Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma

Fang Yi, Chen Zhan, Baojuan Liu, Hu Li, Jianmeng Zhou, Jiaman Tang, Wen Peng, Wei Luo, Qiaoli Chen, Kefang Lai, Fang Yi, Chen Zhan, Baojuan Liu, Hu Li, Jianmeng Zhou, Jiaman Tang, Wen Peng, Wei Luo, Qiaoli Chen, Kefang Lai

Abstract

Background: Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA.

Methods: Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis.

Results: The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05).

Conclusions: Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar. Trial registration ClinicalTrials.gov, number NCT01404013.

Keywords: Budesonide/formoterol; Cough; Cough variant asthma; Eosinophilic airway inflammation; Montelukast.

Conflict of interest statement

All authors reported no conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Summary of study design and visits
Fig. 2
Fig. 2
Trial profile. Full analysis set included all randomly assigned patients who had taken at least one dose of study medication and provided at least one baseline and one post-baseline primary endpoint observation during the treatment period. M: montelukast alone; BF: budesonide/formoterol alone; MBF: montelukast plus budesonide/formoterol
Fig. 3
Fig. 3
Median changes from baseline to week 1, week 4, and week 8 in VAS score (a), daytime CSS (b) and night-time CSS (c) of the patients in three groups. M: montelukast alone; BF: budesonide/formoterol alone; MBF: montelukast plus budesonide/formoterol; VAS: visual analog scale; CSS: cough symptoms score. Error bars indicate IQR
Fig. 4
Fig. 4
Median changes from baseline to week 4, and week 8 in LogC5 (a) and sputum Eos% (b), and mean changes from baseline in FeNO (c) of the patients in three groups. FeNO values were logged. M: montelukast alone; BF: budesonide/formoterol alone; MBF: montelukast plus budesonide/formoterol. Error bars indicate IQR or SD

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