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Disease Progression Modeling in Chronic Obstructive Pulmonary Disease

2019; American Thoracic Society; Volume: 201; Issue: 3 Linguagem: Inglês

10.1164/rccm.201908-1600oc

1535-4970

Alexandra L. Young, Felix Bragman, Bojidar Rangelov, MeiLan K. Han, Craig J. Galbán, David A. Lynch, David J. Hawkes, Daniel C. Alexander, John R. Hurst, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Ferdouse Begum, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline B. Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan M. Laird, Christoph Lange, Sharon M. Lutz, Merry‐Lynn McDonald, Margaret M. Parker, Dandi Qiao, Emily S. Wan, Sungho Won, Phuwanat Sakornsakolpat, Dmitry Prokopenko, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen M. Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raúl San Jośe Estépar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin J.R. van Beek, Bram van Ginneken, Eva M. van Rikxoort, George R. Washko, Carla G. Wilson, Robert L. Jensen, Douglas Curran‐Everett, Jim Crooks, Camille M. Moore, Matthew Strand, J A Hughes, Gregory L. Kinney, Katherine Pratte, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Cristina Martínez, Susan Murray, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei‐Kashani, Jeffrey L. Curtis, Cristina Martínez, Perry G. Pernicano, Nicola A. Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin M. Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun C. Nachiappan, Amit Parulekar, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert A. Wise, Robert Brown, Nadia N. Hansel, Karen M. Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew J. Budoff, H. Keith Fischer, János Pórszász, Harry B. Rossiter, William W. Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene A. Berkowitz, Gloria Westney, Richard Rosiello, David Pace, Gerard J. Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert E. D’Alonzo, Parag Desai, Michael E. Jacobs, Steven Kelsen, V. Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega‐Sanchez, Mark T. Dransfield, William C. Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul J. Friedman, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, Brad Thompson, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank C. Sciurba, Divay Chandra, Carl R. Fuhrman, Joel L. Weissfeld, Antonio Anzueto, Sylvia Adams, Diego Maselli-Caceres, Mario E. Ruiz,

Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1–4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue→Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway→Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = −0.16 [P < 0.001] in the Tissue→Airway group; r = −0.14 [P = 0.011] in the Airway→Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."