Increased Parasite Resistance and Recurrent Airway Obstruction in Horses of a High‐Prevalence Family

Background: Equine recurrent airway obstruction (RAO) shares many characteristics with human asthma. In humans, an inverse relationship between susceptibility to asthma and resistance to parasites is suspected. Hypothesis/Objectives: Members of a high‐incidence RAO half‐sibling family (F) shed fewer strongylid eggs compared with RAO‐unaffected pasture mates (PM) and that RAO‐affected horses shed fewer eggs than RAO‐unaffected half‐siblings. Animals: Seventy‐three F and 73 unrelated, age matched PM. Methods: Cases and controls kept under the same management and deworming regime were examined. Each individual was classified as RAO affected or RAO unaffected and fecal samples were collected before and 1–3 weeks and 3 months after deworming. Samples were analyzed by combined sedimentation‐flotation and modified McMaster methods and classified into 3 categories of 0 eggs per gram of feces (EpG), 1–100 EpG, and >100 EpG, respectively. Results: PM compared with RAO‐affected F had a 16.7 (95% confidence interval [CI]: 2.0–136.3) times higher risk for shedding > 100 EpG compared with 0 EpG and a 5.3 (95% CI: 1.0–27.4) times higher risk for shedding >100 EpG compared with 0 EpG. There was no significant effect when RAO‐unaffected F were compared with their PM. RAO‐unaffected compared with RAO‐affected offspring had a 5.8 (95% CI: 0.0–1.0) times higher risk for shedding 1–100 EpG. Age, sex, breed, and sharing pastures with other species had no significant confounding effects. Conclusion and Clinical Importance: RAO is associated with resistance against strongylid parasites in a high‐prevalence family.     

Evaluation of Right Ventricular Myocardial Function in Healthy Horses With Recurrent Airway Obstruction Using Tissue Doppler Imaging

It has been described in humans that chronic obstructive bronchitis leads to pathologic changes, especially in the right ventricular myocardium due to hypoxia, which can be assessed by tissue Doppler imaging (TDI). In our study, different TDI techniques, that is, pulsed-wave TDI and color TDI, were evaluated for applicability in different scan planes (apical long-axis view and short-axis view) for the analysis of right ventricular myocardial function in six healthy horses (control) and six horses affected with recurrent airway obstruction (RAO) (RAO group). Tissue Doppler imaging was applicable to all scan planes described. Myocardial movement directions in general and the absolute values of TDI parameters were assessable. Significantly reduced early diastolic filling velocities (E), elevated late diastolic filling velocities (A), thereby decreased E/A quotient, prolonged electromechanical coupling periods between electrocardiograph Q-wave and maximal velocities, and compensatory elevated systolic strain as well as diminished displacement could be observed in horses with RAO compared with the control group. To conclude, equine right ventricular myocardial function is assessable by TDI. Significant changes of right ventricular myocardial function could be demonstrated by TDI in horses with RAO compared with matched healthy controls. The hypothesis that RAO potentially leads to right ventricular dysfunction detectable by TDI before conventional echocardiography changes are evident is supported by this explorative study.     

Reproducibility of Airway Responsiveness in Horses Using Flowmetric Plethysmography and Histamine Bronchoprovocation

Background: Inflammatory airway disease has a high prevalence in horses, but is often a diagnostic challenge. Flowmetric plethysmography and histamine bronchoprovocation (FP/HBP) is a simple and effective tool for diagnosis, but reproducibility of these measurements made over time has not been established.
Hypothesis: We hypothesize that the measurement of airway responsiveness in horses using FP/HBP is consistent over both short and long periods of time.
Animals: Twenty-nine healthy adult horses from 2 university herds.
Methods: In this prospective experimental study, airway responsiveness was determined in each horse at day 0 (baseline [BL]) with FP/ HBP, using PC35 (provocative concentration of histamine needed to increase Δ_flow by 35%) as a measure of airway responsiveness. Each horse was re-tested 1–4 weeks after BL (short-term [ST]) and again at 3–12 months after BL (long-term [LT]).
Results: In the ST period, 23/27 (85%) of the horses had a PC35 that was within 1 doubling concentration of histamine of their BL value, with a mean change of 0.52 doubling concentrations (95% CI 0.26–0.79, range 0–2.06). For the LT data, 19/26 (73%) of horses were within 1 doubling concentration of their BL value, with a mean change of 0.81 doubling concentrations (95% CI 0.45–1.17, range 0.14–3.10). There was no significant difference in reproducibility between the 2 groups of subjects.
Conclusions and Clinical Importance: Repeated measurements of airway responsiveness obtained with FP/HBP show acceptable reproducibility over time periods up to a year. However, caution must be used when testing horses when ambient air temperature is low.     

