Background: Walking is a familiar dally activity that is generally limited by breathlessness,whereas cycling is an uncommon physical effort typically limited by leg discomfort.The hypothesis was that patients with chronic obstructive pulmonary disease (COPD) would exhibit greater improvements in exercise endurance and relief of breathlessness with bronchodilator therapy during treadmill walking compared with cycling.Methods: In this randomized,2x2,double-blind,placebo-controlled,crossover trial,20 patients with COPD (age,64+7 years; forced expiratory volume in one second,56±14 percent predicted) performed constant-load endurance exercise on the treadmill and cycle ergometer at 85% of capacity after inhaling normal saline (NS) or aformoterol (ARF) (15μtg).Results: Increases in endurance times and consistency of responses were greater with treadmill walking (△:157+286s;p=0.024;80%improved) than with cycle exercise (△:110+219s;P=0.038;65%improved) with ARF compared with NS.However,these changes were not significantly different.The slope of breathlessness-time (mean△=-29%;P=0.007) and the magnitude of oxygen desaturation were significantly lower with ARF compared with NS during treadmill,but not cycle exercise.Inspiratory capacity values were similar between modes of exercise when comparing the same study medication.Conclusions: Improved endurance times support both constant-load treadmill and cycle exercise to assess the efficacy of bronchodilator therapy in patients with COPD.Unique differences in physiological and perceptual responses with bronchodilation demonstrate advantages of treadmill walking as an exercise stimulus.