The Effect of Long-Term Azithromycin on Objective and Subjective Cough in Chronic Respiratory Disease: A Systematic Review and Meta-analysis of Randomised Controlled Trials and Noncomparative Studies

Abstract

Introduction: Azithromycin is an effective treatment for various respiratory conditions but its effect on cough is poorly understood. We synthesised data from randomised controlled trials (RCTs) and noncomparative studies (NCT) examining its effect on objective and subjective cough.

Methods: After prospective registration on PROSPERO, we searched MEDLINE, EMBASE, and CENTRAL for both RCTs and NCT trials examining the effect azithromycin on cough in respiratory disease.

Results: We identified 1240 studies of which 6 (4 RCTs and 2 NCT studies) were included in the meta-analysis, with a total of 275 patients. Azithromycin was associated with significant improvement in Leicester Cough Questionnaire scores at follow-up when compared to baseline scores (SMD = 0.62 [95% CI 0.12 to 1.12], p = 0.01). However, when only RCTs were synthesised, no significant effect was observed (SMD = 0.12 [95% CI - 0.36 to 0.60], p = 0.62). There was no significant reduction in cough severity VAS score (SMD = - 0.39 [95% CI - 0.92 to 0.14], p = 0.15). There was no significant reduction in objective cough count (SMD = - 0.41 [95% CI - 1.04 to 0.32], p = 0.09).

Conclusion: Azithromycin therapy improves cough-related quality of life in various chronic respiratory diseases; however, there was no significant effect on cough outcomes when only data from RCTs were synthesised. We believe that to accurately identify which patients whose cough would benefit from azithromycin a large-scale clinical trial of patients with a broad spectrum of respiratory diseases, with sufficiently severe cough, should be undertaken with subgroup analysis of individual disease areas.

Keywords: Azithromycin; Chronic respiratory disease; Cough.

Fig. 1

PRISMA flow diagram showing quantities of studies excluded at each stage in the review

Fig. 2

A Risk-of-bias assessment for all RCTs included in this review. B Risk-of-bias assessment for all NCTs included in this review

Fig. 3

A Forest plot of all study data comparing baseline and follow-up LCQ scores with treatment of azithromycin. B Forest plot of randomised controlled trials data comparing LCQ score means changes between both azithromycin with placebo groups

Fig. 4

A Forest plot of all study data comparing baseline and follow-up cough severity VAS scores with treatment of azithromycin. B Forest plot of randomised controlled trials data comparing cough severity VAS score means changes between both azithromycin with placebo groups

Fig. 5

Forest plot of randomised controlled trials data comparing SGRQ score means changes between both azithromycin with placebo groups

Fig. 6

Forest plot of studies with data comparing mean difference of coughs per hour on 24-h cough monitoring at baseline and follow-up with azithromycin treatment