The effect of prostacyclin on asthma precipitated by aspirin.
Inhibition of prostacyclin biosynthesis by aspirin might be expected to promote asthmatic attacks in aspirin-intolerant patients. In vitro, prostacyclin inhibits generation of leukotrienes and opposes their bronchoconstrictive action. In a double-blind study we compared the effects of intravenous infusions of prostacyclin with those of its solvent on bronchoconstriction provoked by threshold doses of aspirin in 9 known aspirin-sensitive asthmatics. The intensity of bronchial obstruction precipitated by aspirin was similar during prostacyclin and placebo infusions. There was no difference in other symptoms of intolerance, except for rhinorrhea which seemed accentuated by prostacyclin (possibly because of nasal vasodilatation). Our results suggest that either the inhibitory effects of prostacyclin on leukotrienes described in vitro do not apply in vivo, or the importance of leukotrienes have been overestimated in this type of asthma. Idiosyncrasy to aspirin, which affects 5-10% of adult asthmatics, was thought several decades to be of allergic background, while in fact numerous and extensive immunological studies ruled out typical IgE--mediated allergic mechanisms for aspirin--induced asthma. In 1974, at the Department of Allergy and Clinical Immunology in Cracow, a novel hypothesis was put forward. If stated that in sensitive patients, precipitation of asthmatic attacks by aspirin and by certain nonsteroidal antiinflammatory drugs (NSAID) results from inhibition of specific enzyme in the bronchi, cyclooxygenase, leading to an imbalance of prostanoids in the respiratory tract. Over the years which followed evidence has been accumulated which strongly support this hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Nizankowska
E
E
Department of Allergy and Clinical Immunology, Copernicus Academy of Medicine, Cracow, Poland.
Czerniawska-Mysik
G
G
Szczeklik
A
A
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000517:prevention & control; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011897:Random Allocation; D012997:Solvents
D012997:Solvents; D011464:Epoprostenol; D001241:Aspirin