Increased Exhaled Cysteinyl-Leukotrienes and 8-Isoprostane in Aspirin-induced Asthma

The pathogenesis of aspirin-induced asthma (AIA) has not yet been clearly elucidated, although eicosanoid metabolites appear to play an important role. We hypothesized that levels of eicosanoids in exhaled air condensate are abnormal in patients with AIA and that they change in patients receiving steroid therapy. We measured cysteinyl-leukotrienes (cys-LTs), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4), and also 8-isoprostane as a marker of oxidative stress, by enzyme immunoassay in exhaled breath condensate from patients with AIA (17 steroid naive; mean age, 41 ± 23 years; FEV1, 63%pred), 26 patients with aspirin-tolerant asthma (ATA) (11 steroid naive; mean age, 47 ± 18 years; FEV1, 69%pred), and 16 healthy subjects (mean age, 45 ± 17 years; FEV1, 93%pred). Cys-LTs were significantly higher in steroid-naive patients with AIA compared with steroid-naive patients with ATA and healthy subjects (152.3 ± 30.4 and 36.6 ± 7.1 versus 19.4 ± 2.8 pg/ml; p < 0.05 and p < 0.05, respectively). Steroid-naive patients with AIA also had higher levels of 8-isoprostane than normal subjects (131.8 ± 31.0 versus 21.9 ± 4.5 pg/ml; p < 0.05). There were significantly lower levels of both cys-LTs and 8-isoprostanes in steroid-treated patients with AIA. There was no difference in either the PGE2 or LTB4 level between the patient groups. This is the first study to show that cys-LTs and 8-isoprostanes are elevated in expired breath condensate of steroid-naive patients with AIA, and that cys-LTs are decreased in steroid-treated patients. Exhaled PGE2 levels are not reduced, so that it is unlikely that a deficiency of PGE2 is an important mechanism, whereas exhaled LTB4 levels are unchanged, indicating an abnormality beyond 5-lipoxygenase.