Background
Chronic obstructive pulmonary disease (COPD) is a serious chronic disease of the airways that affects many people worldwide and currently has only limited treatment options. Sheep have a respiratory system that is in many ways similar to that of humans and can be used as a valid model for the study of airway diseases. The aim of this study was to gain a better understanding of disease pathology in an experimental sheep model of COPD.
Methods
COPD was induced in n=7 sheep following exposure of the lungs to porcine elastase (PE, 50 mg/ml in 5 ml sterile saline) and chronic weekly lung exposures (over 8 weeks) to lipopolysaccharide (LPS, 100 μg/ml in 5 ml saline), delivered via bronchoscopy to the two large caudal lung lobes. The smaller right apical lung lobe in each sheep received saline administrations and served as a healthy control lobe. Control sheep (n=4) that received no PE/LPS lung exposures were also included. Peripheral blood, bronchoalveolar lavage (BAL) and lung function measures were performed throughout the experiment, with lung tissue samples collected and histopathology assessed at post-mortem, 2 weeks following LPS exposures.
Results
Blood and BAL sampling showed significant increases in systemic and local neutrophil levels during the course of disease development. There was a concurrent decrease in lung ventilation within COPD lungs indicative of a decline in breathing capacity over time. Examination of tissue histopathology in Masson’s Trichrome-stained lung sections showed only modest changes in lung airspace and tissue percentages as assessed by mean linear intercept measures. However, there was extensive chronic inflammation of the airways, characterised by neutrophilic and macrophage infiltration, with significant increases in both the airway and parenchymal tissue inflammation scores in COPD compared to saline treated lung lobes.
Conclusions
These studies confirmed chronic airway inflammation and pathophysiological lung changes in a sheep model of COPD, providing similarities to that seen in the lungs of COPD patients. This opens up the opportunity for translational studies using this unique large animal model of COPD.