(FEV3-FEV1)/FVC: a terminal-airflow variable for airway hyperresponsiveness and inflammation prediction in patients with symptoms despite preserved spirometry.

Background: Small-airway function assessment is crucial for asthma diagnosis and management. Abnormalities in terminal airflow deserve attention.

Objective: This study investigated whether the ratio of forced expiratory volume in the second and third seconds to forced vital capacity ([FEV₃-FEV₁]/FVC) correlates with airway hyperresponsiveness (AHR) and inflammation in patients with preserved spirometry.

Methods: This cross-sectional study enrolled patients with FEV₁ ≥ 80% predicted, FEV₁/FVC ≥ 0.7, and recurring asthma-like symptoms. Data included demographics, fractional exhaled nitric oxide (FeNO), impulse oscillometry, and spirometry. Univariate and combined models predicting AHR was analyzed in 553 patients and validated in 561. Correlations between sputum inflammation and spirometrics were also assessed.

Results: AHR⁺ patients exhibited higher (FEV₃-FEV₁)/FVC ratios compared to AHR^-. This ratio showed the strongest association with the methacholine dose causing a 20% FEV₁ decrease (PD₂₀) and the response dose ratio (RDR)(r = -0.26 and 0.39, respectively; P < .001, both). The area under the receiver operating characteristic curve for AHR diagnosis using (FEV₃-FEV₁)/FVC was 0.751, increasing to 0.821 when combined with FeNO, confirmed in the validation cohort. (FEV₃-FEV₁)/FVC was superior to maximal expiratory flow at 50% of forced vital capacity for identifying eosinophilic airway inflammation characterized by elevated FeNO levels. It correlated better with sputum eosinophil count than with the other spirometrics.

Conclusion: Elevated (FEV₃-FEV₁)/FVC were evident in AHR⁺ patients with preserved FEV₁/FVC ratios. It serves as a sensitive marker of AHR and airway inflammation correlating with RDR, PD₂₀, and sputum eosinophils, suggesting its utility in monitoring patients at risk for uncontrolled asthma.