Hay is for horses, but what if it leads to asthma?

Horses shown wearing an air sampling device developed by Dr. Kathleen Ivester to monitor dust levels in the horses' "breathing zone." Photos courtesy of Dr. Laurent Couetil.

A racehorse's lungs are critical to its performance. In fact, after lameness, respiratory disease is the most common cause of poor performance in racehorses. Although a horse's muscles and heart can be strengthened by training, its respiratory system cannot.

According to Laurent L. Couëtil, DVM, PhD, DACVIM-LAIM, professor of veterinary clinical sciences and director of equine research programs at Purdue University College of Veterinary Medicine, as they reach full speed, racehorses take two breaths per second, inhaling 16 L of air per breath. At five furlongs, or five-eighths of a mile, a racehorse consumes 1,800 L of air per minute.

The term “equine asthma” has come to be used as a “unifying descriptor of inflammatory airway disease [IAD], recurrent airway obstruction [RAO], and summer pasture–associated obstructive airway disease.”1 In fact, Dr. Couëtil and colleagues have proposed that the term “mild/moderate equine asthma” replace IAD and “severe equine asthma” replace RAO in the equine literature altogether, although they acknowledge the need to preserve the spectrum of diseases that fall under the “asthma” classification.2

Dr. Couëtil and Kathleen Ivester, DVM, PhD, DACVS, his research colleague at Purdue, recently shed light on some of the environmental factors that play a role in equine asthma.

Unique respiratory physiology of horses

Lung disease affects oxygen intake and gas exchange, the main functions of the respiratory system. Dr. Couëtil's early research focused on oxygen tension in equine arterial blood during treadmill running. “We know horses are unique athletes because when they exercise, their blood oxygen level gets extremely low,” he says. “We don't see that degree of low oxygen tension in any other species.”

Partial pressure of oxygen (PaO2) in healthy animals' arterial blood is about 100 mm Hg at rest, Dr. Couëtil explains. During peak exercise in normal, fit horses, PaO2 drops to 80 mm Hg, and sometimes lower. “Racehorses can tolerate these low levels because they are such tremendous athletes,” he says. A major reason their PaO2 drops so low is that their cardiac system can push blood at extremely high pressure.

“Horses push red cells through the lung and barely have enough time to load up oxygen,” he says. “This low PaO2 is also partly because horses are obligate nose breathers, which has its limitations.” Considering these physiological factors, it's easy to understand why even low-level lung disease would further reduce blood oxygen levels, thus impairing performance.

Recurrent airway obstruction: Severe asthma

When Dr. Couëtil started investigating the more severe form of equine asthma, commonly known as heaves or RAO, it was clear that the cause was the housing and eating of extremely dusty and moldy hay, particularly from round bales. “This is especially bad for horses that are already quite susceptible,” he says. “My colleagues and I think [severe asthma] is more than an allergic type of response to inhaled mold that is enhanced by the presence of endotoxin in the dust particles.”

Inflammatory airway disease: mild/moderate asthma

Dr. Couëtil and his team at Purdue were especially interested in developing sensitive lung function tests, especially for horses showing mild signs. “We wanted to know what prompted the milder form of equine asthma,” he says.

IAD is a widespread syndrome in horses in which lower airway inflammation results in impaired gas exchange and poor racing performance.3 It's the most common chronic airway disease of equine athletes, with a prevalence in racing thoroughbreds estimated to be as high as 80%.⁴

Clinical signs of IAD include coughing, poor performance and excess mucus in the airways. Diagnosis is confirmed by demonstration of an increased percentage of neutrophils, mast cells, eosinophils or a combination of these cell types in the bronchoalveolar lavage fluid (BALF) or “lung wash”; lower airway obstruction; airway hyperresponsiveness; or impaired gas exchange in the absence of both infection and increased respiratory effort at rest.⁵

According to a 2014 study by the Purdue team, exposure to airborne dust and other irritants in the barn environment seems to play a major role in IAD pathogenesis. Their results showed that particulate exposure was significantly higher in horses fed from hay nets inside their stall compared with those fed hay from the ground.⁵

“In the clinic, I would see a lot of athletic horses, especially racehorses, that presented with either coughing or sometimes just ‘poor performance,'” Dr. Couëtil says. “These were healthy horses; they just were not performing well. Instead of being able to perform at 100%, they were at 98%, but in racing, fractions of a second make a difference.”

Development of airway inflammation in otherwise healthy horses occurs upon introduction to barn confinement, with its higher dust environs and higher respirable endotoxin concentrations.5 The barn environment increases not only hay dust but also other particulates and gaseous ammonia, both of which have been implicated in the etiology of IAD, although the pathogenesis of the disease remains largely unknown.

