{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:52:42Z","timestamp":1780087962984,"version":"3.54.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"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":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The rate of decline of lung function is greater than age-related change in a substantial proportion of patients with chronic obstructive pulmonary disease, even after smoking cessation. Regions of the lung adjacent to emphysematous areas are subject to abnormal stretch during respiration, and this biomechanical stress likely influences emphysema initiation and progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess whether quantifying this penumbra of lung at risk would predict FEV1 decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed paired inspiratory-expiratory computed tomography images at baseline of 680 subjects participating in a large multicenter study (COPDGene) over approximately 5 years. By matching inspiratory and expiratory images voxel by voxel using image registration, we calculated the Jacobian determinant, a measure of local lung expansion and contraction with respiration. We measured the distance between each normal voxel to the nearest emphysematous voxel, and quantified the percentage of normal voxels within each millimeter distance from emphysematous voxels as mechanically affected lung (MAL). Multivariable regression analyses were performed to assess the relationship between the Jacobian determinant, MAL, and FEV1 decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The mean (SD) rate of decline in FEV1 was 39.0 (58.6) ml\/yr. There was a progressive decrease in the mean Jacobian determinant of both emphysematous and normal voxels with increasing disease stage (P\u2009&amp;lt;\u20090.001). On multivariable analyses, the mean Jacobian determinant of normal voxels within 2 mm of emphysematous voxels (MAL2) was significantly associated with FEV1 decline. In mild-moderate disease, for participants at or above the median MAL2 (threshold, 36.9%), the mean decline in FEV1 was 56.4 (68.0) ml\/yr versus 43.2 (59.9) ml\/yr for those below the median (P\u2009=\u20090.044).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Areas of normal-appearing lung are mechanically influenced by emphysematous areas and this lung at risk is associated with lung function decline.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT00608764).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201701-0050oc","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T15:32:40Z","timestamp":1494257560000},"page":"569-576","source":"Crossref","is-referenced-by-count":77,"title":["Computed Tomography Measure of Lung at Risk and Lung Function Decline in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"196","author":[{"given":"Surya P.","family":"Bhatt","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine"},{"name":"UAB Lung Health Center, and"},{"name":"UAB Lung Imaging Core, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Bodduluri","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine"},{"name":"UAB Lung Imaging Core, University of Alabama at Birmingham, Birmingham, Alabama"},{"name":"Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa; and"},{"name":"Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"John D.","family":"Newell","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C.","family":"Sieren","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Dransfield","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine"},{"name":"UAB Lung Health Center, and"},{"name":"UAB Lung Imaging Core, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,1]]},"reference":[{"key":"2026032023451527000_bib1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1164\/rccm.201204-0596PP","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary","volume":"187","author":"Vestbo","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023451527000_bib2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1164\/rccm.201106-0992OC","article-title":"Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease","volume":"185","author":"Nishimura","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023451527000_bib3","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1136\/thoraxjnl-2012-201871","article-title":"Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease","volume":"68","author":"Duvoix","year":"2013","journal-title":"Thorax"},{"key":"2026032023451527000_bib4","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1056\/NEJMoa1105482","article-title":"Changes in forced expiratory volume in 1 second over time in COPD","volume":"365","author":"Vestbo","year":"2011","journal-title":"N Engl J Med"},{"key":"2026032023451527000_bib5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1152\/jappl.1967.22.1.95","article-title":"Significance of the relationship between lung recoil and maximum expiratory flow","volume":"22","author":"Mead","year":"1967","journal-title":"J Appl Physiol"},{"key":"2026032023451527000_bib6","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1056\/NEJM200007273430407","article-title":"Chronic obstructive pulmonary disease","volume":"343","author":"Barnes","year":"2000","journal-title":"N Engl J Med"},{"key":"2026032023451527000_bib7","doi-asserted-by":"crossref","first-page":"7485","DOI":"10.1073\/pnas.0913880107","article-title":"Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers","volume":"107","author":"Alford","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026032023451527000_bib8","first-page":"1892","article-title":"Biomechanics of the lung parenchyma: critical roles of collagen and mechanical forces","volume":"2005","author":"Suki","year":"1985","journal-title":"J Appl Physiol"},{"key":"2026032023451527000_bib9","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1164\/ajrccm.164.10.2101083","article-title":"Roles of mechanical forces and collagen failure in the development of elastase-induced emphysema","volume":"164","author":"Kononov","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023451527000_bib10","first-page":"32","article-title":"A distributed nonlinear model of lung tissue