title: Effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung function, bronchoalveolar lavage fluid cytology, and transcription factor expression in airways of horses with recurrent airway obstruction.
abstract: Glucocorticoid (GC) therapy is recognized to be effective for the treatment of recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC are thought to be mediated by suppression of inflammatory gene expression via inhibition of transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). The purpose of this study was to evaluate the effect of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21-isonicotinate on clinical signs, pulmonary function, airway cytology, and activity of NF-kappaB and AP-1 in bronchial cells of RAO-affected horses. Seven horses with RAO were exposed to moldy hay until they developed airway obstruction on 3 separate occasions. In a crossover design, they were then treated with a placebo (injection on day 1), inhaled beclomethasone (500 microg q12h for 10 days), or dexamethasone (0.06 mg/kg, IM on day 1) and monitored for 10 days. Pulmonary function, bronchoalveolar lavage fluid cytology, and NF-kappaB and AP-1 activity in bronchial brushing cells were measured before (day 1) and after treatment (day 10). Treatment with beclomethasone resulted in significantly improved pulmonary function of RAO-affected horses compared with placebo and dexamethasone treatments. However, none of the treatments had an effect on bronchoalveolar lavage fluid cytology or NF-kappaB and AP-1 activity. These findings reveal that, in a model of severe RAO, the benefits of low-dose inhaled beclomethasone on pulmonary function are not accompanied by a decrease in airway inflammatory cells or a suppression of transcription factors NF-kappaB and AP-1 DNA-binding activity.
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, University of Liège, Belgium. couetill@purdue.edu
authors.forename: Laurent L
authors.initials: LL
authors.lastname: Couëtil
authors.forename: Tatiana
authors.initials: T
authors.lastname: Art
authors.forename: Brieuc
authors.initials: B
authors.lastname: de Moffarts
authors.forename: Martine
authors.initials: M
authors.lastname: Becker
authors.forename: Dorothée
authors.initials: D
authors.lastname: Mélotte
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jaspar
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
authors.forename: Pierre
authors.initials: P
authors.lastname: Lekeux
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001507:Beclomethasone / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D018592:Cross-Over Studies; D003908:Dexamethasone Isonicotinate / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D012138:Respiratory Therapy; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D014157:Transcription Factors; D003908:Dexamethasone Isonicotinate; D001507:Beclomethasone