The inhibitory effect of terfenadine and flurbiprofen on early and late-phase bronchoconstriction following allergen challenge in atopic asthma


Dr P. Rafferty, Dept. of Respiratory Medicine, Western Infirmary, Glasgow G11 6NT, U.K.


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 (Dermatagaphoide & 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 < 0·05), and 23·1 ±2·3 after the treatment combination (P < 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 < 0·05), 15·2 ± 2·3% after terfenadine (P < 0·05) and 11·5 ± 3·1% after the treatment combination (P < 0·01). Both terfenadine and flurbiprofen exhibited inhibitory effects on the early and late bronchoconstrictor responses to inhaled allergen implying roles for histamine and cyclo-oxygenase products in both phases of the response. As the inhibitory effect of the drugs was not purely additive when administered in combination, this implies that the bronchoconstrictor actions of histamine and the prostaglandins are not independent following allergen challenge.