COPDGene 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.

View 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 (FEV > 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.

Investigators
Abbreviation
Chronic Obstr Pulm Dis
Publication Date
2019-11-13
Volume
6
Issue
5
Page Numbers
384-399
Pubmed ID
31710793
Medium
Print
Full Title
COPDGene 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.
Authors
Lowe KE, Regan EA, Anzueto A, Austin E, Austin JHM, Beaty TH, Benos PV, Benway CJ, Bhatt SP, Bleecker ER, Bodduluri S, Bon J, Boriek AM, Boueiz AR, Bowler RP, Budoff M, Casaburi R, Castaldi PJ, Charbonnier JP, Cho MH, Comellas A, Conrad D, Costa Davis C, Criner GJ, Curran-Everett D, Curtis JL, DeMeo DL, Diaz AA, Dransfield MT, Dy JG, Fawzy A, Fleming M, Flenaugh EL, Foreman MG, Fortis S, Gebrekristos H, Grant S, Grenier PA, Gu T, Gupta A, Han MK, Hanania NA, Hansel NN, Hayden LP, Hersh CP, Hobbs BD, Hoffman EA, Hogg JC, Hokanson JE, Hoth KF, Hsiao A, Humphries S, Jacobs K, Jacobson FL, Kazerooni EA, Kim V, Kim WJ, Kinney GL, Koegler H, Lutz SM, Lynch DA, MacIntye NR, Make BJ, Marchetti N, Martinez FJ, Maselli DJ, Mathews AM, McCormack MC, McDonald MN, McEvoy CE, Moll M, Molye SS, Murray S, Nath H, Newell JD, Occhipinti M, Paoletti M, Parekh T, Pistolesi M, Pratte KA, Putcha N, Ragland M, Reinhardt JM, Rennard SI, Rosiello RA, Ross JC, Rossiter HB, Ruczinski I, San Jose Estepar R, Sciurba FC, Sieren JC, Singh H, Soler X, Steiner RM, Strand MJ, Stringer WW, Tal-Singer R, Thomashow B, Vegas Sánchez-Ferrero G, Walsh JW, Wan ES, Washko GR, Michael Wells J, Wendt CH, Westney G, Wilson A, Wise RA, Yen A, Young K, Yun J, Silverman EK, Crapo JD