Attenuation of hyperventilation-induced bronchospasm by terfenadine: a new antihistamine

The effect of terfenadine, a selective H1-receptor antagonist devoid of central nervous system side effects, was evaluated on hyperventilation-induced bronchospasm in 11 adult subjects with asthma in a double-blind, placebo-controlled, crossover study. Increases in specific airway resistance (SRaw) were induced by isocapnic hyperventilation with dry air on two occasions, 7 days apart. Before the tests, the subjects received oral terfenadine (120 mg, twice daily) or placebo for 3 days with the last dose administered 3 hours before the test. Baseline SRaw and spirometric values (vital capacity and FEV1) were similar for the two tests. Terfenadine yielded a significant (p less than 0.001) parallel shift to the right of the stimulus (hyperventilation)-response (SRaw) curve; 100% increases in SRaw occurred at ventilation rates of 44 L/min after placebo treatment and 64 L/min after terfenadine treatment. These data suggest that histamine release plays a role in hyperventilation-induced bronchospasm despite the fact that increase in plasma histamine has not been found in this situation, in contrast to exercise-induced bronchospasm.