Fast onset of effect of budesonide/formoterol versus salmeterol/fluticasone and salbutamol in patients with chronic obstructive pulmonary disease and reversible airway obstruction

Background and Objectives: Data on the onset of action of COPD medications are lacking. This study compared the onset of bronchodilation following different inhaled therapies in patients with moderate-to-severe COPD and reversible airway obstruction. Methods: In this double-blind, double-dummy, crossover study, 90 patients (aged >= 40 years; FEV1 30-70% predicted) were randomized to a single dose (two inhalations) of budesonide/formoterol 160/4.5 mu g, salmeterol/fluticasone 25/250 mu g, salbutamol 100 mu g or placebo (via pressurized metered-dose inhalers) on four visits. The primary end-point was change in FEV1 5 min after drug inhalation; secondary end-points included inspiratory capacity (IC) and perception of onset of effect. Results: Budesonide/formoterol significantly improved FEV1 at 5 min compared with placebo (P < 0.0001) and salmeterol/fluticasone (P = 0.0001). Significant differences were first observed at 3 min. Onset of effect was similar with budesonide/formoterol and salbutamol. Improvements in FEV1 following active treatments were superior to placebo after 180 min (all P < 0.0001); both combinations were better than salbutamol at maintaining FEV1 improvements (P <= 0.0001) at 180 min. Active treatments improved IC at 15 and 185 min compared with placebo (P < 0.0001). Maximal IC was greater with budesonide/formoterol than salmeterol/fluticasone (P = 0.0184) at 65 min. Patients reported a positive response to the perceptions of the onset of effect question shortly after receiving active treatments (median time to onset 5 min for active treatments vs 20 min for placebo), with no significant difference between active treatments. Conclusion: Budesonide/formoterol has an onset of bronchodilatory effect in patients with COPD and reversible airway obstruction that is faster than salmeterol/fluticasone and similar to salbutamol.