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

1. The characteristic changes seen in asthma are widely regarded as being caused by local mediator release in the airways, with histamine the first putative mediator in asthma to be identified. 2. We performed a double-blind, randomised, placebo-controlled crossover trial of the effect of 4 weeks treatment with terfenadine 120 mg twice daily in chronic severe asthma. 3. Forty-two subjects (20 male and 22 female) completed the 10 week study. 4. Terfenadine had no significant treatment effect on the primary efficacy variables measured. Mean (95% CI) measurements for terfenadine vs placebo treatment periods were 1.5 vs 1.5 (-0.3, 0.3) l for FEV1, 259 vs 260 (-42, 40) l min-1 for morning PEF and 0.8 vs 0.8 (-0.3, 0.3) for global symptom scores. 5. Bronchodilator use and sleep disturbance, the secondary efficacy variables studied, showed an improvement during terfenadine treatment but this only reached statistical significance for the number of times subjects awoke from sleep (P = 0.04). 6. There was a similar frequency of minor adverse effects reported during placebo (13.6%) and terfenadine (16.7%) treatments. 7. Addition of the potent and specific histamine H1-receptor antagonist terfenadine to maintenance asthma treatment had no significant therapeutic benefit in this group of chronic severe asthmatics.