Does Heaves Adversely Influence the Immune Response?

Heaves results from an inflammatory reaction within the lower airway that is triggered when horses inhale dust and other environmental allergens from hay or bedding.

Heaves—the common name for recurrent airway obstruction (RAO) or chronic obstructive pulmonary disease (COPD)—is one of the most common reasons horses are referred to the Cornell University Hospital for Animals. Primarily afflicting middle-aged and older horses, heaves is an inflammatory condition in the lungs that severely limits the athletic performance of horses.

"Much like asthma in humans, the condition causes a chronic cough, a nasal discharge composed of mucus and inflammatory cells, an accentuated abdominal breathing effort, and exercise intolerance," says Dorothy Ainsworth DVM, MS, PhD, Dipl ACVIM, a large-animal pulmonologist and associate professor of medicine in the Department of Clinical Sciences.

Heaves is triggered when susceptible horses inhale hay dust and other environmental allergens from hay or bedding and develop an inflammatory reaction within the lower airway, similar to asthma in humans. The horse becomes hypersensitive to the inhaled allergens and launches an inflammatory response in defense.

With a new grant from the Harry M. Zweig Memorial Fund, Ainsworth, in collaboration with Judith Appleton MS, PhD, and Douglas Antczak DVM, PhD, is building on her previous Zweig- and USDA-funded research evaluating the immuno-pathogenesis of heaves. In the past she's explored how the immune systems of symptomatic heavey horses exposed to a foreign antigen respond and produce antibodies.

With this new grant, Ainsworth seeks to find out whether a horse that is asymptomatic but prone to the development of heaves will be biased in its immune response to an inhaled vaccine or antigen, as compared to a healthy horse.

"We need to know more about the immune response in heavey horses not only because it is such a common condition afflicting the health and performance of a large percentage of mature horses but also because we don't know if conventional vaccines might adversely affect the airway obstruction in horses whose immune systems have already been challenged by allergens," says Ainsworth. "We just don't know whether the inflammatory condition of heaves might prevent an adequate immune response from developing if we try to vaccinate the horse."

Understanding better whether a horse that already has, or is prone to, heaves has a different sort of immune response to an antigen than a healthy horse is important not only for recurrent airway obstruction but also for other kinds of diseases as well.

For example, consider the case of a young foal infected with intestinal roundworms, says Ainsworth. As part of their life cycle, these parasites migrate through the foal's lungs, establishing a type of immune response known as a T helper cell 2 or Th-2 reaction. This kind of response drives the allergic responses, which are a feature of human asthma. This response is differentiated from another kind of T helper cell known as a Th-1 that protects against bacterial and viral infections within body cells (cellular immunity) and are pro-inflammatory.

What happens if the young foal responds with Th-2 immune response during a roundworm infection (the lung environment is biased toward a Th-2 reaction) and the animal is then challenged by either a bacterial or viral infection?

"The dominating Th-2 environment might attenuate the foal's response to the microbial infection and compromise its ability to clear the secondary bacterial or viral invader," says Ainsworth. "This has been documented in mice, rats, and guinea pigs, not in the horse. The net result is that the Th-2 environment has a negative impact on the pulmonary and systemic health of the foal."

Ultimately Ainsworth's results should benefit not only heaves-affected horses but improve the overall understanding of the equine immune response.

At present, COPD has no cure. Corticosteroids are often prescribed to reduce airway inflammation and relax bronchial constriction, and bronchodilators may be used to relieve respiratory distress.

Once a horse has COPD, it will likely continue to be oversensitive to airborne allergens. A variety of horse management changes can help minimize the horse's exposure to hay dust. Keep the horse outside as much as possible. In the barn, use shavings instead of straw to bed the horse and pellets, alfalfa cubes, and grass silage instead of hay for feed. Managing adjacent stalls in the same way also helps keep hay dust low in the general area. Ventilating the barn via open windows and doors or installing a ventilating system, and storing hay far from the vulnerable horse, also can go a long way in keeping the horse's exposure to the airborne allergens down.

Instead of searching for a cure, Ainsworth's focus is to learn how to best develop vaccines or immuno-therapies not only for healthy horses but also for susceptible horses that are already sick and will need continuing treatment.