The contribution of histamine release and vagal reflexes, alone and in combination, to exercise-induced asthma

Histamine release has been implicated in the pathogenesis of exercise-induced asthma (EIA), and is believed to be partly mediated by vagal stimulation. Our aim was to determine the relationship between the contributions of vagal stimulation (determined by the use of the muscarinic receptor antagonist, ipratropium bromide) and histamine release (determined by the use of the histamine H1-receptor antagonist terfenadine) in EIA. Ten stable asthmatic subjects with documented EIA took part in a randomized double-blind study. Each undertook four identical treadmill exercise tests, following drug therapy with one of the following: nebulized ipratropium bromide, 0.5 mg, terfenadine, 180 mg, by mouth, both active drugs together, and placebo preparations by mouth and by nebulizer. The mean +/- SEM maximum percentage fall in forced expiratory volume in one second (FEV1) after exercise following placebo therapy was 33.6 +/- 3.8%, which significantly decreased to 27.2 +/- 3.6% after terfenadine, to 21.8 +/- 3.9% after ipratropium bromide, and to 15.1 +/- 4.1% after the combination of both drugs. The addition of ipratropium bromide to terfenadine treatment improved on the protection offered by terfenadine alone. We conclude that both histamine release and vagal stimulation contribute independently and additively to EIA.