or the stomach into the lungs is, as of 2005, controversial. However, spread to the lungs from the  blood stream  or the  gut  is uncommon."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5752", "contents": "Once inside the lungs, bacteria then take advantage of any deficiencies in the  immune system  (such as due to  malnutrition  or  chemotherapy ) and multiply. Patients with VAP demonstrate impaired function of key immune cells, including the  neutrophil , both in the blood and in the alveolar space, [ 11 ]  with this impairment being driven by pro-inflammatory molecules such as  C5a . [ 12 ]   These defects in immune function appear to be causally linked to the development of VAP, as they are seen before clinical infection develops. [ 13 ]   A combination of bacterial damage and consequences of the immune response lead to disruption of  gas exchange  with resulting symptoms."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5753", "contents": "Diagnosis of ventilator-associated pneumonia is difficult and is not standardized. [ 14 ]  The criteria used for diagnosis of VAP varies by institution, but tends to be a combination of several of the following radiographic, clinical sign, and laboratory evidence: [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5754", "contents": "As an example, some institutions may require one clinical symptoms such as shortness of breath, one clinical sign such as fever, plus evidence on chest xray and in tracheal cultures. [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5755", "contents": "There is no gold standard for getting cultures to identify the bacteria, virus, or fungus that is causing the pneumonia, and there are invasive and non-invasive strategies for obtaining the culture sample. [ 16 ]  One non-invasive strategy collects cultures from the  trachea  of people with symptoms of VAP. Another is more invasive and advocates a  bronchoscopy  plus  bronchoalveolar lavage  (BAL) for people with symptoms of VAP. Both strategies also require a new or enlarging infiltrate on chest x-ray as well as clinical signs/symptoms such as fever and shortness of breath. There is no strong evidence to suggest that an invasive method to collect cultures is more effective than a non-invasive method. [ 16 ]  In addition, a quantitative approach to assessing the culture (performing a bacterial count of the pathogen that is causing the pneumonia) does not appear to be superior to a qualitative approach (determining the presence of the pathogen). [ 16 ]  In recent years there has been a focus on rapid diagnostics, allowing for detection of significant levels of pathogens before this becomes apparent on microbial cultures. Several approaches have been used, including using host  biomarkers  such as  IL-1\u03b2  and  IL-8 . [ 17 ] [ 18 ]   Alternatively, molecular detection of bacteria has been undertaken, with reports that  amplifying  the pan-bacterial  16S  gene can provide a measure of bacterial load. [ 19 ]  A trial of biomarker-based exclusion of VAP (VAP-RAPID2) demonstrated test effectiveness but did not impact on clinical antibiotic prescribing decisions. [ 20 ]   Studies of pathogen-focussed  molecular diagnostics  have shown more promise in improving  antimicrobial  prescribing, [ 21 ] [ 22 ]  with formal findings from the INHALE randomised controlled trial  awaited .  Highly sensitive molecular diagnostics have the potential to increase antimicrobial use [ 23 ]  as they detect dead or colonising bacteria, a combination of host-immune profiling and microbial detection may provide the optimal diagnostic technique. [ 24 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5756", "contents": "Blood cultures  may reveal the microorganisms causing VAP, but are often not helpful as they are positive in only 25% of clinical VAP cases. [ 25 ]  Even in cases with positive blood cultures, the bacteremia may be from a source other than the lung infection. [ 25 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5757", "contents": "Prevention of VAP involves limiting exposure to resistant bacteria, discontinuing mechanical ventilation as soon as possible, and a variety of strategies to limit infection while  intubated . Resistant bacteria are spread in much the same ways as any communicable disease. Proper  hand washing ,  sterile technique  for invasive procedures, and isolation of individuals with known resistant organisms are all mandatory for effective infection control. A variety of aggressive weaning protocols to limit the amount of time a person spends intubated have been proposed. One important aspect is limiting the amount of sedation that a ventilated person receives."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5758", "contents": "Weak evidence suggests that raising the head of the bed to at least 30 degrees may help prevent VAP, however further research is required to understand the risks associated with this. [ 26 ]   Antiseptic mouthwashes (in particular associated with toothbrushing) such as  chlorhexidine  may also reduce the risk of VAP, [ 27 ]  although the evidence is mainly restricted to those who have undergone cardiac surgery. [ 28 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5759", "contents": "American and Canadian guidelines strongly recommend the use of subglottic secretion drainage (SSD). Special tracheal tubes with an incorporated suction lumen as the EVAC tracheal tube form Covidien / Mallinckrodt can be used for that reason. New cuff technology based on polyurethane material in combination with subglottic drainage (SealGuard Evac tracheal tube from Covidien / Mallinckrodt) showed significant delay in early and late onset of VAP. [ 29 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5760", "contents": "There is little evidence that the use of  silver -coated endotracheal tubes reduces the incidence of VAP in the first ten days of ventilation. [ 30 ]  There is tentative evidence that the use of  probiotics  may reduced the likelihood of getting VAP, however it is unclear if probiotics affect ICU or in-hospital death. [ 31 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5761", "contents": "Treatment of VAP should be matched to known causative bacteria.  However, when VAP is first suspected, the bacteria causing infection is typically not known and broad-spectrum antibiotics are given ( empiric therapy ) until the particular bacterium and its sensitivities are determined.  Empiric antibiotics should take into account both the risk factors a particular individual has for resistant bacteria as well as the local prevalence of resistant microorganisms.  If a person has previously had episodes of pneumonia, information may be available about prior causative bacteria.  The choice of initial therapy is therefore entirely dependent on knowledge of local flora and will vary from hospital to hospital. Treatment of VAP with a single antibiotic has been reported to result in similar outcomes as with a combination of more than one antibiotics, in terms of cure rates, duration of ICU stay, mortality and adverse effects. [ 32 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5762", "contents": "Risk factors for infection with an MDR strain include ventilation for more than five days, recent hospitalization (last 90 days), residence in a  nursing home , treatment in a  hemodialysis  clinic, and prior antibiotic use (last 90 days)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5763", "contents": "Possible empirical therapy combinations include (but are not limited to):"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5764", "contents": "Therapy is typically changed once the causative bacteria are known and continued until symptoms resolve (often 7 to 14 days). For patients with VAP not caused by nonfermenting Gram-negative bacilli (like Acinetobacter, Pseudomonas aeruginosa) the available evidence seems to support the use of short-course antimicrobial treatments (< or =10 days). [ 33 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5765", "contents": "People who do not have risk factors for MDR organisms may be treated differently depending on local knowledge of prevalent bacteria.  Appropriate antibiotics may include  ceftriaxone ,  ciprofloxacin ,  levofloxacin , or  ampicillin/sulbactam ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5766", "contents": "As of 2005, there is ongoing research into inhaled antibiotics as an adjunct to conventional therapy.  Tobramycin  and  polymyxin B  are commonly used in certain centres but there is no strong clinical evidence to support their use."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5767", "contents": "VAP occurring early after intubation typically involves fewer resistant organisms and is thus associated with a more favorable outcome. Because respiratory failure requiring mechanical ventilation is itself associated with a high mortality, determination of the exact contribution of VAP to mortality has been difficult. As of 2006, estimates range from 33% to 50% death in patients who develop VAP. Mortality is more likely when VAP is associated with certain microorganisms ( Pseudomonas ,  Acinetobacter ),  blood stream infections , and ineffective initial antibiotics. VAP is especially common in people who have  acute respiratory distress syndrome  (ARDS). [ 34 ] [ 35 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5768", "contents": "Between 8 and 28% of patients receiving mechanical ventilation are affected by VAP. [ 36 ]  VAP can develop at any time during ventilation, but occurs most often in the first week of mechanical ventilation. [ 3 ]  There is some evidence for gender differences in the course of VAP: men have been found to get VAP more often, but women are more likely to die after contracting VAP. [ 37 ]   Recent reports indicate that patients with  Coronavirus disease 2019  who require  mechanical ventilation  in an  Intensive care unit  are at increased risk of ventilator-associated pneumonia, compared to patients without COVID-19 ventilated in the same unit [ 38 ]  and patients who had  viral pneumonitis  arising from viruses other than  SARS-CoV-2 . [ 39 ]   Why this increased susceptibility should be present remains uncertain, as the noted reports [ 38 ] [ 39 ]  adjusted for duration of ventilation, it is likely that the increased susceptibility relates impaired innate immunity in the lungs. [ 40 ]   However several  observational studies  have identified the use of  glucocorticoids  as a factor associated with increased risk of VAP [ 41 ] [ 42 ]  and other  Hospital-acquired infections . [ 43 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5769", "contents": "Volume-controlled ventilation  may refer to:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5770", "contents": "Winters's formula , [ 1 ]  named after  R. W. Winters , [ 2 ]  is a  formula  used to evaluate  respiratory compensation  when analyzing  acid-base  disorders in the presence of  metabolic acidosis . [ 3 ] [ 4 ]  It can be given as:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5771", "contents": "P \n \n C \n \n O \n \n 2 \n \n \n \n \n = \n ( \n 1.5 \n \u00d7 \n H \n C \n \n O \n \n sgn \n \n \n ) \n + \n 8 \n \u00b1 \n 2 \n \n \n {\\displaystyle P_{CO_{2}}=(1.5\\times HCO_{\\operatorname {sgn} })+8\\pm 2} \n \n ,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5772", "contents": "where  HCO 3 \u2212  is given in  units  of  mEq/L  and  P CO 2  will be in units of  mmHg ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5773", "contents": "Dr. R. W. Winters was an American physician and graduate from  Yale Medical School . He was a professor of pediatrics at  Columbia University College of Physicians and Surgeons . In 1974 he was awarded the Borden Award gold medal by the  American Academy of Pediatrics . [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5774", "contents": "Dr. R. W. Winters conducted an experiment in the 1960s on 60 patients with varying degrees of metabolic acidosis. He aimed to empirically determine a mathematical expression representing the effect of respiratory compensation during metabolic acidosis. He measured the blood pH, plasma PCO2, blood base excess, and plasma bicarbonate concentrations. He focused on the relationship between plasma PCO2 and plasma bicarbonate. Winter's Formula was derived from a linear regression of this relationship between plasma PCO2 and plasma bicarbonate. [ 6 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5775", "contents": "There are four primary acid-base derangements that can occur in the human body - metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. These are characterized by a serum pH below 7.4 (acidosis) or above 7.4 (alkalosis), and whether the cause is from a metabolic process or respiratory process. If the body experiences one of these derangements, the body will try to compensate by inducing an opposite process (e.g. induced respiratory alkalosis for a primary metabolic acidosis). [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5776", "contents": "Respiratory compensation  is one of three major processes the body uses to react to derangements in acid-base status (above or below pH 7.4).  It is slower than the initial  bicarbonate buffer system  in the blood, but faster than  renal compensation . Respiratory compensation usually begins within minutes to hours, but alone will not completely return arterial pH to a normal value (7.4). Winter's Formula quantifies the amount of respiratory compensation during metabolic acidosis. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5777", "contents": "During metabolic acidosis, a decrease in pH stimulates chemoreceptors.  Peripheral chemoreceptors  are found in the aortic and carotid bodies and respond to changes in the PaCO2, the arterial partial pressure of carbon dioxide.  Central chemoreceptors  are found in the brainstem and respond primarily to decreased pH in the cerebrospinal fluid. In response to decreased pH, these chemoreceptors lead to an increase in minute ventilation and increased elimination of carbon dioxide. A decrease in carbon dioxide lowers PaCO2 and pushes arterial pH towards normal. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5778", "contents": "One difficulty in evaluation acid-base derangements is the presence of multiple pathologies. A patient may present with a metabolic acidosis process alone, but they may also have a concomitant respiratory acidosis. Winters's formula gives an expected value for the patient's P CO 2 ; the patient's actual (measured) P CO 2  is then compared to this. Using this information, physicians may elucidate additional causes of the acid-base derangement and identify different treatment options which may not have otherwise been considered. [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5779", "contents": "If the two values correspond,  respiratory compensation  is considered to be adequate."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5780", "contents": "If the measured P CO 2  is higher than the calculated value, there is also a primary  respiratory acidosis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5781", "contents": "If the measured P CO 2  is lower than the calculated value, there is also a primary  respiratory alkalosis ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5782", "contents": "In  physics , the  Young\u2013Laplace equation  ( / l \u0259 \u02c8 p l \u0251\u02d0 s / ) is an algebraic equation that describes the  capillary pressure  difference sustained across the interface between two  static fluids , such as  water  and  air , due to the phenomenon of  surface tension  or  wall tension , although use of the latter is only applicable if assuming that the wall is very thin. The Young\u2013Laplace equation relates the pressure difference to the shape of the surface or wall and it is fundamentally important in the study of static  capillary surfaces . It is a statement of  normal stress  balance for static fluids meeting at an interface, where the interface is treated as a  surface  (zero thickness):\n \n \n \n \n \n \n \n \n \u0394 \n p \n \n \n \n = \n \u2212 \n \u03b3 \n \u2207 \n \u22c5 \n \n \n \n n \n ^ \n \n \n \n \n \n \n \n \n \n = \n \u2212 \n 2 \n \u03b3 \n \n H \n \n f \n \n \n \n \n \n \n \n \n = \n \u2212 \n \u03b3 \n \n ( \n \n \n \n 1 \n \n R \n \n 1 \n \n \n \n \n + \n \n \n 1 \n \n R \n \n 2 \n \n \n \n \n \n ) \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{aligned}\\Delta p&=-\\gamma \\nabla \\cdot {\\hat {n}}\\\\&=-2\\gamma H_{f}\\\\&=-\\gamma \\left({\\frac {1}{R_{1}}}+{\\frac {1}{R_{2}}}\\right)\\end{aligned}}} \n \n \nwhere  \n \n \n \n \u0394 \n p \n \n \n {\\displaystyle \\Delta p} \n \n  is the  Laplace pressure , the pressure difference across the fluid interface (the exterior pressure minus the interior pressure),  \n \n \n \n \u03b3 \n \n \n {\\displaystyle \\gamma } \n \n  is the  surface tension  (or  wall tension ),  \n \n \n \n \n \n \n n \n ^ \n \n \n \n \n \n {\\displaystyle {\\hat {n}}} \n \n  is the unit normal pointing out of the surface,  \n \n \n \n \n H \n \n f \n \n \n \n \n {\\displaystyle H_{f}} \n \n  is the  mean curvature , and  \n \n \n \n \n R \n \n 1 \n \n \n \n \n {\\displaystyle R_{1}} \n \n  and  \n \n \n \n \n R \n \n 2 \n \n \n \n \n {\\displaystyle R_{2}} \n \n  are the principal  radii of curvature . Note that only normal stress is considered, because a static interface is possible only in the absence of tangential stress. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5783", "contents": "The equation is named after  Thomas Young , who developed the qualitative theory of surface tension in 1805, and  Pierre-Simon Laplace  who completed the mathematical description in the following year. It is sometimes also called the Young\u2013Laplace\u2013Gauss equation, as  Carl Friedrich Gauss  unified the work of Young and Laplace in 1830, deriving both the differential equation and boundary conditions using  Johann Bernoulli 's  virtual work  principles. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5784", "contents": "If the pressure difference is zero, as in a soap film without gravity, the interface will assume the shape of a  minimal surface ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5785", "contents": "The equation also explains the energy required to create an  emulsion . To form the small, highly curved droplets of an emulsion, extra energy is required to overcome the large pressure that results from their small radius."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5786", "contents": "The Laplace pressure, which is greater for smaller droplets, causes the diffusion of molecules out of the smallest droplets in an emulsion and drives emulsion coarsening via  Ostwald ripening . [ citation needed ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5787", "contents": "In a sufficiently narrow (i.e., low  Bond number ) tube of circular cross-section (radius  a ), the interface between two fluids forms a  meniscus  that is a portion of the surface of a sphere with radius  R . The pressure jump across this surface is related to the radius and the surface tension \u03b3 by\n \n \n \n \n \u0394 \n p \n = \n \n \n \n 2 \n \u03b3 \n \n R \n \n \n . \n \n \n {\\displaystyle \\Delta p={\\frac {2\\gamma }{R}}.}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5788", "contents": "This may be shown by writing the Young\u2013Laplace equation in spherical form with a  contact angle  boundary condition and also a prescribed height boundary condition at, say, the bottom of the meniscus. The solution is a portion of a sphere, and the solution will exist  only  for the pressure difference shown above. This is significant because there isn't another equation or law to specify the pressure difference;  existence  of solution for one specific value of the pressure difference prescribes it."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5789", "contents": "The radius of the sphere will be a function only of the  contact angle , \u03b8, which in turn depends on the exact properties of the fluids and the container material with which the fluids in question are contacting/interfacing:\n \n \n \n \n R \n = \n \n \n a \n \n cos \n \u2061 \n \u03b8 \n \n \n \n \n \n {\\displaystyle R={\\frac {a}{\\cos \\theta }}}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5790", "contents": "so that the pressure difference may be written as:\n \n \n \n \n \u0394 \n p \n = \n \n \n \n 2 \n \u03b3 \n cos \n \u2061 \n \u03b8 \n \n a \n \n \n . \n \n \n {\\displaystyle \\Delta p={\\frac {2\\gamma \\cos \\theta }{a}}.}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5791", "contents": "In order to maintain  hydrostatic equilibrium , the induced  capillary pressure  is balanced by a change in height,  h , which can be positive or negative, depending on whether the wetting angle is less than or greater than 90\u00b0. For a fluid of  density  \u03c1:\n \n \n \n \n \u03c1 \n g \n h \n = \n \n \n \n 2 \n \u03b3 \n cos \n \u2061 \n \u03b8 \n \n a \n \n \n . \n \n \n {\\displaystyle \\rho gh={\\frac {2\\gamma \\cos \\theta }{a}}.} \n \n \nwhere  g  is the  gravitational acceleration . This is sometimes known as the  Jurin's law  or  Jurin height [ 3 ]  after  James Jurin  who studied the effect in 1718. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5792", "contents": "For a water-filled glass tube in  air  at  sea level :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5793", "contents": "and so the height of the water column is given by:\n \n \n \n \n h \n \u2248 \n \n \n \n \n 1.4 \n \u00d7 \n \n 10 \n \n \u2212 \n 5 \n \n \n \n \n \n m \n \n \n 2 \n \n \n \n a \n \n \n . \n \n \n {\\displaystyle h\\approx {{1.4\\times 10^{-5}}\\mathrm {m} ^{2} \\over a}.} \n \n \nThus for a 2\u00a0mm wide (1\u00a0mm radius) tube, the water would rise 14\u00a0mm. However, for a capillary tube with radius 0.1\u00a0mm, the water would rise 14\u00a0cm (about 6  inches )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5794", "contents": "When including also the effects of  gravity , for a  free surface  and for a pressure difference between the fluids equal to \u0394 p  at the level  h=0 , there is a balance, when the interface is in equilibrium, between \u0394 p , the  hydrostatic pressure  and the effects of  surface tension . The  Young\u2013Laplace  equation becomes:\n \n \n \n \n \u0394 \n p \n = \n \u03c1 \n g \n h \n \u2212 \n \u03b3 \n \n [ \n \n \n \n 1 \n \n \n R \n \n 1 \n \n \n ( \n h \n ) \n \n \n \n + \n \n \n 1 \n \n \n R \n \n 2 \n \n \n ( \n h \n ) \n \n \n \n \n ] \n \n \n \n {\\displaystyle \\Delta p=\\rho gh-\\gamma \\left[{\\frac {1}{R_{1}(h)}}+{\\frac {1}{R_{2}(h)}}\\right]} \n \n \nNote that the  mean curvature  of the fluid-fluid interface now depends on  h ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5795", "contents": "The equation can be  non-dimensionalised  in terms of its characteristic length-scale, the  capillary length :\n \n \n \n \n \n L \n \n c \n \n \n = \n \n \n \n \u03b3 \n \n \u03c1 \n g \n \n \n \n \n , \n \n \n {\\displaystyle L_{c}={\\sqrt {\\frac {\\gamma }{\\rho g}}},} \n \n \nand  characteristic pressure \n \n \n \n \n \n p \n \n c \n \n \n = \n \n \n \u03b3 \n \n L \n \n c \n \n \n \n \n = \n \n \n \u03b3 \n \u03c1 \n g \n \n \n . \n \n \n {\\displaystyle p_{c}={\\frac {\\gamma }{L_{c}}}={\\sqrt {\\gamma \\rho g}}.}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5796", "contents": "For clean water at  standard temperature and pressure , the  capillary length  is ~2  mm ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5797", "contents": "The non-dimensional equation then becomes:\n \n \n \n \n \n h \n \n \u2217 \n \n \n \u2212 \n \u0394 \n \n p \n \n \u2217 \n \n \n = \n \n [ \n \n \n \n 1 \n \n \n \n \n R \n \n 1 \n \n \n \n \n \u2217 \n \n \n ( \n h \n ) \n \n \n \n + \n \n \n 1 \n \n \n \n \n R \n \n 2 \n \n \n \n \n \u2217 \n \n \n ( \n h \n ) \n \n \n \n \n ] \n \n . \n \n \n {\\displaystyle h^{*}-\\Delta p^{*}=\\left[{\\frac {1}{{R_{1}}^{*}(h)}}+{\\frac {1}{{R_{2}}^{*}(h)}}\\right].}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5798", "contents": "Thus, the surface shape is determined by only one parameter, the over pressure of the fluid, \u0394 p *  and the scale of the surface is given by the  capillary length . The solution of the equation requires an initial condition for position, and the gradient of the surface at the start point."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5799", "contents": "The (nondimensional) shape,  r ( z )  of an  axisymmetric  surface can be found by substituting general expressions for  principal curvatures  to give the  hydrostatic   Young\u2013Laplace equations : [ 5 ] \n \n \n \n \n \n \n \n r \n \u2033 \n \n \n ( \n 1 \n + \n \n r \n \n \u2032 \n \n 2 \n \n \n \n \n ) \n \n \n 3 \n \n \n / \n \n \n 2 \n \n \n \n \n \n \n \u2212 \n \n \n 1 \n \n r \n ( \n z \n ) \n \n \n 1 \n + \n \n r \n \n \u2032 \n \n 2 \n \n \n \n \n \n \n \n \n = \n z \n \u2212 \n \u0394 \n \n p \n \n \u2217 \n \n \n \n \n {\\displaystyle {\\frac {r''}{(1+r'^{2})^{{3}/{2}}}}-{\\frac {1}{r(z){\\sqrt {1+r'^{2}}}}}=z-\\Delta p^{*}} \n \n \n \n \n \n \n \n \n \n z \n \u2033 \n \n \n ( \n 1 \n + \n \n z \n \n \u2032 \n \n 2 \n \n \n \n \n ) \n \n 3 \n \n / \n \n 2 \n \n \n \n \n \n + \n \n \n \n z \n \u2032 \n \n \n r \n ( \n 1 \n + \n \n z \n \n \u2032 \n \n 2 \n \n \n \n \n ) \n \n \n 1 \n \n \n / \n \n \n 2 \n \n \n \n \n \n \n = \n \u0394 \n \n p \n \n \u2217 \n \n \n \u2212 \n z \n ( \n r \n ) \n . \n \n \n {\\displaystyle {\\frac {z''}{(1+z'^{2})^{3/2}}}+{\\frac {z'}{r(1+z'^{2})^{{1}/{2}}}}=\\Delta p^{*}-z(r).}"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5800", "contents": "In  medicine  it is often referred to as the  Law of Laplace , used in the context of  cardiovascular physiology , [ 6 ]  and also  respiratory physiology , though the latter use is often erroneous. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5801", "contents": "Francis Hauksbee  performed some of the earliest observations and experiments in 1709 [ 8 ]  and these were repeated in 1718 by  James Jurin  who observed that the height of fluid in a capillary column was a function only of the cross-sectional area at the surface, not of any other dimensions of the column. [ 4 ] [ 9 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5802", "contents": "Thomas Young  laid the foundations of the equation in his 1804 paper  An Essay on the Cohesion of Fluids [ 10 ]  where he set out in descriptive terms the principles governing contact between fluids (along with many other aspects of fluid behaviour).   Pierre Simon Laplace  followed this up in  M\u00e9canique C\u00e9leste [ 11 ]  with the formal mathematical description given above, which reproduced in symbolic terms the relationship described earlier by Young."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5803", "contents": "Laplace accepted the idea propounded by Hauksbee in his book  Physico-mechanical Experiments  (1709), that the phenomenon was due to a force of attraction that was insensible at sensible distances. [ 12 ] [ 13 ]  The part which deals with the action of a  solid  on a  liquid  and the mutual action of two liquids was not worked out thoroughly, but ultimately was completed by  Carl Friedrich Gauss . [ 14 ]   Franz Ernst Neumann  (1798-1895) later filled in a few details. [ 15 ] [ 9 ] [ 16 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5804", "contents": "\u0394P  ( Delta P ) is a mathematical term symbolizing a change (\u0394) in pressure (P)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5805", "contents": "Given that the  head loss   h f  expresses the  pressure  loss  \u0394p  as the height of a column of fluid,"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5806", "contents": "where \u03c1 is the density of the fluid. The  Darcy\u2013Weisbach equation  can also be written in terms of pressure loss:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5807", "contents": "In general, compliance is defined by the change in volume (\u0394 V ) versus the associated change in pressure (\u0394 P ), or  \u0394 V /\u0394 P :"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5808", "contents": "During  mechanical ventilation , compliance is influenced by three main physiologic factors:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5809", "contents": "Lung compliance is influenced by a variety of primary abnormalities of  lung parenchyma , both chronic and acute.  Airway resistance  is typically increased by  bronchospasm  and airway secretions. Chest wall compliance can be decreased by fixed abnormalities (e.g.  kyphoscoliosis ,  morbid obesity ) or more variable problems driven by patient agitation while intubated. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5810", "contents": "Calculating compliance on  minute volume  (V E : \u0394 V  is always defined by  tidal volume  (V T ), but \u0394 P  is different for the measurement of dynamic vs. static compliance."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5811", "contents": "where PIP =  peak inspiratory pressure  (the maximum pressure during inspiration), and PEEP =  positive end expiratory pressure . Alterations in airway resistance,  lung compliance  and chest wall compliance influence C dyn ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5812", "contents": "where P plat  = plateau pressure. P plat  is measured at the end of inhalation and prior to exhalation using an inspiratory hold maneuver. During this maneuver, airflow is transiently (~0.5 sec) discontinued, which eliminates the effects of airway resistance. P plat  is never > PIP and is typically < 3-5 cmH 2 O lower than PIP when airway resistance is normal."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5813", "contents": "Fair use in  Commission on Accreditation for Respiratory Care  Though this image is subject to copyright, its use is covered by the U.S. fair use laws, and the stricter requirements of Wikipedia's non-free content policies, because:\nIt illustrates an educational article about the entity that the logo represents.\nThe image is used as the primary means of visual identification of the article topic.\nIt is a low resolution image, and thus not suitable for production of counterfeit goods.\nThe logo is not used in such a way that a reader would be confused into believing that the article is written or authorized by the owner of the logo.\nIt is not replaceable with an uncopyrighted or freely copyrighted image of comparable educational value."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5814", "contents": "Use of the logo here does not imply endorsement of the organization by Wikipedia or the  Wikimedia Foundation , nor vice versa.\n Fair use \n //en.wikipedia.org/wiki/File:Commission_on_Accreditation_for_Respiratory_Care_Logo_2011.jpg"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5815", "contents": "A modern USB spirometer ( http://www.advancedmedicalengineering.com/spirometer.html )"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5816", "contents": "AME"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5817", "contents": "17 November 2009"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5818", "contents": "http://www.advancedmedicalengineering.com/spirometer.html"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5819", "contents": "See below."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5820", "contents": "GFDL \n GNU Free Documentation License \n //en.wikipedia.org/wiki/Wikipedia:Text_of_the_GNU_Free_Documentation_License"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5821", "contents": "Any user may perform this transfer; refer to  Wikipedia:Moving files to Commons  for details."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5822", "contents": "If this file has problems with  attribution ,  copyright , or is otherwise  ineligible  for Commons, then  remove  this tag and  DO NOT  transfer it; repeat violators may be  blocked  from editing."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5823", "contents": "Example of a modern spirometer report"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5824", "contents": "R Wright"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5825", "contents": "The  American Journal of Respiratory and Critical Care Medicine  is a biweekly  peer-reviewed   medical journal  published by the  American Thoracic Society . It covers the  pathophysiology  and treatment of diseases that affect the  respiratory system , as well as topics of fundamental importance to the practice of  pulmonary ,  critical care , and  sleep medicine . It was established in March 1917 as the  American Review of Tuberculosis . [ 1 ]  Since then there have been several title changes. In 1953 a subtitle was added, \" A Journal of Pulmonary Diseases .\" In 1955 the title became the  American Review of Tuberculosis and Pulmonary Diseases , and in 1959 the  American Review of Respiratory Diseases  (the final \"s\" was dropped in 1966). [ 1 ]  The journal obtained its current title in 1994. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5826", "contents": "The journal was established by the National Tuberculosis Association, which became the  American Lung Association , and which published the journal from 1917 until 1994 when its medical section, the American Thoracic Society, became the publisher. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5827", "contents": "The following persons are or have been  editor-in-chief  of the journal:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5828", "contents": "The journal is abstracted and indexed in:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5829", "contents": "According to the  Journal Citation Reports , the journal has a 2022  impact factor  of 24.7, ranking it 2nd out of 36 journals in the category \"Critical Care Medicine\" and 2nd out of 64 journals in the category \"Respiratory System\". [ 15 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5830", "contents": "The  American Journal of Respiratory Cell and Molecular Biology  is a monthly  peer-reviewed   medical journal  and an official publication of the  American Thoracic Society . It covers research on the structure and function of the  respiratory system  under physiologic and pathophysiologic conditions. It was established in July 1989. The founding  editors-in-chief  were Jerome S. Brody, Robert M. Senior, and Mary C. Williams. John A. Mcdonald served as editor from 1993 to 1998. Kenneth B. Adler ( North Carolina State University ) served as editor from 2009 to 2016. Paul Schumacker ( Northwestern University ) served as editor from October 1, 2016, to October 21, 2023.  Andrew Halayko  ( University of Manitoba ) assumed the editorship on November 1, 2023."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5831", "contents": "The journal is abstracted and indexed in  BIOSIS Previews ,  Current Contents /Life Sciences, Current Contents/Critical Care Medicine,  Embase ,  Index Medicus / MEDLINE / PubMed ,  Science Citation Index Expanded , and  Scopus . According to the  Journal Citation Reports , the journal has a 2022  impact factor  of 6.4. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5832", "contents": "The  Annals of the American Thoracic Society  is an official  medical journal  of the  American Thoracic Society  ( ATS ). It publishes original clinical and epidemiological research in the fields of  pulmonology ,  critical care medicine , and  sleep medicine . [ 2 ]  Known colloquially as the \"White Journal\", the  Annals of the American Thoracic Society  is one of four journals published by the American Thoracic Society, along with the  American Journal of Respiratory and Critical Care Medicine  (\"Blue Journal\"),  American Journal of Respiratory Cell and Molecular Biology  (\"Red Journal\"), and  ATS Scholar . [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5833", "contents": "The  Annals of the American Thoracic Society  is a  peer-reviewed   medical journal  that publishes clinical trials and original scientific research related to adult and pediatric pulmonary and respiratory sleep medicine, as well as adult  critical care medicine , that is applicable to clinical practice, the formative and continuing education of clinical specialists, and the advancement of  public health . With a focus on clinical practice, the journal features original research articles, brief communications,  focused reviews , perspectives, opinions and ideas, and NIH workshop reports. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5834", "contents": "Since 2013, the journal has produced a monthly  podcast  in which clinicians and contributing authors to the  Annals of the American Thoracic Society  discuss a range of topics pertaining to pulmonary, critical care, and sleep medicine in order to help research findings reach a wider audience. [ 6 ] [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5835", "contents": "According to the  Journal Citation Reports , the journal has a 2022  impact factor  of 8.3. [ 8 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5836", "contents": "The journal was established in 2004 as the  Proceedings of the American Thoracic Society , obtaining its current name in 2013. [ 9 ]  The  editor-in-chief  was Alan R. Leff ( University of Chicago Medical Center ). He was succeeded in 2012 by John Hansen-Flaschen ( University of Pennsylvania ). David Lederer ( Columbia University Medical Center ) became the third editor-in-chief on April 1, 2017. Colin Cooke ( University of Michigan ) assumed the interim editor-in-chief role on June 27, 2019, and on January 22, 2020, was named the editor-in-chief for a 5-year term. The journal is published online. [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5837", "contents": "The journal is abstracted and indexed in  Index Medicus / MEDLINE / PubMed ,  Chemical Abstracts ,  Scopus , and the  Science Citation Index Expanded ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5838", "contents": "Annals of Thoracic Medicine  is a  peer-reviewed   medical journal  published by the Saudi Thoracic Society through an agreement with the  Wolters Kluwer  brand  Medknow Publications . [ 1 ]   The journal publishes articles on topics within thoracic medicine, which it defines as \"pulmonology, cardiology, thoracic surgery, transplantation, sleep and breathing, airways disease, and more.\" [ 1 ]  All articles are  open access  and are distributed under a  Creative Commons Attribution-NonCommercial-ShareAlike license . [ 1 ]  The journal was started as a semi-annual publication in 2005 and is now published quarterly."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5839", "contents": "Annals of Thoracic Medicine  is indexed with  DOAJ ,  EMBASE , EMR Index Medicus,  Pubmed Central ,  SCImago Journal Rank ,  SCOPUS ,  Web of Science , and  Science Citation Index Expanded . