{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:46:59Z","timestamp":1791380819487,"version":"4.3.3"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006458","name":"Children's Hospital of Philadelphia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006458","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"National Science Foundation Graduate Research Fellowship Program","doi-asserted-by":"publisher","award":["DGE 1845298"],"award-info":[{"award-number":["DGE 1845298"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Pediatric subglottic stenosis (SGS) is characterized by subglottic narrowing which occurs when pathological fibroblasts deposit extracellular matrix that reduces airway patency. Recent clinical observations have suggested that azithromycin may have favorable impacts on SGS reduction while treating airway infections; furthermore, our recent work in mice demonstrated that the airway microbiome influences SGS. In this work, we characterize the protective effect of azithromycin as an immunomodulatory and antibacterial therapeutic against subglottic stenosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunomodulatory and antifibrotic effects of azithromycin were assessed on TGF\u2010\u03b21\u2010stimulated airway fibroblasts at 10\u2009\u03bcg\/mL for 5\u2009days. Changes in gene expression were quantified by RT\u2010qPCR and myofibroblast differentiation by \u03b1\u2010SMA immunostaining. Murine airways were pretreated (2\u2010weeks) with intranasal azithromycin before SGS injury by a twisted wire brush. Disease severity and immune response were characterized by histology and immunostaining for immune cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic>, azithromycin treatment of TGF\u2010\u03b21\u2010stimulated fibroblasts exhibited strong reductions in extracellular matrix (<jats:italic>COL1A1, LOX<\/jats:italic>) and myofibroblast\u2010related gene expression (<jats:italic>ACTA2<\/jats:italic>). Notably, there was a significant reduction in pro\u2010fibrotic expression, which was observed with 10\u2009\u03bcg\/mL azithromycin. Immunostaining of fibroblasts for \u03b1\u2010SMA revealed strong reductions in the number of positive\u2010staining cells and the intensity of each positive cell. <jats:italic>In vivo<\/jats:italic>, azithromycin exhibited a significant decrease in lamina propria thickness indicative of reduced stenosis with associated changes in T\u2010cell infiltration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, we show azithromycin prevents pro\u2010fibrotic gene expression and myofibroblast differentiation and can help protect mice from developing SGS. This introduces azithromycin as a potential treatment for SGS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 2024<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.31754","type":"journal-article","created":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T12:28:31Z","timestamp":1726316911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Azithromycin Prevents Subglottic Stenosis in Mice"],"prefix":"10.1002","author":[{"given":"Daniel D.","family":"Ghaderi","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8871-8265","authenticated-orcid":false,"given":"Matthew R.","family":"Aronson","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Otolaryngology, Department of Surgery Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Otolaryngology, Department of Surgery Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra S.","family":"McDaid","sequence":"additional","affiliation":[{"name":"Department of Veterinary Resources Children's Hospital of Philadelphia  Philadelphia 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