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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

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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 (V ̇O2peak) 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
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Background Mild equine asthma is presumed to arise in response to environmental exposures but the relative impact of differing inflammatory phenotypes upon performance are largely unexplored. Hypotheses: Airway inflammation negatively affects performance and cytological phenotype varies with environmental exposure. Animals Thoroughbred racehorses in active training and racing. Methods Thoroughbreds were recruited 24‐48 hours before racing. Each horse was eligible for re‐enrollment with each race entry. Within one hour of race completion, physical examination, respiratory endoscopy, and BAL were performed. Respirable and inhalable dust, respirable endotoxin, and respirable β‐glucan exposures were measured at the breathing zone within one week after racing. Controlling for age, trainer, and pulmonary hemorrhage, the relationship between performance, bronchoalveolar lavage fluid (BALF) cytology, and measures of exposure were modeled. Results Performance and BALF data were collected on 64 individual horses from 8 stables for a total of 98 race performances and 79 dust exposure assessments. Evidence of mild equine asthma was found in 80% (78/98) of BALF samples from 52/64 horses. For each percent increase in BALF mast cell and neutrophil proportions, speed figures were reduced by 2.9 (P = .012) and 1.4 (P = .046) points, respectively. Respirable dust concentration was associated with BALF neutrophil proportions (P = .015). Bronchoalveolar lavage fluid mast cell proportions were only associated with respirable β‐glucan exposures (P = .030). Conclusions and Clinical Importance: Mild equine asthma is common in racing horses and negatively impacts performance. The data support that respirable, rather than inhalable, dust exposure measures are pertinent to equine airway health.
Article
A prospective, randomised study assessed the impact of high-intensity racetrack conditioning on aerobic and anaerobic capacities in seasoned Thoroughbred racehorses. The effect of 10 weeks race conditioning and two simulated races on V̇O 2max and maximum accumulated oxygen deficit (MAOD) were evaluated. An incremental treadmill test to determine V̇O 2max , followed by three supramaximal runs to fatigue (at speeds (V105%, V115%, V125%) corresponding to oxygen requirements 105%, 115% and 125% of V̇O 2max , in randomised order) were performed at each timepoint (T1 [pre-conditioning] and T2 [post-conditioning]). Prior to T1, racehorses were briefly de-trained for four-six weeks and given low-level treadmill conditioning to prepare them for the more strenuous race conditioning after T1. Paired variables between T1 and T2 were analysed using a paired t-test. A 2-way RM ANOVA compared variables with >1 measurement. Speed at V̇O 2max (P=0.04) and V̇O 2max (P=0.01) increased with conditioning. Calculated speeds for the supramaximal runs increased for V105% (P=0.02) and V115% (P=0.03) but not for V125% (P=0.08). There was no conditioning effect on time to fatigue (P=0.34), although it was different between all intensities (2.8, 2.2 and 1.4 mins at V105%, V115% and V125% respectively at T2). O 2 demand increased with conditioning (P=0.02) for each supramaximal intensity. On average, horses’ aerobic capacity improved 4.43% after conditioning. MAOD was unchanged with conditioning (P=0.25) and unaffected by exercise intensity. Fit racehorses that have undergone repeated intensive training programs, experience smaller, incremental improvement than completely unfit horses. The anaerobic capacity of previously trained racehorses is relatively stable, despite brief periods of de-training.
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Background: Inhaled corticosteroids are effective in the treatment of equine asthma. A recent study reported that nebulisation of injectable dexamethasone had low systemic bioavailability in healthy horses and could represent a cost-effective therapy for equine inflammatory lung diseases. Objectives: To determine the effects of dexamethasone nebulisation on lung function in severe asthmatic horses. It was hypothesised that dexamethasone administered by nebulisation would be more effective than the same dose administered orally. Study design: Randomised blinded experimental study in severe asthmatic horses. Methods: Twelve severe asthmatic horses in clinical exacerbation were randomly assigned to treatment with 5 mg of dexamethasone sodium phosphate by nebulisation (n = 6) or by oral administration (n = 6), once daily for 7 days. Lung function was evaluated at baseline, after four treatment days (D4) and 24 h after the last dose (D8). The presence of residual bronchospasm was assessed on D8 with N-butylscopolammonium bromide administration (0.3 mg/kg i.v.). A respiratory clinical score was performed daily. Serum cortisol concentration was measured at baseline, D4 and D8. Results: The pulmonary elastance was unchanged in both groups while pulmonary resistance was significantly improved in the oral group on D8 (mean reduction in 1 cm H2 O/L/s [CI: 0.34-1.65, P = 0.003]). All horses had residual bronchospasm at the end of the study. There was a group difference in the respiratory clinical score as it was significantly reduced in the oral group, from D5 to D8. Serum cortisol concentration decreased in all subjects. Main limitations: Low number of horses and lack of placebo group. Conclusions: Considering the lack of improvement of lung function and the hypothalamic-pituitary-adrenal axis suppression, the results of this study do not support aerosolisation of an injectable form of dexamethasone for the treatment of severe equine asthma at the dose and with the nebuliser evaluated.