Effects of formoterol, salmeterol or oxitropium bromide on airway responses to salbutamol in COPD

We examined whether a pretreatment with formoterol, oxitropium bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 mu g formoterol, 50 mu g salmeterol, 200 mu g oxitropium bromide, or placebo on four non consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve tee inhaled salbutamol was then constructed using doses of 100, 100, 200 mu g and 400 mu g - that is, a total cumulative dose of 800 mu g. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 mu g - placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or oxitropium bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.