Abstract
Background 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.
Methods In this observational study, inhaled corticosteroid-naïve adults without previously diagnosed lung disease reporting current respiratory symptoms and showing normal pre- and post-bronchodilator spirometry underwent fractional exhaled nitric oxide (FENO) 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 s (PC20) <16 mg·mL−1 and T2 inflammation was defined as sputum eosinophils >2% and/or FENO >25 ppb.
Results Out of 132 subjects (mean±sd age 57.6±14.2 years, 52% female), 47 (36% (95% CI 28–44%)) showed AHR: 20/132 (15% (95% CI 9–21%)) with PC20 <4 mg·mL−1 and 27/132 (21% (95% CI 14–28%)) with PC20 4–15.9 mg·mL−1. Of 130 participants for whom sputum eosinophils, FENO or both results were obtained, 45 (35% (95% CI 27–43%)) had T2 inflammation. 14 participants (11% (95% CI 6–16%)) had sputum eosinophils >2% and PC20 ≥16 mg·mL−1, suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC20 <4 mg·mL−1 (12/20 (60%)) than in those with PC20 4–15.9 mg·mL−1 (8/27 (30%)) or ≥16 mg·mL−1 (25/85 (29%)) (p=0.01).
Conclusions 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.
Abstract
Asthma and eosinophilic bronchitis may remain undiagnosed in a significant number of subjects reporting respiratory symptoms but with normal spirometry; identification of these subjects should be emphasised to improve their management http://bit.ly/3ToeCrv
Footnotes
Author contributions: All authors made substantial contributions to the conception and design of the work and interpretation of data, revised the work critically for important intellectual content, gave final approval of the version submitted for publication, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. L-P. Boulet and M-È. Boulay drafted the manuscript.
Conflict of interest: L-P. Boulet reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi Regeneron for participation in multicentre studies and research projects proposed by the investigator; royalties from UptoDate and Taylor & Francis; lecture fees from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck and Sanofi; is chair of the Global Initiative for Asthma (GINA) board of directors, president of the Global Asthma Organisation (Interasma), holder of the Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health, and member of the Canadian Thoracic Society Respiratory Guidelines Committee. M-È. Boulay has nothing to disclose. A. Côté reports research grants from GlaxoSmithKline; speaker fees from AstraZeneca, GlaxoSmithKline, Valeo and Sanofi; participation in advisory boards for GlaxoSmithKline, AstraZeneca, Sanofi and Valeo. J.M. FitzGerald has attended advisory boards for GlaxoSmithKline, AstraZeneca, Novartis, Sanofi Regeneron and Theravance; received speaker fees/honoraria from AstraZeneca, GlaxoSmithKline, Sanofi Regeneron and Teva; received research funding from the NIH, Canadian Institute for Health Research, AllerGen National Centre for Excellence, GlaxoSmithKline, AstraZeneca, Sanofi Regeneron, Teva and Novartis, all paid directly to his institution; and was a member of the steering committee for the International Severe Asthma Registry, Principal Investigator for the Canadian Severe Asthma Registry, and member of the GINA Science and Executive Committees. C. Bergeron reports consulting fees from Sanofi, AstraZeneca and Takeda; payments for presentations from Grifols, AstraZeneca, Sanofi and Valeo. C. Lemière reports royalties from UptoDate; consulting fees from GlaxoSmithKline, AstraZeneca and Sanofi; payments for presentations from GlaxoSmithKline, AstraZeneca and Sanofi. M.D. Lougheed reports grants from the Manitoba Workers Compensation Board, Ontario Lung Association, Ontario Thoracic Society, Government of Ontario's Innovation Fund, Queen's University, AstraZeneca and GlaxoSmithKline; payments for co-development and co-presentation of a severe asthma preparation course from the Canadian Thoracic Society and for co-development of an accredited CME module on severe asthma from MDBriefcase; participation on advisory board for AstraZeneca; membership on the Canadian Thoracic Society Asthma Clinical Assembly and Canadian Thoracic Society Asthma Clinical Assembly Steering Committee, Health Quality Ontario's Asthma in Adults and Asthma in Children Quality Standard Advisory Committee; is past chair of the Canadian Thoracic Society Asthma Clinical Assembly, is a Canadian Thoracic Society representative on the Lung Association's board of directors and a Canadian Thoracic Society representative to the European Respiratory Society. K.L. Vandemheen has nothing to declare. S.D. Aaron reports payments for lectures from AstraZeneca, GlaxoSmithKline and Sanofi; participation on advisory boards for AstraZeneca, GlaxoSmithKline, Sanofi and Covis.
Support statement: This work was supported by the Ottawa Hospital Foundation through an anonymous donor and a Canadian Institute of Health Research Foundation Grant (FDN grant 154322). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received July 13, 2022.
- Accepted November 1, 2022.
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