{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:10:17Z","timestamp":1788786617788,"version":"build-2803163510"},"reference-count":159,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Nasal polyposis is a multifactorial disorder arising from complex interactions among cellular, molecular, and inflammatory mechanisms. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and other ion channels are essential for epithelial ion transport, mucosal hydration, and barrier integrity in the nasal airway. Prostaglandin E2 (PGE2) acts not only as an inflammatory mediator but also as a regulator of ion exchange through CFTR-dependent and CFTR-independent pathways. Ionocytes, specialized epithelial cells that regulate ion balance and fluid secretion in the respiratory tract, are closely associated with CFTR function. Both eosinophilic and non-eosinophilic inflammation may alter ionocyte abundance and function, thereby reducing normal CFTR activity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also characterized by diminished PGE2 production. The I3PGE2 hypothesis proposes that CRSwNP results from the combined effects of ion channel dysfunction, persistent inflammation, altered ionocyte number and function, and impaired PGE2 synthesis. Together, these abnormalities disrupt nasal physiology and promote polyp formation. We hypothesize that corticosteroids and biologic therapies may improve CRSwNP by reducing inflammation, restoring ion channel activity, improving ionocyte function, and recovering PGE2 production. These effects enhance hydration and mucociliary clearance, limit mucus accumulation, restore epithelial homeostasis and mucosal host defense, and ultimately contribute to the reduction or resolution of nasal polyps.<\/jats:p>","DOI":"10.3390\/jcm15176908","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"6908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Understanding Nasal Polyposis: The Roles of Ion Channels, Inflammation, Ionocytes, and Prostaglandin E2\u2014The I3PGE2 Hypothesis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7400-4993","authenticated-orcid":false,"given":"C\u00e9sar","family":"Picado","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Roca-Ferrer","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaciones en Red de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jaip.2016.04.012","article-title":"Chronic Rhinosinusitis with Nasal Polyps","volume":"4","author":"Stevens","year":"2016","journal-title":"J. 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