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. JCOPDF
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. JCOPDF
Authors: Surya P Bhatt; Pallavi P Balte; Joseph E Schwartz; Patricia A Cassano; David Couper; David R Jacobs; Ravi Kalhan; George T O'Connor; Sachin Yende; Jason L Sanders; Jason G Umans; Mark T Dransfield; Paulo H Chaves; Wendy B White; Elizabeth C Oelsner Journal: JAMA Date: 2019-06-25 Impact factor: 56.272
Authors: Carlos A Vaz Fragoso; Thomas M Gill; Gail McAvay; Henry Klar Yaggi; Peter H Van Ness; John Concato Journal: J Investig Med Date: 2011-10 Impact factor: 2.895
Authors: Prescott G Woodruff; R Graham Barr; Eugene Bleecker; Stephanie A Christenson; David Couper; Jeffrey L Curtis; Natalia A Gouskova; Nadia N Hansel; Eric A Hoffman; Richard E Kanner; Eric Kleerup; Stephen C Lazarus; Fernando J Martinez; Robert Paine; Stephen Rennard; Donald P Tashkin; MeiLan K Han Journal: N Engl J Med Date: 2016-05-12 Impact factor: 91.245
Authors: M P Swanney; G Ruppel; P L Enright; O F Pedersen; R O Crapo; M R Miller; R L Jensen; E Falaschetti; J P Schouten; J L Hankinson; J Stocks; P H Quanjer Journal: Thorax Date: 2008-09-11 Impact factor: 9.139
Authors: MeiLan K Han; Carlos H Martinez; David H Au; Jean Bourbeau; Cynthia M Boyd; Richard Branson; Gerard J Criner; Ravi Kalhan; Thomas J Kallstrom; Angela King; Jerry A Krishnan; Suzanne C Lareau; Todd A Lee; Kathleen Lindell; David M Mannino; Fernando J Martinez; Catherine Meldrum; Valerie G Press; Byron Thomashow; Laura Tycon; Jamie Lamson Sullivan; John Walsh; Kevin C Wilson; Jean Wright; Barbara Yawn; Patrick M Zueger; Surya P Bhatt; Mark T Dransfield Journal: Lancet Respir Med Date: 2016-05-13 Impact factor: 30.700
Authors: Emily S Wan; Peter J Castaldi; Michael H Cho; John E Hokanson; Elizabeth A Regan; Barry J Make; Terri H Beaty; MeiLan K Han; Jeffrey L Curtis; Douglas Curran-Everett; David A Lynch; Dawn L DeMeo; James D Crapo; Edwin K Silverman Journal: Respir Res Date: 2014-08-06
Authors: Matthew Moll; Dandi Qiao; Elizabeth A Regan; Gary M Hunninghake; Barry J Make; Ruth Tal-Singer; Michael J McGeachie; Peter J Castaldi; Raul San Jose Estepar; George R Washko; James M Wells; David LaFon; Matthew Strand; Russell P Bowler; MeiLan K Han; Jorgen Vestbo; Bartolome Celli; Peter Calverley; James Crapo; Edwin K Silverman; Brian D Hobbs; Michael H Cho Journal: Chest Date: 2020-04-27 Impact factor: 9.410
Authors: Katherine E Lowe; John E Hokanson; Barry J Make; Katherine A Pratte; Elizabeth A Regan; Edwin K Silverman; Kendra A Young; Gregory L Kinney; James D Crapo Journal: Chronic Obstr Pulm Dis Date: 2020-04