title: Increased excretion of leukotriene E4 during aspirin-induced asthma.
abstract: The etiology of aspirin-sensitive asthma is unknown, but a plausible hypothesis is that the inhibitory effect of aspirin on the cyclooxygenase enzyme increases formation of bronchoconstrictor leukotrienes via "shunting" of unmetabolized arachidonic acid into metabolism by the 5-lipoxygenase enzyme. The severity and rapidity of bronchospasm that is induced by cyclooxygenase-inhibiting drugs in aspirin-sensitive asthmatics is directly related to the dose and to the potency of the drug to inhibit the cyclooxygenase enzyme. Since increased leukotriene synthesis has recently been shown to occur during allergen-induced asthma, we have examined whether altered leukotriene synthesis correlates with the degree of either cyclooxygenase inhibition or bronchospasm during asthma that is induced by doses of aspirin that range from 30 to 365 mg in individual patients. Excretion of leukotriene E4 was increased by a mean of 361% +/- 76% (p less than 0.05) during aspirin-induced asthma episodes, but the degree of increase for individual patients did not correlate with the degree of bronchospasm or inhibition of platelet thromboxane B2 formation. Thus although the endogenous synthesis of potent bronchoconstrictor leukotrienes increases during aspirin-induced bronchospasm, it appears unlikely that a direct "shunting" of unmetabolized arachidonate into leukotriene synthesis represents the mechanism of aspirin-induced asthma.
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University, Nashville.
authors.forename: H R
authors.initials: HR
authors.lastname: Knapp
authors.forename: K
authors.initials: K
authors.lastname: Sladek
authors.forename: G A
authors.initials: GA
authors.lastname: Fitzgerald
mesh_terms: D001241:Aspirin; D001249:Asthma / Q000139:chemically induced* / Q000652:urine; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017999:Leukotriene E4; D013189:SRS-A / Q000031:analogs & derivatives* / Q000652:urine
chemical_list: D013189:SRS-A; D017999:Leukotriene E4; D003404:Creatinine; D001241:Aspirin