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. 2025 Jun 24;333(24):2164-2175.
doi: 10.1001/jama.2025.7358.

A Multidimensional Diagnostic Approach for Chronic Obstructive Pulmonary Disease

COPDGene 2025 Diagnosis Working Group and CanCOLD Investigators; Surya P Bhatt  1   2 , Ehsan Abadi  3 , Antonio Anzueto  4   5 , Sandeep Bodduluri  1   2 , Richard Casaburi  6 , Peter J Castaldi  7 , Michael H Cho  7 , Alejandro P Comellas  8 , Douglas J Conrad  9 , Jeffrey L Curtis  10   11 , Chandra Dass  12 , Dawn L DeMeo  7 , Mark T Dransfield  1 , Raul San José Estépar  13 , Eric L Flenaugh  14 , Marilyn G Foreman  14 , Spyridon Fortis  8 , Arnav Gupta  15 , MeiLan K Han  16 , Nicola A Hanania  17 , Craig P Hersh  7 , John E Hokanson  18 , Stephen M Humphries  19 , Miranda Kirby  20 , Ken M Kunisaki  21 , Pei Zhi Li  22 , David A Lynch  19 , Neil R MacIntyre  23 , Barry J Make  15 , David M Mannino  24 , Fernando J Martinez  25 , Charlene E McEvoy  26 , Bruce E Miller  24 , Matthew Moll  7 , Arie Nakhmani  2   27 , John D Newell Jr  28 , Katherine A Pratte  29 , Elizabeth A Regan  30 , Joseph M Reinhardt  31 , Stephen I Rennard  32 , Harry B Rossiter  6 , Matthew J Strand  29 , Rajat Suri  9 , Emily S Wan  7 , Christine H Wendt  21   33 , Gloria E Westney  14 , Carla G Wilson  29 , Robert A Wise  34 , Kendra A Young  18 , Wan C Tan  35 , Edwin K Silverman  7 , James D Crapo  15
Affiliations

A Multidimensional Diagnostic Approach for Chronic Obstructive Pulmonary Disease

COPDGene 2025 Diagnosis Working Group and CanCOLD Investigators et al. JAMA. .

Abstract

Importance: Individuals at risk for chronic obstructive pulmonary disease (COPD) but without spirometric airflow obstruction can have respiratory symptoms and structural lung disease on chest computed tomography. Current guidelines recommend COPD diagnostic schemas that do not incorporate imaging abnormalities.

Objective: To determine whether a multidimensional COPD diagnostic schema that includes respiratory symptoms and computed tomographic imaging abnormalities identifies additional individuals with disease.

Design, setting, and participants: This cohort study included 2 longitudinal cohorts: the Genetic Epidemiology of COPD (COPDGene), which enrolled 10 305 participants between November 9, 2007, and April 15, 2011, with longitudinal follow-up through August 31, 2022; and the Canadian Cohort Obstructive Lung Disease (CanCOLD), which enrolled 1561 participants between November 26, 2009, and July 15, 2015, with follow-up through December 31, 2023.

Exposure: Exposure included the new multidimensional COPD diagnostic schema, defined by (1) major diagnostic category: presence of the major criterion (airflow obstruction based on postbronchodilator forced expiratory volume in the first second of expiration [FEV1]/forced vital capacity ratio <0.70) and at least 1 of 5 minor criteria (emphysema or bronchial wall thickening on computed tomography, dyspnea, poor respiratory quality of life, and chronic bronchitis); or (2) minor diagnostic category: presence of least 3 of 5 minor criteria (which must include emphysema and bronchial wall thickening for individuals with respiratory symptoms potentially due to other causes).

Main outcomes and measures: All-cause mortality, respiratory cause-specific mortality, exacerbations, and annualized change in FEV1.