Efficacy and safety of sound wave treatment of recurrent airway obstruction in horses

Background: One proposed nonmedical therapy for recurrent airway obstruction (RAO) in horses is a handheld acoustic device that propels sound waves from the nose down the tracheobronchial tree where it is intended to dislodge mucous and relax bronchospasm, permitting clearance of mucoid secretions. Objective: To evaluate the effectiveness and safety of this device when used as per the manufacturer's recommendations as a treatment for RAO. Animals: Nine adult horses previously diagnosed with RAO. Methods: Prospective, cross‐over clinical trial. Horses were exposed to a dusty environment until airway obstruction developed as defined by standard lung mechanics (SLM). Horses were randomly assigned to receive either acoustic therapy or a sham treatment for 4 weeks while being maintained in this environment. Horses were evaluated by clinical scores, SLM, and forced expiration regularly for 4 weeks. The opposite treatment was administered after a washout period. Results: Seven horses received the treatment; 9 received the sham. There were no changes (P > .05) in clinical score, maximal change in transpulmonary pressure (ΔP_Lmax), lung resistance (R_L), or the forced expiratory flow rate averaged over the last 75–95% of expiration (FEF_75?95%) over the study period. The device was determined to be safe, although several minor adverse effects were noted, including head tossing, coughing, and chewing during treatment. Conclusions and Clinical Importance: Treatment with this device did not improve clinical signs or lung function in horses with RAO kept in a dusty environment. Currently accepted treatments, including environmental management and medical therapy, should be recommended.     

Clinical Features and Prognostic Variables in 109 Horses with Esophageal Obstruction (1992–2009)

Background: Esophageal obstruction is common in horses and can result in life‐threatening complications. Previous studies have described clinical findings in horses with esophageal obstruction, but there are no reports that attempt to make correlations of clinical findings with outcome. Hypothesis: Specific clinical features of horses with esophageal obstruction are associated with increased likelihood of complications. Animals: One hundred and nine horses with esophageal obstruction. Methods: Retrospective cross‐sectional study. All clinical records of horses admitted between April 1992 and February 2009 for esophageal obstruction were reviewed. The association among 24 clinical, hematological, biochemical, therapeutic variables and the likelihood of complications was investigated by a univariable logistic regression model, followed by multivariable analysis. Results: Multiple logistic regression analysis revealed that intact males (P= .02), age >15 years (P < .01), and a need for general anesthesia (P < .01) were associated with the development of complications after an episode of esophageal obstruction. Increased respiratory rate (>22 breaths/min) and moderate or severe tracheal contamination, although not associated with complications as a whole, significantly increased the risk of developing aspiration pneumonia (P≤ .01). Conclusions and Clinical Importance: Signalment, clinical variables, and endoscopic findings were confirmed as important tools in assessing the severity of the esophageal lesion and pulmonary involvement. Knowledge of risk factors for the development of complications will aid in making informed decisions to optimize treatment and assist in the assessment of prognosis.     

