Effects of formoterol (Oxis Turbuhaler) and ipratropium on exercise capacity in patients with COPD.
Although long-acting inhaled beta 2-agonists improve various outcome measures in COPD, no double-blind study has yet shown a significant effect of these drugs on exercise capacity. In a randomized, double-blind, placebo-controlled, crossover study, patients received formoterol (4, 5, 9, or 18 micrograms b.i.d. via Turbuhaler), ipratropium bromide (80 micrograms t.i.d. via pMDI with spacer), or placebo for 1 week. Main endpoint was time to exhaustion (TTE) in an incremental cycle ergometer test. Secondary endpoints were Borg dyspnoea score during exercise, lung function, and adverse events. Thirty-four patients with COPD were included, mean age 64.8 years, FEV1 55.6% predicted, reversibility 6.1% predicted. All doses of formoterol, and ipratropium significantly improved TTE, FEV1, FEF25-75%, FRC, IVC, RV and sGAW compared with placebo. A negative dose-response relationship was observed with formoterol. Ipratropium increased time to exhaustion more compared with formoterol, 18 micrograms, but not with formoterol, 4.5 and 9 micrograms. No changes in Borg score were found. There was no difference in the adverse event profile between treatments. In conclusion, 1 week of treatment with formoterol and ipratropium significantly improved exercise capacity and lung function compared with placebo. However, a negative dose-response relation for formoterol was unexpected and needs further investigation.
Department of Pulmonary Diseases, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
J J W
JJ
Liesker
V
V
Van De Velde
M
M
Meysman
W
W
Vincken
Per
P
Wollmer
L
L
Hansson
H A M
HA
Kerstjens
U
U
Qvint
R A
RA
Pauwels
D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage*; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
D001993:Bronchodilator Agents; D004983:Ethanolamines; D009241:Ipratropium; D000068759:Formoterol Fumarate