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5840", "contents": "The  Canadian Journal of Respiratory Therapy  (French:  Revue canadienne de la th\u00e9rapie respiratoire ) is a  peer-reviewed   medical journal  covering research on  respiratory therapy  and  pulmonology . It was published on behalf of the  Canadian Society of Respiratory Therapists  by the  Pulsus Group , until this company was acquired by the  OMICS Publishing Group  in 2016. [ 1 ]  This led the society to cancel their publishing agreement with Pulsus. No issues were produced with OMICS. [ 2 ]  The journal partnered with  Canadian Science Publishing [ 2 ]  to publish issues until 2023. As of August 2023 the journal uses the Scholastica platform. The current  editor-in-chief  is Elizabeth Rohrs ( Royal Columbian Hospital ). The journal is open access, indexed in PMC (PubMed Central), Scopus/Embase, Google Scholar, CINAHL, and the Directory of Open Access Journals (DOAJ)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5841", "contents": "The  Canadian Respiratory Journal   is a bimonthly  peer-reviewed   medical journal . It publishes original research and news dealing with respiratory disease, sleep medicine, critical care, and thoracic surgery as well as  continuing medical education  and practice guidelines. It was the official journal of the  Canadian Thoracic Society , the  Canadian Critical Care Society  and the Canadian Sleep Society from 1993 to January 1, 2016, however, its association with these organizations ended when it was purchased from its original publisher, the  Pulsus Group  by the  Hindawi Publishing Corporation . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5842", "contents": "This article about a  medical journal  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5843", "contents": "Chest  is a  peer-reviewed   medical journal  covering  chest   diseases  and related issues, including  pulmonology ,  cardiology ,  thoracic surgery ,  transplantation ,  breathing ,  airway  diseases, and  emergency medicine . The journal was established in 1935. It is the official journal of the  American College of Chest Physicians  which publishes the journal. The  editor-in-chief  is Peter Mazzone (Cleveland Clinic Respiratory Institute)."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5844", "contents": "According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 10.262. [ 7 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5845", "contents": "Chronic Respiratory Disease  is a quarterly  peer-reviewed   medical journal  that covers research in the field of  respiratory disease , including  chronic obstructive pulmonary disease ,  respiratory failure , and  obstructive sleep apnea . The  editors-in-chief  are Mike Morgan ( Glenfield Hospital ), Carolyn Rochester ( Yale University ), and Sally Singh ( Glenfield Hospital ). It was established in 2004 and is published by  SAGE Publications ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5846", "contents": "The  COPD: Journal of Chronic Obstructive Pulmonary Disease  is a  peer-reviewed   medical journal  that covers all aspects of  chronic obstructive pulmonary disease  and its related conditions. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5847", "contents": "The  editor in chief  of  COPD: Journal of Chronic Obstructive Pulmonary Disease  is Vito Brusasco. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5848", "contents": "The  European Respiratory Journal  is a monthly  peer-reviewed   medical journal  covering  respirology . It was established in 1988 and is published by the  European Respiratory Society , of which it is the official journal. The  editor-in-chief  is James D. Chalmers ( University of Dundee ). According to the  Journal Citation Reports , the journal had a 2021  impact factor  of 33.795. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5849", "contents": "Experimental Lung Research  is a  peer-reviewed   medical journal  that publishes original articles in all fields of respiratory tract anatomy, biology, developmental biology, toxicology, and pathology. [ 1 ]  The  editor-in-chief  is Mark Giembycz (Department of Pharmacology and Therapeutics,  University of Calgary ). [ 2 ]  According to the  Journal Citation Reports , the journal has a 2010  impact factor  of 1.069, ranking it 38th out of 46 journals in the category \"Respiratory System\". [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5850", "contents": "Expert Review of Respiratory Medicine  is a bimonthly  peer-reviewed   medical journal  covering  pulmonology . It was established in 2007 and is published by  Taylor & Francis . According to the  Journal Citation Reports , the journal has a 2016  impact factor  of 2.432. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5851", "contents": "Heart & Lung  is a bimonthly  peer-reviewed   nursing journal  covering research on the care of patients with cardiac and pulmonary disorders. It is published by  Mosby  on behalf of the  American Association of Heart Failure Nurses . The journal was established in 1995, with Kathleen S. Stone as its founding  editor-in-chief . Its current editor-in-chief is Nancy S. Redeker ( Yale University )."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5852", "contents": "The journal is abstracted and indexed in  CINAHL ,  MEDLINE , and  PubMed . According to the  Journal Citation Reports , the journal has a 2017  impact factor  of 1.730. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5853", "contents": "This article about a  nursing journal  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5854", "contents": "This article about a  cardiology   journal  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5855", "contents": "The  International Journal of Chronic Obstructive Pulmonary Disease  is a  peer-reviewed   medical journal  focusing on  chronic obstructive pulmonary disease . It was established in 2006; from 2009 it has been available only online. [ 1 ]  It is published by  Dove Medical Press . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5856", "contents": "It is indexed in the  Science Citation Index , [ 3 ]  and the full text of articles are available at  PubMed Central . [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5857", "contents": "The  Journal of Asthma  is a  peer-reviewed   medical journal  that covers  asthma  and related conditions. The  editor-in-chief  is Fulvio Braido ( University of Genoa ). [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5858", "contents": "The  Journal of Asthma and Allergy  is a  peer-reviewed   medical journal  focusing on  asthma  and pulmonary physiology. The journal was established in 2008 and is published by  Dove Medical Press ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5859", "contents": "The Journal of Thoracic and Cardiovascular Surgery  is a monthly  peer-reviewed   medical journal  covering  cardiothoracic surgery ,  cardiology ,  pulmonary medicine , and  vascular disease  published by  Elsevier . It is the official journal of the  American Association for Thoracic Surgery  and the  Western Thoracic Surgical Association ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5860", "contents": "The journal was established in 1931 as the  Journal of Thoracic Surgery . The journal has the second highest impact factor of all  cardiothoracic surgery  journals. According to the  Journal Citation Reports , its 2020  impact factor  is 5.209, ranking it 21st out of 212 journals in the category \"Surgery\". [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5861", "contents": "This article about a  surgery   journal  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5862", "contents": "The  Journal of Thoracic Disease  is a  peer-reviewed   open access   medical journal  covering  pulmonology . It was established in December 2009 and is published monthly by  AME Publishing Company . It is the official journal of the  State Key Laboratory of Respiratory Disease , the  Guangzhou Institute of Respiratory Disease , the First Affiliated Hospital of  Guangzhou Medical University , and the  Society for Thoracic Disease . The  editor-in-chief  is  Zhong Nanshan  (Guangzhou Institute of Respiratory Diseases). According to the  Journal Citation Reports , the journal has a 2016  impact factor  of 2.365. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5863", "contents": "Lung Cancer  is a  peer-reviewed   medical journal  published by  Elsevier  originally published on behalf of the  International Association for the Study of Lung Cancer  (until 2006). As of 2015, it is published on behalf of the  International Lung Cancer Consortium , the  European Thoracic Oncology Platform , and the  British Thoracic Oncology Group . [ 1 ]  It includes original research and review articles of relevance to  lung cancer ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5864", "contents": "The journal is abstracted and indexed in  Current Contents /Clinical Medicine,  EMBASE ,  BIOBASE ,  MEDLINE ,  Oncology Information Service ,  SciSearch , and  Scopus . According to the  Journal Citation Reports ,  Lung Cancer  has a 2020  impact factor  of 5.705, ranking it 13th out of 64 in the category  Respiratory System . [ 2 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5865", "contents": "This article about an  oncology   journal  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5866", "contents": "Lung India  is a  peer-reviewed   open-access   medical journal  published on behalf of the Indian Chest Society. [ 1 ] [ 2 ]  The journal publishes articles on the subject of  respiratory medicine  including  immunology ,  intensive care , sleep medicine,  thoracic surgery , thoracic imaging,  occupational health , and related subjects. [ 1 ]  It is indexed with Caspur, DOAJ, EBSCO Publishing's Electronic Databases, Excerpta Medica/ EMBASE , Expanded Academic ASAP,  JournalSeek , Global Health,  Google Scholar , Health & Wellness Research Center, Health Reference Center Academic,  Hinari , Index Copernicus, Index Medicus for South-East Asia Region, Indian Science Abstracts, IndMed, MANTIS, MedInd, OpenJGate,  ProQuest ,  PubMed , SCOLOAR, SIIC databases, and  Ulrich's Periodicals Directory .\nThe editorial board of Lung India consists of international experts in Pulmonary Medicine. Parvaiz A Koul is the Editor-in-Chief of the journal. The journal is the most popular journal of Pulmonology from India."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5867", "contents": "Pulmonary Circulation  is a  peer-reviewed   medical journal  covering the fields of  pulmonary circulation  and pulmonary vascular disease. It was established in 2011 and is published by  Sage Publications  on behalf of the  Pulmonary Vascular Research Institute , of which it is an official journal. The  editors-in-chief  are Jason X.-J. Yuan and Nicholas W. Morrell."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5868", "contents": "The journal is abstracted and indexed in  BIOSIS Previews [ 1 ]  and  Science Citation Index Expanded . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5869", "contents": "Pulmonary Pharmacology & Therapeutics  is a  medical journal  published by  Elsevier  that covers research on the  pharmacotherapy  of  lung diseases . It was established in 1988 as  Pulmonary Pharmacology  and obtained its current title in 1997."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5870", "contents": "This article about a  pharmacology   journal  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5871", "contents": "Respiratory Care  is a monthly  peer-reviewed   medical journal  published by the  American Association of Respiratory Care . It is abstracted and indexed in  Index Medicus / PubMed  and the  Science Citation Index Expanded . The  editor-in-chief  is Dean R. Hess ( Massachusetts General Hospital  and  Harvard Medical School ). The journal publishes  original research , reviews (narrative and systematic), short reports, correspondence, and editorial articles. It was established in 1956 as  Inhalation Therapy  and obtained its current title in 1970. According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 2.258. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5872", "contents": "Respiratory Care Clinics of North America  ( Respir. Care Clin. N. Am. ) was a  peer-reviewed   healthcare journal  published from 1995 [ 1 ]  to 2006 by  Elsevier . It was indexed by  PubMed / MEDLINE / Index Medicus ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5873", "contents": "This article about a  journal  on  health  or  health care  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5874", "contents": "Respiratory Medicine  is a monthly  peer-reviewed   medical journal  published by  Elsevier  covering research in  pulmonology . According to the  Journal Citation Reports ,  Respiratory Medicine  has a 2020  impact factor  of 3.415. [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5875", "contents": "Respiratory Research  is an  open access   peer-reviewed   medical journal  published by  BioMed Central . It covers all aspects of  respiratory disease , including clinical and basic research. The journal publishes research articles, commentaries,  letters to the editor , and  reviews . [ 1 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5876", "contents": "The journal is abstracted and indexed in  PubMed / MEDLINE , [ 2 ]   Chemical Abstracts Service ,  CAB International ,  Current Contents , [ 3 ]  and the  Science Citation Index Expanded . [ 4 ]  According to the  Journal Citation Reports , its 2016  impact factor  is 3.841, ranking it 8th out of 50 journals in the category \"Respiratory System\". [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5877", "contents": "Respirology  is a  peer-reviewed   medical journal  published by  Wiley  on behalf of the  Asian Pacific Society of Respirology . [ 1 ]  The word  respirology  is derived from the Latin root respirare, \"to breathe\" and the Greek root  logos , \"knowledge\". [ 2 ]  The journal covers  clinical respiratory biology and disease , including  epidemiology ,  intensive and critical care medicine ,  pathology ,  physiology ,  thoracic surgery , and general medicine, as it relates to  respiratory  biology and disease."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5878", "contents": "In 2020, Respirology was included in an expression of concern from  Web of Science   Journal Citation Reports  for excessive self-citation. [ 3 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5879", "contents": "The journal was established in March 1996 by the Asian Pacific Society of Respirology as a quarterly edition. It was subsequently adopted by the Thoracic Society of Australia and New Zealand as its preferred journal, by the Japanese Respiratory Society and the Taiwan Society of Pulmonary and Critical Care Medicine as their preferred English-language journal and by the World Association for Bronchology and Interventional Pulmonology as an official journal. It gradually increased the number of issues to 12 per year. In 2008, an  article processing charge  was introduced. In 2015, the journal moved to online-only delivery."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5880", "contents": "An  open-access  sister journal named  Respirology Case Reports  was launched in 2013. [ 4 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5881", "contents": "In 2020,  Clarivate   Journal Citation Reports  published an expression of concern on a number of journals with extraordinary self-citation rates. Respirology was highlighted for having articles with an atypically large contribution to journal citation metrics, including one article that cited 53 other  Respirology  articles. [ 3 ] [ 5 ]"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5882", "contents": "According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 6.424, ranking it 12th out of 64 journals in the category \"Respiratory System\"."}
+{"id": "WikiPedia_Pulmonology$$$corpus_5883", "contents": "The following persons have been  editor-in-chief  of the journal:"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5884", "contents": "Thorax  is a monthly  peer-reviewed   medical journal  specialising in both clinical and experimental research articles on  respiratory medicine  as well as  paediatrics ,  immunology ,  pharmacology ,  pathology , and  surgery . It was established in 1946 and is published by the  BMJ Group  on behalf of the  British Thoracic Society . The journal is available online by subscription and archived editions of the journal are available free of charge after 1 year. The  editors-in-chief  are"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5885", "contents": "Professor Jennifer Quint, Imperial College London, UK"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5886", "contents": "Professor Mark Griffiths, Imperial College London, UK"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5887", "contents": "Professor Cecilia O'Kane, Queen's University Belfast, UK"}
+{"id": "WikiPedia_Pulmonology$$$corpus_5888", "contents": "Thorax  is abstracted and indexed by  MEDLINE/Index Medicus ,  Science Citation Index ,  Current Contents ,  Excerpta Medica , and  BIOSIS Previews . According to the  Journal Citation Reports , the journal has a 2023  impact factor  of 10.8. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_1", "contents": "Bullectomy  is a surgical procedure in which dilated air-spaces or bullae in  lung parenchyma  are removed. [ 1 ]  Common causes of dilated air-spaces include  chronic obstructive pulmonary disease  and  emphysema . Patients with giant bullae filling half the thoracic volume and compressing relatively normal adjacent parenchyma are recommended for bullectomy. [ 2 ] [ 3 ]  It is also indicated in severe  dyspnea , repeated  respiratory infections  and  spontaneous pneumothorax . [ 4 ]  The size of dilated air-spaces or bullae volume is the most important factor in relation to ventilator capacity post-bullectomy. In cases where the size of bullae are enlarged, bullectomy is indicated if the percentage of forced expiratory volume in one second(FEV1%) is greater than 40% and the regional ventilation over volume dynamic(V/V Dynamic) is greater than 0.5. [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_2", "contents": "Cardiothoracic surgery  is the  field  of  medicine  involved in  surgical treatment  of organs inside the  thoracic cavity  \u2014 generally treatment of conditions of the  heart  ( heart disease ),  lungs  ( lung disease ), and other  pleural  or  mediastinal  structures."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_3", "contents": "In most countries, cardiothoracic surgery is further  subspecialized  into  cardiac surgery  (involving the heart and the  great vessels ) and  thoracic surgery  (involving the lungs,  esophagus ,  thymus , etc.); the exceptions are the  United States ,  Australia ,  New Zealand , the  United Kingdom ,  India  and some  European Union  countries such as  Portugal . [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_4", "contents": "A cardiac surgery  residency  typically comprises anywhere from four to six years (or longer) of training to become a fully qualified surgeon. [ 2 ]  Cardiac surgery training may be combined with thoracic surgery and/or  vascular surgery  and called cardiovascular (CV) / cardiothoracic (CT) / cardiovascular thoracic (CVT) surgery. Cardiac surgeons may enter a cardiac surgery residency directly from  medical school , or first complete a  general surgery  residency followed by a  fellowship . Cardiac surgeons may further sub-specialize cardiac surgery by doing a fellowship in a variety of topics including  pediatric  cardiac surgery,  cardiac transplantation , adult-acquired heart disease, weak heart issues, and many more problems in the heart. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_5", "contents": "The highly competitive Surgical Education and Training (SET) program in Cardiothoracic Surgery is six years in duration, usually commencing several years after completing medical school. Training is administered and supervised via a bi-national (Australia and New Zealand) training program. Multiple examinations take place throughout the course of training, culminating in a final fellowship exam in the final year of training.  Upon completion of training, surgeons are awarded a Fellowship of the  Royal Australasian College of Surgeons  (FRACS), denoting that they are qualified specialists.  Trainees having completed a training program in General Surgery and have obtained their FRACS will have the option to complete fellowship training in Cardiothoracic Surgery of four years in duration, subject to college approval. It takes around eight to ten years minimum of post-graduate (post-medical school) training to qualify as a cardiothoracic surgeon. Competition for training places and for public (teaching) hospital places is very high currently, leading to concerns regarding  workforce planning  in Australia. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_6", "contents": "Historically, cardiac surgeons in  Canada  completed general surgery followed by a fellowship in CV / CT / CVT.  During the 1990s, the Canadian cardiac surgery training programs changed to six-year \"direct-entry\" programs following medical school. The direct-entry format provides residents with experience related to cardiac surgery they would not receive in a general surgery program (e.g.  echocardiography ,  coronary care unit , cardiac catheterization etc.). Residents in this program will also spend time training in thoracic and  vascular surgery . Typically, this is followed by a fellowship in either Adult Cardiac Surgery, Heart Failure/Transplant, Minimally Invasive Cardiac Surgery, Aortic Surgery, Thoracic Surgery, Pediatric Cardiac Surgery or Cardiac ICU. Contemporary Canadian candidates completing general surgery and wishing to pursue cardiac surgery often complete a cardiothoracic surgery fellowship in the United States. The Royal College of Physicians and Surgeons of Canada also provides a three-year cardiac surgery fellowship for qualified general surgeons that is offered at several training sites including the  University of Alberta , the  University of British Columbia  and the  University of Toronto . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_7", "contents": "Thoracic surgery is its own separate 2\u20133 year fellowship of general or cardiac surgery in Canada."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_8", "contents": "Cardiac surgery programs in Canada: [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_9", "contents": "Cardiac surgery training in the  United States  is combined with general  thoracic surgery  and called cardiothoracic surgery or thoracic surgery.  A cardiothoracic surgeon in the U.S. is a physician who first completes a  general surgery  residency (typically 5\u20137 years), followed by a cardiothoracic surgery fellowship (typically 2\u20133 years). The cardiothoracic surgery fellowship typically spans two or three years, but certification is based on the number of surgeries performed as the operating surgeon, not the time spent in the program, in addition to passing rigorous board certification tests.  Two other pathways to shorten the duration of training have been developed: (1) a combined general-thoracic surgery residency consisting of four years of general surgery training and three years of cardiothoracic training at the same institution and (2) an integrated six-year cardiothoracic residency (in place of the general surgery residency plus cardiothoracic residency), which have each been established at many programs (over 20). [ 3 ]   Applicants match into the integrated six-year (I-6) programs directly out of medical school, and the application process has been extremely competitive for these positions as there were approximately 160 applicants for 10 spots in the U.S. in 2010.  As of May 2013, there are 20 approved programs, which include the following:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_10", "contents": "Integrated six-year Cardiothoracic Surgery programs in the United States: [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_11", "contents": "The  American Board of Thoracic Surgery  offers a special pathway certificate in congenital cardiac surgery which typically requires an additional year of fellowship. This formal certificate is unique because congenital cardiac surgeons in other countries do not have formal evaluation and recognition of pediatric training by a licensing body."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_12", "contents": "The earliest operations on the  pericardium  (the sac that surrounds the heart) took place in the 19th century and were performed by  Francisco Romero  (1801) [ 4 ]   Dominique Jean Larrey ,  Henry Dalton , and  Daniel Hale Williams . [ 5 ]  The first surgery on the heart itself was performed by  Norwegian  surgeon  Axel Cappelen  on 4 September 1895 at  Rikshospitalet  in Kristiania, now  Oslo . He  ligated  a bleeding  coronary artery  in a 24-year-old man who had been stabbed in the left  axilla  and was in deep  shock  upon arrival. Access was through a left  thoracotomy . The patient awoke and seemed fine for 24 hours, but became ill with increasing temperature and he ultimately died from what the  post mortem  proved to be  mediastinitis  on the third postoperative day. [ 6 ] [ 7 ]  The first successful surgery of the heart, performed without any complications, was by  Ludwig Rehn  of  Frankfurt ,  Germany , who repaired a stab wound to the right  ventricle  on September 7, 1896. [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_13", "contents": "Surgery in  great vessels  ( aortic coarctation  repair,  Blalock-Taussig shunt  creation, closure of  patent ductus arteriosus ) became common after the turn of the century and falls in the domain of cardiac surgery, but technically cannot be considered heart surgery.  One of the more commonly known cardiac surgery procedures is the  coronary artery bypass graft (CABG) , also known as \"bypass surgery.\""}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_14", "contents": "In 1925 operations on the  heart valves  were unknown.  Henry Souttar  operated successfully on a young woman with  mitral stenosis . He made an opening in the appendage of the left atrium and inserted a finger into this chamber in order to palpate and explore the damaged mitral valve. The patient survived for several years [ 10 ]  but Souttar's physician colleagues at that time decided the procedure was not justified and he could not continue. [ 11 ] [ 12 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_15", "contents": "Cardiac surgery changed significantly after  World War II . In 1948 four surgeons carried out successful operations for  mitral stenosis  resulting from  rheumatic fever .  Horace Smithy  (1914\u20131948) revived an operation due to Dr  Dwight Harken  of the  Peter Bent Brigham Hospital  using a punch to remove a portion of the  mitral valve .  Charles Bailey  (1910\u20131993) at the  Hahnemann Hospital ,  Philadelphia ,  Dwight Harken  in  Boston  and  Russell Brock  at  Guy's Hospital  all adopted Souttar's method. All these men started work independently of each other, within a few months. This time Souttar's technique was widely adopted although there were modifications. [ 11 ] [ 12 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_16", "contents": "In 1947  Thomas Holmes Sellors  (1902\u20131987) of the  Middlesex Hospital  operated on a  Fallot's Tetralogy  patient with  pulmonary stenosis  and successfully divided the stenosed  pulmonary valve . In 1948,  Russell Brock , probably unaware of Sellor's work, used a specially designed dilator in three cases of  pulmonary stenosis . Later in 1948 he designed a punch to resect the  infundibular muscle   stenosis  which is often associated with  Fallot's Tetralogy . Many thousands of these \"blind\" operations were performed until the introduction of heart bypass made direct surgery on valves possible. [ 11 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_17", "contents": "Open heart surgery is a procedure in which the patient's heart is opened and surgery is performed on the internal structures of the heart. It was discovered by  Wilfred G. Bigelow  of the  University of Toronto  that the repair of intracardiac pathologies was better done with a bloodless and motionless environment, which means that the heart should be stopped and drained of blood. The first successful intracardiac correction of a  congenital heart defect  using  hypothermia  was performed by  C. Walton Lillehei  and  F. John Lewis  at the  University of Minnesota  on September 2, 1952. The following year,  Soviet  surgeon  Aleksandr Aleksandrovich Vishnevskiy  conducted the first cardiac surgery under  local anesthesia . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_18", "contents": "Surgeons realized the limitations of hypothermia \u2013 complex intracardiac repairs take more time and the patient needs blood flow to the body, particularly to the  brain . The patient needs the function of the heart and  lungs  provided by an artificial method, hence the term  cardiopulmonary bypass .  John Heysham Gibbon  at Jefferson Medical School in Philadelphia reported in 1953 the first successful use of extracorporeal circulation by means of an  oxygenator , but he abandoned the method, disappointed by subsequent failures. In 1954 Lillehei realized a successful series of operations with the controlled cross-circulation technique in which the patient's mother or father was used as a ' heart-lung machine '.  John W. Kirklin  at the  Mayo Clinic  in Rochester, Minnesota started using a Gibbon type pump-oxygenator in a series of successful operations, and was soon followed by surgeons in various parts of the world. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_19", "contents": "Nazih Zuhdi  performed the first total intentional hemodilution open heart surgery on Terry Gene Nix, age 7, on February 25, 1960, at Mercy Hospital, Oklahoma City, OK. The operation was a success; however, Nix died three years later in 1963. [ 13 ]  In March, 1961, Zuhdi, Carey, and Greer, performed open heart surgery on a child, age  3 + 1 \u2044 2 , using the total intentional hemodilution machine. In 1985 Zuhdi performed Oklahoma's first successful heart transplant on Nancy Rogers at Baptist Hospital. The transplant was successful, but Rogers, who had  cancer , died from an infection 54 days after surgery. [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_20", "contents": "Since the 1990s, surgeons have begun to perform \" off-pump bypass surgery \" \u2013 coronary artery bypass surgery without the aforementioned  cardiopulmonary bypass . In these operations, the heart is beating during surgery, but is stabilized to provide an almost still work area in which to connect the conduit vessel that bypasses the blockage; in the U.S., most conduit vessels are harvested endoscopically, using a technique known as  endoscopic vessel harvesting  (EVH). [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_21", "contents": "Some researchers believe that the off-pump approach results in fewer post-operative complications, such as  postperfusion syndrome , and better overall results. Study results are controversial as of 2007, the surgeon's preference and hospital results still play a major role. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_22", "contents": "A new form of heart surgery that has grown in popularity is  robot-assisted heart surgery . This is where a machine is used to perform surgery while being controlled by the heart surgeon. The main advantage to this is the size of the incision made in the patient. Instead of an incision being at least big enough for the surgeon to put his hands inside, it does not have to be bigger than 3 small holes for the robot's much smaller \"hands\" to get through. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_23", "contents": "Pediatric cardiovascular surgery is surgery of the heart of children. The first operations to repair cardio-vascular [ 15 ]  defects in children were performed by Clarence Crafoord in Sweden when he repaired coarctation of the aorta in a 12-year-old boy. [ 16 ]  The first attempts to palliate congenital heart disease were performed by Alfred Blalock with the assistance of William Longmire, Denton Cooley, and Blalock's experienced technician, Vivien Thomas in 1944 at Johns Hopkins Hospital. [ 17 ]   Techniques for repair of congenital heart defects without the use of a bypass machine were developed in the late 1940s and early 1950s.  Among them was an open repair of an atrial septal defect using hypothermia, inflow occlusion and direct vision in a 5-year-old child performed in 1952 by Lewis and Tauffe. C. Walter Lillihei used cross-circulation between a boy and his father to maintain perfusion while performing a direct repair of a ventricular septal defect in a 4-year-old child in 1954. [ 18 ]  He continued to use cross-circulation and performed the first corrections of tetralogy of Fallot and presented those results in 1955 at the American Surgical Association. In the long-run, pediatric cardiovascular surgery would rely on the cardiopulmonary bypass machine developed by Gibbon and Lillehei as noted above. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_24", "contents": "The development of cardiac surgery and cardiopulmonary bypass techniques has reduced the mortality rates of these surgeries to relatively low ranks. For instance, repairs of congenital heart defects are currently estimated to have 4\u20136% mortality rates. [ 19 ] [ 20 ]  A major concern with cardiac surgery is the incidence of  neurological  damage.  Stroke  occurs in 5% of all people undergoing cardiac surgery, and is higher in patients at risk for stroke. [ 21 ]  A more subtle constellation of  neurocognitive deficits  attributed to  cardiopulmonary bypass  is known as  postperfusion syndrome , sometimes called \"pumphead\". The symptoms of postperfusion syndrome were initially felt to be permanent, [ 22 ]  but were shown to be transient with no permanent neurological impairment. [ 23 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_25", "contents": "To assess the performance of surgical units and individual surgeons, a popular risk model has been created called the  EuroSCORE .  This takes a number of health factors from a patient and using precalculated logistic regression coefficients attempts to give a percentage chance of survival to discharge.  Within the UK this EuroSCORE was used to give a breakdown of all the centres for cardiothoracic surgery and to give some indication of whether the units and their individual surgeons performed within an acceptable range. The results are available on the CQC website. [ 24 ]   The precise methodology used has however not been published to date nor has the raw data on which the results are based. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_26", "contents": "Infection represents the primary non-cardiac complication from cardiothoracic surgery. Infections include mediastinitis, infectious myo- or pericarditis, endocarditis, cardiac device infection, pneumonia, empyema, and bloodstream infections.  Clostridioides difficile  colitis can develop when prophylactic or post-operative antibiotics are used."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_27", "contents": "Post-operative patients of cardiothoracic surgery are at risk of nausea, vomiting, dysphagia, and aspiration pneumonia. [ 25 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_28", "contents": "A pleurectomy is a surgical procedure in which part of the  pleura  is removed. It is sometimes used in the treatment of  pneumothorax  and  mesothelioma . [ 26 ]  In case of pneumothorax, only the apical and the diaphragmatic portions of the parietal pleura are removed. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_29", "contents": "Lung volume reduction surgery, or LVRS, can improve the quality of life for certain patients with  COPD  of  emphysematous  type, when other treatment options are not enough. Parts of the  lung  that are particularly damaged by emphysema are removed, allowing the remaining, relatively good lung to expand and work more efficiently.  The beneficial effects are correlated with the achieved reduction in residual volume. [ 27 ]   Conventional LVRS involves  resection  of the most severely affected areas of emphysematous, non- bullous  lung (aim is for 20\u201330%). This is a surgical option involving a  mini-thoracotomy  for patients in end stage COPD due to underlying emphysema, and can improve lung  elastic recoil  as well as  diaphragmatic function . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_30", "contents": "The National Emphysema Treatment Trial (NETT) was a large multicentre study (N = 1218) comparing LVRS with non-surgical treatment. Results suggested that there was no overall survival advantage in the LVRS group, except for mainly upper-lobe emphysema + poor exercise capacity, and significant improvements were seen in exercise capacity in the LVRS group. [ 28 ]  Later studies have shown a wider scope of treatment with better outcomes. [ 29 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_31", "contents": "Possible complications of LVRS include prolonged air leak (mean duration post surgery until all  chest tubes  removed is 10.9 \u00b1 8.0 days. [ 30 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_32", "contents": "In people who have a predominantly upper lobe emphysema, lung volume reduction surgery could result in better health status and lung function, though it also increases the risk of early mortality and adverse events. [ 31 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_33", "contents": "LVRS is used widely in Europe, though its application in the United States is mostly experimental. [ 32 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_34", "contents": "A less invasive treatment is available as a  bronchoscopic lung volume reduction  procedure. [ 33 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_35", "contents": "Not all lung cancers are suitable for surgery. The  stage , location and cell type are important limiting factors. In addition, people who are very ill with a poor  performance status  or who have inadequate pulmonary reserve would be unlikely to survive. Even with careful selection, the overall operative death rate is about 4.4%. [ 34 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_36", "contents": "In  non-small cell lung cancer staging , stages IA, IB, IIA, and IIB are suitable for surgical resection. [ 35 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_37", "contents": "Pulmonary reserve is measured by  spirometry . If there is no evidence of undue shortness of breath or  diffuse parenchymal lung disease , and the FEV 1  exceeds 2 litres or 80% of predicted, the person is fit for  pneumonectomy . If the FEV 1  exceeds 1.5 litres, the patient is fit for lobectomy. [ 36 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_38", "contents": "There is weak evidence to indicate that participation in exercise programs before lung cancer surgery may reduce the risk of complications after surgery. [ 37 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_39", "contents": "A prolonged air leak (PAL) can occur in 8\u201325% of people following lung cancer surgery. [ 38 ] [ 39 ]  This complication delays chest tube removal and is associated with an increased length of hospital stay following a lung resection (lung cancer surgery). [ 40 ] [ 41 ]  The use of  surgical sealants  may reduce the incidence of prolonged air leaks, however, this intervention alone has not been shown to results in a decreased length of hospital stay following lung cancer surgery. [ 42 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_40", "contents": "There is no strong evidence to support using  non-invasive positive pressure ventilation  following lung cancer surgery to reduce pulmonary complications. [ 43 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_41", "contents": "Decortication  is a  medical  procedure involving the  surgical  removal of the surface layer,  membrane , or fibrous cover of an  organ .  