RESPIRATORY

Respiratory Infections May Be Risk Factor for Mild Equine Asthma

By Marie Rosenthal MS

Just about every veterinarian knows to look at the stable environment when diagnosing a horse for inflammatory airway disease (IAD) or mild/moderate equine asthma, but there may also be an association with certain infectious agents, according to Eric A. Richard, DVM, PhD, the head of clinical biology and senior researcher at LABÉO Frank Duncombe, in Normandy, France.

“There does appear to be some association between infection and mild equine asthma,” said Dr. Richard, although he added this is a relatively new area of research, and definitive data are lacking.

“We know the environment is involved in the occurrence of the disease, but there are fewer data about infectious agents,” he said.

Horses with mild equine asthma usually present with a history of chronic cough for at least 3 weeks, often at the beginning of training or exercise, as well as increased mucus in the trachea.

“Obviously there is inflammatory reaction; there are some allergic reactions; genetic predisposition and maybe, the influence of several pathogenic agents in the presentation of the disease. So, it's mainly a multifactorial syndrome,” he said at the ACVIM Forum 2023, held recently in Philadelphia.

“But mild asthma is NOT an infectious disease,” he said, “The horses do not show fever or symptoms like that. We're clearly not talking about an infectious disease, but the possible influence of several pathogens in the occurrence of the disease. We are talking about risk factors.”

Although fungi, especially in the form of contaminated hay, have a clear association, the association of organisms in the airway is less so.

Bacteria

Several studies have found an association between bacteria and mild equine asthma. A longitudinal study by a group in Newmarket, England, which looked at Thoroughbreds, found Streptococcus zooepidemicus was associated significantly with an increase in tracheal mucus, but not necessarily mild equine asthma.

“So, there is a significant association between the detection of Strep zoo in the trachea wash and the occurrence of increased mucus,” Dr. Richard said. “Just remember it's only detection of the bacteria in the trachea wash. We're not talking about confirmation [of disease].”

Another paper from Australia showed a significant association between the isolation of bacteria and coughing, especially when there were high counts of bacteria in the tracheal wash, but most horses did not have high bacterial counts in the tracheal wash. In those that had higher bacterial counts, they found S. zooepidemicus, S. pneumoniae, S. sanguinis, Pasteurella and Bordetella bronchiseptica.

Another study by the Newmarket group saw a significant association between several streptococcal organisms, as well as Mycoplasma and Actinobacillus with the diagnosis of equine asthma. However, the diagnosis of equine asthma was not made based on cytology of the bronchoalveolar lavage (BAL), but on mucus and trachea wash samples.

“Also, the detection of these bacteria is decreasing with age. So, being younger than 1 year is a significant risk factor,” he said, but added, “Obviously older horses can develop asthma, too.”

Dr. Richard’s group tried to quantify the number of bacteria in horses with airway inflammation compared with controls and found no bacteria in about one-third of the tracheal wash samples of the control horses, but about 12% were positive primarily for S. zooepidemicus, Actinobacillus equuli and Pasteurella, but the bacteria count was low with about 1,000 to 4,000 CFU/mL in the control horses.

About 36% of the samples among the horses with airway disease were also sterile, and about 14% were positive for primarily for the same organisms as the control group, but the colony count was much higher with 50,000 to 10 million CFU/mL.

“There is some, I would say, strong evidence about the association between bacteria and either clinical signs and diagnosis of mild equine asthma. Please keep in mind that you know strong association does not mean causality,” he said, but more research needs to confirm these associations.

Viruses

Viruses, however, are a little more complicated. The typical suspects for viral association would be equine herpesvirus (EHV), equine rhinitis virus (ERV), equine influenza virus (EIV), adenoviruses and coronaviruses, but the data are not as clear as they are for bacteria, Dr. Richard said.

One study found no significant relationship between mucus and cough and EHV-1 and EHV-4, EIV or adenovirus by serology.

Another study found the incidence of new cases were low, based on serology. “All those studies did not find a relationship between viral seroconversion and the onset of mild equine asthma,” Dr. Richard said.

However, in 1 study, they found the seroconversion for EHV 1 month afterward was associated significantly with mild equine asthma.

“The problem with the seroconversion is you have to sample the horse twice about 3 weeks apart to see if there's an increase in the antibody titers; the titer on 1 day is not significant, but you may have obviously some delayed response and positive association,” he said.

“So, there might be some involvement of viruses in mild asthma, even if it's not fully clear,” he said.

However, all these studies relied on serology, which is not the best methodology for detecting viral infections. Today, viruses can be detected by various types of polymerase chain reaction (PCR) tests.

“We're now able to detect viruses and to determine viral load in the sample. So, we have better tools [to gather] more relevant data for observing the association between those viruses and the occurrence of mild equine asthma,” he said.

In a retrospective study done at his laboratory about 15 years ago, using more than 700 respiratory samples from tracheal wash and BAL, they found EHV-2 to be associated significantly with the airway inflammation of the horse compared with controls.

“The detection of EHV-2 was significantly associated with the airway inflammation and abnormalities of the epithelial cells,” he said.

A longitudinal study in Sweden investigated the viral load of nasal swabs and found EHV-2 and EHV-5 were not associated with poor performance, levels of serum amyloid A, respiratory clinical signs or tracheal mucus in Standardbred horses studied over 13 months.

A case-control study done in North America among various breeds of horses with mild asthma versus controls found a significant increase in seroprevalence ERV-A and IAD. For some unknown reason ERV-A appears to be more prevalent in North America than Europe, he said, which might influence these results.

They also detected EHV-2 in the respiratory samples of mild asthmatic horses only and not on control horses, which he found unusual because most horses have been exposed to herpes by the time they are older. His group did a prospective study in Standardbred horses and found EHV-5 by PCR in 90% of horses and EHV-2 in more than 76% of horses.

“But [in the North American study] no association was found between the different clinical signs, such as coughing and exercise intolerance and the detection of the virus. And interestingly, in this paper, cytology of BAL fluid was performed and there was no association between pulmonary function and the detection of those viruses by PCR,” he said.

His group also wanted to know whether samples taken by nasal swab were as good as those taken by tracheal wash, because there are several advantages to nasal swab samples: they are easier, faster and cheaper to do. However, his group also compared samples taken by nasal swab and tracheal wash and found “no agreement” between the samples by PCR.

“This means if you detect viral genome for any kind of virus in the nasal swabs, you have no idea if you are going to find this virus in the trachea wash. And if you find it in the trachea wash, you don't know about nasal swabs. And that's important because if there is an association between viral detection and clinical signs or mild asthma, it might also be related to the sample that has been performed.”

He did find that EHV-2 and ERV-B in the tracheal wash was significantly associated with coughing and mucus.

Fungi

Fungi in hay have been associated with mild equine asthma, but there are fewer data about fungal detection in the airways of horses with mild equine asthma. One study in Europe of more than 700 horses investigated because of poor performance detected fungi in the trachea wash in 55% of samples by culture and 79% by cytology.

“The authors found a significant association between fungal detection in trachea wash, and the diagnosis of mild equine asthma,” Dr. Richard said.

Horses that are kept on pasture rather than in stalls may be exposed less to fungal spores in hay, and so might have a lower risk for fungal respiratory disease, he said.

Various studies point of a possible association between bacterial, viruses and fungi and mild asthma, but the presence of an organism does not mean that it caused the asthma. However, it is looking more likely that the presence of infection could be a risk factor for the development of asthma. MeV