Comparison of Skin Prick Tests with In Vitro Allergy Tests in the Characterization of Horses with Recurrent Airway Obstruction

We intended to identify relevant immunoallergic factors and to compare skin prick tests (SPTs) and in vitro allergy tests in the characterization of horses with recurrent airway obstruction (RAO), so as to ascertain that SPTs perform better. Forty Lusitano/cross-Lusitano horses (30 RAO cases and 10 healthy control horses)—a very valuable autochthonous breed—were studied. Clinical history, thoracic radiography, respiratory tract endoscopy, and bronchoalveolar lavage were used for diagnosis. Serum samples of all 40 horses and undiluted bronchoalveolar lavage fluid samples of 21 RAO horses and 6 control horses were submitted for evaluation by an allergen-specific immunoglobulin E (IgE) enzyme-linked immunosorbent assay. SPTs were performed on the 40 horses. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for all diagnostic methods. Agreement between diagnostic methods was assessed by kappa statistic (Κ). Chi-square test with Yates correction showed SPT results from the RAO and control groups to be statistically different (P < .05). SPTs showed higher sensitivity, specificity, positive predictive value, and negative predictive value than both enzyme-linked immunosorbent assay tests. In human medicine, SPTs are considered to be the gold standard of allergy tests. Neither serum IgE nor bronchoalveolar lavage fluid IgE reliably detected allergen hypersensitivity, compared with SPT. SPTs performed significantly better overall than both in vitro tests. Low sensitivity of the in vitro assays indicates the need for continued study to elucidate a more sensitive specific IgE test.     

Efficacy of Hyperimmunized Plasma in the Treatment of Horses with Acute Colitis

Colitis in the adult horse is a life-threatening clinical condition that can be caused by any of several enteric pathogens. This study was conducted to determine whether treating horses with plasma obtained from donors that were hyperimmunized against the common equine diarrheal pathogens Clostridium difficile, Clostridium perfringens, and Salmonella sp shortens the duration of diarrhea in acute colitis. To evaluate the efficacy of plasma treatment, 42 horses with acute onset of diarrhea were studied. Horses were enrolled if they were of age >1 year, duration of diarrhea at presentation was <72 hours, and they had not received equine plasma within the last 3 months. In addition, the serum cortisol concentrations of horses with acute diarrhea were studied.Horses were randomized to receive hyperimmunized plasma, control plasma (collected from nonimmunized horses), or no plasma therapy. Clinical parameters and fecal consistency were observed until resolution, discharge, or death, and complete blood counts (CBCs) and biochemical profiles were collected throughout the study. A total of 38 horses completed the study. The mean duration of diarrhea was 40.7 ± 9.8 (mean ± SEM) hours, 119.2 ± 56.1 hours, and 72.0 ± 24.5 hours for the hyperimmunized plasma, normal plasma (NP), and control groups, respectively. Using survival analysis techniques, this difference did not achieve statistical significance (P = .374). Serum cortisol was found to be increased in all horses at presentation and to decrease with time in all treatment groups. There was no difference in cortisol concentrations between the three treatment groups studied (P = .237).     

Pulmonary dysfunction and skeletal muscle changes in horses with RAO

BACKGROUND: Chronic pulmonary diseases (recurrent airway obstruction [RAO]) have been reported to alter skeletal muscle cells in humans. The purpose of this study was to evaluate a potential relationship between pulmonary and muscle variables in horses with a clinical diagnosis of RAO. Muscle biopsies from healthy horses and from horses with RAO were investigated and the relationship between the severity of lung disease and the degree of muscular changes was determined. HYPOTHESIS: We hypothesized that chronic pulmonary disease can lead to changes of the skeletal muscle in horses. ANIMALS: Fifteen healthy horses (control) and 50 horses with RAO were examined. METHODS: In a prospective clinical trial, a complete lung examination was performed in all horses. In all horses, muscle enzyme activity at rest and after exercise and muscle biopsies from the M. gluteus medius were examined. RESULTS: None of the horses had clinical or histologic signs of primary or neurogenic myopathies. According to the clinical, endoscopic, and radiographic findings and with a scoring system, the horses with RAO were grouped according to the severity of pulmonary findings (15 horses mild, 24 horses moderate, 11 horses severe RAO). Pathologic changes of the skeletal muscle (fiber atrophy or fiber hypertrophy, myofibrillar degeneration, hyperplasia of mitochondria, and ragged-red-like fibers) were identified in most horses with RAO but in only a few individual control horses. In addition, a marked depletion of muscle glycogen storage was evident in the RAO horses but not in the control group. Other pathologic changes of skeletal muscle such as centralized nuclei and regenerating fibers were rare, but were more frequent in horses with lung diseases than in the control group. The degree of muscle cell changes was also graded with a scoring system and correlated with the severity of pulmonary disease (r= 0.55). CONCLUSION: Chronic pulmonary disease in horses is associated with structural changes in skeletal muscle. CLINICAL IMPORTANCE: Because chronic pulmonary disease may affect muscles, early and effective therapy may prevent these changes. This finding could be of clinical importance but requires further studies.     

