{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:01:46Z","timestamp":1790431306426,"version":"4.1.0"},"reference-count":26,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T00:00:00Z","timestamp":1611360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009010","name":"Novartis Pharmaceuticals UK Limited","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004628","name":"MedImmune","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004628","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006259","name":"Teva Pharmaceutical Industries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006259","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007560","name":"Chiesi Farmaceutici","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jaci-inpractice.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Allergy and Clinical Immunology: In Practice"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.jaip.2020.12.062","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T02:41:28Z","timestamp":1610937688000},"page":"2691-2701.e1","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"title":["Factors Associated with Frequent Exacerbations in the UK Severe Asthma Registry"],"prefix":"10.1016","volume":"9","author":[{"given":"Freda","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Busby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam G.","family":"Heaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Menzies-Gow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Pfeffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel H.","family":"Mansur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Brightling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Niven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil C.","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekha","family":"Chaudhuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitesh","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Gore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aashish","family":"Vyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Subramanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaip.2020.12.062_bib1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12916-016-0657-8","article-title":"The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases","volume":"14","author":"Mukherjee","year":"2016","journal-title":"BMC Med"},{"key":"10.1016\/j.jaip.2020.12.062_bib2","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1136\/thx.2010.137414","article-title":"Refractory asthma in the UK: cross-sectional findings from a UK multicentre registry","volume":"65","author":"Heaney","year":"2010","journal-title":"Thorax"},{"key":"10.1016\/j.jaip.2020.12.062_bib3","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1136\/thoraxjnl-2013-204114","article-title":"The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry","volume":"70","author":"O'Neill","year":"2015","journal-title":"Thorax"},{"key":"10.1016\/j.jaip.2020.12.062_bib4","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1164\/rccm.201505-1003LE","article-title":"Risk factors for frequent severe exacerbations in late-onset eosinophilic asthma","volume":"192","author":"de Groot","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaip.2020.12.062_bib5","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1111\/cea.12762","article-title":"Exacerbation risk in severe asthma is stratified by inflammatory phenotype using longitudinal measures of sputum eosinophils","volume":"46","author":"Walsh","year":"2016","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.jaip.2020.12.062_bib6","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.rmed.2016.08.006","article-title":"Predictors of frequent exacerbations in (ex)smoking and never smoking adults with severe asthma","volume":"118","author":"Westerhof","year":"2016","journal-title":"Respir Med"},{"key":"10.1016\/j.jaip.2020.12.062_bib7","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1164\/rccm.201602-0419OC","article-title":"Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations","volume":"195","author":"Denlinger","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaip.2020.12.062_bib8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jaip.2013.11.013","article-title":"Clinical burden and predictors of asthma exacerbations in patients on guideline-based steps 4-6 asthma therapy in the TENOR cohort","volume":"2","author":"Calhoun","year":"2014","journal-title":"J\u00a0Allergy Clin Immunol Pract"},{"key":"10.1016\/j.jaip.2020.12.062_bib9","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1183\/09031936.05.00037905","article-title":"Risk factors of frequent exacerbations in difficult-to-treat asthma","volume":"26","author":"ten Brinke","year":"2005","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaip.2020.12.062_bib10","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/cea.12179","article-title":"Frequent exacerbators\u2014a distinct phenotype of severe asthma","volume":"44","author":"Kupczyk","year":"2014","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.jaip.2020.12.062_bib11","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1034\/j.1399-3003.1999.14d29.x","article-title":"Development and validation of a questionnaire to measure asthma