Naoya Tanabe1,2, Dragoş M Vasilescu1, Cameron J Hague3, Kohei Ikezoe1, Darra T Murphy3, Miranda Kirby4,1, Christopher S Stevenson5, Stijn E Verleden6, Bart M Vanaudenaerde6, Ghislaine Gayan-Ramirez6, Wim Janssens6, Harvey O Coxson1, Peter D Paré1, James C Hogg1. 1. The University of British Columbia Centre for Heart Lung Innovation, 539747, Vancouver, British Columbia, Canada. 2. Kyoto University Graduate School of Medicine Department of Respiratory Medicine, 215651, Kyoto, Japan; ntana@kuhp.kyoto-u.ac.jp. 3. The University of British Columbia Department of Radiology, 478400, Vancouver, British Columbia, Canada. 4. Ryerson University Department of Physics, 536636, Toronto, Ontario, Canada. 5. Janssen Disease Interception Accelerator, London, United Kingdom of Great Britain and Northern Ireland. 6. KU Leuven, 26657, Department of Chronic disease, metabolism and aging, Laboratory of Respiratory diseases, Leuven, Belgium.
Abstract
RATIONALE: While centrilobular (CLE) and paraseptal (PSE) emphysema are commonly identified on multi-detector computed tomography (MDCT), little is known about the pathology associated with PSE compared to CLE. OBJECTIVE: To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD). METHODS: Air-inflated frozen lung specimens (n=6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. Frozen tissue cores were taken from central (n=8) and peripheral (n=8) regions of each lung, scanned with microCT, and processed for histology. The core locations were registered to the MDCT and a percentage of PSE or CLE was assigned by radiologists to each of the regions. MicroCT scans were used to measure number and structural change of terminal bronchioles. Further, microCT based volume fractions of centrilobular (CLE%) and paraseptal (PSE%) emphysema allowed classifying cores into mild emphysema, CLE-dominant, and PSE-dominant. MEASUREMENTS AND MAIN RESULTS: PSE% measured on MDCT and microCT were positively associated (p=0.015). Number of terminal bronchioles per ml of lung and cross-sectional lumen area were significantly lower while wall area percent was significantly higher in CLE-dominant compared to mild emphysema and PSE-dominant regions (all p<0.05), whereas no difference was found between PSE-dominant and mild emphysema samples (all p>0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (p=0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared to CLE regions. CONCLUSIONS: The terminal bronchioles are relatively preserved while neutrophilic inflammation is increased in PSE-dominant regions compared to CLE-dominant regions in patents with COPD.
RATIONALE: While centrilobular (CLE) and paraseptal (PSE) emphysema are commonly identified on multi-detector computed tomography (MDCT), little is known about the pathology associated with PSE compared to CLE. OBJECTIVE: To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD). METHODS: Air-inflated frozen lung specimens (n=6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. Frozen tissue cores were taken from central (n=8) and peripheral (n=8) regions of each lung, scanned with microCT, and processed for histology. The core locations were registered to the MDCT and a percentage of PSE or CLE was assigned by radiologists to each of the regions. MicroCT scans were used to measure number and structural change of terminal bronchioles. Further, microCT based volume fractions of centrilobular (CLE%) and paraseptal (PSE%) emphysema allowed classifying cores into mild emphysema, CLE-dominant, and PSE-dominant. MEASUREMENTS AND MAIN RESULTS: PSE% measured on MDCT and microCT were positively associated (p=0.015). Number of terminal bronchioles per ml of lung and cross-sectional lumen area were significantly lower while wall area percent was significantly higher in CLE-dominant compared to mild emphysema and PSE-dominant regions (all p<0.05), whereas no difference was found between PSE-dominant and mild emphysema samples (all p>0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (p=0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared to CLE regions. CONCLUSIONS: The terminal bronchioles are relatively preserved while neutrophilic inflammation is increased in PSE-dominant regions compared to CLE-dominant regions in patents with COPD.
Entities:
Keywords:
COPD; Emphysema; MicroCT; Small airway disease
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