{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:23:21Z","timestamp":1791275001675,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether airway wall thickening and emphysema (1) make independent contributions to the severity of COPD and (2) show independent aggregation in families of individuals with COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Index cases with COPD and their smoking siblings underwent spirometry and were offered high-resolution computed tomography scans of the thorax to assess the severity of airway wall thickening and emphysema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A total of 3,096 individuals were recruited to the study, of whom 1,159 (519 probands and 640 siblings) had technically adequate high-resolution computed tomography scans without significant non\u2013COPD-related thoracic disease. Airway wall thickness correlated with pack-years smoked (P \u2264 0.001) and symptoms of chronic bronchitis (P &amp;lt; 0.001). FEV1 (expressed as % predicted) was independently associated with airway wall thickness at a lumen perimeter of 10 mm (P = 0.0001) and 20 mm (P = 0.0013) and emphysema at \u2212950 Hounsfield units (P &amp;lt; 0.0001). There was independent familial aggregation of both the emphysema (adjusted odds ratio, 2.1; 95% confidence interval, 1.1\u20134.0; P \u2264 0.02) and airway disease phenotypes (P &amp;lt; 0.0001) of COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Airway wall thickening and emphysema make independent contributions to airflow obstruction in COPD. These phenotypes show independent aggregation within families of individuals with COPD, suggesting that different genetic factors influence these disease processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200801-059oc","type":"journal-article","created":{"date-parts":[[2008,6,19]],"date-time":"2008-06-19T21:50:45Z","timestamp":1213912245000},"page":"500-505","source":"Crossref","is-referenced-by-count":249,"title":["Airway Wall Thickening and Emphysema Show Independent Familial Aggregation in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"178","author":[{"given":"Bipen D.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Medicine and"},{"name":"Institute of Public Health, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey O.","family":"Coxson","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada"},{"name":"Division of Respiratory Medicine and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreekumar G.","family":"Pillai","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvar G. N.","family":"Agusti\u0301","sequence":"additional","affiliation":[{"name":"Hospital Universitari Son Dureta, CIBER Enfermedades Respiratorias and Fundacio\u0301n Caubet-Cimera, Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M. A.","family":"Calverley","sequence":"additional","affiliation":[{"name":"University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio F.","family":"Donner","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease, S. Maugeri Foundation, Veruno, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Make","sequence":"additional","affiliation":[{"name":"National Jewish Medical and Research Center, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nestor L.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen I.","family":"Rennard","sequence":"additional","affiliation":[{"name":"University of Nebraska, Omaha, Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen","family":"Vestbo","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, Copenhagen, Denmark"},{"name":"North West Lung Centre, Wythenshawe Hospital, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiel F. M.","family":"Wouters","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie P.","family":"Hiorns","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Nakano","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia G.","family":"Camp","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola V.","family":"Nasute Fauerbach","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Screaton","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Utah, Salt Lake City, Utah; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne H.","family":"Anderson","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Levy","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Lake","sequence":"additional","affiliation":[{"name":"The Channing Laboratory and Pulmonary and Critical Care Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin K.","family":"Silverman","sequence":"additional","affiliation":[{"name":"The Channing Laboratory and Pulmonary and Critical Care Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Lomas","sequence":"additional","affiliation":[{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,9,1]]},"reference":[{"key":"2026032102232665100_BIB1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1164\/rccm.200703-456SO","volume":"176","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB2","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1056\/NEJMoa032158","volume":"350","year":"2004","journal-title":"N Engl J