Effects of long-term use of macrolides in patients with non-cystic fibrosis bronchiectasis: a meta-analysis of randomized controlled trials

BACKGROUND The purpose of this study was to evaluate the clinical benefits and safety of the long-term use of macrolides in patients with non-cystic fibrosis (non-CF) bronchiectasis. METHODS Embase, Pubmed, the Cochrane Library and Web of Science databases were searched from inception up to March 2014. The primary outcome was the improvement of exacerbations of bronchiectasis. Secondary endpoints included changes of microbiology, lung function, quality of life, sputum volume, adverse events and macrolide resistance. RESULTS The literature search yielded 139 studies, ten of which containing 601 patients were included in this meta-analysis. Macrolides showed a statistically-significant improvement in reducing acute exacerbations per patient during follow-up treatment (RR = 0.55, 95% CI: 0.47, 0.64, P < 0.001), increasing the number of patients free from exacerbations (OR = 2.81, 95% CI: 1.85, 4.26, P < 0.001), and prolonging time to a first exacerbation (HR = 0.38, 95% CI: 0.28, 0.53, P < 0.001). Macrolides maintenance treatment was superior to control with respect to attenuating FEV1 decline (p = 0.02), improving sputum volume (p = 0.009) and SGRQ total scores (p = 0.02), but showed a higher risk of adverse events, especially diarrhea (OR = 5.36; 95% CI: 2.06, 13.98, P = 0.0006). Eradication of pathogens was improved in the macrolide group (OR = 1.76, 95% CI: 0.91, 3.41, P = 0.09), while pathogen resistance caused by macrolides dramatically increased (OR = 16.83, 95% CI: 7.26, 38.99, P < 0.001). The new appearance of a microbiologic profile or participant withdrawal due to adverse events showed no significant differences between the two groups. CONCLUSION In patients with non-CF bronchiectasis, macrolide maintenance treatment can effectively reduce frequency of exacerbations, attenuate lung function decline, decrease sputum volume, improve quality of life, but may be accompanied with increased adverse events (especially diarrhea) and pathogen resistance.