{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:58:56Z","timestamp":1791410336707,"version":"4.3.3"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T00:00:00Z","timestamp":1575244800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01 HL089897"],"award-info":[{"award-number":["U01 HL089897"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01 HL089856"],"award-info":[{"award-number":["U01 HL089856"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K24 HL138188"],"award-info":[{"award-number":["K24 HL138188"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 CX000911"],"award-info":[{"award-number":["I01 CX000911"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009655","name":"Sunovion","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100009655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec>\n<jats:title>Abstract<\/jats:title>\n<jats:p>Impaired single breath carbon monoxide diffusing capacity (DLCO) is associated with emphysema. Small airways disease (SAD) may be a precursor lesion to emphysema, but the relationship between SAD and DLCO is undescribed. We hypothesized that in mild COPD, functional SAD (fSAD) defined by computed tomography (CT) and Parametric Response Mapping methodology would correlate with impaired DLCO. Using data from ever-smokers in the COPDGene cohort, we established that fSAD correlated significantly with lower DLCO among both non-obstructed and GOLD 1\u20132 subjects. The relationship between DLCO with CT-defined emphysema was present in all GOLD stages, but most prominent in severe disease.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT00608764?term=00608764&amp;draw=1&amp;rank=1\">NCT00608764<\/jats:ext-link>. Registry: COPDGene. Registered 06 February 2008, retrospectively registered.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12931-019-1237-1","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T09:06:14Z","timestamp":1575277574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Relationship between diffusion capacity and small airway abnormality in COPDGene"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4207-641X","authenticated-orcid":false,"given":"Rachel N.","family":"Criner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Hatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"Galb\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella A.","family":"Kazerooni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith C.","family":"McCormack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Casaburi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"MacIntyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Make","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J.","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wassim W.","family":"Labaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Lan K.","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,2]]},"reference":[{"key":"1237_CR1","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1056\/NEJM196806202782501","volume":"278","author":"JC Hogg","year":"1968","unstructured":"Hogg JC, Macklem PT, Thurlbeck WM. Site and nature of airway obstruction in chronic obstructive lung disease. N Engl J Med. 1968;278:1355\u201360.","journal-title":"N Engl J Med"},{"key":"1237_CR2","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1056\/NEJMoa1106955","volume":"365","author":"JE McDonough","year":"2011","unstructured":"McDonough JE, Yuan R, Suzuki M, Seyednejad N, Elliott WM, Sanchez PG, Wright AC, Gefter WB, Litzky L, Coxson HO, et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med. 2011;365:1567\u201375.","journal-title":"N Engl J Med"},{"key":"1237_CR3","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/S2213-2600(18)30196-6","volume":"6","author":"HK Koo","year":"2018","unstructured":"Koo HK, Vasilescu DM, Booth S, Hsieh A, Katsamenis OL, Fishbane N, Elliott WM, Kirby M, Lackie P, Sinclair I, et al. Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study. Lancet Respir Med. 2018;6:591\u2013602.","journal-title":"Lancet Respir Med"},{"key":"1237_CR4","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1159\/000329871","volume":"83","author":"SE D'Anna","year":"2012","unstructured":"D'Anna SE, Asnaghi R, Caramori G, Appendini L, Rizzo M, Cavallaro C, Marino G, Cappello F, Balbi B, Di Stefano A. High-resolution computed tomography quantitation of emphysema is correlated with selected lung function values in stable COPD. Respiration. 2012;83:383\u201390.","journal-title":"Respiration."},{"key":"1237_CR5","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1164\/rccm.201811-2083OC","volume":"200","author":"DM Vasilescu","year":"2019","unstructured":"Vasilescu DM, Martinez FJ, Marchetti N, Galban CJ, Hatt C, Meldrum CA, Dass C, Tanabe N, Reddy RM, Lagstein A, et al. Non-invasive imaging biomarker identifies small airway damage in severe COPD. Am J Respir Crit Care Med. 2019;200:575\u201381.","journal-title":"Am J Respir Crit Care Med"},{"key":"1237_CR6","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1164\/rccm.201511-2219OC","volume":"194","author":"SP Bhatt","year":"2016","unstructured":"Bhatt SP, Soler X, Wang X, Murray S, Anzueto AR, Beaty TH, Boriek AM, Casaburi R, Criner GJ, Diaz AA, et al. Association between functional small airway disease and FEV1 decline in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2016;194:178\u201384.","journal-title":"Am J Respir Crit Care Med"},{"key":"1237_CR7","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.acra.2019.02.003","volume":"26","author":"WW Labaki","year":"2019","unstructured":"Labaki WW, Gu T, Murray S, Hatt CR, Galban CJ, Ross BD, Martinez CH, Curtis JL, Hoffman EA, Pompe E, et al. Voxel-wise longitudinal parametric response mapping analysis of chest computed tomography in smokers. Acad Radiol. 