{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:07:23Z","timestamp":1789470443483,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Laryngeal stenosis is a fibroinflammatory disease of dysregulated wound healing and excessive collagen deposition lacking effective pharmacological prophylaxis. Pirfenidone is an antifibrotic agent. We compared topical versus systemic pirfenidone for preventing glottic stenosis in a bleomycin\u2010induced rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty male Wistar rats underwent endoscopic bleomycin\u2010induced glottic and subglottic injury and were randomized to topical pirfenidone (10\u2009mg per application; Days 0, 3, 7, 14), systemic pirfenidone (40\u2009mg\/kg\/day orally, 14\u2009days), or untreated control. After 4\u2009weeks, larynges were harvested for macroscopic stenosis grading by two blinded observers and semi\u2010quantitative (0\u20133) histopathological and immunohistochemical scoring. Groups were compared with Fisher's exact and Kruskal\u2013Wallis tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010five animals (control\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097; systemic\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099; topical\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099) completed the study. Five died (3 control, 1 per treated group; log\u2010rank\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.386). Macroscopic stenosis differed among groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.015), being reduced in systemic (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014) and topical (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010) groups versus control, with no difference between routes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.531). A sensitivity analysis assigning the deaths the worst outcome (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930) gave the same result (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011). Submucosal fibrosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005) and collagen\u20101 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) differed overall; pairwise reductions were significant only for systemic versus control. Epithelial damage, inflammation, TGF\u2010\u03b21, \u03b1\u2010SMA, and CD4 did not differ significantly.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both routes significantly reduced macroscopic glottic stenosis, with no significant difference between them, whereas antifibrotic effects on fibrosis and collagen\u20101 were confined to systemic administration. Topical pirfenidone warrants further study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>N\/A (basic science\/preclinical animal study).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.70932","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:56:26Z","timestamp":1789469786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pirfenidone for Glottic Stenosis: Topical Versus Systemic Routes in a Bleomycin Rat Model"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3576-0953","authenticated-orcid":false,"given":"Serap Sahin","family":"Onder","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Acibadem University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1345-2503","authenticated-orcid":false,"given":"Begum","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Health Sciences, Kartal Training and Research Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kutay","family":"Mengi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Health Sciences, Kartal Training and Research Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asiye Isin Dogan","family":"Ekici","sequence":"additional","affiliation":[{"name":"Department of Pathology Acibadem University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Surmeli","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Acibadem University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Asli Sahin","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Health Sciences, Kartal Training and Research Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24956"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.23771"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.30908"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-024-09004-1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24410"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115995"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.27079"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052421"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599817706930"},{"issue":"8","key":"e_1_2_10_11_1","first-page":"E2545","article-title":"M2 Macrophages Promote Collagen 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