Corticosteroids and Antigen Avoidance Decrease Airway Smooth Muscle Mass in an Equine Asthma Model

Abstract

Recent studies suggest that airway smooth muscle remodeling is an early event in the course of asthma. Little is known of the effects of long-term antigen avoidance and inhaled corticosteroids on chronically established airway remodeling. We sought to measure the effects of inhaled corticosteroids and antigen avoidance on airway remodeling in the peripheral airways of horses with heaves, a naturally occurring asthma-like disease. Heaves-affected adult horses with ongoing airway inflammation and bronchoconstriction were treated with fluticasone propionate (with and without concurrent antigen avoidance) (n = 6) or with antigen avoidance alone (n = 5). Lung function and bronchoalveolar lavage were performed at multiple time points, and peripheral lung biopsies were collected before and after 6 and 12 months of treatment. Lung function improved more quickly with inhaled corticosteroids, but eventually normalized in both groups. Inflammation was better controlled with antigen avoidance. During the study period, corrected smooth muscle mass decreased from 12.1 ± 2.8 × 10(-3) and 11.3 ± 1.2 × 10(-3) to 8.3 ± 1.4 × 10(-3) and 7.9 ± 1.0 × 10(-3) in the antigen avoidance and fluticasone groups, respectively (P = 0.03). At 6 months, smooth muscle mass was significantly smaller compared with baseline only in the fluticasone-treated animals. The subepithelial collagen area was lower at 12 months than at baseline in both groups. During the study period, airway smooth muscle remodeling decreased by approximately 30% in both groups, although the decrease was faster in horses receiving inhaled corticosteroids. Inhaled corticosteroids may accelerate the reversal of smooth muscle remodeling, even if airway inflammation is better controlled with antigen avoidance.

Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways

“…Pulmonary function, BAL fluid and endobronchial biopsies (see below) were obtained at baseline and then 1, 3, 6, 7 and 12 months later. As previously reported, 18 both treatments resulted in improved airway function, although it was more rapidly observed when horses were treated with inhaled fluticasone than with antigen avoidance strategies alone. Conversely, normalisation of BALF neutrophilia was present only when horses were at pasture without hay feeding.…”

“…The increased (+)insert isoform to total SMMHC ratio during clinical exacerbation is not permanent, as it can be reversed by antigenic avoidance strategies (studies 1 and 3) or by the use of inhaled corticosteroids despite continuous antigen challenge and persisting airway inflammation (study 2 18 ). In study 2, the decrease of the (+)insert isoform to total SMMHC ratio coincided with the normalisation of pulmonary neutrophilia only in the antigen avoidance-treated group.…”

“…18 In brief, 11 adult heaves-affected horses were housed indoors and exposed to hay until they all exhibited clinical signs suggesting airflow obstruction (Baseline). Antigen exposition induced an airflow limitation in horses with heaves with increased pulmonary resistance and lung elastance values.…”

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…”

“…Clinical signs and airway obstruction can be reversed by administration of corticosteroids, bronchodilators, or changing the environment 4, 5, 6. Recurrent airway obstruction principally affects horses over 7 years of age 7, 8.…”