Thesis--Wisconsin. / Vita. Includes bibliographical references (leaves 14-18).

<p>Mild-moderate equine asthma (EA) is a commonly encountered disease of racehorses that affects performance. Decreasing dust exposure is crucial in the treatment of equine asthma. Dry hay, because of its high dust content, is known to increase the risk of airway inflammation. Feeding haylage, steamed hay, or hay pellets instead can help to decrease dust exposure. Haylage may also contribute to the resolution of airway inflammation by providing higher levels of omega-3 polyunsaturated fatty acids (Ω-3). Higher levels of Ω-3 are associated with an increase in pro-resolving lipid mediators (PRLM), essential molecules in the resolution of airway inflammation. </p> <p> The studies presented in this dissertation were designed to test the hypothesis that feeding low-dust forages would decrease airway inflammation in racehorses, and that haylage would provide superior resolution of airway inflammation compared to other low dust forages due to changes in systemic Ω-3 and PRLM concentrations associated with increased dietary Ω-3 intake.</p> <p>Three clinical trials were conducted to determine the effect of low-dust forages on airway inflammation. Environmental exposures were measured at the breathing zone, and bronchoalveolar lavage (BAL), and differential cytology counts were performed as measure of airway inflammation. </p> <p>The first clinical trial was a pilot study performed with 7 Standardbred racehorses. Horses were randomly assigned to eat hay (n=3) or haylage (n=4) for 6 weeks while in training. Measurements were performed at baseline and after 2, 4, and 6 weeks. Results showed a decrease in respirable dust, and β-glucan exposure in the horses fed haylage when compared to those fed hay. BAL neutrophil proportion was significantly lower at weeks 2, 4, and 6 when compared to baseline and at week 6 when compared to horses fed hay. </p> <p> The second clinical trial was performed on 19 mild asthmatic horses from the teaching herd. The diet of these horses was changed from dry hay to haylage (n=9) or hay pellets (n=10) for 6 weeks. Measurements were performed at baseline, week 3, and week 6. Results indicated that horses eating haylage and hay pellets were exposed to similar dust levels that were significantly lower than when they were eating dry hay. BAL neutrophil proportion was significantly lower in horses eating haylage when compared to baseline and to horses eating hay pellets at week 6. Horses eating haylage exhibited a significant decrease in stearic acid concentration at week 6. Pro-resolving lipid mediators (Resolvin D1, Resolvin E1, and Lipoxin A₄) did not affect neutrophil apoptosis or efferocytosis <i>in vitro</i>.</p> <p>The third clinical trial was performed on 73 thoroughbred racehorses actively racing and training. Horses were randomly assigned to eat dry hay or to change the forage to steamed hay or haylage. No other change in the management of the horses was allowed. Measurements were performed at baseline (n=73), week 3 (n=69), and week 6 (n=53). Results indicated that respirable dust exposure was significantly reduced when racehorses were fed steamed hay or haylage in place of dry hay. Respirable dust exposure was positively associated with BAL neutrophil proportions. Feeding haylage also significantly decreased exposure to respirable endotoxins. Horses eating haylage for 3 weeks had significantly lower BALF neutrophil proportion when compared with baseline. Also, at week 3, horses eating haylage showed a significant decrease in mast cell proportion, and horses eating steamed hay had a significant decrease in eosinophil proportion. At week 6, horses eating haylage maintained significantly lower BALF neutrophil proportions compared to baseline, and horses eating hay for 6 weeks. Concentration of Ω-3 and PRLM were not increased in horses eating haylage when compared to horses fed hay. Eicosapentaenoic acid was significantly higher on the horses eating haylage when compared to horses eating steamed hay. </p> <p>In conclusion, feeding low-dust forages is sufficient to decrease breathing zone exposure of horses to respirable dust. Despite similar dust exposure, haylage was the only low-dust forage that resulted in resolution of neutrophilic airway inflammation; however, the mechanism remains unclear.</p>

No description available.

This study investigated proteomic changes in bronchoalveolar lavage fluid (BALF) of beef calves to identify alterations related to development of naturally occurring bovine respiratory disease. BALF was collected from 162 healthy beef calves soon after weaning and transportation. Two-dimensional gel electrophoresis and mass spectrometric analysis revealed calves that later developed pneumonia had significantly lower levels of anti-inflammatory proteins including annexin A1, RAGE-binding protein, apolipoprotein-A, heat shock protein beta-1 and thioredoxin, but higher levels of antioxidant and pro-inflammatory proteins such as immunoglobulin light chain variable region, cyclophilin A, serum albumin precursor and glutathione S-transferase P. Difference in gel electrophoresis-based analysis further showed lower levels of annexin A1, annexin A2, peroxiredoxin I, calycyphosin, superoxide dismutase, macrophage capping protein and dihydrodiol dehydrogenase 3 in the calves that later developed pneumonia. Differences in annexin levels were partially confirmed by Western blot analysis. In healthy calves, immunohistochemistry revealed cytoplasmic expression of annexin A1 in surface epithelium of large airways, tracheobronchial submucosal glands, and goblet cells, and to a lesser degree in small airways but not in alveolar epithelium. Flow cytometry and immunocytochemistry labeled annexin A1 in blood and bronchoalveolar lavage neutrophils, monocytes, macrophages and lymphocytes. Annexin A2 expression was detected in surface epithelium of small airways, some mucosal lymphocytes, and endothelium, with weak expression in large airways, tracheobronchial submucosal glands and alveolar epithelium. For both proteins, the level of expression was similar in tissues collected 5 days after intrabronchial challenge with M. haemolytica compared to that from sham-inoculated calves. A sandwich ELISA for annexin A1 was developed. For use with BALF, the working range was 0.3-317 ng/ml and the sensitivity was 0.8 ng/ml. The coefficient of variation of intra-assay and the between assays was less than 20%. Together, these findings reveal annexins A1 and A2 as promising biomarkers of susceptibility to BRD in healthy at-risk calves. Further, the anti-inflammatory and pro-resolving functions of these proteins suggest roles in the pathogenesis of bacterial pneumonia of feedlot cattle. / Natural Sciences and Engineering Council (NSERC), Ontario Cattlemen’s Association, Ontario Ministry of Agriculture and Food and Ontario Veterinary College Fellowship Program