Effect on lung function and morning activities of budesonide/formoterol versus salmeterol/fluticasone in patients with COPD.
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.
Partridge
Martyn R
MR
Faculty of Medicine, Imperial College London, NHLI Division at Charing Cross Hospital, London, UK. m.partridge@imperial.ac.uk
Schuermann
Wolfgang
W
Beckman
Ola
O
Persson
Tore
T
Polanowski
Tomasz
T
D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019819:Budesonide / Q000009:adverse effects / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D000068297:Fluticasone-Salmeterol Drug Combination; D019819:Budesonide; D000420:Albuterol; D000068759:Formoterol Fumarate