A case of the heaves: Veterinarians deal with recurrent airway obstruction in horses

Confined, stabled horses have to contend with a lack of fresh air and the inability to continually nibble on fresh grass. In addition, they're exposed to potential contamination in their environment from dust; more than 50 types of molds; toxins associated with dried forage, bedding and stale air; and a mixture of noxious gas (ammonia, hydrogen sulfide, methane, carbon dioxide) and airborne dust—both organic and inorganic.

All these pollutants can negatively impact horses' respiratory systems. Indeed, such horses have an increased risk of developing a chronic, recurrent and debilitating respiratory syndrome, says Jean-Pierre Lavoie, DMV, Dipl. ACVIM, professor of equine internal medicine at Université de Montréal, Canada.

This respiratory syndrome, called recurrent airway obstruction (RAO), or heaves, occurs in up to 20 percent of adult horses in the cold northern hemisphere and in temperate climes. Current thought, according to Lavoie, is that RAO "likely results from complex interactions between innate and acquired immune responses, environment and genetic susceptibility." Horses with heaves exhibit a chronic disorder of the airway and present with variable and recurring airflow obstruction, bronchial hyperresponsiveness and airway inflammation. They also show increased respiratory effort at rest, cough and decreased exercise performance.

"What we know for certain about heaves is that in many horses it's precipitated by stabling," says Ed Robinson, BVetMed, PhD, Matilda R. Wilson Chair in Large Animal Clinical Sciences at Michigan State University's College of Veterinary Medicine. "Our current understanding is that it's exacerbated from inhaling the particles from hay, such as stable dust. Heaves is defined as a recurrent airway obstruction caused by inhalation of inorganic dust."

A horse with labored breathing at rest, without infection as a cause of these signs, is suffering from heaves, says Renaud Léguillette, DMV, MSc, PhD, Dipl. ACVIM, associate professor of equine internal medicine, Veterinary Clinical and Diagnostic Sciences, University of Calgary Veterinary Medicine Department. Horses have such a large lung capacity that when their lungs aren't functioning well enough to properly respire at rest, the problem of inflammation can become extensive.

"Once you see a horse with heaves, it's really too late, as the damage is severe enough to disrupt normal breathing," says Léguillette. All of the lung tissue is severely damaged, affected by a lot of inflammation and lung tissue remodeling. The damage is a triad of

• Bronchoconstriction

• Inflammation—inflammatory cell accumulation in the airway affects the small bronchi and alveoli

• Mucous plugs, or overproduction of mucous in the small airways.

"The three insults combined are really terrible for proper lung function," Léguillette says. "The bronchoconstriction narrows the airways, plus increased mucous accumulation causes the airway to be constricted and partially blocked, which severely limits normal breathing."

True allergy?

Researchers have asked, is RAO initiated via the same mechanism that true allergies are—as allergen binds to IgE, promoting mast cell release of various mediators of inflammation, such as cytokines and histamine? Or does it result from a nonspecific inflammatory response to inhaled pro-inflammatory agents such as molds, endotoxins, particulates and noxious gases present in the breathing zone of stabled horses.

In the case of the allergic response, once the pro-inflammatory mediators are released, a cascade of mucous secretion, vasodilation, microvascular leakage and airway smooth muscle contraction may ensue. The result is narrowing of the airway lumen and obstruction. Theoretically, a second phase response is T-cell mediation of an asthmatic response.

For horses with RAO, what's the immune mechanism? "We don't know that in horses," says Robinson. "We're pretty certain heaves is not a typical IgE-mediated allergic immune response." It has all the characteristics of an allergic disease, he notes. Horses exposed to certain environments get airway obstruction and airway inflammation. For example, if an RAO horse is purchased in New York and is then moved to a stable in Kansas, it might not show heaves in that environment, Robinson says. "Heaves seems to be related to something in the local environment that causes the problem."

In people, hayfever is mediated via mast cells. But that doesn't appear to be the case in equine heaves. "It does seem to have the characteristics of an allergic disease, but the exact immune response is not understood," says Robinson. "Skin tests don't predict the allergens that will cause heaves. The measurement of IgE doesn't predict the things that are going to initiate the disease. So it's not a classical IgE immune-response hypersensitivity."

Another aspect that isn't typical of allergy—neutrophils are found in the airway of horses with heaves. Says Lavoie, "Usually with allergy, it's more mast cells or eosinophils—granulocytes nonetheless—similar but different.

