Closing volume predicts the FEV1 response to bronchodilators in patients with COPD

Abstract

Background: to date, a reliable functional predictor of acute bronchodilator response in terms of forced expiratory volume in 1 second (FEV1) in patients with COPD does not exist. We hypothesized that ventilation inhomogeneity may have a role in the distribution of inhaled drugs.

Aim: to explore which physiological parameter is predictive of FEv1 response in patients with COPD

Methods: an interventional, randomized, double blind, double dummy study was conducted in the Pulmonary Rehabilitation Unit of S. Maugeri, Milan, Italy. The acute effects of tiotropium 18 µg (TIO) and indacaterol 150 µg (IND) on closing volume (CV) and ventilation inhomogeneity were investigated in patients with moderate to very severe COPD. Patients underwent body plethysmography, arterial blood gas analysis, dyspnea assessment, and simultaneous recording of single-breath N2 test and transpulmonary pressure-volume curve (PLV), before and 1 h after drug administration.

Results: 50 stable COPD patients, 25 per arm, (mean±SD age 70±7 yr, 82% men) were enrolled. Pre-bronchodilator and post-bronchodilator parameters did not differ between groups (ΔFEV1 90±110 vs. 60±110 mL, for IND and TIO;P=0.296), therefore results were pooled. ΔFEV1 significantly correlated with baseline vital capacity (Pearson coefficient, VC, 0.283; P=0.047), total lung capacity (TLC, 0.295; P=0.038) and closing volume to VC ratio (CV/VC, 0.483;P=0.023). In a multivariate regression model, only CV/VC significantly predicted the FEV1 response to bronchodilators (Beta -0.010; 95%CI: -0.017,-0.002; P=0.013).

Conclusion: the amount of closed airways during drug inhalation affects the response to bronchodilators in terms of airflow obstruction.