Background: Patients with chronic obstructive pulmonary disease (COPD) often experience symptoms and problems with activities early in the morning. This is the first study to compare the effect of budesonide/formoterol and salmeterol/fluticasone on lung function, symptoms and activities early in the morning.
Methods: Lung function (peak expiratory flow [PEF] and forced expiratory volume in 1 second [FEV( 1)]) and symptoms were measured at bedside and activities were measured during the morning using a six-item questionnaire concerning basic morning routines. In a randomised, double-blind, multicentre, cross-over study, 442 patients with COPD aged >or=40 years (pre-bronchodilator FEV(1) <or=50%; FEV(1)/vital capacity <70%) received budesonide/formoterol (320/9 microg, one inhalation twice daily) dry powder inhaler (DPI) or salmeterol/fluticasone (50/500 microg, one inhalation twice daily) DPI daily, for 1 week each, separated by a 1- to 2-week washout. Lung function (PEF and FEV(1)) shortly after rising from bed in the morning, symptoms and basic morning activities were assessed by electronic diary (e-Diary) recordings.
Results: Budesonide/formoterol and salmeterol/fluticasone treatment increased morning PEF 5 minutes post-dose, measured as a mean improvement from baseline over the full study period (primary endpoint; adjusted mean change: 15.1 l/min and 14.2 l/min, respectively [difference 1.0 l/min; p = 0.603]). Mean morning FEV(1) improved more following budesonide/ formoterol treatment versus salmeterol/fluticasone at 5 minutes (0.12 l versus 0.09 l; p = 0.090) and 15 minutes (0.14 l versus 0.10 l; p < 0.05) post-dose. Budesonide/formoterol demonstrated a more rapid onset of effect as reflected by increases in e-Diary-recorded PEF and FEV( 1) from pre-dose to 5 and 15 minutes post-dose (all p < 0.001) and spirometry at the clinic measured after the first dose (FEV(1) p < 0.001; 5 minutes post-dose). Improvements in symptom scores within 15 minutes after drug administration were similar for both drugs, but budesonide/formoterol treatment resulted in significantly greater improvements in total morning activities score (getting washed, dried, dressed, eating breakfast and walking around the home; 0.22 versus 0.12 respectively, p < 0.05). Both treatments were well tolerated.
Conclusions: Short-term treatment with budesonide/formoterol DPI or salmeterol/fluticasone DPI was effective in patients with COPD. Budesonide/formoterol had a more rapid onset of effect compared with salmeterol/fluticasone and resulted in greater improvements in ability to perform morning activities despite the lower inhaled corticosteroid dose.