Effect of Transvenous Electrical Cardioversion on Plasma Cardiac Troponin I Concentrations in Horses with Atrial Fibrillation

Background: Whether electrical cardioversion of cardiac arrhythmias results in cardiomyocyte damage is unknown.
Objective: To describe effect of transvenous electrical cardioversion (TVEC) on plasma cardiac troponin I (cTnI) concentration in horses.
Animals: All horses presented to the Cornell University Hospital for Animals for cardioversion of atrial fibrillation between May 2006 and October 2008 were eligible for inclusion in the study. Owners of 14 horses elected for TVEC and each horse was then enrolled (16 procedures).
Methods: Prospective observational study measuring concentrations of plasma cTnI before and after TVEC.
Results: Median cTnI concentration increased from 0.045 ng/mL at baseline (range 0.0–0.20 ng/mL) to 0.11 ng/mL after TVEC (range 0.0–3.73 ng/mL) ( P = .036). This increase was not associated with the number of shocks delivered, maximal energy delivered, cumulative energy delivered, chronicity of atrial fibrillation before cardioversion, or positioning of the pulmonary artery catheter.
Conclusions: The increase in cTnI is unlikely to be clinically important. The increase might be correlated with persistent atrial dysfunction after TVEC, suggesting that a longer convalescent period after the procedure could be warranted.     

Tissue Doppler Imaging and Two-dimensional Speckle Tracking of Left Ventricular Function in Horses Affected with Recurrent Airway Obstruction before and after Clenbuterol Treatment

Cardiac effects of the β₂-adrenergic agent clenbuterol have been the focus of many studies, but effects on myocardial velocities and myocardial deformation parameters have not yet been evaluated in horses affected with recurrent airway obstruction (RAO) using tissue Doppler imaging (TDI) and two-dimensional speckle tracking (2DST). In our study, 7 horses affected by RAO were treated over 14 days with clenbuterol, 0.8 μg/kg every 12 hours. Standard echocardiographic, TDI (pulsed wave and color TDI), and 2DST examinations were performed before and after the treatment period. Myocardial function was recorded in the right parasternal short-axis view. Percent of fractional shortening and two-dimensional echocardiography (2DE) measurements did not show any significant changes after 2 weeks of treatment. Early diastolic velocity, E, increased significantly after clenbuterol in the left ventricular free wall (LVFW; P = .001). The E/late diastolic velocity (A) quotient (P = .003) and the isovolumetric contractility (P = .035) also increased significantly after treatment. Time parameters, particularly the time interval between the Q-wave in the echocardiograph and atrial release, the time of diastole and Tei index (parameter of global ventricular function), decreased significantly after clenbuterol administration in the LVFW (P = .014/P = .028/P = .015, respectively). The 2DE speckle tracking revealed a significant increase of the early diastolic systolic strain rate (P = .01) in the LVFW after therapy. In conclusion, 2 weeks of treatment with clenbuterol at a dosage of 0.8 μg/kg every 12 hours led to improved cardiac function in severely RAO-affected horses. This could be a sign of myocardial restoration (re-remodeling) after therapy.     

