title: Combined budesonide/formoterol therapy in conjunction with allergen avoidance ameliorates house dust mite-induced airway remodeling and dysfunction.
abstract: Allergic asthma is characterized by airway inflammation in response to chronic allergen exposure, resulting in remodeling of the airway wall accompanied by dysfunctional airway physiology. However, a link between the immune-inflammatory response to allergen and changes to airway structure and physiology has not yet been fully elucidated. Moreover, the impact of inhaled corticosteroids and beta(2)-agonists, the primary pharmacotherapy for asthma, on this process has not been completely evaluated. In this study, we employed a murine model of chronic exposure to a common environmental aeroallergen, house dust mite, to recapitulate the phenotype of clinical asthma. By examining the therapeutic effects of corticosteroid/beta(2)-agonist combination therapy with budesonide/formoterol (BUD/FORM) in this model of airway disease, we endeavored to determine the impact of BUD/FORM on lung inflammation, structure, and physiology. BUD/FORM was delivered either while allergen exposure was ongoing (concurrent therapy) or following the cessation of allergen exposure (postexposure therapy). Our results show that airway inflammation was substantially reduced in BUD/FORM-treated mice in the concurrent therapy group, whereas in the postexposure therapy group airway inflammation spontaneously resolved. In contrast, BUD/FORM was most effective in resolving several aspects of airway remodeling and bronchial hyperreactivity when delivered in conjunction with allergen withdrawal. This study demonstrates that although both BUD/FORM therapy and allergen avoidance independently reduce airway inflammation, only BUD/FORM therapy in conjunction with allergen avoidance can effectively reverse airway remodeling and bronchial hyperreactivity induced by chronic allergen exposure.
authors.affiliation: Department of Pathology and Molecular Medicine, Michael G. DeGroote Centre for Learning and Discovery, McMaster University, 1200 Main St. West, Hamilton, Ontario, Canada.
authors.forename: Jill R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Pacitto
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wong
authors.forename: Elliot W
authors.initials: EW
authors.lastname: Archer
authors.forename: Stefan
authors.initials: S
authors.lastname: Eirefelt
authors.forename: Anna
authors.initials: A
authors.lastname: Miller-Larsson
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
mesh_terms: D000199:Actins / Q000378:metabolism; D000485:Allergens / Q000276:immunology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D000068759:Formoterol Fumarate; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy; D039981:Pyroglyphidae / Q000276:immunology*; D012140:Respiratory Tract Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D000199:Actins; D000485:Allergens; D001993:Bronchodilator Agents; D004983:Ethanolamines; D016210:Methacholine Chloride; D019819:Budesonide; D003094:Collagen; D000068759:Formoterol Fumarate