The central theme of this proposal is to better understand mechanisms of altitude related illness, to develop demographic, biochemical (serum and plasma), and genetic predictors (or combinations of predictors) of who may be most susceptible to altitude sickness as well as to develop protocols to help optimize acclimatization practice. The adaptive and/or maladaptive processes that lead to altitude-related symptoms (mild to severe) remain obscure and no clear predictors of illness have been found other than the rate of ascent, the altitude of exposure and activity level at altitude. Two specific aims will be pursued over the proposed 3 years of study. The first is to quantify the incidence, timing, severity and duration of altitude symptoms at the South Pole. Symptoms will be assessed at sea level (McMurdo Station) and at 6 time periods while at altitude to follow the time course of symptom resolution. In a subgroup of subjects, the current practice of prophylactic use of Acetazolamide will be assessed in a placebo controlled fashion. The second aim is to determine the incremental value of baseline demographic characteristics, biochemical measures (serum and plasma), nighttime physiological monitoring (quantification of oxygen saturation, heart rate variability and respiration) and candidate gene polymorphisms on the ability to predict symptoms of altitude illness. Biochemical markers and candidate genes will be those directly influencing the ventilatory drive, vascular tone, vascular and tissue fluid regulation, inflammation and oxygen carrying capacity of the blood, including peptide hormones and autocoids (or the genes that encode such proteins or their receptors). In a subgroup of more symptomatic subjects and relatively asymptomatic subjects, gene expression studies will be performed on peripheral blood mononuclear cells to help guide the choice of candidate genes, which may increase or decrease susceptibility to altitude symptoms. The research will focus on the mild to moderate symptoms often experienced with acute exposure to moderate altitude. Results from this study will help identify personnel (through the development of algorithms) that may be at increased risk for developing more severe altitude symptoms (and therefore may require more effective preventive measures) and improve current altitude-illness preventive procedures at South Pole. Findings will also be applicable to the general population (altitude sojourners), to commercial air travel (pressurized to low to moderate altitudes), the space program (long term space flight at reduced atmospheric pressures) and may provide insight into clinical pathologies that result in low oxygen tensions in the blood or tissues (e.g., lung disease, obstructive sleep apnea and heart failure). As a part of this project, a web site will be developed that links with local secondary school programs as well as mountaineering and clinical web sites that inform students, climbers and the general population about altitude-related illness. In addition, with the help of secondary school teachers, a curriculum will be developed on altitude adaptation, symptoms and prevention.
