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-kB (NF-kB) 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-kB 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 mg 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-kB 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 RAOaffected horses compared with placebo and dexamethasone treatments. However, none of the treatments had an effect on bronchoalveolar lavage fluid cytology or NF-kB 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-kB and AP-1 DNA-binding activity.

Fluticasone Propionate Aerosol is More Effective for Prevention than Treatment of Recurrent Airway Obstruction

“…We saw no such decrease in our short‐term trial, a result similar to another investigation in which FP (2 mg q12h) improved lung function within 2 weeks but neutrophil numbers in BALF were unchanged 2 . The same variable results have been reported in trials with DEX, in which longer‐term drug administration has been associated with a decrease in BALF neutrophil percentage, 13,15–17 but short‐term administration 18 or administration of a low dose (0.04 mg/kg) caused no change 19 …”

Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse

“…The first signs of clinical improvement could only be seen after four days of treatment. Although this would indicate a complex trans-repressive mechanism of action, Couteil et al could not show a decrease in pro-inflammatory transcription factors (NF-kappaB, AP-1) in the BALF despite clinical signs improving significantly [9]. These findings are in line with our results and suggest that clinical improvement (in our study inhibition of bronchoconstriction) was achieved through a fast-acting non-genomic mechanism.…”

“…Beclomethasone dipropionate (BDP) is a widely administered inhaled corticosteroid in equine practice [7,8], although in vivo studies have shown that the marked improvement of clinical signs of airway obstruction after administration of low-dose inhaled beclomethasone was not accompanied by a decrease in airway inflammatory cells or a suppression of transcription factors NF-kB and AP-1 DNA-binding activity [9]. …”

Investigating the Link between Particulate Exposure and Airway Inflammation in the Horse

“…Changes include increases in lung elastance, resistance, and transpulmonary pressures, and decreased dynamic lung compliance, with accompanying decline in arterial O 2 tension and increased arterial CO 2 tension . When dust exposure is minimized, RAO horses enter remission, with resolution of clinical and cytologic signs and improvement in lung resistance and transpulmonary pressure measurements …”