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Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced bronchoconstriction in asthmatics: evidence of contribution of prostaglandins.
Eur Respir J. 1997 Apr; 10(4):866-71.ER

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+Show Affiliations

Istituto Malattie Apparato Respiratolio Universita' di Catania, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

9150326

Citation

Polosa, R, et al. "Activity of Inhaled Lysine Acetylsalicylate (L-ASA) On Bradykinin-induced Bronchoconstriction in Asthmatics: Evidence of Contribution of Prostaglandins." The European Respiratory Journal, vol. 10, no. 4, 1997, pp. 866-71.
Polosa R, Milazzo VL, Magrì S, et al. Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced bronchoconstriction in asthmatics: evidence of contribution of prostaglandins. Eur Respir J. 1997;10(4):866-71.
Polosa, R., Milazzo, V. L., Magrì, S., Pagano, C., Paolino, G., Santonocito, G., Prosperini, G., & Crimi, N. (1997). Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced bronchoconstriction in asthmatics: evidence of contribution of prostaglandins. The European Respiratory Journal, 10(4), 866-71.
Polosa R, et al. Activity of Inhaled Lysine Acetylsalicylate (L-ASA) On Bradykinin-induced Bronchoconstriction in Asthmatics: Evidence of Contribution of Prostaglandins. Eur Respir J. 1997;10(4):866-71. PubMed PMID: 9150326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced bronchoconstriction in asthmatics: evidence of contribution of prostaglandins. AU - Polosa,R, AU - Milazzo,V L, AU - Magrì,S, AU - Pagano,C, AU - Paolino,G, AU - Santonocito,G, AU - Prosperini,G, AU - Crimi,N, PY - 1997/4/1/pubmed PY - 1997/4/1/medline PY - 1997/4/1/entrez SP - 866 EP - 71 JF - The European respiratory journal JO - Eur. Respir. J. VL - 10 IS - 4 N2 - 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. SN - 0903-1936 UR - https://www.unboundmedicine.com/medline/citation/9150326/Activity_of_inhaled_lysine_acetylsalicylate__L_ASA__on_bradykinin_induced_bronchoconstriction_in_asthmatics:_evidence_of_contribution_of_prostaglandins_ L2 - http://erj.ersjournals.com/cgi/pmidlookup?view=long&amp;pmid=9150326 DB - PRIME DP - Unbound Medicine ER -