The procedure is usually performed when the  lung  is covered by a thick, inelastic  pleural peel  restricting lung expansion.  In a non-medical aspect, decortication is the removal of the bark, husk, or outer layer, or peel of an object. [ 1 ]  It may also be done in the treatment of  chronic laryngitis . It is the primary treatment for  fibrothorax ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_42", "contents": "Decortication is performed under general  anaesthesia .  It is a major thoracic operation that has traditionally required a full  thoracotomy . Since the early '90s this procedure has increasingly been performed using more minimally invasive  thoracoscopy . All fibrous tissue is removed from the visceral pleural peel and  pus  is subsequently drained from the pleural space. [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_43", "contents": "Other than the overall health of the patients, there are no absolute contraindications. In some lung-disease patients, the lung will not expand after removal of the pleural peel, rendering the surgery futile. Other diseases that render decortication futile are narrowing of the large airway stenosis and uncontrolled pleural infection. With these conditions, the lung will not expand to fill the thorax space. A major surgery called a pleuropneumonectomy can be the only available option, but only if the patient has been worked up before the surgery. Pleuropneumonectomy is a major surgery with a very high mortality and high invasiveness. [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_44", "contents": "The  Eloesser flap  is a surgical procedure developed by  Dr. Leo Eloesser  in 1935 at the  San Francisco General Hospital . [ 1 ]  It was originally intended to aid with drainage of  tuberculous empyemas , since at the time there were no effective medications to treat  tuberculosis . The procedure was used extensively [ 2 ]  until the development of  effective antimicrobial therapy for tuberculosis  in the late 1940s and early 1950s. [ 3 ]  It is still used occasionally for chronic  empyemas . [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_45", "contents": "As originally described by Dr. Eloesser, the procedure started with cutting a 2 inch wide, U-shaped flap of skin on the side of the chest wall underneath the  axilla  and  scapula . The section of  rib  under the top of the flap was also removed. The finger-like skin flap was then inserted into the cavity made in the chest wall and sewn into the inner pleural lining of the chest. The edges of the incision are then brought together. [ 1 ]  The flap allows for 1) passive drainage of the pleural space and 2) negative pressure to develop in the thoracic cavity due to it being easier for air to escape than to enter the chest. The lung can then expand to the chest wall and seal the inner opening of the flap. [ 3 ]  Other surgeons have subsequently proposed modifications to the procedure. [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_46", "contents": "The Eloesser flap is still utilized for patients with chronic empyemas who have not improved despite being treated with  antibiotics  and first line surgical procedures to remove pus and re-expand the lung such as  decortication  or  video-assisted thoracoscopic surgery . [ 4 ]  Often they are thought to be too ill for more definitive procedures such as a major  thoracotomy  or  muscle flap transposition . [ 5 ]  In a recent case series, the most common reasons to need an Eloesser flap were  parapneumonic effusions  and postresection empyemas, with only 9% done for  tuberculosis . [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_47", "contents": "A downside to the procedure is that a permanent drainage path from the  thoracic cavity  is made and will need prolonged wound care and dressing changes. [ 4 ] [ 5 ]  Complications can also include sepsis. [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_48", "contents": "Prior to the development of the Eloesser flap in the 1930s, the main surgical treatments for chronic tuberculous empyema were an open thoracotomy or chest tube drainage. In his original published description of the procedure, Dr. Eloesser wrote that he felt that those options were \"unsatisfactory\" as he felt they led to secondary infection and death. [ 1 ]  Another option included removing the infected fluid with a needle through the chest wall (percutaneous drainage) but it often quickly reaccumulated. Dr. Eloesser explained that when developing his procedure he wished to maintain drainage as with a chest tube to allow the lung to re-expand but without the presence of the chest tube that he felt \"tends to keep up fever and sepsis.\" [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_49", "contents": "A  heart\u2013lung transplant  is a procedure carried out to replace both failing  heart  and  lungs  in a single operation. Due to a shortage of suitable donors and because both heart and lung have to be transplanted together, it is a rare procedure; only about a hundred such transplants are performed each year in the United States. [ United States-centric ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_50", "contents": "The patient is  anesthetised . When the donor organs arrive, they are checked for fitness; if any organs show signs of damage, they are discarded and the operation cancelled."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_51", "contents": "Once suitable donor organs are present, the surgeon makes an incision starting above and finishing below the sternum, cutting all the way to the bone. The skin edges are retracted to expose the sternum. Using a bone saw, the sternum is cut down the middle. Rib spreaders are inserted in the cut, and spread the ribs to give access to the heart and lungs of the patient."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_52", "contents": "The patient is connected to a  heart\u2013lung machine , which circulates and oxygenates blood. The surgeon removes the failing heart and lungs. Most surgeons endeavour to cut blood vessels as close as possible to the heart to leave room for trimming, especially if the donor heart is of a different size than the original organ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_53", "contents": "The donor heart and lungs are positioned and sewn into place. As the donor organs warm up to body temperature, the lungs begin to inflate. The heart may  fibrillate  at first \u2013 this occurs because the  cardiac muscle  fibres are not contracting synchronously. Internal paddles can be used to apply a small electric shock to the heart to restore proper rhythm."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_54", "contents": "Once the donor organs are functioning normally, the heart\u2013lung machine is withdrawn, and the chest is closed."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_55", "contents": "Most candidates for heart\u2013lung transplants have life-threatening damage to both their heart and lungs. In the US, most prospective candidates have between twelve and twenty-four months to live. At any one time, there are about 250 people registered for heart\u2013lung transplantation at the  United Network for Organ Sharing  (UNOS) in the US, of which around forty will die before a suitable donor is found. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_56", "contents": "Conditions which may necessitate a heart\u2013lung transplant include:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_57", "contents": "Candidates for a heart\u2013lung transplant are usually required to be:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_58", "contents": "Most patients spend several days in  the intensive care unit  after the operation. If there are no complications (e.g.,  infection ,  rejection ), some are able to return home after just two weeks in hospital. Patients will be given  anti-rejection drugs  and  antibiotics  to prevent infection as the anti-rejection drugs weakens the immune system. A schedule of frequent follow up visits is necessary."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_59", "contents": "The success rate of heart\u2013lung transplants has improved significantly in recent years. The British  National Health Service  states that the survival rate is now around 85%, one year after the transplant was performed. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_60", "contents": "In 2004, there were only 39 heart\u2013lung transplants performed in the entire United States and only 75 worldwide. By comparison, in that same year there were 2,016 heart and 1,173 lung transplants. [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_61", "contents": "Norman Shumway  laid the groundwork for heart lung transplant with his experiments into heart transplant at  Stanford  in the mid-1960s. [ citation needed ]  Shumway conducted the first adult heart transplant in the US in 1968. [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_62", "contents": "The first successful heart transplant was performed in South Africa in 1967. [ 4 ]  The first successful heart\u2013lung transplant was performed at Stanford in the United States, by  Bruce Reitz  on  Mary Gohlke  in 1981. [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_63", "contents": "Magdi Yacoub  performed the first heart-lung transplant in the United Kingdom in 1983. [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_64", "contents": "Australia's first heart-lung transplant was conducted by  Victor Chang  at  St Vincent's Hospital, Sydney  in 1986. [ 7 ]  Iran's first heart-lung transplant was performed in Tehran in 2002. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_65", "contents": "Isolated lung perfusion  is a  surgical procedure  during which the  circulation of blood  to the  lungs  is separated from the circulation of blood through the rest of the body, and a drug is delivered directly into the lung circulation. This allows a higher concentration of  chemotherapy  to reach  tumors  in the lungs."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_66", "contents": "This article incorporates  public domain material  from  Dictionary of Cancer Terms .  U.S. National Cancer Institute ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_67", "contents": "This  oncology  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_68", "contents": "Lobectomy of the lung  is a  surgical  operation where a  lobe  of the  lung  is removed. [ 1 ]  It is done to remove a portion of diseased lung, such as early  stage   lung cancer . [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_69", "contents": "The most common type of lobectomy is known as a  thoracotomy .  When this type of surgery is done the chest is opened up.  An incision will be made on the side of the chest where the affected area of the lung is located. The incision will be in between the two ribs located in that area.  The surgeon will then be able to have access to the chest cavity once the two involved ribs have been pried open. The surgeon will then be able to remove the lobe where the problem is contained. [ 3 ] \nAnother less invasive lobectomy procedure can be performed through a  video assisted surgery , where the surgeon does not need to pry the two ribs open in order to get access.  A few small incisions are made and surgical tools are inserted into the chest cavity aided by a small video camera. The video images will be projected onto a screen that the surgeon can see. Once the problem area is located the small tools that were previously inserted will be utilized to perform the surgery. [ 3 ]  Once the surgery is complete, the patient will remain in the intensive care unit of the hospital for a day. They will then remain in a regular hospital room for about 4 to 7 days. [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_70", "contents": "As with any surgery, complications may occur. Post lobectomy air leak is a significant clinical problem, [ 5 ]  and patients undergoing pulmonary resections often present with postoperative air leaks. [ 6 ]  Other risk factors include infections, reactions to anesthesia, bleeding,  pneumothorax  and  bronchopleural fistula . [ 7 ]  New methods for sealing tissue are evaluated in research studies, aimed to determine their efficacies in preventing air leakages. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_71", "contents": "The main infection that a patient runs the risk of is  pneumonia . Pneumothorax occurs when there is air trapped between the lung and the chest wall; this can leave the patient's lung unable to fully inflate (\"collapsed lung\"). A bronchopleural fistula is when there is a tube-like opening that allows air to escape. [ 9 ]  Minimally invasive surgery is beneficial for patient outcome, with reduced risk of complications. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_72", "contents": "Once the surgery is complete, the patient will remain in the intensive care unit of the hospital for a day. They will then remain in a regular hospital room for about 4 to 7 days. [ 4 ]   After the patient returns home they typically remain in recovery for about four to six weeks, although some patients may be able to return to work and normal activities sooner. [ medical citation needed ]   Pain is very common amongst patients for quite some time after a lobectomy and doctors will usually prescribe pain medication to help with this. [ 11 ]   Chest tubes are left inside the patient in order to help excess fluid drain and are removed after a few days. Before removal, doctors must ensure that there is no air or  fluid leaking from them. [ 11 ]   In addition to this, follow-up appointments will be scheduled with the patient's doctor. X-rays will be taken of the patient's lung to make sure everything is healing properly. Patients that have had a lobectomy with no major risks shall recover in no longer than three months. [ medical citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_73", "contents": "Lung transplantation , or  pulmonary transplantation , is a surgical procedure in which one or both  lungs  are replaced by lungs from a donor. Donor lungs can be retrieved from a living or deceased donor. A living donor can only donate one  lung lobe . With some lung diseases, a recipient may only need to receive a single lung. With other lung diseases such as  cystic fibrosis , it is imperative that a recipient receive two lungs. While lung transplants carry certain associated risks, they can also extend life expectancy and enhance the quality of life for those with  end stage pulmonary disease . [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_74", "contents": "Lung transplantation is the therapeutic measure of last resort for patients with end-stage lung disease who have exhausted all other available treatments without improvement. A variety of conditions may make such surgery necessary. As of 2005, the most common reasons for lung transplantation in the  United States  were: [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_75", "contents": "Despite the severity of a patient's respiratory condition, certain pre-existing conditions may make a person a poor candidate for lung transplantation: [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_76", "contents": "The history of  organ transplants  began with several attempts that were unsuccessful due to  transplant rejection . Animal experimentation by various pioneers, including  Vladimir Demikhov  and Henry Metras, [ 5 ]  during the 1940s and 1950s first demonstrated that the procedure was technically feasible.  James Hardy  of the  University of Mississippi  performed the first human lung transplant on June 11, 1963. [ 6 ] [ 7 ] [ 8 ]  Following a single-lung transplantation, the patient, identified later as convicted murderer John Richard Russell, [ 9 ]  survived for 18 days. From 1963 to 1978, multiple attempts at lung transplantation failed because of  rejection  and problems with  anastomotic  bronchial healing (i.e. reconnection of  Bronchial passages ). It was only after the invention of the  heart-lung machine , coupled with the development of  immunosuppressive drugs  such as  ciclosporin , that organs such as the lungs could be transplanted with a reasonable chance of patient recovery. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_77", "contents": "The first successful transplant surgery involving the lungs was a  heart-lung transplant , performed by Dr.  Bruce Reitz  of  Stanford University  in 1981 on a woman who had idiopathic  pulmonary hypertension . [ 11 ] [ 12 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_78", "contents": "In 1988, Vera Dwyer, a woman from  County Sligo  in  Ireland , was diagnosed with an irreversible, chronic and fibrotic lung disease. Later on that year, she received a single lung transplant in the UK. In November 2018, Ms. Dwyer was recognized as the world's longest surviving single lung transplant recipient in an event at the  Mater Hospital  in  Dublin . [ 15 ] [ 16 ]  She died in 2021, thirty-three years after her transplant. [ 17 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_79", "contents": "There are certain requirements for potential lung donors, due to the needs of the potential recipient. In the case of living donors, this is also in consideration of how the surgery will affect the donor: [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_80", "contents": "While a transplant center is free to set its own criteria for transplant candidates, certain requirements are generally agreed upon: [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_81", "contents": "Patients who are being considered for placement on the organ transplant list undergo extensive medical tests to evaluate their overall health status and suitability for transplant surgery. [ 20 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_82", "contents": "Before 2005, donor lungs within the United States were allocated by the  United Network for Organ Sharing  on a  first-come, first-served  basis to patients on the transplant list. This was replaced by the current system, in which prospective lung recipients of age of 12 and older are assigned a  lung allocation score  or LAS, which takes into account various measures of the patient's health. The new system allocates donated lungs according to the immediacy of need rather than how long a patient has been on the transplant list. Patients who are under the age of 12 are still given priority based on how long they have been on the transplant waitlist. The length of time spent on the list is also the deciding factor when multiple patients have the same lung allocation score. [ 21 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_83", "contents": "Patients who are accepted as good potential transplant candidates must carry a pager with them at all times in case a donor organ becomes available. These patients must also be prepared to move to their chosen transplant center at a moment's notice. Such patients may be encouraged to limit their travel within a certain geographical region in order to facilitate rapid transport to a transplant center. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_84", "contents": "A lobe transplant is a surgery in which part of a living or deceased donor's lung is removed and used to replace the recipient's diseased lung. In living donation, this procedure requires the donation of lobes from two different people, replacing a lung on each side of the recipient. Donors who have been properly screened should be able to maintain a normal quality of life despite the reduction in lung volume. In deceased lobar transplantation, one donor can provide both lobes. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_85", "contents": "Many patients can be helped by the transplantation of a single healthy lung. The donated lung typically comes from a donor who has been pronounced  brain-dead . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_86", "contents": "Certain patients may require both lungs to be replaced. This is especially the case for people with  cystic fibrosis , due to the bacterial colonization commonly found within such patients' lungs; if only one lung were transplanted, bacteria in the native lung could potentially infect the newly transplanted organ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_87", "contents": "Some respiratory patients may also have severe  cardiac disease  which would necessitate a heart transplant. These patients can be treated by a surgery in which both lungs and the heart are replaced by organs from a donor or donors. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_88", "contents": "A particularly involved example of this has been termed a \"domino transplant\" in the media. First performed in 1987, this type of transplant typically involves the transplantation of a heart and lungs into recipient A, whose own healthy heart is removed and transplanted into recipient B. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_89", "contents": "While the surgical details will depend on the type of transplant, many steps are common to all these procedures. Before operating on the recipient, the transplant surgeon inspects the donor lung(s) for signs of damage or disease. If the lung or lungs are approved, then the recipient is connected to an  IV  line and various monitoring equipment, including  pulse oximetry . The patient will be given  general anesthesia , and a machine will breathe for him or her. [ 23 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_90", "contents": "It takes about one hour for the pre-operative preparation of the patient. A single lung transplant takes about four to eight hours, while a double lung transplant takes about six to twelve hours to complete. A history of prior chest surgery may complicate the procedure and require additional time. [ 23 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_91", "contents": "In single-lung transplants, the lung with the worse pulmonary function is chosen for replacement. If both lungs function equally, then the right lung is usually favored for removal because it avoids having to maneuver around the heart, as would be required for excision of the left lung. [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_92", "contents": "In a single-lung transplant the process starts out after the donor lung has been inspected and the decision to accept the donor lung for the patient has been made. An incision is generally made from under the shoulder blade around the chest, ending near the sternum. An alternate method involves an incision under the breastbone. [ 2 ]  In the case of a singular lung transplant the lung is collapsed, the blood vessels in the lung tied off, and the lung removed at the  bronchial  tube. The donor lung is placed, the blood vessels and bronchial tube reattached, and the lung reinflated. To make sure the lung is satisfactory and to clear any remaining blood and mucus in the new lung a  bronchoscopy  will be performed. When the surgeons are satisfied with the performance of the lung the chest incision will be closed. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_93", "contents": "A double-lung transplant, also known as a bilateral transplant, can be done either sequentially, en bloc, or simultaneously. Sequential is more common than en bloc. [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_94", "contents": "The transplantation process starts after the donor lungs are inspected and the decision to transplant has been made. An incision is then made from under the patient's armpit, around to the sternum, and then back towards the other armpit; this is known as a clamshell incision. Another approach can be achieved with bilateral anterior thoracotomies. [ 24 ]  Intraoperatively, lung transplantation can be performed with the use of extracorporeal membrane oxygenation, cardiopulmonary bypass (heart-lung machine) or without any mechanical circulatory support. Intraoperative mechanical circulatory support can be required due to severe pulmonary hypertension, haemodynamic instability or inability to tolerate one-lung ventilation. [ 25 ]  In the case of a sequential transplant the recipient's lung with the poorest  lung functions  is collapsed, the blood vessels tied off, and cut at the corresponding  bronchi . The new lung is then placed and the blood vessels reanastomosed (reconnected). To make sure the bronchial anastomosis is satisfactory before transplanting the other a  bronchoscopy  is performed."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_95", "contents": "Immediately following the surgery, the patient is placed in an  intensive care unit  for monitoring, normally for a period of a few days. The patient is put on a  ventilator  to assist breathing. Nutritional needs are generally met via  total parenteral nutrition , although in some cases a  nasogastric tube  is sufficient for feeding.  Chest tubes  are put in so that  excess fluids  may be removed. Because the patient is confined to bed, a  urinary catheter  is used. IV lines are used in the neck and arm for  monitoring  and giving medications. [ 23 ] \nAfter a few days, barring any complications, the patient may be transferred to a general inpatient ward for further recovery. The average hospital stay following a lung transplant is generally one to three weeks, though complications may require a longer period of time. [ 23 ]  After this stage, patients are typically required to attend rehabilitation gym for approximately 3 months to regain fitness. Light weights, exercise bike, treadmill, stretches and more are all a part of the rehabilitation programme. Postoperative rehabilitation is crucial for the outcomes of transplant recipients and has evolved since the late 20th century. [ 26 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_96", "contents": "There may be a number of side effects following the surgery. Because certain  nerve  connections to the lungs are cut during the procedure, transplant recipients cannot feel the urge to cough or feel when their new lungs are becoming congested. They must therefore make conscious efforts to take deep breaths and cough in order to clear secretions from the lungs. [ 27 ]  Their  heart rate  responds less quickly to exertion due to the cutting of the  vagus nerve  that would normally help regulate it. [ 28 ]  They may also notice a change in their voice due to potential damage to the nerves that coordinate the  vocal cords . [ 28 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_97", "contents": "Evidence suggests that exercise may contribute to speeding up physical recovery in adults after lung transplantation, helping to minimize disability from physical inactivity, both pre and post-transplant. [ 29 ]  However, there are no detailed guidelines on how exercise should be performed in this type of population. [ 29 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_98", "contents": "The results obtained from a 2021 Systematic Review concluded that the effects of exercise in this population are still very questionable. [ 29 ]  While some studies do report benefits taken from exercising, while others have not reached the same conclusions. [ 29 ]  Nonetheless, the articles involved in this systematic review reported enhancements in muscle strength and increased bone mineral density as well as improvements in 6MWT. [ 29 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_99", "contents": "Post-transplant patients are held from driving for the first 3 months pending an assessment of the patient's capacity to drive; this assessment is usually performed by an  occupational therapist . Eyesight, physical ability to do simple actions such as check blind spots, wear a seat belt safely without the wound site being affected and hand eye coordination are all assessed. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_100", "contents": "Hygiene becomes more important in everyday living due to the  immunosuppressant  drugs which are required every day to prevent transplant rejection. Lack of a strong immune system leaves transplant recipients vulnerable to infections. Care must be taken in food preparation and hygiene as  gastroenteritis  becomes more of a risk. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_101", "contents": "As with any surgical procedure, there are risks of bleeding and infection. The newly transplanted lung itself may fail to properly heal and function. Because a large portion of the patient's body has been exposed to the outside air,  sepsis  is a possibility, so  antibiotics  are given preventatively. Other complications include  Post-transplant lymphoproliferative disorder , a form of  lymphoma  due to the immune suppressants, and gastrointestinal inflammation and ulceration of the stomach and esophagus."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_102", "contents": "Transplant rejection  is a primary concern, both immediately after the surgery and continuing throughout the patient's life. Because the transplanted lung or lungs come from another person, the recipient's  immune system  will see it as an invader and attempt to neutralize it. Transplant rejection is a serious condition and must be treated as soon as possible."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_103", "contents": "Signs of rejection: [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_104", "contents": "In order to prevent transplant rejection and subsequent damage to the new lung or lungs, patients must take a regimen of  immunosuppressive drugs . Patients will normally have to take a combination of these medicines in order to combat the risk of rejection. This is a lifelong commitment, and must be strictly adhered to. The immunosuppressive regimen is begun just before or after surgery. Usually the regimen includes  ciclosporin ,  azathioprine  and  corticosteroids , but as episodes of rejection may reoccur throughout a patient's life, the exact choices and dosages of immunosuppressants may have to be modified over time. Sometimes  tacrolimus  is given instead of ciclosporin and  mycophenolate mofetil  instead of azathioprine."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_105", "contents": "The immunosuppressants that are needed to prevent organ rejection also introduce some risks. By lowering the body's ability to mount an immune reaction, these medicines also increase the chances of infection.  Antibiotics  may be prescribed in order to treat or prevent such infections. In turn, infection may increase the risk of rejection, and generally an interaction may prevail between both risks. [ 30 ]  Certain medications may also have  nephrotoxic  or other potentially harmful side-effects. Other medications may also be prescribed in order to help alleviate these side effects. There is also the risk that a patient may have an  allergic reaction  to the medications. Close follow-up care is required in order to balance the benefits of these drugs versus their potential risks."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_106", "contents": "Chronic rejection, meaning repeated bouts of rejection symptoms beyond the first year after the transplant surgery, occurs in approximately 50% of patients. [ 31 ]  Such chronic rejection presents itself as  bronchiolitis obliterans , or less frequently,  atherosclerosis . [ 31 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_107", "contents": "These statistics are based on data from 2008. The source data made no distinction between living and deceased donor organs, nor was any distinction made between lobar, single, and double lung transplants. [ 32 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_108", "contents": "Transplanted lungs typically last three to five years before showing signs of failure."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_109", "contents": "A 2019 cohort study of nearly 10,000 lung transplant recipients in the US demonstrated significantly improved long-term survival using sirolimus + tacrolimus (median survival 8.9 years) instead of mycophenolate mofetil + tacrolimus (median survival 7.1 years) for immunosuppressive therapy starting at one year after transplant. Since sirolimus is not administered until at least 3\u201312 months after transplant, these median survival estimates were conditional on surviving 1 year post-transplant. [ 33 ] \nAs lung transplantation has improved since the late 20th century with advancements in perioperative management, surgical technique and postoperative rehabilitation, 5-year survival has increased even up to 60-70%. [ 34 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_110", "contents": "Mediastinoscopy  is a procedure that enables visualization of the contents of the  mediastinum , usually for the purpose of obtaining a  biopsy . [ 1 ]  Mediastinoscopy is often used for staging of  lymph nodes  of  lung cancer  or for diagnosing other conditions affecting structures in the mediastinum such as  sarcoidosis  or  lymphoma ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_111", "contents": "Mediastinoscopy involves making an incision approximately 1\u00a0cm above the  suprasternal notch  of the  sternum , or breast bone. Dissection is carried out down to the pretracheal space and down to the  carina . A scope ( mediastinoscope ) is then advanced into the created tunnel which provides a view of the mediastinum. The scope may provide direct visualization or may be attached to a video monitor."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_112", "contents": "Mediastinoscopy provides access to mediastinal lymph node levels 2, 4, and 7."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_113", "contents": "Historically, mediastinoscopy has been the gold standard for the staging of lung cancer. However, with advances in minimally invasive procedures and imaging, mediastinoscopy usage has declined significantly from 2006 to 2010. [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_114", "contents": "Extended mediastinoscopy  is a technique which allows access to the pre-aortic (station 6) and  aortopulmonary window  (station 5) lymph nodes. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_115", "contents": "Parasternal mediastinotomy, aka, a Chamberlain procedure, is the standard approach to access lymph nodes at  stations 5 and 6 . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_116", "contents": "Pleurodesis  is a medical procedure in which part of the  pleural space  is artificially obliterated. [ 1 ]  It involves the adhesion of the visceral and the costal pleura. The mediastinal pleura is spared."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_117", "contents": "Pleurodesis is performed to prevent recurrence of  spontaneous pneumothorax  or  pleural effusion , and can be done chemically or mechanically.  It is generally avoided in patients with  cystic fibrosis  if possible, because  lung transplantation  becomes more difficult following this procedure.  Previous pneumothorax with or without pleurodesis is not a contraindication to subsequent lung transplantation. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_118", "contents": "Chemicals such as  bleomycin ,  tetracycline  (e.g.,  minocycline ), [ 2 ]   povidone-iodine , or a  slurry  of  talc  can be introduced into the pleural space through a chest drain. The instilled chemicals cause irritation between the parietal and the visceral layers of the pleura which closes off the space between them and prevents further fluid from accumulating. [ 3 ]  Pharmacy-prepared chemicals for pleurodesis should be clearly labeled \"NOT FOR IV ADMINISTRATION\" [ 4 ]  to avoid potentially fatal wrong-site medication errors. [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_119", "contents": "Sterile talc powder , administered intrapleurally via a  chest tube , is indicated as a  sclerosing agent  to decrease the recurrence of malignant pleural effusions in symptomatic patients. It is usually performed at the time of a diagnostic thoracoscopy. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_120", "contents": "Povidone iodine  is equally effective and safe as talc, and may be preferred because of easy availability and low cost. [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_121", "contents": "Chemical pleurodesis is a painful procedure, and so patients are often  premedicated  with a sedative and analgesics. A  local anesthetic  may be instilled into the pleural space, or an  epidural  catheter may be placed for anesthesia. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_122", "contents": "Surgical pleurodesis, also known as mechanical or abrasive pleurodesis, may be performed via  thoracotomy  or  thoracoscopy . This involves mechanically irritating the apical and the costal  pleura , often with a scratchpad (a small  foam pad  with  coated abrasive ) normally used for cleaning  electrocautery  blade tips. Moreover,  surgical removal of parietal pleura  is an effective way of achieving stable pleurodesis. [ 7 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_123", "contents": "Alternatively, tunneled pleural catheters (TPCs) may be placed in an outpatient setting and often result in auto-pleurodesis, whereby portable vacuum bottles are used to evacuate the pleural fluid. Routine evacuation keeps the pleura together, resulting in physical agitation by the catheter, which slowly causes the pleura to scar together. This method, though the minimally invasive and minimal cost solution, takes an average of about 30 days to achieve pleurodesis and is therefore the slowest means of achieving pleurodesis among other modalities. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_124", "contents": "Conservative management of primary spontaneous pneumothorax is noninferior to interventional management, with a lower risk of serious adverse events. [ 9 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_125", "contents": "A  pneumonectomy  (or pneumectomy) is a  surgical  procedure to remove a  lung . It was first successfully performed in 1933 by Dr. Evarts Graham. This is not to be confused with a lobectomy or segmentectomy, which only removes one part of the lung."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_126", "contents": "There are two types of pneumonectomy: simple and extrapleural. A simple pneumonectomy removes just the lung. An extrapleural pneumonectomy also takes away part of the diaphragm, the parietal pleura, and the pericardium on that side. