Physiological Risk Factors for Severe High-Altitude Illness A Prospective Cohort Study

Rationale: An increasing number of persons, exposed to high altitude for leisure, sport, or work, may suffer from severe high-altitude illness. Objectives: To assess, in a large cohort of subjects, the association between physiological parameters and the risk of altitude illness and their discrimination ability in a risk prediction model. Methods: A total of 1,326 persons went through a hypoxic exercise test before a sojourn above 4,000 m. They were then monitored up at high altitude and classified as suffering from severe high-altitude illness (SHAI) or not. Analysis was stratified according to acetazolamide use. Measurements and Main Results: Severe acute mountain sickness occurred in 314 (23.7%), high-altitude pulmonary edema in 22 (1.7%), and high-altitude cerebral edema in 13 (0.98%) patients. Among nonacetazolamide users (n = 917), main factors independently associated with SHAI were previous history of SHAI (adjusted odds ratios [aOR], 12.82; 95% confidence interval [CI], 6.95-23.66; P < 0.001), ascent greater than 400 m/day (aOR, 5.89; 95% CI, 3.78-9.16; P < 0.001), history of migraine (aOR, 2.28; 95% CI, 1.28-4.07; P = 0.005), ventilatory response to hypoxia at exercise less than 0.78 L/minute/kg (aOR, 6.68; 95% CI, 3.83-11.63; P < 0.001), and desaturation at exercise in hypoxia equal to or greater than 22% (aOR, 2.50; 95% CI, 1.52-4.11; P < 0.001). The last two parameters improved substantially the discrimination ability of the multivariate prediction model (C-statistic rose from 0.81 to 0.88; P < 0.001). Preventive use of acetazolamide reduced the relative risk of SHAI by 44%. Conclusions: In a large population of altitude visitors, chemosensitivity parameters (high desaturation and low ventilatory response to hypoxia at exercise) were independent predictors of severe high-altitude illness. They improved the discrimination ability of a risk prediction model.