Small airway dysfunction in asthmatic patients treated with as-needed SABA monotherapy: A perfect storm

Background: Short-acting beta agonist (SABA)-only treatment is associated with poor asthma control and adverse clinical outcomes. The importance of small airway dysfunction (SAD) is increasingly recognized in asthma, but less is known in patients using SABA-only therapy. We aimed to investigate the impact of SAD on asthma control in an unselected cohort of 60 adults with physician-diagnosed intermittent asthma treated with as-needed SABA monotherapy.

Methods: All patients underwent standard spirometry and impulse oscillometry (IOS) at the first visit and were stratified by the presence of SAD defined by IOS (fall in resistance 5-20 Hz [R5-R20]>0.07 kPa × s*L^-1). Univariable and multivariable analyses were used to analyze cross-sectional relationships between clinical variables and SAD.

Results: SAD was present in 73% of the cohort. Compared with patients without SAD, adults with SAD had a higher number of severe exacerbations (65.9% versus 25.0%, p < 0.05), higher use of annual SABA canisters (median (IQR), 3 (1.75-3) versus 1 (1-2), p < 0.001), and significantly less well-controlled asthma (11.7% versus 75.0%, p < 0.001). Spirometry parameters were similar between patients with IOS-defined SAD and those without SAD. The multivariable logistic regression analysis showed that exercise-induced bronchoconstriction symptoms (EIB, odds ratio [OR] 31.18; 95%CI:4.85-365.00) and night awakenings due to asthma (OR 30.30; 95%CI:2.61-1141.00) were independent predictors of SAD, with a high predictive power of the model incorporating these baseline predictors (AUC 0.92).

Conclusions: EIB and nocturnal symptoms are strong predictors of SAD in asthmatic patients using as-needed SABA-monotherapy, helping to distinguish subjects with SAD among patients with asthma when IOS cannot be performed.