{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:03:14Z","timestamp":1791421394882,"version":"4.3.3"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p &lt; 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were \u22120.50 (95% CI: \u22120.81, \u22120.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I2 = 81%). Although a significant improvement in St George\u2019s Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of \u22124.42 (95% CI: \u22129.0, 0.16; p = 0.06; I2 = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo.<\/jats:p>","DOI":"10.3390\/diseases11040152","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T03:33:51Z","timestamp":1698377631000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Effectiveness and Safety of Long-Term Macrolide Therapy for COPD in Stable Status: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8386-3052","authenticated-orcid":false,"given":"Kazunori","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto 861-4193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nara Medical University, Nara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3074-2235","authenticated-orcid":false,"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Yokohama City University Hospital, Yokohama 236-0004, Japan"},{"name":"Department of Respiratory Medicine, Yokohama Minami Kyousai Hospital, Yokohama 236-0037, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Somekawa","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Yokohama City University Hospital, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0214-1571","authenticated-orcid":false,"given":"Fumihiro","family":"Kashizaki","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Yokohama Minami Kyousai Hospital, Yokohama 236-0037, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harumi","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Yokohama Minami Kyousai Hospital, Yokohama 236-0037, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Yokohama Minami Kyousai Hospital, Yokohama 236-0037, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Horita","sequence":"additional","affiliation":[{"name":"Chemotherapy Center, Yokohama City University Hospital, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Yokohama City University Hospital, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7452-9191","authenticated-orcid":false,"given":"Shigeo","family":"Muro","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nara Medical University, Nara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Yokohama City University Hospital, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref_1","unstructured":"GBD Chronic Respiratory Disease Collaborators (2020). 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Care Med."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/11\/4\/152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:12:45Z","timestamp":1760130765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/11\/4\/152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,27]]},"references-count":56,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["diseases11040152"],"URL":"https:\/\/doi.org\/10.3390\/diseases11040152","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,27]]}}}