{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:49:27Z","timestamp":1790794167978,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Long\u2010term trajectories of asthma with fixed airflow obstruction (FAO) may reveal links to inflammatory endotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We investigated whether measures of asthma control and airway inflammation and remodelling differed by long\u2010term FAO status in moderate\u2010to\u2010severe asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adults enrolled in the Difficult Asthma Study assessed initially using serial Asthma Control Questionnaire (ACQ), exacerbation history, spirometry and sputum cytology over 12\u00a0months, as well as endoscopic bronchial biopsy with airway smooth muscle (ASM) quantification, were revaluated three or more years later with questionnaires and spirometry. FAO was defined as a persistent post\u2010bronchodilator forced expired volume in one second (FEV<jats:sub>1<\/jats:sub>)\u2010to\u2010forced vital capacity ratio below 0.70.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010two participants (mean\u00a0\u00b1\u00a0SD age 48\u00a0\u00b1\u00a011\u00a0years; 50% female; 75% atopic; asthma duration 24\u00a0\u00b1\u00a014\u00a0years) returned for follow\u2010up assessment (median interval 7.9\u00a0years; IQR: 5.4\u20108.8\u00a0years). Compared to participants without FAO (n\u00a0=\u00a028), those with FAO at baseline and long\u2010term follow\u2010up (n\u00a0=\u00a018) had higher baseline sputum neutrophil content and ASM, and a higher exacerbation frequency that persisted at long\u2010term follow\u2010up. Sputum eosinophils, ACQ and long\u2010term FEV<jats:sub>1<\/jats:sub> decline did not differ. Participants with incident FAO at long\u2010term follow\u2010up (n\u00a0=\u00a016) had higher baseline exacerbation frequency, sputum eosinophil content, higher ACQ scores and greater decline in FEV<jats:sub>1<\/jats:sub>, whereas baseline ASM was similar to those without FAO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In moderate\u2010to\u2010severe asthma, long\u2010term FAO is characterized by neutrophilic sputum inflammation and airway remodelling, but FEV<jats:sub>1<\/jats:sub> decline is similar to those without FAO. Long\u2010term incident FAO is preceded by higher exacerbation frequency, higher sputum eosinophil content and significant FEV<jats:sub>1<\/jats:sub> decline.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13714","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T20:20:24Z","timestamp":1595622024000},"page":"39-48","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Asthma and fixed airflow obstruction: Long\u2010term trajectories suggest distinct endotypes"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0619-5799","authenticated-orcid":false,"given":"Benjamin M.","family":"Smith","sequence":"first","affiliation":[{"name":"McGill University Health Centre Research Institute Montreal QC Canada"},{"name":"Meakins\u2010Christie Laboratories of McGill University Montreal QC 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