Effect of an inhaled glucocorticosteroid (budesonide) on post-antigen induced increases in airway responsiveness.
We examined the effects of an inhaled glucocorticosteroid, budesonide, on antigen-induced early and late bronchial responses and the development 24 h after challenge of increased airway responsiveness to carbachol in allergic sheep. Six allergic sheep were used for this study and, on occasions separated by at least three weeks, they were treated: with placebo (treatment 1); 16 h and 20 min prior to antigen challenge with budesonide (treatment 2); 16 h and 20 min prior to and 8 h after antigen challenge with budesonide (treatment 3); or 16 h and 1 h prior to and 8 h after antigen challenge with budesonide (treatment 4). Airway responsiveness to carbachol was determined prior to and 24 h after antigen challenge by measuring specific lung resistance (sRL) after administering increasing doses of carbachol aerosol (0.5, 1 and 2.5% w/v) and determining the concentration of carbachol needed to increase sRL 150% over baseline (PC150). Placebo treatment did not affect the early or late increases in sRL after airway challenge with Ascaris suum antigen; 24 h after challenge, airway responsiveness to carbachol increased (p less than 0.05); at this time, PC150 was (mean +/- SEM) 0.88 +/- 0.15% as compared to 1.56 +/- 0.26% before challenge. Both treatments 2 and 3 blunted the early response to antigen and blocked the late response, but treatment 2 did not modify the antigen-induced increase in airway responsiveness, whereas treatment 3 did. Treatment 4 blocked both antigen-induced responses and was effective in blunting the increased airway responsiveness. These results suggest that antigen-induced increases in airway responsiveness: occur 24 h after a challenge in allergic sheep with early and late responses; can be blunted by budesonide; and are not dependent on the late response.
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000947:Antigens, Helminth; D001200:Ascaris / Q000276:immunology; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D019819:Budesonide; D002217:Carbachol / Q000037:antagonists & inhibitors; D004334:Drug Administration Schedule; D005938:Glucocorticoids / Q000494:pharmacology*; D011282:Pregnenediones / Q000494:pharmacology*; D012756:Sheep
D000947:Antigens, Helminth; D005938:Glucocorticoids; D011282:Pregnenediones; D019819:Budesonide; D002217:Carbachol