Montelukast improves air trapping, not airway remodeling, in patients with moderate-to-severe asthma: a pilot study

Abstract

Background Evidence has demonstrated that the distal lung, which includes airways of <2 mm in diameter and lung parenchyma, constitutes an important component of asthma pathology. Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and bronchoconstrictors involved in the asthmatic process. Guidelines recommend the leukotriene-modifying agents for asthma treatment. We hypothesized that a leukotriene receptor antagonist with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combination would improve small airways function in moderate-to-severe asthmatics evaluated by physiological tests and high-resolution computed tomography (HRCT) analysis. This study was performed at a tertiary university hospital in Beijing. Methods This was a randomized, double-blind, parallel study performed in 38 patients with moderate-to-severe asthma treated with salmeterol/fluticasone (SFC) plus montelukast (SFC+M) or SFC plus placebo over 24 weeks. Small airway function was assessed by physiological studies and HRCT image analysis. Results Montelukast significantly improved air trapping as expressed by the residual volume (RV)/total lung capacity (TLC). Over 24 weeks of treatment, RV/TLC was improved by (15.41±6.67)% in patients receiving SFC+M while RV/TLC was decreased by (8.57±10.26)% in patients receiving SFC alone, the difference between the two groups was significant (P=0.02). There was a trend towards a significant difference in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) in the SFC+M group compared to that in the SFC group ((17.87±8.17)% vs. (12.28±9.20)%, P=0.056). There was no significant change in percentage wall area (WA%) after 24 weeks of add-on treatment with montelukast. Patients receiving SFC+M showed significant improvement in the ratio of CT-determined values at full expiration to those at full inspiration (E/I ratio) (0.894±0.005 vs. 0.871±0.003, P=0.002). Conclusion We have shown, using lung function tests and HRCT image technique, that add-on therapy with montelukast improves distal lung function reflected by air trapping, but not airway wall thickness in moderate-to-severe asthma. (ClinicalTrials.gov number, NCT00699062)