title: Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced bronchoconstriction in asthmatics: evidence of contribution of prostaglandins.
abstract: When administered by inhalation, bradykinin provokes dose-related bronchoconstriction in asthmatic subjects by a mechanism believed to involve activation of sensory nerve endings. However, little is known of the change in airway responsiveness to bradykinin after cyclo-oxygenase blockade. The aim of the present study was to investigate the effect of the potent cyclo-oxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation, on bradykinin-induced bronchoconstriction in a group of 12 asthmatic subjects. The subjects attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg x mL(-1)) or matched placebo (glycine, solution of 30 mg x mL(-1)) 15 min prior to bronchoprovocation tests with bradykinin and methacholine in a randomized, double-blind order with at least a 5 day interval. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1), and responsiveness to agonists was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration both of L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, with gradual recovery within 20 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to bradykinin in 11 of the 12 subjects studied, the geometric mean (range) values for PC20 bradykinin increasing significantly (p<0.001) by 1.7 doubling dose from 0.55 (0.11-5.05) to 1.72 (0.26-6.05) mg x mL(-1) after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. It is concluded that administration of lysine acetylsalicylate by inhalation protects the asthmatic airways against bradykinin-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the bronchoconstriction to kinins in human asthma.
authors.affiliation: Istituto Malattie Apparato Respiratolio Universita' di Catania, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Polosa
authors.forename: V L
authors.initials: VL
authors.lastname: Milazzo
authors.forename: S
authors.initials: S
authors.lastname: Magrì
authors.forename: C
authors.initials: C
authors.lastname: Pagano
authors.forename: G
authors.initials: G
authors.lastname: Paolino
authors.forename: G
authors.initials: G
authors.lastname: Santonocito
authors.forename: G
authors.initials: G
authors.lastname: Prosperini
authors.forename: N
authors.initials: N
authors.lastname: Crimi
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000704:Analysis of Variance; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001920:Bradykinin / Q000008:administration & dosage; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D011453:Prostaglandins / Q000378:metabolism*
chemical_list: D016085:Bronchoconstrictor Agents; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D016210:Methacholine Chloride; D008239:Lysine; D001241:Aspirin; D001920:Bradykinin; C010395:acetylsalicylic acid lysinate