Louis-Philippe Boulet, Marie-Ève Boulay, Andréanne Côté, J. Mark FitzGerald, Céline Bergeron, Catherine Lemière, M. Diane Lougheed, Katherine L. Vandemheen, Shawn D. Aaron
European Respiratory Journal 2022; DOI: 10.1183/13993003.01194-2022

Abstract

Background Subjects without a previous history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness in association with underlying eosinophilic (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 FeNO measurement, methacholine challenge test, and induced sputum analysis. Airway hyperresponsiveness was defined as a provocative concentration of methacholine inducing a 20% fall in forced expiratory volume in one second (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 age±sd: 57.6±14.2 years, 52% women), 47 (36%; 95%CI: 28%-44%) showed airway hyperresponsiveness; 20 (15%; 9%-21%) with PC₂₀ <4 mg·mL⁻¹ and 27 (21%; 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%; 27%-43%) had T2 inflammation. Fourteen participants (11%; 6%-16%) had sputum eosinophils >2% and a PC₂₀ ≥16 mg·mL⁻¹, suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with a PC₂₀ <4 mg·mL⁻¹ (60%) than in those with a PC₂₀ 4-16 mg·mL⁻¹ (30%) or PC₂₀ >16 mg·mL⁻¹ ((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.