Efficacy and Safety of Maintenance Regimens for Adolescent and Adult Asthmatics With Exercise-Induced Bronchospasm: Systematic Review and Network Meta-Analysis

Background: Exercise-induced bronchospasm (EIB) commonly coexists with asthma. However, the data on the efficacy of maintenance therapies for asthma with EIB are scarce. Objective: This network meta-analysis assessed the comparative efficacy and safety of maintenance regimens for asthmatics with EIB. Methods: We searched PubMed, Scopus, Embase, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials (RCTs) that addressed the efficacy and safety of maintenance treatments in adolescent and adult asthmatics with EIB from inception to April 2024. The primary outcome was the change in forced expiratory volume in 1 second postexercise after maintenance therapy. The secondary outcome focused on treatment-related adverse events (AEs). Results: Eleven RCTs involving 1054 patients were included. Low-dose inhaled corticosteroid (ICS)-montelukast significantly improved EIB with a mean difference (95% confidence interval) of 14.96% (9.61, 20.31), followed by low- to medium-dose (LM-dose) ICS-salmeterol 13.7% (8.68, 18.72), high-dose ICS 13.30% (1.34, 25.26), montelukast 11.35% (5.76, 16.95), ICS-vilanterol 9.24% (4.41, 14.07), zafirlukast 8.80% (2.28, 15.32), LM-dose ICS 7.55% (3.48, 11.63), and as-needed ICS-formoterol 6.91% (2.07, 11.75). Low-dose ICS-montelukast and LM-dose ICS-salmeterol were comparably effective. There were no significant efficacy differences among ICS monotherapy, as-needed ICS-formoterol, and antileukotrienes. Antileukotrienes were inferior to ICS monotherapy in reducing asthma exacerbation. Long-acting β₂-agonist (LABA)-induced tachyphylaxis may occur despite using alongside ICS. Conclusion: Low-dose ICS and as-needed ICS-formoterol were equally effective in managing asthmatics with EIB. The addition of antileukotrienes or LABA to ICS should be considered for more severe cases, with close monitoring to assess treatment response and detect potential tachyphylaxis or AEs.