Small Airway Dysfunction Is an Independent Exacerbation Risk Biomarker in the Mild, Well-Controlled Patient With Asthma: A Frequently Unrecognized High-Risk Phenotype

Background: Although current guidelines for asthma diagnosis and management have proven relatively successful, many patients with asthma continue to experience poor asthma control and exacerbations. This may be due to a failure to recognize that patients with mild, well-controlled asthma commonly have small airway dysfunction (SAD), which is associated with a significant exacerbation risk. Objective: We aimed to better characterize how well SAD, determined by impulse oscillometry, is associated with prior exacerbations in the Global Initiative for Asthma–defined mild, well-controlled asthma phenotype. Methods: In 170 adults with mild, well-controlled asthma, we determined the presence of SAD by impulse oscillometry metrics of peripheral airway resistance between 5 and 20 Hz and peripheral airway reactance as the area under the reactance curve at cut points of 0.10 kPa/L per second and 1.0 kPa/L, respectively. We also assessed the associations among SAD, FEV1, FeNO, blood eosinophilia, and extra-fine inhaled corticosteroids (ICS) with prior exacerbations. A multivariate analysis evaluated which variables were independently associated with prior exacerbations. Results: Small airway dysfunction was present in 27.6% of the population, and prior exacerbations in 34.1%. Exacerbations were greater in those with SAD (82.9% vs 15.4%; P < .001) and lower in those receiving extra-fine ICS (27.7% vs 55.3%; P < .05). Small airway dysfunction and extra-fine ICS were both independently associated with prior exacerbations; SAD increased and extra-fine ICS decreased exacerbation risk. Conclusions: In the patient with mild, well-controlled asthma, SAD and prior exacerbations are common. Small airway dysfunction and extra-fine ICS are respectively independently associated with increased or decreased exacerbations. Detecting SAD could result in early extra-fine ICS intervention, potentially preventing future exacerbations in this phenotype.