COPDGene® 2019: Redefining the diagnosis of chronic obstructive pulmonary disease

Katherine E. Lowe, Elizabeth A. Regan, Antonio Anzueto, Erin Austin, John H.M. Austin, Terri H. Beaty, Panayiotis V. Benos, Christopher J. Benway, Surya P. Bhatt, Eugene R. Bleecker, Sandeep Bodduluri, Jessica Bon, Aladin M. Boriek, Adel R.E. Boueiz, Russell P. Bowler, Matthew Budoff, Richard Casaburi, Peter J. Castaldi, Jean Paul Charbonnier, Michael H. ChoAlejandro Comellas, Douglas Conrad, Corinne Costa Davis, Gerard J. Criner, Douglas Curran-Everett, Jeffrey L. Curtis, Dawn L. DeMeo, Alejandro A. Diaz, Mark T. Dransfield, Jennifer G. Dy, Ashraf Fawzy, Margaret Fleming, Eric L. Flenaugh, Marilyn G. Foreman, Spyridon Fortis, Hirut Gebrekristos, Sarah Grant, Philippe A. Grenier, Tian Gu, Abhya Gupta, Mei Lan K. Han, Nicola A. Hanania, Nadia N. Hansel, Lystra P. Hayden, Craig P. Hersh, Brian D. Hobbs, Eric A. Hoffman, James C. Hogg, John E. Hokanson, Karin F. Hoth, Albert Hsiao, Stephen Humphries, Kathleen Jacobs, Francine L. Jacobson, Ella A. Kazerooni, Victor Kim, Woo Jin Kim, Gregory L. Kinney, Harald Koegler, Sharon M. Lutz, David A. Lynch, Neil R. MacIntye, Barry J. Make, Nathaniel Marchetti, Fernando J. Martinez, Diego J. Maselli, Anne M. Mathews, Meredith C. McCormack, Merry Lynn N. McDonald, Charlene E. McEvoy, Matthew Moll, Sarah S. Molye, Susan Murray, Hrudaya Nath, John D. Newell, Mariaelena Occhipinti, Matteo Paoletti, Trisha Parekh, Massimo Pistolesi, Katherine A. Pratte, Nirupama Putcha, Margaret Ragland, Joseph M. Reinhardt, Stephen I. Rennard, Richard A. Rosiello, James C. Ross, Harry B. Rossiter, Ingo Ruczinski, Raul San Jose Estepar, Frank C. Sciurba, Jessica C. Sieren, Harjinder Singh, Xavier Soler, Robert M. Steiner, Matthew J. Strand, William W. Stringer, Ruth Tal-Singer, Byron Thomashow, Gonzalo Vegas Sánchez-Ferrero, John W. Walsh, Emily S. Wan, George R. Washko, J. Michael Wells, Chris H. Wendt, Gloria Westney, Ava Wilson, Robert A. Wise, Andrew Yen, Kendra Young, Jeong Yun, Edwin K. Silverman, James D. Crapo

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

Original languageEnglish (US)
Pages (from-to)384-399
Number of pages16
JournalChronic Obstructive Pulmonary Diseases
Volume6
Issue number5
DOIs
StatePublished - 2019

Keywords

  • COPD
  • COPD Genetic Epidemiology study
  • COPD diagnosis
  • COPDGene
  • Chronic obstructive pulmonary disease
  • GOLD
  • Global initiative for chronic Obstructive Lung Disease
  • PRISm
  • Preserved ratioimpaired spirometry
  • Spirometry

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Lowe, K. E., Regan, E. A., Anzueto, A., Austin, E., Austin, J. H. M., Beaty, T. H., Benos, P. V., Benway, C. J., Bhatt, S. P., Bleecker, E. R., Bodduluri, S., Bon, J., Boriek, A. M., Boueiz, A. R. E., Bowler, R. P., Budoff, M., Casaburi, R., Castaldi, P. J., Charbonnier, J. P., ... Crapo, J. D. (2019). COPDGene® 2019: Redefining the diagnosis of chronic obstructive pulmonary disease. Chronic Obstructive Pulmonary Diseases, 6(5), 384-399. https://doi.org/10.15326/jcopdf.6.5.2019.0149