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When testing the response to β₂-agonist drugs in severe chronic obstructive pulmonary disease (COPD), a dose-response assessment should be undertaken. This study compares the time course of inhaled salmeterol (25, 50 and 75 μg) and formoterol (12, 24 and 36 μg) at different doses in a group of 12 patients with partially reversible, but severe COPD (FEV₁ of 12–32% of predicted values after β₂-agonist drugs had been withheld for 24 h). All doses of salmeterol and formoterol induced a significant (P<0·01) spirometric improvement over the 12-h monitoring period, when compared to the spirometric improvement after placebo, but while formoterol induced a dose-dependent increase of the FVC, FEV₁ and FEF₅₀, this was not the case for salmeterol. In fact, 75 μg salmeterol did not produce a further improvement of these parameters. Mean peak bronchodilation, expressed as the increase in FEV₁ over baseline …