Dr. Couëtil and his team wanted to understand the role of inflammation on lung function and performance in a real-life situation at the racetrack. They also wanted to determine what causes mastocytic airway inflammation. “Our hypothesis concerned three potential factors: (1) infectious agents (e.g. bacteria, viruses), (2) the environment (e.g. exposure to dust) and (3) horse factors, either a genetic component or innate susceptibility in some individuals.

“As the carriers of aeroallergens, particulates could be expected to induce eosinophilic and mastocytic airway inflammation if this phenotype does indeed arise as a consequence of hypersensitivity,” the authors state. “However, research directly linking changes in BALF cytology to measures of natural environmental exposure was lacking.”

To monitor dust exposure in horses in real-life situations, “we fixed samplers on the halter right around their nose, enabling us to determine how much dust they were exposed to,” Dr. Couëtil explains.3 “Using this method, we could detect how much endotoxin or β-glucan was present in cell walls to give us an idea of its exposure. We equipped horses for hours with these collection devices when they were in the stall so we could see what they were breathing. We also measured the general dust level in the barn.”⁵ Many similar studies have been conducted in the past, but their samplers were placed in the barns or in stalls rather than on the horses themselves.

Horses shown wearing an air sampling device developed by Dr. Kathleen Ivester to monitor dust levels in the horses' "breathing zone." Photos courtesy of Dr. Laurent Couetil.

Results of their study of 1- to 3-year old thoroughbreds newly entering training confirmed that “airway inflammation in young horses most commonly manifests as an increase in airway mast cells, eosinophils or both.”5 The researchers concluded that “IAD develops in response to inhaled environmental irritants and offers the first epidemiologic evidence that eosinophilic IAD might represent a hypersensitivity to inhaled particulate allergens.”5 Eosinophils respond to respirable dust particles, so a small horse breathes these particles deep into its lungs.

Using multivariate analysis, the researchers found a negative association between lung inflammation/performance and two types of cells in the lungs, neutrophils and mast cells. Neutrophils are associated with innate immunity, mast cells with an allergic response. “The mast cell inflammation led to a greater decline in performance, presumably because this type of cell has a tendency to make the airway shut down, a phenomenon known as airway hyperreactivity or airway hyperresponsiveness,” Dr. Couëtil explains. “It makes sense that this would have a greater negative effect on performance.”

Interestingly, the nature of the dust itself affected the degree of airway inflammation. Smaller-particle, respirable dust was associated with neutrophilic inflammation, whereas β-glucan (a component of mold and fungi and a surrogate marker for exposure to inhaled molds) was associated with mast cells.

Results from the 2014 study suggest an association between what the horse was inhaling through the nose and a specific type of inflammation in its lung cells, verified via BALF.3 “That was the first evidence that there was a relationship between dust exposure and inflammation in the lungs. There was no association between the barn dust level and lung inflammation,” Dr. Couëtil says.

“Our research has focused a lot on the role of particulate exposure,” says Dr. Ivester. “We found that the most meaningful measurement, as Dr. Couëtil noted, is done using the sampling device on the horse so you can see what it's exposed to within its breathing zone. We found that the most critical dust particles were ‘respirable dust,' which are extremely small. They get down deep into the lung, where they have their effect on airway inflammation.”

“The fact that net placement, as well as the use of hay nets themselves, have an impact on equine asthma was very surprising to us,” Dr. Couëtil adds. “Hay nets are used extensively not only to assist with feeding but also to limit in-stall boredom. This enabled us to compare horses fed hay on the stall floor versus in a hay net, and placement of the hay net inside or outside the stall door. We found a fourfold higher dust exposure in the horses eating from hay nets inside the stall.” Dr. Ivester says horses fed from hay nets essentially keep their nose next to the net the entire time they are eating; this is not the case when horses eat from the ground.

The team also studied horses at Indiana racetracks bedded with fine sawdust instead of straw. “Although one would suspect fine sawdust to be dustier than straw, it turns out the sawdust particles are fairly large-more than 100 microns-so they don't go deep in the lung,” Dr. Couëtil says. “We're convinced that most of the dust exposure is from the hay versus the bedding or other sources in the barn. Even in stalls we suspected had high ammonia concentration, the effect on the horse was nondetectable.”

When they compared the effects of changing bedding with changing forage, researchers found that what the horse was eating had the largest effect on its dust exposure. “Dry hay, regardless of quality, tends to generate a lot more dust than other forages (such as hay that is steamed or wetted down, haylage, pelleted feed or hay cubes),” Dr. Ivester says. “And low-quality hay is going to be more dusty than good-quality hay. If we can figure out the best way to feed racehorses in stalls, we can have some meaningful reduction in their exposures.”

