Altitude Symptoms at the South Pole

该提案的中心主题是更好地了解高原相关疾病的机制，开发人口统计学，生化（血清和血浆）和遗传预测因子（或预测因子的组合），以及开发协议，以帮助优化适应性实践。导致与海拔高度有关的症状（轻度至重度）的适应和/或适应不良过程仍然不清楚，除了上升速度、暴露的海拔高度和在海拔高度的活动水平之外，没有发现疾病的明确预测因素。在拟议的三年研究期间，将追求两个具体目标。首先是量化南极高原症状的发生率、时间、严重程度和持续时间。将在海平面（麦默多站）和6个时间段评估症状，同时在海拔高度跟踪症状消退的时间进程。在一个受试者亚组中，将以安慰剂对照的方式评估当前预防性使用乙酰唑胺的实践。第二个目的是确定基线人口统计学特征、生化指标（血清和血浆）、夜间生理监测（氧饱和度、心率变异性和呼吸的定量）和候选基因多态性对预测高原病症状的能力的增量值。生物化学标记和候选基因将是直接影响血液的排泄驱动、血管张力、血管和组织液调节、炎症和携氧能力的那些，包括肽激素和autocoids（或编码这些蛋白质或其受体的基因）。在一个亚组中，有症状的受试者和相对无症状的受试者，将对外周血单核细胞进行基因表达研究，以帮助指导候选基因的选择，这些基因可能增加或减少对高原症状的易感性。这项研究将集中在轻度至中度症状经常经历急性暴露于中度海拔。这项研究的结果将有助于确定人员（通过算法的开发），可能会增加发展更严重的高原症状的风险（因此可能需要更有效的预防措施），并改善南极目前的高原疾病预防程序。研究结果也将适用于一般人群（高空旅居者）、商业航空旅行（加压至低至中等高度）、太空计划（在降低的大气压下进行长期太空飞行），并可能提供对导致血液或组织中低氧张力的临床病理学的见解（例如，肺病、阻塞性睡眠呼吸暂停和心力衰竭）。作为该项目的一部分，将开发一个网站，与当地中学方案以及登山和临床网站链接，向学生、登山者和普通民众通报与海拔有关的疾病。此外，在中学教师的帮助下，将编制关于高原适应、症状和预防的课程。

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.