Ventilation heterogeneity and oscillometry predict asthma control improvement following step‐up inhaled therapy in uncontrolled asthma
Francesca Tang, Sandra Rutting, Catherine Farrow, Katrina O. Tonga, Joanna C. Watts, Jessica R. Dame‐Carrol, Amy Bertolin, Gregory G. King, Cindy Thamrin, David G. Chapman
Abstract
ABSTRACT Background and objective Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple‐breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high‐dose ICS/LABA treatment. Methods A total of 19 subjects (14 females, mean age: 29.9 ± 13.6 years) with uncontrolled asthma, as defined by an ACQ5 > 1.5, taking 500 μg/day fluticasone equivalent or less, underwent spirometry, plethysmography, fractional exhaled FeNO, forced oscillatory resistance (Rrs 5Hz ) and reactance (Xrs 5Hz ), and indices of MBNW ventilation heterogeneity (lung clearance index (LCI), diffusion‐convection‐dependent (Sacin) and convection‐dependent (Scond)). Measurements were made before and after 8 weeks of treatment with fluticasone/formoterol combination inhaler 250/10 μg, 2 puffs twice daily. Results Treatment improved ACQ5 ( P = 0.0002), FEV 1 ( P = 0.02), FVC ( P = 0.04), FeNO ( P = 0.0008), Xrs 5Hz ( P = 0.01), LCI ( P = 0.0002), Sacin ( P = 0.006) and Scond ( P = 0.01). At baseline, ACQ5 correlated with Xrs 5Hz (r s = 0.52, P = 0.03) and Rrs 5Hz (r s = 0.55, P = 0.02). The improvement in ACQ5 was predicted by more abnormal baseline LCI ( P = 0.03), Scond ( P = 0.02) and Rrs 5Hz ( P = 0.006). Baseline Scond was the best predictor of a clinically meaningful improvement in asthma control (ΔACQ > 0.5, ROC‐AUC = 0.91, P = 0.007). Conclusion Step‐up to high‐dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs 5Hz and MBNW. Baseline MBNW and FOT parameters correlated with the improvement in symptoms and may predict a positive response to up‐titration in uncontrolled asthmatic patients.