"When we started to work on the immunological component of the disease, we found the bronchial lavage from horses with heaves express cytokines, which are similar to those we see with allergy, a Th2 profile," Lavoie continues. "We know that heaves is not a true allergic response, in which within 30 or 45 minutes of exposure to the allergen, you'll start to see clinical signs. When we take horses with heaves and bring them into the stables, some horses will become symptomatic within a day, but others will take several days to show signs. With heaves, we don't see the initial stage of the disease—the immediate allergic response. However, the rest of the response looks like an allergy because it's pretty much related to exposure to antigen, primarily to hay. If we expose a horse with heaves to feeding on hay, it becomes symptomatic. If we remove the hay, the clinical signs essentially disappear."

Initially, it was uncommon to see Th2-type, response-associated neutrophils, Lavoie says. At that time neutrophils were not considered an important part of the asthmatic response in people. "But during the past 10 years that has changed, where today there's a lot of interest regarding the role of neutrophils in asthma. Our grant work was to try to understand how Th2-type cytokines could activate neutrophils."

His studies have shown that, using recombinant proteins, "if we make equine IL-4 and expose them to neutrophils, it activates the neutrophils," says Lavoie. "Also, if you expose endothelial cells from the pulmonary artery of horses to IL-4, they'll produce cytokines, mediators that are chemotactic factors to neutrophils. We and others have done a large body of studies showing that Th2-type cytokines contribute to not only attracting neutrophils within the airways, but also activating them."

Robinson says RAO is different from human asthma, which tends to diminish as people age. "There is no 'childhood' heaves, i.e., young foals getting heaves. It's a disease of older horses; 8 to 10 years old is the common age of onset."

Lavoie agrees, adding, "We do see young horses, even weanlings, coughing, but it's rare to see foals with RAO. The process of airway remodeling, the changes in the lung architecture, including increases in smooth muscle surrounding the airways, probably takes years to occur."

Airway remodeling

A critical portion of Lavoie's research involves the physical changes that take place within the lungs of horses with heaves—a buildup (which gets more severe over time) of smooth muscle surrounding the airway tissue. Eventually, a lot of these horses are euthanized because they're difficult to manage.

"We think the reason they become increasingly severe is because of the changes occurring within the lungs surrounding the airways, as is true in human asthma," Lavoie says. "We reported that horses with heaves have two to three times more smooth muscle surrounding the airways than age-matched control healthy horses. The more muscle present, the more likely the contraction is going to be. The lumen of the airways is reduced in diameter, therefore air is not moving freely through the airway. And with the increased smooth muscle, there's increased contraction of the airway, making breathing even more difficult."

In further research, Lavoie studied airway remodeling, taking lung biopsy samples from deceased horses and from horses with heaves over time (a few months or years). In the live horses with severe cases of heaves, they documented the same thing they saw in the necropsied samples.

Lavoie tried to reverse this increase in smooth muscle remodeling. His team studied a group of horses with heaves—half were pastured on pelleted feed for a year and the other half were treated with inhaled corticosteroids for a year. Initially, the horses treated with corticosteroids were stabled. After six months they continued the treatment and put them on pasture. They measured smooth muscle surrounding the airways before the treatment, at six months and again at a year. Mathilde Leclere, DMV, a graduate student in Lavoie's lab, showed there's a decrease in the amount of smooth muscle surrounding the airway after treatment with inhaled corticosteroids, but they were very far from reversing it even after a year. The researchers also showed if they kept horses with heaves stabled for a few weeks, smooth muscle mass didn't change, since remodeling is inherently a very gradual process.

Leclere also looked at what was responsible for the decrease in airway smooth muscle, as they hope to eventually develop targeted therapy that may allow for restoration of lung tissue to normal status, if possible.

Another Université de Montréal graduate student, Emilie Lanctot-Setlakwe, DMV, is looking at the collagen content present between the epithelium and the smooth muscle. "She found there's an increase in collagen, so there is also some fibrosis taking place in the lung tissue of horses with heaves. We're trying to determine if this is reversible or not," Lavoie says.

These studies show airway remodeling, or the change in airway architecture, takes place during a period of several years. "That's probably why we rarely see the severity of clinical signs of airway disease in young horses," Lavoie says. "Coughing may be present, though the horse lung has an incredible reserve compared with the human lung. The severe disease process takes years to develop, and we rarely see the lung damage of heaves in young horses at rest."

Attempts at control—a confluence of factors

Heaves is a chronic condition. The propensity to develop airway obstruction doesn't go away, so such horses have to be continually managed. Add to this the fact that the stable is a complex environment, and you see that there are many factors to consider.

"We know endotoxin present in hay dust plays a role in the inflammation response," says Robinson. "When trying to figure out what to do to help the affected animal, there's no point where a horse owner can decide to try to take 'this' or 'that' out of the horse's bedding or hay, because they'll never know exactly what to take out."

