Effects of umeclidinium/vilanterol (UME/VIL) versus umeclidinium (UME) on exertional dyspnea and respiratory mechanics in moderate COPD

We examined the physiological rationale for using a dual long-acting bronchodilator versus its anticholinergic component as treatment for dyspnea and exercise intolerance in moderate COPD patients. Methods: This randomized, double-blind, crossover study examined UME/VIL 125/25μg vs UME 125μg in GOLD grade 2 COPD. After each 4-week treatment period, pulmonary function and symptom-limited constant-load (75%max) cycle tests were performed. Diaphragm electromyography (EMGdi), esophageal (Pes) and gastric pressure (Pga) were measured during exercise in 9 subjects. Results: 14 subjects (post-bronchodilator FEV₁= 69±9%predicted; mean±SD) completed the study. Both treatments significantly improved spirometry and airway resistance. UME/VIL had larger increases in FEV₁ (+0.16±0.15 L; p<0.01) but no added reduction in lung hyperinflation compared with UME. At isotime during exercise after UME/VIL vs UME: “unpleasantness of breathing” fell 0.8±1.3 Borg units (p<0.05); ventilation increased 3L/min, mean inspiratory and expiratory flow increased, and expiratory muscle activity (Pga) decreased (all p<0.05). There were no treatment differences in endurance time, breathing pattern, operating lung volumes, inspiratory neural drive (EMGdi %maximum) or respiratory muscle effort (Pes tidal swings %maximum) during exercise. Conclusions: UME/VIL compared with UME conveyed added improvement in airway function at rest and during exercise and less perceived breathing unpleasantness. Failure to increase exercise endurance with UME/VIL versus UME is likely due to the lack of additional reduction in lung hyperinflation, inspiratory neural drive or respiratory effort.