Dose-dependent inhibitory effect of inhaled beclomethasone on late asthmatic reactions and increased responsiveness to methacholine induced by toluene diisocyanate in sensitised subjects

To determine whether inhaled beclomethasone, both at low and at high doses, inhibits late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 9 sensitised subjects. Low dose beclomethasone (200 μg bid), high dose beclomethasone aerosol (1000 μg bid), and placebo were administered for 7 days before TDI inhalation challenge to each subject, according to a double-blind, crossover study design. The washout period between the treatments was at least 1 week. When the subjects were treated with placebo, forced expiratory volume in 1 sec (FEV₁) markedly decreased after exposure to TDI. By contrast, high dose beclomethasone prevented the late asthmatic reaction and the low dose partially inhibited the reaction. With placebo the mean (±SE) value of FEV₁ 4 h after exposure to TDI was 2.6 ± 0.17 L, which went to 3.3±0.12 after low dose beclomethasone, and to 3.5±0.15 L after high dose of beclomethasone (significant difference in the decrease of FEV₁ in the 8 h after exposure to TDI, between treatments: F = 9.87, (P < 0.001), After treatment with placebo or with low dose beclomethasone, airway responsiveness to methacholine increased 8 h after exposure to TDI. With placebo, the PD₂₀ decreased from 0.66 mg (Geometric Standard Error of the Mean [GSEM], 1.38) to 0.18 mg (GSEM, 1.46); with low dose inhaled beclomethasone, the PD₂₀ decreased from 0.93 mg (GSEM, 1.42) to 0.36 mg (GSEM, 1.63). By contrast, airway responsiveness to methacholine did not change 8 h after exposure to TDI in subjects treated with high dose inhaled beclomethasone: the PD₂₀ was 0.78 mg (GSEM, 1.51) before and 0.71 mg (GSEM, 1.58) after exposure to TDI. The protective effect of beclomethasone was obtained without side effects and without changes in serum cortisol levels (08.00) in any of the nine examined subjects. These results suggest that the inhibitory effect of inhaled beclomethasone on TDI-induced late asthmatic reactions and increased responsiveness is dose-dependent.