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

Abstract

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. 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. 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. 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. 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.