{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:59:35Z","timestamp":1792364375947,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical & Translational Med"],"published-print":{"date-parts":[[2022,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Exacerbation\u2010prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U\u2010BIOPRED cohort.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We compared features of FE (\u22652 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat \u22652 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 317 patients, 62.4% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short\u2010acting beta\u2010agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated with eczema, short\u2010acting beta\u2010agonist use and asthma control index. CEA cell adhesion molecule 5 (\n CEACAM5)<\/jats:italic>\n was the only differentially expressed transcript in bronchial biopsies between PE and IE. There were no differentially expressed genes in the other four compartments. There were higher expression scores for type 2, T\u2010helper type\u201017 and type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The FE group and its PFE subgroup are associated with poor asthma control while expressing higher type 1 and type 2 activation pathways compared to IE and PIE, respectively.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ctm2.816","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T23:31:52Z","timestamp":1651015912000},"source":"Crossref","is-referenced-by-count":23,"title":["Clinical and transcriptomic features of persistent exacerbation\u2010prone severe asthma in U\u2010BIOPRED cohort"],"prefix":"10.1002","volume":"12","author":[{"given":"Uruj","family":"Hoda","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute Imperial College London, and Biomedical Research Unit Royal Brompton and Harefield NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stelios","family":"Pavlidis","sequence":"additional","affiliation":[{"name":"Department of Computing & Data Science Institute Imperial College London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna T.","family":"Bansal","sequence":"additional","affiliation":[{"name":"Acclarogen Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute Imperial College London, and Biomedical Research Unit Royal Brompton and Harefield NHS Trust London UK"},{"name":"Research Centre for Allergy and Clinical Immunology Asahi General 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