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_127", "contents": "The most common reason for a pneumonectomy is to remove  tumorous  tissue arising from  lung cancer . Other reasons can arise are a traumatic lung injury, bronchiectasis, tuberculosis, a congenital defect, and fungal infections. [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_128", "contents": "The operation will reduce the respiratory capacity of the patient, and before conducting a pneumonectomy, survivability after the removal has to be assessed. If at all possible, a  pulmonary function test  (PFT) should be done. It has been found that forced expiratory volume in one second (FEV1) and diffusion capacity of the lungs (DLCO) provides the best indicator of survival. [ 3 ]  Other tools can be used to assess effectiveness as well, such as cardiopulmonary exercise testing to measure maximal oxygen consumption (VO 2  max), stair climbing, shuttle walk test, and a 6-minute walk test. [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_129", "contents": "If someone has severe valvular disease, severe pulmonary hypertension, or poor ventricular function or if cancer has spread from the lungs into the other intra-abdominal structures, ribs, or contralateral hemithorax, it is contraindicated. [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_130", "contents": "Posterolateral thoracotomy using the fourth or fifth intercostal space is the most common approach used for pneumonectomy. In case of inflammatory and infectious indications, excision of the fifth rib may be necessary to achieve adequate surgical exposure if there is rib crowding. [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_131", "contents": "Video-assisted thoracoscopic surgery (VATS) approach: VATS pneumonectomy is a safe and feasible treatment for advanced malignant and benign diseases and has lower morbidity. [ 7 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_132", "contents": "Robotic pneumonectomy for lung cancer is a safe procedure and a reasonable alternative to thoracotomy. With a sound technique most procedures can be completed robotically without any major complications. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_133", "contents": "After a pneumonectomy is performed, changes in the thoracic cavity occur to compensate for the altered anatomy. The remaining lung hyperinflates as well as shifting over along with the  heart  towards the now empty space. This space is full of air initially after surgery, but then it is absorbed, and fluid eventually takes its place. [ 9 ]  The fluid which fills the residual space in the chest cavity slowly gelatinizes into a proteinaceous material, and the chest scaffold collapses slightly. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_134", "contents": "As with the  kidneys , it is often possible for a person to live with just one lung. Although it is not possible for the lung to re-grow like the  liver , the body is able to compensate for the reduced lung capacity by slow and gradual expansion of the other remaining lung. Post-pneumonectomy patients in due time reach about 70\u201380 percent of their pre-surgery lung function. [ 10 ]  People have been able to return to near-normal lives, including running marathons after a pneumonectomy, provided there has been adequate cardio-pulmonary conditioning. [ 11 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_135", "contents": "Most common complications after a pneumonectomy are:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_136", "contents": "Pneumonolysis , sometimes referred to as  plombage , is the separation of an adherent  lung  from the  pleura , to permit collapse of the lung. It was formerly used to treat  tuberculosis  before effective medications were developed. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_137", "contents": "The underlying theory of the treatment was the belief that if the diseased lobe of the lung was physically forced to collapse, it would heal quickly. There were positive results in tuberculosis therapy following plombage in the decades of the 1930s, 1940s and early-1950s. However, with the introduction of drugs which were effective in destroying the tuberculosis bacterium ( Mycobacterium tuberculosis ), plombage treatment fell into disfavor. In addition, complications of plombage began to appear in patients who had been so treated. These complications included hemorrhage, infection and fistulization (abnormal opening between two hollow organs) of the bronchus, aorta, esophagus and skin. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_138", "contents": "The technique involved surgically creating a cavity underneath the ribs in the upper part of the chest wall and filling this space with some inert material. A variety of substances were typically used and included air, olive or mineral oil, gauze, paraffin wax, rubber sheeting or bags and Lucite balls. The inserted material would force the upper lobe of the lung to collapse. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_139", "contents": "A  pulmonary thrombectomy  is an  emergency   surgical  procedure used to remove  blood clots  from the  pulmonary arteries ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_140", "contents": "Mechanical thrombectomies can be surgical (surgical thrombectomy) or percutaneous (percutaneous thrombectomy). [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_141", "contents": "Surgical thrombectomies were once popular but were abandoned because of poor long-term outcomes. Recently, in selected patients, they have gone through a resurgence with the revision of the surgical technique. [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_142", "contents": "Pulmonary thrombectomies and  pulmonary thromboendarterectomies  (PTEs) are both operations that remove thrombus. Aside from this similarity they differ in many ways."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_143", "contents": "In  thoracic surgery , a  pulmonary thromboendarterectomy  ( PTE ), also referred to as  pulmonary endarterectomy  ( PEA ), [ 1 ]  is an  operation  that removes organized  clotted  blood ( thrombus ) from the  pulmonary arteries , which supply blood to the lungs. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_144", "contents": "Surgery is indicated in patients with pulmonary artery emboli that are surgically accessible. Thrombi are usually the cause of recurrent/chronic  pulmonary emboli  and therefore of chronic thromboembolic  pulmonary hypertension  (CTEPH). [ 2 ]  PTE is the only definitive treatment option available for CTEPH. [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_145", "contents": "Due to the nature of the procedure, patients with significant hemodynamic or ventilation complications or impairments may be unable to undergo PTE."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_146", "contents": "A PTE has significant risk; mortality for the operation is typically 5%, but less in centers with high volume and experience. Individuals with favorable hemodynamic risk profiles also demonstrate lower mortality rates (1.3%). [ 3 ]  PTEs are risky because of the nature of the procedure.  PTEs involve a full  cardiopulmonary bypass  (CPB), deep  hypothermia  and cardioplegia (a crystalline fluid which stops the heart from beating). Actual removal of the embolus is carried out in a  standstill operation  (deep hypothermia and periods of cessation of circulation). [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_147", "contents": "There are a number of reasons why these high-risk elements of the procedure are necessary. CPB is needed to divert blood from the heart and lungs and supply the body with oxygen and blood while the pulmonary vasculature is operated on. Cardioplegia is initiated as the approach to the pulmonary arteries is performed through the pericardium, a fibrous sac surrounding the heart. Furthermore, movement from the heart makes delicate work on the closely attached pulmonary arteries complex. Hypothermia is necessary as the embolus is very delicate and the risk of disruption is high, in order to appropriately visualize the clot and remove it a bloodless field is required. Clot visualization is achieved through dissection of the pulmonary arteries which is technically challenging. If possible the clot is removed in a single piece to avoid the formation of mobile emboli. In order to achieve this CPB is periodically stopped, resulting in a complete cessation of blood circulation. This is only feasible if the patient is hypothermic (cooled to 18\u201320 \u00b0C) as metabolism is slowed and the body can better tolerate the resulting lack of blood supply. [ 5 ]  Circulatory arrest is limited to 20 minute intervals to protect brain function. Typically an experienced surgeon can perform an entire unilateral procedure in this time. After each interval of arrest circulation is continued for 10 minutes or until pulmonary venous oxygen saturation is at least 90%. [ 6 ]   Bypass time is typically 345 minutes. [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_148", "contents": "There are emerging alternative options available that seek to limit neurologic complications resulting from hypothermia and circulatory arrest. Currently these options have not been shown to be superior to the previously described technique. They include use of moderate hypothermia, antegrade cerebral artery perfusion without total circulatory arrest, and negative pressure application to the left ventricle. [ 7 ] [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_149", "contents": "It is important to note that acute  pulmonary embolectomy  is a dramatically different procedure. It's typically performed without hypothermia as the structure of the clot is different, and the emergent nature presents different operative priorities. [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_150", "contents": "Recovery from this procedure can be complex. Thoracic surgery, CBP and cardioplegia are associated with their own complications and management challenges, as is hypothermia. Specifically, endartectomy is associated with reperfusion pulmonary edema and \"pulmonary artery steal\". Reperfusion pulmonary edema occurs in up to 30% of patients and is a result of changes in permeability to the vascular endothelium. Management of this condition may require the use of supportive ventilation including BiPAP ( bidirectional positive airway pressure ) and fluid management with diuretics. In patients who are non responsive to this management  extra corporeal circulation  may be indicated. Each of these strategies are complex and require careful consideration of patient physiology. [ 12 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_151", "contents": "Pulmonary artery steal occurs in 70% of patients. It is related to changes in blood flow over areas of pulmonary vasculature that have been newly exposed from the endarectomy. The result is insufficient oxygenation though the mechanism causing this remains obscure. Treatment is supportive with oxygen, and ventilation, and the condition is typically self limiting. [ 13 ] [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_152", "contents": "The benefits of PTEs are significant.  Most patients after surgery no longer suffer from  shortness of breath  and therefore have a much improved  quality of life .  Further,  pulmonary vascular resistance  usually drops back to close normal levels. Since the pulmonary resistance is proportional to the pressure driving the pulmonary flow ( \n \n \n \n P \n = \n Q \n \u22c5 \n R \n \n \n {\\displaystyle P=Q\\cdot R} \n \n ), it follows that the pulmonary pressure decreases.  This in turn means that the work per time (power) decreases because it is equal to the pressure gradient times the  volumetric flow , which in this case is the cardiac output.  As a result of the operation, patients are spared from pulmonary hypertension and further  right ventricular hypertrophy .  Most pleasing is that patients who previously had right heart dysfunction often recover function. [ 15 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_153", "contents": "As of 2008, the  UCSD Medical Center 's cardiothoracic surgery department, led by  Stuart W. Jamieson , was widely recognized as a pioneer in the relatively new surgery, having performed more PTEs than the rest of the world combined (over 3000 since 1970 out of a total of 4500 worldwide) with the lowest mortality rate. [ 16 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_154", "contents": "In the UK, PTE is offered only at one centre, [ 17 ]  Royal Papworth Hospital, [ 18 ]  led by surgeon Mr David Jenkins. [ 19 ]  He is one of just four surgeons in the UK qualified to perform pulmonary endarterectomy surgery, all based at Royal Papworth, which is one of the most active centres in the world for this operation with approximately 190 operations performed each year and a total caseload since 1996 of more than 2,000. [ 20 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_155", "contents": "The operation features in a BBC Two documentary called 'Surgeons: At the Edge of Life', broadcast on Tuesday 6 October 2020. [ 21 ]  The footage shows the patient's entire body being drained of blood and cooled to 20 degrees Celsius \u2013 half the normal temperature \u2013 in order to enable the surgery to occur."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_156", "contents": "PTEs and  pulmonary thrombectomies  are both operations that removed thrombus from the lung's arterial vasculature.  Aside from this similarity they differ in many ways."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_157", "contents": "A  pulmonary tractotomy  is a surgical technique to treat a penetrating lung injury. The tract of the lung injury is opened, and open bronchi and blood vessels are ligated (sewn)."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_158", "contents": "Emergency surgery  for a penetrating lung injury, e.g. an accident or a gunshot, is associated with a very high  mortality rate . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_159", "contents": "Such lung injuries cannot be treated with simple surgery; they cannot be oversewn. If treated with simple surgery, blood vessels within the tract of the lung injury may continue to bleed and result in a  haematoma  which should be avoided. Or the patient may suffer a pulmonary  air embolism  and subsequently die. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_160", "contents": "Penetrating lung injuries can be treated with a formal lung resection or with pulmonary tractotomy. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_161", "contents": "Pulmonary tractotomy is a lung sparing technique. It can prevent the need for formal lung resection. Its advantages over segmental lung resection include that it can be performed quicker; it offers a rapid way to control bleeding ( haemorrhage ) and air leaks in patients with penetrating lung injuries. Also, pulmonary tractotomy can preserve healthy pulmonary tissue ( parenchyma ); this naturally is not possible with lung resection. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_162", "contents": "However, overall patient outcome is the same with pulmonary tractotomy and lung resection; both are viable surgical treatment options. This is because patient outcome in penetrating lung injury is related mainly to the severity of injury, rather than the type of treatment. [ 7 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_163", "contents": "Thoracoscopy  is a  medical procedure  involving internal examination,  biopsy  and/or  resection / drainage  of  disease  or  masses  within the  pleural cavity , [ 1 ]  usually with  video assistance .  Thoracoscopy may be performed either under  general anaesthesia  or under  sedation  with  local anaesthetic . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_164", "contents": "Thoracoscopy was first performed by  Sir Francis Cruise  of the Mater Misericordiae Hospital in Dublin in conjunction with Dr Samuel Gordon in 1865. [ 2 ]  It was further developed by  Hans Christian Jacobaeus , a  Swedish   internist  in 1910 for the treatment of  tuberculous  intra-thoracic adhesions. He used a  cystoscope  to examine the thoracic cavity, developing his technique over the next twenty years. Today, thoracoscopy is performed using specialized thoracoscopes. These instruments include a  light source  and a  lens  for  viewing  and may have ports through which other instruments may be inserted for the purpose of tissue removal and manipulation. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_165", "contents": "Video-assisted thoracoscopic surgery  (VATS) is a  surgical  operation involving thoracoscopy, usually performed by a  thoracic surgeon  using general or local/regional anaesthesia with additional sedation as necessary. It has historically also been referred to as  pleuroscopy . A wide variety of diagnostic and therapeutic procedures may be performed with this technique which has become very popular and increasingly so since the early 1990s. Prior to this, limited diagnostic procedures were done using variations on the cystoscope since 1910. Advances in direct optical visualization were quickly surpassed when video cameras were attached to the  endoscopes . The advent of  endoscopic stapling  was also a major advance so that complicated procedures such as  pulmonary lobectomy  could be performed safely. VATS can be useful for the diagnosis of undefined  interstitial lung diseases . [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_166", "contents": "A  thoracotomy  is a surgical procedure to gain access into the  pleural  space of the  chest . [ 1 ]  It is performed by surgeons (emergency physicians or paramedics under  certain circumstances ) to gain access to the thoracic organs,  most commonly the  heart , the  lungs ,  or the  esophagus , or for access to the thoracic  aorta  or the anterior  spine  (the latter may be necessary to access tumors in the spine). A thoracotomy is the first step in  thoracic surgeries  including  lobectomy  or  pneumonectomy  for  lung cancer  or to gain thoracic access in  major trauma ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_167", "contents": "There are many different surgical approaches to performing a thoracotomy. Some common forms of thoracotomies include:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_168", "contents": "Upon completion of the surgical procedure, the  chest  is closed. One or more  chest tubes \u2014with one end inside the opened  pleural cavity  and the other submerged under saline solution inside a sealed container, forming an airtight drainage system\u2014are necessary to remove air and fluid from the  pleural cavity , preventing the development of  pneumothorax  or  hemothorax ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_169", "contents": "In addition to  pneumothorax , complications from thoracotomy include air leaks,  infection , bleeding and  respiratory failure . [ 9 ]  Postoperative pain is universal and intense, generally requiring the use of  opioid   analgesics  for moderation, as well as interfering with the recovery of respiratory function. Paraplegia complicating thoracotomy is rare but catastrophic. [ 10 ] [ 11 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_170", "contents": "In nearly all cases, one or more  chest tubes  are placed. These tubes are used to drain air and fluid until the patient heals enough to take them out (usually a few days).  Complications such as  pneumothorax ,  tension pneumothorax , or  subcutaneous emphysema  can occur if these chest tubes become clogged. [ 12 ]   Furthermore, complications such as pleural effusion or  hemothorax  can occur if the chest tubes fail to drain the fluid around the lung in the pleural space after a thoracotomy. [ 13 ]   Clinicians should be on the look out for  chest tube  clogging as these tubes have a tendency to become occluded with fibrinous material or clot in the post operative period, and when this happens, complications ensue."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_171", "contents": "Pain following a thoracotomy may be treated by the use of a  nerve block  known as a  rhomboid intercostal block . [ 14 ]  In the long term, post-operative chronic pain can develop, known as thoracotomy pain syndrome, and may last from a few years to a lifetime. Treatment to aid pain relief for this condition includes intra-thoracic nerve blocks/opiates and  epidurals , although results vary from person to person and are dependent on numerous factors. A recent  Cochrane review  concluded that there is moderate-quality evidence that  regional anaesthesia  may reduce the risk of developing persistent postoperative pain three to 18 months after thoracotomy. [ 15 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_172", "contents": "Video-assisted thoracoscopic surgery  (VATS) is a less invasive alternative to thoracotomy in selected cases, much like  laparoscopic surgery . There are lesser postoperative complications and better long-term survival following VATS lobectomy compared to open thoracotomy lobectomy for NSCLC. VATS lobectomy does not compromise patient safety or the oncological efficacy. [ 16 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_173", "contents": "Thoracic epidural analgesia or paravertebral blockade have shown to be the most effective methods for post-thoracotomy pain control. However, contraindications to neuraxial anesthesia include hypovolemia, shock, increase in ICP, coagulopathy or thrombocytopenia, sepsis, or infection at puncture site. Comparing thoracic epidural analgesia and paravertebral blockade, paravertebral blockade reduced the risks of developing minor complications, however paravertebral blockade was as effective as thoracic epidural blockade in controlling acute pain. [ 17 ]   Transcutaneous electrical nerve stimulation  has also shown to be useful in the management of post-thoracotomy pain. Specifically, it has been found to be a good adjunct in the management of moderate to severe post-thoracotomy pain and effective as a lone modality in mild post-thoracotomy pain (e.g. after video-assisted thoracoscopy). [ 18 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_174", "contents": "Video-assisted thoracoscopic surgery  ( VATS )  lobectomy  is an approach to  lung cancer  surgery."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_175", "contents": "Anatomic lung resection, i.e. pulmonary  lobectomy  or  pneumonectomy , in conjunction with removal of the  lymph nodes  from the  mediastinum  is the treatment modality that provides the greatest chance of long-term survival in patients with early stage  non-small cell lung cancer .  Anatomic lung resections require a dissection of the pulmonary  hilum  with individual ligation and division of the  pulmonary artery ,  pulmonary vein , and the  bronchus  where these enter the lung.  In the setting of  lung cancer , the rationale for anatomic lung resection is a complete removal of a lung  tumor  along with the  lymphatics  that drain that  tumor  to assure that any tumor cells present in the  lymphatics  will also be removed; lesser resections have been shown to be associated with a higher risk of local recurrence and diminished long-term survival.  A cornerstone of surgical treatment of early stage lung cancer is aggressive removal of  lymph nodes  from the mediastinum; this enhances the likelihood of removing all cancer cells (complete resection) and identifies patients who will require additional treatment (i.e.  adjuvant chemotherapy ).  An important consideration when performing anatomic lung resection is to spare as much lung tissue as possible; while lobectomy and pneumonectomy are equivalent cancer operations, the risk of complications and  morbidity  is considerably less with lobectomy. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_176", "contents": "Traditionally, pulmonary  lobectomy  is performed through a poster-lateral  thoracotomy  incision; over decades, thoracotomy has demonstrated its effectiveness in providing access to structures in the thorax and is in general tolerated by patients. Thoracotomy, as most commonly performed, requires cutting through one or more major muscles of the chest wall including the  latissimus dorsi ,  pectoralis  or  serratus  muscles, and spreading of the  ribs  with a rib spreader. Because the joints of the ribs with the  vertebral bodies  have only limited flexibility, the use of a rib spreader usually results in  rib fracture  in the process of rendering the interspace between the ribs wide enough to perform a pulmonary lobectomy. Because of this,  thoracic  surgeons generally intentionally remove a section of one or more ribs in an effort to prevent splintered  rib fracture  associated with the use of the rib spreader.  There is wide consensus that  thoracotomy  is one of the most painful incisions that patients can undergo.  In the initial post-operative setting after  thoracotomy , the use of  epidural   catheters ,  patient-controlled analgesia  pumps for  intravenous   narcotic  administration, and  intravenous   ketorolac  are commonplace and patients generally require a 7- to 10-day hospital stay before their pain is adequately controlled with oral  opioid   analgesics  that they can take at home.  A great deal of emphasis is placed on post-operative  pulmonary toilet  because the incisional pain associated with  thoracotomy  leads to a decreased ability of patients to cough and clear  bronchial  secretions, which in turn leads to an increased risk of persistent  atelectasis  (collapsed areas of lung) or  pneumonia .  Finally, to allow time for the divided muscles and bone fractures to heal, patients must refrain from strenuous activity or lifting greater than 5\u00a0lbs for 6 weeks after surgery. [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_177", "contents": "Video-assisted thoracoscopic surgery , or VATS, came into widespread use in the 1990s and early on in its development practitioners began to perform  lobectomy  via VATS incisions. [ 3 ]  The advantage of VATS over  thoracotomy  is that major chest wall muscles are not divided and ribs are not spread.  This leads to reductions in the intensity and duration of post-operative pain and allows patients to return to full activity more quickly."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_178", "contents": "VATS lobectomy is the same as lobectomy performed via thoracotomy in that the  pulmonary artery ,  pulmonary vein , and  bronchus  to the involved pulmonary  lobe  are individually dissected, ligated and divided.  Generally,  endoscopic  stapling devices are used to ligate and divide the vessels and the  bronchus  however conventional  suture  material can also be used.  During VATS lobectomy, the structures being operated on are not directly visualized with the naked eye but are visualized solely with a rigid  thoracoscope .  A  camera  attached to the thoracoscope transmits the image to a video screen, which allows surgeons and assistants to observe the flow of the operation.  Surgical specimens are placed into a water-tight bag and removed from the chest without morcellization (i.e. breaking up the specimen into small pieces before removal); this prevents seeding of the VATS incisions with tumor cells and allows for an intact specimen for  pathology  examination and  cancer staging .  Removal of  lymph nodes  from the  mediastinum  is not compromised by VATS and remains a cornerstone of the surgical therapy of lung cancer.  Visualization is enhanced due to the magnification afforded by the  fiberoptic  thoracoscope and a 30-degree angle of visualization aids in looking around corners.  However, because the incisions are too small to allow passage of the surgeon's hands into the  thorax , the surgeon's tactile input is compromised.  VATS operations rely on a thorough understanding of pulmonary anatomy to allow for strategically placed incisions (usually 3\u20135 incisions total).  The main advantages of VATS over thoracotomy are that major muscles of the chest wall are not divided and rib spreaders that can lead to rib fractures or  costovertebral joint  pain are not used.  This results in a hospital length of stay after VATS  lobectomy  generally reported to range from 3\u20135 days, [ 4 ]  or roughly half that for lobectomy via thoracotomy."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_179", "contents": "Not all patients are candidates for VATS lobectomy.  The classic indication for a VATS approach to lobectomy is early stage  lung cancer  in which the primary  tumor  is 3\u00a0cm or less in diameter and located toward the periphery of the lung  parenchyma .  Tumors that are located close to the major blood vessels or airway where these enter the lung or larger tumors associated with tumor spread to  lymph nodes  in the central regions of the lung may require the enhanced tactile input afforded by  thoracotomy  to make sure the tumors are resected with a negative margin, i.e. that the tumor is surrounded completely by a margin of non-cancerous tissue, and that  arteries  and airways to portions of the lung that are not being removed are preserved intact.  In addition, patients who have had pre-operative  chemotherapy  or  radiation  for  lung cancer  or previous chest surgeries may not be candidates for VATS due to scarring around the major blood vessels that makes dissection via VATS difficult. But recent evidence suggests that thoracoscopic lobectomy is a feasible approach for selected patients undergoing resection after induction therapy, and is associated with shorter hospital stay and chest tube duration. [ 5 ]  Cases in which a lung tumor invades the chest wall and an en bloc resection of ribs must be performed to achieve negative  resection margins  generally are felt to abrogate the value of VATS. Also  pneumonectomy  by VATS is a safe and feasible treatment for both benign and malignant lung diseases that induces acceptable damage and has lower morbidity. [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_180", "contents": "Because of the lesser chest wall trauma of VATS compared to  thoracotomy , elderly patients have been shown to tolerate  lobectomy  by VATS better than via thoracotomy. [ 7 ]   Patients who require  chemotherapy  after surgery have been shown to be more likely to succeed in completing the prescribed course of  chemotherapy  after VATS lobectomy compared to lobectomy via thoracotomy. [ 8 ]   Along with the lesser  chest wall  trauma and improved pulmonary mechanics, a lesser level of  cytokine  disturbance has been reported after VATS lobectomy compared to thoracotomy. [ 9 ]   From the standpoint of  medical economics , VATS lobectomy is less expensive than  lobectomy  performed via  thoracotomy  because hospital  length of stay  and number of days in the  intensive care unit  are significantly reduced. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_181", "contents": "Video-assisted thoracoscopic surgery (VATS)  is a type of  minimally invasive   thoracic surgery  performed using a small  video camera  mounted to a  fiberoptic   thoracoscope  (either 5\u00a0mm or 10\u00a0mm caliber), with or without angulated visualization, which allows the  surgeon  to see  inside the chest by viewing the  video  images relayed onto a  television screen , and perform  procedures  using elongated  surgical instruments . The camera and instruments are inserted into the patient's  chest cavity  through small incisions in the  chest wall , usually via specially designed guiding tubes known as \"ports\"."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_182", "contents": "VATS procedures are done using either conventional surgical instruments or  laparoscopic  instruments.  Unlike with laparoscopy,  carbon dioxide   insufflation  is not generally required in VATS due to the inherent rigidity of the  thoracic cage .  However, lung deflation on the side of the operated chest is a must to be able to visualize and pass instruments into the thorax; this is usually effected with a  double-lumen endotracheal tube  that allows for single-lung ventilation, or a one-side bronchial occlusion delivered via a standard single-lumen  tracheal tube . [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_183", "contents": "VATS came into widespread use beginning in the early 1990s.  Operations that traditionally were carried out with thoracotomy or sternotomy that today can be performed with VATS include: biopsy for diagnosis of  pulmonary ,  pleural  or mediastinal pathology; decortication for empyema;  pleurodesis  for recurrent  pleural effusions  or spontaneous  pneumothorax ;  surgical stapler -assisted  wedge resection  of lung masses; resection of  mediastinal  or pleural masses;  thoracic sympathectomy  for  hyperhidrosis ; operations for  diaphragmatic hernias  or paralysis;  esophageal resection  or resection of esophageal masses or  diverticula ; and  VATS lobectomy /mediastinal  lymphadenectomy  for lung cancer. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_184", "contents": "Similarly to  laparoscopy , VATS has enjoyed widespread use for technically straightforward operations such as pulmonary  decortication ,  pleurodesis , and lung or pleural biopsies, while more technically demanding operations such as esophageal operations, mediastinal mass resections, or  pulmonary lobectomy  for early stage lung cancer, have been slower to catch on and have tended to remain confined to selected centers.  It is expected that advanced VATS techniques will continue to grow in numbers spurred by patient demand and greater surgeon comfort and familiarity with the techniques."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_185", "contents": "The main advantage of VATS is that the smaller  postoperative wounds  drastically reduce the risk for  wound infection  and  dehiscence , which allows for a faster recovery by the patient and a greater chance for the wound to heal. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_186", "contents": "Traditional thoracic surgery requires opening the chest through  thoracotomy  or  sternotomy  incisions, which are significantly traumatic to the body.  Sternotomy requires the use of a  sternal saw  to split the  sternum  and a  retractor  to spread apart the divided sternum to allow visualization and access to the thoracic structures.  Thoracotomy, as most commonly performed, requires division of one or more major muscles of the chest wall including the  latissimus ,  pectoralis  or  serratus  muscles, along with spreading of the ribs with a  rib spreader .  Because the  costovertebral joints  have only limited flexibility, the use of a rib spreader usually results in  iatrogenic   rib fractures , which can lead to  complications  like a  flail chest  or  intercostal   neuralgia .  Because of this, thoracic surgeons generally intentionally use a  bone cutter  to remove section of one or more ribs in an effort to prevent jagged rib fractures.  Although sternotomy and thoracotomy have been proven over decades to provide highly effective access to thoracic structures and in general are tolerated by patients, both incisions have the potential for causing significant pain that may last for extended periods and both prevent the patients from heavy lifting or strenuous activity for weeks in order to heal, and can still result in  malunions  and  nonunions .  The great advantage of VATS over sternotomy or thoracotomy is the avoidance of muscle division and bone-cutting, which allows for reduced  postoperative pain , shorter duration of hospital stay and quicker return to full activity. [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_187", "contents": "Wedge resection of the lung  is a  surgical  operation where a part of a  lung  is removed. It is done to remove a localized portion of diseased lung, such as early  stage   lung cancer . [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_188", "contents": "This  surgery  article is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_189", "contents": "The  Blalock\u2013Thomas\u2013Taussig shunt  ( BTT shunt ), [ 1 ]  previously known as the  Blalock\u2013Taussig Shunt  ( BT shunt ), [ 2 ]  is a surgical procedure used to increase blood flow to the lungs in some forms of  congenital heart disease [ 3 ]  such as  pulmonary atresia  and  tetralogy of Fallot , which are common causes of  blue baby syndrome . [ 3 ]  The procedure involves connecting a branch of the  subclavian artery  or  carotid artery  to the  pulmonary artery . In modern practice, this procedure is temporarily used to direct blood flow to the lungs and relieve cyanosis while the infant is waiting for corrective or definitive surgery when their heart is larger. The BTT shunt is used in the first step of the three-stage palliation (the  Norwood procedure )."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_190", "contents": "While the originally described Blalock\u2013Thomas\u2013Taussig shunt directly connected the subclavian and pulmonary arteries, in contemporary practice a modified version of the procedure, the mBTT shunt, is more commonly used. [ 2 ] [ 4 ]  In the modified Blalock\u2013Thomas\u2013Taussig shunt, a length of artificial tubing typically made from  PTFE  ( Gore-tex ) is sewn between either the subclavian or the carotid artery and the corresponding side branch of the pulmonary artery. [ 4 ]  This modification removes the need to cut off blood supply and makes it easier to regulate the blood flow to the lungs. Some centers now use a shunt directly from the right ventricle to the pulmonary artery, a  Sano shunt . This is done to avoid the reduced diastolic blood flow in the  coronary circulation  associated with the mBTT shunt. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_191", "contents": "The original procedure was named for  Alfred Blalock , surgeon, Culloden, GA (1899\u20131964),  Helen B. Taussig , cardiologist, Baltimore/Boston (1898\u20131986) and  Vivien Thomas  (1910\u20131985) who was at that time Blalock's laboratory assistant. They all helped to develop the procedure. Taussig, who treated hundreds of infants and children with this disorder, had observed that children with a cyanotic heart defect and a  patent ductus arteriosus  (PDA) lived longer than those without the PDA. It, therefore, seemed to her that a shunt that mimicked the function of a PDA might relieve the tetralogy patients' poor oxygenation. In 1943, having broached the possibility of a surgical solution to  Robert Gross  of Boston without success, Taussig approached Blalock and Thomas in their Hopkins laboratory in 1943. According to the account of the original consultation between the three provided in Vivien Thomas' 1985 autobiography  Partners of the Heart , Taussig carefully described the anomaly of Tetralogy of Fallot, but made no suggestion about the specific surgical correction required, observing merely that it should be possible to get more blood to the lungs, \"as a plumber changes pipes around.