{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:30:29Z","timestamp":1790803829762,"version":"4.1.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"vor","delay-in-days":1422,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S025340\/1"],"award-info":[{"award-number":["MR\/S025340\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["G0601361"],"award-info":[{"award-number":["G0601361"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K002449\/1"],"award-info":[{"award-number":["MR\/K002449\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S025340\/1"],"award-info":[{"award-number":["MR\/S025340\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["G0601361"],"award-info":[{"award-number":["G0601361"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K002449\/1"],"award-info":[{"award-number":["MR\/K002449\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Longitudinal modeling of current wheezing identified similar phenotypes, but their characteristics often differ between studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We propose that a more comprehensive description of wheeze may better describe trajectories than binary information on the presence\/absence of wheezing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We derived six multidimensional variables of wheezing spells from birth to adolescence (including duration, temporal sequencing, and the extent of persistence\/recurrence). We applied partition-around-medoids clustering on these variables to derive phenotypes in five birth cohorts. We investigated within- and between-phenotype differences compared with binary latent class analysis models and ascertained associations of these phenotypes with asthma and lung function and with polymorphisms in asthma loci 17q12\u201321 and CDHR3(cadherin-related family member 3).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Analysis among 7,719 participants with complete data identified five spell-based wheeze phenotypes with a high degree of certainty: never (54.1%), early-transient (ETW) (23.7%), late-onset (LOW) (6.9%), persistent (PEW) (8.3%), and a novel phenotype, intermittent wheeze (INT) (6.9%). FEV1\/FVC was lower in PEW and INT compared with ETW and LOW and declined from age 8 years to adulthood in INT. 17q12\u201321 and CDHR3polymorphisms were associated with higher odds of PEW and INT, but not ETW or LOW. Latent class analysis- and spell-based phenotypes appeared similar, but within-phenotype individual trajectories and phenotype allocation differed substantially. The spell-based approach was much more robust in dealing with missing data, and the derived clusters were more stable and internally homogeneous.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Modeling of spell variables identified a novel intermittent wheeze phenotype associated with lung function decline to early adulthood. Using multidimensional spell variables may better capture wheeze development and provide a more robust input for phenotype derivation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202108-1821oc","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T14:35:01Z","timestamp":1642689301000},"page":"883-893","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":49,"title":["Modeling Wheezing Spells Identifies Phenotypes with Different Outcomes and Genetic Associates"],"prefix":"10.1093","volume":"205","author":[{"given":"Sadia","family":"Haider","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Granell","sequence":"additional","affiliation":[{"name":"Medical Research Council Integrative Epidemiology Unit, Population Health 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