Oxidative Stress and Interaction of Endothelin Receptors in Airways of Clinically Healthy Horses

Endothelin-1 (ET-1), a physiological as well as an inflammatory mediator, causes contraction of airway smooth muscles by binding to endothelin-A (ETA) and endothelin-B (ETB) receptors. We investigated the interaction between endothelin receptors on contractions and oxidative stress of bronchial rings of clinically healthy horses. Rings for response studies were set in tissue chambers containing oxygenated Tyrode’s solution. Concentration-response relationships were determined for ET-1 on control rings, rings incubated with ETA antagonist (BQ123), rings incubated with ETB antagonists (IRL 1038 and BQ788), and rings incubated with all antagonists combined. For oxidative stress studies, rings were incubated for 30 minutes separately with ET-1, ETA antagonist + ET-1, ETB antagonists + ET-1, and all three antagonists + ET-1. The control rings were not treated with any agents. Electron paramagnetic resonance (EPR) method was used to measure total reactive oxygen species (ROS), superoxide, and peroxynitrite. Results showed that ET-1 caused dose-dependent contractions which were increased by ETA blockade and decreased by ETB blockade. Combined blockade significantly inhibited the response to ET-1. Regarding the oxidative stress, ET-1 and its antagonists significantly reduced the total ROS. Superoxide production was significantly decreased by ETA antagonist and completely abolished when ETA and ETB antagonists were combined. Peroxynitrite production was not changed significantly. The study suggested that an interaction between ET receptors exists in the expression of contractile responses and oxidative stress. ET-1 attenuated oxidative stress by decreasing total ROS. ETA receptors may be primarily responsible for superoxide production. It appears that ET-1 does not affect peroxynitrite production in normal equine tissues.     

Relationships Among Plasma Proteins,Hematological Values,and Gender in Thoroughbred and Miniature Horses

Our objective was to investigate the relationships among plasma proteins, hematological values, and gender in Thoroughbred (nine females and 16 males) and miniature (30 females and four males) horses. Twenty-two protein bands, ranging from 8 to 264 kDa, were detected in horse plasma. Red blood cells, hemoglobin, and hematocrit were negatively correlated (r ≤ −0.29; P < .05) with bands 13 and 17 but positively correlated (r ≥ 0.40; P < .01) with band 3. A negative correlation (r ≤ −0.27; P < .05) was detected between bands 1, 8, and lymphocytes. Neutrophils were positively correlated with bands 1 and 8. Basophils had a positive correlation (r = 0.36) with band 12 and negative correlation with bands 11 (r = −0.30) and 13 (r = −0.48). Platelets had positive correlations (r ≥ 0.24; P < .10) with bands 3, 4, 5, 10, 14, 19, and 22. The relative intensities of protein bands 4, 16, and 22 were affected (P < .05) by an interaction of breed and gender. Gender effects (P < .05) were detected for plasma protein bands 1 (1.6 vs. 2.4 ± 0.23), 5 (2.6 vs. 3.6 ± 0.25), and 11 (8.7 vs. 13.2 ± 1.1), respectively, for females and males. Breed effects (P < .05) were detected for plasma protein bands 5 (2.5 vs. 3.8 ± 0.25) and 11 (9.0 vs. 12.9 ± 1.1), respectively, for Thoroughbreds and miniatures. When developing new pathophysiological tools for equine disease diagnosis and therapy, breed and gender effects should be considered.     

Health Factors Associated with Microchip Insertion in Horses

The objectives of this study were to characterize the inflammatory response after microchip insertion, evaluate pain response and swelling at the microchip insertion site, and measure migration of the microchips. Eighteen mature Quarter Horse mares were separated by expected parturition dates and then assigned randomly to treatment groups. The microchip group (n = 7) had microchips inserted using a sterile needle and syringe; the sham group (n = 7) had a needle inserted but no microchip; and the control group (n = 4) had no insertion. The inflammatory response was measured over a 2-week period by measuring dermal temperature, response to pressure, and swelling at the insertion site and plasma serum amyloid A (SAA). For the migration component of the study, radiographs of the seven microchipped horses were taken over 6 months after insertion. These radiographs allowed measurement between a select vertebral point and the microchip. The microchip and sham insertion did not cause a detectable increase in temperature. Algometer readings, used to quantify pressure necessary to induce a pain threshold response, indicated that microchip insertion area was more sensitive than sham insertion at 2 hours, day 1, and day 3 post insertion. Visible swelling began 2 hours postinsertion and resolved by day 3. SAA concentrations were affected by day following insertion, but not by treatment group. Increases in SAA concentration could not be matched with local insertion reactions. Migration was not detected in any of the horses during the 6 months within a 0.7-cm margin of error.     

