{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T09:24:36Z","timestamp":1787304276039,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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>Background: Childhood asthma is clinically heterogeneous, yet simple clinical approaches for describing concurrent disease burden are limited. We tested whether a two-axis phenotype matrix\u2014built from early-onset and\/or high-burden wheeze and atopic load\u2014is associated cross-sectionally with treatment-defined severity and control in school-aged children with asthma. This exploratory, unvalidated classification requires prospective external validation before clinical use. Methods: In a two-center retrospective cross-sectional study, 337 children aged 6\u201312 years with physician-confirmed asthma were classified into four clinical strata (low-burden, familial\/atopic-dominant, wheeze-dominant, atopic-wheezing). The primary outcome was moderate-to-severe asthma, defined by controller treatment step and deliberately independent of acute events. Variables independently associated with the outcomes were identified using multivariable logistic regression with prespecified sensitivity analyses; trends across ordered wheezing-onset categories were assessed using the Cochran\u2013Armitage trend test, adjusted associations were confirmed by likelihood-ratio tests, and secondary outcomes were false-discovery-rate corrected. Results: The atopic-wheezing stratum was the largest group (140\/337, 41.5%) and carried the highest burden: moderate-to-severe asthma 49.3% vs. 17.4% in low-burden and uncontrolled asthma 42.1% vs. 13.0% (both q &lt; 0.01). Adverse outcomes were generally more frequent with earlier wheezing onset (moderate-to-severe asthma 26.9% to 57.9% from no early wheeze to onset \u2264 12 months; p for trend &lt;0.001). After adjustment, the atopic-wheezing stratum had the largest adjusted odds ratios for both moderate-to-severe asthma (aOR 4.49, 95% CI 1.91\u201310.54) and uncontrolled asthma (aOR 4.78, 95% CI 1.85\u201312.35), and remained significant across all sensitivity analyses. Passive smoke exposure was independently associated with uncontrolled asthma (aOR 1.86, 95% CI 1.13\u20133.05) but not severity. The FEV1\/FVC z-score differed significantly across strata and was lowest in the atopic-wheezing group (median z-score \u22121.28 vs. +0.10 in low-burden; p &lt; 0.001). Conclusions: The co-occurrence of high atopic load with early-onset or high-burden wheezing defined the clinical stratum with the highest observed treatment requirement and poorest control, using only routine history and standard allergy work-up. Passive smoke exposure was independently associated with uncontrolled asthma.<\/jats:p>","DOI":"10.3390\/jcm15166459","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"6459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early-Life Wheezing and Atopic Burden Are Associated with Treatment-Defined Asthma Severity and Control in School-Age Children: A Two-Center Cross-Sectional Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9416-9058","authenticated-orcid":false,"given":"Mehmet \u015eirin","family":"Kaya","sequence":"first","affiliation":[{"name":"Department of Pediatric Immunology and Allergy, \u015eanl\u0131urfa Training and Research Hospital, \u015eanl\u0131urfa 63040, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2667-0291","authenticated-orcid":false,"given":"Asena P\u0131nar","family":"Sefer","sequence":"additional","affiliation":[{"name":"School of Medicine, Department of Pediatrics, Division of Allergy and Immunology, Recep Tayyip Erdo\u011fan University, Rize 53200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1382-2906","authenticated-orcid":false,"given":"S\u00fcmeyye","family":"Baysal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology and Allergy, \u015eanl\u0131urfa Training and Research Hospital, \u015eanl\u0131urfa 63040, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5738-4979","authenticated-orcid":false,"given":"Serdar","family":"G\u00f6kta\u015f","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology and Allergy, SB\u00dc Van Training and Research Hospital, Van 65000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-8630","authenticated-orcid":false,"given":"Burcu","family":"Koluk\u0131sa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology and Allergy, SB\u00dc Van Training and Research Hospital, Van 65000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1056\/NEJM199501193320301","article-title":"Asthma and wheezing in the first six years of life","volume":"332","author":"Martinez","year":"1995","journal-title":"N. 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