Reduced Exercise Ventilatory Efficiency in Healthy Young Adults at Moderate Altitude

Physiological responses to exercise at high altitude are well characterized, whereas considerably less is known about the integrated cardiopulmonary response to acute exposure to moderate altitude. We investigated the ventilatory, metabolic, and cardiovascular responses to exercise at 2325 m in healthy, non-acclimatized subjects. Thirteen healthy young adults (age range 22–37 years) living at sea level underwent maximal cardiopulmonary exercise testing (CPET) both at sea level (Rome, Italy; ~50 m) and within 1–2 days of arrival at moderate altitude (Asmara, Eritrea; 2325 m). The V′E/V′CO2 slope, calculated before the respiratory compensation point, was the primary outcome. Exercise capacity, ventilatory responses, end-tidal gases, cardiovascular variables, and symptom perception were also assessed. The V′E/V′CO2 slope increased from 26.2 ± 2.5 at sea level to 30.5 ± 2.9 at moderate altitude (mean paired difference +4.4, 95% CI 3.3–5.5; p < 0.001), corresponding to an approximately 17% increase in the V′E/V′CO2 slope. Peak ventilation increased (108.3 ± 37.2 vs. 127.9 ± 41.7 L/min; p = 0.003), while breathing reserve decreased (33.3 ± 11.3% vs. 20.7 ± 12.1%; p = 0.004). PETCO2 was significantly lower at moderate altitude at rest and throughout exercise. Conversely, peak V′O2, peak work rate, peak heart rate, and O2 pulse did not significantly differ between conditions. Leg fatigue was greater at moderate altitude, whereas the increase in perceived breathlessness did not reach statistical significance. In healthy, non-acclimatized young adults, acute exposure to moderate altitude was associated with increased ventilatory demand and a higher V′E/V′CO2 slope, without statistically significant changes in peak aerobic performance or the main cardiovascular parameters. These findings suggest that enhanced ventilation represents a prominent early physiological response to moderate-altitude hypobaric hypoxia.