Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling

Increased airway smooth muscle mass is a prominent feature of asthmatic airway remodeling. Airway smooth muscle hyperplasia occurs in rodent models of experimental asthma, but the relevance of such finding to spontaneously occurring disease in large mammals is unknown. We examined horses with heaves, a naturally occurring equine asthma related to sensitization and exposure to moldy hay. We hypothesized that airway remodeling occurs in heaves and shares disease mechanisms with asthma. We quantified the airway smooth muscle mass and the numbers of proliferating and apoptotic airway smooth muscle cells in 5 horses with heaves and 5 control horses using morphometric techniques. Cell proliferation was detected in tissue sections by immunostaining for proliferating cell nuclear antigen, and apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling of fragmented DNA. Both signals were colocalized with smooth muscle specific α-actin. Horses with heaves had a significant increase in the amount of smooth muscle in the airways (nearly triple that of the controls) associated with increased myocyte proliferation (7-fold proliferating cell nuclear antigen–positive airway myocytes) and apoptosis (6-fold). Heaves involves airway smooth muscle growth associated with myocyte hyperplasia, which may contribute to the growth, and increased myocyte apoptosis that may reflect a compensatory mechanism serving to limit the abnormal smooth muscle growth. Airway smooth muscle remodeling in heaves may be involved in the mechanism of airway hyperresponsiveness and chronic lung function impairment in a way comparable to human asthma.