Severe Equine Asthma: Abnormal Airway Smooth Muscle Explained

Horses with severe equine asthma (SEA) harbor a high number of neutrophils, a specific type of white blood cell, in their airways. New research shows that after being exposed to environmental allergens, such as lipopolysaccharide (LPS), neutrophils release microscopic extracellular vesicles capable of stimulating the growth of airway smooth muscles.^* Inflammation and excessive growth of airway smooth muscle, also called airway remodeling, cause airway obstruction, making it harder for asthmatic horses to expel air from their lungs.

“Microscopic vesicles are produced by all cells and contain molecules involved in intercellular communication. Data from human and equine asthmatic patients suggest that extracellular vesicles release signaling molecules that could directly enhance the proliferation of airway smooth muscle,” explained Kathleen Crandell, Ph.D., a Kentucky Equine Research nutritionist.

LPS, a component of bacterial cell walls omnipresent in the environment, is a known trigger for SEA. This is why experts recommend turning out horses rather than maintaining them in barns with poor ventilation where LPS abounds.

To evaluate the effect of LPS stimulation on extracellular vesicles and airway smooth muscle mass, a herd of horses with SEA was recruited. Neutrophils were collected from the blood of these horses during times of quiescent disease or acute exacerbations. Extracellular vesicles were isolated from the neutrophils and incubated in cell cultures containing airway smooth muscle cells from the same horses harvested through biopsy.

“The extracellular vesicles were collected from horses when not suffering a current bout of SEA and again during acute exacerbation. When stimulated with LPS, the vesicles spurred proliferation of the airway smooth muscle cells,” Crandell explained.

The research team therefore concluded that inhaling environmental LPS, a common environmental contaminant, could contribute to the development of asthma by activating neutrophils that release extracellular vesicles. The contents of the vesicles can then lead to excessive airway smooth muscle growth, also known as airway remodeling.

“Pasture turnout helps minimize exposure to LPS and other asthma-inducing allergens. When not possible, mitigating the effects of stabling by supplementing horses with the long-chain polyunsaturated omega-3 fatty acids DHA and EPA found in marine-derived oils is recommended. Benefits of DHA- and EPA-mediated inflammatory response include reduction in inflammation and allergic reactivity,” Crandell said.

The most recent ACVIM consensus statement on inflammatory airway disease recommends DHA for horses with inflammatory airway disease/equine asthma.^** EO-3, a product developed by Kentucky Equine Research, contains both DHA and EPA, and is a suitable supplement for horses with SEA.

^*S. Mainguy-Seers, F. Beaudry, C. Fernandez-Prada, J.G. Martin, and J.-P. Lavoie. Neutrophil extracellular vesicles and airway smooth muscle proliferation in the natural model of severe asthma in horses. Cells 11(21):3347.

 ^**Couëtil, L.L., J.M. Cardwell, V. Gerber, J.-P. Lavoie, R. Léguillette, and E.A. Richard.  2016. Inflammatory airway disease of horses—Revised consensus statement. Journal of Veterinary Internal Medicine 30(2):503-515.