Effects of once daily dosing with inhaled budesonide on airway hyperresponsiveness and airway inflammation following repeated low-dose allergen challenge in atopic asthmatics
Gm. Gauvreau et al., Effects of once daily dosing with inhaled budesonide on airway hyperresponsiveness and airway inflammation following repeated low-dose allergen challenge in atopic asthmatics, CLIN EXP AL, 30(9), 2000, pp. 1235-1243
Background Repeated low-dose allergen challenge increases airway hyperrespo
nsiveness and sputum eosinophils in atopic asthmatics. Inhaled corticostero
ids attenuate the airway responses to high-dose allergen challenge, but hav
e not been evaluated against repeated low dose challenge.
Objective This study evaluates the effects of once daily treatments of two
doses of inhaled budesonide on airway responses to repeated low-dose allerg
en challenge.
Methods Eight atopic asthmatics with a dual airway responses to inhaled all
ergen were recruited into a randomized, double-blind crossover, placebo-con
trolled study. In the mornings of four consecutive days (day 1-day 4), subj
ects inhaled budesonide 100 mu g, 400 mu g, or placebo, 30 min before inhal
ing a concentration of allergen causing a 5% early fall in FEV1. Airway hyp
erresponsiveness to methacholine and sputum eosinophils were measured at ba
seline, on the afternoon of day 2, day 4, and 24 h after the last challenge
. There was a 1-week washout between each of the three treatment periods.
Results The repeated low-dose allergen challenge induced increases in the p
ercentage sputum eosinophils from 2.0 +/- 0.7% at baseline to 16.6 +/- 7.1%
on day 4 (P = 0.002), and this effect was reduced by once daily budesonide
100 mu g to 5.6 +/- 1.8% (P = 0.01) and by once daily budesonide 400 mu g
to 3.1 +/- 0.9% (P=0.004). Also, the allergen-induced methacholine airway h
yperresponsiveness which occurred by day 4 (P=0.03) of the repeated low dos
e challenge was inhibited by budesonide 400 mu g (P = 0.017).
Conclusion Both budesonide 100 mu g and 400 mu g inhaled once daily signifi
cantly reduces allergen-induced sputum eosinophilia after repeated low dose
challenge; however, only the higher dose also attenuates the allergen-indu
ced airway hyperresponsiveness.