Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic factor.
BACKGROUND
The pathogenesis of high-altitude pulmonary edema (HAPE) is considered an altered permeability of the alveolar-capillary barrier secondary to intense pulmonary vasoconstriction and high capillary pressure, but previous bronchoalveolar lavage (BAL) findings in well-established HAPE are also consistent with inflammatory etiologic characteristics.


OBJECTIVE
To determine whether inflammation is a primary event in HAPE and to define the temporal sequence of events in HAPE.


METHODS
Case study from July through August 1999 of 10 subjects with susceptibility to HAPE and 6 subjects resistant to HAPE, all of whom are nonprofessional alpinists with previous mountaineering experience above 3000 m.


METHODS
Pulmonary artery pressure measurements and BAL findings at low altitude (490 m) and shortly before or at the onset of HAPE at an altitude of 4559 m.


RESULTS
Subjects who were HAPE susceptible had higher mean (SD) pulmonary artery systolic blood pressures at 4559 m compared with HAPE-resistant subjects (66 vs 37 mm Hg; P =.004). Despite development of HAPE in the majority of HAPE-susceptible subjects, there were no differences in BAL fluid total leukocyte counts between resistant and susceptible subjects or between counts taken at low and high altitudes. Subjects who developed HAPE had BAL fluid with high concentrations of plasma-derived proteins and erythrocytes, but there was no increase in plasma concentrations of surfactant protein A and Clara cell protein. The chest radiograph score was 12.7 for the 3 HAPE-susceptible subjects who developed HAPE before BAL was performed; they were lavaged within 3 to 5 hours. The remainder of the HAPE-susceptible group was lavaged before edema was apparent on radiographs. However, 6 subjects from the HAPE-susceptible group who developed HAPE on the following day had a score on bronchoscopy of 1.5, which increased to 4.6, reflective of mild pulmonary edema. In HAPE cases, there were no elevations in a number of proinflammatory cytokines and eicosanoid and nitric oxide metabolites.


CONCLUSIONS
Early HAPE is characterized by high pulmonary artery pressures that lead to a protein-rich and mildly hemorrhagic edema, with normal levels of leukocytes, cytokines, and eicosanoids. HAPE is a form of hydrostatic pulmonary edema with altered alveolar-capillary permeability.
Swenson
Erik R
ER
Pulmonary and Critical Care Section, S-111-Pulm, Veterans Affairs Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA. eswenson@u.washington.edu
Maggiorini
Marco
M
Mongovin
Stephen
S
Gibbs
J Simon R
JS
Greve
Ilona
I
Mairbäurl
Heimo
H
Bärtsch
Peter
P
D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000150:complications* / Q000276:immunology; D001784:Blood Gas Analysis; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D001999:Bronchoscopy; D016207:Cytokines / Q000378:metabolism; D004452:Echocardiography; D015777:Eicosanoids / Q000378:metabolism; D004906:Erythrocyte Count; D005260:Female; D006470:Hemorrhage; D006801:Humans; D007249:Inflammation; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000502:physiology*; D011654:Pulmonary Edema / Q000000981:diagnostic imaging / Q000209:etiology* / Q000276:immunology; D011859:Radiography; D012709:Serum Albumin / Q000378:metabolism
D016207:Cytokines; D015777:Eicosanoids; D012709:Serum Albumin