{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:22:49Z","timestamp":1792812169787,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":2397,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Pooling data from multiple cohorts and extending the time frame across childhood should minimize study-specific effects, enabling better characterization of childhood wheezing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To analyze wheezing patterns from early childhood to adolescence using combined data from five birth cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used latent class analysis to derive wheeze phenotypes among 7,719 participants from five birth cohorts with complete report of wheeze at five time periods. We tested the associations of derived phenotypes with late asthma outcomes and lung function, and investigated the uncertainty in phenotype assignment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified five phenotypes: never\/infrequent wheeze (52.1%), early onset preschool remitting (23.9%), early onset midchildhood remitting (9%), persistent (7.9%), and late-onset wheeze (7.1%). Compared with the never\/infrequent wheeze, all phenotypes had higher odds of asthma and lower forced expiratory volume in 1 second and forced expiratory volume in 1 second\/forced vital capacity in adolescence. The association with asthma was strongest for persistent wheeze (adjusted odds ratio, 56.54; 95% confidence interval, 43.75\u201373.06). We observed considerable within-class heterogeneity at the individual level, with 913 (12%) children having low membership probability (&amp;lt;0.60) of any phenotype. Class membership certainty was highest in persistent and never\/infrequent, and lowest in late-onset wheeze (with 51% of participants having membership probabilities &amp;lt;0.80). Individual wheezing patterns were particularly heterogeneous in late-onset wheeze, whereas many children assigned to early onset preschool remitting class reported wheezing at later time points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>All wheeze phenotypes had significantly diminished lung function in school-age children, suggesting that the notion that early life episodic wheeze has a benign prognosis may not be true for a proportion of transient wheezers. We observed considerable within-phenotype heterogeneity in individual wheezing patterns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.201811-837oc","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T15:58:29Z","timestamp":1553011109000},"page":"868-876","source":"Crossref","is-referenced-by-count":105,"title":["Distinguishing Wheezing Phenotypes from Infancy to Adolescence. A Pooled Analysis of Five Birth Cohorts"],"prefix":"10.1093","volume":"16","author":[{"given":"Ceyda","family":"Oksel","sequence":"first","affiliation":[{"name":"Department of Paediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Granell","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Fontanella","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Simpson","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-5060","authenticated-orcid":false,"given":"Steve","family":"Turner","sequence":"additional","affiliation":[{"name":"Child Health, University of Aberdeen, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Devereux","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Hasan","family":"Arshad","sequence":"additional","affiliation":[{"name":"David Hide Asthma and Allergy Research Centre, Isle of Wight, United Kingdom"},{"name":"Respiratory Biomedical Research Unit, University Hospitals Southampton NHS Foundation Trust, Southampton, United Kingdom and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare S.","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Roberts","sequence":"additional","affiliation":[{"name":"David Hide Asthma and Allergy Research Centre, Isle of Wight, United Kingdom"},{"name":"Respiratory Biomedical Research Unit, University Hospitals Southampton NHS Foundation Trust, Southampton, United Kingdom and"},{"name":"Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Holloway","sequence":"additional","affiliation":[{"name":"David Hide Asthma and Allergy Research Centre, Isle of Wight, United Kingdom"},{"name":"Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cullinan","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Henderson","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Custovic","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2026012203383941100_bib1","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 Engl J Med"},{"key":"2026012203383941100_bib2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jaci.2013.05.041","article-title":"Joint modeling of parentally reported and physician-confirmed wheeze identifies children with persistent troublesome wheezing","volume":"132","author":"Belgrave","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"2026012203383941100_bib3","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/j.jaci.2011.02.002","article-title":"Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA","volume":"127","author":"Savenije","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"2026012203383941100_bib4","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1046\/j.1365-2222.2003.01657.x","article-title":"Characterization of wheezing phenotypes in the first 10 years of life","volume":"33","author":"Kurukulaaratchy","year":"2003","journal-title":"Clin Exp Allergy"},{"key":"2026012203383941100_bib5","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1080\/1744666X.2017.1257940","article-title":"Asthma phenotypes in childhood","volume":"13","author":"Deliu","year":"2017","journal-title":"Expert Rev Clin Immunol"},{"key":"2026012203383941100_bib6","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11882-015-0542-0","article-title":"Distinguishing asthma phenotypes using machine learning approaches","volume":"15","author":"Howard","year":"2015","journal-title":"Curr Allergy Asthma Rep"},{"key":"2026012203383941100_bib7","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1164\/rccm.201810-1956CI","article-title":"Childhood asthma: advances using machine learning and mechanistic studies","volume":"199","author":"Saglani","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203383941100_bib8","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/j.jaci.2018.10.059","article-title":"STELAR; Breathing Together investigators. Causes of variability in latent phenotypes of childhood wheeze","volume":"143","author":"Oksel","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"2026012203383941100_bib9","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fped.2018.00258","article-title":"Classification of pediatric asthma: from phenotype discovery to clinical practice","volume":"6","author":"Oksel","year":"2018","journal-title":"Front Pediatr"},{"key":"2026012203383941100_bib10","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4104\/pcrj.2014.00008","article-title":"Wheezing