Cases have also been reported between 1,500–2,500 metres or 4,900–8,200 feet in people who are at a higher risk or are more vulnerable to the effects of high altitude.

HAPE remains the major cause of death related to high-altitude exposure, with a high mortality rate in the absence of adequate emergency treatment.

[6] The Lake Louise Consensus Definition for high-altitude pulmonary edema has set widely used criteria for defining HAPE symptoms.

[8] 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).

[9] In studies performed at sea level, HAPE-s people were found to have exaggerated circulatory response to both hypoxia at rest and during exercise.

[9] Microneurographic recordings in these individuals developed a direct link between PAP rise and sympathetic nervous system over-activation, which could explain the exaggerated response to hypoxia in these persons.

[9] 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.

[citation needed] 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.

[9] Initial symptoms are vague and include shortness of breath, decreased exercise ability, increased recovery time, fatigue, and weakness, especially with walking uphill.

[9][3] 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.

The grades of mild, moderate, or severe HAPE are assigned based upon symptoms, clinical signs, and chest x-ray results for individuals.

[15][3] Additional medications that are being considered for prevention but require further research to determine efficacy and treatment guidelines include acetazolamide, salmeterol, tadalafil (and other PDE5 inhibitors), and dexamethasone.

Salmeterol is considered an adjunctive therapy to nifedipine, though only in highly susceptible climbers with clearly demonstrated recurrence of HAPE.

[15][3] 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.

[3][9][15] Notably, each of these medications acts to block hypoxic pulmonary hypertension, lending evidence to the proposed pathophysiology of HAPE outlined above.

[2][3][9][20] However, descent is not mandatory in people with mild HAPE and treatment with warming techniques, rest, and supplemental oxygen can improve symptoms.

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.

[19] 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”.