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

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          Abstract

          Rationale: Evidence suggests damage to small airways is a key pathologic lesion in chronic obstructive pulmonary disease (COPD). Computed tomography 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 control subjects.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-computed tomography analysis of terminal bronchioles (TBs; last generation of conducting airways) and emphysema.Measurements and Main Results: PRM analysis was conducted to differentiate functional small airways disease (PRMfSAD) from emphysema (PRMEmph). In COPD lungs, TB numbers were reduced (P = 0.01); surviving TBs had increased wall area percentage (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 TBs, 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).Conclusions: PRMfSAD identifies areas of lung tissue with TB loss, luminal narrowing, and obstruction. This is the first confirmation that an imaging biomarker can identify terminal bronchial pathology in established COPD and provides a noninvasive imaging methodology to identify small airway damage in COPD.

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          Author and article information

          Journal
          American Journal of Respiratory and Critical Care Medicine
          Am J Respir Crit Care Med
          American Thoracic Society
          1073-449X
          1535-4970
          February 22 2019
          February 22 2019
          Affiliations
          [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 &amp; Crit Care Medicine, Philadelphia, Pennsylvania, United States
          [17 ]University of Michigan, Pulmonary &amp; Critical Care, Ann Arbor, Michigan, United States;
          Article
          10.1164/rccm.201811-2083OC
          6727153
          30794432
          9fe19b72-eab5-4639-a864-636372740c8b
          © 2019
          History

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