HYPOXIC CHALLENGES AT ALTITUDE: MECHANISTIC INSIGHTS AND TRANSLATIONAL APPROACHES TO HIGH-ALTITUDE ILLNESS

High-Altitude Illness (HAI) refers to a spectrum of hypoxia-related syndromes occurring above 2,500 meters, ranging from mild acute mountain sickness (AMS) to life-threatening conditions like high-altitude cerebral edema (HACE) and pulmonary edema (HAPE). With the rise in trekking, tourism, and military operations in high-altitude regions, HAI has emerged as a significant public health concern. AMS typically develops within 6–12 hours of ascent, presenting with headache, dizziness, nausea, fatigue, and disturbed sleep. If untreated, AMS can progress to HACE, characterized by ataxia, altered mental status, and coma, or to HAPE, marked by dyspnea, cough, cyanosis, and pulmonary crackles. The underlying mechanisms include cerebral vasodilation, oxidative stress, and blood–brain barrier disruption in AMS/HACE, while HAPE results from abnormal hypoxic pulmonary vasoconstriction and alveolar-capillary leakage. Diagnosis is primarily clinical, with the Lake Louise Score being the most widely used tool despite field limitations. Prevention relies on gradual acclimatization, staged ascent, and avoidance of alcohol or sedatives, which improve ventilatory and hematologic adaptation. Pharmacologic options like acetazolamide, dexamethasone, and nifedipine may be useful in high-risk or rapid ascents, while newer therapies such as phosphodiesterase-5 inhibitors and iron supplementation are under study. The mainstay of treatment remains halting ascent and initiating descent, supplemented by oxygen and drug therapy when required. Prognosis is generally favorable with timely intervention, but delays, especially in HACE or HAPE, can be fatal.