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

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.

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State of the Art. A Structural and Functional Assessment of the Lung via Multidetector-Row Computed Tomography: Phenotyping Chronic Obstructive Pulmonary Disease

Proceedings of the American Thoracic Society ◽

10.1513/pats.200603-086ms ◽

2006 ◽

Vol 3 (6) ◽

pp. 519-532 ◽

Cited By ~ 114

Author(s):

E. A. Hoffman

Keyword(s):

Computed Tomography ◽

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Functional Assessment ◽

State Of The Art ◽

Chronic Obstructive ◽

Multidetector Row Computed Tomography ◽

Obstructive Pulmonary Disease ◽

Multidetector Row

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Evaluation of cigarette smoke-induced emphysema in mice using quantitative micro-computed tomography

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00366.2014 ◽

2015 ◽

Vol 308 (10) ◽

pp. L1039-L1045 ◽

Cited By ~ 23

Author(s):

Mamoru Sasaki ◽

Shotaro Chubachi ◽

Naofumi Kameyama ◽

Minako Sato ◽

Mizuha Haraguchi ◽

...

Keyword(s):

Computed Tomography ◽

Cigarette Smoke ◽

Structural Changes ◽

Chronic Obstructive ◽

Micro Ct ◽

Micro Computed Tomography ◽

Obstructive Pulmonary Disease ◽

Calculated Volume ◽

Lung Ct ◽

Time Point

Chronic cigarette smoke (CS) exposure provokes variable changes in the lungs, and emphysema is an important feature of chronic obstructive pulmonary disease. The usefulness of micro-computed tomography (CT) to assess emphysema in different mouse models has been investigated, but few studies evaluated the dynamic structural changes in a CS-induced emphysema mouse model. A novel micro-CT technique with respiratory and cardiac gating has resulted in high-quality images that enable processing for further quantitative and qualitative analyses. Adult female C57BL/6J mice were repeatedly exposed to mainstream CS, and micro-CT scans were performed at 0, 4, 12, and 20 wk. Emphysema was also histologically quantified at each time point. Air-exposed mice and mice treated with intratracheal elastase served as controls and comparisons, respectively. End-expiratory lung volume, corresponding to functional residual volume, was defined as the calculated volume at the phase of end-expiration, and it evaluated air trapping. The end-expiratory lung volumes of CS-exposed mice were significantly larger than those of air controls at 12 and 20 wk, which was in line with alveolar enlargement and destruction by histological quantification. However, CS exposure neither increased low attenuation volume nor decreased the average lung CT value at any time point, unlike the elastase-instilled emphysema model. CS-exposed mice had rather higher average lung CT values at 4 and 12 wk. This is the first study characterizing a CS-induced emphysema model on micro-CT over time in mice. Moreover, these findings extend our understanding of the distinct pathophysiology of CS-induced emphysema in mice.

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COPD beyond proximal bronchial obstruction: phenotyping and related tools at the bedside

European Respiratory Review ◽

10.1183/16000617.0010-2019 ◽

2019 ◽

Vol 28 (152) ◽

pp. 190010 ◽

Cited By ~ 4

Author(s):

Thibaut Capron ◽

Arnaud Bourdin ◽

Thierry Perez ◽

Pascal Chanez

Keyword(s):

Secretory Protein ◽

Pulmonary Vasculature ◽

Minor Role ◽

Chronic Obstructive ◽

Bronchial Obstruction ◽

Forced Oscillation Technique ◽

Small Airways ◽

Micro Computed Tomography ◽

New Paradigm ◽

Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterised by nonreversible proximal bronchial obstruction leading to major respiratory disability. However, patient phenotypes better capture the heterogeneously reported complaints and symptoms of COPD. Recent studies provided evidence that classical bronchial obstruction does not properly reflect respiratory disability, and symptoms now form the new paradigm for assessment of disease severity and guidance of therapeutic strategies. The aim of this review was to explore pathways addressing COPD pathogenesis beyond proximal bronchial obstruction and to highlight innovative and promising tools for phenotyping and bedside assessment. Distal small airways imaging allows quantitative characterisation of emphysema and functional air trapping. Micro-computed tomography and parametric response mapping suggest small airways disease precedes emphysema destruction. Small airways can be assessed functionally using nitrogen washout, probing ventilation at conductive or acinar levels, and forced oscillation technique. These tests may better correlate with respiratory symptoms and may well capture bronchodilation effects beyond proximal obstruction.Knowledge of inflammation-based processes has not provided well-identified targets so far, and eosinophils probably play a minor role. Adaptative immunity or specific small airways secretory protein may provide new therapeutic targets. Pulmonary vasculature is involved in emphysema through capillary loss, microvascular lesions or hypoxia-induced remodelling, thereby impacting respiratory disability.

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