Effects of acetazolamide on exercise performance in patients with COPD going to high altitude: randomised controlled trial

ERJ Open Res. 2025 Jan 20;11(1):00767-2024. doi: 10.1183/23120541.00767-2024. eCollection 2025 Jan.

Abstract

Background: In patients with COPD, preventive treatment with acetazolamide reduces adverse health effects during altitude travel. We investigated whether preventive acetazolamide treatment modifies exercise performance in COPD patients going to high altitude.

Methods: In this randomised, double-blind trial, lowlanders with COPD, forced expiratory volume in 1 s (FEV1) 40-80% predicted, were assigned to acetazolamide (375 mg per 24 h) or placebo treatment starting 24 h before ascent and while staying at 3100 m. Patients performed progressive cycling exercise to exhaustion at 760 m, before taking the study drug, and within 4 h after arrival at 3100 m. The primary outcome was the maximal power output (Wmax).

Results: 103 patients (32 women), mean±sd age 57.2±8.1 years, FEV1 66±11% predicted, were included in per-protocol analyses. In 53 patients receiving acetazolamide, Wmax and oxygen uptake (V'O2 max) at 760 m and 3100 m were 105±27 and 91±25 W, and 18.0±4.8 and 15.5±3.7 mL·min-1·kg-1 (p<0.001, both changes). Corresponding Wmax and V'O2 max in 50 patients receiving placebo were 107±34 and 97±28 W, and 18.9±6.0 and 17.2±5.0 mL·min-1·kg-1 (p<0.001, both changes). Between-group differences (95% CI) in altitude-induced Wmax changes were -3.0 W (-8.7 to +2.7, p=0.305) and in V'O2 max changes were -0.8 mL·min-1·kg-1 (-2.1 to +0.5, p=0.213). Acetazolamide mitigated the altitude-induced reduction of P aO2 by 0.7 kPa (0.1 to 1.3, p=0.016). At 3100 m, maximal work rate with respiratory exchange ratio ≤1 was greater with acetazolamide than with placebo by 10.1 W (4.0 to 16.2, p=0.022).

Conclusions: In lowlanders with COPD, preventive treatment with acetazolamide did not modify the altitude-induced reduction in maximal work rate. However, acetazolamide enhanced arterial oxygenation and submaximal, moderate-intensity work capacity compared with placebo.