Effects of a cyclo-oxygenase inhibitor, flurbiprofen, and an H1 histamine receptor antagonist, terfenadine, alone and in combination on allergen induced immediate bronchoconstriction in man.

Abstract

The effect of flurbiprofen, a potent cyclo-oxygenase inhibitor, on histamine and methacholine reactivity was assessed in seven atopic subjects with asthma. Flurbiprofen 150 mg daily for three days displaced the histamine-FEV, concentration-response curve to the right by 1.5 doubling doses, whereas no effect was observed on the response to methacholine. Subsequently the effects of flurbiprofen and terfenadine, a specific H, histamine receptor antagonist, on allergen induced bronchoconstriction were studied in seven atopic but non-asthmatic subjects. The subjects inhaled the concentration of grass pollen allergen that had previously been shown to produce a 20% fall in FEV, on separate occasions after prior treatment with placebo, flurbiprofen 150 mg daily for three days, terfenadine 180 mg three hours before challenge, and the combination of flurbiprofen and terfenadine. After placebo, allergen challenge caused a mean (SEM) maximum fall in FEV, of 37-6% (2 6%) after 20 (3 7) minutes, followed by a gradual recovery to within 1 5 % of baseline at 60 minutes. Terfenadine reduced the maximum allergen provoked fall in FEV, to 21-5% (2-2%) and reduced the area under the time-response curve (AUC) by 50% (6%). Flurbiprofen alone reduced the mean maximum fall in FEV, to 29-6% (3-2%) and reduced the AUC by 26%. The effect of the combination of flurbiprofen and terfenadine did not differ significantly from that of terfenadine alone. We conclude that histamine and prostaglandins contribute to immediate allergen induced bronchoconstriction and that a complex interaction occurs between the two classes of mediators.

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma

“…The PTGDR is located at chromosome 14q22.1 and is the receptor for PGD2 that may contribute to the asthma phenotype, which is characterized by pulmonary vasodilation, bronchoconstriction and recruitment of eosinophils. [7][8][9] The effects of the PTGDR on asthma were shown with a mouse study; the asthmatic symptoms of PTGDR À/À mice were improved compare with wild-type mice. 8 In addition, PGD2 15 and LTC4 16,17 are both derived from arachidonic acid.…”

“…6 PGD2 may contribute to pulmonary vasodilation, bronchoconstriction, and the recruitment of eosinophils, basophils and T-lymphocytes. [7][8][9] PGD2 exerts its biological actions through the PGD2 receptor (PTGDR), which is localized to chromosome 14q22.1 and has been associated with asthma. 10 The association between asthma and PTGDR function has been recently studied with a mouse model.…”

A double‐blind, placebo controlled study of the effect of the specific histamine H1‐receptor antagonist, terfenadine, in chronic severe asthma.

“…This comes from the increase in plasma histamine concentrations coincident with the development of airflow obstruction [15] and the ability of HI-receptor antagonists to attenuate the airflow obstruction [16]. This suggests that HI-receptor blockade could be therapeutically effective against the clinical correlate of acute allergen exposure as seen during the pollen season.…”

Anti-inflammatory Activity of Ailanthus altissima in Ovalbumin-Induced Lung Inflammation

“…8) Measurements of eicosanoids and their metabolites in bronchoalveolar lavage fluid (BALF) after inhaled allergen challenge of asthmatics suggest that resident mast cells, infiltrating eosinophils, basophils and macrophages are responsible for leukotrienes (LTs) and prostaglandins (PGs) in the early and late bronchoconstrictor responses. 9,10) Eicosanoids are inflammatory mediators that are biosynthesized in many cell types by cyclooxygenases (COX) and lipoxygenases (LOX). They are strongly associated with inflammatory disorders, acute as well as chronic inflammation.…”

“…9,10) Eicosanoids are inflammatory mediators that are biosynthesized in many cell types by cyclooxygenases (COX) and lipoxygenases (LOX). They are strongly associated with inflammatory disorders, acute as well as chronic inflammation.…”