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Long-term macrolide treatment for the prevention of acute exacerbations in COPD: a systematic review and meta-analysis

Authors Cui Y, Luo L, Li C, Chen P, Chen Y

Received 24 July 2018

Accepted for publication 16 October 2018

Published 22 November 2018 Volume 2018:13 Pages 3813—3829


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Chunxue Bai

Yanan Cui,1 Lijuan Luo,1 Chenbei Li,2 Ping Chen,1 Yan Chen1

1Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; 2Biomedical Clinical Medicine, The Queen Marry University of London of Nanchang University, Jiangxi, China

Background: Acute exacerbation of COPD (AECOPD) is associated with an increased hospitalization and mortality. Azithromycin and erythromycin are the recommended drugs to reduce the risk of exacerbations. However, the most suitable duration of therapy and drug-related adverse events are still a matter of debate. The aim of this meta-analysis was to assess the current evidence regarding the efficacy and safety of long-term macrolide treatment for COPD.
Materials and methods: We comprehensively searched PubMed, Embase, the Cochrane Library, and the Web of Science and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and retrospective studies.
Results: Eleven RCTs and one retrospective study including a total of 2,151 cases were carried out. Long-term macrolide treatment significantly reduced the total number of cases with one or more exacerbations (OR=0.40; 95% CI=0.24–0.65; P<0.01) and the rate of exacerbations per patient per year (risk ratio [RR]=0.60; 95% CI=0.45–0.78; P<0.01). Subgroup analyses showed that the minimum duration for drug efficacy for both azithromycin and erythromycin therapy was 6 months. In addition, macrolide therapy could improve the St George Respiratory Questionnaire (SGRQ) total score (P<0.01) but did not achieve the level of clinical significance. The frequency of hospitalizations was not significantly different between the treatment and control groups (P=0.50). Moreover, chronic azithromycin treatment was more likely to increase adverse events (P<0.01).
Conclusion: Prophylactic azithromycin or erythromycin treatment has a significant effect in reducing the frequency of AECOPD in a time-dependent manner. However, long-term macrolide treatment could increase the occurrence of adverse events and macrolide resistance. Future large-scale, well-designed RCTs with extensive follow-up are required to identify patients in whom the benefits outweigh risks.

Keywords: AECOPD, macrolide, azithromycin, adverse events

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