control","volume":"14","author":"Juniper","year":"1999","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaip.2020.12.062_bib12","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jaci.2009.11.033","article-title":"Overall asthma control: the relationship between current control and future risk","volume":"125","author":"Bateman","year":"2010","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.jaip.2020.12.062_bib13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jaci.2010.08.042","article-title":"Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation","volume":"127","author":"Meltzer","year":"2011","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.jaip.2020.12.062_bib14","author":"Jackson"},{"key":"10.1016\/j.jaip.2020.12.062_bib15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1183\/09031936.00202013","article-title":"International ERS\/ATS guidelines on definition, evaluation and treatment of severe asthma","volume":"43","author":"Chung","year":"2014","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaip.2020.12.062_bib16","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1164\/rccm.201806-1182OC","article-title":"Remotely monitored therapy and nitric oxide suppression identifies nonadherence in severe asthma","volume":"199","author":"Heaney","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaip.2020.12.062_bib17","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1214\/15-EJS1035","article-title":"Computationally efficient confidence intervals for cross-validated area under the ROC curve estimates","volume":"9","author":"LeDell","year":"2015","journal-title":"Electron J Stat"},{"key":"10.1016\/j.jaip.2020.12.062_bib18","doi-asserted-by":"crossref","first-page":"b2393","DOI":"10.1136\/bmj.b2393","article-title":"Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls","volume":"338","author":"Sterne","year":"2009","journal-title":"BMJ"},{"key":"10.1016\/j.jaip.2020.12.062_bib19","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.jaci.2015.01.028","article-title":"The influence of asthma control on the severity of virus-induced asthma exacerbations","volume":"136","author":"Jackson","year":"2015","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.jaip.2020.12.062_bib20","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.jaci.2014.08.015","article-title":"Development and validation of a novel risk score for asthma exacerbations: the risk score for exacerbations","volume":"135","author":"Bateman","year":"2015","journal-title":"J\u00a0Aallergy Clin Immunol"},{"key":"10.1016\/j.jaip.2020.12.062_bib21","first-page":"1","article-title":"Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice","volume":"9","author":"Price","year":"2016","journal-title":"J\u00a0Asthma Allergy"},{"key":"10.1016\/j.jaip.2020.12.062_bib22","first-page":"PA5468","article-title":"Overlapping biologic exacerbation clusters in asthma and chronic obstructive pulmonary disease have distinct sputum mediator and microbiome profiles","volume":"52","author":"Ghebre","year":"2018","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaip.2020.12.062_bib23","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12890-019-0906-7","article-title":"Severe exacerbations in moderate-to-severe asthmatics are associated with increased pro-inflammatory and type 1 mediators in sputum and serum","volume":"19","author":"Ghebre","year":"2019","journal-title":"BMC Pulm Med"},{"key":"10.1016\/j.jaip.2020.12.062_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/S2213-2600(21)00004-7","article-title":"A\u00a0prospective observational study of the inflammatory profile of Mepolizumab EXacerbations in participants with severe refractory eosinophilic asthma (the MEX study)","author":"McDowell","year":"2021","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.jaip.2020.12.062_bib25","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/thoraxjnl-2018-212709","article-title":"Change in type-2 biomarkers and related cytokines with prednisolone in uncontrolled severe oral corticosteroid dependent asthmatics: an interventional open-label study","volume":"74","author":"Busby","year":"2019","journal-title":"Thorax"},{"key":"10.1016\/j.jaip.2020.12.062_bib26","first-page":"918","article-title":"Targeted routine asthma care in general practice using telephone triage","volume":"55","author":"Gruffydd-Jones","year":"2005","journal-title":"Br J Gen Pract"}],"container-title":["The Journal of Allergy and Clinical Immunology: In Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213219821000544?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213219821000544?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T05:27:53Z","timestamp":1761974873000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213219821000544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["S2213219821000544"],"URL":"https:\/\/doi.org\/10.1016\/j.jaip.2020.12.062","relation":{},"ISSN":["2213-2198"],"issn-type":[{"value":"2213-2198","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Factors Associated with Frequent Exacerbations in the UK Severe Asthma Registry","name":"articletitle","label":"Article Title"},{"value":"The Journal of Allergy and Clinical Immunology: In Practice","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaip.2020.12.062","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.","name":"copyright","label":"Copyright"}]}}