Respiratory Molecules Could Lead to Customized Equine Asthma Treatments
Not all equine asthma cases are the same. In fact, they can vary considerably depending on which molecules are involved. This can change the way veterinarians pinpoint treatments to address the action of those molecules, according to veterinary researchers.
One important aspect seems to be the activity of mast cells, a type of immune cell that releases different molecules when lung tissues are inflamed. By identifying the subtype of mast cell in asthmatic horses, scientists might be able to better diagnose the type of asthma on a molecular level, said Jane S. Woodrow, DVM, MS, PhD, Dipl. ACVIM (LAIM), of the University of Pennsylvania’s New Bolton Center Hospital for Large Animals, in Kennett Square.
“There are different populations of airway inflammatory cells in mild/moderate versus severe and even within mild to moderate asthma,” Woodrow said. “To best treat and manage horses with asthma, we need to better understand its pathophysiology—in other words, the changes that occur that accompany the disease.
“Using the terms mild, moderate, and severe does relate to the severity of clinical signs observed,” she continued. “But it also reflects the type of airway inflammatory cells involved in the disease.”
Mast Cells: Discreet but Often Critical in Asthma
Mast cells are immune cells involved in inflammatory reactions, Woodrow said. These products have many different roles in asthma, including bronchoconstriction, amplification of the allergic response, and the recruitment of other inflammatory cells.
In humans, identifying the various products of mast cells has helped clinicians identify the type of asthma and how to treat it better with more closely adapted pharmaceuticals, she said.
Mast cells themselves, however, are not easy to identify in laboratory analyses because they are few in number, said Woodrow. In the past, researchers have attempted to recognize mast cells by staining certain molecules the cells tend to harbor. The problem is mast cells frequently release those molecules, so the researchers can’t find them within the cells’ cytoplasm.
Recently, advanced molecular techniques have made it possible to identify mast cell subtypes, Woodrow said. The process, known as molecular phenotyping, “has led to easier identification of mast cells, and their specific mast cell type, in samples in which it has been historically harder to identify mast cells,” she said.
Diagnosing Equine Asthma More Precisely
Currently, veterinarians diagnose asthma in horses based on their history, physical examination, bronchoalveolar lavage fluid (BALF) cell analyses, and sometimes lung function tests, Woodrow said. The BALF analysis in asthmatic horses usually includes increased percentages of neutrophils, mast cells, and/or eosinophils (neutrophils and eosinophils being white blood cell types), without any signs of bacterial or fungal infections.
Testing Molecular Phenotyping in Horses’ Airway Fluids
Woodrow and her fellow researchers evaluated 19 asthmatic horses—including 14 with severe asthma and five with mild/moderate asthma—as well as 11 healthy controls. The animals, which ranged in age from 8 to 26 years, belonged either to the University of Tennessee College of Veterinary Medicine’s teaching herd or to clients who had brought their horses to the university’s veterinary clinic for respiratory assessment.
The researchers carried out physical exams, took jugular blood samples, and performed bronchoalveolar lavage on all the horses.
They found that horses with severe asthma had higher percentages of molecules known as CXCL-8, TNF-a, and IFN-g compared to clinically healthy horses, she said, which is similar to what is seen in human asthmatic patients.
The moderately asthmatic horses had a slightly elevated mast cell presence compared to healthy horses, but severely asthmatic horses did not show a clinically significant difference. The small mild/moderate asthma group limited their ability to assess mast cell molecular phenotype and inflammatory proteins, Woodrow explained.
A Research Call for More Cases
The findings do not mean horses lack biological flags for categorizing their asthma but, rather, that researchers must continue working with greater numbers of horses to find the biomarkers to create more targeted treatment, said Woodrow.
“Not all cases of asthma are the same, as reflected in a variety of airway inflammatory cells involved,” she said. “I need a much larger sample size to better define these and increased numbers of all currently defined categories of asthma from different parts of the country. As in any disease, the better we understand the development of the said disease, the better we can diagnose and treat it.”
Woodrow recommends all horses with suspected asthma undergo BAL with cytological evaluation—if anything, for the sake of scientific data collection.
“Right now the cytological evaluation may not change the treatments recommended,” she said. “But the better we understand the pathophysiology and how each horse responds to therapy through the collection of objective data—such as BAL cytology, lung function testing, and clinical signs—we may have better individualized treatments for specific categories of equine asthma. A horse with severe neutrophilic airway inflammation is likely to need different treatments than a horse with eosinophilic/mast cell airway inflammation.”
Veterinarians, researchers, and owners interested in the project can contact Woodrow directly at firstname.lastname@example.org.
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