Influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in COPD

We examined the influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in patients with partially reversible stable COPD. Twenty outpatients inhaled one or two puffs of formoterol (12 microg puff(-1)), or placebo. Two hours after inhalation, a dose-response curve to inhaled oxitropium bromide (100 microg puff(-1)) or placebo was constructed using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 microg oxitropium bromide. Doses were given at 20-min intervals and measurements made 15 min after each dose. On six separate days, all patients received one of the following: (1) formoterol 12 microg + oxitropium bromide 600 microg, (2) formoterol 12 microg + placebo, (3) formoterol 24 microg + oxitropium bromide 600 microg, (4) formoterol 24 microg + placebo, (5) placebo + oxitropium bromide 600 microg, or (6) placebo + placebo. Both formoterol 12 microg and 24 microg induced a good bronchodilation (formoterol 12 microg, 0.19-0.20 l; formoterol 24 microg 0.22-0.24 l). The dose-response curve of oxitropium, but not placebo, showed an evident increase in FEV1, with a further significant increase of respectively 0.087 l and 0.082 l after the formoterol 12 microg and formoterol 24 microg pre-treatment. This study shows that improved pulmonary function in patients with stable COPD may be achieved by adding oxitropium 400-600 microg to formoterol. There is not much difference in bronchodilation between combining oxitropium with formoterol 12 microg or 24 microg. In any case, formoterol 24 microg alone seems sufficient to achieve the same bronchodilation induced by oxitropium 600 microg alone in most patients.