phenotypes in young children: an historical cohort study","volume":"23","author":"Cano-Garcinu\u00f1o","year":"2014","journal-title":"Prim Care Respir J"},{"key":"2026012203383941100_bib11","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1164\/rccm.200406-695OC","article-title":"Wheeze phenotypes and lung function in preschool children","volume":"171","author":"Lowe","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203383941100_bib12","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1136\/thx.2007.093187","article-title":"Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood","volume":"63","author":"Henderson","year":"2008","journal-title":"Thorax"},{"key":"2026012203383941100_bib13","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1164\/rccm.201307-1198OC","article-title":"Clinical and epidemiologic phenotypes of childhood asthma","volume":"189","author":"Depner","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203383941100_bib14","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1183\/09031936.00120810","article-title":"Identifying adult asthma phenotypes using a clustering approach","volume":"38","author":"Siroux","year":"2011","journal-title":"Eur Respir J"},{"key":"2026012203383941100_bib15","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.jaci.2013.08.002","article-title":"Comparison of phenotypes of childhood wheeze and cough in 2 independent cohorts","volume":"132","author":"Spycher","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"2026012203383941100_bib16","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.jaci.2016.01.046","article-title":"Associations of wheezing phenotypes with late asthma outcomes in the Avon Longitudinal Study of Parents and Children: A population-based birth cohort","volume":"138","author":"Granell","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"2026012203383941100_bib17","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1046\/j.1365-3016.2001.00325.x","article-title":"ALSPAC-the Avon longitudinal study of parents and children. I. Study methodology","volume":"15","author":"Golding","year":"2001","journal-title":"Paediatr Perinat Epidemiol"},{"key":"2026012203383941100_bib18","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1183\/09031936.99.13358599","article-title":"Domestic aeroallergen exposures among infants in an English town","volume":"13","author":"Atkinson","year":"1999","journal-title":"Eur Respir J"},{"key":"2026012203383941100_bib19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1053\/rmed.2001.1236","article-title":"The prevalence of asthma and wheezing illnesses amongst 10-year-old schoolchildren","volume":"96","author":"Kurukulaaratchy","year":"2002","journal-title":"Respir Med"},{"key":"2026012203383941100_bib20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1034\/j.1399-3038.13.s.15.3.x","article-title":"The national asthma campaign Manchester asthma and allergy study","volume":"13","author":"Custovic","year":"2002","journal-title":"Pediatr Allergy Immunol"},{"key":"2026012203383941100_bib21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1164\/rccm.200402-220OC","article-title":"Antioxidant intake in pregnancy in relation to wheeze and eczema in the first two years of life","volume":"171","author":"Martindale","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203383941100_bib22","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1586\/1744666X.2013.836450","article-title":"Characterizing wheeze phenotypes to identify endotypes of childhood asthma, and the implications for future management","volume":"9","author":"Belgrave","year":"2013","journal-title":"Expert Rev Clin Immunol"},{"key":"2026012203383941100_bib23","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1183\/13993003.00718-2015","article-title":"Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence","volume":"47","author":"Duijts","year":"2016","journal-title":"Eur Respir J"},{"key":"2026012203383941100_bib24","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1164\/rccm.200504-525OC","article-title":"Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence","volume":"172","author":"Morgan","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203383941100_bib25","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1093\/ije\/30.6.1473","article-title":"Risk factor associations with wheezing patterns in children followed longitudinally from birth to 3 1\/2 years","volume":"30","author":"Sherriff","year":"2001","journal-title":"Int J Epidemiol"},{"key":"2026012203383941100_bib26","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/j.1365-2222.2012.04010.x","article-title":"Childhood wheezing phenotypes and FeNO in atopic children at age 8","volume":"42","author":"van der Valk","year":"2012","journal-title":"Clin Exp Allergy"},{"key":"2026012203383941100_bib27","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1411532","article-title":"Lung-function trajectories leading to chronic obstructive pulmonary disease","volume":"373","author":"Lange","year":"2015","journal-title":"N Engl J Med"},{"key":"2026012203383941100_bib28","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1164\/rccm.201608-1561LE","article-title":"Low lung function in young adult life is associated with early mortality","volume":"195","author":"Vasquez","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203383941100_bib29","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1164\/rccm.201604-0753OC","article-title":"A distinct low lung function trajectory from childhood to the fourth decade of life","volume":"194","author":"Berry","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203383941100_bib30","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S2213-2600(18)30100-0","article-title":"Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life","volume":"6","author":"Bui","year":"2018","journal-title":"Lancet Respir Med"},{"key":"2026012203383941100_bib31","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/S2213-2600(18)30099-7","article-title":"Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies","volume":"6","author":"Belgrave","year":"2018","journal-title":"Lancet Respir Med"}],"container-title":["Annals of the American Thoracic Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/16\/7\/868\/66386162\/annalsats_16_7_868.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/16\/7\/868\/66386162\/annalsats_16_7_868.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:42:17Z","timestamp":1769071337000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/annalsats\/article\/16\/7\/868\/8423955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7,1]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1513\/annalsats.201811-837oc","relation":{},"ISSN":["2329-6933","2325-6621"],"issn-type":[{"value":"2329-6933","type":"print"},{"value":"2325-6621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2019,7,1]]}}}