Effect of the combination of two bronchodilators on breathlessness in patients with chronic obstructive pulmonary disease. A crossover clinical trial

Abstract

Background. Dyspnea is the major limiting symptom for patients with chronic obstructive pulmonary disease (COPD). This study was designed to investigate the impact of the combination of two bronchodilators on perception of dyspnea in these patients. Methods. Twenty patients with moderate to severe COPD (age was [mean±standard deviation (SD)] 64±7 years, FEV 1/FVC ratio was 45±11%) were randomized in a crossover, double-blind, placebo-controlled clinical trial to receive two puffs of either ipratropium bromide plus salbutamol (IB + S), IB + placebo (P), S + P, or P + P through metered dose inhalers (MDIs) daily over a 2-week period for each combination. At the end of each period, spirometry was obtained at baseline and 15, 30, 60, and 120 min after bronchodilator. Dyspnea was evaluated using a Borg scale during a 12-min walking test (12-MWT) performed at baseline and 120 min after MDIs use. In addition, the dyspnea component of the Chronic Respiratory Disease Questionnaire (CRDQ) and a diary of symptoms were used to evaluate this symptom. Results. After 15 days of treatment, FEV 1 improved significantly with all three combinations of MDIs containing bronchodilator agents. In comparison with placebo, significant improvement in dyspnea during 12-MWT was observed only when the combination of IB + S was used. No significant changes in CRDQ or patients' symptom diaries were observed with any combinations used. Conclusions. Combination of the two bronchodilators used in this study appears to alleviate perception of dyspnea more than use of either agent alone.