Effects of once daily dosing with inhaled budesonide on airway hyperresponsiveness and airway inflammation following repeated low-dose allergen challenge in atopic asthmatics.
BACKGROUND
Repeated low-dose allergen challenge increases airway hyperresponsiveness and sputum eosinophils in atopic asthmatics. Inhaled corticosteroids attenuate the airway responses to high-dose allergen challenge, but have 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 allergen challenge.


METHODS
Eight atopic asthmatics with a dual airway responses to inhaled allergen were recruited into a randomized, double-blind crossover, placebo-controlled study. In the mornings of four consecutive days (day 1-day 4), subjects inhaled budesonide 100 microg, 400 microg, or placebo, 30 min before inhaling a concentration of allergen causing a 5% early fall in FEV1. Airway hyperresponsiveness to methacholine and sputum eosinophils were measured at baseline, 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 percentage 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 microg to 5.6 +/- 1.8% (P = 0. 01) and by once daily budesonide 400 microg to 3.1 +/- 0.9% (P = 0. 004). Also, the allergen-induced methacholine airway hyperresponsiveness which occurred by day 4 (P = 0.03) of the repeated low dose challenge was inhibited by budesonide 400 microg (P = 0.017).


CONCLUSIONS
Both budesonide 100 microg and 400 microg inhaled once daily significantly reduces allergen-induced sputum eosinophilia after repeated low dose challenge; however, only the higher dose also attenuates the allergen-induced airway hyperresponsiveness.
Gauvreau
G M
GM
Asthma Research Group, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, Canada.
Sulakvelidze
I
I
Watson
R M
RM
Inman
M D
MD
Rerecich
T J
TJ
O'Byrne
P M
PM
D000328:Adult; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology
D000485:Allergens; D001993:Bronchodilator Agents; D019819:Budesonide