High Altitude Pulmonary Edema
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High-altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic
pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive edema, liquid accumulation in the parenchyma, tissue and pulmonary alveolus, air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia an ...
that occurs in otherwise healthy people at altitudes typically above . However, cases have also been reported between in more vulnerable subjects. Classically, HAPE occurs in persons normally living at low altitude who travel to an altitude above 2,500 meters (8,200 feet). Re-entry HAPE is also an entity that has been described in persons who normally live at high altitude but who develop pulmonary edema after returning from a stay at low altitude. It is severe presentation of
altitude sickness Altitude sickness, the mildest form being acute mountain sickness (AMS), is the harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Sympt ...
. There are many factors that can make a person more
susceptible Susceptibility may refer to: Physics and engineering In physics the susceptibility is a quantification for the change of an extensive property under variation of an intensive property. The word may refer to: * In physics, the susceptibility of ...
to developing HAPE, including genetic factors, but detailed understanding is lacking and currently under investigation. HAPE remains the major cause of death related to high-altitude exposure, with a high mortality rate in the absence of adequate emergency treatment.


Signs and symptoms

Physiological and symptomatic changes often vary according to the altitude involved. The Lake Louise Consensus Definition for high-altitude pulmonary edema has set widely used criteria for defining HAPE symptoms. In the presence of a recent gain in altitude, the presence of the following: Symptoms: at least two of: *
Shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
at rest * Cough * Weakness or decreased exercise performance * Chest tightness or congestion Signs: at least two of: * Crackles or wheezing (while breathing) in at least one lung field * Central blue skin color *
Tachypnea Tachypnea, also spelt tachypnoea, is a respiratory rate greater than normal, resulting in abnormally rapid and shallow breathing. In adult humans at rest, any respiratory rate of 1220 per minute is considered clinically normal, with tachypnea be ...
(rapid breathing) *
Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
(rapid heart rate) Acute mountain sickness and high altitude cerebral edema may also be present in conjunction with HAPE, however these symptoms may be subtle or not present at all. The most reliable sign of HAPE is severe fatigue or exercise intolerance, especially in a climber that was previously not displaying this symptom.


Risk factors

There are multiple factors that can contribute to the development of HAPE, including sex (male), genetic factors, prior development of HAPE, ascent rate, cold exposure, peak altitude, intensity of physical exertion, and certain underlying medical conditions (e.g., pulmonary hypertension). Anatomic abnormalities that are predisposing include congenital absence of pulmonary artery, and left-to-right intracardiac shunts (e.g., atrial and ventricular septal defects), both of which increase pulmonary blood flow. HAPE-susceptible (HAPE-s) individuals were also found to be four times more likely to have a
patent foramen ovale Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...
(PFO) than those who were HAPE-resistant. There is currently no indication or recommendation for people with PFO to pursue closure prior to extreme altitude exposure. In studies performed at sea level, HAPE-s people were found to have exaggerated circulatory response to both hypoxia at rest and during exercise. In these individuals, the
pulmonary artery pressure A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the ''main pulmonary artery'' or ''pulmonary trunk'' from the heart, and ...
(PAP) and
pulmonary vascular resistance Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be ca ...
(PVR) were shown to be abnormally high. Microneurographic recordings in these individuals developed a direct link between PAP rise and
sympathetic nervous system The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
over-activation, which could explain the exaggerated response to hypoxia in these persons.
Endothelial tissue The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
dysfunction has also been linked to development of HAPE, including reduced synthesis of NO (a potent
vasodilator Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...
), increased levels of
endothelin Endothelins are peptides with receptor (biochemistry), receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when gene ex ...
(a potent vasconstrictor), and an impaired ability to transport sodium and water across the
epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
and out of the
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * ...
. Data on the genetic basis for HAPE susceptibility is conflicting and interpretation is difficult. Genes implicated in the development of HAPE include those in the renin-angiotensin system (RAS), NO pathway, and hypoxia-inducible factor pathway (HIF). Future genomic testing could provide a clearer picture of the genetic factors that contribute to HAPE.