\"  Although Taussig was not aware of it at that time, Blalock and Thomas had already experimented with such an  anastomosis , one that Blalock had conceived years earlier for a different purpose but which had the unanticipated effect of re-routing blood to the lungs. The operation involved the joining of the subclavian artery to the pulmonary artery. After meeting with Taussig, the two men set about perfecting the operation in the animal lab, with Thomas performing the subclavian-to-pulmonary anastomosis alone in some 200 laboratory dogs, then adapting the instruments for the first human surgery from those used on the experimental animals and coaching Blalock through the first 100 operations on infants. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_192", "contents": "Thomas' autobiographical account, corroborated by the participants in the early tetralogy operations ( Denton Cooley  and the late William P. Longmire, Jr., intern and resident respectively during the surgery) has led to the recent conclusion that Thomas' contribution, both experimentally and clinically, was so critical that he should have received credit for the procedure along with Blalock and Taussig. However, because of the racial prejudices of the time, and the academic custom which generally precluded mention of non-degreed lab assistants (Thomas had no formal education beyond high school), he did not receive the honor of having the shunt named after him. The 2004 HBO television movie  Something the Lord Made , based on  Washingtonian  writer Katie McCabe's 1989 article of the same name, was made about his role in the historic Blue Baby surgery, as was the 2003 public television documentary  Partners of the Heart. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_193", "contents": "Bronchoscopic lung volume reduction   (BLVR)  is a procedure to reduce the  volume  of air within the  lungs . BLVR was initially developed in the early 2000s [ 1 ] [ 2 ]  as a minimally invasive treatment for severe  COPD  that is primarily caused by  emphysema . BLVR evolved from earlier surgical approaches first developed in the 1950s [ 3 ]  to reduce lung volume by removing damaged portions of the lungs via  pneumonectomy  or  wedge resection . Procedures include the use of  valves , coils, or thermal vapour ablation. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_194", "contents": "BLVR involves the use of valves, coils, or thermal vapour ablation. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_195", "contents": "Endobronchial valves  are inserted using a  bronchoscope  into sections of the lungs damaged by emphysema. Endobronchial valves are  medical devices  that allow air to exit these sections but not to re-enter. The valves, in effect, cause damaged lung tissue to deflate, thereby reducing the excessive lung volume (hyperinflation) caused by emphysema. Two endobronchial valves have been approved by the FDA for BLVR: Zephyr and Spiration. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_196", "contents": "Zephyr, manufactured by Pulmonx Corporation, obtained FDA approval in June, 2018, [ 4 ]  after a clinical research trial (LIBERATE) [ 5 ]  led by principal investigator Gerard Criner, MD, of Temple University Hospital. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_197", "contents": "In the trial, a total of 190 subjects were randomized across 24 hospital sites into two groups. One group received an endobronchial valve. The other received \u201cstandard of care\u201d (SOC) under the current guidelines for hyperinflation due to emphysema. The trial found the endobronchial valve reduced residual lung volume and improved exercise tolerance as compared to the SOC group. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_198", "contents": "Spiration, manufactured by Spiration, Inc., obtained FDA approval in December, 2018, [ 6 ]  after a clinical trial (EMPROVE) [ 7 ]  showed the valve improved pulmonary function scores among trial participants. The Spiration valve subsequently was first used in treatment by Dr. Criner at Temple University Hospital. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_199", "contents": "BLVR valves are placed into the lungs using a  catheter  through a bronchoscope. During the one-hour procedure, the patient receives anesthesia through an intravenous line. After the procedure, patients usually remain in the hospital for at least four days. During hospitalization, the patient receives a series of chest X-rays to monitor the position of the valves. An outpatient follow-up appointment is scheduled for seven to 10 days after the procedure. Additional imaging tests, such as X-rays, and bronchoscopies may be required [ 8 ]  weeks, months or years following the initial BLVR procedure. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_200", "contents": "Clinical research has found that BLVR confers measurable benefits, including:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_201", "contents": "BLVR also carries risks, among them:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_202", "contents": "The first clinical research study of BLVR valve implantation was published in the  New England Journal of Medicine  in 2010. [ 16 ]  Since that time, nearly 80 additional papers have been published related to the efficacy [ 17 ] [ 18 ]  of BLVR, inclusion criteria, [ 19 ]  anesthesia management [ 20 ]  during BLVR, and related topics. Key studies include:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_203", "contents": "Cardioplegia  is a solution given to the heart during cardiac surgery, to minimize the damage caused by  myocardial ischemia  while the heart is paused."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_204", "contents": "The word  cardioplegia  combines the Greek  cardio  meaning the \"heart\", and  plegia  \"paralysis\". [ 1 ]  Technically, this means arresting or stopping the heart so that surgical procedures can be done in a still and bloodless field. Most commonly, however, the word  cardioplegia  refers to the solution used to bring about  asystole  of the heart, or heart paralysis. One of the first physicians to use the term cardioplegia was Dr. Lam in 1957. However his work on the myocardial protection was preceded serendipitously by  Sydney Ringer  in the late 1800s. At that time Ringer and colleagues noticed that tap water had the ability to increase contractility of the heart, likely due to its high calcium content. Sydney Ringer also commented on the importance of potassium ion concentration on depressing intrinsic heart rhythm. Through a series of experiments performed on frog and canine hearts, reversible arrest was achieved with potassium ions with the consequence of ventricular fibrillation and observed  myocardial   necrosis . These early experiments started nearly 50 years of work that has led to variety of  perfusion  strategies available today."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_205", "contents": "The main goals of hypothermic cardioplegia are:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_206", "contents": "The most common procedure for accomplishing asystole is infusing cold cardioplegic solution into the  coronary circulation . This process protects the  myocardium , or heart muscle, from damage during the period of ischemia. [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_207", "contents": "To achieve this, the patient is first placed on  cardiopulmonary bypass . This device, otherwise known as the heart-lung machine, takes over the functions of gas exchange by the lung and blood circulation by the heart. Subsequently, the heart is isolated from the rest of the blood circulation by means of an occlusive cross-clamp placed on the  ascending aorta  proximal to the  innominate artery .  During this period of heart isolation, the heart is not receiving any blood flow, thus no oxygen for metabolism.  As the cardioplegia solution distributes to the entire myocardium, the ECG will change and eventually asystole will ensue. Cardioplegia lowers the metabolic rate of the heart muscle, thereby preventing cell death during the ischemic period of time."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_208", "contents": "Cardioplegic solution is the means by which the ischemic myocardium is protected from cell death. This is achieved by reducing myocardial metabolism through a reduction in cardiac work load and by the use of hypothermia."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_209", "contents": "Chemically, the high potassium concentration present in most cardioplegic solutions decreases the membrane resting potential of cardiac cells. The normal  resting potential  of ventricular myocytes is about -90 mV. [ 4 ]  When extracellular cardioplegia displaces blood surrounding myocytes, the membrane voltage becomes less negative and the cell depolarizes more readily. The depolarization causes contraction, intracellular calcium is sequestered by the sarcoplasmic reticulum via ATP-dependent Ca 2+  pumps, and the cell relaxes (diastole).  However, the high potassium concentration of the cardioplegia extracellular prevents repolarization. \nThe resting potential on ventricular myocardium is about \u221284\u00a0mV at an extracellular K +  concentration of 5.4\u00a0mmol/L. Raising the K +  concentration to 16.2\u00a0mmol/L raises the resting potential to \u221260\u00a0mV, a level at which muscle fibers are inexcitable to ordinary stimuli.  When the resting potential approaches \u221250\u00a0mV,  sodium channels are inactivated, resulting in a diastolic arrest of cardiac activity. [ 5 ]  Membrane inactivation gates, or  h   Na +  gates, are voltage dependent. The less negative the membrane voltage, the more  h  gates that tend to close. If partial depolarization is produced by a gradual process such as elevating the level of extracellular K + , then the gates have ample time to close and thereby inactivate some of the Na +  channels.  When the cell is partially depolarized, many of the Na +  channels are already inactivated, and only a fraction of these channels is available to conduct the inward Na +  current during phase 0 depolarization. [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_210", "contents": "The use of two other cations, Na +  and Ca 2+ , also can be used to arrest the heart.  By removing extracellular Na +  from perfusate, the heart will not beat because the action potential is dependent upon extracellular Na +  ions.  However, the removal of Na +  does not alter the resting membrane potential of the cell.  Likewise, removal of extracellular Ca 2+  results in a decreased contractile force, and eventual arrest in diastole. An example of a low [K + ] low [Na + ] solution is  histidine-tryptophan-ketoglutarate .  Conversely, increasing extracellular Ca 2+  concentration enhances contractile force.  Elevating Ca 2+  concentration to a high enough level results in cardiac arrest in systole.  This unfortunate irreversible event is referred to as \"stone-heart\" or rigor."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_211", "contents": "Hypothermia is the other key component of most cardioplegic strategies.  It is employed as another means to further lower myocardial metabolism during periods of  ischemia . The  Van 't Hoff equation  allows calculation that oxygen consumption will drop by 50% for every 10\u00a0\u00b0C reduction in temperature. This  Q 10  effect combined with a chemical cardiac arrest can reduce myocardial oxygen consumption (MVO 2 ) by 97%. [ 7 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_212", "contents": "Cold cardioplegia is given into the heart through the aortic root. Blood supply to the heart arises from the aortic root through  coronary arteries . Cardioplegia in diastole ensures that the heart does not use up the valuable energy stores ( adenosine triphosphate ). Blood is commonly added to this solution in varying amounts from 0 to 100%. Blood acts a buffer and also supplies nutrients to the heart during ischemia."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_213", "contents": "Once the procedure on the heart vessels ( coronary artery bypass grafting ) or inside the heart such as  valve replacement  or correction of  congenital heart defect , etc. is over, the cross-clamp is removed and the isolation of the heart is terminated, so normal blood supply to the heart is restored and the heart starts beating again."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_214", "contents": "The cold fluid (usually at 4\u00a0\u00b0C)  ensures that the heart cools down to a temperature of around 15\u201320\u00a0\u00b0C, thus slowing down the metabolism of the heart and thereby preventing damage to the heart muscle. This is further augmented by the cardioplegia component which is high in potassium."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_215", "contents": "When solution is introduced into the  aortic root  (with an  aortic cross-clamp  on the distal aorta to limit systemic circulation), this is called antegrade cardioplegia.  When introduced into the  coronary sinus , it is called retrograde cardioplegia. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_216", "contents": "Whilst there are several cardioplegic solutions commercially available; there are no clear advantages of one cardioplegic solution over another. Some cardioplegias, such as del Nido or Histidine-Tryptophan-Ketoglutamate solutions, offer an advantage over blood and other crystalloid cardioplegia as they only require one administration during short cardiac surgeries, compared to multiple doses required by blood and other crystalloid. [ 9 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_217", "contents": "In coronary surgery, there are various alternatives to cardioplegia to perform the operation. One is  off-pump  coronary surgery where the surgery is done without the need of a cardiopulmonary bypass machine. Another is to use cross-clamp fibrillation whereby the heart fibrillates whilst on cardiopulmonary bypass in order to perform the distal anastomoses. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_218", "contents": "Cardiac surgical cases were performed with the aid of a cardiopulmonary pump, without cardioplegia or other means of protecting the heart. High mortality rates due to cardiac injury though, made surgeons to look on how to protect the heart. In 1955  D.G. Melrose  suggested \u2018\u2019elective cardiac arrest\u2019\u2019, a technique already used for other purposes, in order to protect the heart from ischemia- since cardiac muscle is not working, oxygen demands should be low. In the 1960\u2019s other groups introduced ice slur applied all over the heart\u2019s surface. The rationale was to decrease the temperature of the heart, thus to reduce oxygen demands further. [ 11 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_219", "contents": "The next decades many investigators (Bretschneider, Kirch and others)  came up with various solutions that could pause the heart without damaging cardiac muscle. In the same period, surgeons found out delivery roots for cardioplegia, other than the commonly used antegrade. Buckberg in North America and Menasche in Europe, introduced retrograde cardioplegia method, via a catheter inserted in Coronary Sinus and thus perfusing the heart in a retrograde fashion. [ 11 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_220", "contents": "Chest drains  are  surgical drains  placed within the  pleural space  to facilitate removal of unwanted substances ( air ,  blood ,  fluid , etc.) in order to preserve  respiratory functions  and  hemodynamic  stability.  Some chest drains may utilize a  flutter valve  to prevent retrograde flow, but those that do not have physical valves employ a  water trap seal  design, often aided by continuous  suction  from a  wall suction  or a  portable vacuum pump ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_221", "contents": "The active maintenance of an intrapleural negative pressure via chest drains builds the basis of  chest drain management , as an intrapleural pressure lower than the surrounding  atmosphere  allows easier  lung  expansion and thus better  alveolar   ventilation  and  gas exchange ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_222", "contents": "The so-called \"central vacuum\" was the first sub-atmospheric pressure device available. Sub-atmospheric pressure of around 100\u00a0cm of water column was historically generated at a central location in the hospital. This \"central vacuum\" was available throughout the entire hospital, as it was proved via a tubing system. It was referred to as \"wall suction\". [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_223", "contents": "Reduction  valves  that reduce the negative pressure to a therapeutically reasonable range were commercially available later. Due to this, multi-chamber suction \u2013 the use of three-chamber systems \u2013 was developed. In the 1960s, the first pumps (Emerson-Pump) were available. These and other systems launched later generated a fixed \"negative pressure\". These pumps couldn't compensate for an inadequate position of the collection chamber of a siphon. Since 2008, an electronically driven and regulated system is available, generating a \"negative pressure\" on demand."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_224", "contents": "External  suction  (previously referred to as active suction) is used to create a sub-atmospheric pressure at the tip of a  catheter . As the atmospheric pressure is lower compared to the  intrapleural  pressure, the lack of external suction (which was previously referred to as passive suction) is used to drain air and fluids. [ 1 ]  Traditional drainage systems are not able to suction sub-atmospheric pressure in the pleural space. These systems only allow for a regulation of pressure via the system itself but cannot regulate sub-atmospheric pressure in the pleural space. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_225", "contents": "Two different principles are used in chest drainage management: The Heber-Drain principle and the  B\u00fclau -Drain principle.\nThe \"Heber-Drain\" is based on the Heber principle, which uses hydrostatic pressure to transfer fluid from the chest to a collection canister. It produces permanent passive suction. As the Heber drain is a classical  gravity  drain, the canister must be placed below chest level to be active. The difference in height between the floor and the patient bed determines the resultant sub-atmospheric pressure. With a difference, for example, of 70\u00a0cm in height, a pressure of minus 70\u00a0cm of water is created. A water seal component is always combined with a Heber-Drain."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_226", "contents": "The \"B\u00fclau-Drain\" is based on the B\u00fclau principle and creates a permanent passive suction within a closed system that is based on the Heber-Drain principle. The  pulmonologist  Gotthard B\u00fclau (1835-1900) used this system in 1875 for the first time for the treatment of  pleural empyema . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_227", "contents": "This type of drainage is mainly used in  cardiac surgery .  Mediastinal  drains are placed behind the  sternum  and/or next to the heart. The main indication in these cases is the monitoring of post-operative bleeding. Whether these drains are used with active suction or not depends on factors such as personal preference and experience of the physician, individual patient-related factors etc... [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_228", "contents": "Drainage of the  pericardium  can be achieved by puncture (transcutaneously) or surgically. In the first case, small-bore  catheters  not suitable for the drainage of blood (e.g. hemopericard) are used. Pericardial drains are mostly used with the help of gravity. As a pericardial drain is placed surgically, a largo bore drain is used with a decreased probability of clogging. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_229", "contents": "The simplest system that is sufficient for chest drainage is a one-chamber system. It uses either a Heber-drain or an active suction source and comprises a single collection canister. For active or passive air evacuation, a water seal component is attached. To ensure that all air is sucked out when using a Heber-drain, manual support might be needed. To prevent a  pneumothorax  or  subcutaneous emphysema  when the patient is not able to breathe out or cough out surplus air, the height between the patient bed and the ground might need adjustment.\nAs air leaks are not always easy to observe, some one-chamber systems are limited when it comes to the treatment of huge air leaks, especially when the patient produces a lot of foam."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_230", "contents": "In a two-chamber system air and fluid are directed to a first collection canister.  Gravity  keeps the fluid in the first canister, whereas air is directed into a second canister. The air can either actively or passively be released via a water seal. Two-chamber systems are mainly used for patients with huge air leaks. These patients often produce foam due to protein rich  surfactant  that might enter the tubing toward the patient. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_231", "contents": "Early three-chamber systems used an extra glass bottle filled with water as a third water- vacuometer  chamber in addition to a two-chamber system. The sub-atmospheric pressure was controlled with a pipe. The higher the pipe depth, the lower the generated pressure in the  pleural space.  These systems were used in times of the central vacuum and are not used anymore as they caused accidents and were not very ease to use. The mechanics of these systems depended on high flows (20l/min) for the system to be considered active."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_232", "contents": "In modern portable, digital chest drainage systems, the collection chamber is integrated into the system. During the suction process, fluid will be collected in the chamber and air discharged into the  atmosphere . [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_233", "contents": "Digital chest drainage systems have many advantages compared to traditional, analogue systems:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_234", "contents": "Electronic systems do not apply permanent suction but monitor the patient very closely and are activated when needed. On average, after an uncomplicated  lobectomy , an electronic pump is active for 90 minutes within 2.5 days."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_235", "contents": "A  chest tube  (also  chest drain ,  thoracic catheter ,  tube thoracostomy  or  intercostal drain ) is a  surgical drain  that is inserted through the  chest wall  and into the  pleural space  or the  mediastinum . The insertion of the tube is sometimes a lifesaving procedure. The tube can be used to remove clinically undesired substances such as air ( pneumothorax ), [ 1 ]  excess fluid ( pleural effusion  or  hydrothorax ),  blood  ( hemothorax ),  chyle  ( chylothorax ) or  pus  ( empyema ) from the intrathoracic space. An intrapleural chest tube is also known as a  B\u00fclau drain  or an  intercostal catheter  (ICC), and can either be a thin, flexible silicone tube (known as a \"pigtail\" drain), or a larger, semi-rigid,  fenestrated  plastic tube, which often involves a  flutter valve  or  underwater seal ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_236", "contents": "The concept of  chest drainage  was first advocated by  Hippocrates  when he described the treatment of  empyema  by means of incision, cautery and insertion of metal tubes. [ 2 ]  However, the technique was not widely used until the influenza epidemic of 1918 to evacuate post-pneumonic empyema, which was first documented by Dr. C. Pope, on a 22-month-old infant. [ 3 ]  The use of chest tubes in postoperative thoracic care was reported in 1922, [ 4 ]  and they were regularly used post-thoracotomy in  World War II , though they were not routinely used for emergency tube  thoracostomy  following acute trauma until the  Korean War . [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_237", "contents": "Medical uses of chest tube are as follows: [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_238", "contents": "Contraindications to chest tube placement include refractory  coagulopathy  and presence of a diaphragmatic hernia, as well as  hepatic hydrothorax . [ 7 ]  Additional contraindications include scarring in the pleural space (adhesions)."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_239", "contents": "Complications that are sometimes associated with chest tubes include the potential for clogging, air leaks, infection,  hemorrhage , re-expansion  pulmonary edema . Injury to the  liver ,  spleen  or  diaphragm  is also possible if the tube is placed behind (inferior) to the  pleural cavity  or is mispositioned. Injuries to the thoracic  aorta  and  heart  can also occur. [ 5 ] [ 8 ]  The rate of complications of chest tubes inserted for trauma-related treatment needs has been estimated at approximately 19%. [ 9 ]  The rate of complications is variable and other estimations have been made that share a rate of closer to 40%. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_240", "contents": "Complications that arise while the chest tube is being inserted or within the first day of the insertional procedure include a risk of injury to organs near the insertional site. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_241", "contents": "Complications that arise after the tube has been inserted for one day or longer include the potential for tube blockages (obstruction), air leaks, kinking, or entrapment in the lung fissure once the lung has been expanded. Chest tube clogging can lead to retained blood around the heart and lungs that can contribute to complications and increase mortality. [ 11 ]  A common complication after thoracic surgery that arises within 30\u201350% of patients are air leaks.  If a chest tube clogs when there is an air leak the patient will develop a pneumothorax.  This can be life-threatening. [ 12 ]  Here, digital  chest drainage systems  can provide real time information as they monitor  intra-pleural  pressure and air leak flow, constantly. [ 13 ]   Keeping vigilant about chest tube clogging is imperative for the team taking care of the patient in the early postoperative period."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_242", "contents": "Minor complications include a subcutaneous  hematoma  or  seroma , anxiety, shortness of breath, and cough (after removing large volume of fluid). In most cases, the chest tube related pain goes away after the chest tube is removed, however, chronic pain related to chest tube induced scarring of the intercostal space is not uncommon. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_243", "contents": "Subcutaneous emphysema  indicates backpressure created by undrained air, often caused by a clogged chest tube or insufficient negative pressure. [ citation needed ]   If a person has subcutaneous emphysema, it is likely their chest tube is not draining and consideration should be given if it should be unclogged or another tube should be placed so that the air leaking from the lung can be adequately drained."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_244", "contents": "Problems keeping the site clean or with sterilizing instruments can lead to infections. [ 10 ]  When chest tubes are placed due to either blunt or penetrating trauma, antibiotics may decrease the risks of infectious complications. [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_245", "contents": "There is also a risk of complications after the chest tube has been removed. [ 10 ]  Potential complications include problems with re-sealing the chest that can lead to trapped air or if a  foreign object  is retained in the chest after the procedure. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_246", "contents": "Chest tubes are commonly made from clear plastics like  PVC  and soft  silicone . Chest tubes are made in a range of sizes measured by their external diameter from 6 Fr to 40 Fr. Chest tubes, like most catheters, are measured in  French catheter scale . For adults, 20 Fr to 40 Fr (6.7 to 13.3mm external diameter) are commonly used, and 6 Fr to 26 Fr for children. Conventional chest tubes feature multiple drainage fenestrations in the section of the tube which resides inside the patient, as well as distance markers along the length of the tube, and a radiopaque stripe which outlines the first drainage hole. [ 5 ]  Chest tubes are also provided in right angle, trocar, flared, and tapered configurations for different drainage needs. As well, some chest tubes are coated with  heparin  to help prevent thrombus formation, though the effect of this is disputed. [ 16 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_247", "contents": "Chest tube have an end hole (proximal, toward the patient) and a series of side holes.  The number of side holes is generally 6 on most chest tubes.  The length of tube that has side holes is the effective drainage length (EDL).  In chest tubes designed for pediatric heart surgery, the EDL is shorter, generally by only having 4 side holes. [ 17 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_248", "contents": "Channel style chest drains, also called Blake drains, are so-called  silastic  drains made of silicone and feature open flutes that reside inside the patient. Drainage is thought to be achieved by capillary action, allowing the fluids to travel through the open grooves into a closed cross section, which contains the fluid and allows it to be suctioned through the tube. [ 18 ]   Though these chest tubes are more expensive than conventional ones, they are theoretically less painful. [ 19 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_249", "contents": "A  chest drainage  system is typically used to collect chest drainage (air, blood, effusions). Most commonly, drainage systems use three chambers which are based on the three-bottle system. The first chamber allows fluid that is drained from the chest to be collected. The second chamber functions as a \"water seal\", which acts as a one way valve allowing gas to escape, but not reenter the chest. Air bubbling through the water seal chamber is usual when the patient coughs or exhales but may indicate, if continual, a pleural or system leak that should be evaluated critically. It can also indicate a leak of air from the lung. The third chamber is the suction control chamber. The height of the water in this chamber regulates the negative pressure applied to the system. A gentle bubbling through the water column minimizes evaporation of the fluid and indicates that the suction is being regulated to the height of the water column. In this way, increased wall suction does not increase the negative pressure of the system. Newer drainage systems eliminate the water seal using a mechanical check-valve, and some also use a mechanical regulator to regulate the suction pressure. Systems which employ both these are dubbed \"dry\" systems, whereas systems that retain the water seal but use a mechanical regulator are called \"wet-dry\" systems. Systems which use a water seal and water column regulator are called \"wet\" systems. Dry systems are advantageous as tip-overs of wet systems can spill and mix with blood, mandating the replacement of the system. Even newer systems are smaller and more ambulatory so the patient can be sent home for drainage if indicated. [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_250", "contents": "The free end of the tube is usually attached to an underwater seal, below the level of the chest. This allows the air or fluid to escape from the pleural space, and prevents anything returning to the chest. Alternatively, the tube can be attached to a  flutter valve . This allows patients with  pneumothorax  to remain more mobile. [ 20 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_251", "contents": "More recently digital or  electronic chest drainage systems  have been introduced. An onboard motor is used as vacuum source along with an integrated suction control canister and water seal. These systems monitor the patient and will alert if the measured data are out of range. Due to the digital control of the negative pressure, the system is able to objectively quantify the presence of a pleural or system leak. Digital drainage systems allow clinicians to mobilize patients early, even for those on continuous suction, which is difficult to accomplish with the traditional water-seal system under suction. [ 12 ] [ 21 ]  Application of such systems can also lead to a reduction in complications. [ 22 ] [ 23 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_252", "contents": "It can be inserted in an area described as the \"safe zone\", which is a region bordered by the lateral border of pectoralis major, a horizontal line inferior to the axilla, the anterior border of latissimus dorsi and a horizontal line superior to the nipple. [ 24 ]   This should translate to the tube being inserted into the fifth intercostal space slightly anterior to the mid axillary line. [ 25 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_253", "contents": "Chest tubes are usually inserted under  local anesthesia . The skin over the area of insertion is first cleansed with  antiseptic  solution, such as iodine, before  sterile  drapes are placed around the area. The local anesthetic is injected into the skin and down to the muscle, and after the area is numb a small incision is made in the skin and a passage made through the skin and muscle into the chest. The tube is placed through this passage. If necessary, patients may be given additional  analgesics  for the procedure. Once the tube is in place it is sutured to the skin to prevent it falling out and a dressing applied to the area. Once the drain is in place, a  chest radiograph  will be taken to check the location of the drain. The tube stays in for as long as there is air or fluid to be removed, or risk of air gathering."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_254", "contents": "Chest tubes can also be placed using a trocar, which is a pointed metallic bar used to guide the tube through the chest wall. This method is less popular due to an increased risk of iatrogenic lung injury. Placement using the  Seldinger technique , in which a blunt guidewire is passed through a needle (over which the chest tube is then inserted) has been described."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_255", "contents": "Protocols to maintain chest tube patency by preventing chest tube clogging are necessary."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_256", "contents": "The placement technique for postoperative drainage (e.g.  cardiac surgery ) differs from the technique used for emergency situations. At the completion of open cardiac procedures, chest tubes are placed through separate stab incisions, typically near the inferior aspect of the sternotomy incision. In some instances multiple drains may be used to evacuate the mediastinal, pericardial, and pleural spaces. The drainage holes are placed inside the patient and the chest tube is passed out through the incision. Once the tube is in place, it is sutured to the skin to prevent movement. The chest tube is then connected to the drainage canister using additional tubing and connectors and connected to a suction source, typically regulated to -20\u00a0cm of water. [ 18 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_257", "contents": "After suturing,  dressings  are applied for hygienical reasons covering the wound. First, a y-slit  compress  is used around the tube. Second, a compress (10 x 10\u00a0cm) is placed on top and finally an  adhesive plaster  is added in a way that tension is avoided. A bridle rein is recommended to fix the tube to the skin. This tape bridge will prevent the tube from moving backwards and the possibility to cause clogging. It also prevents pain as it reduces tension on the fixation stitch. Alternatively, a large adhesive plaster that functions like a tape bridge may be used. [ 26 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_258", "contents": "Chest tubes should be kept free of dependent loops, kinks, and obstructions which may prevent drainage. [ 27 ]  In general, chest tubes are not clamped except during insertion, removal, or when diagnosing air leaks. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_259", "contents": "Chest tube clogging with blood clots of fibrinous material is common. When this occurs, it can result in retained blood around the heart or lungs that can lead to complications such as hematoma that needs to be drained, effusions, empyema, or, in the long term, fibrothorax.  Thus its critical to maintain chest tube patency.   Manual manipulation, often called milking, stripping, fan folding, or tapping, of chest tubes is commonly performed to clear chest tube obstructions. However these approaches are controversial.  No conclusive evidence has demonstrated that any of these techniques are more effective than the others, and no method has shown to improve chest tube drainage. [ 28 ]  Furthermore, chest tube manipulation has proved to increase negative pressure, which may be detrimental, and painful to the patient. [ 28 ]  For these reasons, many hospitals do not allow these types of manual tube manipulations. [ 29 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_260", "contents": "One option is active chest tube clearance without breaking the sterile field.  According to a consensus of multiple experts in cardiac surgery, anesthesia and critical care in 2019 the ERAS Guidelines for Perioperative Care recommends active clearance of chest tubes to prevent retained blood and other complications. [ 30 ]  Makeshift efforts such as open chest tube clearing that involves breaking the sterile environment separating the chest tube from the drainage canister tubing to suction it out should not be performed. [ 31 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_261", "contents": "The chest tube can only be removed when the subject clinical condition is stable, the lungs are fully aerated as seen on chest X-ray, chest tube drainage is less than 200 cc per day, and there is no air leak into the lungs pleura. [ 32 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_262", "contents": "In December 2018 the  European Respiratory Journal  published correspondences that raise the possibility of improving mobility as well as patient outcomes by placing a chest tube more optimally. [ 33 ] [ 34 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_263", "contents": "Endoscopic thoracic sympathectomy  ( ETS ) is a surgical procedure in which a portion of the  sympathetic nerve  trunk in the  thoracic  region is destroyed. [ 1 ] [ 2 ]  ETS is used to treat excessive sweating in certain parts of the body ( focal hyperhidrosis ), facial  flushing ,  Raynaud's disease  and  reflex sympathetic dystrophy . By far the most common complaint treated with ETS is sweaty palms ( palmar hyperhidrosis ).  