AltitudeOmics: The Integrative Physiology of Human Acclimatization to Hypobaric Hypoxia and Its Retention upon Reascent

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p

深入理解人体对低氧的反应，对于全球数百万在高海拔低氧环境中旅行、居住或工作的人群健康至关重要。尽管过去百年间已有数十项相关研究，但调控人体低氧习服的核心机制仍未完全明晰。本高海拔组学（AltitudeOmics）项目旨在填补这一研究空白。本项目的研究目标有二：其一，阐明成功低氧习服的表型特征，并评估该表型的留存情况；其二，以本研究发现为基础，开展配套的机制研究。本研究通过如下方案表征低氧习服过程：招募21名受试者，令其在5260米海拔环境中习服16天，期间检测动脉血氧合状态、血红蛋白浓度（[Hb]）、急性高原病（AMS, Acute Mountain Sickness）、认知功能与运动表现的变化。随后，为探究习服表型的留存情况，我们令受试者在1525米海拔停留7天（n=14）或21天（n=7）后，再次重返5260米海拔环境。在受试者处于5260米海拔16天时，我们观测到如下结果：1）动脉血氧合状态与血红蛋白浓度均有所提升（与急性低氧状态相比：动脉血氧分压（PaO2）升高9±4 mmHg，达到45±4 mmHg；动脉血二氧化碳分压（PaCO2）进一步下降6±3 mmHg，降至21±3 mmHg；血红蛋白浓度升高1.8±0.7 g/dL，达到16±2 g/dL）；2）未出现急性高原病；3）认知功能得到改善；4）运动表现提升8±8%（所有变化均满足p