Med"},{"key":"2026032102232665100_BIB3","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(04)16900-6","volume":"364","year":"2004","journal-title":"Lancet"},{"key":"2026032102232665100_BIB4","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1136\/thx.49.5.473","volume":"49","year":"1994","journal-title":"Thorax"},{"key":"2026032102232665100_BIB5","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1136\/thx.2006.072777","volume":"62","year":"2007","journal-title":"Thorax"},{"key":"2026032102232665100_BIB6","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.2214\/ajr.163.5.7976869","volume":"163","year":"1994","journal-title":"Am J Roentgenol"},{"key":"2026032102232665100_BIB7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1148\/radiology.159.1.3952318","volume":"159","year":"1986","journal-title":"Radiology"},{"key":"2026032102232665100_BIB8","first-page":"541","volume":"133","year":"1986","journal-title":"Am Rev Respir Dis"},{"key":"2026032102232665100_BIB9","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1164\/ajrccm.162.3.9907120","volume":"162","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB10","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1164\/rccm.200601-037OC","volume":"173","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB11","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1136\/bmj.1.6077.1645","volume":"1","year":"1977","journal-title":"BMJ"},{"key":"2026032102232665100_BIB12","first-page":"195","volume":"115","year":"1977","journal-title":"Am Rev Respir Dis"},{"key":"2026032102232665100_BIB13","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1164\/ajrccm\/137.2.286","volume":"137","year":"1988","journal-title":"Am Rev Respir Dis"},{"key":"2026032102232665100_BIB14","first-page":"32","volume":"45","year":"1989","journal-title":"Thorax"},{"key":"2026032102232665100_BIB15","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/S0140-6736(06)68516-4","volume":"367","year":"2006","journal-title":"Lancet"},{"key":"2026032102232665100_BIB16","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1164\/ajrccm.157.6.9706014","volume":"157","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB17","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1164\/ajrccm.164.8.2105002","volume":"164","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB18","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0025-7125(05)70451-X","volume":"80","year":"1996","journal-title":"Med Clin North Am"},{"key":"2026032102232665100_BIB19","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/rr34","volume":"2","year":"2001","journal-title":"Respir Res"},{"key":"2026032102232665100_BIB20","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1164\/rccm.200611-1723OC","volume":"176","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB21","first-page":"A507","volume":"169","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB22","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1513\/pats.200603-087MS","volume":"3","year":"2006","journal-title":"Proc Am Thorac Soc"},{"key":"2026032102232665100_BIB23","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1183\/09031936.02.00023202","volume":"20","year":"2002","journal-title":"Eur Respir J"},{"key":"2026032102232665100_BIB24","first-page":"1","volume":"118","year":"1978","journal-title":"Am Rev Respir Dis"},{"key":"2026032102232665100_BIB25","first-page":"1107","volume":"152","year":"1994","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB26","first-page":"659","volume":"123","year":"1981","journal-title":"Am Rev Respir Dis"},{"key":"2026032102232665100_BIB27","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1164\/ajrccm.159.3.9805067","volume":"159","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB28","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1164\/ajrccm.152.2.7633722","volume":"152","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB29","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1164\/rccm.200407-874OC","volume":"171","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1164\/ajrccm.154.1.8680679","volume":"154","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102232665100_BIB31","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1148\/radiol.2382042196","volume":"238","year":"2006","journal-title":"Radiology"},{"key":"2026032102232665100_BIB32","first-page":"1","volume":"39","year":"2004","journal-title":"Invest Radiol"},{"key":"2026032102232665100_BIB33","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1148\/radiology.197.3.7480750","volume":"197","year":"1995","journal-title":"Radiology"},{"key":"2026032102232665100_BIB34","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/00004728-199601000-00006","volume":"20","year":"1996","journal-title":"J Comput Assist Tomogr"},{"key":"2026032102232665100_BIB35","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1056\/NEJM196806202782501","volume":"278","year":"1968","journal-title":"N Engl J Med"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/178\/5\/500\/67444059\/ajrccm_178_5_500.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/178\/5\/500\/67444059\/ajrccm_178_5_500.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T06:23:37Z","timestamp":1774074217000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/178\/5\/500\/8525872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9,1]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2008,9,1]]},"published-print":{"date-parts":[[2008,9,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.200801-059oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,9]]},"published":{"date-parts":[[2008,9,1]]}}}