The inhibitory effect of terfenadine and flurbiprofen on early and late-phase bronchoconstriction following allergen challenge in atopic asthma.
We have studied the effect of cyclo-oxygenase inhibition and H1-receptor antagonism on the early and late bronchoconstrictor responses to inhaled allergen in mild atopic asthmatics. In the first phase of the study histamine inhalation challenge tests were performed in seven mild, atopic asthmatics 2 h after treatment with placebo or flurbiprofen (50, 100 or 150 mg). Flurbiprofen in these single doses had no effect on histamine reactivity. Ten atopic asthmatics participated in the second phase of the study in which the time course of the bronchoconstrictor response to inhalation of allergen was observed on four separate occasions after treatment with (a) placebo, (b) flurbiprofen, 150 mg, (c) terfenadine 180 mg, and (d) the combination of flurbiprofen and terfenadine. On each occasion subjects inhaled a concentration of allergen (Dermatagaphoides pteronyssinus, grass pollen) that had previously been shown to produce a 30% fall in FEV1 (PC30 allergen). The mean maximum fall in FEV1 during the early reaction was 33.2 +/- 3.3% from the post-saline baseline value following placebo and this was reduced to 27.5 +/- 5.3% after flurbiprofen (n.s.), 20.3 +/- 3.2% after terfenadine (P less than 0.05), and 23.1 +/- 2.3 after the treatment combination (P less than 0.05). Seven subjects developed late asthmatic reactions (LAR) after placebo and in these subjects the mean maximum fall in PEFR during the LAR was reduced from 22.6 +/- 3.1% after placebo to 16.7 +/- 3.2% after flurbiprofen (P less than 0.05), 15.2 +/- 2.3% after terfenadine (P less than 0.05) and 11.5 +/- 3.1% after the treatment combination (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Immunopharmacology Group, Southampton General Hospital, U.K.
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M
Hamid
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P
Rafferty
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ST
Holgate
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D001985:Bronchial Provocation Tests; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D008297:Male; D016593:Terfenadine
D000485:Allergens; D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D005480:Flurbiprofen; D016593:Terfenadine; D006632:Histamine