Effect of an inhaled glucocorticosteroid on mast cell and smooth muscle beta 2 adrenergic tolerance in mild asthma.
BACKGROUND
Regular inhaled beta 2 agonist therapy is associated with loss of bronchoprotection to indirect bronchial provocation challenges such as allergen or adenosine monophosphate (AMP), while directly acting challenge is less affected, implying preferential mast cell tolerance. Glucocorticosteroids may reverse such beta 2 adrenoreceptor tolerance and upregulate mast cell beta 2 adrenoceptor function.


METHODS
The effect of single high dose glucocorticosteroids on terbutaline induced loss of bronchoprotection was studied in a placebo controlled, double blind, cross-over study. Fifteen asthmatic subjects who were not taking inhaled glucocorticosteroids underwent two 10-day treatment periods with terbutaline (500 micrograms four times daily via Turbohaler), each followed by a single dose of inhaled budesonide (800 micrograms via Turbohaler) or identical placebo.


RESULTS
Regular treatment with terbutaline resulted in significant loss of bronchoprotection to AMP (mean difference (95% CI) -1.7 (-3.0 to 0.4) doubling dilutions) but not to methacholine (mean difference -0.1 (-1.0 to 0.8) doubling dilutions). Single high dose budesonide increased the protective effect of terbutaline more to AMP than to methacholine challenge (+0.76 (0.3) doubling dilutions compared with +0.13 (0.4) doubling dilutions, respectively). The mean (SE) difference between budesonide and placebo for methacholine challenge was 0.08 (0.14) whereas that for AMP was 0.075 (0.15); p = NS. The difference in PC20 was not statistically significant when compared with placebo for either challenge agent.


CONCLUSIONS
Inhaled glucocorticosteroids in a single dose had no significant effect in restoring terbutaline induced loss of bronchoprotection, implying that mast cell beta 2 adrenoceptor sensitivity is not restored by a single dose of an inhaled glucocorticosteroid in asthma.
Yates
D H
DH
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Worsdell
M
M
Barnes
P J
PJ
D000249:Adenosine Monophosphate; D000280:Administration, Inhalation; D000287:Administration, Topical; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D016210:Methacholine Chloride; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects; D013726:Terbutaline / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D016085:Bronchoconstrictor Agents; D005938:Glucocorticoids; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate; D019819:Budesonide; D013726:Terbutaline