The intervention is controversial and illegal in some jurisdictions. Like any surgical procedure, it has risks; the endoscopic sympathetic block (ESB) procedure and those procedures that affect fewer nerves have lower risks."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_264", "contents": "Sympathectomy physically destroys relevant nerves anywhere in either of the two  sympathetic trunks , which are long chains of nerve  ganglia  located bilaterally along the vertebral column (a localisation which entails a low risk of injury) responsible for various important aspects of the  peripheral nervous system  (PNS). Each nerve trunk is broadly divided into three regions: cervical ( neck ),  thoracic  (chest), and  lumbar  (lower back). The most common area targeted in sympathectomy is the upper thoracic region, that part of the sympathetic chain lying between the first and fifth thoracic vertebrae."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_265", "contents": "The most common  indications  for thoracic sympathectomy are focal hyperhidrosis (that specifically affects the hands and underarms),  Raynaud syndrome , and facial blushing when accompanied by focal hyperhidrosis. It may also be used to treat  bromhidrosis , [ 3 ]  although this usually responds to non-surgical treatments, [ 4 ]  and sometimes people with  olfactory reference syndrome  present to surgeons requesting sympathectomy. [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_266", "contents": "There are reports of ETS being used to achieve cerebral revascularization for people with  moyamoya disease , [ 6 ]  and to treat headaches, hyperactive bronchial tubes, [ 7 ]   long QT syndrome , [ 8 ] [ 9 ] [ 10 ]  social phobia, [ 11 ]  anxiety, [ 12 ]  and other conditions."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_267", "contents": "ETS involves dissection of the main  sympathetic trunk  in the upper thoracic region of the  sympathetic nervous system , irreparably disrupting neural messages that ordinarily would travel to many different organs, glands and muscles. It is via those nerves that the brain is able to make adjustments to the body in response to changing conditions in the environment, fluctuating emotional states, level of exercise, and other factors to maintain the body in its ideal state (see  homeostasis )."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_268", "contents": "Because these nerves also regulate conditions like excessive blushing or sweating, which the procedure is designed to eliminate, the normative functions these physiological mechanisms perform will be disabled or significantly impaired by sympathectomy. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_269", "contents": "There is much disagreement among ETS surgeons about the best surgical method, optimal location for nerve dissection, and the nature and extent of the consequent primary effects and side effects. When performed endoscopically as is usually the case, the surgeon penetrates the chest cavity making multiple incisions about the diameter of a straw between ribs. This allows the surgeon to insert the video camera (endoscope) in one hole and a surgical instrument in another. The operation is accomplished by dissecting the nerve tissue of the main sympathetic chain. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_270", "contents": "Another technique, the clamping method, also referred to as 'endoscopic sympathetic blockade' (ESB) employs titanium clamps around the nerve tissue, and was developed as an alternative to older methods in an unsuccessful attempt to make the procedure reversible. Technical reversal of the clamping procedure must be performed within a short time after clamping (estimated at a few days or weeks at most), and a recovery, evidence indicates, will not be complete."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_271", "contents": "Sympathectomy works by disabling part of the autonomic nervous system (and thereby disrupting its signals from the brain), through surgical intervention, in the expectation of removing or alleviating the designated problem. Many non-ETS doctors have found this practice questionable chiefly because its purpose is to destroy  functionally disordered , yet anatomically typical nerves. [ 13 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_272", "contents": "Exact results of ETS are impossible to predict, because of considerable anatomic variation in nerve function from one patient to the next, and also because of variations in surgical technique. The autonomic nervous system is not anatomically exact and connections might exist which are unpredictably affected when the nerves are disabled. This problem was demonstrated by a significant number of patients who underwent sympathectomy at the same level for hand sweating, but who then presented a reduction or elimination of feet sweating, in contrast to others who were not affected in this way. No reliable operation exists for foot sweating except lumbar sympathectomy, at the opposite end of the sympathetic chain."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_273", "contents": "Thoracic sympathectomy will change many bodily functions, including  sweating , [ 14 ]  vascular responses, [ 15 ]   heart rate , [ 16 ]  heart  stroke volume , [ 17 ] [ 18 ]   thyroid ,  baroreflex , [ 19 ]   lung volume , [ 18 ] [ 20 ]  pupil dilation, skin temperature and other aspects of the  autonomic nervous system , like the essential  fight-or-flight response . It reduces the physiological responses to strong emotions, such as fear and laughter, diminishes the body's physical reaction to both pain and pleasure, and inhibits cutaneous sensations such as  goose bumps . [ 14 ] [ 18 ] [ 21 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_274", "contents": "A large study of psychiatric patients treated with this surgery showed significant reductions in  fear ,  alertness  and  arousal . [ 22 ]  Arousal is essential to consciousness, in regulating attention and information processing, memory and emotion. [ 23 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_275", "contents": "ETS patients are being studied using the autonomic failure protocol headed by David Goldstein, M.D. Ph.D., senior investigator at the U.S National Institute of Neurological Disorders and Stroke. He has documented loss of thermoregulatory function, cardiac denervation, and loss of  vasoconstriction . [ 24 ] \nRecurrence of the original symptoms due to nerve regeneration or nerve sprouting can occur within the first year post surgery. Nerve sprouting, or abnormal nerve growth after damage or injury to the nerves can cause other further damage. Sprouting sympathetic nerves can form connections with sensory nerves, and lead to pain conditions that are mediated by the SNS. Every time the system is activated, it is translated into pain. This sprouting and its action can lead to  Frey's syndrome , a recognized after effect of sympathectomy, when the growing sympathetic nerves innervate salivary glands, leading to excessive sweating regardless of environmental temperature through olfactory or gustatory stimulation."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_276", "contents": "In addition, patients have reported lethargy, depression, weakness, limb swelling, lack of libido, decreased physical and mental reactivity, oversensitivity to sound, light and stress and weight gain (British Journal of Surgery 2004; 91: 264\u2013269)."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_277", "contents": "ETS has both the normal risks of surgery, such as bleeding and infection, conversion to open chest surgery, and several specific risks, including permanent and unavoidable alteration of nerve function. It is reported that a number of patients - 9 since 2010, mostly young women - have died during this procedure due to major intrathoracic bleeding and cerebral disruption. Bleeding during and following the operation may be significant in up to 5% of patients. [ 25 ]   Pneumothorax  (collapsed lung) can occur (2% of patients). [ 25 ]   Compensatory hyperhidrosis  (or reflex hyperhidrosis) is common over the long term. [ 25 ]   The rates of severe compensatory sweating vary widely between studies, ranging from as high as 92% of patients. [ 26 ]   Of those patients that develop this side effect, about a quarter in one study said it was a major and disabling problem. [ 27 ]  35% of people affected have to change their clothes several times a day as a result. [ 28 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_278", "contents": "A severe possible consequence of thoracic sympathectomy is corposcindosis (split-body syndrome), in which the patient feels that they are living in two separate bodies, because sympathetic nerve function has been divided into two distinct regions, one dead, and the other hyperactive. [ 29 ] [ medical citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_279", "contents": "Additionally, the following side effects have all been reported by patients: Chronic muscular pain, numbness and weakness of the limbs, Horner's Syndrome, anhidrosis (inability to sweat), hyperthermia (exacerbated by anhidrosis and systemic thermoregulatory dysfunction), neuralgia, paraesthesia, fatigue and amotivationality, breathing difficulties, substantially diminished physiological/chemical reaction to internal and environmental stimuli, somatosensory malfunction, aberrant physiological reaction to stress and exertion, Raynaud\u2019s disease (albeit a possible indication for surgery), reflex hyperhidrosis, altered/erratic blood pressure and circulation, defective fight or flight response system, loss of adrenaline, eczema and other skin conditions resulting from exceptionally dry skin, rhinitis, gustatory sweating (also known as Frey's syndrome). [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_280", "contents": "Other long-term adverse effects include:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_281", "contents": "Other side effects are the inability to raise the heart rate sufficiently during exercise with instances requiring an  artificial pacemaker  after developing  bradycardia  being reported as a consequence of the surgery. [ 30 ] [ 35 ] [ 36 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_282", "contents": "The Finnish Office for Health Care Technology Assessment concluded more than a decade ago in a 400-page systematic review that ETS is associated with an unusually high number of significant immediate and long-term adverse effects. [ 37 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_283", "contents": "Quoting the Swedish National Board of Health and Welfare statement:  \"The method can give permanent side effects that in some cases will first become obvious only after some time. One of the side effects might be increased perspiration on different places on your body. Why and how this happens is still unknown. According to the research available about 25-75% of all patients can expect more or less serious perspiration on different places on their body, such as the trunk and groin area, this is  Compensatory sweating \". [ 38 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_284", "contents": "In 2003, ETS was banned in its birthplace, Sweden, due to inherent risks, and complaints by disabled patients. In 2004, Taiwanese health authorities banned the procedure on people under 20 years of age. [ 39 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_285", "contents": "Sympathectomy developed in the mid-19th century, when it was learned that the  autonomic nervous system  runs to almost every organ, gland and muscle system in the body.  It was surmised that these nerves play a role in how the body regulates many different body functions in response to changes in the external environment, and in emotion. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_286", "contents": "The first sympathectomy was performed by Alexander in 1889. [ 40 ]  Thoracic sympathectomy has been indicated for  hyperhidrosis  (excessive sweating) since 1920, when Kotzareff showed it would cause  anhidrosis  (total inability to sweat) from the  nipple  line upwards. [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_287", "contents": "A lumbar sympathectomy was also developed and used to treat excessive sweating of the feet and other ailments, and typically resulted in  impotence  and retrograde ejaculation in men. Lumbar sympathectomy is still being offered as a treatment for plantar hyperhidrosis, or as a treatment for patients who have a bad outcome (extreme 'compensatory sweating') after thoracic sympathectomy for palmar hyperhidrosis or blushing; however, extensive sympathectomy risks  hypotension ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_288", "contents": "Endoscopic sympathectomy itself is relatively easy to perform; however, accessing the nerve tissue in the chest cavity by conventional surgical methods was difficult, painful, and spawned several different approaches in the past. The  posterior  approach was developed in 1908, and required  resection  (sawing off) of ribs. A supraclavicular (above the collar-bone) approach was developed in 1935, which was less painful than the posterior, but was more prone to damaging delicate  nerves  and  blood vessels . Because of these difficulties, and because of disabling  sequelae  associated with sympathetic denervation, conventional or \"open\" sympathectomy was never a popular procedure, although it continued to be practiced for hyperhidrosis,  Raynaud's disease , and various psychiatric disorders. With the brief popularization of  lobotomy  in the 1940s, sympathectomy fell out of favor as a form of  psychosurgery ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_289", "contents": "The endoscopic version of thoracic sympathectomy was pioneered by Goren Claes and Christer Drott in  Sweden  in the late 1980s. The development of  endoscopic  \"minimally invasive\" surgical techniques has decreased the recovery time from the surgery and increased its availability. Today, ETS surgery is practiced in many countries throughout the world predominantly by vascular surgeons."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_290", "contents": "British Journal of Surgery 2004; 91: 264\u2013269"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_291", "contents": "Ex vivo lung perfusion , EVLP, is a form of  machine perfusion  aimed at sustaining the active aerobic cellular metabolism of donor lungs outside the donor's body prior to  lung transplantation . This medical preservation technique typically occurs within a specialised machine engineered to mimic the conditions of the  natural circulatory system . The machine supplies the lung with  perfusate  and ventilates it using a protective  mechanical ventilator  under human body temperature. This allows the delivery of essential nutrients and oxygen to the donor lung, supporting metabolic functions and allowing for prolonged preservation up to 17 hours. [ 1 ] [ 2 ]  The three major EVLP protocols at present are the  Toronto protocol ,  Lund protocol , and  Organ Care System  protocol. [ 3 ]  These EVLP protocols can be effective in rendering initially rejected donor lungs suitable for transplantation through reassessment and damage repair, thus widening the donor lung pools. [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_292", "contents": "The primary function of the lungs is to facilitate  gas exchange , supplying oxygen to the bloodstream while removing carbon dioxide from the blood. [ 6 ]  This process occurs in the  alveoli , tiny air sacs where oxygen and carbon dioxide move between the lungs and blood through a thin barrier."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_293", "contents": "Perfusion  in lung physiology refers to the passage of blood through the  pulmonary circulation , where it comes in close contact with the alveolar air. [ 7 ]  The efficiency of gas exchange is significantly influenced by the distribution and adequacy of blood flow, or perfusion, to various parts of the lungs. In a healthy lung, perfusion is optimally matched with ventilation (airflow), ensuring efficient gas exchange. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_294", "contents": "In vivo  lung perfusion occurs within the living organism and is tightly regulated by various physiological mechanisms, including responses to oxygen and carbon dioxide levels. [ 9 ]   Ex vivo  lung perfusion, on the other hand, is a controlled process outside the body, where donor lungs are connected to a  perfusion machine . Unlike  in vivo  perfusion, EVLP can be adjusted to optimise conditions for lung repair and assessment without the constraints of the body's  immune  and  coagulation systems . [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_295", "contents": "Perfusion  of organs, the conceptual framework of EVLP, was first discovered by Alexis Carrel and Charles Lindbergh in the 1930. [ 11 ]  Their pioneering experiments spanned various organs (heart, kidney, thyroid, ovary, adrenal glands, and spleen), laying the groundwork for organ preservation through perfusion. Lung perfusion in particular was used to study  pulmonary physiology  from the early 1990s. [ 12 ] [ 13 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_296", "contents": "Stig Steen and his team demonstrated the first clinical application of EVLP at the University Hospital of Lund in 2001. [ 14 ]  The team's objective was to evaluate the quality of lungs obtained from a non-heart-beating donor through EVLP. During EVLP, the metabolic activities in the lungs were continuously monitored. Following a reassessment that confirmed its suitability as a donor lung, the lung underwent transplantation. According to Steen's team, the recipient experienced \"good\" lung function during the initial five months of follow-up. [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_297", "contents": "Steen's team then attempted to improve the quality of donor lungs that were initially rejected for transplantation using EVLP. The team acquired nine initially rejected donor lungs and reconditioned them through short-period EVLP according to the Lund protocol. Subsequent reassessment concluded that six of the nine lungs became apt for transplantation, [ 15 ]  and all six recipients of the reconditioned lungs survived for three months. [ 16 ]  Successful reconditioning cases of rejected lungs through EVLP provided evidences that EVLP can be effective in improving the viability of donated lungs."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_298", "contents": "Later, the Toronto group refined Lund protocol by introducing the concept of extended EVLP. The Toronto protocol enabled the delivery of treatment at  normothermia , i.e., body temperature. [ 4 ]  Furthermore, portable EVLP called the Organ Care System (OCS) protocol was developed by an American biotechnology company TransMedics. OCS allows the assessments of the donor lungs during organ transportation. [ 17 ]  At present, the majority of transplant programs utilise either the Toronto or OCS Lung protocol, and some incorporate these techniques with further adaptations. [ 17 ] [ 18 ] [ 19 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_299", "contents": "The  Toronto Protocol  is currently one of the most widely adopted EVLP protocol, esteemed for its established performance and safety record. [ 20 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_300", "contents": "Both lungs obtained from brain death donors and donors after cardiac death undergo the Toronto protocol if they meet the listed eligibility criteria. The selection process involves a preliminary assessment of the lung's condition through  imaging ,  bronchoscopy , and  gas exchange measurements ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_301", "contents": "Donor lungs exhibiting insufficient oxygenation, as indicated by a  PaO 2 /FiO 2  ratio  below 300 mmHg, due to factors such as infection or aspiration, are subject to re-evaluation and conditioning through EVLP to improve their suitability for transplantation. However, some donor lungs with extreme damages were often excluded from assessment across various clinical studies. [ 21 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_302", "contents": "Following is the current eligibility criteria for Toronto protocol. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_303", "contents": "Toronto protocol is a low flow strategy that targets to reach 40% of the expected  cardiac output  to reduce the likelihood of oedema formation. To avoid  haemolysis , the Toronto Protocol opts for the use of an  acellular  perfusate rather than the blood-based perfusate containing  red blood cells .  Extracorporeal membrane oxygenation  (ECMO) machine is frequently used as a protective ventilator, and centrifugal pumps are used to pump the perfusates."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_304", "contents": "First, surgical tubes called  cannulas  are inserted into the pulmonary artery and left atrium, followed by intubation of the trachea or main bronchus. The EVLP circuit is then primed with a solution containing  methylprednisolone  (steroid),  heparin , and  antibiotics . Next, the lung is connected to the EVLP circuit and ventilator. Perfusion is initiated at a low flow rate, gradually increasing to the target flow of 40%. Meanwhile, the perfusate temperature is raised to normothermia. Ventilation begins once the perfusate reaches 37\u02daC, with some adjustments made to ensure adequate circulation and ventilation. Throughout the process, the lung's condition is closely monitored to optimise its function for transplantation. [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_305", "contents": "The  Lund protocol  is the first high-functioning EVLP protocol introduced by Steen from the University Hospital in Lund in 2000. [ 23 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_306", "contents": "The Lund protocol reconsiders donor lungs that were initially deemed unsuitable for transplantation. The exclusion criteria of the Lund protocol are the presence of any severe lung damages,  malignant cells  except brain tumours, and signs of  hepatitis  and  HIV . [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_307", "contents": "The Lund protocol utilises a roller pump, blood-based perfusate, and an ECMO ventilator. Red blood cells account for 14% of the Steen perfusate\u2013that is,  haematocrit  level is kept at 14%. [ 14 ]  The Lund protocol achieves a complete target flow, which is 100% of the cardiac output. This level of flow parallels the post-perfusion conditions encountered by transplanted lungs. [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_308", "contents": "In the Lund protocol, the main procedures involve reconditioning and assessment. During the reconditioning phase, various measures are taken to improve lung function. This includes recruiting  atelectasis \u2013partial collapses of the lungs, controlling inflammation using a  leukocyte  filter, circulating  antimicrobials  and  glucocorticoids  during perfusion, which typically lasts for 1 to 2 hours. [ 14 ]  After the reconditioning phase, the lungs undergo assessment to evaluate their suitability for transplantation. If the lungs meet the necessary standards, they proceed to preparation for transplant. However, if the reconditioning results are unsatisfactory, perfusion continues to provide the lungs with additional time for recovery. Should inadequate reconditioning persist, the donor lung is considered unsuitable and is subsequently discarded. [ 14 ] [ 24 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_309", "contents": "The  Organ Care System  (OCS) protocol is the first portable EVLP system designed to assess the donor lung functionality during the transportation of donated organs."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_310", "contents": "The OCS protocol utilises a blood-based perfusate, ventilator, and pumps. Similar to the Lund protocol, the OCS protocol employs a blood-based perfusate but with a higher  haematocrit  level ranging from 15-25%. [ 10 ]  Bellows pump is used for ventilation, and pulsatile pump is used for perfusion. The target flow of the OCS protocol ranges from 2 to 2.5 litres per minute. [ 25 ]  Organ Care System\u2122 by Transmedics is currently the only commercially available EVLP devices that adopts the OCS protocol. [ 26 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_311", "contents": "In both the Toronto and Lund systems, the donor lung is subject to low temperature  cryopreservation  from the point of harvest until it is linked to the EVLP circuit upon arrival at the recipient's hospital. [ 27 ]  This cryopreservation period adds to the  cold ischaemia time , which, if prolonged, can lead to substantial lung injury in the recipient, potentially resulting in  transplant rejection . [ 28 ]  OCS protocol could minimise the cold ischaemia time, as the OCS lungs are kept at 37\u02daC throughout the entire  ex   vivo  ventilation and perfusion process."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_312", "contents": "On one hand, study findings indicate that lungs preserved with the OCS protocol demonstrate short-term outcomes similar to those preserved using standard cold storage techniques. [ 29 ]  On the other hand, the study suggests that long-term mortality rates might be notably lower among recipients who receive lungs preserved with the OCS protocol compared to those preserved via standard cold storage methods. [ 29 ]  It is noted by researchers that further investigation into the outcomes associated with the OCS protocol is needed."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_313", "contents": "EVLP can be useful in the reconditioning of lungs affected by  pulmonary oedema ,  trauma , or  infection . [ 30 ]  It is particularly beneficial for lungs with borderline function or prolonged ischaemic times."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_314", "contents": "Alveolar collapse  or fluid buildup in lungs often cause atelectasis, which results in reduced gas exchange. EVLP addresses this issue by mechanically ventilating the lungs, thereby inflating the collapsed parts. [ 26 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_315", "contents": "Inflammation  and infection are prevalent complications with donor lungs. To mitigate these issues, EVLP facilitates the direct administration of  anti-inflammatory drugs  and antibiotics into the lung\u2019s blood vessels. This intervention aids in reducing inflammation, treating existing infections, and thereby improving the health and functionality of the lung before transplantation. [ 31 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_316", "contents": "Furthermore, an aggressive protocol with EVLP can enable the transplantation of some previously rejected donor lungs. These lungs typically exhibit atelectasis and a low PaO2/FiO2 ratio. [ 32 ]  Through the use of EVLP, these lungs can be rehabilitated and deemed suitable for transplantation, thus expanding the pool of viable donor lungs."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_317", "contents": "EVLP ensures the viability of lungs from high-risk donors for transplantation, optimising lung utilisation and improving transplant outcomes. Patients who received EVLP-treated lungs showed excellent short-term and long-term survival rates, alongside improved graft function. [ 33 ]  These recipients had comparable, if not superior, survival rates and function compared to those transplanted using  conventional methods . Additionally, the use of EVLP has been associated with a reduction in the incidence of  primary graft dysfunction , a fatal complication following lung transplantation. [ 34 ]  During the EVLP process, a  bronchoscope  is used to remove any secretions or blockages in the rejected donor lungs. This procedure enhances post-transplantation breathing capabilities."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_318", "contents": "Through rehabilitation and detailed assessment of once rejected donor lungs, EVLP can expand the donor lung pool. This technique\u2019s potential to improve the quality and increase the availability of donor lungs underscores its significance in the field of lung transplantation. [ 35 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_319", "contents": "As the donor lung comes into close contact with the circuit materials during EVLP, its exposure to pro-inflammatory conditions is inevitable. [ 36 ]  Studies have shown that EVLP induces a significant up-regulation of inflammation-related genes like  microribonucleic acid (miR)-17  and  miR-548b . [ 37 ] [ 38 ]  Moreover, increase in the production of inflammation-inducing  cytokines  over time in the EVLP perfusate was reported. [ 39 ]  Targeting these inflammatory pathways prior to or during EVLP could be necessary to minimise the risk of inflammatory responses-triggered organ rejection. [ 36 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_320", "contents": "EVLP has a potential to trigger  ventilator-induced lung injury  (VILI) due to the use of mechanical ventilators for air flows into the donor lung, possibly resulting in irreversible functional or structural damage. [ 36 ] [ 40 ]  The most commonly used ventilation protocol in EVLP nowadays is positive-pressure ventilation (PPV) protocol, which carries a higher risk of inducing VILI compared to other protocols like negative-pressure ventilation (NPV). [ 41 ] [ 42 ] [ 43 ]  Some attempts have been made to modify the protocol to NPV, and preclinical trials support that NPV protocol can be equally effective in EVLP. [ 41 ] [ 42 ]  Yet, further clinical validation is warranted by the researchers to validate this intervention."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_321", "contents": "According to a multi-centre observational study, the expenses associated with EVLP were significantly greater compared to the conventional lung transplantation. [ 18 ]  The high cost was attributed to the costly operation machine, frequent replacement of the perfusate, and prolonged length of stay in  intensive care unit . [ 36 ]  While the cost of training transplant staff on EVLP may contribute to the overall expenses, the exact cost of incorporating EVLP remains unclear due to the absence of standardised guidelines for EVLP. [ 26 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_322", "contents": "The  Fontan procedure  or  Fontan\u2013Kreutzer procedure  is a  palliative  surgical procedure used in children with univentricular hearts. It involves diverting the  venous   blood  from the  inferior vena cava  (IVC) and  superior vena cava  (SVC) to the  pulmonary arteries . The procedure varies for differing congenital heart pathologies. For example, in  tricuspid atresia , the procedure can be done where the blood does not pass through the morphologic  right ventricle ; i.e., the systemic and pulmonary circulations are placed in series with the functional single ventricle. By contrast, in  hypoplastic left heart syndrome , the heart is more reliant on the more functional right ventricle to provide blood flow to the systemic circulation. The procedure was initially performed in 1968 by  Francis Fontan  and Eugene Baudet from Bordeaux, France, published in 1971, simultaneously described in July 1971 by Guillermo Kreutzer from Buenos Aires, Argentina, presented at the Argentinean National Cardilogy meeting of that year and finally published in 1973. [ 1 ] [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_323", "contents": "The Fontan Kreutzer procedure is used in pediatric patients who possess only a single functional ventricle, either due to lack of a heart valve (e.g.  tricuspid  or  mitral atresia ), an abnormality of the pumping ability of the heart (e.g.  hypoplastic left heart syndrome  or  hypoplastic right heart syndrome ), or a complex congenital  heart disease  where a bi-ventricular repair is impossible or inadvisable. The surgery allows blood to be delivered to the lungs via central venous pressure rather than via the right ventricle. [ 3 ]  Patients typically present as neonates with cyanosis or congestive heart failure. [ 4 ]  Fontan completion is usually carried out when the patient is 2\u20135 years of age, but is also performed before 2 years of age. [ 5 ] [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_324", "contents": "There are four variations of the Fontan procedure: [ 7 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_325", "contents": "The  Fontan-Kreutzer  procedure is the third procedure in the staged surgical palliation. [ 8 ]  It is performed in children born with congenital heart disease without two functional ventricles and an effective parallel blood flow circuit. [ 9 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_326", "contents": "The first stage is known as the  Norwood  procedure. This stage generally involves combining the pulmonary artery and aorta to form a larger vessel for blood to get to the body. An artificial tube or shunt can be placed from this larger vessel to the pulmonary arteries so that blood can get from the heart to the lungs. The wall between the left and right atrium can be removed to allow the mixing of oxygenated and de-oxygenated blood. [ 10 ] [ 11 ] [ 12 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_327", "contents": "The second stage is called the  hemi-Fontan  or the  Bidirectional Glenn  procedure . This intermediary stage incorporates the shifting of oxygen-poor blood from the top of the body to the lungs. [ 13 ]  The  superior vena cava  (SVC), which carries blood returning from the upper parts of the body, is disconnected from the heart and instead redirects the blood into the pulmonary arteries. [ 13 ]  The  inferior vena cava  (IVC), which carries blood returning from the lower body, continues to connect to the  right atrium . [ 14 ] [ 12 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_328", "contents": "The third stage is called the  Fontan-Kreutzer  procedure  which involves redirecting the blood from the  inferior vena cava  to the lungs. [ 8 ]  At this point, the oxygen-poor blood from upper and lower body flows through the lungs without being pumped (driven only by the pressure that builds up in the veins or central venous pressure). This improves the lower than normal oxygen levels and results in one functional ventricle that is responsible  for supplying blood to the rest of the body. There are currently three various modern techniques for the Fontan procedure which include: Atriopulmonary connection, lateral tunnel total cavopulmonary connection, and extracardiac conduit."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_329", "contents": "After Fontan Kreutzer completion, blood must flow through the lungs without being pumped by the heart.  Therefore, children with high  pulmonary vascular resistance  may not tolerate a Fontan procedure.  Often,  cardiac catheterization  is performed to check the resistance before proceeding with the surgery.  This is also the reason a Fontan procedure cannot be done immediately after birth; the pulmonary vascular resistance is high  in utero  and takes months to drop.\nFontan procedure is also contraindicated in those with pulmonary artery hypoplasia and significant mitral insufficiency. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_330", "contents": "In the short term, children can have trouble with  pleural effusions  (fluid building up around the lungs).  This can require a longer stay in the hospital for drainage with  chest tubes .  To address this risk, some surgeons make a fenestration from the venous circulation into the atrium.  When the pressure in the veins is high, some of the oxygen-poor blood can escape through the fenestration to relieve the pressure.  However, this results in  hypoxia , so the fenestration may eventually need to be closed by an  interventional cardiologist ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_331", "contents": "In a 2016 review, Dr. Jack Rychik, head of the Single Ventricle Survivorship Program at  Children's Hospital of Philadelphia  summarized the long-term consequences of Fontan circulation as an \"indolent and progressive state of heart failure\" with predictable long-term consequences on several organ systems. [ 15 ]  Chronic  venous hypertension  from the stasis and lowered cardiac output are assumed to be at the root of lymphatic complications such as  chylothorax ,  protein losing enteropathy  and  plastic bronchitis . These complications may occur in the immediate post-operative period as well as in the medium and long term. New interventional and surgical strategies have been investigated to relieve the lymphatic complications associated with the Fontan circulation. [ 16 ]  Concerns about damage to the liver have emerged more recently, as the Fontan circulation produces congestion and  lymphedema  in this organ. This can lead towards progressive  hepatic fibrosis  and other complications of  Fontan-associated liver disease . [ 17 ]  Screening protocols and treatment standards are emerging in the light of these discoveries. [ 15 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_332", "contents": "Because of structural and electrochemical changes related to scarring after the procedure,  arrhythmias  are common.  Pacemakers  are placed in as many as 7% of patients who undergo the Fontan procedure. [ 18 ]  While the need for pacemakers may be related to the underlying cardiac anomaly, there is sufficient evidence that the surgery itself lead to the need for cardiac pacing."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_333", "contents": "The Fontan procedure is  palliative  \u2014 not curative \u2014 but more than 80% of the cases  can result in normal or near-normal growth, development, exercise tolerance, and good quality of life. [ 19 ]  However, 10% or more of patients may eventually require  heart transplantation , [ 20 ]  and given the long-term consequences of chronic venous hypertension and insidious organ damage, freedom from morbidity is unlikely in the long term. New approaches to the management of failing Fontans or other clinical deterioration have included lymphatic decompression surgical procedures & intervention,  Ventricular assist devices  or other mechanical support therapies as either bridge to transplantation or destination therapies. [ 21 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_334", "contents": "Renal complications may occur. This is attributed to the circulatory changes in blood flow as well as possible exposure to nephrotoxic medications, iodine contrast agents, and long term cyanotic and ischemic nephropathy. Abnormalities including chronic kidney disease and impaired renal function have been shown with measured renal function. [ 22 ]  Popular markers, such as proteinuria and microalbuminuria, are used in the measurement renal function."