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Effect of inhaled prostaglandin D2 in normal and atopic subjects, and of pretreatment with leukotriene D4.
Thorax. 1997 Jun; 52(6):513-8.T

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 micrograms 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 micrograms 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.

Authors+Show Affiliations

Department of Respiratory Medicine, King's College School of Medicine and Dentistry, London, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9227716

Citation

Sampson, S E., et al. "Effect of Inhaled Prostaglandin D2 in Normal and Atopic Subjects, and of Pretreatment With Leukotriene D4." Thorax, vol. 52, no. 6, 1997, pp. 513-8.
Sampson SE, Sampson AP, Costello JF. Effect of inhaled prostaglandin D2 in normal and atopic subjects, and of pretreatment with leukotriene D4. Thorax. 1997;52(6):513-8.
Sampson, S. E., Sampson, A. P., & Costello, J. F. (1997). Effect of inhaled prostaglandin D2 in normal and atopic subjects, and of pretreatment with leukotriene D4. Thorax, 52(6), 513-8.
Sampson SE, Sampson AP, Costello JF. Effect of Inhaled Prostaglandin D2 in Normal and Atopic Subjects, and of Pretreatment With Leukotriene D4. Thorax. 1997;52(6):513-8. PubMed PMID: 9227716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of inhaled prostaglandin D2 in normal and atopic subjects, and of pretreatment with leukotriene D4. AU - Sampson,S E, AU - Sampson,A P, AU - Costello,J F, PY - 1997/6/1/pubmed PY - 1997/6/1/medline PY - 1997/6/1/entrez SP - 513 EP - 8 JF - Thorax JO - Thorax VL - 52 IS - 6 N2 - 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 micrograms 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 micrograms 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. SN - 0040-6376 UR - https://www.unboundmedicine.com/medline/citation/9227716/Effect_of_inhaled_prostaglandin_D2_in_normal_and_atopic_subjects_and_of_pretreatment_with_leukotriene_D4_ L2 - https://thorax.bmj.com/lookup/pmidlookup?view=long&amp;pmid=9227716 DB - PRIME DP - Unbound Medicine ER -