Acute high-altitude illness: risk factors, susceptibility prediction, and personalized prevention and treatment
Abstract
Background and objectives: Acute high-altitude illness (AHAI) comprises a spectrum of related conditions arising from exposure to high altitude, such as acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). This study aimed to synthesize the existing evidence, delineate the risk factors and susceptibility predictors of AHAI, and outline personalized prevention and treatment strategies, as well as to identify key directions for future research.
Methods: A systematic search of PubMed and Web of Science was conducted, such as clinical studies, systematic reviews, and authoritative guidelines published up to August 2025. No formal meta-analysis was performed; a narrative synthesis approach was employed to integrate the existing evidence.
Results: Hypoxemia is the central pathophysiological driver of acute AHAI. Immutable host characteristics (age, sex, ethnicity, and genetic susceptibility) and modifiable comorbidities jointly influence baseline risk and disease trajectory. Current predictive approaches include hypoxic exercise testing and multifactorial risk scores; however, prospective, rigorously validated tools suitable for routine clinical use remain limited. Prevention and treatment strategies span non-pharmacological acclimatization, oxygen therapy, and pharmacologic interventions (e.g., acetazolamide, dexamethasone, calcium-channel blockers, and PDE5 inhibitors), with varying levels of evidence. Emerging therapies,…
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