Diagnosing equine asthma

Horses with asthma appear clinically normal at rest except for occasional coughing, so diagnosis requires advanced techniques such as endoscopic detection of increased tracheal mucus accumulation or demonstration of increased proportions of inflammatory cells recovered in BALF.

In their 2018 study, Ivester and colleagues evaluated performance and BALF findings from 64 thoroughbreds from eight stables for a total of 98 race performances and 79 dust exposure assessments.4 Within one hour of completing a race, physical examination, respiratory endoscopy and BALF evaluation were conducted.

Respirable dust, respirable endotoxin and respirable β-glucan exposures were measured at the breathing zone within one week after racing. Controlling for age, trainer and the presence of pulmonary hemorrhage, the relationship between performance, BALF cytology and measures of dust and particulate exposure were modeled.4

Evidence of mild equine asthma was found in 80% (78/98) of BALF samples from 52 of the 64 horses. For each percent increase in BALF mast cell and neutrophil proportions, speed figures were reduced by 2.9 and 1.4 points, respectively. Respirable dust concentration was associated with BALF neutrophil proportions. BALF mast cell proportions were only associated with respirable β-glucan exposures,” the researchers say.

Racetrack veterinarians commonly use endoscopy rather than BALF evaluation in horses with signs of breathing problems. Horses with airway inflammation tend to produce more mucus in their lungs, which can be seen on endoscopy as increased mucus accumulation in the trachea, especially if the endoscopy is performed within an hour after a race. Mucus accumulation can alert a veterinarian that the horse might have equine asthma. Otherwise, most signs are minimal. BALF is the better test for collecting cells from the deep lung.

The results from the 2018 study by Ivester and colleagues show that exposure to dust among horses stalled at a racetrack results in airway inflammation, thus negatively affecting performance. They also confirmed results from their earlier study:5 that extremely fine dust-particles about 4 microns in size (“respirable dust”)-leads to airway disease deep in the lungs.4 Visible dust-particles about 100 microns (“inhalable dust”)-was not associated with inflammation. Therefore, respirable rather than inhalable dust exposure measures are pertinent to equine airway health, the investigators say.

"What horses are fed and how they are housed has a huge impact on what their exposures will be,” Dr. Ivester says. “We've been looking at ways to modify management in an effort to minimize the risk of airway inflammation, because we found that management has a direct effect on racing performance.

Although racehorses kept in stalls are susceptible to equine asthma, all horses in confinement or fed dry hay are potentially exposed to higher levels of dust and mold. Performance horses, particularly racehorses, are most susceptible.

Horsemen and veterinarians are often surprised that the incidence of mild equine asthma is as high as 80%, largely because it's often subclinical. Although horses with mild to moderate asthma have some respiratory inflammation, they don't always show overt signs. About 14% of horses with asthma have an intermittent cough, and decreased performance is often attributable to other factors.

"There are many different types of inflammation, especially in young horses,” Dr. Ivester says. “Which type develops seems to depend heavily upon what the strongest exposure is. What we consider nonspecific inflammation of neutrophils in the lung wash we see more in relation to the overall respirable dust exposure and the endotoxin exposure. We see a lot of mast cell inflammation in the lungs of young horses. That seems to be most directly related to the β-glucan exposure, and that's mostly related to fungal exposure, specific fungal products or allergens the horses are reacting to.”

Managing equine asthma

Often, treatments proven to work in horses with severe asthma are used empirically in performance horses with mild asthma. It is clear that environmental management is the only thing that reliably reduces the presence of inflammatory cells. Even treating with corticosteroids doesn't have as strong an effect as modifying the environment.

Some histopathology studies have shown structural changes in the lungs of horses with asthma. It would be interesting to get some longitudinal data and follow those horses beyond their short (three-to-five-year) racing career to gauge the long-term impact of early dust exposure. If these horses move on to other types of performance, their function may be affected in ways not yet recognized.

References

1. Bond S, Léguillette R, Richard ER, et al. Equine asthma: Integrative biologic relevance of a recently proposed nomenclature. J Vet Intern Med 2018;32:2088-2098.

2. Couëtil LL, Cardwell JM, Gerber V, et al. Inflammatory airway disease of horses-revised consensus statement. J Vet Intern Med 2016;30(2):503-515.

3. Couëtil LL, Hoffman AM, Hodgson J, et al. Inflammatory airway disease of horses. J Vet Intern Med 2007;21:356-361.

4. Ivester KM, Couëtil LL, Moore GE. An observational study of environmental exposures, airway cytology, and performance in racing thoroughbreds. J Vet Intern Med 2018;32(5):1754-1762.

5. Ivester KM, Couëtil LL, Moore GE, et al. Environmental exposures and airway inflammation in young thoroughbred horses. J Vet Intern Med 2014;28:918-924.