Airway inflammation and hyperresponsiveness in subjects with respiratory symptoms and normal spirometry

• Published in: The European respiratory journal Vol. 61; no. 3; p. 2201194
• Main Authors: Boulet, Louis-Philippe, Boulay, Marie-Ève, Côté, Andréanne, FitzGerald, J. Mark, Bergeron, Céline, Lemière, Catherine, Lougheed, M. Diane, Vandemheen, Katherine L., Aaron, Shawn D.
• Format: Journal Article
• Language: English
• Published: England 01.03.2023
• Subjects: Adult; Aged; Asthma - complications; Asthma - diagnosis; Asthma - drug therapy; Bronchial Provocation Tests - methods; Bronchitis - diagnosis; Bronchodilator Agents - therapeutic use; Eosinophils; Female; Forced Expiratory Volume; Humans; Inflammation - diagnosis; Male; Methacholine Chloride; Middle Aged; Nitric Oxide - analysis; Spirometry; Sputum - chemistry
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/13993003.01194-2022

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. 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 ( ) 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 (PC ) <16 mg·mL and T2 inflammation was defined as sputum eosinophils >2% and/or >25 ppb. 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 PC <4 mg·mL and 27/132 (21% (95% CI 14-28%)) with PC 4-15.9 mg·mL . Of 130 participants for whom sputum eosinophils, 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 PC ≥16 mg·mL , suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC <4 mg·mL (12/20 (60%)) than in those with PC 4-15.9 mg·mL (8/27 (30%)) or ≥16 mg·mL (25/85 (29%)) (p=0.01). 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.