Repeated Peripheral Airway Hyperpnea Causes Inflammation and Remodeling in Dogs

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Abstract
Known. 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....