EVALUATION OF SINGLE-DOSE INHALED CORTICOSTEROID ACTIVITY WITH AN ALLERGEN CHALLENGE MODEL

Background: Inhaled corticosteroids are the most;commonly used antiinf lammatory agents for asthma. There is no simple may to compare objecti vely the relative potency of inhaled corticosteroids. The allergen-ind uced lute asthmatic response (LAR) can be suppressed by a single dose of inhaled corticosteroid. Objective: This study was undertaken to eva luate LAR as a model for the determination of the relative potency of single doses of inhaled corticosteroids. Methods: We compared doses of 200 and 800 mu g of a highly active inhaled corticosteroid (budesonid e) with placebo and a marginally active investigational inhaled cortic osteroid (D5159). Ten atopic patients with asthma completed a randomiz ed, double-blind, double-dummy, multicenter, four-way, crossover trial , A standardized allergen challenge with the identical dose of allerge n was performed 10 minutes after each of four blinded, single-dose tre atments: 200 mu g of budesonide, 800 mu g of budesonide, 8 mg of D5159 , and placebo, all administered from Turbuhaler. The LAR was recorded as the maximum percent fall in FEV1 between 4 and 7 hours, and the all ergen-induced increase in methacholine airway responsiveness at 24 hou rs was recorded as the Delta log PC20 from the day before to the day a fter allergen challenge. Results: There were no significant difference s in the early asthmatic responses during the 4 days; the mean maximum percent in FEV1 fall ranged between 19.5% and 22%. D5159 produced a s light inhibition of the LAR with maximum percent fall in FEV1 recorded as 28.8% +/- 5.0% for D5159 versus 34.1% +/- 4.8% for placebo (p < 0. 05). There was a greater reduction recorded after administration of th e two doses of budesonide. The mean LAR was 15.1% +/- 3.8% for 200 mu g of budesonide and 11.2% +/- 2.3% for 800 mu g of budesonide (p < 0.0 1 compared with placebo and D5159). The two doses of budesonide were n ot statistically different. Airway responsiveness to methacholine incr eased by 1.07 doubling doses 24 hours after allergen challenge. This i ncreased airway responsiveness was slightly, but not significantly, re duced by the three active treatments (0.6 to 0.91 doubling doses). Con clusion: The allergen-induced LAR model was able to differentiate a si ngle dose of an active inhaled corticosteroid from placebo and a highl y potent inhaled corticosteroid from a weak inhaled corticosteroid. Th e model did not differentiate between 2 fourfold doses of the highly a ctive inhaled corticosteroid (at the doses used in this study), neithe r for the fall in FEV1 nor for the increase in airway hyperresponsiven ess.