Pathophysiology

Though it remains a topic of intense investigation, multiple studies and reviews over the last several years have helped to elucidate the proposed mechanism of HAPE. The inciting factor of HAPE is the decrease in partial pressure of arterial
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
caused by the lower air pressure at high altitudes (
pulmonary gas pressures The factors that determine the values for alveolar pO2 and pCO2 are: *The pressure of outside air *The partial pressures of inspired oxygen and carbon dioxide *The rates of total body oxygen consumption and carbon dioxide production *The rates of ...
). The resultant
hypoxemia Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia has many causes, and often causes hypoxia as the blood is not supplying enough oxygen to the tissues of the body ...
is then thought to precipitate the development of: # Increased pulmonary arterial and capillary pressures ( pulmonary hypertension) secondary to
hypoxic pulmonary vasoconstriction Hypoxic pulmonary vasoconstriction (HPV), also known as the Euler-Liljestrand mechanism, is a physiological phenomenon in which small pulmonary arteries constrict in the presence of alveolar hypoxia (low oxygen levels). By redirecting blood flow fr ...
. # Increased capillary pressure (
hydrostatic pressure Fluid statics or hydrostatics is the branch of fluid mechanics that studies the condition of the equilibrium of a floating body and submerged body "fluids at hydrostatic equilibrium and the pressure in a fluid, or exerted by a fluid, on an imme ...
) with over-distention of the capillary beds and increased permeability of the vascular
endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
, also known as "stress failure." This leads to subsequent leakage of cells and proteins into the
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * ...
, aka pulmonary edema. Hypoxic pulmonary vasoconstriction (HPV) occurs diffusely, leading to arterial vasoconstriction in all areas of the lung. This is evidenced by the appearance of "diffuse," "fluffy," and "patchy" infiltrates described on imaging studies of climbers with known HAPE. Although higher pulmonary arterial pressures are associated with the development of HAPE, the presence of pulmonary hypertension may not in itself be sufficient to explain the development of
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
; severe pulmonary hypertension can exist in the absence of clinical HAPE in subjects at high altitude.


Diagnosis

The diagnosis of HAPE is entirely based on symptoms and many of the symptoms overlap with other diagnoses. Before HAPE was understood it was commonly confused with pneumonia which resulted in inappropriate treatment. HAPE generally develops in the first 2 to 4 days of hiking at altitudes >2,500 meters (8,200 ft), and symptoms seem to worsen most commonly on the second night. Initial symptoms are vague and include
shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
, decreased exercise ability, increased recovery time, fatigue, and weakness, especially with walking uphill. People then develop a dry, persistent cough, and often
cyanosis Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...
of the lips. Another cardinal feature of HAPE is the rapid progression to dyspnea at rest. The development of pink, frothy, or frankly bloody
sputum Sputum is mucus that is coughed up from the lower airways (the trachea and bronchi). In medicine, sputum samples are usually used for a naked eye examination, microbiological investigation of respiratory infections and cytological investigations ...
are late features of HAPE. In some cases, people will develop concomitant neurological features such as poor coordination, altered consciousness, or cerebral edema (
High-altitude cerebral edema High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves di ...
). On physical exam, increased breathing rates, increased heart rates, and a low-grade fever 38.5o (101.3o F) are common.
Listening Listening is giving attention to a sound or action. When listening, a person hears what others are saying and tries to understand what it means. The act of listening involves complex affective, cognitive and behavioral processes. Affective proce ...
to the lungs may reveal
crackles Crackles are the clicking, rattling, or crackling noises that may be made by one or both lungs of a human with a respiratory disease during inhalation. They are usually heard only with a stethoscope ("on auscultation"). Pulmonary crackles a ...
in one or both lungs, often starting in the right middle lobe. Imaging studies such as
X-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10  picometers to 10  nanometers, corresponding to frequencies in the range 30&nb ...
and CT imaging of the chest may reveal thoracic infiltrates that can be seen as opaque patches. One distinct feature of HAPE is that
pulse oximetry Pulse oximetry is a noninvasive method for monitoring a person's oxygen saturation. Peripheral oxygen saturation (SpO2) readings are typically within 2% accuracy (within 4% accuracy in 95% of cases) of the more accurate (and invasive) reading of ...
saturation levels ( SpO2) are often decreased from what would be expected for the altitude. People typically do not appear as ill as SpO2 and chest X-ray films would suggest. Giving extra oxygen rapidly improves symptoms and SpO2 values; in the setting of infiltrative changes on chest X-ray, this is nearly pathognomonic for HAPE.


