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Am J Respir Crit Care Med. 2019 Feb 22. doi: 10.1164/rccm.201811-2083OC. [Epub ahead of print]

Non-Invasive Imaging Biomarker Identifies Small Airway Damage in Severe COPD.

Author information

1
University of British Columbia, The James C Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Vancouver, British Columbia, Canada.
2
Cornell Medical College, New York, New York, United States.
3
Temple University School of Medicine, Pulmonary and Critical Care Medicine, Philadelphia, Pennsylvania, United States.
4
Center for Molecular Imaging, Michigan, Michigan, United States.
5
Imbio LLC, Minneapolis, Minnesota, United States.
6
University of Michigan, Ann Arbor, Michigan, United States.
7
Lewis Katz School of Medicine at Temple University, 12314, Philadelphia, Pennsylvania, United States.
8
Kyoto university, Kyoto, Japan.
9
University of Michigan, Department of Radiology, Center for Molecular Imaging, Ann Arbor, Michigan, United States.
10
University of Michigan, Taubman Center, Ann Arbor, Michigan, United States.
11
University of Michigan, Biostatistics, Ann Arbor, Michigan, United States.
12
University of Michigan/VA Hospital, Ann Arbor, United States.
13
University of British Columbia, UBC James Hogg Research Centre, Heart + Lung Institute, Vancouver, British Columbia, Canada.
14
UBC, Anesthesiology, pharmacology and Therapeutics, Vancouver, British Columbia, Canada.
15
University of Michigan, Radiology, Ann Arbor, Michigan, United States.
16
Temple University Hospital, Pulm & Crit Care Medicine, Philadelphia, Pennsylvania, United States.
17
University of Michigan, Pulmonary & Critical Care, Ann Arbor, Michigan, United States ; mrking@umich.edu.

Abstract

RATIONALE:

Evidence suggests damage to small airways is a key pathologic lesion in chronic obstructive pulmonary disease (COPD). Computed Tomography (CT) densitometry has been demonstrated to identify emphysema, but no such studies have been performed linking an imaging metric to small airway abnormality.

OBJECTIVES:

To correlate ex vivo Parametric Response Mapping (PRM) analysis to in vivo lung tissue measurements of patients with severe COPD treated by lung transplantation and controls.

METHODS:

Resected lungs were inflated, frozen, and systematically sampled, generating 33 COPD (n=11 subjects) and 22 control tissue samples (n=3 subjects) for micro CT analysis of terminal bronchiole (TB) (last generation of conducting airways) and emphysema.

MEASUREMENTS:

PRM analysis was conducted to differentiate functional small airways disease (PRMfSAD) from emphysema (PRMEmph).

RESULTS:

In COPD lungs, TB numbers were reduced (p=0.01); surviving TB had increased wall area % (p<0.001), decreased circularity (p<0.001), reduced cross sectional luminal area (p<0.001), and greater airway obstruction (p=0.008). COPD lungs had increased airspace size (p<0.001) and decreased alveolar surface area (p<0.001). Regression analyses demonstrated unique correlations between PRMfSAD and TB with decreased circularity (p<0.001), decreased luminal area (p<0.001) and complete obstruction (p=0.008). PRMEmph correlated with increased airspace size (p<0.001), decreased alveolar surface area (p=0.003) and fewer alveolar attachments per TB (p=0.01).

CONCLUSION:

PRMfSAD identifies areas of lung tissue with TB loss, luminal narrowing, and obstruction. This is first confirmation that an imaging biomarker can identify terminal bronchial pathology in established COPD and provides a non-invasive imaging methodology to identify small airway damage in COPD.

KEYWORDS:

Airways disease; COPD; Imaging; microCT

PMID:
30794432
DOI:
10.1164/rccm.201811-2083OC

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