Greater effect of inhaled budesonide on adenosine 5'-monophosphate-induced than on sodium-metabisulfite-induced bronchoconstriction in asthma.
Inhaled glucocorticosteroids (GCS) decrease airway responsiveness (AR) in asthma by mechanisms that may involve suppressing airway inflammation and a reduction in the number of inflammatory cells in the airways. To investigate the functional response to a reduction in airway inflammatory cells in asthma, we studied the effects of inhaled budesonide on AR to three different bronchial challenges, adenosine 5'-monophosphate (AMP), which primarily activates mast cells; methacholine (MCh), a direct stimulus, and sodium metabisulfite (MBS), a neural stimulus. In a double-blind randomized crossover manner, with a washout period of 28 days, 12 subjects with mild asthma underwent inhalation challenge with doubling increments of MCh, MBS, and AMP before and after 14 days of treatment with budesonide 0.8 mg twice daily from a multidose dry-powder delivery system (Turbohaler) or matched placebo. Treatment with budesonide reduced AR to MCh and MBS to a similar degree, displacing the dose-response curve of each agonist to the right by 1.17 (95% confidence intervals, 0.34 to 2.00) and 1.06 (0.34 to 1.78) doubling dilutions, respectively, when compared with placebo (p less than 0.01). Budesonide caused an additional and significantly greater reduction in AR to AMP, displacing the dose-response curve to the right by 2.92 (2.12 to 3.72) doubling dilutions when compared with placebo (p less than 0.001) and to the other challenges (p less than 0.01). We conclude that budesonide reduces AR to MCh and MBS by an action common to the effects of both direct and neural stimuli on airway smooth muscle contraction. The greater reduction in AR to AMP suggests that budesonide may have an additional action by reducing airway mast cell numbers and/or function.
O'Connor
B J
BJ
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Ridge
S M
SM
Barnes
P J
PJ
Fuller
R W
RW
D000249:Adenosine Monophosphate; D000280:Administration, Inhalation; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide; D004311:Double-Blind Method; D004341:Drug Evaluation; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D016210:Methacholine Chloride; D011282:Pregnenediones / Q000008:administration & dosage*; D013447:Sulfites
D001993:Bronchodilator Agents; D005938:Glucocorticoids; D011282:Pregnenediones; D013447:Sulfites; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate; C005200:sodium metabisulfite; D019819:Budesonide