The effect of lower airway inflammation on inflammatory cytokine gene expression in bronchoalveolar lavage fluid and whole blood in racing Thoroughbreds.

BACKGROUND: Immunological mechanisms involved in the pathogenesis of mild to moderate equine asthma (MEA) are not completely understood. There are limited data on bronchoalveolar lavage fluid (BALF) and blood inflammatory cytokine profiles in racehorses with MEA, and the effect of racing on inflammatory cytokines is unknown. HYPOTHESIS/OBJECTIVES: We hypothesized that inflammatory cytokine gene expression in BALF and resting blood would be higher in racehorses with lower airway inflammation compared to healthy controls, and that gene expression in blood collected immediately post-race would be increased compared to resting blood in racehorses with lower airway inflammation. ANIMALS: 38 racing Thoroughbreds (samples: 30 resting blood, 22 post-race BALF, 41 post-race blood). METHODS: Prospective observational study. Inflammatory cytokine gene expression was determined in resting blood, post-race BALF and post-race blood from racehorses with lower airway inflammation and controls. RESULTS: Lower airway inflammation was diagnosed in 79 % of racehorses (23 % neutrophilic, 67 % mastocytic, and 10 % mixed). There was no difference in gene expression in BALF or resting blood between racehorses with lower airway inflammation and controls. IL-8 gene expression was higher in post-race blood compared to resting peripheral blood, regardless of disease (p = 0052). BALF neutrophil proportions increased with increasing IL-1ß gene expression in all sample types (p = 0.0025). BALF mast cell proportions increased with increasing TNF-α gene expression in post-race blood (p = 0.015). CONCLUSIONS AND CLINICAL IMPORTANCE: Lower airway inflammation was common in a population of racehorses without respiratory signs or exercise intolerance. Exercise alone increased peripheral blood IL-8 gene expression. Inflammatory cytokine gene expression was not increased in BALF or resting blood in horses with subclinical lower airway inflammation, precluding its diagnostic utility in clinical practice.

Concentrations of cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid of cats with experimentally induced asthma.

OBJECTIVE: To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. ANIMALS: 19 cats with experimentally induced asthma and 5 control cats. PROCEDURE: Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. RESULTS: Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. CONCLUSIONS AND CLINICAL RELEVANCE: Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

Repeated peripheral airway hyperpnea causes inflammation and remodeling in dogs.

INTRODUCTION/PURPOSE: Elite winter athletes have an increased incidence of asthma, the cause of which is unknown. Strenuous exercise, particularly while breathing cold air, results in airway cooling and desiccation. We used a canine model of hyperpnea with cold, dry air to test the hypothesis that repeated cooling and desiccation of peripheral airways can cause asthma-like pathology. METHODS: Canine sublobar airways were challenged with room temperature, dry air insufflated though a bronchoscope to simulate the mucosal cooling and desiccation that occurs in human peripheral airways during strenuous cold weather exercise. Airways were challenged once daily on four consecutive days, and control and challenged airways were harvested 24 h after the last challenge for histological analyses. RESULTS: Repeated challenge caused airway obstruction and remodeling that persisted for at least 24 h. The percentage of mucosal squamous epithelium increased with a corresponding decrease in ciliated epithelium. Challenged airways had thicker lamina propria that contained greater concentrations of eosinophils, neutrophils, and mast cells when compared with control airways. The severity of airway obstruction was correlated with mucosal condition, airway thickness, and eosinophil infiltration. With the exception of mast cell infiltration, all changes were reversed within 1 wk of cessation of challenges. CONCLUSIONS: We conclude that repeated cooling and desiccation of peripheral airways can cause airway remodeling similar to that seen in asthma. These findings, in concert with other reports using this model, support the hypothesis that asthma-like symptoms found in winter athletes may be the result of repeated hyperpnea with cold air.