Abstract
The characteristics that predict progression to overt chronic obstructive pulmonary disease (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 Subpopulations and Intermediate Outcome Measures in COPD Study (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 (FEV1) to forced vital capacity (FVC) ratio, CT-measured residual volume (RVCT) to total lung capacity (TLCCT) ratio 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 with 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 (OR 5.7 (95% CI 2.4–13.2) in upper versus lower RVCT/TLCCT tertile; 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.
Abstract
Radiographic lung volumes and related computed tomography measures that represent air trapping are associated with an accelerated decline in lung function and can identify susceptible smokers at increased risk of progressing to overt COPD http://bit.ly/32QqiKQ
Footnotes
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Author contributions: Conceived and designed the current study: M. Arjomandi. Developed study protocols: M. Arjomandi, S. Zeng, I. Barjaktarevic, R.G. Barr, E.R. Bleecker, R.P. Bowler, R.G. Buhr, G.J. Criner, A.P. Comellas, C.B. Cooper, D.J. Couper, J.L. Curtis, M.T. Dransfield, M.K. Han, N.N. Hansel, E.A. Hoffman, R.J. Kaner, R.E. Kanner, J.A. Krishnan, R. Paine III, S.P. Peters, S.I. Rennard and P.G. Woodruff. Collected data: I. Barjaktarevic, R.G. Barr, E.R. Bleecker, R.P. Bowler, R.G. Buhr, G.J. Criner, A.P. Comellas, C.B. Cooper, D.J. Couper, J J.L. Curtis, M.T. Dransfield, M.K. Han, N.N. Hansel, E.A. Hoffman, R.J. Kaner, R.E. Kanner, J.A. Krishnan, R. Paine III, S.P. Peters, S.I. Rennard and P.G. Woodruff. Analysed and interpreted data: M. Arjomandi, S. Zeng, I. Barjaktarevic, R.G. Barr, R.P. Bowler, R.G. Buhr, A.P. Comellas, C.B. Cooper, D.J. Couper, J.L. Curtis, M.T. Dransfield, M.K. Han, N.N. Hansel, E.A. Hoffman, R.J. Kaner, R.E. Kanner, J.A. Krishnan, R. Paine III, S.P. Peters, S.I. Rennard and P.G. Woodruff. Prepared and edited the manuscript: M. Arjomandi, S. Zeng, I. Barjaktarevic, R.G. Barr, R.P. Bowler, R.G. Buhr, A.P. Comellas, C.B. Cooper, D.J. Couper, J.L. Curtis, M.T. Dransfield, M.K. Han, N.N. Hansel, E.A. Hoffman, R.J. Kaner, R.E. Kanner, J.A. Krishnan, R. Paine III, S.P. Peters, S.I. Rennard and P.G. Woodruff. Obtained funding: M. Arjomandi, I. Barjaktarevic, R.G. Barr, E.R. Bleecker, R.P. Bowler, R.G. Buhr, G.J. Criner, A.P. Comellas, C.B. Cooper, D.J. Couper, J.L. Curtis, M.T. Dransfield, M.K. Han, N.N. Hansel, E.A. Hoffman, R.J. Kaner, R.E. Kanner, J.A. Krishnan, R. Paine III, S.P. Peters, S.I. Rennard and P.G. Woodruff.
Support statement: SPIROMICS was supported by contracts from the NIH/NHLBI (HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune, Bayer, Bellerophon Therapeutics; Boehringer Ingelheim Pharmaceuticals, Inc., Chiesi Farmaceutici S.p.A., Forest Research Institute, Inc., GlaxoSmithKline, Grifols Therapeutics, Inc., Ikaria, Inc., Novartis Pharmaceuticals Corporation, Nycomed GmbH, ProterixBio, Regeneron Pharmaceuticals, Inc., Sanofi, Sunovion, Takeda Pharmaceutical Company and Theravance Biopharma. Funding for the work on this manuscript was also provided by the Flight Attendant Medical Research Institute (M. Arjomandi). Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: S. Zeng reports salary support from United States Department of Veterans Affairs, during the conduct of the study.
