Effects of formoterol (Oxis® Turbuhaler®) and ipratropium on exercise capacity in patients with COPD

AbstractAlthough long-acting inhaled β2-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 μg b.i.d. via Turbuhaler®), ipratropium bromide (80 μg 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 μg, but not with formoterol, 4.5 and 9 μg. 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