European Respiratory Society, ERJ Open Research, p. 00643-2022, 2023
DOI: 10.1183/23120541.00643-2022
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The 2022 asthma guidelines emphasise inhaled long-acting beta2-agonist formoterol as part of first treatment step, and therefore formoterol use among athletes will likely increase. However, prolonged supratherapeutic use of inhaled beta2-agonist impairs training outcomes in moderately-trained men. Here, we investigated whether inhaled formoterol, at therapeutic doses, imposes detrimental effects in endurance-trained individuals of both sexes.Fifty-one endurance-trained participants (31/20 male/female; maximal oxygen consumption(V′O2max): (mean±sd) 62±6/52±5 mLO2/min·kg−1) inhaled formoterol (n=26, 24 µg) or placebo (n=25) twice-daily for 6 weeks. At baseline and follow-up, we assessed V′O2maxand incremental exercise performance during a bike-ergometer ramp-test, body composition by Dual-Energy-X-ray-absorptiometry, muscle oxidative capacity by high-resolution mitochondrial-respirometry, enzymatic activity assays and immunoblotting, intravascular volumes by carbon-monoxide rebreathing, and cardiac left ventricle mass and function by echocardiography.Compared to placebo, formoterol increased lean body mass by 0.7 kg (95%CI: 0.2 to 1.2, treatment×trial p=0.022), but decreased V′O2max5% (treatment×trial p=0.013) and incremental exercise performance 3% (treatment×trial p<0.001). Formoterol also lowered muscle citrate synthase activity 15% (treatment×trial, p=0.063), mitochondrial complex-II and III content (treatment×trial p=0.028 and p=0.007, respectively), and maximal mitochondrial respiration through complex-I and I+II by 14% and 16% (treatment×trial p=0.044 and p=0.017, respectively). No apparent changes were observed in cardiac parameters and intravascular blood volumes. All effects were sex-independent.Our findings demonstrate that inhaled therapeutic doses of formoterol impair aerobic exercise capacity in endurance-trained individuals, which is in part related to impaired muscle mitochondrial oxidative capacity. Thus, if low-dose formoterol fails to control respiratory symptoms in asthmatic athletes, physicians may consider alternative treatment options.