TEV/FEV₃ as a coherent metric of small airway dysfunction in childhood asthma

Background: Spirometry is an unrivalled tool for determining asthma and asthma severity. The ratio of forced expiratory volume (FEV) in 1 second (FEV₁) to forced vital capacity (FVC) and the forced expiratory flow between 25% and 75% of FVC (FEF_25-75) are well-known markers of airway obstruction, but they are limited by low reproducibility, particularly in children. In this study, we defined terminal expiration volume (TEV) as FEV in 3 seconds forced expiratory volume in 3 seconds (FEV₃) minus forced expiratory volume in 1 seconds (FEV₁) and investigate whether TEV/FEV₃ can function as a coherent marker to compensate for existing markers. Methods: This retrospective study comprised 980 children ages ≤ 18 years who underwent spirometry and the bronchial provocation testing. TEV/FEV₃ was compared with regard to asthma presence and severity. The findings were verified with an external validation group (n = 105). Results: FEV₃ was obtained in 837 children (85.4%). TEV/FEV₃ was significantly higher in patients with asthma than in patients who did not have asthma (17.1 ± 5.5 versus 12.0 ± 4.4, p < 0.001). External validation with 73 patients showed similar results (18.0 ± 5.9 in asthma versus 10.2 ± 5.1 in non-asthma, p < 0.001). The discriminatory power of TEV/FEV₃ for asthma was comparable with that of FEF_25-75 (p = 0.804). TEV/FEV₃ significantly increased with asthma severity (mild, 16.1 ± 5.4; moderate, 17.7 ± 5.4; severe, 22.0 ± 5.3; p < 0.001). For patients who could not achieve FEV₃, FEF_25-75 demonstrated no significant difference between mild and moderate asthma, and could not discriminate asthma or asthma severity. Conclusion: TEV/FEV₃ is a new metric that may help diagnose and determine asthma severity by using conventional spirometry by assessing small airway dysfunction. TEV/FEV₃ promotes a reassessment of the reliability of other spirometric parameters, particularly in young children. Caution is needed in interpreting the result of spirometry in children who cannot achieve FEV₃.