Glucocorticoids are the cornerstone of drug treatment for equine asthma, but there are important knowledge gaps, according to the authors of a just-published review.
Despite substantial research efforts to improve the treatment and outcome for horses with asthma, glucocorticoids remain the drug of choice, Sophie Mainguy-Seers and Jean-Pierre Lavoie noted in the Journal of Veterinary Internal Medicine.
The ability of glucocorticoids to relieve airway obstruction explains their extensive use, they said, despite potential harmful effects.
“However, much is yet to be uncovered concerning glucocorticoid use in horses with asthma, including the comparative efficacy of the different drugs, the determination of minimal effective doses and the mechanisms underlying their variable modulation of airway inflammation.”
The researchers, with the University of Montreal in Canada, set out to report and compare the many effects of the various glucocorticoids used in asthmatic horses, with a focus on the impact on lung function, airway inflammation, and bronchial remodeling.
The authors noted that asthma is a frequent and debilitating pulmonary disease affecting horses worldwide. Severe asthma occurs mostly in horses living in temperate climates exposed to antigenic triggers, such as molds and dust in hay and bedding.
Diagnosis involves exclusion of other respiratory diseases, characterization of airway inflammation and, ideally, an assessment of lung function.
Milder forms affect horses of all ages. The presence of a cough or nasal discharge suggests a respiratory condition in some cases, but the diagnosis is less straightforward in instances where poor performance is the only complaint.
Antigen avoidance is the strategy of choice to manage severe asthma and it is achieved by modifying the diet, mainly by replacing dry hay by less dusty hay alternatives, and by reducing the environmental antigenic exposure. However, this approach is not always feasible or adequately implemented, and weeks to months can be required to normalize lung function.
Glucocorticoids have the advantage of relieving airway obstruction much faster than antigen avoidance, they said, making these drugs central to the treatment of asthma.
They noted that although glucocorticoids have been mainly studied in horses with severe asthma, their use is also extended to treat milder forms, and they are generally considered effective to control pasture asthma.
Mainguy-Seers and Lavoie, who examined nearly 150 scientific papers for their review, said their work highlighted the potency of glucocorticoids in relieving airway obstruction in asthma, but also underlined the varying clinical response.
These variable results undoubtedly reflected differences in research protocols, including differences in the severity of asthma, the glucocorticoid used, and the dose given.
Several studies investigated the effects of glucocorticoid treatment together with modification of diet or stabling conditions. “Although this is likely more representative of clinical management in the field, it further complicates the evaluation of the specific impacts of glucocorticoid administration,” they said.
However, even in controlled research settings, environmental conditions cannot be completely standardized.
Most available glucocorticoids successfully relieve airway obstruction, they said, but normalization of neutrophilic inflammation would not be expected unless antigen avoidance is also implemented.
The authors said several facets of glucocorticoid use warranted further investigation:
- Few studies have assessed glucocorticoid treatment in horses with mild and moderate asthma, including their impact on performance in sport or racehorses. The usefulness of adding glucocorticoid to environmental management in this condition remains to be determined.
- Some airway inflammation is not controlled by potent anti-inflammatory drugs such as glucocorticoids. Therefore, a better understanding of the role of neutrophils in asthma would help determine if glucocorticoids reduce the harmful activities of leukocytes.
- Understanding the specific contributions of genomic and nongenomic actions of glucocorticoids, as well as the signaling pathways implicated in the beneficial effects on bronchoconstriction and remodeling would be useful for the development of alternative therapies.
- Only partial reversibility of bronchial remodeling is achieved with long-term inhaled glucocorticoids in severe asthma. Would their systemic administration, or use in combination with other drug therapies, improve long-term management? The possible synergy between β2-adrenoreceptor agonists and glucocorticoids to control airway inflammation and remodeling merits further investigation.
- Studies to compare the available inhaled and systemic glucocorticoids would be useful to establish the value of each drug and the minimal effective dose of systemic glucocorticoids. The authors noted that much drug information is extrapolated from human data. Obtaining equine-specific knowledge in this area, such as oral bioavailability and protein-binding, would help guide clinical recommendations and reduce the risks of harmful effects.
- Investigations specifically monitoring adverse events could allow veterinarians to weigh the pros and cons more clearly when using glucocorticoids. However, such a study would require a large number of horses. The possible association between laminitis and a diagnosis of severe equine asthma needs to be examined further.
- The impacts of other factors, such as environmental conditions, the microbiome, and physiological states, such as aging, sex, and estrus variation, on disease severity and treatment response to glucocorticoids require investigation. A definition of glucocorticoid resistance is needed to characterize uncontrolled asthma and to guide clinicians and researchers toward precision medicine.
Mainguy-Seers and Lavoie are affiliated with the Faculty of Veterinary Medicine, part of the Department of Clinical Sciences at the University of Montreal.
Funding for the review was provided by the Fonds de Recherche du Québec en Santé, in a doctoral scholarship for Mainguy-Seers.
Glucocorticoid treatment in horses with asthma: A narrative review. Sophie Mainguy-Seers and Jean-Pierre Lavoie. Journal of Veterinary Internal Medicine, 03 June 2021 https://doi.org/10.1111/jvim.16189