The study of mechanism concerning aspirin-induced asthma

Research Project

Project/Area Number	60570345
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Respiratory organ internal medicine
Research Institution	Fukui Medical School
Principal Investigator	SAGA Tsutomu Fukui medical School , assistant professor, 医学部, 講師 (70135060)
Co-Investigator(Kenkyū-buntansha)	ISHIZAKI Takeshi Fukui medical School, assistant professor, 医学部, 助手 (80151364)
Project Period (FY)	1985 – 1986
Project Status	Completed (Fiscal Year 1986)
Budget Amount *help	¥1,400,000 (Direct Cost: ¥1,400,000) Fiscal Year 1986: ¥400,000 (Direct Cost: ¥400,000) Fiscal Year 1985: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords	aspirin-induced Asthma / bronchial asthma / intractable asthma / non-steroidal / anti-inflammatory drugs / arachidonic acid cascade / prostaglandin / 5-リポキシゲナーゼ阻害剤
Research Abstract	The mechanism of aspirin-induced asthma (AIA) were studied clinically and experimentally. Indomethacine strongly enchanced the inhaled <LTD_4> induced increase of Paw in guinea-pigs whitch were pretreated by OKY-046. AA-861, one of 5-lipoxygenase inhibitor, had no effect on this phenomenon. From these result, the increases of Paw by inhaled <LTD_4> were not depend on 5-lipoxygenase pathway but depend on deprivation of bronchodilatory prostaglandins. In clinical study, 7 AIA and 7 non-AIA were challenged by intravenously administered sulpyrin. <FEV_(1.0)> and plasma prostanoid were measured at the point of before challenge, 10 and 30 min after challenge. <FEV_(1.0)> droped more than 15% from base line in 5 of 7 AIA but 0 of 7 non-AIA. Plasma prostanoid of AIA revealed significant decrease in 6-keto <PGF_1> <alpha> and 6-keto <PGF_1> <alpha> / TX <-B_2> ratio at 10 to 30 min after challenge. However there were no significant changes in TX <-B_2> between AIA and non-AIA. Plasma histamine also revealed significant increase in AIA compaire to non-AIA after this sulpyrin challenge. Our experimental and clinical results are compatible with the hypothesis concerning aspirin hypersensitivity, namely aspirin induces the deprivation of bronchodilatory PG, whitch in turn promotes the release of histamine and produces bronchoconstriction resembling immediate allergic reaction.