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 studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship. Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response.


METHODS
Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium bromide as needed. These subjects had positive allergen and methacholine inhalation tests and FEV1 greater than 70% of predicted value. A double-blind, randomized, cross-over study compared placebo and budesonide 100, 200, and 400 microg administered by means of Turbuhaler twice 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 compared with placebo, but there was no significant difference between the 3 doses of budesonide, and no dose response was demonstrated. The methacholine PC20 was significantly larger after all budesonide treatments compared with placebo (P = .024), but there was no difference between the 3 doses. There was a progressive increase in the allergen PC15 chronologically (sequence effect) that was not explained by improvement in FEV1 or airway responsiveness; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20. Statistical adjustment for sequence effect did not alter allergen PC15 statistics.


CONCLUSIONS
A 7-day course of budesonide administered by means of Turbuhaler at 200, 400, or 800 microg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo. There was, however, no difference between the 3 doses. Therefore this method with these doses is not useful for providing assessment of relative potency.
Swystun
V A
VA
Royal University Hospital, University of Saskatchewan, Department of Medicine, Saskatoon, Canada.
Bhagat
R
R
Kalra
S
S
Jennings
B
B
Cockcroft
D W
DW
D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016085:Bronchoconstrictor Agents / Q000276:immunology; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride / Q000276:immunology; D008875:Middle Aged; D010919:Placebos
D000485:Allergens; D000893:Anti-Inflammatory Agents; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D010919:Placebos; D016210:Methacholine Chloride; D019819:Budesonide