Inhaled PGE(2) prevents aspirin-induced bronchoconstriction and urinary LTE(4) excretion in aspirin-sensitive asthma

Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E(2) (PGE(2)) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinary leukotriene E(4) (u-LTE(4)) in seven aspirin-sensitive subjects with asthma. Each subject performed two challenges with a single dose of LASA that caused a decrease in FEV(1) of 20% or more in a preliminary test, immediately after inhaling 100 mu g PGE(2) in 4 ml saline or placebo, according to a randomized double-blind protocol. FEV(1) was recorded at 30-min intervals for 4 h. u-LTE(4) was measured by combined high-performance liquid chromatography enzyme immunoassay at 2-h intervals. After placebo, LASA caused an obstructive reaction in all patients, with a maximum decrease in FEV(1) of 35 +/- 5% with respect to baseline. u-LTE(4) rose from 911 +/- 261 picograms (pg)/mg creatinine at baseline to a maximum value of 2249 +/- 748 after challenge. Inhaled PGE(2) provided almost complete protection in all patients. Baseline u-LTE(4) was 883 +/- 243 pg/mg creatinine and did not change significantly during the test, reaching a maximum value of 864 +/- 290 (p < 0.05 versus placebo). These results confirm that PGE(2) is highly effective in preventing aspirin-induced asthma and suggest that this effect is mediated by inhibition of sulfidopeptide leukotriene production.