The horse owner, instead, needs to focus on reducing the particulate exposure. The best solution is pasturing these horses. For many horses with heaves, keeping them on pasture grass in spring and summer and in run-in sheds with pelleted food during winter can help keep them free of signs of disease—though this may not be practical for many clients.

"One concern about horses eating hay is that they sink their noses directly into the hay net or manger. As they tug at the hay, they create dust," says Robinson. "Also, if it's a show horse, people need to think about this when they travel with the animal."

Owners and equine specialists should also think about reducing particles in the stable. "Keep the doors and windows open. For a particularly 'heavey' horse, take it off hay and give it something that has less dust, such as a complete pelleted feed," Robinson says.

Soaking hay may be an easy solution because it significantly reduces the particles. But note it also may wash out the nutrients. "Unless the horse eats it all at once, it dries out again. As it dries, it may grow more mold," Robinson cautions.

Stall cleaning is another factor. Consider a horse that has been away from its stall for 24 hours, and the stall hasn't been cleaned out during that time, Robinson says. Mold grows in the bedding, the horse walks on it and the spores are kicked up into the stall environment as a cloud of dust. Clients with RAO-afflicted horses should be educated about keeping the stall cleaned and the horse out of the stall while it's being mucked out.

"I'm not as concerned about the bedding, per se, but about getting the chaff hay out of the bedding," says Robinson. "The particles from hay are a lot more of a concern that the particles from straw, which are larger and don't get very far into the lungs."

A final factor, says Robinson, is noxious gases, such as ammonia, which are respiratory irritants and enhance the production of mucous, so they may contribute to airway obstruction.

"With heaves, often a little bit of this by itself may not cause a problem," says Robinson, "but when it's mixed with a little bit of that, the two together may have a synergistic effect. There are all kinds of interactions between particles, endotoxins, molds, ozone, ammonia—all are in some way interacting with each other. But predicting what exactly may be affecting a particular horse—that's not easy. One almost needs a diary to keep track of what may be the problem."

And stabling is not a problem for all horses, just for certain RAO-afflicted horses, he continues. "I have a former graduate student who has a 'heavey' horse that she can manage quite well housed in a stable. She has a low-dust stall for it, but its big trigger is a dusty arena. If it goes outside and runs around a dusty arena, it will be affected. Similarly, some horses are affected by certain pollens outdoors. Some horses have seasonal problems, and you can manage those with the proper medications at those times of the year."

Overall solution—limit exposure

As noted, the main concern for horses with heaves is to limit their exposure to organic dust. "If horses are confined to stables, turn them outside as much as possible. Put the horses completely off hay, and feed them pellets or cubes," says Léguillette. Léguillette also recommends the use of hay steamers. The steam kills molds and bacteria and washes the hay to decrease dust and organic particles. "They seem to work very well. I strongly recommend preventing exposure to organic dust as much as possible. I also recommend that people turn their horses out when they sweep the barn area or when bedding the stall to reduce exposure to dust, and to wet the barn area when they sweep to keep the dust down. If people are turning their horses out, even for only a few hours per day, it should be at the time they're cleaning the stall and barn areas. Wait a couple of hours before bringing the horse back into the barn."

In Calgary, researchers even found that horses that had been turned outside during cold weather did better than those left in confinement with dust. "The barn is a bad place for accumulation of dust, especially for horses with lung disease," Léguillette says.

The main implication of this research interest—changes occurring in the lungs of horses with heaves are quite severe, says Lavoie. "It's probable that once these horses are heave-affected, once the disease has progressed, it might be too late to reverse the condition. One probably needs to intervene much earlier.

"What we don't know at this point for those horses with mild asthma or inflammatory airway disease: Do those animals go on to develop more severe disease? We need to recognize early on horses that will eventually develop heaves and apply appropriate therapy or change their environment to change this progression, which eventually causes this severe decline in airway function."

Suggested reading

1. Lavoie JP. Heaves in horses: Allergy or non-specific response to environmental antigens, in Proceedings. 11th Geneva Congress on Equine Medicine and Surgery. 2009;23-26.

2. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses. Respirology 2001;16(7):1027-1046.

3. Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner E, et al. Effect of antigenic exposure on airway smooth muscle remodeling in an equine model of chronic asthma. Am J Cell Mol Biol 2001;45(1):181-187.

4. Wasko AJ, Barkema HW, Nicol J, et al. Evaluation of a risk-screening questionnaire to detect equine lung inflammation: results of a large field study. Eq Vet J 2001;43(2):145-152.

Ed Kane, PhD, is a researcher and consultant in animal nutrition. He is an author and editor on nutrition, physiology and veterinary medicine with a background in horses, pets and livestock. Kane is based in Seattle.