ACTIVITY OF INHALED LYSINE ACETYLSALICYLATE (L-ASA) ON BRADYKININ-INDUCED BRONCHOCONSTRICTION IN ASTHMATICS - EVIDENCE OF CONTRIBUTION OF PROSTAGLANDINS

When administered by inhalation, bradykinin provokes dose-related bron choconstriction in asthmatic subjects by a mechanism believed to invol ve activation of sensory nerve endings. However, little is known of th e change in airway responsiveness to bradykinin after cyclo-oxygenase blockade. The aim of the present study was to investigate the effect o f the patent cyclo-oxygenase inhibitor, lysine acetylsalicylate L-ASA) , administered by inhalation, on bradpkinin-induced bronchoconstrictio n in a group of 12 asthmatic subjects. The subjects attended the labor atory on four separate occasions to receive nebulized L-ASA (solution of 90 mg.mL(-1)) or matched placebo (glycine, solution of 30 mg.mL(-1) ) 15 min prior to bronchoprovocation tests with bradykinin and methach oline in a randomized, double-blind order with at least a 5 day interv al. Changes in airway calibre were followed as forced expiratory volum e in one second (FEV1), and responsiveness to agonists was expressed a s the provocative concentration causing a 20% fall in FEV1 from baseli ne (PC20). Administration both of LASA and glycine solution caused a s mall but significant acute fall in FEV1 from baseline, with gradual re covery within 20 min. When compared to placebo, inhaled L-ASA reduced the aim ay responsiveness to bradykinin in 11 of the 12 subjects studi ed, the geometric mean (range) values for PC20 bradykinin increasing s ignificantly (p<0.001) by 1.7 doubling dose from 0.55 (0.11-5.05) to 1 .72 (0.26-6.05) mg mL(-1) after placebo and L-ASA, respectively. No si gnificant change in airway responsiveness to methacholine was recorded after L-ASA. It is concluded that administration of lysine acetylsali cylate by inhalation protects the asthmatic airways against bradykinin -induced bronchoconstriction, thus suggesting that endogenous prostagl andins may play a contributory role in the bronchoconstriction to kini ns in human asthma.