Severity

The severity of HAPE is graded. The grades of mild, moderate, or severe HAPE are assigned based upon symptoms, clinical signs, and chest x-ray results for individuals. The symptoms that are taken in to account while evaluation the severity of HAPE are difficulty breathing while exerting or while at rest, the presence of a cough and the quality of that cough, and the level of fatigue of the patient. On physical exam of a suspected HAPE patient the exam findings used to grade the severity are the heart rate, respiratory rate, signs of cyanosis, and severity of lung sounds. Both symptoms and signs on physical exam can be used to evaluate a patient in the field. Chest X-rays are also used to evaluate the severity of HAPE when they are available.


Differential diagnosis

Differential diagnosis: *
Pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
*
Bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...
* Mucous plugging *
Pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
*
Acute coronary syndrome Acute coronary syndrome (ACS) is a syndrome (a set of signs and symptoms) due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies. The most common symptom is centrally loca ...
*
Acute decompensated heart failure Acute decompensated heart failure (ADHF) is a sudden worsening of the signs and symptoms of heart failure, which typically includes difficulty breathing (dyspnea), edema, leg or feet swelling, and Fatigue (medical), fatigue. ADHF is a common and ...
*
Asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...
*
Reactive airway disease Reactive airway disease (RAD) is an informal label that physicians apply to patients with symptoms similar to those of asthma. An exact definition of the condition does not exist. Individuals who are typically labeled as having RAD generally have ...
*
Exercise-associated hyponatremia Exercise-associated hyponatremia, is a fluid-electrolyte disorder caused by a decrease in sodium levels (hyponatremia) during or up to 24 hours after prolonged physical activity. This disorder can develop when marathon runners or endurance event at ...
*
Pneumothorax A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve ...


Prevention

The primary recommendation for the prevention of HAPE is gradual ascent. The suggested rate of ascent is the same that applies to the prevention of acute mountain sickness and
high-altitude cerebral edema High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves di ...
. The Wilderness Medical Society (WMS) recommends that, above , climbers * not increase the sleeping elevation by more than a day, and * include a rest day every 3–4 days (i.e., no additional ascent). In the event that adherence to these recommendations is limited by terrain or logistical factors, the WMS recommends rest days either before or after days with large gains. Overall, WMS recommends that the average ascent rate of the entire trip be less than per day. The most studied and preferred medication for prevention of HAPE is
nifedipine Nifedipine (3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate), sold under the brand name Adalat and Procardia, among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Ra ...
, a pulmonary
vasodilator Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...
which prevents the altitude induced pulmonary hypertension. The recommendation for its use is strongest for individuals with a history of HAPE. According to published data, treatment is most effective if given one day prior to ascent and continued for four to five days, or until descent below 2,500 meters (8,200 ft). Additional medications that are being considered for prevention but require further research to determine efficacy and treatment guidelines include
acetazolamide Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), urine alkalin ...
,
salmeterol Salmeterol (sold in China as Qitai) is a long-acting β2 adrenergic receptor agonist (LABA) used in the maintenance and prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD) symptoms. Symptoms of bronchos ...
,
tadalafil Tadalafil, sold under the brand name Cialis among others, is a medication used to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension. It is taken by mouth. Onset is typically within half ...
(and other
PDE5 inhibitors A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating drug that works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vessels supplyi ...
), and
dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...
. Acetazolamide has proven to be clinically effective, but formal studies are lacking. Salmeterol is considered an adjunctive therapy to nifedipine, though only in highly susceptible climbers with clearly demonstrated recurrence of HAPE. Tadalafil was found to be effective at preventing HAPE in HAPE-s individuals during rapid ascent, but optimal dosing and frequency has yet to be established. Use of dexamethasone is currently indicated for the treatment of moderate-to-severe acute mountain sickness, as well as
high-altitude cerebral edema High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves di ...
. It has also been found to prevent HAPE, but its routine use is not yet recommended. Notably, each of these medications acts to block hypoxic pulmonary hypertension, lending evidence to the proposed pathophysiology of HAPE outlined above. It is recommended that those who go to high altitude avoid alcohol or sleeping medications.


