Rationale: To examine the nature of the obstruction in terminal bronchioles prior to the onset of emphysematous destruction. Methods: Explanted lungs from patients with COPD (n=6) treated by lung transplantation and unused donor lungs (n=4) served as controls. These lungs were inflated to TLC with air and frozen solid by suspending them in liquid nitrogen vapor. Each lung was cut into 2 cm−thick slices in the plane of preoperative CT scan and a core of frozen tissue approximately 1 cm in diameter and 2 cm in length were removed from each slice and processed for micro−CT examination. The mean linear intercept (Lm) was measured by microCT (McDonough et al ATS 2008) and cores of tissue from COPD lungs where Lm fell within the normal range were compared to cores of tissue from the control cases. The examination of the complete microCT scan of each core and identifying the terminal bronchioles (TB) by observing their entry into respiratory bronchioles allowed TB to be counted and expressed /ml of tissue. Adjustment of the TB image in the x−y plane and shifting to the z−plane allows measurements of the TB lumen area crosssection at its narrowest point. Results: The number of terminal bronchioles /ml of lung tissue fell from 6.9 ± 2.3 /ml in control lung tissue to 1.3 ± 1.3 /ml lung (p<0.01). in tissue from COPD cases where Lm was in the control range. The minimal lumen area of the TB from the COPD lung tissue was reduced compared to control p<0.05. Conclusion: Terminal bronchiolar narrowing and obliteration is an important cause of small airway obstruction prior to the onset of emphysematous destruction in COPD. This abstract is funded by: CIHR and P50 HL084922−02, P50 HL084948−02 and BC Lung.
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