Improved Pulmonary Gas Exchange at Altitude Is Due to Pulmonary Vascular Adaptation to Chronic Hypoxia in Urban Residents

Willixhofer, Robin, Laura Gochicoa-Rangel, Anna Apostolo, Jeness Campodonico, Elisabetta Salvioni, Ada De-Los- Santos-Martínez, Alejandro Reyes-García, Luis Torre-Bouscoulet, Sergio Harari, Federico Tagariello, and Piergiuseppe Agostoni. Improved pulmonary gas exchange at altitudes is due to pulmonary vascular adaptation to chronic hypoxia in urban residents. High Alt Med Biol. 00:00-00, 2025. Background: Chronic exposure to high altitude induces physiological adaptations in the lung, but the specific mechanisms of alveolar-capillary gas exchange adaptation in urban populations remain incompletely understood. Methods: We assessed altitude-related alveolar capillary membrane gas diffusion adaptations in Milan (lowlanders, 120 m) and Mexico City (highlanders, 2,240 m). A 1:1 nearest-neighbor matching by age and sex was performed. Results: Comparison between healthy young adults (n = 246, age LCO: 31.7 27.4-39.0 vs. 28.2 24.6-32.8 ml/min/mmHg, p p p n = 142) with balanced age and sex distributions (standardized mean differences p p p = 0.045). Conclusions: These findings suggest vascular, rather than membrane, adaptation to chronic hypoxia in high-altitude urban residents.