Treatment

The recommended first line treatment is descent to a lower altitude as quickly as possible, with symptomatic improvement seen in as few as 500 to 1,000 meters (1,640 feet to 3,281 feet). However, descent is not mandatory in people with mild HAPE and treatment with warming techniques, rest, and supplemental oxygen can improve symptoms. Giving oxygen at flow rates high enough to maintain an SpO2 at or above 90% is a fair substitute for descent. In the hospital setting, oxygen is generally given by
nasal cannula The nasal cannula (NC) is a device used to deliver supplemental oxygen or increased airflow to a patient or person in need of respiratory help. This device consists of a lightweight tube which on one end splits into two prongs which are placed ...
or
face mask The face is the front of an animal's head that features the eyes, nose and mouth, and through which animals express many of their emotions. The face is crucial for human Personal identity, identity, and damage such as scarring or developmental d ...
for several hours until the person is able to maintain oxygen saturations above 90% while breathing the surrounding air. In remote settings where resources are scarce and descent is not feasible, a reasonable substitute can be the use of a
portable hyperbaric chamber Portable may refer to: General * Portable building, a manufactured structure that is built off site and moved in upon completion of site and utility work * Portable classroom, a temporary building installed on the grounds of a school to provide a ...
, which simulates descent, combined with additional oxygen and medications. As with prevention, the standard medication once a climber has developed HAPE is
nifedipine Nifedipine (3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate), sold under the brand name Adalat and Procardia, among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Ra ...
, although its use is best in combination with and does not substitute for descent, hyperbaric therapy, or oxygen therapy. Though they have not formally been studied for the treatment of HAPE, phosphodiesterase type 5 inhibitors such as
sildenafil Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...
and
tadalafil Tadalafil, sold under the brand name Cialis among others, is a medication used to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension. It is taken by mouth. Onset is typically within half ...
are also effective and can be considered as add-on treatment if first-line therapy is not possible; however, they may worsen the headache of mountain sickness. There is no established role for the inhaled beta-agonist salmeterol, though its use can be considered.
Dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...
has a potential role in HAPE, though there are currently no studies to support its effectiveness as treatment. However, as outlined in the 2014 WMS Practice Guidelines, its use is recommended for the treatment of people with concomitant HAPE and
HACE High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves di ...
at the treatment doses recommended for HACE alone. Additionally, they support its use in HAPE with neurologic symptoms or hypoxic encephalopathy that cannot be distinguished from HACE.


Epidemiology

Rates of HAPE differs depending on
altitude Altitude or height (also sometimes known as depth) is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The exact definition and reference datum varies according to the context ...
and speed of ascent. In general, there is about a 0.2 to 6 percent incidence at , and about 2 to 15 percent at . The higher incidence of 6% has been seen when climbers ascend at a rate > 600m/day. It has been reported that about 1 in 10,000 skiers who travel to moderate altitudes in Colorado develop HAPE; one study reported 150 cases over 39 months at a Colorado resort located at . About 1 in 50 climbers who ascended Denali [] developed pulmonary edema, and as high as 6% of climbers ascending rapidly in the Alps []. In climbers who had previously developed HAPE, re-attack rate was up to 60% with ascent to in a 36-hour time period, though this risk was significantly reduced with slower ascent rates. It is believed that up to 50% of people suffer from subclinical HAPE with mild edema to the lungs but no clinical impairment.


History

HAPE was recognized by physicians dating back to the 19th century but was originally attributed to “high altitude pneumonia”. The first documented case of pulmonary edema, confirmed by autopsy, was probably that of Dr Jacottet who died in 1891 in the Observatoire Vallot below the summit of
Mont Blanc Mont Blanc (french: Mont Blanc ; it, Monte Bianco , both meaning "white mountain") is the highest mountain in the Alps and Western Europe, rising above sea level. It is the second-most prominent mountain in Europe, after Mount Elbrus, and i ...
. After participating in a rescue on the mountain, the doctor refused to return. Instead, he spent further two nights at an altitude of with obvious AMS symptoms and died on the second night. This condition was subsequently noticed in otherwise healthy climbers who would die shortly after arriving at high altitudes. It was not until 1960 that Charles Houston, an internal medicine physician in Aspen, published a case report of 4 individuals participating in high elevation activities that he had diagnosed with “edema of the lungs”. He described chest X-rays with edema and non-specific changes on EKG. Even though these cases had been termed high altitude pneumonia in the past, Houston indicated that these cases were “acute pulmonary edema without heart disease”.


See also

*
Hazards of outdoor recreation Outdoor recreation, such as hiking, camping, canoeing, cycling, or skiing, entails risks, even if participants do not recklessly place themselves in harm's way. In some circumstances, such as being in remote locations or in extreme weather conditio ...
*
High-altitude cerebral edema High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves di ...
(HACE) * High-altitude flatus expulsion (HAFE)


References


External links

{{DEFAULTSORT:High-Altitude Pulmonary Edema Lung disorders Mountaineering and health