INHALED LYSINE ACETYLSALICYLATE (L-ASA) ATTENUATES THE BRONCHOCONSTRICTOR RESPONSE TO ADENOSINE 5'-MONOPHOSPHATE (AMP) IN ASTHMATIC SUBJECTS

When administered by inhalation, adenosine 5'-monophosphate (AMP) prov okes dose-related bronchoconstriction in asthmatic subjects by a mecha nism believed to involve mast cell mediator release, However, Little i s known of the change in airway responsiveness to AMP after cyclo-oxyg enase blockade. The aim of this study was to investigate the effect of the potent cyclo-oxygenase inhibitor, lysine acetylsalicylate (L-ASA) administered by inhalation, on AMP-induced bronchoconstriction in a g roup of nine asthmatic subjects. The subjects studied attended the lab oratory on six separate occasions to receive nebulized L-ASA (solution of 90 mg . ml(-1)) or matched placebo (glycine solution, 30 mg . ml(- 1)) 15 min prior to bronchoprovocation tests with AMP, histamine and m ethacholine in a randomized, double-blind order. Changes in airway cal ibre were followed as forced expiratory volume in one second (FEV1) an d agonist responsiveness was expressed as the provocative concentratio n causing a 20% fall in FEV1 from baseline (PC20). Administration of b oth L-ASA and glycine solution caused a small but significant acute fa ll in FEV1 from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to AMP in all the subjects studied, the geometric mean (range) values for PC20, AMP increasing significantly from 36.3 (7.9-250.5) to 101.8 (27.2-1300) mg . ml(-1) after placebo and L-ASA, respectively, Moreove r, nebulized L-ASA induced a small but significant reduction in ah-way responsiveness to histamine, the geometric mean (range) PC20 values f or histamine increasing from 2.77 (1.05-5.49) to 4.36 (1.69-11.24) mg . ml(-1) after placebo and L-ASA, respectively, No significant change in airway responsiveness to methacholine was recorded after L-ASA. Adm inistration of L-ASA by inhalation protects the asthmatic airways agai nst AMP and, to a lesser extent, histamine-induced bronchoconstriction , thus suggesting that endogenous prostaglandins may play a contributo ry role in the airways response to AMP in human asthma.