Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model.
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.
Department of Veterinary Clinical Sciences, Université de Montréal, Saint-Hyacinthe, Quebec, Canada.
Mathilde
M
Leclere
Anouk
A
Lavoie-Lamoureux
Philippe
P
Joubert
Fabien
F
Relave
Emilie Lanctot
EL
Setlakwe
Guy
G
Beauchamp
Christian
C
Couture
James G
JG
Martin
Jean-Pierre
JP
Lavoie
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000494:pharmacology; D056151:Airway Remodeling / Q000187:drug effects; D000403:Airway Resistance; D000730:Androstadienes / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D055745:Bronchioles / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000068298:Fluticasone; D006734:Horse Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006736:Horses; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009000:Monocytes / Q000378:metabolism; D009130:Muscle, Smooth / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D052179:Antigens, Plant; D001993:Bronchodilator Agents; D016207:Cytokines; D018836:Inflammation Mediators; D018809:Proliferating Cell Nuclear Antigen; D003094:Collagen; D000068298:Fluticasone