A Multidimensional Diagnostic Approach for Chronic Obstructive Pulmonary Disease
Authors: Surya P. Bhatt, Ehsan Abadi, Antonio Anzueto, Sandeep Bodduluri, Richard Casaburi, Peter J. Castaldi, Michael H. Cho, Alejandro P. Comellas, Douglas J. Conrad, Jeffrey L. Curtis, Chandra Dass, Dawn L. DeMeo, Mark T. Dransfield, Raul San José Estépar, Eric L. Flenaugh, Marilyn G. Foreman, Spyridon Fortis, Arnav Gupta, MeiLan K. Han, Nicola A. Hanania, Craig P. Hersh, John E. Hokanson, Stephen M. Humphries, Miranda Kirby, Ken M. Kunisaki, Pei Zhi Li, David A. Lynch, Neil R. MacIntyre, Barry J. Make, David M. Mannino, Fernando J. Martinez, Charlene E. McEvoy, Bruce E. Miller, Matthew Moll, Arie Nakhmani, John D. Newell, Katherine A. Pratte, Elizabeth A. Regan, Joseph M. Reinhardt, Stephen I. Rennard, Harry B. Rossiter, Matthew J. Strand, Rajat Suri, Emily S. Wan, Christine H. Wendt, Gloria E. Westney, Carla G. Wilson, Robert A. Wise, Kendra A. Young, Wan C. Tan, Edwin K. Silverman, James D. Crapo
Journal: JAMA (2025)

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. To determine whether a multidimensional COPD diagnostic schema that includes respiratory symptoms and computed tomographic imaging abnormalities identifies additional individuals with disease. 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 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). All-cause mortality, respiratory cause-specific mortality, exacerbations, and annualized change in FEV1. 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). 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.