The effects of inhaled budesonide and formoterol in combination and alone when given directly after allergen challenge.
BACKGROUND
The use of combination inhaled budesonide and formoterol as maintenance and reliever therapy significantly improves the risk and the time to exacerbations in asthma.


OBJECTIVE
To explore the mechanisms underlying the effect of the reliever dose on exacerbations by examining the effect of combination therapy on the allergen challenge model when given after allergen exposure.


METHODS
In a randomized, double-blind crossover study, single doses of budesonide/formoterol (400/12 mug), formoterol (12 mug), budesonide (400 mug), or placebo were administered during the acute bronchoconstriction response (early airway response) immediately after allergen inhalation in 15 patients with mild asthma. Allergen-induced late airway response (LAR), sputum inflammatory markers, airway hyperresponsiveness, and exhaled nitric oxide were measured.


RESULTS
All active treatments significantly attenuated the LAR, with budesonide/formoterol significantly better than its monocomponents (maximum FEV(1) fall: placebo, [mean +/- SEM] 21.2% +/- 3.1%; budesonide/formoterol, 4.2% +/- 1.4%; formoterol, 7.5% +/- 1.7%; budesonide, 10.4% +/- 1.6%). Allergen-induced change in methacholine PC(20) was significantly attenuated by budesonide/formoterol, but not by its monocomponents. Sputum cell counts and exhaled nitric oxide increased significantly after all allergen challenges, with no significant attenuation by any of the treatments. Therapy with combination and formoterol alone, but not budesonide, significantly reduced the early airway response.


CONCLUSIONS
A single dose of budesonide/formoterol was superior to its monocomponents in attenuating the allergen-induced LAR and airway hyperresponsiveness. These effects may represent the contribution of the reliever dose to the budesonide/formoterol maintenance and reliever regimen.


CONCLUSIONS
The protective effect against allergic airway responses with a single reliever dose of budesonide/formoterol is predominantly related to greater functional antagonism of airway smooth muscles.
Duong
MyLinh
M
Firestone Institute for Respiratory Health, St Joseph's Hospital and McMaster University Medical Center, McMaster University, Hamilton, Ontario, Canada. duongmy@mcmaster.ca <duongmy@mcmaster.ca>
Gauvreau
Gail
G
Watson
Richard
R
Obminski
George
G
Strinich
Tara
T
Evans
Michelle
M
Howie
Karen
K
Killian
Kieran
K
O'Byrne
Paul M
PM
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D019819:Budesonide / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology
D000485:Allergens; D004983:Ethanolamines; D016210:Methacholine Chloride; D019819:Budesonide; D000068759:Formoterol Fumarate