{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:25:14Z","timestamp":1793395514878,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL122328"],"award-info":[{"award-number":["R01 HL122328"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K24 HL138188"],"award-info":[{"award-number":["K24 HL138188"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R35 CA197701"],"award-info":[{"award-number":["R35 CA197701"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation fellowships (D.M.V.); Canadian Institutes for Health Research and Michael Smith Foundation for Health Research","award":["I01 CX000911"],"award-info":[{"award-number":["I01 CX000911"]}],"id":[{"id":"https:\/\/ror.org\/020x39229","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI120526"],"award-info":[{"award-number":["R01 AI120526"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI 117371"],"award-info":[{"award-number":["R21 AI 117371"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Resected lungs were inflated, frozen, and systematically sampled, generating 33 COPD (n\u2009=\u200911 subjects) and 22 control tissue samples (n\u2009=\u20093 subjects) for micro\u2013computed tomography analysis of terminal bronchioles (TBs; last generation of conducting airways) and emphysema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>PRM analysis was conducted to differentiate functional small airways disease (PRMfSAD) from emphysema (PRMEmph). In COPD lungs, TB numbers were reduced (P\u2009=\u20090.01); surviving TBs had increased wall area percentage (P\u2009&amp;lt;\u20090.001), decreased circularity (P\u2009&amp;lt;\u20090.001), reduced cross-sectional luminal area (P\u2009&amp;lt;\u20090.001), and greater airway obstruction (P\u2009=\u20090.008). COPD lungs had increased airspace size (P\u2009&amp;lt;\u20090.001) and decreased alveolar surface area (P\u2009&amp;lt;\u20090.001). Regression analyses demonstrated unique correlations between PRMfSAD and TBs, with decreased circularity (P\u2009&amp;lt;\u20090.001), decreased luminal area (P\u2009&amp;lt;\u20090.001), and complete obstruction (P\u2009=\u20090.008). PRMEmph correlated with increased airspace size (P\u2009&amp;lt;\u20090.001), decreased alveolar surface area (P\u2009=\u20090.003), and fewer alveolar attachments per TB (P\u2009=\u20090.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201811-2083oc","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T13:36:28Z","timestamp":1550842588000},"page":"575-581","source":"Crossref","is-referenced-by-count":157,"title":["Noninvasive Imaging Biomarker Identifies Small Airway Damage in Severe Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-4365","authenticated-orcid":false,"given":"Drago\u015f M.","family":"Vasilescu","sequence":"first","affiliation":[{"name":"University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando 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Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra","family":"Dass","sequence":"additional","affiliation":[{"name":"Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Kyoto University, Kyoto, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishindra M.","family":"Reddy","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Lagstein","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Ross","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wassim W.","family":"Labaki","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Murray","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Meng","sequence":"additional","affiliation":[{"name":"University of British Columbia, Vancouver, British Columbia, Canada"},{"name":"Weill Cornell Medical College, New York, New York"},{"name":"Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania"},{"name":"University of Michigan, Ann Arbor, Michigan"},{"name":"Imbio, Minneapolis, Minnesota"},{"name":"Kyoto University, Kyoto, Japan; and"},{"name":"VA Ann Arbor Healthcare System, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Curtis","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, Michigan"},{"name":"VA Ann Arbor Healthcare System, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tillie L.","family":"Hackett","sequence":"additional","affiliation":[{"name":"University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella A.","family":"Kazerooni","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard J.","family":"Criner","sequence":"additional","affiliation":[{"name":"Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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