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_335", "contents": "It is estimated in 2018 there was an 85% for a survival rate of thirty years following a Fontan procedure and there are approximately 50,000 to 70,000 people in the world with Fontan circulation. [ 23 ]  It is approximated that 40% of people with Fontan circulation are \u226518 years of age. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_336", "contents": "A normal heart system has a series circuit with the right ventricle pumping blood into the pulmonary circulation. After exchanging gases, the blood is delivered to the left ventricle (and systemic arteries) through the pulmonary veins. In Fontan circulation, the right ventricle does not exist (or is bypassed), and the venae cavae are attached directly to the pulmonary artery. [ 24 ]  After oxygenation, the blood is pumped into the aorta by the unique, single ventricle. Because of the missing right ventricle, the force driving blood through the lungs is strongly reduced. This causes engorgement of the venous circulation, the most frequent complication of the Fontan procedure."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_337", "contents": "Fontan circulation can influence the  peripartum  or pregnant physiologic states. Pregnancy has historically been discouraged in Fontan patients due to high rates of miscarriage, cardiovascular compromise, or increased mortality. Many complications have been attributed to flawed placental function. However, improvements of the Fontan operation have resulted in pregnancies with lower incidence of heart and vascular compromise in the mother. [ 25 ]  Complications that may occur in the fetus may include, but are not limited to: oligohydramnios, preterm birth, low birth weight, small size for gestational age, or still birth. Maternal complications can include, but are not limited to: heart failure, thromboembolism, arrhythmias, and preeclampsia. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_338", "contents": "The Fontan procedure was initially described in 1971 by  Dr. Francis Fontan  (1929\u20132018) from Bordeaux, France.  Prior to this, the surgical treatment for tricuspid atresia consisted of creating a  shunt  between a systemic artery and the  pulmonary artery  ( Blalock-Taussig shunt ) or the  superior vena cava  and the pulmonary artery (Glenn shunt).  These procedures were associated with high mortality rates, commonly leading to death before the age of one year. [ 26 ]    In an attempt to improve this, Fontan was engaged in research between 1964 and 1966 endeavouring to fully redirect flow from the superior and inferior vena cavae to the pulmonary artery. [ 27 ]  His initial attempts in dogs were unsuccessful and all experimental animals died within a few hours; however, despite these failures, he successfully performed this operation in a young woman with  tricuspid atresia  in 1968 with Dr. Eugene Baudet. [ 26 ]  The operation was completed on a second patient in 1970, and after a third case the series was published in the international journal  Thorax  in 1971. [ 28 ]  Dr. Guillermo Kreutzer from Buenos Aires, Argentina (b. 1934), without any knowledge of Fontan's experience, performed a similar procedure in July, 1971 without placing a valve in the Inferior Vena Cava inlet and introduced the concept of \"fenestration\" \u2013 leaving a small atrial septal defect to serve as a pop-off valve for the circulation. [ 29 ] [ 26 ]  Techniques have been improved to include the lateral tunnel and use of an extracardiac conduit for congenital heart diseases beyond tricuspid atresia (hypoplastic left heart syndrome, etc). [ 30 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_339", "contents": "Median sternotomy  is a type of  surgical  procedure in which a vertical inline  incision  is made along the  sternum , after which the sternum itself is divided using a  sternal saw . [ 1 ]  This procedure provides access to the heart and lungs for surgical procedures such as  heart transplant ,  lung transplant , corrective surgery for  congenital heart defects , or  coronary artery bypass surgery . [ 2 ] [ 3 ] [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_340", "contents": "The median sternotomy was first proposed by Herbert M. N. Milton in 1897. [ 5 ]  Since the first successful open heart operation in 1953, most cardiac surgeons initially used the bilateral anterior  thoracotomy , which was a very complication-prone and painful approach. [ 6 ]  In 1957, after the demonstration of the superiority of median sternotomy, it became the standard incision and has remained so until today. [ 5 ]  Through this approach, the surgeon can see the entire heart and control the whole operative field visually and tactically. Cardiac surgery through sternotomy is safe and efficient, and is considered to be the gold standard for surgical treatment of all congenital and acquired heart diseases resulting in low failure rates and excellent proven long-term outcomes. [ 7 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_341", "contents": "Cardiac surgery via median sternotomy is performed in over 1 million patients per year worldwide. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_342", "contents": "The  Nuss procedure  is a  minimally invasive  procedure, invented in 1987 by Dr. Donald Nuss and his colleagues, Dr. Daniel Croitoru and Dr. Robert Kelly, for treating  pectus excavatum . [ 1 ] [ 2 ] [ 3 ]  He developed it at  Children's Hospital of The King's Daughters , in  Norfolk, Virginia . The operation typically takes approximately two hours. [ 4 ] :\u200a1277"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_343", "contents": "Through two small incisions in the side of the chest, an introducer is pushed along posterior to the  sternum  and ribs, and anterior to the heart and lungs. Then a concave  stainless steel  bar is slipped under the sternum, through the incisions in the side of the chest. A third, smaller incision is made to insert a  thoracoscope  (small camera) used to help guide the bar. Taller patients, older patients, or patients requiring extensive correction may receive two or more bars.  All bars may be placed through two incisions or additional incisions may be made. The bar is then flipped, and the sternum pops out. To support the bar and keep it in place, a metal plate called a stabilizer may be inserted with the bar on one side of the torso.   PDS sutures  may also be used in addition to the stabilizer. The stabilizer fits around the bar and into the ribcage. The bar and stabilizer are secured with  sutures  that dissolve in about six months."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_344", "contents": "Kevlar strings may also be attached to the lower ribcage to prevent costal flaring. This option is often not preferred by surgeons as it can cause extreme amounts of additional pain during recovery and up until the strings are removed."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_345", "contents": "Some surgeons have achieved excellent results using only pericostal sutures, without the use of stabilizers. [ 4 ]   For older children who have more ossified bones, an additional option the surgeon has is to make an incision across the sternum so the bar is attached with a wire to the sternum to avoid bar displacement.  Older children's bones do not conform as easily to the bar, thus increasing the risk of bar displacement, so the wire attaching the bar directly to the sternum may help avoid a second surgery to correct bar displacement."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_346", "contents": "Eventually, the bar is secured with muscle tissue that regrows during the recovery time.  Although initially recommended only for younger patients, the Nuss procedure is now commonly used on patients in their thirties and forties with excellent results. [ 5 ] :\u200a342\u20133"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_347", "contents": "Postoperative evaluation indicates a significant improvement in pulmonary function studies and a high proportion of patients report improvements in well-being and an increase in exercise tolerance. [ 5 ] :\u200a341"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_348", "contents": "Although this procedure is categorized as \"minimally invasive\", post-operative pain control can be quite challenging, thus requiring multi-modal pain management including epidural  anesthetics . Nurses who attend these patients post operation generally concur that this operation is one of the more difficult recoveries of any operations for children. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_349", "contents": "The retrosternal passage performed in the Nuss procedure carries a high risk of damaging the heart. This is why multiple sternal elevation systems have been developed to increase the space between the heart and the sternum in order to pass the thoracoplasty rod more safely. [ 6 ] [ 7 ] [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_350", "contents": "Recovery time is generally four to five days as an in-patient, depending on the patient age, activity level, co-morbidities and post-operative complications (if any), followed by time at home to overcome the pain and to let the bar settle into place. Sleep will be hampered because of the pain, discomfort and inability to sleep on either side of the body. Breathing can be difficult because of the stiffness of the bar and post-operative pain, but this generally improves within a few weeks to a month. Patients younger than fifteen often require only two to four weeks at home after being discharged from the hospital for recovery. However, older children and adults typically require a greater recovery time due to the increased ossification (and thus decreased flexibility) of their bones. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_351", "contents": "In this case, the difficulty and length of recovery should be carefully considered prior to making the decision to undergo the operation, as the limitations to lifestyle, functionality and comfort can be dramatic for many months.  This cannot be understated for older children, which is why many doctors do not recommend this procedure unless medically necessary (i.e. not for cosmetic reasons). Fully grown adults may require from four weeks to many months before they can resume normal activities, including work. For six to twenty-four hours after the operation, the patient generally will have a  Foley catheter  to minimize risk of movement that could displace bar, and because the epidural can interfere with normal urination. The patient may also receive thoracic  epidural  analgesia in the back for two to five days depending on patient recovery. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_352", "contents": "Studies using  sonography  have shown post-operative changes in many patients such as an acute angulation of the  costochondral junction  and  rib fractures  near the pectus bar. Such changes occurred especially in patients who were older than 10 years or who underwent a high elevation of the sternum. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_353", "contents": "For six weeks, physical activity should be limited (i.e. no running or strenuous physical activity, and lifting is limited to ten pounds or less). Walking for exercise and breathing exercises aid in recovery. It is sometimes suggested that weight-training should be limited or eliminated for up to three months. It is also recommended that any sports where contact may occur should be avoided. However, aerobic sports are, in fact, encouraged, as results after bar removal are best maintained in patients who have stimulated their cardiopulmonary systems while the bar was in place. [ 5 ] :\u200a343\u200a \nThe restoration of the patients' physical abilities can take up to ten months. However, in the majority of cases, patients report a return to their preoperative physical state after roughly six months. Many patients choose to return to work at this point. Despite this physical recovery, patients are recommended to avoid more physical situations such as contact sports until after the bar has been removed."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_354", "contents": "Many Pectus Excavatum patients exhibit psychological symptoms associated with the cosmetic appearance of their disorder. For many, it is the driving force behind undergoing the Nuss procedure. The recovery from these psychological symptoms can also take some time, though many patients report improvements in confidence and  self-esteem  after only a few weeks, once the effects of the surgery can be noticed. Ultimately, almost all patients report a noticeable improvement in their confidence and body image after they have completely recovered from the operation."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_355", "contents": "After a period of two to four years, [ 5 ] :\u200a343\u200a  the  surgical stainless steel  bar is removed from the patient's chest. This procedure lasts approximately ninety minutes.  The length of time that the patient stays at the hospital following the bar removal procedure varies, depending on the amount of new bone growth surrounding the bar.  Accordingly, the length of time may range from a few hours to several days, or up to one week. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_356", "contents": "Iatrogenic  damage to the heart and lungs during the procedure is a concern. Scopes (cameras) are often utilized by the surgical team to minimize this risk. There is still an extremely minor risk of abrasion or puncture. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_357", "contents": "Air in the chest (pneumothorax) is one of the more frequent complications. A chest tube may be required or aggressive breathing exercises and close monitoring may be adequate. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_358", "contents": "With the use of stabilizers and PDS sutures, bar displacement rarely occurs. [ 4 ] :\u200a1276,\u200a1280\u200a [ 5 ] :\u200a340\u20131\u200a   If these methods of bar fixation are not used, bar displacement may occur. This can be quite painful and requires some sort of intervention: either bar removal, or repositioning of the bar with some sort of bar fixation. Patients should understand prior to the surgery that if bar displacement occurs soon after surgery, a second surgery will be immediately required which is even a more difficult recovery as the patient is already weakened and in pain.   High impact trauma, such as car accidents can dislodge the bars, causing extreme pain. This is the reason for the restriction on driving, because a sudden defensive maneuver, such as a jerk of the steering wheel, could dislodge the bar up to six weeks directly after the surgery."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_359", "contents": "Other complications which may occur include hemothorax, pleural effusion, pericarditis, wound infection and pneumonia and acquired scoliosis. [ 5 ] :\u200a340\u200a  Vigorous incentive spirometry is used to prevent pneumonia. [ 5 ] :\u200a341\u200a  Some patients are allergic to one of the components of stainless steel. [ 5 ] :\u200a341\u200a   As a result, allergy testing is now routinely done prior to surgery.  In the event of an allergy, a titanium bar will be used."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_360", "contents": "Older children may also struggle with adjusting to living in their changed bodies during the several months of healing due to the pain and limitations."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_361", "contents": "A  tracheobronchoplasty  is a surgical procedure performed at limited medical facilities across the  United States .  [ 1 ]  It consists of a  thoracic surgery  during which mesh is sutured to the outside of the patient's trachea through a series of hundreds of knots.  These  sutures  are in turn pulled taught which subsequently 'opens' the collapsed tissue in the  tracheal  wall creating an opening with which to process air.  The hope is eventually, this 'scaffolding' of sorts will scar over thereby strengthening the structure and making it permanent. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_362", "contents": "Recovery time is typically six to nine months and the patient should see gradual improvement in voice control, reduced coughing and an increased ability to move air more effectively.  Not all patients with  tracheobronchomalacia  can be considered candidates for this procedure.  However, it does offer an alternative for those patients who are unable to tolerate the more traditional  stent  therapy. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_363", "contents": "A  transmediastinal gunshot wound  (TMGSW) is a  penetrating injury  to a person's  thorax  in which a  bullet  enters the  mediastinum , possibly damaging some of the major structures in this area.  Hemodynamic  instability has been reported in about 50% of cases with a  mortality rate  ranging from 20% to 49%. Some studies have shown marked improvement in the mortality rate of patients who survived transfer to the operating room rather than being treated surgically in the ER."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_364", "contents": "Complications caused by a TMGSW can range from mild to life-threatening depending on which structures are damaged. It can be rapidly lethal if a major structure is involved. Some of the possible complications caused by a TMGSW are:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_365", "contents": "Previously, every stable patient who suffered a TMGSW received extensive evaluation that included  chest radiography , oesophagography, esophagoscopy,  angiography ,  bronchoscopy , or  cardiac ultrasound . Grossman et al. found evidence that the trajectory of the bullet can be delineated with the use of  computed tomographic scan  (CT). Subsequently, other studies demonstrated the use of CT as a screening tool for stable patients who suffered TMGSW is a reliable tool for ruling out, diagnosing, and avoiding missed injuries. For example, Stassen et al. showed data of 22 stable patients who were screened with CT, chest X-ray and  abdominal ultrasound ; seven patients showed a positive CT scan and required additional evaluation, and of these seven patients, three required surgical management. [ 1 ]  Additionally the work of Burack et al., [ 2 ]  whose evaluation of stable patients with penetrating injuries to the mediastinum \u2014 this time including stab wounds \u2014 relied mostly on CT and ultrasound, showed similar results. The work of Ibirogba et al. did so, as well. [ 3 ]  Recent data suggest that the use of CT scan with some additional noninvasive techniques, such as ultrasound and chest roentgenogram, are reliable screening tools to decide whether patients need further evaluation.  [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_366", "contents": "The criteria to define a patient as stable or unstable could have variations from institution to institution.  For example, Burack  et al.  used a list of six criteria in his paper that defined an unstable hemodynamic state:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_367", "contents": "One common criteria found in literature is a sustained systolic  blood pressure  of less than 100 mmHg, but this can be an oversimplification. Patients with clinical evidence of possible TMGSW that are considered unstable receive no further evaluation and are taken to surgery immediately. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_368", "contents": "Stable patients are evaluated with CT, ultrasound, and/or chest X-ray as the institution's protocol specifies. When this initial survey is negative, patients can be observed with conservative management. In many cases, chest tubes are required due to concomitant lesions in the  pleural cavity . If possible lesions are found (for example, a missile track near the  trachea  or  esophagus , or pneumomediastinum), further investigation follows with oesophagography, esophagoscopy, angiography, or bronchoscopy as needed to rule out or confirm such a lesion, and decide whether surgical repair is warranted."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_369", "contents": "Unstable patients are managed by operative exploration of the mediastinum. Moribund patients go through an emergency department  thoracotomy . This measure is taken because at their arrival in the emergency room, these patients are in such critical condition that they would not survive long enough to be transferred to an operating room. Outcome is very poor. Burack  et al. [ 2 ]  reported only 2.8% survival of such patients in his study. In a study by Van Waes et al., (which included all thoracic-penetrating injuries, not just transmediastinal) survival after emergency department thoracotomy was 25%. [ 4 ]  In other circumstances the unstable patient is immediately transferred to the operating room for exploration by thoracotomy or sternotomy. Survival rate has been reported as high as 75 percent when the patient is able to reach the OR. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_370", "contents": "Hilal bin Ali bin Hilal Al-Sabti  ( Arabic :   \u0645\u0639\u0627\u0644\u064a \u0627\u0644\u062f\u0643\u062a\u0648\u0631 \u0647\u0644\u0627\u0644 \u0628\u0646 \u0639\u0644\u064a \u0628\u0646 \u0647\u0644\u0627\u0644 \u0627\u0644\u0633\u0628\u062a\u064a ) was born on October 27, 1972. On June 16, 2022, His Majesty Sultan  Haitham Bin Tariq  has issued a Royal Decree appointing Dr. Hilal bin Ali bin Hilal Al Sabti, as the new Minister of Health. [ 1 ] [ 2 ]   He succeeded His Excellency Dr. Ahmed Al Saidi on this new role. [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_371", "contents": "Prior to becoming the Minister of Health, Dr. Al Sabti served as the Executive President of  Oman Medical Specialty Board  (OMSB), from May 2015 to June 2022, [ 4 ]  under Royal  Decree  No. 24/2015. [ 5 ] [ 6 ] [ 7 ]   Hilal is a  Senior Consultant  Cardiothoracic Surgeon at  Sultan Qaboos University Hospital (SQUH) . [ 8 ] [ 9 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_372", "contents": "In 2014, the first  artificial heart  transplantation procedure in the  Sultanate  was done by a cardiac surgery team led by Al Sabti, for a patient suffering from  heart failure . [ 10 ]  In April 2015, a cardiac surgery team of Sultan Qaboos University Hospital has managed to plant a valve inside a valve in the  aorta  and  mitral  valves through a  catheter .  A first-of-its-kind surgery in the world done on a pregnant woman.  The cardiac surgery team was led by Al Sabti. [ 11 ]   Dr. Hilal contributed in the first Thoracab procedure done in Oman and Middle East. [ 12 ]   In 2013 a team of cardiac surgeons, under the leadership of Dr. Hilal, and cardiac anesthetists at Sultan Qaboos University Hospital, successfully conducted TAVI procedures to four patients aged over 75 years. [ 13 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_373", "contents": "Recently, an operation was carried out by the SQUH medical team of surgeons headed by Dr. Hilal Al Sabti.  The patient, who is a mother of three, was suffering from a rare heart condition known as automatic coronary dissection, which disease affects the coronary arteries of the heart and occurs more often in women under the age of 50 years. The woman was having elevated heart enzymes and the dissection in coronary arteries are expanding to the branch arteries. The surgical team successfully performed an operation by replacing three arteries in the heart. The procedure was accompanied by the use of a new technique that demonstrated the advanced skills of the surgical team.  A medical team at Sultan Qaboos University Hospital has managed to save the patient's life.  SQUH added that  \u201cThe surgery will be documented and published as a scientific paper in a refereed international scientific journal, so that the benefit is widespread among specialists in cardiothoracic surgery around the world,\u201d . [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_374", "contents": "Dr. Al Sabti was blessed by  His Majesty Sultan Qaboos bin Said , to be honoured with GCC Medal in Civil Service and Administrative Development, on May 1, 2019. [ 15 ]  He was also conferred by His Majesty Sultan Qaboos bin Said, the Oman Civil Order (3rd class) in November 2015 along with other Excellencies, in appreciation to their active role in performing national duties. [ 16 ]   Dr. Hilal was also conferred an  Honorary Fellowship  by the  College of Anaesthesiologists of Ireland  in May 2019. [ 17 ] [ 18 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_375", "contents": "His Majesty Sultan  Haitham bin Tariq  conferred him the Second Class of the  Civil Order of Oman  on 18 November 2024. [ 19 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_376", "contents": "Dr. Al Sabti held the post of Deputy Director-General for Clinical Affairs at Sultan Qaboos University Hospital from 2010 to 2013, strengthening the University Hospital\u2019s liaison with other international universities for  training ,  education  and  research . [ 20 ] [ 21 ]  He was a patron of the establishment of the first Hybrid Operating room in Oman in Sultan Qaboos University. [ 22 ]  Dr. Al Sabti is involved in various  charity  projects, educational talks, health awareness campaigns, and participation in Ministry of Health, SQUH, and OMSB Committees. [ 23 ] [ 24 ] [ 25 ]  He is a member of international and local associations."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_377", "contents": "In scholarly activities, Dr. Al Sabti has numerous publications in peer-reviewed journals. [ 26 ] [ 27 ]  His research works are reflected in his  Google Scholar ,  ResearchGate  and  PubMed Direct  accounts.  The intent to continuously publish is enhanced by his collaboration with various local and international research groups. [ 28 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_378", "contents": "Oman Medical Specialty Board described Dr. Al Sabti as an innovative and visionary leader, an agent of change and opportunities, who has a documented track record of accomplishments and the aspirations to improve the quality of  health care  in the Sultanate. [ 29 ]  OMSB was led to achieving various major Milestones:"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_379", "contents": "Dr. Al Sabti earned his MD degree from Sultan Qaboos University (SQU), Muscat, Oman and did his General Surgery Residency in the same university. [ 54 ]   He completed his residency training in Cardiac Surgery at McGill University, Canada while obtaining a Master of Science degree in Experimental Surgery. [ 55 ]   He obtained his Board certification in Cardiac Surgery from the Royal College of Physicians and Surgeons of Canada in 2005.  He continued his professional development through a Fellowship in Minimal Invasive Cardiac Surgery at Hamburg Eppendorf University Hospital, Germany. [ 56 ]   Dr. Al Sabti was the First Omani to attend Leadership for Physician executive's course in Harvard Medical School in 2009; and the first Omani physician to attend  the  Oxford  University  Strategic  Leadership  Program  in  November  2013. [ 57 ]  Dr. Al Sabti pioneered the establishment of Cardiothoracic Surgery Division in Sultan Qaboos University Hospital \u2013 established in 2006. [ 58 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_380", "contents": "As a student, Dr. Al Sabti received numerous awards, one of which is the National/International Research Award in Fraser Gurd Surgical Day, 2nd Prize for the Residents Presentations in Research in McGill University 2002. [ 59 ]   He also received \"Best Resident Teacher Award\" in Cardiac Surgery for 2005 in McGill University, Canada; as well as \"Best Student Award\" in 1995 from the Department of Pharmacology, Sultan Qaboos University, Oman."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_381", "contents": "The  American Board of Thoracic Surgery  is an  American  surgical  organization  devoted to  thoracic surgery. [ 1 ]  The ABTS will soon shut down their access to the Self-Education Self Assessment in Thoracic Surgery."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_382", "contents": "This article about a medical organization or association is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_383", "contents": "The  Association of Cardiothoracic Surgical Assistants (ACSA)  is a professional body in the  United Kingdom  that ACSA represents a body of non-medical practitioners working in  cardiothoracic surgery , performing a range of skilled interventions. It was formed in 1997. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_384", "contents": "The ACSA supports its members by providing educational meetings, discussion forums and professional advice. Members also can receive indemnity cover at a reduced cost from the  Medical Protection Society  and receive a newsletter, have access to a members' forum and to archived educational material. ACSA represents its members in the  Society of Cardiothoracic Surgery  and has helped to develop the  National Curriculum  framework for surgical care practitioners."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_385", "contents": "In 1997, 12 surgical assistants from the UK met to discuss the future of cardiothoracic surgical assistants in the UK; a motion was passed to form the Association of Cardiothoracic Surgical Assistants (ACSA). Richard Ward was elected as its inaugural president, and the association identified the need for a support network and standard education and qualification practices."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_386", "contents": "The same year, the Society of Cardiothoracic Surgery, the Royal College of Surgeons of Great Britain and Ireland and ACSA formulated the Surgeons' Assistant Diploma in Cardiothoracic Surgery. In 1998, ACSA identified a need to run a revision course for future candidates for the diploma. This course has since run with great success."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_387", "contents": "In 2004, the title of Surgical Practitioner was reviewed by the United Kingdom Department of Health. The title was later changed once again to \"Surgical Care Practitioner (SCP)\". This title is still used today although it should be said that it is still only a working title due to disputes with other groups. The same year, work began on the National Curriculum Framework for SCPs, started by the Department of Health."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_388", "contents": "ACSA worked with many other organisations including the Royal College of Surgeons, the  National Association of Assistants in Surgical Practice , the  Association for Perioperative Practice , the  Association of Surgeons in Training , the  Association of Operating Department Practitioners , the  British Orthopaedic Trainees Association , and the  Royal College of Obstetricians and Gynaecologists ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_389", "contents": "In 2006 the National Curriculum framework was published. In 2007 ACSA and SCTS decided to start holding their  Annual General Meetings  to coincide with each other."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_390", "contents": "Steven Bryant went on to become president of ACSA for two years, during this time Steven attended many meetings at the RCS and other organisations such as the 'new ways of working' department, set up  by the last government to discuss the future development of the surgical assistant/care practitioner. He is widely credited as one of the leading lights in the profession and in 2011 became the first non-medically qualified practitioner to become an examiner for the RCS diploma. Steven Bryant continues to work at Papworth hospital in Cambridgeshire as the lead scp Papworth Hospital is regarded as one of the main training centres for SA/SCP  training in the UK and abroad."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_391", "contents": "The  European Association for Cardio-Thoracic Surgery  ( EACTS ) is a membership organisation devoted to the practice of  cardiothoracic surgery . The mission statement of the association is to advance education in the field of cardiac, thoracic and vascular interventions; and promote research into cardiovascular and thoracic physiology, pathology and therapy, with the aim to correlate and disseminate the results for the public benefit. Within the EACTS there is a large number of committees working on various issues in order to improve cardio-thoracic surgery. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_392", "contents": "EACTS was founded as a  European  organisation. However, its membership is now spread all over the world in all continents representing some 70 countries. Since its foundation in 1986 more than 3500 members have been admitted, and the interest in applying for membership has grown considerably during the last few years. [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_393", "contents": "The EACTS Annual Meeting is the largest cardio-thoracic meeting in the world [ citation needed ]  focusing on scientific developments and research in the following specialities: Acquired Cardiac Disease, Congenital Heart Disease, Vascular Disease and Thoracic Disease. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_394", "contents": "The EACTS publishes two journals focused on high-quality research and cardio thoracic surgery education and one website featuring video based cardio-thoracic tutorials these are:  European Journal of Cardio-Thoracic Surgery (EJCTS) ,  Interactive Cardiovascular and Thoracic Surgery (ICVTS) , and  Multimedia Manual of Cardio-Thoracic Surgery (MMCTS)   [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_395", "contents": "The Quality Improvement Programme was launched in 2012 to facilitate continuing improvement of clinical outcomes in adult cardiac surgery through improving education, and various research initiatives. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_396", "contents": "The organisation has collaborated with the  European Society of Cardiology , the  American Heart Association ,  Oxford University , and other organizations to produce clinical practice guidelines and consensus statements related to the treatment of cardiovascular disease. [ 3 ] [ 4 ] [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_397", "contents": "Hyperhidrosis  is a  medical condition  in which a person exhibits excessive  sweating , [ 1 ] [ 2 ]  more than is required for the  regulation of body temperature . [ 3 ]  Although it is primarily a physical burden, hyperhidrosis can deteriorate the quality of life of the people who are affected from a psychological, emotional, and social perspective. [ 4 ]  In fact, hyperhidrosis almost always leads to psychological as well as physical and social consequences. [ 5 ]  People suffering from it present difficulties in professional fields, more than 80% experiencing a moderate to severe emotional impact from the disease [ 6 ]  and half are subject to  depression ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_398", "contents": "This excess of sweat happens even if the person is not engaging in tasks that require muscular effort, and it does not depend on the exposure to heat. [ 7 ]  Common places to sweat can include underarms, face, neck, back, groin, feet, and hands. It has been called by some researchers 'the silent handicap'. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_399", "contents": "Both  diaphoresis  and  hidrosis  can mean either  perspiration  (in which  sense  they are  synonymous  with  sweating [ 9 ] [ 10 ] ) or  excessive perspiration , in which case they refer to a specific, narrowly defined, clinical disorder."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_400", "contents": "Hyperhidrosis can either be  generalized , or  localized  to specific parts of the body. Hands, feet, armpits, groin, and the facial area are among the most active regions of perspiration due to the high number of  sweat glands  ( eccrine glands  in particular) in these areas. When excessive sweating is localized (e.g. palms, soles, face, underarms, scalp) it is referred to as  primary  hyperhidrosis or  focal hyperhidrosis . Excessive sweating involving the whole body is termed  generalized  hyperhidrosis or secondary hyperhidrosis. It is usually the result of some other, underlying condition. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_401", "contents": "Primary or  focal  hyperhidrosis may be further divided by the area affected, for instance, palmoplantar hyperhidrosis (symptomatic sweating of only the hands or feet) or  gustatory hyperhidrosis  (sweating of the face or chest a few moments after eating certain foods). [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_402", "contents": "Hyperhidrosis can also be classified by onset, either congenital (present at birth) or acquired (beginning later in life). Primary or  focal hyperhidrosis  usually starts during adolescence or even earlier and seems to be inherited as an  autosomal  dominant genetic trait. It must be distinguished from  secondary  hyperhidrosis, which can start at any point in life, but usually presents itself after 25 years of age. Secondary hyperhidrosis commonly accompanies conditions such as diabetes mellitus, Parkinson's disease, hyperthyroidism, hyperpituitarism, anxiety disorder, pheochromocytoma, and menopause. [ 11 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_403", "contents": "One classification scheme uses the amount of skin affected. [ 12 ]  In this scheme, excessive sweating in an area of 100\u00a0 cm 2  (16\u00a0 in 2 ) or more is differentiated from sweating that affects only a small area. [ 13 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_404", "contents": "Another classification scheme is based on possible causes of hyperhidrosis. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_405", "contents": "The cause of primary hyperhidrosis is unknown.  Anxiety  or excitement can exacerbate the condition. A common complaint of people is a nervous condition associated with sweating, then  sweat more because the person is nervous . Other factors can play a role, including certain  foods  and  drinks ,  nicotine ,  caffeine , and  smells . [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_406", "contents": "Similarly, secondary (generalized) hyperhidrosis has many causes including certain types of  cancer , disturbances of the  endocrine system ,  infections , and medications. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_407", "contents": "Primary (focal) hyperhidrosis has many causes."