Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 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 E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinary leukotriene E4 (u-LTE4) in seven aspirin- sensitive subjects with asthma. Each subject performed two challenges with a single dose of LASA that caused a decrease in FEV1 of 20% or more in a preliminary test, immediately after inhaling 100 \u3bcg PGE2 in 4 ml saline or placebo, according to a randomized double-blind protocol. FEV1 was recorded at 30-min intervals for 4 h. u-LTE4 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 FEV1 of 35 \ub1 5% with respect to baseline. u-LTE4 rose from 911 \ub1 261 picograms (pg)/mg creatinine at baseline to a maximum value of 2249 \ub1 748 after challenge. Inhaled PGE2 provided almost complete protection in all patients. Baseline u-LTE4 was 883 \ub1 243 pg/mg creatinine and did not change significantly during the test, reaching a maximum value of 864 \ub1 290 (p < 0.05 versus placebo). These results confirm that PGE2 is highly effective in preventing aspirin-induced asthma and suggest that this effect is mediated by inhibition of sulfidopeptide leukotriene production