To investigate the role of H1 receptor-mediated effects in allergic rhinitis, we challenged 12 allergic volunteers with allergen 2 hours after administration of either placebo or 60 mg of terfenadine. Filter paper discs were used for the unilateral administration of allergen and the collection of nasal secretions. Secretion weights, levels of histamine in recovered nasal secretions, and nasal airway resistance (NAR) were measured for each nostril separately, and the number of sneezes was counted. After placebo treatment, allergen challenge led to significant increases in ipsilateral and contralateral secretion weights, ipsilateral histamine levels, ipsilateral NAR, and sneezing. Contralateral histamine levels were not elevated. H1 antagonism with terfenadine markedly reduced the number of sneezes and partially decreased ipsilateral and contralateral secretion weights, without affecting the increase in NAR. Terfenadine premedication also lowered the amount of histamine in ipsilateral secretions after allergen challenge. Performing identical nasal challenges with a 10-fold lower dose of antigen produced similar results. Previous studies showed that terfenadine had no effect on methacholine provocation and completely abolished ipsilateral and contralateral secretion weights after histamine challenge. We conclude that sneezing after allergen challenge is caused almost exclusively by a reflex initiated through H1 receptors and that H1 antagonism has no influence on allergen-induced increases in NAR. Unilateral allergen challenge leads to bilateral increases in secretion weights, which are only partially inhibited by terfenadine, suggesting the involvement of mediators other than histamine in the nasonasal reflex. As reported earlier, terfenadine also decreases allergen-induced histamine release after challenge with the highest dose of antigen.
Adult Airway Resistance