Budesonide added to formoterol contributes to improved exercise tolerance in patients with COPD.
BACKGROUND
Breathlessness and exercise intolerance frequently impact the daily life of patients with COPD.


METHODS
This double-blind, multicentre, three-period crossover study randomised 111 patients with COPD (mean age 64 years, mean FEV(1) 38% of predicted normal) to budesonide/formoterol 320/9 microg, formoterol 9 microg or placebo, twice daily for 1 week, following a 1-week run-in period with 1-week wash-out between treatments. Terbutaline (0.5 mg/dose) was used as needed. The primary efficacy variable was exercise endurance time (EET) at 75% peak work capacity with cycle ergometry assessed 1 h post-morning dose.


RESULTS
Budesonide/formoterol prolonged EET 1 h post-morning dose versus formoterol by 69 s (P < 0.005) and placebo by 105 s (P < 0.0001) and improved inspiratory capacity (IC) at isotime during exercise versus formoterol by 8% (P = 0.011) and placebo by 16% (P < 0.0001). Borg score at isotime was reduced by 0.48 (P = 0.12) and 0.78 (P = 0.014) compared with formoterol and placebo, respectively. At the repeated cycle test 6 h after morning dose, the effect on EET still favoured budesonide/formoterol over formoterol and placebo, while the isotime IC and Borg score were similar but better than placebo for the active study drugs. Budesonide/formoterol and formoterol improved health status (St George's Respiratory Questionnaire total score: mean difference versus placebo -2.4 and -2.2, respectively). All treatments were well tolerated.


CONCLUSIONS
Budesonide/formoterol resulted in a significant improvement in endurance time 1 h after the last morning dose in a 1-week treatment period versus formoterol and placebo. This study demonstrates, for the first time, the benefit of inhaled corticosteroids in addition to long-acting beta(2)-agonists on exercise tolerance in COPD patients. www.clinicaltrials.gov registration number: NCT00489853.
Worth
Heinrich
H
Medical Department I, Fürth Hospital, Fürth, Germany. med1@klinikum-fuerth.de
Förster
Karin
K
Eriksson
Göran
G
Nihlén
Ulf
U
Peterson
Stefan
S
Magnussen
Helgo
H
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D004417:Dyspnea / Q000188:drug therapy* / Q000503:physiopathology; D004983:Ethanolamines / Q000008:administration & dosage*; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D001993:Bronchodilator Agents; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate