@article {1675126,
	title = {COPDGene 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease},
	journal = {Chronic Obstr Pulm Dis},
	volume = {6},
	number = {5},
	year = {2019},
	month = {2019 Nov},
	pages = {384-399},
	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{\textregistered}), 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{\textregistered} 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{\textregistered} 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.},
	issn = {2372-952X},
	doi = {10.15326/jcopdf.6.5.2019.0149},
	author = {Lowe, Katherine E and Regan, Elizabeth A and Anzueto, Antonio and Austin, Erin and Austin, John H M and Beaty, Terri H and Benos, Panayiotis V and Benway, Christopher J and Bhatt, Surya P and Bleecker, Eugene R and Bodduluri, Sandeep and Bon, Jessica and Boriek, Aladin M and Boueiz, Adel Re and Bowler, Russell P and Budoff, Matthew and Casaburi, Richard and Castaldi, Peter J and Charbonnier, Jean-Paul and Cho, Michael H and Comellas, Alejandro and Conrad, Douglas and Costa Davis, Corinne and Criner, Gerard J and Curran-Everett, Douglas and Curtis, Jeffrey L and DeMeo, Dawn L and Diaz, Alejandro A and Dransfield, Mark T and Dy, Jennifer G and Fawzy, Ashraf and Fleming, Margaret and Flenaugh, Eric L and Foreman, Marilyn G and Fortis, Spyridon and Gebrekristos, Hirut and Grant, Sarah and Grenier, Philippe A and Gu, Tian and Gupta, Abhya and Han, MeiLan K and Hanania, Nicola A and Hansel, Nadia N and Hayden, Lystra P and Hersh, Craig P and Hobbs, Brian D and Hoffman, Eric A and Hogg, James C and Hokanson, John E and Hoth, Karin F and Hsiao, Albert and Humphries, Stephen and Jacobs, Kathleen and Jacobson, Francine L and Kazerooni, Ella A and Kim, Victor and Kim, Woo Jin and Kinney, Gregory L and Koegler, Harald and Lutz, Sharon M and Lynch, David A and MacIntye, Neil R and Make, Barry J and Marchetti, Nathaniel and Martinez, Fernando J and Maselli, Diego J and Mathews, Anne M and McCormack, Meredith C and McDonald, Merry-Lynn N and McEvoy, Charlene E and Moll, Matthew and Molye, Sarah S and Murray, Susan and Nath, Hrudaya and Newell, John D and Occhipinti, Mariaelena and Paoletti, Matteo and Parekh, Trisha and Pistolesi, Massimo and Pratte, Katherine A and Putcha, Nirupama and Ragland, Margaret and Reinhardt, Joseph M and Rennard, Stephen I and Rosiello, Richard A and Ross, James C and Rossiter, Harry B and Ruczinski, Ingo and Estepar, Raul San Jose and Sciurba, Frank C and Sieren, Jessica C and Singh, Harjinder and Soler, Xavier and Steiner, Robert M and Strand, Matthew J and Stringer, William W and Tal-Singer, Ruth and Thomashow, Byron and Vegas S{\'a}nchez-Ferrero, Gonzalo and Walsh, John W and Wan, Emily S and Washko, George R and Michael Wells, J and Wendt, Chris H and Westney, Gloria and Wilson, Ava and Wise, Robert A and Yen, Andrew and Young, Kendra and Yun, Jeong and Silverman, Edwin K and Crapo, James D}
}