{"title":"Efficacy and safety of long-term macrolide therapy for non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis","authors":"Natsuki Nakagawa , Masashi Ito , Takanori Asakura , Nobuyuki Horita , Yasushi Obase , Hiroshi Mukae","doi":"10.1016/j.resinv.2024.09.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Long-term macrolide therapy for non-cystic fibrosis bronchiectasis (NCFB) can play a significant role. However, such data are insufficient regarding the efficacy against severe exacerbation and adverse effects, including the emergence of macrolide-resistant pathogens and prolonged macrolide use beyond 1 year.</div></div><div><h3>Methods</h3><div>Randomized controlled trials (RCTs) and prospective observational studies comparing the efficacy and safety of macrolides and placebo in adult patients with NCFB were screened on April 10, 2024. The primary outcome was severe exacerbation frequency.</div></div><div><h3>Results</h3><div>Ten RCTs ≤1 year study durations were included. Most studies mainly included patients with a history of >2 exacerbations. Macrolides had a tendency to reduce the frequency of severe exacerbations compared with placebo (odds ratio = 0.54, 95% confidence interval (CI) = 0.25–1.18). Macrolides significantly reduced the frequency of exacerbations (rate ratio = 0.58, 95% CI = 0.48–0.69), prolonged the time to first exacerbation (rate ratio = 0.41, 95% CI = 0.30–0.55), improved the changes in SGRQ scores [mean difference (MD) = -3.99, 95% CI = −4.63–3.44] and percent predicted forced expiratory volume in 1 s (MD = −2.30, 95% CI = 0.26–4.33), and reduced sputum volume (gram) (MD = −7.44, 95% CI = −9.15–5.74). Additionally, macrolides did not increase drug-related adverse events leading to discontinuation. Qualitative SR of pathogens indicated macrolides might increase the number of macrolide-resistant oropharyngeal and sputum pathogens and the emergence of <em>Pseudomonas aeruginosa</em>.</div></div><div><h3>Conclusions</h3><div>Our results support macrolide therapy for patients with NCFB. Studies with an observation period of >1 year or those focusing on patients with/without a minimal exacerbation history are required to determine the long-term effects on patients with NCFB.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1079-1087"},"PeriodicalIF":2.4000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory investigation","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212534524001436","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Long-term macrolide therapy for non-cystic fibrosis bronchiectasis (NCFB) can play a significant role. However, such data are insufficient regarding the efficacy against severe exacerbation and adverse effects, including the emergence of macrolide-resistant pathogens and prolonged macrolide use beyond 1 year.
Methods
Randomized controlled trials (RCTs) and prospective observational studies comparing the efficacy and safety of macrolides and placebo in adult patients with NCFB were screened on April 10, 2024. The primary outcome was severe exacerbation frequency.
Results
Ten RCTs ≤1 year study durations were included. Most studies mainly included patients with a history of >2 exacerbations. Macrolides had a tendency to reduce the frequency of severe exacerbations compared with placebo (odds ratio = 0.54, 95% confidence interval (CI) = 0.25–1.18). Macrolides significantly reduced the frequency of exacerbations (rate ratio = 0.58, 95% CI = 0.48–0.69), prolonged the time to first exacerbation (rate ratio = 0.41, 95% CI = 0.30–0.55), improved the changes in SGRQ scores [mean difference (MD) = -3.99, 95% CI = −4.63–3.44] and percent predicted forced expiratory volume in 1 s (MD = −2.30, 95% CI = 0.26–4.33), and reduced sputum volume (gram) (MD = −7.44, 95% CI = −9.15–5.74). Additionally, macrolides did not increase drug-related adverse events leading to discontinuation. Qualitative SR of pathogens indicated macrolides might increase the number of macrolide-resistant oropharyngeal and sputum pathogens and the emergence of Pseudomonas aeruginosa.
Conclusions
Our results support macrolide therapy for patients with NCFB. Studies with an observation period of >1 year or those focusing on patients with/without a minimal exacerbation history are required to determine the long-term effects on patients with NCFB.