Repetitive hyperpnoea causes peripheral airway obstruction and eosinophilia

Hyperpnoea of canine peripheral airways with dry air results in airway obstruction, mucosal damage, and inflammation. The purpose of this study was to evaluate the effect of repeated dry air challenge (DAC) on airway obstruction, reactivity and the development of airway inflammation in dogs. Canine peripheral airways received DAC (delivered under general anaesthesia through a bronchoscope) every 48 h for two weeks. Peripheral airway resistance and reactivity were measured prior to each DAC. After the final DAC, bronchoalveolar lavage fluid (BALF) cells and soluble mediators from challenged and control airways were measured. Repeated bronchoscopy had no effect on airway mechanics. Repeated DAC produced cumulative increases in peripheral airway resistance and peak obstructive response to DAC. The response to hypocapnia was also increased in airways receiving repeated DAC. However, when the response to agonists was expressed as a change from baseline, consistent significant increases were not observed. Repeated bronchoscopy produced insignificant changes in BALF cells and eicosanoid mediators. Repeated DAC produced marked eosinophilic inflammation and increased prostaglandins D2, E2, and F2alpha, as well as leukotrienes C4-E4. In conclusion, repeated dry air challenge in dogs in vivo causes persistent airway obstruction and inflammation not unlike that found in human asthma.