Effect of inhaled prostaglandin D-2 in normal and atopic subjects, and of pretreatment with leukotriene D-4

Background - Prostaglandin (PG) D-2 is a potent bronchoconstrictor mediator and is found, together with leukotriene (LT) D-4, in bronchoalveolar lavage fluid during the early response to allergen challenge in asthmatic subjects. The potency of PGD(2) has not been established in normal and atopic non-asthmatic subjects, nor has the contribution of cholinergic mechanisms to PGD(2) induced bronchoconstriction in normal subjects. Mediators released simultaneously may interact, so the effect of pre-inhalation of LTD4 on PGD(2) responsiveness was investigated. Methods - Six normal and six atopic non-asthmatic subjects performed histamine and PGD(2) challenges on separate occasions. Eight normal subjects performed PGD(2) challenges immediately before and 45 minutes after inhalation of 200 mu g oxitropium bromide or placebo. Bronchial responsiveness to PGD(2) was established in six normal subjects immediately after pretreatment with saline or non-bronchoconstricting doses of methacholine or LTD4 (challenge 1), and again at six hours (challenge 2). All studies were performed in a double blind, randomised, crossover fashion. Results - PGD(2) was 25-fold and 18-fold more potent as a bronchoconstrictor than histamine in atopic non-asthmatic and normal subjects, respectively. Responsiveness (PC(35)sGaw) to histamine and PGD(2) correlated significantly (r = 0.917, n = 12, p<0.001). Oxitropium bromide in a dose of 200 mu g inhibited PGD(2) induced bronchoconstriction by 37.5%, although in two of these subjects no inhibition was seen. Pre-inhalation of LTD4 and methacholine shifted the dose-response curve of PGD(2) to the left by 4.6-fold and 2.4-fold, respectively. Conclusions - PGD(2) is a potent bronchoconstrictor in normal subjects, which is partly mediated by cholinergic mechanisms in some subjects. No significant interaction was found between LTD4 and PGD(2) in six normal subjects.