Mechanisms of dyspnoea relief and improved exercise endurance after furosemide inhalation in COPD

Background: This study examined the effects of inhaled furosemide on the ventilatory and perceptual response to high-intensity constant-load cycle exercise in chronic obstructive pulmonary disease (COPD). Methods: In a randomised, double-blind, placebo-controlled, crossover study, 20 patients with COPD (mean (SD) forced expiratory volume in 1 s 45 (15)% predicted) received either nebulised furosemide 40 mg or placebo on two separate days. Thirty minutes after each treatment, patients performed pulmonary function tests and a symptom-limited cycle exercise test at 75% of their maximum incremental work rate. Changes in spirometry, plethysmographic lung volumes, dynamic operating lung volumes, ventilation, breathing pattern, cardiovascular function, dyspnoea intensity and exercise endurance time were compared between treatments. Results: Compared with placebo, treatment with furosemide resulted in a mean (SD) decrease in dyspnoea intensity at the highest equivalent exercise time (ie, isotime for each patient) of 0.9 (1.0) Borg units (p < 0.01) and an increase in exercise endurance time of 1.65 (0.63) min (p < 0.05). These improvements were associated with increases in dynamic inspiratory capacity, tidal volume and mean tidal expiratory flow rates at isotime (p < 0.01). The eight patients whose exercise endurance time improved by >1 min had greater changes in operating lung volumes (p < 0.05), submaximal oxygen pulse (p < 0.05) and oxygen uptake (p= 0.05) than those in whom exercise endurance time did not improve. Conclusion: Alleviation of exertional dyspnoea after single-dose furosemide inhalation in COPD is multifactorial but improvements in dynamic ventilatory mechanics are contributory in some individuals.