High altitude pulmonary edema

High altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema (fluid accumulation in the lungs) that occurs in otherwise healthy mountaineers at altitudes typically above 2500 m. Some cases, however, have been reported also at lower altitudes (between 1500 - 2500 m in highly vulnerable subjects), although what makes some people susceptible to HAPE is not currently known. HAPE remains the major cause of death related to high-altitude exposure with a high mortality in absence of adequate emergency treatment.

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:

Symptoms: at least two of:
 * Difficulty in breathing (dyspnea) 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 cyanosis (blue skin color)
 * Tachypnea (rapid shallow breathing)
 * Tachycardia (rapid heartrate)

Clinical symptoms are unlikely. Blood oxygen levels remain >90%.
 * Intermediate Altitudes (1500-2500 m or 4900-8200 feet)

Clinical symptoms are common and may develop after 2-3 days. Blood oxygen levels may drop below 90% or lower during exercise. Prior acclimatisation will decrease the severity of the symptoms.
 * High Altitude (2500-3500 m or 8200-11500 feet)

Blood oxygen levels are <90%, even at rest. Progressive deterioration may occur despite acclimatisation.
 * Extreme Altitude (>5800 m or 19000 feet)

Causes
The initial cause of HAPE is a shortage of oxygen which is caused by the lower air pressure at high altitudes. The mechanisms by which this shortage of oxygen causes HAPE are poorly understood, but two processes are believed to be important:
 * 1) Increased pulmonary arterial and capillary pressures (pulmonary hypertension) secondary to hypoxic pulmonary vasoconstriction.
 * 2) An idiopathic non-inflammatory increase in the permeability of the vascular endothelium.

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: severe pulmonary hypertension can exist in the absence of clinical HAPE in subjects at high altitude.

Incidence
The incidence of clinical HAPE in unacclimatized travelers exposed to high altitude (~4000 m) appears to be less than 1%. The U.S. Army Pike's Peak Research Laboratory has exposed sea-level-resident volunteers rapidly and directly to high altitude; during 30 years of research involving about 300 volunteers (and over 100 staff members), only three have been evacuated with suspected HAPE.

Predisposing factors
Individual susceptibility to HAPE is difficult to predict. The most reliable risk factor is previous susceptibility to HAPE, and there is likely to be a genetic basis to this condition, perhaps involving the gene for angiotensin converting enzyme (ACE). Recently, scientists have found the similarities between low amounts of 2,3-BPG (also known as 2,3-DPG) with the occurrence of HAPE at high altitudes.

Research
In order to help understand the factors that make some individuals susceptible to HAPE, the International HAPE Database was set up in 2004. Individuals who have previously suffered from HAPE can register with this confidential database in order to help researchers study the condition.

Treatment
The standard and most important treatment is to descend to lower altitude as quickly as possible, preferably by at least 1000 metres. Oxygen should also be given if possible. Symptoms tend to quickly improve with descent, but less severe symptoms may continue for several days. The standard drug treatments for which there is strong clinical evidence are dexamethasone. and nifedipine Phosphodiesterase inhibitors such as tadalafil are also effective but may worsen the headache of mountain sickness.