Combination of corticosteroid therapy and allergen avoidance reverses allergen-induced airway remodeling in mice

Abstract

Allergen avoidance and anti-inflammatory therapy are standard therapeutic approaches guidelines advocate to control asthma symptoms. Currently, it is not known whether such strategies reduce airway remodeling. We have therefore used a mouse model of allergen-induced airway remodeling to determine whether allergen avoidance combined with corticosteroid therapy can reverse established airway remodeling. Mice were sensitized to ovalbumin and then repetitively challenged with intranasal ovalbumin for 3 months to develop structural features of airway remodeling including peribronchial fibrosis and increased thickness of the peribronchial smooth muscle layer. At this time point, mice were treated with allergen avoidance, allergen avoidance and corticosteroids, or corticosteroids for 1 month to determine whether either strategy could reverse established airway remodeling. Mice repetitively challenged with ovalbumin developed peribronchial fibrosis (increased total lung collagen and increased peribronchial trichrome staining) as well as increased thickness of the peribronchial smooth muscle layer. Allergen avoidance significantly reduced airway inflammation and mucus expression, slightly reduced peribronchial fibrosis, and had no effect on the thickness of the peribronchial smooth muscle layer. Addition of corticosteroids to allergen avoidance significantly reduced levels of peribronchial fibrosis as well as the thickness of the peribronchial smooth muscle layer. Allergen avoidance reduces airway inflammation and mucus expression but has more limited immediate effects on reducing structural features of established airway remodeling. The combination of allergen avoidance and corticosteroid therapy is effective in reversing established features of airway remodeling including peribronchial fibrosis and the increased thickness of the smooth muscle layer.