Browsing by Author "Bond, Stephanie Laura"

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    Mild Equine Asthma: Effects of Commonly Used Treatments on the Respiratory Microbiota, Inflammatory Gene Expression, and Aerobic Performance during High-Intensity Exercise
    (2019-04-29) Bond, Stephanie Laura; Léguillette, Renaud; Scott, W. Michael; Bayly, Warwick M.; Easton, Paul A.
    Mild equine asthma (MEA) is an inflammatory airway disease of the horse which affects a large proportion of the equine population. The pathogenesis of MEA is not fully elucidated, however, it is widely assumed to be a multifactorial disease, with expression of clinical signs largely influenced by environment. There is very little information available on the effects of treatment, which is typically focused on reducing airway inflammation through corticosteroid administration. Investigations into the equine respiratory environment in states of health and MEA were performed using: i) High-throughput sequencing techniques (16S and ITS2) to report the respiratory microbiota and mycobiota respectively, and ii) changes in relative inflammatory mRNA cytokine expression in bronchoalveolar lavage fluid (BALF). Changes in expression of inflammatory cytokine mRNA, equine herpesvirus (EHV)-1,2,4,5 glycoprotein B gene expression and changes in respiratory bacterial and fungal communities following dexamethasone treatment of healthy horses and those with MEA are explored. A portable equine ergospirometry system was used to determine the efficacy of treatment designed to reduce lung inflammation on aerobic (V̇O2peak) and anaerobic performance in horses with MEA. There were clear differences between the lower respiratory tract environment in healthy horses versus MEA. There was a clear separation in both the microbiota - Streptococcus was increased in horses with MEA – and relative inflammatory cytokine expression. Horses with MEA had a lower concentration of IL-10 in BALF than healthy controls, consistent with human asthmatics. There was significant up-regulation of IL-17 in horses with MEA, suggesting these horses exhibit “allergic” airway inflammation in response to environmental antigens. The single most important factor in the prevention and treatment of MEA appears to be environmental improvement, manifest by reduced inhaled particulate matter. Treatment with injected dexamethasone in horses with MEA was associated with down-regulation of IL-5, indicating a shift away from a dysregulated Th-2 response. Treatment with dexamethasone significantly affected the microbiota diversity, but not the mycobiota, which was overwhelmed by the effect of a sustained dusty environment. There is strong evidence that without environmental modifications, corticosteroid therapy alone fails to normalize airway neutrophilia. Treatment significantly increased V̇O2peak by an average 11.7% (saline) to 14.6% (dexamethasone).