Bronchodilator Response of TEV/FEV3 and Its Implications in Pediatric Asthma

Abstract

The diagnosis of asthma in children is challenging due to limitations of conventional spirometry, which primarily assesses large airway function and requires considerable patient effort. Terminal expiration volume (TEV)/forced expiratory volume in 3 seconds (FEV3) has been proposed as a new metric that may help assess small airway dysfunction, where TEV represents the volume difference between FEV3 and forced expiratory volume in 1 seconds (FEV1) and reflects terminal expiratory airflow. We aimed to evaluate the bronchodilator response (BDR) of TEV/FEV3 (BDR-TEV/FEV3) as an index reflecting variable small airway obstruction in children. This retrospective study included 1,199 children who underwent both spirometry and bronchial provocation testing for asthma at a tertiary hospital between January 2017 and December 2019. BDR-TEV/FEV3 was compared according to asthma status and severity. The findings were verified using an external validation group (n = 105). We also explored the association between BDR-TEV/FEV3 and established indices of airway inflammation. BDR-TEV/FEV3 was significantly higher in children with asthma than in those without asthma (3.74% vs. 1.81%, P < 0.001) and showed a stepwise increment with asthma severity (P for trend < 0.001). Moreover, BDR-TEV/FEV3 showed a positive correlation with changes in airflow limitation markers, impulse oscillometry parameters, and inflammatory markers such as eosinophil count and fractional exhaled nitric oxide. The change in TEV/FEV3 after bronchodilator inhalation significantly differed between asthmatic and non-asthmatic children and across asthma severity groups. BDR-TEV/FEV3 may be used as a parameter to assess the reversibility of small airway obstruction in children with asthma.