Effect of inhaled prostaglandin D₂ in normal and atopic subjects, and of pretreatment with leukotriene D₄

Sampson, Sally E., Sampson, Anthony P. and Costello, John F. (1997) Effect of inhaled prostaglandin D₂ in normal and atopic subjects, and of pretreatment with leukotriene D₄. Thorax, 52 (6), 513-518. (doi:10.1136/thx.52.6.513).

Abstract

Background - Prostaglandin (PG) D₂ is a potent bronchoconstrictor mediator and is found, together with leukotriene (LT) D₄, in bronchoalveolar lavage fluid during the early response to allergen challenge in asthmatic subjects. The potency of PGD₂ has not been established in normal and atopic non-asthmatic subjects, nor has the contribution of cholinergic mechanisms to PGD₂ induced bronchoconstriction in normal subjects. Mediators released simultaneously may interact, so the effect of pre-inhalation of LTD₄ on PGD₂ responsiveness was investigated. Methods - Six normal and six atopic non-asthmatic subjects performed histamine and PGD₂ challenges on separate occasions. Eight normal subjects performed PGD₂ challenges immediately before and 45 minutes after inhalation of 200 μg oxitropium bromide or placebo. Bronchial responsiveness to PGD₂ 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 - PGD₂ was 25-fold and 18-fold more potent as a bronchoconstrictor than histamine in atopic non-asthmatic and normal subjects, respectively. Responsiveness (PC₃₅sGaw) to histamine and PGD₂ correlated significantly (r=0.917, n=12, p<0.001). Oxitropium bromide in a dose of 200 μg inhibited PGD₂ 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 PGD₂ to the left by 4.6-fold and 2.4-fold, respectively. Conclusions - PGD₂ 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 PGD₂ in six normal subjects.

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Contributors

Author: Anthony P. Sampson

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