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 stud ies with the allergen-induced late asthmatic response have failed to s how a useful dose-response relationship. Treatment for several days wi th inhaled corticosteroids will also inhibit the allergen-induced earl y asthmatic response. Methods: Twelve atopic asthmatic subjects were s tudied during a season when no medications were required except ipratr opium bromide as needed. These subjects had positive allergen and meth acholine inhalation tests and FEV1 greater than 70% of predicted value . A double-blind, randomized, cross-over study compared placebo and bu desonide 100, 200, and 400 mu g administered by means of Turbuhaler tw ice 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 com pared with placebo, but there was no significant difference between th e 3 doses of budesonide, and no dose response was demonstrated. The me thacholine PC20 was significantly larger after all budesonide treatmen ts compared with placebo (P = .024), but there was no difference betwe en the 3 doses. There was a progressive increase in the allergen PC15 chronologically (sequence effect) that was not explained by improvemen t in FEV1 or airway responsiveness; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20. Statisti cal adjustment for sequence effect did not alter allergen PC15 statist ics. Conclusion: A 7-day course of budesonide administered by means of Turbuhaler at 200, 400, or 800 mu g per day provided marked and signi ficant inhibition of the allergen-induced early asthmatic response com pared with placebo. There was, however, no difference between the 3 do ses. Therefore this method with these doses is not useful for providin g assessment of relative potency.