Dynamics of eicosanoids in peripheral blood cells during bronchial provocation in aspirin-intolerant asthmatics

The underlying mechanisms of bronchoconstriction in aspirin-intolerant asthmatics (AIAs) are still unknown, but the hypothesis of an altered metabolism of arachidonic acid is generally accepted. So far, no in vitro test for aspirin intolerance is available. The hypothesis that the profile of eicosanoid mediators is changed in AIA-even before aspirin challenge was tested. The release of prostaglandin E2 (PGE2), peptidoleukotrienes and histamine was measured using competitive enzyme immunoassays in 10 asthmatics with a history of aspirin intolerance, 10 controls and eight aspirin-tolerant asthmatics (ATAs) before and after bronchial provocation with lysine-aspirin. Comparing basal release of eicosanoids before challenge, peptidoleukotrienes were significantly elevated and PGE2 was vastly reduced in AIAs, whereas ATAs had elevated basal peptidoleukotrienes but only slightly reduced basal PGE2. The decrease in forced expiratory volume in one second (FEV1) was not associated with changes in histamine release. After aspirin challenge, there was a massive increase of already elevated peptidoleukotrienes in AIAs, but not in ATAs. Arachidonic acid-induced PGE2 release in AIAs was not significantly changed, whereas it was significantly reduced in ATAs and healthy controls. Histamine release was unaffected by aspirin challenge in all three groups. There is a typically altered profile of eicosanoids in aspirin-intolerant asthmatics which could make in vitro diagnosis of aspirin intolerance possible.