Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma.
BACKGROUND
Combining inhaled corticosteroids with long-acting beta(2)-agonists results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma.


OBJECTIVE
We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling.


METHODS
Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment.


RESULTS
Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle area. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area.


CONCLUSIONS
The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol.
Kelly
Margaret M
MM
Firestone Institute for Respiratory Health, Department of Medicine, St Joseph's Healthcare and McMaster University Medical Center, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
O'Connor
Terence M
TM
Leigh
Richard
R
Otis
Joceline
J
Gwozd
Carol
C
Gauvreau
Gail M
GM
Gauldie
Jack
J
O'Byrne
Paul M
PM
D000199:Actins / Q000187:drug effects; D000280:Administration, Inhalation; D000328:Adult; D056151:Airway Remodeling / Q000187:drug effects*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004802:Eosinophilia / Q000188:drug therapy; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009130:Muscle, Smooth / Q000187:drug effects; D013183:Sputum / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000199:Actins; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate