TOLERANCE TO THE PROTECTIVE EFFECT OF SALMETEROL ON ALLERGEN CHALLENGE

Long-term treatment with inhaled beta(2)-agonists may be associated wi th a deterioration in asthma control, potentially due to tolerance. Re gular use of short-acting beta(2)-agonists has been shown to induce to lerance to allergen or adenosine 5'-monophosphate challenge. The aim o f the study was to detect the efficacy of a single dose and a short-te rm treatment with salmeterol, a long-acting beta(2)-agonist, to protec t against early asthmatic reaction (EAR) to allergen. Eight subjects w ith mild allergic asthma underwent two treatment periods in which subj ects performed an allergen challenge (specific bronchial provocation t est) protected by a single dose (50 mu g) of salmeterol (Salm-1) follo wed by a second specific bronchial provocation test after regular trea tment with salmeterol for 1 week (Salm-2), or a single dose of placebo (Plac-1) and regular treatment (1 week) with placebo (Plac-2). Each s ubject performed both treatments in a randomized order. Each time alle rgen challenge was performed 1 h after last drug inhalation and it was stopped when the same provocative dose of allergen of a previous scre ening allergen challenge was achieved. The maximum decrease in FEV(1) and area under curve in the first hour after allergen inhalation were significantly lower in Salm-1 (max Delta FEV(1)%, median [range]: 4%[0 to 9]) with respect to Salm-2, Plac-1, Plac-2 (24%[13 to 38], 31%[19 to 50], 30%[6 to 44], respectively, p < 0.001]); there was no differen ce among Salm-2, Plac-1 and Plac-2. In Salm-1, all subjects were prote cted against EAR, whereas in Salm-2 only 2 subjects showed a partial p rotection. In conclusion the protective effect of a single dose of sal meterol against allergen-induced EAR was lost after regular treatment with salmeterol for 1 week. The clinical relevance of this mechanism r emains to be elucidated.