Hypoxic Lung Whiteout: Further Clearing but More Questions from on High

High-altitude pulmonary edema (HAPE) is an uncommon form of life-threatening noncardiogenic pulmonary edema that occurs when a person ascends too high and too fast. It begins within 1 to 2 days of a gain in altitude. It has an incidence of 0.1% to 15%, depending on ascent rate, individual susceptibility (as reflected by previous episodes of HAPE), and likely coexisting cardiopulmonary disease (1). Its pathogenesis, once mysterious, is now understood in some detail.

High-altitude pulmonary edema begins when a critical level of hypoxic pulmonary vasoconstriction (HPV) causes mean pulmonary arterial pressure to exceed 35 to 40 mm Hg (2). This, in association with regional (segmental and subsegmental) differences in the strength of HPV (3) and hypoxic venoconstriction (2), probably causes capillary pressures to exceed 20 mm Hg in areas of lesser HPV and higher blood flow (2). Pressures of this magnitude in the unconditioned lung microvasculature lead to capillary stress failure (overperfusion edema), in which the alveolar–capillary barrier becomes permeable enough for high-molecular-weight proteins and fluid to leak into the alveolar space. Ultimately, this process disrupts the basement membranes and endothelial and epithelial cell membranes, leading to alveolar hemorrhage (1, 4, 5). The evidence for this chain of events is that high pulmonary arterial pressure precedes HAPE, reduction in pulmonary arterial pressure by any means (descent, oxygen, nitric oxide, portable hyperbaric bags, and pulmonary vasodilators) is effective therapy, and HAPE-susceptible people have very strong pulmonary vascular responses to hypoxia and exercise (1).

Two other theories of pathogenesis may, in association with increased microvascular pressures, lead to or contribute to HAPE. One theory is that HAPE involves a pulmonary inflammatory reaction to hypoxia, leading to increased capillary permeability. According to the other theory, HAPE involves a constitutional or hypoxia-mediated depression of active alveolar …