Local heterogeneity of normal lung parenchyma and small airways disease are associated with COPD severity and progression.

"Declarations Ethics approval and consent to participateOur study was a secondary analysis of data from COPDGene (ClinicalTrials.gov: NCT00608764), a large Health Insurance Portability and Accountability Act-compliant prospective multi-center observational study. In Phase 1 (2007–2012) and Phase 2 (2013–2017), 5-year follow-up, written and informed consent was obtained from all participants and the study was approved by local institutional review boards of all 21 centers. Consent for publicationOur study did not require consent for publication from individuals as it was a secondary analysis of data from COPDGene (ClinicalTrials.gov: NCT00608764). Written and informed consent for the COPDGene study was obtained from all participants and the study was approved by local institutional review boards of all 21 centers. For our study, data from COPDGene was anonymized and our authors had no access to identifying information for COPDGene study participants. Competing interestsWassim W. Labaki reports personal fees from Continuing Education Alliance. Benjamin A. Hoff and Craig J. Galban are co-inventors and patent holders of tPRM, which the University of Michigan has licensed to Imbio, LLC. Craig J. Galban is co-inventor and patent holder of PRM, which the University of Michigan has licensed to Imbio, LLC. Benjamin A. Hoff and Craig J. Galban have financial interest in Imbio, LLC. Charles R. Hatt is employed by Imbio, LLC. David A. Lynch reports funds paid to the institution from NIH and personal payments from Boehringer Ingelheim. MeiLan K. Han reports personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, Regeneron, Amgen, UpToDate, Altesa Biopharma, Medscape, NACE, MDBriefcase and Integrity. She has received either in kind research support or funds paid to the institution from the NIH, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation and the American Lung Association. She has participated in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution. She has received stock options from Meissa Vaccines and Altesa Biopharma. For the remaining authors none were declared. Competing interests Wassim W. Labaki reports personal fees from Continuing Education Alliance. Benjamin A. Hoff and Craig J. Galban are co-inventors and patent holders of tPRM, which the University of Michigan has licensed to Imbio, LLC. Craig J. Galban is co-inventor and patent holder of PRM, which the University of Michigan has licensed to Imbio, LLC. Benjamin A. Hoff and Craig J. Galban have financial interest in Imbio, LLC. Charles R. Hatt is employed by Imbio, LLC. David A. Lynch reports funds paid to the institution from NIH and personal payments from Boehringer Ingelheim. MeiLan K. Han reports personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, Regeneron, Amgen, UpToDate, Altesa Biopharma, Medscape, NACE, MDBriefcase and Integrity. She has received either in kind research support or funds paid to the institution from the NIH, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation and the American Lung Association. She has participated in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution. She has received stock options from Meissa Vaccines and Altesa Biopharma. For the remaining authors none were declared."

"Funding This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health Grants R01 HL139690 (to CJG), R01 HL150023 (to MKH, CJG, and CRH) and T32 HL 007749 (to JMW) and by the National Heart, Lung, and Blood Institute of the National Institutes of Health Grants U01 HL089897 and U01 HL089856 and by NIH contract 75N92023D00011, which support the COPDGene study. The COPDGene study (NCT00608764) has also been supported by the COPD Foundation through contributions made to an Industry Advisory Committee that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer and Sunovion."