The Confounding Effects of Thoracic Gas Compression on Measurement of Acute Bronchodilator Response

Abstract

Improvement in FEV(1) is a main endpoint in clinical trials assessing the efficacy of bronchodilators. However, the effect of bronchodilators on maximal expiratory flow may be confounded by thoracic gas compression (TGC). To determine whether TGC confounds effect of albuterol on FEV(1). We evaluated the response to albuterol inhalation in 10 healthy subjects, 9 subjects with asthma, and 15 subjects with chronic obstructive pulmonary disease (COPD) with mean (SD) age in years of 38 (SD, 11), 45 (SD, 11), and 64 (SD, 8), respectively. Lung mechanics were measured at baseline and 20 minutes after inhalation of 180 micro g of albuterol. We then applied a novel method to calculate FEV(1) corrected for the effect of TGC (NFEV(1)). Prior to albuterol administration, NFEV(1) was significantly higher than FEV(1). However, post-albuterol inhalation, FEV(1) increased more than NFEV(1) because of reduced TGC. In multiple regression analysis, the changes in TGC, inspiratory lung resistance, and ratio of residual volume to total lung capacity postalbuterol predicted more than 75% of FEV(1) improvement in patients with COPD. Improvements in FEV(1) after albuterol in patients with COPD are due to reduction of lung resistance, hyperinflation, and TGC. The latter is negligible during tidal breathing. Thus, although reduction of lung resistance and hyperinflation may result in improved dyspnea with a bronchodilator, the contribution of TGC reduction to improvement of FEV(1) may not exert any meaningful clinical effect during tidal breathing. This fact has to be taken into consideration when assessing the efficacy of new bronchodilators.