Results: Among 9416 adults in COPDGene (mean [SD] age at enrollment, 59.6 [9.0] years; 5035 [53.5%] were men; 3071 [32.6%] were Black; 6345 (67.4%) were White; 4943 [52.5%] currently smoked), 811 of 5250 individuals (15.4%) without airflow obstruction were newly classified as having COPD by minor diagnostic category, and 282 of 4166 individuals (6.8%) with airflow obstruction were classified as not having COPD. Reclassified individuals with a new COPD diagnosis had greater all-cause mortality (adjusted hazard ratio, 1.98; 95% CI, 1.67-2.35; P < .001) and respiratory-specific mortality (adjusted hazard ratio, 3.58; 95% CI, 1.56-8.20; P = .003), more exacerbations (adjusted incidence rate ratio, 2.09; 95% CI, 1.79-2.44; P < .001), and more rapid FEV1 decline (adjusted β = -7.7 mL/y; 95% CI, -13.2 to -2.3; P = .006) compared with individuals classified as not having COPD. Among individuals with airflow obstruction on spirometry, those no longer classified as having COPD based on this new diagnostic schema had outcomes similar to those without airflow obstruction. Among 1341 adults in CanCOLD, individuals newly classified as having COPD experienced more exacerbations (adjusted incidence rate ratio, 2.09; 95% CI, 1.25-3.51; P < .001).

