UBC Theses and Dissertations

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UBC Theses and Dissertations

Understanding the variable human response to hypoxia : physiological, genetic, and epidemiological investigations of acute mountain sickness susceptibility MacInnis, Martin J.


High-altitude (and simulated high-altitude) environments can be extraordinarily stressful for low-altitude organisms because of the reduced oxygen availability (i.e. hypoxia). Humans, who live primarily at low altitude, can adjust physiologically (i.e., acclimatise or acclimate) to hypoxic environments; however, the human acclimatisation response to hypoxia is highly variable, evident from the differential susceptibility to acute altitude illnesses, such as acute mountain sickness (AMS). For my dissertation, I attempted to identify some of the physiological, genetic, and epidemiological variables that could explain the variation in hypoxia tolerance. I conducted (i) two studies using a normobaric hypoxia chamber at the University of British Columbia; (ii) two field studies in a mountainous region of the Nepalese Himalaya; and (iii) two meta-anaylyses. The most important findings of my dissertation are that (i) oxygen saturation (SPO₂) and heart rate (HR) were not strong markers of AMS susceptibility in laboratory or field settings; (ii) a low fraction of exhaled nitric oxide (FENO) was associated with increased susceptibility to AMS in the laboratory but not in the field; (iii) physiological responses (FENO, SPO₂, HR, blood pressure) to hypoxia were repeatable on two normobaric hypoxia exposures; (iv) AMS severity was lower on the second of two identical normobaric hypoxia exposures (but headache severity was similar); (v) in a large Nepalese sample, age, sex, ascent rate, and preventative strategies were associated with AMS susceptibility; (vi) the severity of AMS was similar in brothers; (vii) there were biogeographical differences in AMS susceptibility in the Nepalese sample; (viii) polymorphisms of the FAM149A gene were associated with AMS severity; (ix) AMS history was a poor predictor of future AMS outcomes; and (x) sleep quality was weakly related to other AMS symptoms. In conclusion, this dissertation demonstates that the measured physiological variables (FENO, SPO₂, HR, blood pressure) were not associated with AMS status, that a genetic basis to the variation in AMS susceptibility is likely, and that the Lake Louise Score definition of AMS should be amended. Our understanding of acute altitude tolerance in humans may be aided by the redefinition of AMS.

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