Macrolides for the long-term management of asthma--a meta-analysis of randomized clinical trials

Abstract

Background: Macrolide antibiotics, which have anti-inflammatory and immune modulatory effects, have been studied as adjuncts for the management of asthma. However, results have been contradictory and trials underpowered. We therefore sought to conduct a meta-analysis of randomized controlled trials (RCT).

Methods: All RCT of prolonged macrolides (3+ weeks) for asthma treatment, published up to January 2013 in MEDLINE, Scopus, CINAHL, Highwire, and The Cochrane Collaboration Library, were included. Fixed- or random-effects models were used to calculate pooled weighted or standard mean differences (WMD or SMD, respectively).

Results: A total of 12 studies were included for analysis. The pooled effect of macrolides on FEV1 (eight trials, 381 subjects) was not significant (SMD 0.05, 95% CI -0.14-0.25), but there was a significant increase in peak expiratory flow (four trials, 419 subjects; WMD 6.7, 95% CI 1.35-12.06). Pooled analysis also showed significant improvements in symptom scores (eight studies, 478 subjects; WMD -0.46, 95% CI -0.60 to -0.32), quality of life (five trials, 346 subjects; WMD 0.18, 95% CI 0.001-0.37), and airway hyper-reactivity (two trials, 131 subjects; SMD 1.99, 95% CI 0.46-3.52). Post hoc evaluation showed limited statistical power to detect significant differences in FEV1.

Conclusions: Macrolide administration for asthma for three or more weeks was not associated with improvement in FEV1, but produced significant improvements in peak expiratory flow, symptoms, quality of life, and airway hyper-reactivity. Macrolides may therefore be beneficial as adjunct asthma therapy. Future trials, focusing on long-term safety and effectiveness, should use standardized outcomes and procedures.

Keywords: anti-asthmatic agents; asthma; macrolides; meta-analysis.