Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen

Background: A simple laboratory method to evaluate relative potency of inhaled corticosteroids in asthma would be valuable. Single-dose studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship. Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response. Methods: Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium bromide as needed. These subjects had positive allergen and methacholine inhalation tests and FEV₁ greater than 70% of predicted value. A double-blind, randomized, crossover study compared placebo and budesonide 100, 200, and 400 μg administered by means of Turbuhaler twice daily for 7 days with 6-day washout periods. Methacholine PC₂₀ was measured before and after 6 days of treatment, and allergen PC₁₅ was measured after 7 days of treatment. Results: The allergen PC₁₅ (n = 11) was significantly larger (P = .0001) for all doses of budesonide compared with placebo, but there was no significant difference between the 3 doses of budesonide, and no dose response was demonstrated. The methacholine PC₂₀ was significantly larger after all budesonide treatments compared with placebo (P = .024), but there was no difference between the 3 doses. There was a progressive increase in the allergen PC₁₅ chronologically (sequence effect) that was not explained by improvement in FEV₁ or airway responsiveness; sequence effects were not seen for FEV₁ or for pretreatment or posttreatment methacholine PC₂₀. Statistical adjustment for sequence effect did not alter allergen PC₁₅ statistics. Conclusion: A 7-day course of budesonide administered by means of Turbuhaler at 200, 400, or 800 μg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo. There was, however, no difference between the 3 doses. Therefore this method with these doses is not useful for providing assessment of relative potency.