Within-breath differences in respiratory system resistance (Rrs) during tidal breathing have been reported in patients with asthma1. In patients with severe asthma, our objective was to better understand within-breath differences in Rrs, their response to bronchodilator therapy, and their relationship to asthma control and ventilation heterogeneity. Therefore, we performed respiratory oscillometry (RO) to estimate total, central and peripheral airways resistance during inspiration and expiration in severe asthma subjects before and after bronchodilator.
Healthy (n=9) and severe asthma subjects (n=21) performed RO and 129Xe MRI during a single visit. Al assessments were performed pre- and post-bronchodilator by severe asthma subjects, whom also completed the Asthma Control Questionnaire (ACQ-5). RO was performed according to guidelines2 (tremoFlo C-100, Thorasys Thoracic Medical Systems Inc., Canada) to obtain inspiratory and expiratory Rrs at 5Hz (Rrs5Hz), 19Hz (Rrs19Hz) and the frequency dependence of resistance (Rrs5-19Hz). Ventilation heterogeneity was quantified using the 129Xe MRI ventilation-defect-percent (VDP)3. ANOVA and paired t-tests were performed to evaluate within-group differences and unpaired t-tests for between-group differences. Relationships were evaluated using Spearman correlations.
Figure 1 shows Rrs5Hz (A), Rrs19Hz (B) and Rrs5-19Hz (C) during inspiration and expiration for healthy (6F/3M, age 42±13years, BMI=25±6kg/m2, FEV1=99±12%pred) and severe asthma subjects (13F/8M, age 51±12years, BMI=29±5kg/m2, FEV1=54±17%pred, ACQ-5=2.7±1.3, 7 on biologics, 11 prednisone dependent). In healthy subjects, Rrs5Hz, Rrs19Hz and Rrs5-19Hz were not different during inspiration and expiration. However, severe asthma subjects’ Rrs5Hz was greater during expiration than inspiration both pre- (p=0.01) and post-bronchodilator (p=0.0006). Pre-bronchodilator, Rrs19Hz was lower during expiration than inspiration (p<0.0001), whereas Rrs5-19Hz was greater during expiration than inspiration (p=0.0006). Inspiratory, expiratory, and the withinbreath differences in Rrs19Hz and Rrs5-19Hz decreased post-bronchodilator. Despite bronchodilator therapy, Rrs5-19Hz remained greater during expiration than inspiration (p<0.0001), but there was no longer a within-breath difference in Rrs19Hz. Within-breath differences in Rrs19Hz were correlated with 129Xe MRI VDP pre- (r=0.71, p=0.003) and postbronchodilator (r=0.51, p=0.04). Only pre-bronchodilator Rrs5-19Hz during expiration was correlated with ACQ-5 (r=0.45, p=0.047).
Central and peripheral airways resistance as estimated by Rrs19Hz and Rrs5-19Hz, respectively, differ during inspiration and expiration in severe asthma, but not healthy subjects. While within-breath differences in both Rrs19Hz and Rrs5-19Hz were reduced following bronchodilator, Rrs5-19Hz remained greater during expiration. Future work will determine if intraluminal obstruction by mucus and/or cels contributes to these differences and their clinical relevance. 1Paredi P et al. Thorax 2010;65(3):263-7; 2King GG et al. ERJ 2020;55:1900753; 3Svenningsen S et al. JMRI 2013;38(6):1521-30.