2019;26:306\u201312.","journal-title":"Acad Radiol"},{"key":"1237_CR8","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1183\/13993003.02377-2014","volume":"46","author":"B-G Harvey","year":"2015","unstructured":"Harvey B-G, Strulovici-Barel Y, Kaner RJ, Sanders A, Vincent TL, Mezey JG, Crystal RG. Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity. Eur Respir J. 2015;46:1589\u201397.","journal-title":"Eur Respir J"},{"key":"1237_CR9","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1136\/thoraxjnl-2012-203108","volume":"68","author":"M Kirby","year":"2013","unstructured":"Kirby M, Owrangi A, Svenningsen S, Wheatley A, Coxson HO, Paterson NAM, McCormack DG, Parraga G. On the role of abnormal DLCO in ex-smokers without airflow limitation: symptoms, exercise capacity and hyperpolarised helium-3 MRI. Thorax. 2013;68:752\u20139.","journal-title":"Thorax."},{"key":"1237_CR10","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1164\/ajrccm.158.3.9801045","volume":"158","author":"AF Gelb","year":"1998","unstructured":"Gelb AF, Zamel N, Hogg JC, M\u00fcller NL, Scheiin MJ. Pseudophysiologic emphysema resulting from severe small-airways disease. Am J Respir Crit Care Med. 1998;158:815\u20139.","journal-title":"Am J Respir Crit Care Med"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-019-1237-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12931-019-1237-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-019-1237-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T19:50:43Z","timestamp":1606765843000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-019-1237-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1237"],"URL":"https:\/\/doi.org\/10.1186\/s12931-019-1237-1","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"21 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This research letter presents an analysis of the COPDGene study registered on Clinicaltrials.gov (NCT00608764). The protocol was reviewed and approved by the Institutional Review Boards for each participating center (National Jewish Health, HS-1883a; Brigham and Women\u2019s Hospital, 2007-P-000554\/2; Baylor College of Medicine, H-22209; Michael E. DeBakey VAMC, H<sup>\u2212\u200922202<\/sup>; Columbia University Medical Center, IRB-AAAC9324; Duke University Medical Center, Pro00004464; Johns Hopkins University, NA_00011524; Los Angeles Biomedical Research Institute, 12756\u201301; Morehouse School of Medicine, 07\u20131029; Temple University, 11369; University of Alabama at Birmingham, FO70712014; University of California, San Diego, 070876; University of Iowa, 200710717; Ann Arbor VA, PCC 2008\u2013110732; University of Minnesota, 0801\u2009M24949; University of Pittsburgh, RO07120059; University of Texas Health Sciences Center at San Antonio, HSC20070644H; Health Partners Research Foundation, 07\u2013127; University of Michigan, HUM00014973; Minneapolis VA Medical Center, 4128-A; Fallon Clinic, 1143).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RNC, EAK, NM, RC, WWL \u2013 none.CRH \u2013 An employee of and has stock options in Imbio LLC, which has licensed the PRM technology for use as FDA-approved commercial software.DAL - Reports grants from NHLBI and has a pending patent entitled Systems and Methods for Classifying Severity of COPD.CJG \u2013 Is co-inventor of PRM, which is licensed to Imbio by the University of Michigan.MM \u2013 Reports other support from UpToDate.BM \u2013 Reports funding from the NHLBI for the COPDGene study; grants and medical advisory boards from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, and Sunovian; personal fees for DSMB from Spiration and Shire\/Baxalta; CME personal fees from WebMD, National Jewish.Health, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, SPIRE Learning, Ultimate Medical Academy, Catamount Medical, Eastern Pulmonary Society, Catamount Medical Communications Medscape, Eastern VA Medical Center, Academy Continued Healthcare Learning, and Mt. Sinai Medical Center; royalties from Up-To-Date; medical advisory boards from Novartis, Phillips, Third Pole, Science 24\/7, and Vernoa; and grants from Pearl.FJM - Receives personal fees and non-financial support from American College of Chest Physicians, AstraZeneca, Boehringer Ingelheim, ConCert, Genentech, GlaxoSmithKline, Inova Fairfax Health System, Miller Communications, National Association for Continuing Education, Novartis, Pearl Pharmaceuticals, PeerView Communications, Prime Communications Puerto Rican Respiratory Society, Chiesi, Sunovion, Theravance, Physicians Education Resource, Canadian Respiratory Network, Teva, and Dartmouth. Receives non-financial support from ProterrixBio, Gilead, Nitto, Potomac, University of Alabama Birmingham, and Zambon. Receives personal fees from Columbia University, Integritas, MD Magazine, Methodist Hospital Brooklyn, New York University, UpToDate, WebMD\/MedScape, Western Connecticut Health Network, Patara\/Respivant, PlatformIQ, American Thoracic Society, Rockpointe, Rare Disease Healthcare Communications, and France Foundation. He receives grants from the NIH. He also receives other support from Afferent\/Merck, Biogen, Veracyte, Prometic, Bayer, Bridge Biotherapeutics, and ProMedior.JLC - Reports grants from NIH\/NHLBI, NIH\/NIAID, the Department of Veterans Affairs, and the Department of Defense.MKH - Reports grants from NIH, personal fees from BI, GSK, AZ, and Mylan. She also receives other support from Novartis and Sunovion.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"269"}}