elasticity","volume":"1997","author":"Maksym","year":"1985","journal-title":"J Appl Physiol"},{"key":"2026032023451527000_bib11","first-page":"503","article-title":"Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: possible role of collagen remodeling","volume":"2005","author":"Ito","year":"1985","journal-title":"J Appl Physiol"},{"key":"2026032023451527000_bib12","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1073\/pnas.0808414106","article-title":"A zipper network model of the failure mechanics of extracellular matrices","volume":"106","author":"Ritter","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026032023451527000_bib13","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.pupt.2011.04.027","article-title":"Mechanical failure, stress redistribution, elastase activity and binding site availability on elastin during the progression of emphysema","volume":"25","author":"Suki","year":"2012","journal-title":"Pulm Pharmacol Ther"},{"key":"2026032023451527000_bib14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.acra.2013.01.019","article-title":"Registration-based lung mechanical analysis of chronic obstructive pulmonary disease (COPD) using a supervised machine learning framework","volume":"20","author":"Bodduluri","year":"2013","journal-title":"Acad Radiol"},{"key":"2026032023451527000_bib15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1164\/rccm.201511-2219OC","article-title":"Association between functional small airway disease and FEV1 decline in chronic obstructive pulmonary disease","volume":"194","author":"Bhatt","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023451527000_bib16","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3109\/15412550903499522","article-title":"Genetic epidemiology of COPD (COPDGene) study design","volume":"7","author":"Regan","year":"2010","journal-title":"COPD"},{"key":"2026032023451527000_bib17","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1118\/1.3193526","article-title":"Mass preserving nonrigid registration of CT lung images using cubic B-spline","volume":"36","author":"Yin","year":"2009","journal-title":"Med Phys"},{"key":"2026032023451527000_bib18","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.acra.2016.10.011","article-title":"Lung mass in smokers","volume":"24","author":"Washko","year":"2017","journal-title":"Acad Radiol"},{"key":"2026032023451527000_bib19","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3389\/fphys.2016.00287","article-title":"Mechanical forces accelerate collagen digestion by bacterial collagenase in lung tissue strips","volume":"7","author":"Yi","year":"2016","journal-title":"Front Physiol"},{"key":"2026032023451527000_bib20","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1016\/j.bpj.2010.09.018","article-title":"Mechanical forces regulate elastase activity and binding site availability in lung elastin","volume":"99","author":"Jesudason","year":"2010","journal-title":"Biophys J"},{"key":"2026032023451527000_bib21","first-page":"29","article-title":"On the elasticity of the lungs","volume":"110","author":"Carson","year":"1820","journal-title":"Philos Trans R Soc Lond"},{"key":"2026032023451527000_bib22","doi-asserted-by":"crossref","first-page":"8829","DOI":"10.1073\/pnas.96.16.8829","article-title":"Complexity of terminal airspace geometry assessed by lung computed tomography in normal subjects and patients with chronic obstructive pulmonary disease","volume":"96","author":"Mishima","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026032023451527000_bib23","doi-asserted-by":"crossref","first-page":"e44993","DOI":"10.1371\/journal.pone.0044993","article-title":"Longitudinal study of spatially heterogeneous emphysema progression in current smokers with chronic obstructive pulmonary disease","volume":"7","author":"Tanabe","year":"2012","journal-title":"PLoS One"},{"key":"2026032023451527000_bib24","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1056\/NEJMoa0805800","article-title":"A 4-year trial of tiotropium in chronic obstructive pulmonary disease","volume":"359","author":"Tashkin","year":"2008","journal-title":"N Engl J Med"},{"key":"2026032023451527000_bib25","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1164\/rccm.200712-1869OC","article-title":"Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study","volume":"178","author":"Celli","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023451527000_bib26","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1378\/chest.11-2837","article-title":"Lung function decline in male heavy smokers relates to baseline airflow obstruction severity","volume":"142","author":"Mohamed Hoesein","year":"2012","journal-title":"Chest"},{"key":"2026032023451527000_bib27","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1136\/thx.2010.145995","article-title":"CT-quantified emphysema in male heavy smokers: association with lung function decline","volume":"66","author":"Mohamed Hoesein","year":"2011","journal-title":"Thorax"},{"key":"2026032023451527000_bib28","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1164\/rccm.2112096","article-title":"Smoking and lung function of Lung Health Study participants after 11 years","volume":"166","author":"Anthonisen","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023451527000_bib29","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1164\/ajrccm.154.1.8680679","article-title":"Comparison of computed density and microscopic morphometry in pulmonary emphysema","volume":"154","author":"Gevenois","year":"1996","journal-title":"Am J Respir Crit Care Med"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/196\/5\/569\/67125728\/ajrccm_196_5_569.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/196\/5\/569\/67125728\/ajrccm_196_5_569.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T03:45:55Z","timestamp":1774064755000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/196\/5\/569\/8499071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,1]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,9,1]]},"published-print":{"date-parts":[[2017,9,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201701-0050oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,9]]},"published":{"date-parts":[[2017,9,1]]}}}