Dorothy Ainsworth Examines Immunotherapy for Treatment of COPD
Earlier Zweig funding allowed Ainsworth (left) to record for the first time the electrical activity in animal diaphragms during high intensity exercise.
As a child, Dorothy Ainsworth, DVM, MS, PhD, Dipl ACVIM, wanted to be a riding instructor. These days, her expertise has far surpassed her early aspirations but still largely center on the horse. She is a highly valued instructor at the College of Veterinary Medicine at Cornell, where she was just honored by the 1998 graduating class as the 1998-99 Norden Distinguished Teacher. She also is a pioneering researcher working on ways to unravel the complexities of the respiratory physiology of the horse in efforts to determine why thousands of athletic horses are unable to perform to their potential.
Ainsworth, a large-animal pulmonologist, is an associate professor of medicine in the department of clinical sciences and section chief of large-animal medicine in the Equine and Farm Animal Hospitals at Cornell. Several years ago she discovered that claims that the diaphragm played only a minor role in the generation of air flow patterns in animals was wrong. Through a series of very technically difficult experiments with dogs, and later with horses, Ainsworth recorded for the first time the diaphragm's electrical activity in an animal during high intensity exercise. These experiments were partially funded by the Zweig Memorial Fund.
"We think that allergen desensitization through immunotherapy just may be a viable and safe treatment option for COPD in all kinds of horses, including racehorses."
We showed that the diaphragm is, indeed, an important and active muscle in exercise and that it probably does not normally fatigue despite the development of severe arterial hypoxemia and hypercapnia, says Ainsworth. Her diaphragm work has made it possible to evaluate diaphragm function in the horse for the first time and to study under what circumstances the diaphragm fatigues.
Ainsworth's Zweig research is now turning to chronic obstructive pulmonary disease (COPD), commonly known as "heaves."
"COPD is a common disorder of horses in the northeast and midwest who are fed hay diets and stabled indoors," she explains. "Affected horses exhibit a chronic cough, nasal discharge, and an accentuated abdominal breathing effort referred to as a 'heave'."
One mode of treating affected horses is to try to keep the animals outdoors so they won't be exposed as often to inhaled environmental allergens contained within feedstuffs or bedding; researchers believe these allergens trigger an immune-mediated inflammatory reaction within the lower airways, much like asthma in humans. For numerous reasons, however, owners don't like to keep their horses outside 24 hours a day.
Ainsworth says the drug therapy currently used to treat COPD-the administration of oral glucocorticoids such as prednosolone and/or dexamethasone-is far from ideal. It can have serious health side effects including, among other problems, suppression of the immune system, a decrease in bone and muscle mass, thinning of the skin, and the induction of a negative protein balance.
Ainsworth is using new support from the Zweig Memorial Fund to objectively and scientifically investigate the efficacy of immunotherapy in COPD-affected horses. This tactic will work as a "vaccination" against specific allergens believed to trigger the immune reactions.
"Preliminary studies have suggested that this may be an effective therapy for COPD and we know that immunotherapy has been used in the treatment of allergic respiratory diseases in man and in dogs," Ainsworth points out.
To study immunotherapy's viability for COPD, Ainsworth and her collaborators, including vet school immunologist Judith Appleton, M.S., Ph.D., will identify COPD-prone horses and obtain baseline data on them. The horses will then be challenged for up to 10 days with natural allergen exposures from a diet of hay, grain, and corn and being kept in stalls bedded with straw. After measuring the horses' allergic reactions after exposure to these substances (using skin tests) and eliminating any horses that don't react, the horses will be immunized over a six-month period with a mixture of purchased purified allergens. During that time, they will be removed from the natural allergen challenges in their feed and bedding.
After six months, the horses' allergic reactions will be remeasured and they will once again be challenged in the natural allergen environment. Then their measurements will be taken one more time to see if, in fact, they no longer react negatively to the allergens in their environment because of their "vaccinations."
"We think that allergen desensitization through immunotherapy just may be a viable and safe treatment option for COPD in all kinds of horses, including racehorses, and may be able to safely restore cardiopulmonary function in affected horses," Ainsworth concludes.