High-Altitude Pulmonary Edema Is Initially Caused by an Increase in Capillary Pressure

TLDR

HAPE is marked by severe pulmonary hypertension and inflammatory changes in bronchoalveolar lavage fluid. The study aims to determine whether HAPE is primarily driven by increased capillary pressure or increased permeability. The authors measured capillary pressure via occlusion and permeability via 67Ga‑transferrin escape in 16 HAPE‑susceptible and 14 control subjects at low altitude and after ascent to 4559 m. At high altitude, HAPE‑susceptible subjects showed markedly higher pulmonary artery and capillary pressures, and all who developed HAPE had capillary pressures above 19 mm Hg, while permeability changes were minimal, indicating that elevated capillary pressure initiates HAPE.

Abstract

Background —High-altitude pulmonary edema (HAPE) is characterized by severe pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of inflammation. It is not known, however, whether the primary event is an increase in pressure or an increase in permeability of the pulmonary capillaries. Methods and Results —We studied pulmonary hemodynamics, including capillary pressure determined by the occlusion method, and capillary permeability evaluated by the pulmonary transvascular escape of 67 Ga-labeled transferrin, in 16 subjects with a previous HAPE and in 14 control subjects, first at low altitude (490 m) and then within the first 48 hours of ascent to a high-altitude laboratory (4559 m). The HAPE-susceptible subjects, compared with the control subjects, had an enhanced pulmonary vasoreactivity to inspiratory hypoxia at low altitude and higher mean pulmonary artery pressures (37±2 versus 26±1 mm Hg, P <0.001) and pulmonary capillary pressures (19±1 versus 13±1 mm Hg, P <0.001) at high altitude. Nine of the susceptible subjects developed HAPE. All of them had a pulmonary capillary pressure >19 mm Hg (range 20 to 26 mm Hg), whereas all 7 susceptible subjects without HAPE had a pulmonary capillary pressure <19 mm Hg (range 14 to 18 mm Hg). The pulmonary transcapillary escape of radiolabeled transferrin increased slightly from low to high altitude in the HAPE-susceptible subjects but remained within the limits of normal and did not differ significantly from the control subjects. Conclusions —HAPE is initially caused by an increase in pulmonary capillary pressure.