The Effect of Adding Oral Dexamethasone to Feed Alterations on the Airway Cell Inflammatory Gene Expression in Stabled Horses Affected with Recurrent Airway Obstruction

Abstract

Background: Chemokine expression in airway epithelium and bronchoalveolar lavage fluid (BALF) cells of horses with recurrent airway obstruction (RAO) is increased.Hypothesis: For RAO-affected horses that are stabled and fed a pelleted ration, the addition of oral dexamethasone further improves pulmonary function and reduces inflammatory gene expression in pulmonary cells.Animals: Twelve RAO-affected horses. Methods: In a randomized cross-over experiment, the effect of feeding pellets in lieu of hay to stabled, RAO-affected horses was compared with the effect of feeding pellets and administering a 21-day decreasing dose regimen of oral dexamethasone on the expression (by kinetic polymerase chain reaction) of interleukin-8 (IL-8), chemokine (C-X-C motif) ligand 2 (CXCL2), IL-1b, IL-6, and b-actin in the BALF cells and of IL-8, CXCL2, 2 IL-1 receptor (IL-1R2), Toll-like receptor 4 (TLR4), and glyceraldehyde 3-phosphate dehydrogenase in the bronchial epithelium 2 days after the final dose.Results: Both treatments reduced airway neutrophilia and breathing efforts but the addition of dexamethasone was associated with fewer treatment failures. Compared with feed changes alone, dexamethasone administration further reduced the expression of IL-8, CXCL2, and IL-1b in the BALF cells 3.3-, 2.5-, and 4.7-fold, respectively. In the airway epithelium, both treatments were equally efficacious in reducing the expression of IL-8 and CXCL2 expression relative to pretreatment values, but either treatment failed to alter the expression of IL-1R2 and TLR4.Conclusions and Clinical Importance: For a rapid and consistent improvement in pulmonary function and a reduction in inflammatory gene expression of the BALF cells, a decreasing dose of oral dexamethasone in combination with feed alterations is more efficacious for horses that must remain stabled.

Efficacy of oral prednisolone and dexamethasone in horses with recurrent airway obstruction in the presence of continuous antigen exposure

“…Cornelisse et al. (2004) showed a transient improvement in pulmonary function after a single dose of oral dexamethasone at 0.082 and 0.164 mg/kg bwt dosage and DeLuca et al. (2008) reported fewer treatment failures when oral dexamethasone (tapering dose over 3 weeks: 0.165–0.04 mg/kg bwt q.…”

Inflammatory Airway Disease of Horses—Revised Consensus Statement

“…One study found that long‐term dexamethasone and fluticasone treatment did not reverse the airway neutrophilia when RAO horses are kept indoors and exposed to hay even after 6–7 months 6. Other studies showed an additive effect on clinical signs, airway neutrophilia, and inflammatory cytokines in RAO horses when combining corticosteroid treatment with measures to improve air quality 6, 115, 116…”

Heaves, an asthma‐like disease of horses

“…In heaves, as in allergen‐induced asthma, removing the offending antigens is central to the control of the disease 205,206 . Grass pasture leads to alleviation of clinical signs, and normalization of conventional lung function tests and BALF neutrophilia 129,207,208 . Clinical signs subside in days to weeks, depending on age, and severity or duration of the disease 209 .…”