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

Although current guidelines for asthma diagnosis and management have proven relatively successful, many asthmatics continue to experience poor asthma control and exacerbations. This may be due to a failure to recognize that mild, well-controlled asthmatics 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 (IOS), is associated with prior exacerbations in the GINA defined mild, well-controlled asthma phenotype. In 170 adults with mild, well-controlled asthma we determined the presence of SAD by IOS metrics of peripheral airway resistance between 5Hz and 20Hz (Rrs5 - Rrs20) and peripheral airway reactance as area under the reactance curve (AX) at cut points of 0.10 kPa/L/s and 1.0 kPa/L respectively. We also assessed the association between 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. SAD was present in 27.6% and prior exacerbations in 34.1% of the population. Exacerbations were greater in those with SAD (82.9% versus 15.4%, p < .001), lower in those receiving extra fine ICS (27.7% versus 55.3% p< .05). SAD and extra fine ICS were both independently associated with prior exacerbations, with SAD increasing and extra fine ICS decreasing exacerbation risk. In the mild, well-controlled asthmatic, SAD and prior exacerbations are common. SAD and extra fine ICS are independently associated with increased or decreased exacerbations respectively. Detecting SAD could result in early extra fine ICS intervention potentially preventing future exacerbations in this phenotype.