Why Horses Are Trapped by Severe Asthma

Neutrophil extracellular traps, or NETs, help ward off many types of infections. In the case of asthma, however, NETs have a darker side and appear to be key players in driving severe disease. New research shows that NET levels can be used to predict severe asthma and may also serve as a potential target for treating severely asthmatic horses.^*

Produced by infection-fighting white blood cells, NETs are composed of genetic material (DNA), proteins, peptides, and enzymes. NETs “catch” infection-causing microorganisms to stop them from spreading throughout the body and destroy them with their antimicrobial properties.

“Excessive NET production or delayed elimination may, however, have harmful effects in immune-mediated disorders. In mouse and human research, NETs are thought to influence environment-driven allergic asthma and neutrophilic asthma, respectively,” explained Catherine Whitehouse, M.S., a nutrition advisor for Kentucky Equine Research.

In horses, severe asthma, often triggered by exposure to environmental allergens, is characterized by a primarily neutrophilic inflammation of the lower airways. Neutrophils are a type of white blood cell that play a role in fighting infections and are the first cells recruited to the site of an allergic reaction.

“High numbers of neutrophils are found in bronchoalveolar lavage fluid (BALF) collected from the horse’s lungs and lower airways during a lung wash. The presence of these white blood cells is a cardinal feature of severe equine asthma,” Whitehouse said.

These neutrophils can therefore release NETs into the horse’s lower airways, which may be detrimental, potentially contributing to lung damage.

Twenty-one horses diagnosed with asthma underwent a lung wash to measure NETs in the BALF. Fourteen of those horses were diagnosed with severe equine asthma with the remainder having moderate asthma. The veterinary research team found:

• NETs were only found in BALF collected from severely asthmatic horses; and
• A significant positive association between NET levels and neutrophil numbers was identified.

“Because BALF NETs are unique to horses with severe asthma, they are a good predictor of disease severity,” suggested Whitehouse.

These findings also support the hypothesis that pathways leading to moderate and severe asthma are distinct, and that NETs may be a driving factor in the development of severe equine asthma. If so, then developing medications targeting NETs, either their production or breakdown, would be an interesting avenue to explore.

Currently, managing severe equine asthma is a multipronged approach that addresses allergen avoidance, bronchodilation, and airway inflammation.

“Experts also recommend supplementing horses with severe equine asthma with omega-3 fatty acids, particularly the long-chain omega-3 fatty acids. The specific long-chain omega-3 fatty acids DHA and EPA from marine sources such as fish oil are more biologically active than plant-based, short-chain omega-3 fatty acids. DHA and EPA produce metabolites that have anti-inflammatory properties that provide body-wide health benefits,” added Whitehouse.

 ^*Janssen, P., I. Tosi, A. Hego, P. Marechal, T. Marichal, and C. Radermecker. 2022. Neutrophil extracellular traps are found in bronchoalveolar lavage fluids of horses with severe asthma and correlate with asthma severity. Frontiers in Immunology 13:921077.