Pathological Comparisons of Paraseptal and Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease

Abstract

Rationale: Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE. Objectives: 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 micro-computed tomography (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. Furthermore, microCT-based volume fractions of CLE and PSE allowed classifying cores into mild emphysema, CLE-dominant, and PSE-dominant. Measurements and Main Results: The percentages of PSE measured on MDCT and microCT were positively associated (P = 0.015). The number of terminal bronchioles per milliliter of lung and cross-sectional lumen area were significantly lower and wall area percentage was significantly higher in CLE-dominant regions compared with 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 with CLE regions. Conclusions: The terminal bronchioles are relatively preserved, whereas neutrophilic inflammation is increased in PSE-dominant regions compared with CLE-dominant regions in patients with COPD.