A better understanding of the genetic and immunological factors involved in severe asthma in horses is required to pin down the underlying mechanisms involved in the disease, according to the authors of a just-published review.
That knowledge could be used to enhance and individualize therapies, providing a better outcome for affected animals.
Severe equine asthma affects up to 20% of adult horses in the northern hemisphere. It develops when genetically susceptible individuals are exposed to environments with high concentrations of airborne particles capable of triggering airway inflammation.
Many antigens have been linked to the development of equine asthma. It is thought that airway inflammation results from the effects of multiple allergens, to which individuals are susceptible in unique ways.
The disease has been mostly associated with hay feeding and stabling, but summer pasture-associated cases of severe asthma also occur.
Fungal spores, bacterial endotoxins, forage and storage mites, microbial toxins, peptidoglycans, proteases, pollen and plant debris, as well as inorganic particles, trigger clinical signs of disease.
Affected horses develop a cough, nasal discharge and increased respiratory effort at rest, due to the rise in neutrophil recruitment, mucus plugging, bronchospasm and airway remodeling.
Management normally involves avoidance of the allergens and the use of corticosteroids and bronchodilators to reduce airway inflammation and bronchoconstriction and improve lung function.
However, some horses are unresponsive to corticosteroid treatment, posing a challenge to clinicians. Thus, the identification of antigens and the development of antigen screening tests are central to treatment of the disease, and will enable a personalized approach using specific immunotherapy.
Joana Simões, Mariana Batista and Paula Tilley, in their review in the journal Animals, said the genetic and immunological mechanisms associated with the disease are complex and varied, involving different inflammatory pathways.
The trio, from Portuguese institutions, set out to evaluate reported findings around the genetic and immunological background of severe equine asthma, and discuss further areas of research with the potential to advance treatment and outcomes for affected horses.
They concluded that further characterization of the disease’s genetic background is fundamental in order to improve current knowledge of the pathways involved in the heritability and expression of severe asthma.
Reported genetic research to date focuses mostly on a well-described subpopulation of Swiss Warmblood horses, which limits the applicability of these findings to the general horse population.
Nonetheless, the reported genetic diversity and complexity observed in these studies likely occurs in other individuals, although, potentially, other genes and pathways may be involved.
Thus, research on a larger, more diverse group of asthma-affected horses with detailed genetic background is needed to further contribute to the description of the genetic events that take place in horses.
The authors said the immunological mechanisms that fuel inflammation and structural changes in the airways still lack detail.
Several cytokines, chemokines and inflammatory cells participate in the development and progression of asthma. However their precise characterization is still unclear.
Inconsistencies in reported studies may arise from differences in their experimental design and methods.
They said co-operation between research groups, together with research based on large multi-center populations of client-owned asthma-affected horses, could potentially solve this problem.
More uniform methods and protocols would enable the comparison of reported results, allowing a better definition of the genetic and immune mechanisms associated with asthma.
More studies using genomic, transcriptomic, proteomic and metabolomic analysis would help improve understanding of the condition, they said.
The impact of the lung and gut microbiome also needs to be assessed, they said, since these microbes regulate the immune innate response from an early age and can also promote airway hyper-reactivity and inflammation in asthmatic individuals.
Better immunological and genetic characterization will likely help to identify of disease subtypes and, more importantly, contribute to the development of new therapeutic targets.
For example, anti-interleukin targeted therapies, using monoclonal antibodies, could help manage the disease, especially in horses with resistance to corticosteroids.
This, they said, is currently being researched in human asthma, where identification of disease subtypes associated with specific cytokine profiles has led to the development of monoclonal antibodies.
Since the precise cytokine profiles of equine asthma are not fully understood, current research is focusing on identifying the allergens that trigger airway inflammation, and how immunotherapy can help regulate the inflammatory response. Results are promising, they said.
Also, determining specific allergen susceptibility can contribute to the development of specific immunotherapy and, in theory, help devise environmental management plans for affected horses.
New diagnostic tools based on genetics or disease biomarkers would be of significant value to equine veterinarians, especially if they are able to positively identify a severely asthmatic horse during remission.
Current diagnosis relies mostly on invasive methods which are not suitable for evaluating treatment response, since it requires repeated measurements.
Systemic blood biomarkers and exhaled breath condensate are attractive alternatives to undertaking a lung lavage, they said.
Current research shows the complexities of the genetic and inflammatory pathways involved in severe asthma, and variations are to be expected between subsets of individuals, they said. A deeper knowledge of the disease’s immunological pathways will allow the definition of disease subtypes, the identification of inflammatory biomarkers of diagnostic value, and a personalized therapeutic approach for horses targeting the inflammatory pathways involved in the disease.
Simões is with the University of Lisbon; Batista is with the Veterinary and Animal Research Centre, Associate Laboratory for Animal and Veterinary Science; and Tilley is with Lusófona University.
Simões, J.; Batista, M.; Tilley, P. The Immune Mechanisms of Severe Equine Asthma—Current Understanding and What Is Missing. Animals 2022, 12, 744. https://doi.org/10.3390/ani12060744