New Thoughts on Treatment of Equine Asthma

A diagnosis of equine asthma syndrome may include one of several respiratory disorders, from inflammatory airway disease (IAD) to heaves (chronic obstructive pulmonary disorder or COPD). Treatment often involves systemic or inhaled corticosteroid drugs and fish oil supplements, such as EO•3, a potent marine-derived oil rich in the omega-3 fatty acids DHA and EPA. Both glucocorticoids and fish oil have anti-inflammatory properties believed to decrease airway inflammation caused by the influx of various white blood cells, including neutrophils, into the airways.

Dexamethasone and inhaled fluticasone decrease airway hyperresponsiveness, a condition characterized by the constriction of respiratory structures. Unfortunately, improvement does not translate to a diminishment in the clinical signs of equine asthma syndrome. In addition, the number of inflammatory cells in the lower airways does not decline following treatment with dexamethasone or fluticasone.

A Canadian research team* reported recently that one explanation for the lack of an asthmatic horse’s response to corticosteroids could be “neutrophil extracellular traps.”

“Neutrophils respond poorly to glucocorticoids, even high levels of inhaled formulations, whereas other types of inflammatory cells such as eosinophils and T lymphocytes significantly decrease in the airways following treatment,” explained Laura Petroski, B.V.M.S., a veterinarian at Kentucky Equine Research.

“The latest research shows that this lack of responsiveness occurs because neutrophils release long strands of decondensed genetic material and proteins into the space around them. These accumulations, which are now referred to as ‘neutrophil extracellular traps’ or NETs, cause airway obstruction that is nonresponsive to inhaled corticosteroids,” she said.

In addition to NETs, the inflammatory protein called interleukin-17 (IL-17) makes neutrophils resistant to the effects of glucocorticoids. In this study, six horses with severe neutrophilic asthma were recruited to better understand NETs and IL-17.

“Researchers hypothesized that IL-17 contributes to NET formation and, if affirmed, this knowledge could potentially serve as a novel treatment target,” Petroski said.

Neutrophils were collected from the blood and bronchoalveolar lavage of the horses, and IL-17 was evaluated. The researchers noted the following:

• Neutrophils collected from the airways of asthmatic horses had enhanced NET formation in vitro (the laboratory setting). These neutrophils were responsive to glucocorticoid application;
• Neutrophils collected from the blood of asthmatic horses did not have enhanced NET formation;
• IL-17 was increased in cells collected from lung-wash fluid, and the levels of IL-17 were unaffected by glucocorticoid therapy; and
• To the researchers’ surprise, IL-17 decreased NET formation.

While researchers continue to study NETs and other factors contributing to glucocorticoid failure, horse owners should consider alternate strategies for managing equine asthma, such as maintaining horses on pasture whenever possible, protecting the horse from excessive dust and debris, soaking hay, and offering a proven fish oil supplement, like EO•3.

*Vargas, A., R. Boivin, P. Cano, et al. 2018. Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma. Respiratory Research 18(1):207.