Inhaled formoterol impairs aerobic exercise capacity in endurance-trained individuals: a randomised controlled trial. Issue 2 (24th April 2023)

• Record Type: Journal Article
• Authors: Jessen, Søren; Lemminger, Anders; Backer, Vibeke; Fischer, Mads; Di Credico, Andrea; Breenfeldt Andersen, Andreas; Bangsbo, Jens; Hostrup, Morten
• Is Part Of: ERJ open research. Volume 9:Issue 2(2023)
• Publication Date: 2023-04-24
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; Respiration; Respiratory organs -- Diseases; Respiratory organs -- Diseases -- Treatment; Respiratory Tract Diseases; Electronic journals; Fulltext; Internet Resources; Periodicals; Periodical; 616.2005
• DOI: 10.1183/23120541.00643-2022
• Languages: English
• ISSNs: 2312-0541

Abstract

Background: The 2022 Global Initiative for Asthma guidelines emphasise the inhaled long-acting β2 -agonist formoterol as part of the first treatment step, and therefore formoterol use among athletes will probably increase. However, prolonged supratherapeutic use of inhaled β2 -agonists impairs training outcomes in moderately trained men. We investigated whether inhaled formoterol, at therapeutic doses, imposes detrimental effects in endurance-trained individuals of both sexes. Methods: 51 endurance-trained participants (31 male, 20 female; mean±sd maximal oxygen consumption ( V̇ O2 max ) 62±6 mL·min −1 ·kg bw −1 and 52±5 mL·min −1 ·kg bw −1, respectively) inhaled formoterol (24 µg; n=26) or placebo (n=25) twice daily for 6 weeks. At baseline and follow-up, we assessed V̇ O2 max and 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. Results: Compared to placebo, formoterol increased lean body mass by 0.7 kg (95% CI 0.2–1.2 kg; treatment×trial p=0.022), but decreased V̇ O2 max by 5% (treatment×trial p=0.013) and incremental exercise performance by 3% (treatment×trial p<0.001). In addition, formoterol lowered muscle citrate synthase activity by 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 complexes 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. Conclusion: 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. Prolonged treatment with inhaled formoterol impairs aerobic exercise capacity in endurance-trained individuals. Physicians may consider alternative treatment options if low-dose formoterol fails to control airway symptoms in asthmatic athletes. https://bit.ly/3vLsjHM