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_408", "contents": "A variety of cancers have been associated with the development of secondary hyperhidrosis including  lymphoma ,  pheochromocytoma ,  carcinoid  tumors (resulting in  carcinoid syndrome ), and tumors within the  thoracic cavity . [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_409", "contents": "Certain endocrine conditions are also known to cause secondary hyperhidrosis including  diabetes mellitus  (especially when  blood sugars are low ),  acromegaly ,  hyperpituitarism ,  pheochromocytoma  (tumor of the  adrenal glands , present in 71% of patients) and various forms of  thyroid disease . [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_410", "contents": "Use of  selective serotonin reuptake inhibitors  (e.g.,  sertraline ) is a common cause of medication-induced secondary hyperhidrosis. [ 4 ]  Other medications associated with secondary hyperhidrosis include  tricyclic antidepressants ,  stimulants ,  opioids ,  nonsteroidal anti-inflammatory drugs  (NSAIDs),  glyburide ,  insulin ,  anxiolytic  agents,  adrenergic agonists , and  cholinergic agonists . [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_411", "contents": "Symmetry of excessive sweating in hyperhidrosis is most consistent with primary hyperhidrosis. [ 4 ]  To diagnose this condition, a dermatologist gives the person a physical exam. This includes looking closely at the areas of the body that sweat excessively. A dermatologist also asks very specific questions. This helps the physician understand why the person has excessive sweating. Sometimes medical testing is necessary. Some patients require a test called the sweat test. This involves coating some of their skin with a powder that turns purple when the skin gets wet. [ citation needed ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_412", "contents": "Excessive sweating affecting only one side of the body is more suggestive of secondary hyperhidrosis and further investigation for a neurologic cause is recommended. [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_413", "contents": "Antihydral cream is one of the solutions prescribed for hyperhidrosis for palms. [ 14 ] [ 15 ]  Topical agents for hyperhidrosis therapy include  formaldehyde  lotion and topical anticholinergics. These agents reduce perspiration by  denaturing   keratin , in turn occluding the pores of the  sweat glands . They have a short-lasting effect. Formaldehyde is classified as a probable human  carcinogen . Contact sensitization is increased, especially with formalin.  Aluminium chlorohydrate  is used in regular  antiperspirants . However, hyperhidrosis requires solutions or gels with a much higher concentration. These antiperspirant solutions or hyperhidrosis gels are especially effective for treatment of  axillary  or underarm regions. It takes three to five days to see improvement. The most common side-effect is  skin irritation . For severe cases of plantar and palmar hyperhidrosis, there has been some success with conservative measures such as higher strength aluminium chloride antiperspirants. [ 16 ]  Treatment algorithms for hyperhidrosis recommend topical antiperspirants as the first line of therapy for hyperhidrosis. The International Hyperhidrosis Society has published evidence-based treatment guidelines for  focal  and generalized hyperhidrosis. [ 17 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_414", "contents": "Prescription medications called  anticholinergics , often taken by mouth, are sometimes used in the treatment of both generalized and focal hyperhidrosis. [ 18 ]  Anticholinergics used for hyperhidrosis include  propantheline ,  glycopyrronium bromide  or  glycopyrrolate ,  oxybutynin ,  methantheline , and  benzatropine . Use of these drugs can be limited, however, by side-effects, including dry mouth,  urinary retention , constipation, and visual disturbances such as  mydriasis  and  cycloplegia . For people who find their hyperhidrosis is made worse by anxiety-provoking situations ( public speaking , stage performances, special events such as weddings, etc.), taking an anticholinergic medicine before the event may help. [ 19 ]  In 2018, the U.S.  Food and Drug Administration  (FDA) approved the  topical  anticholinergic  glycopyrronium tosylate  for the treatment of primary axillary hyperhidrosis. [ 20 ] [ 21 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_415", "contents": "For peripheral hyperhidrosis, some people have found relief by simply ingesting crushed ice water. Ice water helps to cool excessive body heat during its transport through the blood vessels to the extremities, effectively lowering overall body temperature to normal levels within ten to thirty minutes. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_416", "contents": "Injections of  botulinum toxin  type A can be used to block neural control of sweat glands. The effect can last from 3\u20139 months depending on the site of injections. [ 23 ]  This use has been approved by the U.S.  Food and Drug Administration  (FDA). [ 24 ]  The duration of the beneficial effect in primary palmar hyperhidrosis has been found to increase with repetition of the injections. [ 25 ]  The Botox injections tend to be painful. Various measures have been tried to minimize the pain, one of which is the application of ice."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_417", "contents": "This was first demonstrated by Khalaf Bushara and colleagues as the first nonmuscular use of BTX-A in 1993. [ 26 ]  BTX-A has since been approved for the treatment of  severe primary axillary hyperhidrosis  (excessive underarm sweating of unknown cause), which cannot be managed by topical agents. [ when? ] [ 27 ] [ 28 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_418", "contents": "miraDry , a  microwave -based device, has been tried for excessive underarm perspiration and appears to show promise. [ 29 ]  With this device, rare but serious side effects exist and are reported in the literature, such as paralysis of the upper limbs and  brachial plexus . [ 30 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_419", "contents": "Tap water  iontophoresis  as a treatment for palmoplantar hyperhidrosis was originally described in the 1950s. [ 31 ]  Studies showed positive results and good safety with tap water iontophoresis. [ 32 ]  One trial found it decreased sweating by about 80%. [ 33 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_420", "contents": "Sweat gland removal or destruction is one surgical option available for axillary hyperhidrosis (excessive underarm perspiration). There are multiple methods for sweat gland removal or destruction, such as sweat gland suction, retrodermal curettage, and axillary liposuction, Vaser, or Laser Sweat Ablation. Sweat gland suction is a technique adapted for liposuction. [ 34 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_421", "contents": "The other main surgical option is  endoscopic thoracic sympathectomy  (ETS), which cuts, burns, or clamps the thoracic ganglion on the main sympathetic chain that runs alongside the spine. Clamping is intended to permit the reversal of the procedure. ETS is generally considered a \"safe, reproducible, and effective procedure and most patients are satisfied with the results of the surgery\". [ 35 ]  Satisfaction rates above 80% have been reported, and are higher for children. [ 36 ] [ 37 ]  The procedure brings relief from excessive hand sweating in about 85\u201395% of people. [ 38 ]  ETS may be helpful in treating axillary hyperhidrosis, facial blushing and facial sweating, but failure rates in people with facial blushing and/or excessive facial sweating are higher and such people may be more likely to experience unwanted side effects. [ 39 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_422", "contents": "ETS side-effects have been described as ranging from trivial to devastating. [ 40 ]  The most common side-effect of ETS is compensatory sweating (sweating in different areas than prior to the surgery). Major problems with compensatory sweating are seen in 20\u201380% of people undergoing the surgery. [ 41 ] [ 42 ] [ 43 ]  Most people find the compensatory sweating to be tolerable while 1\u201351% claim that their quality of life decreased as a result of  compensatory sweating .\" [ 36 ]  Total body perspiration in response to heat has been reported to increase after sympathectomy. [ 44 ]  The original sweating problem may recur due to nerve regeneration, sometimes as early as 6 months after the procedure. [ 41 ] [ 42 ] [ 45 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_423", "contents": "Other possible side-effects include  Horner's Syndrome  (about 1%),  gustatory  sweating (less than 25%) and excessive dryness of the palms (sandpaper hands). [ 46 ]  Some people have experienced cardiac sympathetic denervation, which can result in a 10% decrease in heart rate both at rest and during exercise, resulting in decreased exercise tolerance. [ 47 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_424", "contents": "Percutaneous sympathectomy is a minimally invasive procedure similar to the botulinum method, in which nerves are blocked by an injection of  phenol . [ 48 ]  The procedure provides temporary relief in most cases. Some physicians advocate trying this more conservative procedure before resorting to surgical sympathectomy, the effects of which are usually not reversible."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_425", "contents": "Hyperhidrosis can have physiological consequences such as cold and clammy hands, dehydration, and skin infections secondary to maceration of the skin. Hyperhidrosis can also have devastating emotional effects on one's individual life. [ 49 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_426", "contents": "Those with hyperhidrosis may have greater stress levels and more frequent depression. [ 50 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_427", "contents": "Excessive sweating or focal hyperhidrosis of the hands interferes with many routine activities, [ 51 ]  such as securely grasping objects. Some people with focal hyperhidrosis sufferers avoid situations where they will come into physical contact with others, such as greeting a person with a handshake. Hiding embarrassing sweat spots under the armpits limits the affected person's arm movements and pose. In severe cases, shirts must be changed several times during the day and require additional showers both to remove sweat and control body odor issues or microbial problems such as acne, dandruff, or athlete's foot. Additionally, anxiety caused by self-consciousness to the sweating may aggravate the sweating. Excessive sweating of the feet makes it harder for people to wear slide-on or open-toe shoes, as the feet slide around in the shoe because of sweat. [ 52 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_428", "contents": "Some careers present challenges for people with hyperhidrosis. For example, careers that require the use of a knife may not be safely performed by people with excessive sweating of the hands. The risk of  dehydration  can limit the ability of some to function in extremely hot (especially if also humid) conditions. [ 53 ]  Even the playing of musical instruments can be uncomfortable or difficult because of sweaty hands. [ 54 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_429", "contents": "It is estimated that the incidence of focal hyperhidrosis may be as high as 2.8% of the population of the United States. [ 51 ]  It affects men and women equally, and most commonly occurs among people aged 25\u201364 years, though some may have been affected since early childhood. [ 51 ]  About 30\u201350% of people have another family member affected, implying a  genetic  predisposition. [ 51 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_430", "contents": "In 2006, researchers at  Saga University  in Japan reported that primary palmar hyperhidrosis maps to gene locus 14q11.2\u2013q13. [ 55 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_431", "contents": "The  Journal of Cardiothoracic Surgery  is an  open access ,  peer-reviewed  online journal that encompasses all aspects of research in  cardiothoracic surgery .The Journal publishes original scientific research related to all domains of cardiac, vascular and thoracic surgery."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_432", "contents": "1) Editorial Board:  https://cardiothoracicsurgery.biomedcentral.com/about/editorial-board"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_433", "contents": "2) Instruction for Authors:  https://www.biomedcentral.com/about/foreditors"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_434", "contents": "This article about a  surgery   journal  is a  stub . You can help Wikipedia by  expanding it ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_435", "contents": "See tips for writing articles about academic journals . Further suggestions might be found on the article's  talk page ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_436", "contents": "Lung surgery  is a type of  thoracic surgery  involving the repair or removal of  lung  tissue, [ 1 ]  and can be used to treat a variety of conditions ranging from  lung cancer  to  pulmonary hypertension . Common operations include anatomic and nonanatomic resections,  pleurodesis  and  lung transplants . Though records of lung surgery date back to the  Classical Age , new techniques such as  VATS  continue to be developed."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_437", "contents": "The first written records of lung surgery were provided by  Hippocrates , where he described a treatment for thoracic  empyema  by means of drainage. [ 2 ]  Thoracic procedures became more viable with the advent of  positive pressure ventilation , [ 3 ]  introduced by  Samuel Meltzer  in 1909. This technique enables surgeons to conduct open chest procedures without risking  hypoxia , [ 4 ]  significantly decreasing patient mortality and is presently used in conjunction with  double-lumen endotracheal intubation  to isolate the ventilation of the affected lung during surgery. [ 5 ]  The 20th century saw further innovation of new procedures, such as the first-ever  pneumonectomy  performed by  Evarts Graham  in 1933. [ 6 ]  A breakthrough in minimally invasive lung surgery was also achieved in the form of  thoracoscopy , developed by  Hans Christian Jacobaeus  in 1910 as a method to diagnose  tuberculosis . Thoracoscopy was later used by surgeons to perform chest operations without  open thoracotomy . [ 7 ]  However, the latter remains a widely used method to access the  pleural cavity . [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_438", "contents": "Before the advent of  tuberculosis chemotherapy  in the 1940s, the disease was treated via collapse therapy. [ 9 ]  This involved the creation of an artificial  pneumothorax , aimed at resting the infected lung to limit infection spread and accelerate healing. The traumatic nature of collapse therapy and the discovery of antituberculosis drugs has rendered the former obsolete. [ 10 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_439", "contents": "Lung cancer can be classified into two main types:  non-small cell lung cancer  (NSCLC) and  small cell lung cancer  (SCLC). NSCLC, the most common of the two types, is a group of cancers including  squamous cell carcinoma ,  adenocarcinoma  and  large cell carcinoma . [ 11 ]  SCLC is highly aggressive and consists of small ovoid cells. [ 12 ]  Surgical resection is used curatively in stage I-III NSCLC and  palliatively  in stage IV. [ 13 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_440", "contents": "A  pneumothorax , also known as a collapsed lung, is a collection of air outside the lung in the pleural cavity. [ 14 ]  Depending on etiology, a pneumothorax is classified as spontaneous, traumatic and  iatrogenic . A spontaneous pneumothorax is further classified as primary and secondary, with the former occurring in individuals with no clinical lung disease and the latter occurring as a complication of preexisting lung disease. [ 15 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_441", "contents": "Chronic obstructive pulmonary disease  (COPD) is a group of diseases that results in airflow blockage and therefore cause breathing-related issues. COPD includes  emphysema  as well as chronic  bronchitis . [ 16 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_442", "contents": "Cystic fibrosis  is a genetic disease, caused by a mutation that results in defects in movement of salt and water in and out of cells which can cause sticky mucus in the body\u2019s tubes and passageways such as in the lungs. [ 17 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_443", "contents": "Pulmonary hypertension  occurs as a result of excess pressure in the blood vessels from the heart to the lungs. An increased amount of muscle in the walls of the blood vessels to the lung is prominent in cases with pulmonary hypertension. Although there are treatments such as  oxygen therapy  and medicine that is given to reduce swelling, lung transplantation may be necessary in some extreme cases. [ 18 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_444", "contents": "Idiopathic pulmonary fibrosis  causes the lungs to become scarred which results in a difficulty in breathing. The causes are of this disease is still not fully known, however, prevention methods include self-care such as stopping smoking and exercising. Medicines such as  pirfenidone  and  nintedanib  are also commonly used in order to reduce the rate of scarring in the lungs. Lung transplantation is effective in certain cases, however this depends on the availability of healthy donor lungs. [ 19 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_445", "contents": "Anatomic resections refer to procedures where a section of the lung is removed with respect to lobar or segmental anatomy. [ 20 ]  These include pneumonectomies, lobectomies and segmentectomies and are commonly used for the treatment of NSCLC. Preoperative evaluations for resections include cancer  staging  via a chest  CT scan  and  PET scan , followed by assessments of pulmonary reserve volume and cardiac function to determine the amount of lung tissue that can be safely removed without developing pulmonary insufficiency. [ 21 ]  Following tissue removal, the resultant bronchial stumps are pressurised under water to check for air leaks before the resection is deemed complete. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_446", "contents": "A  pneumonectomy  is the surgical removal of an entire lung. Due to the high morbidity and mortality of the procedure, its viability for treating lung cancer is a subject of debate. [ 23 ]  However, pneumonectomies are still used for lung carcinomas that are large and centrally located or have invaded the interlobar fissures. Another indication for the use this procedure is lung destruction due to chronic infections."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_447", "contents": "During a pneumonectomy, the pleural cavity is accessed through a  thoracotomy . With direct access to the tumour, the need for pneumonectomy is reassessed. After surgeons decide to proceed with the procedure, the  hilar structures  are dissected sequentially. The pulmonary artery, then the pulmonary veins, are divided via stapling. Next, the main bronchus is divided using a scalpel and the lung is removed from the pleural cavity. The bronchial stump is subsequently closed by  polyglactin   sutures . Finally,  mediastinal  lymph nodes are dissected. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_448", "contents": "A  lobectomy  is the surgical removal of one of the five  lung lobes  (right upper, right middle, right lower, left upper and left lower lobes). [ 24 ]  Lobectomies are the most common type of lung surgery and the standard operation for most NSCLC patients. [ 25 ]  Though specific surgical techniques vary for each lobe, the general workflow is identical. The lobe to be resected is first visualized through  thoracotomy  or  thoracoscopy . Next, the surrounding  lymph nodes  are harvested to check for metastasis. After confirmation that no metastasis has taken place, the vasculature of the lobe is controlled by blood vessel division using a  stapler . Stapling is also used to divide the lobar bronchus and subsequently separate the lobe along the lung fissure(s). After the lobe is removed, lymph node dissection is completed."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_449", "contents": "Specific considerations exist for certain lobes. Right middle lobectomies are not usually carried out alone and are instead part of a bilobectomy alongside a right upper or lower lobectomy. Left upper lobectomies require additional caution to avoid arterial branches from the fissure and proximal  pulmonary artery . [ 21 ]  Another risk is the proximity of the  recurrent laryngeal nerve  to the upper mediastinal lymph nodes, which increases its risk of injury during lymph node dissection. [ 26 ]  Thus, a swallowing study is required if nerve damage is suspected postoperatively. [ 13 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_450", "contents": "A sleeve lobectomy is a lobectomy that is coupled with the removal of a part of the main bronchus. The ends of the bronchus are then rejoined to reattach any remaining lung lobes. [ 27 ]  This procedure is performed in lieu of pneumonectomy when surgeons determine the removal of the entire lung to be unnecessary for centrally located tumours. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_451", "contents": "Segmentectomies  are the surgical removal of  bronchopulmonary segments  and often involve the removal of two adjacent segments. The pulmonary arterial branches to the segments are first identified then divided. Next, stapling is used to divide the segmental bronchi and separate the segments from the lung. [ 13 ]  Compared to lobectomies, this procedure has higher survivability for stage 1A patients with tumours \u2264 2\u00a0cm in diameter. [ 28 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_452", "contents": "Non-anatomic resections refer to the removal of lung tissue without respect to lobar or segmental anatomy. They can be used to treat a variety of lung diseases such as NSCLC and tuberculosis."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_453", "contents": "A  wedge resection  is the non-anatomic removal of a triangular-shaped piece of tissue from the lungs. The utility of wedge resection in NSCLC is disputed. Wedge resection is currently used in NSCLC patients with low pulmonary function, or for pulmonary tuberculosis patients with multiple lesions which do not respect intersegmental boundaries. [ 13 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_454", "contents": "A bleb resection is the surgical removal of one or more  blebs , small collections of air between the lung and visceral pleura. Blebs may combine to form larger cysts named bullae. The rupture of blebs or bullae results in air leaking into the pleural space, causing a spontaneous pneumothorax. In most cases, patients will be unaware of blebs until they are detected by CT scans or cause noticeable symptoms such as chest pain. [ 29 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_455", "contents": "Bleb resections may be done via mini-thoracotomy or thoracoscopy. After inspection of the chest cavity, identified blebs are removed via dissection and stapling. To prevent future bleb formation, this procedure is often accompanied by pleurodesis. [ 22 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_456", "contents": "A pneumothorax is commonly treated with needle aspiration of air followed by  chest tube  drainage. In the case of a recurrent pneumothorax,  pleurodesis  may be used to prevent further air accumulation. [ 14 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_457", "contents": "Pleurodesis is the obliteration of the pleural space, achieved by adhering the visceral pleura on the lung surface to the costal pleura of the chest wall. Adhesion is caused by  inflammation  and subsequent scarring of the pleural layers. Inflammation may be induced by either physical or chemical irritation. The former is commonly used in younger patients and involves surgical abrasion. The latter involves the instillation of chemical sclerosant, usually sterile  talc , via a chest tube. Other sclerosing agents include  tetracycline  and  bleomycin . [ 30 ]  After sclerosant instillation, the patient may be moved through various positions to ensure even distribution. [ 13 ]  Due to the pain of this operation, it is accompanied by  local anaesthesia . Pleurodesis is also used in recurrent  pleural effusion , a common result of lung cancer. [ 30 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_458", "contents": "Lung transplant  is defined as \u2018an operation to remove and replace a diseased lung with a healthy human lung from a donor. A donor is most commonly known to be a deceased person, however, in very rare cases a section of the lung that is required for a patient can be transplanted from a living donor. Lung transplants are usually required when a patient has advanced lung disease whereby the disease is also unresponsive to other methods of treatment. Another significant reason for a lung transplant to be considered as a necessary option is if the patients\u2019 life expectancy is predicted to be under three years without the lung transplant procedure taking place. Typical conditions that are treated with a lung transplant include COPD, cystic fibrosis, pulmonary hypertension and idiopathic pulmonary fibrosis. [ 31 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_459", "contents": "Methods for the preservation of donor lungs are imperative in order to increase availability of lungs for transplantation which therefore increases the efficacy of the treatment as more available lungs for transplantation leads to more people being applicable to undergo the treatment/transplantation. Before an organ is removed from the donor for transplantation, the donor organ is commonly flushed free of blood with a preservation solution that is prepared to be ice-cold which also contains essential elements such as electrolytes and nutrients. Furthermore, when the organ is removed from the donor, it is packaged in wet ice for preservation of the organ. [ 32 ]  A therapy called  ex-vivo lung perfusion  that is commonly used for the donor lung just before transplantation provides an enhancement of the quality of the organ and can potentially make previously unsuitable organs, safe for transplantation. [ 33 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_460", "contents": "All lung surgeries breach the pleural cavity, which disrupts the negative intrapleural pressure and prevents normal breathing. [ 34 ]  Surgical trauma may also lead to  pleural effusion , further disrupting intrapleural pressure. [ 35 ]  To counteract these disruptions, a  chest tube  which is attached to a drainage system consisting of a collection chamber, one-way water valve and suction chamber is inserted into the patient. This enables air and fluid to be unidirectionally extracted from the pleural cavity. [ 36 ]  Chest tubes are usually removed one week after surgery along with any stitches or staples in the incisions."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_461", "contents": "Patients experiencing shortness of breath will be guided through deep breathing or coughing exercises by a physician or respiratory therapist. In severe cases, the patient will also receive oxygen supplementation through a mask or nostril tube. [ 37 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_462", "contents": "A pneumonectomy comes with its own risks whereby the most common complications are  cardiac arrhythmia  as well as atrial fibrillation (or flutter), which commonly occurs in the first three days following the surgery. Furthermore, additional risks following this surgery include: cardiac herniation, pulmonary complications (e.g.  pneumonia ), bronchopleural fistula,  pulmonary oedema , multi-organ dysfunction, acute lung injury,  acute respiratory distress syndrome  (ARDS) and postoperative acute kidney injury. [ 38 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_463", "contents": "Lobectomies share many of the complications that come with a pneumonectomy. However, additional risks that can result from a lobectomy include  empyema , which is an area of pus in the chest cavity, as well as  pleural effusion , which occurs as a result of fluid in the space between the lung and inner chest wall. [ 39 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_464", "contents": "Similar to other anatomic resections, cardiac arrhythmia is a major complication for segmentectomy. Additionally,  hemorrhage  in the pleural cavity may occur due to injury to the pulmonary artery or its branches. Patients may also develop a  contralateral  pneumothorax, necessitating the placement of a chest tube to eliminate air within the pleural cavity. [ 40 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_465", "contents": "Wedge resections share the complications of anatomic resections. [ 41 ]  However, the former generally has lower patient mortality. [ 30 ]  The major complications of bleb resection are prolonged air leak and pneumothorax recurrence. [ 42 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_466", "contents": "Pleurodesis may lead to a fever due to the induced inflammatory response. [ 43 ]  Chemical pleurodesis, specifically that using talc, may also cause ARDS via the  systemic absorption  of sclerosant. [ 44 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_467", "contents": "Lung transplantation is an intricate treatment that can provide efficient results, however, there are risks that come with this procedure which include: bleeding, infection, blockage of the blood vessels to the new lungs, blockage of the airways, severe  pulmonary oedema  as well as potential blood clot formation. [ 45 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_468", "contents": "Lung surgeries can be perceived as invasive procedures that may cause side effects such as bruising, swelling, numbness, pain, scarring and infection. However, new methods such as  video-assisted thoracoscopic surgery  (VATS) provide a minimally invasive method which can eliminate diseased parts of the lungs and lymph nodes. A development of thoracoscopy, VATS utilizes small, high-resolution cameras which are inserted into the chest through small incisions. This grants surgeons a high degree of visibility into the pleural cavity despite making smaller incisions, resulting in quicker patient recovery. [ 46 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_469", "contents": "Moreover, treatment for lung cancer has been further developed with the use of  robotic surgery  as a method for treatment. This method involves the use of robotic arms which are manipulated by a surgeon at a console, enabling more precise movements and providing the surgeon with 3D vision of the surgical site. [ 47 ]  Similar to VATS, robotic surgery has also been found to be minimally invasive and is extremely useful for removing certain parts of lung tissue that are diseased as well as surrounding lymph nodes. [ 48 ]  However, comparisons of current robotic methods with VATS have shown no significant differences in patient outcome. [ 49 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_470", "contents": "Rib removal  is  surgery  to remove one or more  ribs .  Rib resection  is the removal of part of a rib. [ 1 ]  The procedures are done for various medical reasons. A number of celebrities have been falsely rumoured to have had ribs removed as a form of  body modification . [ 2 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_471", "contents": "Rib removal may be medically approved in several situations. If a rib is fractured in such a way that it might puncture a vital organ, it may be safer to remove it than wait for it to heal. [ 1 ]  A  cancerous rib  may be removed to stop the cancer from spreading. [ 1 ]  Rib bone material may be used for a  bone graft . [ 1 ]  The excess pressure of  thoracic outlet syndrome  may be reduced by rib removal. [ 1 ]  Major surgery to the thoracic cavity, such as  open heart surgery , may require removal of ribs to allow access to the organ being operated on. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_472", "contents": "Victorian fashion  valued a  wasp waist  and  hourglass figure  for women. This was achieved through laced  corsets . Twentieth-century rumors hold that some women had their lower ribs removed to facilitate tighter lacing of the waist. In 1931, corset-maker Rosa Binner alleged that French actress  Polaire  had had her lowest rib removed in the 1890s. [ 3 ]   Germaine Greer 's  second-wave feminist  book  The Female Eunuch  gives the practice as an example of male-directed distortion of the female body. [ 4 ]  Valerie Steele's history of the corset finds no evidence of such a procedure, and with Lynne Kutsche argues the mortal danger of surgery of the era makes it extremely implausible. [ 5 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_473", "contents": "Barbara Mikkelson of  Snopes.com  suggests that  Florenz Ziegfeld  might have started such a rumor about his prot\u00e9g\u00e9e  Anna Held  to publicize her career. [ 6 ]   Similar stories have been spread about later celebrities.  Cher  hired a physician in 1990 to confirm that she has a full set of ribs. [ 6 ]  It was rumored that  Marilyn Manson  had ribs removed to facilitate  autofellatio . [ 7 ] \nInterviewed for a  Vogue  article in 2000, John E. Sherman of  Weill Cornell Medical College  said that while such a procedure was theoretically possible, there was no record of it in the medical literature. [ 8 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_474", "contents": "Amanda Lepore  claimed that she had skirted the law to obtain a similar surgery.  She was quoted saying \"'I've had my boobs done, and my lips done, my bottom lip reduced, and my bottom rib broken and pushed in\u2014I think  Raquel Welch  and  Cher  did that, too. It's illegal in the US, but I had it done in Mexico. They break the  floating rib  in the back and push it in, so there's no scar.\" in an interview. [ 9 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_475", "contents": "In October 2015, internet model and self-proclaimed \"living doll\"  Pixee Fox  documented the procedure to remove her six lower ribs on her  Tumblr  account. The procedure shortened rather than fully removed the ribs. [ 10 ]  In an interview with  Closer , she stated that it was difficult to find a doctor willing to perform the surgery. [ 11 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_476", "contents": "The Society of Thoracic Surgeons  is a Chicago, Illinois (US)-based  medical specialty   professional society  in the field of  cardiothoracic surgery . Membership worldwide includes more than 7,500 surgeons, researchers, and other health care professionals who are part of the cardiothoracic surgery team. The Society's official journal is  The Annals of Thoracic Surgery ."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_477", "contents": "The STS National Database was established in 1989 as an initiative for quality improvement and patient safety among cardiothoracic surgeons. The Database has four components\u2014the Adult Cardiac Surgery Database (ACSD), the General Thoracic Surgery Database (GTSD), the Congenital Heart Surgery Database (CHSD), and the Intermacs Database\u2014and now houses more than 7.5 million surgical records. The STS National Database has grown to be the largest database of its kind in medicine and is one of the pioneers in the analysis and reporting of risk-adjusted outcomes in cardiothoracic surgery. [ 1 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_478", "contents": "In late 2010, the Society launched an initiative through which participants of the ACSD could voluntarily report their performance on coronary artery bypass grafting (CABG) surgeries. Since then, ACSD public reporting has evolved to include aortic valve replacement (AVR) surgery and CABG+AVR; outcomes for isolated mitral valve replacement or mitral valve repair (MVRR) and combined MVRR+CABG are planned to be reported in early 2019. Public reporting from the CHSD was added in 2015, and public reporting from the GTSD began in 2017.  Consumer Reports  and  U.S. News & World Report  have both relied upon STS Public Reporting Online data for their respective hospital ratings programs. [ 2 ] [ 3 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_479", "contents": "To meet the needs of an expanding specialty, a group of established young thoracic surgeons, led primarily by  Dr. R. Adams Cowley  of Baltimore, met in the late 1950s to exchange ideas concerning the feasibility of another thoracic surgical society. [ 4 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_480", "contents": "By April 1963, a committee comprising Dr. Cowley (Chairman), Dr. Francis X. Byron of Los Angeles, Dr. Clifford F. Storey of San Diego, Dr. J. Maxwell Chamberlain of New York, Dr. John D. Steele of San Fernando, Calif., Dr. Byron H. Evans of Fresno, Calif., Dr. Edgar P. Mannix of Manhasset, NY, Dr. Earle B. Kay of Cleveland, and Dr. John E. Miller of Baltimore, recommended that the a new society for thoracic and cardiovascular surgery be established. [ 5 ]  A planning committee was appointed, and an STS constitution was finalized in August 1963 at the home or Dr. Robert K. Brown in Denver. Officers and councilors were elected on October 31, 1963, and included Dr. Paul C. Samson as president, Dr. Thomas H. Burford as vice president, Dr. Byron as secretary, and Dr. John E. Steele as editor of  The Annals of Thoracic Surgery . [ 6 ]"}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_481", "contents": "The first STS Annual Meeting was held in St. Louis in January 1965."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_482", "contents": "The initial management activities of STS were conducted from the office of Dr. J. Maxwell Chamberlain in New York. By 1969, when membership in the Society had grown to approximately 700, it was decided that management activities would be handled by a professional management organization. Smith, Bucklin and Associates (SBA) managed STS from 1969 to 2002, but in the later years of the SBA era, the Society's leadership felt the organization had grown so robust that it was time to hire a staff of dedicated STS employees."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_483", "contents": "The transition to self-management was successfully implemented under the direction of Mark B. Orringer, MD, who completed his term as STS President, and William A. Baumgartner, MD, his successor as President."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_484", "contents": "On June 1, 2002, STS opened its headquarters office in the American College of Surgeons building in Chicago with 9.5 full-time employee equivalents, including Executive Director & General Counsel Robert A. Wynbrandt, and a membership that had grown to more than 4,100. In 2004, a dedicated STS office in Washington, DC, was established; by 2018, the STS staff in Chicago and Washington had grown to approximately more than 65 full-time employees, and membership had grown to more than 7,500."}
+{"id": "WikiPedia_Thoracic_surgery$$$corpus_485", "contents": "STS manages and provides staff support for five affiliate organizations, including its charitable arm, The Thoracic Surgery Foundation."}