{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:30:41Z","timestamp":1761006641410,"version":"build-2065373602"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Previous in vitro transcriptomic profiling suggests azithromycin exerts its effects in patients with chronic rhinosinusitis (CRS) via modulation of type 1 inflammation and restoration of epithelial barrier function. We wished to verify these postulated effects using in vitro models of epithelial repair and in vivo transcriptional profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Functional effects of azithromycin in CRS were verified using in vitro models of wounding. The mechanism of the effect of azithromycin was assessed in vivo using transcriptomic profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Academic medical center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Effects of azithromycin on the speed of epithelial repair were verified in a wounding model using primary nasal epithelial cells (pNEC) from CRS patients. Nasal brushings collected pre\u2010and posttreatment during a placebo\u2010controlled trial of azithromycin for CRS patients unresponsive to surgery underwent transcriptomic profiling to identify implicated pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Administration of azithromycin improved the wound healing rates in CRS pNECs and prevented the negative effect of <jats:italic>Staphylococcus aureus<\/jats:italic> on epithelial repair. In vivo, response to azithromycin was associated with downregulation in pathways of type 1 inflammation, and upregulation of pathways implicated in the restoration of the cell cycle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Restoration of healthy epithelial function may represent a major mode of action of azithromycin in CRS. In vitro models show enhanced epithelial repair, while in vivo transcriptomics shows downregulation of pathways type 1 inflammation accompanied by upregulation of DNA repair and cell\u2010cycle pathways. The maximal effect in patients with high levels of type 1\u2010enhanced inflammation suggests that azithromycin may represent a novel therapeutic option for surgery\u2010unresponsive CRS patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ohn.355","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T05:49:55Z","timestamp":1682920195000},"page":"1055-1063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Azithromycin Mechanisms of Action in CRS Include Epithelial Barrier Restoration and Type 1 Inflammation Reduction"],"prefix":"10.1002","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3180-3047","authenticated-orcid":false,"given":"Axel E.","family":"Renteria","sequence":"first","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l'Universite\u0301 de Montre\u0301al (CRCHUM)  Montre\u0301al Quebec Canada"},{"name":"De\u0301partement 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