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.

Inflammatory Airway Disease of Horses—Revised Consensus Statement

“…It is thought that the risks of developing adverse effects associated with this treatment might be increased compared to inhaled corticosteroids,118 although the evidence is weak. Inhaled beclomethasone and fluticasone can be administered by metered dose inhaler via specialized delivery devices 115, 119, 120, 121. However, a fluticasone propionate metabolite was observed in the blood and urine when the drug was administered by inhalation at therapeutic doses,122 and adrenal suppression was detected after administration of beclomethasone dipropionate by inhalation 118…”

Equine asthma: Integrative biologic relevance of a recently proposed nomenclature

“…Inflammatory cell populations in the lung represent a balance between cellular recruitment, via airway epithelial cell and macrophage‐derived chemotactic cytokines, and removal, via apoptosis and phagocyte‐mediated clearance. Lung granulocytes (neutrophils and macrophages) in horses with RAO exhibit altered apoptosis, which together with increased activity of transcription factors such as nuclear factor‐κB (NF‐κB) and activator protein‐1 (AP‐1) might contribute to the maintenance of neutrophilic inflammation in horses treated with glucocorticoids and maintained in an allergenic environment . Whilst no age‐related trends in BALF cytological profiles in horses with IAD or RAO have been reported, there is an age‐associated increase in mRNA expression of IFN‐γ producing lymphocytes in stimulated BAL cells .…”

Review of glucocorticoid therapy in horses. Part 2: Clinical use of systemic glucocorticoids in horses

“…; Couëtil et al . ). As was mentioned previously, the parenteral route is more efficacious for critical cases, but once the condition is stable, the enteral route is widely used due to the ease of administration (Robinson et al .…”

“…or inhaled beclomethasone dipropionate (Couëtil et al . ). Even though pulmonary function testing responses and clinical signs of airway obstruction improve by administration of beclomethasone, the magnitude of response is less marked than the response of i.m.…”

“…In a study by Couëtil et al . (), RAO challenged horses weighing between 341 and 521 kg, were treated with either low dose beclomethasone dipropionate (500 μg every 12 h) for 10 days or one single injection of dexamethasone isonicotinate (0.06 mg/kg bwt i.m.). After 10 days, the horses treated with the inhaler showed significant improvement in respiratory function, when compared with the horses treated with dexamethasone i.m.…”