Analysis of airway pathology in COPD using a combination of computed tomography, micro-computed tomography and histology

Author:

Tanabe NaoyaORCID,Vasilescu Dragoş M.,Kirby Miranda,Coxson Harvey O.,Verleden Stijn E.,Vanaudenaerde Bart M.,Kinose Daisuke,Nakano Yasutaka,Paré Peter D.,Hogg James C.

Abstract

The small conducting airways are the major site of obstruction in chronic obstructive pulmonary disease (COPD). This study examined small airway pathology using a novel combination of multidetector row computed tomography (MDCT), micro-computed tomography (microCT) and histology.Airway branches visible on specimen MDCT were counted and the dimensions of the third- to fifth-generation airways were computed, while the terminal bronchioles (designated TB), preterminal bronchioles (TB-1) and pre-preterminal bronchioles (TB-2) were examined with microCT and histology in eight explanted lungs with end-stage COPD and seven unused donor lungs that served as controls.On MDCT, COPD lungs showed a decrease in the number of 2–2.5 mm diameter airways and the lumen area of fifth-generation airways, while on microCT there was a reduction in the number of terminal bronchioles as well as a decrease in the luminal areas, wall volumes and alveolar attachments to the walls of TB, TB-1 and TB-2 bronchioles. The combination of microCT and histology showed increased B-cell infiltration into the walls of TB-1 and TB-2 bronchioles, and this change was correlated with a reduced number of alveolar attachments in COPD.Small airways disease extends from 2 mm diameter airways to the terminal bronchioles in COPD. Destruction of alveolar attachments may be driven by a B-cell-mediated immune response in the preterminal bronchioles.

Funder

National Institutes of Health

Canadian Institutes of Health Research

Publisher

European Respiratory Society (ERS)

Subject

Pulmonary and Respiratory Medicine

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