The purpose of this manuscript is to revise and update the previous consensus statement on inflammatory airway disease (IAD) in horses. Since 2007, a large number of scientific articles have been published on the topic and these new findings have led to a significant evolution of our understanding of IAD.
The 2019 Havemeyer Workshop brought together researchers and clinicians to discuss the latest information on Equine Asthma and provide future research directions. Current clinical and molecular asthma phenotypes and endotypes in humans were discussed and compared to asthma phenotypes in horses. The role of infectious and non-infectious causes of equine asthma, genetic factors and proposed disease pathophysiology were reviewed. Diagnostic limitations were evident by the limited number of tests and biomarkers available to field practitioners. The participants emphasized the need for more accessible, standardized diagnostics that would help identify specific phenotypes and endotypes in order to create more targeted treatments or management strategies. One important outcome of the workshop was the creation of the Equine Asthma Group that will facilitate communication between veterinary practice and research communities through published and easily accessible guidelines and foster research collaboration.
The term “equine asthma” has been proposed as a unifying descriptor of inflammatory airway disease (IAD), recurrent airway obstruction (RAO), and summer pasture‐associated obstructive airway disease. Whilst the term will increase comprehensibility for both the lay and scientific communities, its biologic relevance must be compared and contrasted to asthma in human medicine, recognizing the limited availability of peer‐reviewed equine‐derived data, which are largely restricted to clinical signs, measures of airway obstruction and inflammation and response to therapy. Such limitations constrain meaningful comparisons with human asthma phenotypes. Suggested minimum inclusion criteria supporting the term asthma, as well as similarities and differences between IAD, RAO, and multiple human asthma phenotypes are discussed. Furthermore, differences between phenotype and severity are described, and typical features for equine asthma subcategories are proposed. Based on shared features, we conclude that mild/moderate (IAD) and severe (RAO) equine asthma are biologically appropriate models for both allergic and non‐allergic human asthma, with RAO (severe equine asthma) also being an appropriate model for late‐onset asthma. With the development of new biologic treatments in humans and the application of more targeted therapeutic approaches in the horse, it would appear appropriate to further investigate the allergic (Th‐2) and non‐allergic (non‐Th‐2) phenotypes of equine asthma. Further research is required to more fully determine the potential clinical utility of phenotype classification.
Osteomyelitis is a major problem worldwide and is devastating due to the potential for limb-threatening sequelae and mortality. Osteomyelitis pathogens are bone-attached biofilms, making antibiotic delivery challenging. Here we describe a novel osteoadsorptive bisphosphonate-ciprofloxacin conjugate (BV600022), utilizing a “target and release” chemical strategy, which demonstrated a significantly enhanced therapeutic index versus ciprofloxacin for the treatment of osteomyelitis in vivo. In vitro antimicrobial susceptibility testing of the conjugate against common osteomyelitis pathogens revealed an effective bactericidal profile and sustained release of the parent antibiotic over time. Efficacy and safety were demonstrated in an animal model of periprosthetic osteomyelitis, where a single dose of 10 mg/kg (15.6 µmol/kg) conjugate reduced the bacterial load by 99% and demonstrated nearly an order of magnitude greater activity than the parent antibiotic ciprofloxacin (30 mg/kg, 90.6 µmol/kg) given in multiple doses. Conjugates incorporating a bisphosphonate and an antibiotic for bone-targeted delivery to treat osteomyelitis biofilm pathogens constitute a promising approach to providing high bone-antimicrobial potency while minimizing systemic exposure.
Thirty-eight endurance horses underwent clinical and ancillary examinations, including haematological and biochemical evaluation, standardised exercise tests both on a treadmill and in the field, Doppler echocardiography, impulse oscillometry, video endoscopy and collection of respiratory fluids. All of the examined poorly performing horses were affected by subclinical diseases, and most of them had multiple concomitant disorders. On the contrary, the well-performing horses were free of any subclinical disease. The most frequently diagnosed diseases were respiratory disorders, followed by musculoskeletal and cardiac problems. Poor performers exhibited lower speeds at blood lactate concentration of 4 mmol/l (VLA4) and at heart rates of 160 (V160) and 200 bpm (V200) on the treadmill and in the field, as well as slower recovery of heart rate.
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