{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:02:03Z","timestamp":1792450923131,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victor Babes University of Medicine and Pharmacy Timisoara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Chronic adenoiditis is a major contributor to persistent middle ear dysfunction (PMED) in children; however, clinical evolution varies considerably despite similar anatomical obstruction. This study aimed to identify inflammatory endotypes of chronic adenoiditis using unsupervised clustering and to evaluate their association with PMED through mechanistic and predictive modeling. Materials and Methods: A retrospective cohort of 236 children (3\u201312 years) with chronic adenoiditis and otitis media with effusion was analyzed. Clinical, endoscopic, audiological, and hematologic inflammatory parameters (eosinophils, NLR, ELR, CRP, IgE) were included. K-means clustering identified inflammatory endotypes. Associations with PMED at six months were evaluated using multivariate logistic regression and mediation analysis. Predictive performance was compared using logistic regression, random forest, and gradient boosting models, with SHAP-based interpretability and decision curve analysis. Results: Three distinct endotypes were identified: eosinophilic (28%), neutrophilic (41%), and fibrotic\u2013obstructive (31%). PMED occurred in 44% of the fibrotic endotype compared with 22% in the eosinophilic group (p &lt; 0.001). In multivariate analysis, the fibrotic endotype independently predicted PMED (OR = 3.48, 95% CI 1.92\u20136.31), alongside PTA &gt; 30 dB (OR = 2.91) and NLR &gt; 3.5 (OR = 2.36). Mediation analysis showed that hearing impairment accounted for 34% of the effect of anatomical obstruction on persistence. Gradient boosting achieved superior discrimination (AUC = 0.90) and demonstrated the highest net clinical benefit. Conclusions: Chronic adenoiditis comprises biologically distinct inflammatory endotypes with differential risk of persistent middle ear dysfunction. Integrating inflammatory profiling with machine learning enhances mechanistic understanding and risk stratification, supporting precision-based management in pediatric otorhinolaryngology.<\/jats:p>","DOI":"10.3390\/medicina62030537","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:12:25Z","timestamp":1773400345000},"page":"537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inflammatory Endotypes of Chronic Adenoiditis and Their Impact on Persistent Middle Ear Dysfunction: A 2-Year Retrospective Translational Study Integrating Clustering and Machine Learning Approaches"],"prefix":"10.3390","volume":"62","author":[{"given":"Diana","family":"Szekely","sequence":"first","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5755-179X","authenticated-orcid":false,"given":"Flavia","family":"Zara","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Patrascu","sequence":"additional","affiliation":[{"name":"Department of Functional Sciences, Victor Babes University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-3060","authenticated-orcid":false,"given":"Cristina Stefania","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Cristina","family":"Barb","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-7636","authenticated-orcid":false,"given":"Dorin","family":"Novacescu","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Discipline of Histology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3410-3870","authenticated-orcid":false,"given":"Alexia","family":"Manole","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Iovanescu","sequence":"additional","affiliation":[{"name":"ENT Department, Victor Babes University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gheorghe","family":"Iovanescu","sequence":"additional","affiliation":[{"name":"ENT Department, Victor Babes University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.5603\/FHC.2012.0082","article-title":"Production of cytokines by mononuclear cells of hypertrophic adenoids in children with otitis media with effusion","volume":"50","author":"Ilendo","year":"2012","journal-title":"Folia Histochem. 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