Conflict of interest: I. Barjaktarevic reports grants from AMGEN, grants and personal fees from GE Healthcare, personal fees from Grifols, AstraZeneca, CSL Behring, Boehringer Ingelheim, Verona Pharma and Fisher and Pykel Healthcare, outside the submitted work.
Conflict of interest: R.G. Barr reports grants from NIH, Foundation for the NIH and COPD Foundation, during the conduct of the study; grants from Alpha1 Foundation, personal fees (royalties) from UpToDate, outside the submitted work.
Conflict of interest: E.R. Bleecker reports grants from SARP, AsthmaNET, SPIROMICS, Pharmacogenetics and Foundation NIH, involvement in clinical trials administered through Wake Forest School of Medicine for Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, Genentech/Roche, GlaxoSmithKline, Janssen/Johnson & Johnson, Novartis, Pfizer, Sanofi-Regeneron and Teva, personal fees for consultancy from Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, Genentech/Roche, GlaxoSmithKline, Knopp, Novartis and Sanofi/Regeneron, outside the submitted work.
Conflict of interest: R.P. Bowler reports having served on advistory boards for Boehringer-Ingelheim and Abbott Nutrition, outside the submitted work.
Conflict of interest: R.G. Buhr reports personal fees from GlaxoSmithKline, outside the submitted work.
Conflict of interest: G.J. Criner has nothing to disclose.
Conflict of interest: A.P. Comellas reports grants from NIH, during the conduct of the study; non-financial support for consultancy from VIDA Diagnostics, outside the submitted work.
Conflict of interest: C.B. Cooper has nothing to disclose.
Conflict of interest: D.J. Couper reports grants from NHLBI (NIH) and COPD Foundation, during the conduct of the study; grants from NHLBI (NIH), outside the submitted work.
Conflict of interest: J.L. Curtis reports grants from NIH/NHLBI (U01HL137880), during the conduct of the study; and grants from Department of Veterans Affairs (I01 CX000911), NIH/NIAID (R01 AI120526, R21 AI 117371), Department of Defense (W81XWH-15-1-0705, PR150432) and MedImmune, Corp. Ltd, outside the submitted work.
Conflict of interest: M.T. Dransfield reports grants from NIH, during the conduct of the study; grants from Department of Defense, NIH and the American Lung Association, personal fees for consultancy and involvement with contracted clinical trials for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, PneumRx/BTG and Boston Scientific, involvement with contracted clinical trials for Novartis, Yungjin and Pulmonx, personal fees for consultancy from Genentech, Quark Pharmaceuticals and Mereo, outside the submitted work.
Conflict of interest: M.K. Han reports personal fees from GSK, BI and AZ, non-financial support from Novartis and Sunovion, outside the submitted work.
Conflict of interest: N.N. Hansel reports grants and personal fees for consultancy from AstraZeneca and GSK, grants from Boehringer Ingelheim, NIH and COPD Foundation, personal fees for consultancy from Mylan, outside the submitted work.
Conflict of interest: E.A. Hoffman reports grants from NIH, during the conduct of the study; and 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: R.J. Kaner reports personal fees from Boehringer Ingelheim, Roche/Genentech, Medimmune/AstraZeneca, Gilead, Celgene and Janssen, outside the submitted work.
Conflict of interest: R.E. Kanner has nothing to disclose.
Conflict of interest: J.A. Krishnan has nothing to disclose.
Conflict of interest: R. Paine III reports grants from NHLBI and COPD Foundation, during the conduct of the study; grants from Department of Veterans Affairs, outside the submitted work.
Conflict of interest: S.P. Peters, reports grants from NIH, NHLBI as the PI of the Wake Forest Clinical Site for the SPIROMICS COPD Program, during the conduct of the study.
Conflict of interest: S.I. Rennard 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: P.G. Woodruff reports personal fees for consultancy from Theravance, AstraZeneca, Regeneron, Sanofi, Genentech, Roche and Janssen, outside the submitted work.
Conflict of interest: M. Arjomandi reports salary support from United States Department of Veterans Affairs, grants and salary support from United States National Institute of Health, during the conduct of the study.
- Received November 21, 2018.
- Accepted July 17, 2019.
- Copyright ©ERS 2019
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