Effect of Inhaled Prostaglandin E2 on Methacholine and Leukotriene D4 Airway Responsiveness in Asthmatic Subjects

Previous studies in asthmatics have demonstrated that the endogenous release of inhibitory prostaglandins limits the bronchoconstrictor response to repeated challenges with exercise and histamine, and that inhaled prostaglandin (PG) E 2 attenuates allergen‐induced asthmatic responses and exercise bronchoconstriction in asthmatics. Inhaled PGE 2 does not significantly attenuate methacholine airway responsiveness. These results, taken together, indicate that inhaled PGE 2 attenuates the bronchoconstriction caused by stimuli, such as allergen and exercise, that result in bronchoconstriction through cysteinyl leukotriene (LT) release. The purpose of this study was to determine whether inhaled PGE 2 could selectively attenuate LTD 4 ‐induced bronchoconstriction in seven stable asthmatic subjects. Each subject was studied on four different study days. On two occasions the subjects inhaled 100 mg PGE 2 , 30 mins before a methacholine, or LTD 4 challenge test. On the other two study days, the subjects were pretreated with its diluent. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV 1 ) (PC 20 ). PGE 2 pretreatment significantly increased the LTD 4 PC 20 , but not the methacholine PC 20 . The mean LTD 4 PC 20 increased from 2.00 mg/mL (%SEM 1.65) after diluent pretreatment to 3.01 mg/mL (%SEM 1.64) after PGE 2 pretreatment (P=0.008). The mean methacholine PC 20 was 1.28 mg/mL (%SEM 1.68) after diluent pretreatment and 1.62 mg/mL (%SEM 1.46) after PGE 2 pretreatment (P=0.28). These results suggest that PGE 2 partially attenuates LTD 4 ‐induced bronchoconstriction; however, the magnitude of the effect is unlikely to account for its attenuation of exercise and allergen‐induced bronchoconstriction.