Airway Remodeling in Ferrets with Cigarette Smoke Induced COPD using µCT Imaging Supplement File

Abstract RATIONALE: Structural changes to airway morphology such as increased bronchial wall thickness (BWT) and airway wall area are cardinal features of chronic obstructive pulmonary disease (COPD). Ferrets are a recently established animal model uniquely exhibiting similar clinical and pathological characteristics of COPD as humans, including chronic bronchitis. OBJECTIVES: Develop a µCT method for evaluating structural changes to the airways in ferrets, and assess whether the effects of smoking induce changes consistent with chronic bronchitis in humans. METHODS: Ferrets were exposed to mainstream cigarette smoke or air control twice daily for 6 months. µCT was conducted in vivo at 6 months; a longitudinal cohort was imaged monthly. Manual measurements of BWT, luminal diameter (LD), and BWT:LD ratio were conducted, and confirmed by a semi-automated algorithm. The square root of bronchial wall area (WA) vs. luminal perimeter was determined on an individual ferret basis. MEASUREMENTS AND MAIN RESULTS: Smoke exposed ferrets reproducibly demonstrated 34% increased BWT (P