{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:08:01Z","timestamp":1779455281940,"version":"3.53.1"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The airway epithelium plays a central role in host defense, inflammatory signaling, and disease progression across infectious, inflammatory, and genetic respiratory disorders. Human nasal epithelial organoids have emerged as accessible and patient-specific in vitro platforms with increasing translational relevance. This systematic review aimed to critically evaluate the current evidence on nasal epithelial organoid models, focusing on donor characteristics, culture methodologies, differentiation strategies, and translational applications. Methods: A systematic search of PubMed\/MEDLINE, Embase, Scopus, Ovid MEDLINE, and Cochrane Library was conducted for studies published between 1990 and April 2026. The review followed PRISMA guidelines and was structured according to the PICOTS framework. Eligible studies included in vitro experimental investigations using human-derived nasal epithelial organoids in infectious, inflammatory, or precision medicine contexts. Risk of bias was assessed using the QUIN tool. Results: Seventeen studies met the inclusion criteria. Applications clustered into three principal domains: infectious disease modeling, inflammatory and epithelial remodeling research, and cystic fibrosis precision medicine. Most studies employed expandable three-dimensional Matrigel-embedded organoids or organoid-derived air\u2013liquid interface systems. Infection-focused studies demonstrated variant-specific viral replication dynamics and epithelial immune responses, while inflammatory models reproduced disease-associated differentiation and remodeling phenotypes. Cystic fibrosis oriented studies showed that organoid swelling and electrophysiological assays correlate with CFTR functional rescue and, in selected cases, clinical response. Methodological heterogeneity across protocols and outcome reporting precluded quantitative synthesis. Conclusions: Human nasal epithelial organoids represent versatile translational platforms bridging accessible patient-derived tissue and advanced airway disease modeling. Although variability in culture protocols and functional benchmarks limits standardization, these models hold significant promise for mechanistic investigation, therapeutic stratification, and precision medicine applications.<\/jats:p>","DOI":"10.3390\/jcm15114016","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"4016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nasal Epithelial Organoids as Translational Platforms in Inflammatory, Infectious, and Precision Medicine Applications: A Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8717-7121","authenticated-orcid":false,"given":"Veronica","family":"Scocca","sequence":"first","affiliation":[{"name":"Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Lauda","sequence":"additional","affiliation":[{"name":"Gruppo Otologico, Via Giacomo Morigi, 41, 29121 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Nocini","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6479-6130","authenticated-orcid":false,"given":"Giovanni","family":"Dell'Aversana Orabona","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/S2213-2600(21)00164-8","article-title":"Global, Regional, and National Burden of Respiratory Tract Cancers and Associated Risk Factors from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"9","author":"Ebrahimi","year":"2021","journal-title":"Lancet Respir. 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