SUSTAINED PROTECTION AGAINST DISTILLED WATER PROVOCATION BY A SINGLE-DOSE OF SALMETEROL IN PATIENTS WITH ASTHMA

The long-acting beta(2)-agonist salmeterol inhibits in vitro the relea se of inflammatory mediators up to 20 h, These mediators are involved in ultrasonically nebulized distilled water (UNDW)-induced bronchocons triction, We investigated whether salmeterol provides prolonged protec tion against UNDW provocation and whether this effect was paralleled b y its bronchodilator effects, Nineteen asthmatic patients (mean forced expiratory volume in one second (FEV1) 84.8% predicted, mean provocat ive concentration of histamine producing a 20% decrease in FEV1 0.65 m g.mL(-1)) participated in this randomized, double-blind, placebo-contr olled crossover trial, After measuring baseline FEV1, patients inhaled 50 mu g salmeterol or placebo by metered-dose inhaler, FEV1 was measu red after 20 and 40 min, and UNDW provocations and FEV1 measurements w ere performed after 10, 20 and 34 h, Compared to placebo, salmeterol c aused marked bronchodilatation from 20 min up to 20 h after inhalation . Salmeterol also provided more than 20 h of protection against UNDW p rovocation (still more than one doubling dose), Protection beyond the period of bronchodilatation did not occur, Eleven subjects had a signi ficant reduction in provocative dose of UNDW causing a 20% fall in FEV 1 (PD2O,UNDW) values between 10 and 20 h, at a time when there was sti ll persistent bronchodilation, No correlation existed between changes in FEV1 and changes in PD20,UNDW, From the equations of regression lin es between FEV1 and corresponding PD20,UNDW values, it was calculated that only similar to 25% of the afforded protection was explained by b ronchodilatation. In conclusion, a single dose of salmeterol induces b oth bronchodilatation and protection independently of this bronchodila tion against a physiological bronchoconstrictor stimulus for more than 20 h.