Recurrent airway obstruction: A review

Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity‐mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fundamental immunological mechanisms leading to establishment of the classic disease phenotype. This review, as well as giving a clinical overview of recurrent airway obstruction, summarises much of the work in these areas that have culminated in a more thorough understanding of this debilitating disease.     

Identification of Equine Herpesvirus 5 in Horses with Lymphoma

Equine multinodular pulmonary fibrosis, equine herpesvirus 5 (EHV-5), and multicentric lymphoma were discovered in one patient. Review of gamma herpesvirus activity in humans revealed a propensity for lymphoproliferative disorders associated with infection. The objective was to determine the frequency of EHV-5 in lymphoma tissues and compare with the frequency found in the lymph nodes of clinically normal horses. Case control investigation of lymphoma-positive tissues and analysis via polymerase chain reaction (PCR) for EHV-5 was performed on 12 horses. Prospective collection and PCR analysis of lymph nodes (mesenteric or submandibular) for EHV-5 was performed on 21 control horses. Thirteen samples of lymphoma-positive tissues and fluid were submitted for PCR analysis for EHV-5. Of these, 67% was positive. In the control horse population, 14% was positive for EHV-5 (P = .004). Neoplastic samples positive for EHV-5 were classified as T-cell rich B-cell lymphoma (three), T-cell lymphoma (one), one was nondifferentiated, and two were not stained. Gamma herpesviruses in humans have been associated with lymphoproliferative diseases such as Kaposi sarcoma and Burkitt lymphoma. This study reveals an increased frequency of EHV-5 (gamma herpesvirus) in horses diagnosed with lymphoma compared with healthy control horses. Although the exact role this virus plays in the initiation or perpetuation of lymphoproliferative neoplasia is unknown, EHV-5 may be an etiologic agent associated with the development of some types of equine lymphoma.     

Association between Hyperglycemia and Survival in 228 Horses with Acute Gastrointestinal Disease

Background: Glucose homeostasis is dysregulated in critically ill humans resulting in hyperglycemia and decreased survival. Hyperglycemia is common in horses presenting with abdominal crisis, and this might be associated with a worse prognosis for survival.
Objective: To determine if hyperglycemia in horses with acute abdominal disease is associated with increased odds of failure to survive to hospital discharge.
Animals: Two hundred and twenty-eight adult horses with acute gastrointestinal disease.
Methods: Observational retrospective study. Records of horses > 1 year of age presenting for treatment of colic over a 3-year period were reviewed. Data collected included age, duration of colic, glucose, heart rate, PCV, total protein, anion gap, cost of hospitalization, breed, sex, pain at admission, diagnosis, whether surgery was performed, and life status at hospital discharge. Potential risk factors for nonsurvival were screened by univariable logistic regression and the best-fitting univariable model was used as the basis for multivariable regression modeling.
Results: Mean blood glucose was 155 mg/dL (8.5 mM) with 45% of the population above the reference range; 16.7% (38 of 228) of horses had severe hyperglycemia (>195 mg/dL; 10.7 mM). Factors associated with increased odds of failure to survive included glucose, severity of pain at admission, heart rate, PCV, anion gap, and diagnosis. The best-fitting multivariable model included glucose and diagnosis, with age included as a confounding variable. The model correctly classified outcome for 92.5% of horses.
Conclusions and Clinical Importance: This study has confirmed prior reports that hyperglycemia is common in horses with colic and is associated with a worse prognosis for survival to hospital discharge.