This randomized, double-blind, crossover study examined the physiological rationale for using a dual long-acting bronchodilator (umeclidinium/vilanterol (UME/VIL)) versus its muscarinic-antagonist component (UME) as treatment for dyspnea and exercise intolerance in moderate COPD. After each 4-week treatment period, subjects performed pulmonary function and symptom-limited constant-work rate cycling tests with diaphragm electromyogram (EMGdi), esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressure measurements. Fourteen subjects completed the study. Both treatments improved spirometry and airway resistance. UME/VIL had larger increases in FEV1 (+0.14±0.23L, p<0.05) but no added reduction in lung hyperinflation compared with UME. Isotime during exercise after UME/VIL versus UME (p<0.05): "unpleasantness of breathing" fell 0.8±1.3 Borg units; mean expiratory flow and ventilation increased; Pdi and Pga decreased. There were no treatment differences in endurance time, breathing pattern, operating lung volumes, inspiratory neural drive (EMGdi) or respiratory muscle effort (Pes swings) during exercise. UME/VIL compared with UME was associated with reduced breathing unpleasantness reflecting improved airway and respiratory muscle function during exercise.
Keywords: Bronchodilators; Dyspnea; Exercise; Respiratory mechanics; Respiratory neural drive.
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