THE EFFECT OF INHALED SALMETEROL ON METHACHOLINE RESPONSIVENESS IN SUBJECTS WITH ASTHMA UP TO 12 HOURS

The duration of the protective effect of 50 and 100-mu-g of inhaled salmeterol against methacholine-induced bronchoconstriction was compared with that of 200-mu-g of inhaled salbutamol in 12 patients with asthma with a baseline FEV1 of at least 70% and a provocative concentration of inhaled methacholine causing a 20% fall in FEV1 (PC20) greater-than-or-equal-to 8 mg/ml. The study was placebo controlled, double blind, randomized, and crossover. The bronchodilating effect was no longer significant 4 hours after inhalation of salbutamol, whereas the effect was still present 12 hours after administration of 50 and 100-mu-g of salmeterol. All active treatments caused PC20 to increase at 1 hour (p < 0.05). PC20 (milligrams per milliliter) thus reached 3.7 +/- 0.8 after placebo, 13.8 +/- 3.0 after 50-mu-g of salmeterol, 23.2 +/- 4.7 after 100-mu-g of salmeterol, and 13.9 +/- 3.4 after 200-mu-g of salbutamol. The protective effect of 200-mu-g of salbutamol was no longer significant at 4 hours, whereas both doses of salmeterol protected against methacholine challenge up to 12 hours after inhalation (p < 0.01). An increased incidence of tremor (2/12) and palpitations (2/12) was recorded after inhalation of 100-mu-g of salmeterol. We conclude that inhalation of 50 or 100-mu-g of salmeterol causes a long-lasting bronchodilatation and protects against methacholine-induced bronchoconstriction for at least 12 hours.