The role of antileukotriene therapy in COPD management: a systematic review and meta-analysis of randomized controlled trials

Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is a prevalent lung condition that impairs breathing and daily activities, manifesting symptoms such as a persistent cough, shortness of breath, and chest tightness. Antileukotrienes, including Montelukast, Zafirlukast, and Zileuton, are used to manage inflammation in asthma; however, according to the 2025 GOLD reports, their efficacy in treating COPD remains unclear. This systematic review and meta-analysis aim to evaluate the role of antileukotriene therapy in patients with COPD. Method This systematic review was reported in accordance with the PRISMA guidelines. In July 2023, a comprehensive search was conducted across Scopus, Web of Science, PubMed, Cochrane Library, and Embase. The review included only randomized controlled trials that compared anti-leukotriene agents with a placebo. A meta-analysis was performed on Forced Expiratory Volume in 1 s(FEV1), Leukotriene B4(LTB4), and Myeloperoxidase(MPO), utilizing standardized mean differences(SMD) with a 95% confidence interval(CI). C-reactive protein(CRP), quality of life and adverse events data were summarized narratively. Results This meta-analysis encompassed nine randomized controlled trials involving a total of 506 participants. The findings indicated that anti-leukotriene therapy led to a significant overall improvement in FEV1 (SMD = 0.63, 95%CI 0.15 to 1.11, p = 0.01), although high heterogeneity was noted(I 2 = 83%). A subgroup analysis focusing specifically on leukotriene receptor antagonists revealed a more consistent and potent effect on FEV1 (SMD = 1.00, 95%CI 0.75 to 1.25, p < 0.001) with low heterogeneity. Notably, both Montelukast(SMD = 1.15) and Zafirlukast(SMD = 0.75) displayed significant benefits. In contrast, no significant improvements were found in the inflammatory markers LTB4 (SMD=-0.42) or MPO (SMD=-0.14). CRP results were inconclusive, while quality of life scores showed improvement in the montelukast groups. Adverse events were comparable between groups or reduced in the experimental group. Conclusion Analysis indicates that anti-leukotriene therapy, particularly with Montelukast and Zafirlukast, may lead to a modest improvement in lung function and quality of life. Subgroup analyses suggest a potential benefit specifically for Montelukast, although this requires further confirmation. In contrast, Zileuton, which operates via a different mechanism, did not demonstrate any beneficial effects. Given the limitations in sample size and heterogeneity, these findings should be considered exploratory, and additional research is essential to validate these results in larger studies.