Conclusions and relevance: A new COPD diagnostic schema integrating respiratory symptoms, respiratory quality of life, spirometry, and structural lung abnormalities on computed tomographic imaging newly classified some individuals as having COPD. These individuals had an increased risk of all-cause and respiratory-related death, frequent exacerbations, and rapid lung function decline compared with individuals classified as not having COPD. Some individuals with airflow obstruction without respiratory symptoms or evidence of structural lung disease were no longer classified as having COPD.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bhatt reported grants from the National Institutes of Health (NIH) during the conduct of the study; consulting fees from Apreo, AstraZeneca, Chiesi, Genentech, GSK, Boehringer Ingelheim, Sanofi, Regeneron, Merck, Verona Pharma, and Polarean; honoraria from Integrity CE, IlluminateHealth, HorizonCME, Integritas Communications, and Medscape; and grants from Sanofi/Regeneron, Genentech, and Nuvaira paid to his institution outside the submitted work. Dr Anzueto reported consulting fees from GSK, AstraZeneca, Sanofi/Regeneron, Viatris Pharma, Pfizer, and Abbott during the conduct of the study. Dr Castaldi reported grants from Sanofi and Bayer and consulting fees from Genentech and Verona Pharma outside the submitted work. Dr Cho reported grants from NIH during the conduct of the study, grants from Bayer, and consulting fees from BMS and Apogee outside the submitted work. Dr Comellas reported grants from NIH and nonfinancial support from VIDA Diagnostics as an unpaid consultant during the conduct of the study and grants from NIH outside the submitted work. Dr Curtis reported grants from NIH/National Heart, Lung, and Blood Institute (NHLBI) and the COPD Foundation to his institution during the conduct of the study; grants from NIH/NHLBI and the Department of Veterans Affairs to his institution outside the submitted work; and consulting fees from AstraZeneca (2020-2021), CSL Behring (2021-2022), and Genentech (2023 to present). Dr DeMeo reported grants from NIH during the conduct of the study and grants from the Alpha-1 Foundation and Bayer outside the submitted work. Dr Dransfield reported grants from NIH during the conduct of the study; grants from the Department of Defense and American Lung Association; royalties from UpToDate; consulting fees from GSK, COPD Foundation, and Apreo; and nonfinancial support from Aer Therapeutics outside the submitted work. Dr San José Estépar reported grants from NHLBI during the conduct of the study; being the founder of and holding stock in Quantitative Imaging Solutions; grants from Gossamer Bio and Boehringer Ingelheim; and being a member of the CRIS Cancer Foundation and serving on its advisory board outside the submitted work. Dr Fortis reported grants from the Office of Rural Health, consulting for the Society of Hospital Medicine, and owning stock in ROMTech outside the submitted work. Dr Han reported grants from NIH during the conduct of the study; fees for consulting on COPD therapeutic product development from GSK, AstraZeneca, Boehringer Ingelheim, Novartis, Pulmonx, Teva, Verona Pharma, Mylan, Sanofi, Roche, DevPro, Aerogen, Polarian, Regeneron, Amgen, Genentech, Altesa Biopharma, Apreo Health, and RS Biotherapeutics; fees for consulting on cough therapeutic product development from Merck; fees for consulting on COPD educational content development from UpToDate, Medscape, NACE, MDBriefCase, Integrity, MedWiz, Cipla, and Chiesi; grants from Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, COPD Foundation, and the American Lung Association paid to his institution; serving on a data and safety monitoring board for Novartis and Medtronic, with funds paid to his institution; and owning stock in Meissa Vaccines and Altesa outside the submitted work. Dr Hanania reported advisory fees from GSK, Genentech, Verona Pharma, and AstraZeneca; grants from GSK, Sanofi, Amgen, AstraZeneca, Genentech, Cheisi, and Regeneron to her institution outside the submitted work; and advisory and speaker fees from Sanofi and Regeneron. Dr Hersh reported grants from NHLBI to his institution during the conduct of the study; grants from Bayer to his institution; and consulting fees from Apogee Therapeutics, Chiesi, Genentech, Ono Pharma, Sanofi, Takeda, and Verona Pharma outside the submitted work. Dr Kirby reported consulting fees from VIDA Diagnostics outside the submitted work. Dr Kunisaki reported grants from NIH during the conduct of the study and fees from Nuvaira for data and safety monitoring board activities outside the submitted work. Dr Lynch reported grants from NHLBI during the conduct of the study and consulting fees from Sanofi outside the submitted work. Dr MacIntyre reported a contract from COPDGene during the conduct of the study and consulting fees from Inogen outside the submitted work. Dr Make reported grants from NHLBI provided to and controlled by National Jewish Health for COPDGene study data collection analysis and his salary during the conduct of the study; continuing medical education activity for Mt Sinai, WebMD, Temple University, Eastern Pulmonary Conference, Pri-Med, and American College of Chest Physicians outside the submitted work; disease-state presentations for GSK and Verona Pharma; providing a medical presentation for Boston University; serving on the medical advisory board for Sanofi, Verona Pharma, Regeneron, GSK, and AstraZeneca; and serving on the data and safety monitoring board for Mt Sinai and Baystate Medical Center. Dr Mannino reported consulting fees from AstraZeneca, GSK, Chiesi, Regeneron, Amgen, Roche, UpToDate, and Schlesinger Law Firm outside the submitted work. Dr Martinez reported grants from AstraZeneca (a partner in the SPIROMICS program and NHLBI CAPTURE validation study); grants from Chiesi (a partner in the SPIROMICS program); grants and fees for consulting from GSK (a partner in the SPIROMICS program and NHLBI CAPTURE validation study); grants and consulting fees from Sanofi/Regeneron (partners in the SPIROMICS program); grants from NHLBI; grants from DevPro and Novartis for a phase 2 COPD study; conducting a COPD disease-state study without honorarium for Roche during the conduct of the study; conducting continuing medical education for UpToDate outside the submitted work; holding a patent for CAPTURE licensed to Weill Cornell Medicine; and serving on an event adjudication committee for Medtronic. Dr McEvoy reported grants from NHLBI to her institute during the conduct of the study; and grants from GSK, AstraZeneca, and the Centers for Disease Control and Prevention to her institute outside the submitted work. Dr Miller reported consulting fees from the COPD Foundation and owning stock in GSK outside the submitted work. Dr Moll reported grants from NHLBI during the conduct of the study; having a contract with Genentech; and consulting fees from Sanofi, Verona Pharma, Dialectica, Axon Advisors, Expert Witness, 2nd.MD, and Thea Health outside the submitted work. Dr Newell reported grants from NIH during the conduct of the study; consulting fees from VIDA Diagnostics; royalties from Elsevier outside the submitted work; having patents pending for the University of Iowa and VIDA Diagnostics; holding patents for VIDA Diagnostics; owning stock and stock options with VIDA Diagnostics; and serving as the medical advisor to VIDA Diagnostics. Dr Pratte reported grants from National Jewish Health (salary funded by awards R01 HL137995 and R01 HL129937) during the conduct of the study. Dr Regan reported grants from NHLBI during the conduct of the study. Dr Reinhardt reported grants from NIH to the University of Iowa, owning stock in VIDA Diagnostics, and grants from the Roy J. Carver Charitable Trust to the University of Iowa during the conduct of the study; and expert witness fees from Auris Health outside the submitted work. Dr Rennard reported serving as medical director for the Alpha-1 Foundation; consultation fees from RespirAI, RS Biotherapeutics, Roche Diagnostics, Verona Pharma, and Beyond Air outside the submitted work; serving on the advertisement board for Sanofi/Regeneron; holding a patent for diagnostics for COPD exacerbation, with royalties paid to the University of Nebraska; and serving as founder and president of Great Plains Biometric, LLC, a spinoff company developing wearable diagnostics. Dr Rossiter reported grants from NIH (R01 HL166850, R01 HL151452, and R01 HL153460), University of California Office of the President/Tobacco Related Disease Research Program (T31IP1666), and the Department of Defense/US Army Medical Research Acquisition Activity (HT9425-24-1-0249); conducting clinical research for GSK, Genentech, Mezzion, Regeneron, Respira, United Therapeutics, and Intervene Immune; consulting fees from Roche and Duke University (for NIH/1OT2HL156812) outside the submitted work; and nonfinancial support from the University of Leeds outside the submitted work. Dr Strand reported grants from NIH during the conduct of the study. Dr Suri reported serving on the advisory panel for Verona Pharma outside the submitted work. Dr Wan reported serving on the advisory panel for Verona Pharma and serving as a speaker for MJH outside the submitted work. Dr Wise reported consulting fees from Kamada; grants from Chiesi and Sanofi/Regeneron; serving on a clinical end point committee for BIPI; and serving on an advisory committee for AstraZeneca outside the submitted work. Dr Young reported grants from NIH/NHLBI during the conduct of the study. Dr Silverman reported grants from NIH during the conduct of the study and grants from Bayer and Northpond Labs outside the submitted work. No other disclosures were reported.

