Montelukast Combined with ICS/LABA Improves Clinical Outcomes in Moderate-to-Severe Persistent Asthma by Modulating T-Lymphocyte Subset-Related Cytokine Profiles.

Abstract

Introduction: Glucocorticoids and montelukast, an anti-leukotriene agent, target different inflammatory pathways. This study aims to investigate the immunological synergy of their combination.

Methods: A prospective, randomized, controlled, open-label study was conducted. Overall, 234 patients were randomly assigned to two groups for a 12-week treatment period: control group (ICS + long-acting beta₂ agonist [LABA]; n = 118): budesonide 400 μg/day (200 μg twice daily) + formoterol 18 μg/day (9 μg twice daily); combination group (n = 116): same ICS + LABA regimen + montelukast 10 mg orally once daily.

Results: At week 12, the ICS + LABA + Mon group demonstrated significantly greater improvements in pre-bronchodilator FEV₁ compared with the ICS + LABA group (mean change: +239.0 ± 70.5 mL vs. +141.2 ± 47.9 mL; between-group difference 97.8 mL; 95% CI: 82.4-113.2; p < 0.001). Asthma control improved more substantially with combination therapy, as shown by greater ACQ-6 score reductions, with the mean score in the combination group approaching the well-controlled threshold. Immunologically, combination therapy produced a significantly greater increase in IFN-γ and Treg cytokines IL-10 and TGF-β, alongside more pronounced suppression of T helper 2 (Th2) cytokines (IL-4, IL-5, and IL-13) and the Th17 cytokine IL-17.

Conclusion: The addition of montelukast to ICS + LABA therapy significantly enhances pulmonary function, asthma control, and suppression of eosinophilic airway inflammation in moderate-to-severe persistent asthma via a favorable immunological shift characterized by enhanced Th1 and Treg responses and more potent suppression of Th2 and Th17 pathways.