Studies of occupational acute mountain sickness (AMS) have not focused on the more severe end of the spectrum to date. Aims To examine risk factors associated with the development of occupational AMS severe enough to receive treatment in a compression chamber. Methods A nested case referent study in a cohort of high-altitude (4000 m) mine workers, comparing cases of severe, chamber-treated AMS to matched referents. Using logistic regression, we tested potential risk factors based on premorbid

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... rveillance examinations, including cigarette smoking (current smoking, smoking intensity and exhaled carbon monoxide [CO]). Results There were 15 cases and 30 controls. In multivariate analysis including age, sex and place of residence, current smoking was associated with increased risk of severe AMS (odds ratio [OR] 10.0; 95% confidence interval [CI] 1.5-67.4), taking into account any prior, less severe AMS event, which was also a potent risk factor (OR 33.3; 95% CI 2.8-390). Smoking intensity (cigarettes per day) and exhaled CO were also statistically significantly associated with severe AMS. Conclusions Cigarette smoking is a strong, previously under-appreciated risk factor for severe AMS. Because this is a modifiable factor, these findings suggest that workplace-based smoking cessation should be tested as an intervention to prevent such morbidity.