(FEV₃-FEV₁)/FVC: A Terminal-Airflow Variable for Airway Hyperresponsiveness and Inflammation Prediction in Patients With Symptoms Despite Preserved Spirometry.

Abstract

Small-airway function assessment is crucial for asthma diagnosis and management. Abnormalities in terminal airflow deserve attention. This study investigated whether (FEV₃-FEV₁)/FVC correlates with airway hyperresponsiveness (AHR) and inflammation in patients with preserved spirometry. This cross-sectional study enrolled patients with FEV₁ of 80% predicted or greater, FEV₁/FVC of 0.7 or greater, and recurring asthma-like symptoms. Data included demographics, FeNO, impulse oscillometry, and spirometry. Univariate and combined models predicting AHR were analyzed in 553 patients and validated in 561. We also assessed correlations between sputum inflammation and spirometrics. Airway-hyperresponsive patients exhibited higher (FEV₃-FEV₁)/FVC ratios compared with those who were negative for AHR. This ratio showed the strongest association with the methacholine dose causing a 20% FEV₁ decrease and the response dose ratio (r = -0.26 and 0.39, respectively; P < .001 for both). The area under the receiver operating characteristic curve for AHR diagnosis using (FEV₃-FEV₁)/FVC was 0.751, increasing to 0.821 when it was combined with FeNO, as confirmed in the validation cohort. Moreover, (FEV₃-FEV₁)/FVC was superior to maximal expiratory flow at 50% of FVC for identifying eosinophilic airway inflammation characterized by elevated FeNO levels. It correlated better with sputum eosinophil count than with the other spirometrics. Elevated (FEV₃-FEV₁)/FVC levels were evident in AHR-positive patients with preserved FEV₁/FVC ratios. They serve as a sensitive marker of AHR and airway inflammation correlating with the response dose ratio, a provocative dose causing a 20% fall in FEV₁, and sputum eosinophils, suggesting their utility in monitoring patients at risk for uncontrolled asthma.