COMPARISON OF SALMETEROL AND ALBUTEROL-INDUCED BRONCHOPROTECTION AGAINST ADENOSINE-MONOPHOSPHATE AND HISTAMINE IN MILD ASTHMA

Short-acting beta(2)-agonists provide greater protection to bronchocon striction induced by adenosine-5'-monophosphate (AMP) than does methac holine. Because AMP produces bronchoconstriction through release of me diators from mast cells, and methacholine directly constricts airway s mooth muscle, this suggests that beta(2)-agonists stabilize mast cells in vivo. This in vivo property has not been demonstrated with long-ac ting beta(2)-agonists. We undertook two double-blind, randomized, cros sover, placebo-controlled studies to investigate the effects of salmet erol and albuterol on airway responsiveness (AR) to AMP and histamine in patients with mild asthma. In the first study, 19 patients attended on four occasions to inhale salmeterol 50 mu g or placebo 2 h before challenge with AMP or histamine. In the second study 16 patients (13 o f whom had participated in the first study) were studied in a similar fashion but inhaled albuterol 400 mu g or placebo 30 min prior to chal lenge. Salmeterol reduced AR to AMP and histamine by 3.4 +/- 0.3 and 3 .9 +/- 0.3 doubling doses, respectively (NS). In contrast, albuterol d emonstrated a greater protective effect on AMP than on histamine, redu cing AR by 5.1 +/- 0.3 and 3.8 +/- 0.2 doubling doses, respectively (p < 0.005). Thus, in contrast to albuterol, salmeterol did not demonstr ate mast-cell stabilizing properties in vivo at a time corresponding t o maximal bronchodilatation. These findings might be explained by the unique pharmacologic profile of salmeterol in combination with the dif ferential beta(2)-adrenoceptor pharmacology of bronchial mast cells an d bronchial smooth muscle.