Comment in

References

    1. Adeloye D, Song P, Zhu Y, Campbell H, Sheikh A, Rudan I; NIHR RESPIRE Global Respiratory Health Unit . Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir Med. 2022;10(5):447-458. doi: 10.1016/S2213-2600(21)00511-7 - DOI - PMC - PubMed
    1. Agustí A, Celli BR, Criner GJ, et al. Global Initiative for Chronic Obstructive Lung Disease 2023 report: GOLD executive summary. Am J Respir Crit Care Med. 2023;207(7):819-837. doi: 10.1164/rccm.202301-0106PP - DOI - PMC - PubMed
    1. Qaseem A, Wilt TJ, Weinberger SE, et al. ; American College of Physicians; American College of Chest Physicians; American Thoracic Society; European Respiratory Society . Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011;155(3):179-191. doi: 10.7326/0003-4819-155-3-201108020-00008 - DOI - PubMed
    1. National Institute for Health and Care Excellence . Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Published December 5, 2018. Updated July 26, 2019. Accessed August 3, 2024. https://www.nice.org.uk/guidance/ng115/chapter/Recommendations#diagnosin... - PubMed
    1. Regan EA, Lynch DA, Curran-Everett D, et al. ; Genetic Epidemiology of COPD (COPDGene) Investigators . Clinical and radiologic disease in smokers with normal spirometry. JAMA Intern Med. 2015;175(9):1539-1549. doi: 10.1001/jamainternmed.2015.2735 - DOI - PMC - PubMed

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