RT Journal Article SR Electronic T1 Radiographic Lung Volumes Predict Progression to COPD in Smokers with Preserved Spirometry in SPIROMICS JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1802214 DO 10.1183/13993003.02214-2018 A1 Mehrdad Arjomandi A1 Siyang Zeng A1 Igor Barjaktarevic A1 R. Graham Barr A1 Eugene R. Bleecker A1 Russell P. Bowler A1 Russell G. Buhr A1 Gerard J. Criner A1 Alejandro P. Comellas A1 Christopher B. Cooper A1 David J. Couper A1 Jeffrey L. Curtis A1 Mark T. Dransfield A1 MeiLan K. Han A1 Nadia N. Hansel A1 Eric A. Hoffman A1 Robert J. Kaner A1 Richard E. Kanner A1 Jerry A. Krishnan A1 Robert Paine III A1 Stephen P. Peters A1 Stephen I. Rennard A1 Prescott G. Woodruff A1 , YR 2019 UL http://erj.ersjournals.com/content/early/2019/07/17/13993003.02214-2018.abstract AB The characteristics that predict progression to overt COPD in smokers without spirometric airflow obstruction are not clearly defined.We conducted a post-hoc analysis of 849 current and former smokers (≥20 pack-years) with preserved spirometry from the SPIROMICS cohort who had baseline computed tomography (CT) scans of lungs and serial spirometry. We examined whether CT-derived lung volumes representing air trapping could predict adverse respiratory outcomes and more rapid decline in spirometry to overt COPD using mixed effect linear modelling.Among these subjects with normal forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC), CT-measured residual volume to total lung capacity ratio (RVCT/TLCCT) varied widely, from 21% to 59%. Over 2.5±0.7 years of follow-up, subjects with higher RVCT/TLCCT had a greater differential rate of decline in FEV1/FVC; those in the upper RVCT/TLCCT tertile had a 0.66% [95%CI=0.06%–1.27%] faster rate of decline per year compared to those in the lower tertile (p=0.015) regardless of demographics, baseline spirometry, respiratory symptoms score, smoking status (former versus current), or smoking burden (pack-years). Accordingly, subjects with higher RVCT/TLCCT were more likely to develop spirometric COPD (odds ratio=5.7 [95%CI=2.4–13.2] in upper versus lower RVCT/TLCCTtertile; p<0.001). Other CT indices of air trapping showed similar patterns of association with lung function decline; however, when all CT indices of air trapping, emphysema, and airway disease were included in the same model, only RVCT/TLCCT retained its significance.Increased air trapping based on radiographic lung volumes predicts accelerated spirometry decline and progression to COPD in smokers without obstruction.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Arjomandi reports other from United States Department of Veterans Affairs, grants and other from United States National Institute of Health, during the conduct of the study.Conflict of interest: Siyang Zeng reports other from United States Department of Veterans Affairs, during the conduct of the study; .Conflict of interest: Dr. Barjaktarevic reports grants from AMGEN, grants and personal fees from GE Healthcare, personal fees from Grifols, personal fees from Astra Zeneca, personal fees from CSL Behring, personal fees from Boehringer Ingelheim, personal fees from Verona Pharma, personal fees from Fisher and Pykel Healthcare, outside the submitted work.Conflict of interest: Dr. Barr reports grants from NIH, grants from Foundation for the NIH, grants from COPD Foundation, during the conduct of the study; grants from Alpha1 Foundation, personal fees from UpToDate, outside the submitted work.Conflict of interest: Dr. Bleecker reports grants from SARP, AsthmaNET, SPIROMICS, Pharmacogenetics, Foundation NIH, other from Amgen, AstraZeneca-MedImmune, Boehringer-Ingelheim, Genentech/Roche, GlaxoSmithKline, Janssen/Johnson &amp; Johnson, Novartis, Pfizer, Sanofi-Regeneron, Teva, personal fees from Amgen, AstraZeneca-MedImmune, Boehringer-Ingelheim, Genentech/Roche, GlaxoSmithKline, Knopp, Novartis, Sanofi/Regeneron, outside the submitted work.Conflict of interest: Dr. Bowler reports having served on advistory boards for Boehringer-Ingelheim and Abbott Nutrition, outside the submitted work.Conflict of interest: Dr. Buhr reports personal fees from GlaxoSmithKline, outside the submitted work.Conflict of interest: Dr. criner has nothing to disclose.Conflict of interest: Dr. Comellas reports grants from NIH, during the conduct of the study; non-financial support from VIDA Diagnostics, outside the submitted work.Conflict of interest: Dr. Cooper has nothing to disclose.Conflict of interest: Dr. Couper reports grants from NHLBI (NIH), grants from COPD Foundation, during the conduct of the study; grants from NHLBI (NIH), outside the submitted work.Conflict of interest: Dr. Curtis reports grants from NIH/NHLBI, during the conduct of the study; and grants from Department of Veterans Affairs, NIH/NIAID, Department of Defense, and MedImmune, Corp. Ltd. , outside the submitted work.Conflict of interest: Dr. Dransfield reports grants from NIH, during the conduct of the study; grants from Department of Defense , personal fees and other from Boehringer Ingelheim, personal fees and other from GlaxoSmithKline, other from Novartis, personal fees and other from AstraZeneca, other from Yungjin, personal fees and other from PneumRx/BTG, other from Pulmonx, personal fees from Genentech, other from Boston Scientific , personal fees from Quark Pharmaceuticals, grants from NIH, personal fees from Mereo, grants from American Lung Association, outside the submitted work.Conflict of interest: Dr. Han reports personal fees from GSK, personal fees from BI, personal fees from AZ, non-financial support from Novartis, non-financial support from Sunovion, outside the submitted work.Conflict of interest: Dr. Hansel reports grants and personal fees from AstraZeneca, grants and personal fees from GSK, grants from Boehringer Ingelheim, grants from NIH, grants from COPD Foundation, personal fees from Mylan, outside the submitted work.Conflict of interest: Dr. Hoffman reports grants from NIH, during the conduct of the study; and Eric Hoffman is a founder and shareholder of VIDA Diagnostics, a company commercialising lung image analysis software developed, in part, at the University of Iowa.Conflict of interest: Dr. Kaner reports personal fees from Boehringer Ingelheim, personal fees from Roche/Genentech, personal fees from Medimmune/Astra Zeneca, personal fees from Gilead, personal fees from Celgene, from Janssen, outside the submitted work.Conflict of interest: Dr. Kanner has nothing to disclose.Conflict of interest: Dr. Krishnan has nothing to disclose.Conflict of interest: Dr. Paine reports grants from NHLBI, grants from COPD Foundation, during the conduct of the study; grants from Department of Veterans Affairs, outside the submitted work.Conflict of interest: Dr. Peters, MD, PhD reports grants from NIH, NHLBI, during the conduct of the study.Conflict of interest: SR is employed by AstraZeneca, Cambridge, UK and also retains Professorship and a part-time appointment at the the University of Nebraska Medical Center, Omaha, NE, USA.Conflict of interest: Dr. Woodruff reports personal fees from Theravance, personal fees from Astra Zeneca, personal fees from Regeneron, personal fees from Sanofi, personal fees from Genentech, personal fees from Roche, personal fees from Janssen, outside the submitted work.