{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:15:17Z","timestamp":1789560917239,"version":"build-2803163510"},"reference-count":33,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"name":"Canadian Institute of Health Research Foundation","award":["FDN#154322"],"award-info":[{"award-number":["FDN#154322"]}]},{"DOI":"10.13039\/501100022085","name":"Ottawa Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022085","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2022,11,1]]},"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Subjects without a previous history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness (AHR) in association with underlying eosinophilic (type 2 (T2)) inflammation, consistent with undiagnosed asthma. However, the prevalence of undiagnosed asthma in these subjects is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this observational study, inhaled corticosteroid-na\u00efve adults without previously diagnosed lung disease reporting current respiratory symptoms and showing normal pre- and post-bronchodilator spirometry underwent fractional exhaled nitric oxide (<jats:italic>F<\/jats:italic><jats:sub>ENO<\/jats:sub>) measurement, methacholine challenge testing and induced sputum analysis. AHR was defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1\u2005s (PC<jats:sub>20<\/jats:sub>) &lt;16\u2005mg\u00b7mL<jats:sup>\u22121<\/jats:sup>and T2 inflammation was defined as sputum eosinophils &gt;2% and\/or<jats:italic>F<\/jats:italic><jats:sub>ENO<\/jats:sub>&gt;25\u2005ppb.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Out of 132 subjects (mean\u00b1<jats:sc>sd<\/jats:sc>age 57.6\u00b114.2\u2005years, 52% female), 47 (36% (95% CI 28\u201344%)) showed AHR: 20\/132 (15% (95% CI 9\u201321%)) with PC<jats:sub>20<\/jats:sub>&lt;4\u2005mg\u00b7mL<jats:sup>\u22121<\/jats:sup>and 27\/132 (21% (95% CI 14\u201328%)) with PC<jats:sub>20<\/jats:sub>4\u201315.9\u2005mg\u00b7mL<jats:sup>\u22121<\/jats:sup>. Of 130 participants for whom sputum eosinophils,<jats:italic>F<\/jats:italic><jats:sub>ENO<\/jats:sub>or both results were obtained, 45 (35% (95% CI 27\u201343%)) had T2 inflammation. 14 participants (11% (95% CI 6\u201316%)) had sputum eosinophils &gt;2% and PC<jats:sub>20<\/jats:sub>\u226516\u2005mg\u00b7mL<jats:sup>\u22121<\/jats:sup>, suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC<jats:sub>20<\/jats:sub>&lt;4\u2005mg\u00b7mL<jats:sup>\u22121<\/jats:sup>(12\/20 (60%)) than in those with PC<jats:sub>20<\/jats:sub>4\u201315.9\u2005mg\u00b7mL<jats:sup>\u22121<\/jats:sup>(8\/27 (30%)) or \u226516\u2005mg\u00b7mL<jats:sup>\u22121<\/jats:sup>(25\/85 (29%)) (p=0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Asthma, underlying T2 airway inflammation and eosinophilic bronchitis may remain undiagnosed in a high proportion of symptomatic subjects in the community who have normal pre- and post-bronchodilator spirometry.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.01194-2022","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T16:10:20Z","timestamp":1668701420000},"page":"2201194","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Airway inflammation and hyperresponsiveness in subjects with respiratory symptoms and normal spirometry"],"prefix":"10.1183","volume":"61","author":[{"given":"Louis-Philippe","family":"Boulet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-\u00c8ve","family":"Boulay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9anne","family":"C\u00f4t\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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