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1. Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression

Author

Adel Boueiz, Yale Chang, Michael H. Cho, George R. Washko, Raul San José Estépar, Russell P. Bowler, James D. Crapo, Dawn L. DeMeo, Jennifer G. Dy, Edwin K. Silverman, Peter J. Castaldi, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Stephanie Santorico, John Hokanson, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Marilyn Foreman, Brian Hobbs, Robert Busch, Dandi Qiao, Eitan Halper-Stromberg, Ferdouse Begum, Sungho Won, Sharon Lutz, David A. Lynch, Harvey O. Coxson, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, John D. Newell, James C. Ross, Raul José Estépar, Berend C. Stoel, Juerg Tschirren, Eva van Rikxoort, Bram van Ginneken, Carla G. Wilson, Mustafa Al Qaisi, Teresa Gray, Alex Kluiber, Tanya Mann, Jered Sieren, Douglas Stinson, Joyce Schroeder, Edwin Van Beek, Robert Jensen, Douglas Everett, Anna Faino, Matt Strand, Carla Wilson, John E. Hokanson, Gregory Kinney, Kendra Young, Katherine Pratte, Lindsey Duca, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Venkata Bandi, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Arun Nachiappan, Francine Jacobson, R. Graham Barr, Byron Thomashow, John Austin, Belinda D’Souza, Gregory D.N. Pearson, Anna Rozenshtein, Neil MacIntyre, Lacey Washington, H. Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Janos Porszasz, Hans Fischer, Matthew Budoff, Harry Rossiter, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, J. Michael Wells, Surya Bhatt, Hrudaya Nath, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro Cornellas, John Newell, Brad Thompson, MeiLan Han, Ella Kazerooni, Carlos Martinez, Joanne Billings, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Genome-wide association study, Comorbidity, Critical Care and Intensive Care Medicine, Severity of Illness Index, Gastroenterology, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Forced Expiratory Volume, Internal medicine, medicine, Humans, COPD, Distribution (pharmacology), 030212 general & internal medicine, Aged, business.industry, Middle Aged, respiratory system, medicine.disease, respiratory tract diseases, Pulmonary Emphysema, 030228 respiratory system, Genetic epidemiology, Radiological weapon, Cohort, Disease Progression, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Female, Metabolic syndrome, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Contains fulltext : 194255.pdf (Publisher’s version ) (Open Access) BACKGROUND: Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. METHODS: We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. RESULTS: Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. CONCLUSIONS: Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

Published
2018
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2. Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD

Author

Lacey Washington, Kalpalatha K. Guntupalli, John Newell, Adam L. Friedlander, Joyce D. Schroeder, Rebecca Leek, Robert H. Brown, Tadashi Allen, Edwin K. Silverman, Barry J. Make, Douglas Stinson, Stephanie A. Santorico, Richard Rosiello, Neil R. MacIntyre, David A. Lynch, Tanya Mann, Deborah L. Thompson, Joel L. Weissfeld, J. Michael Wells, William Lunn, Jeffrey L. Curtis, Edwin J R van Beek, Dawn L. DeMeo, Francine L. Jacobson, Antara Mallampalli, Matthew J. Budoff, Philip Alapat, Robert O. Crapo, Raúl San José Estépar, Carlos Orozco, Geoffrey McLennan, Nan M. Laird, Iuliana Ionita, Barbara J. Klanderman, Harvey O. Coxson, Peter Bercz, Craig P. Hersh, George R. Washko, H. Page McAdams, Paul Ferguson, R. Graham Barr, Robert M. Steiner, Anastasia Rodionova, Elizabeth Guy, Amir Sharafkhaneh, Dennis E. Niewoehner, Hans Fischer, Victor Kim, Hrudaya Nath, Kathryn L. Rice, John P. Reilly, Charles Trinh, John H. M. Austin, Douglas Everett, C. Santiago Restrepo, Joseph H. Tashjian, John E. Hokanson, Richard Casaburi, Robert L. Jensen, Fernando J. Martinez, Mark T. Dransfield, James Murphy, Antonio Anzueto, Jessica Bon, Gloria Westney, Terri H. Beaty, Lynn B. Gerald, Nicola A. Hanania, Chandra Dass, Alejandro P. Comellas, Alex Kluiber, Xavier Soler, Joe W. Ramsdell, Frank C. Sciurba, Philip F. Judy, Elizabeth A. Regan, Jordan A. Zach, Jonathan M. Samet, MeiLan K. Han, Janos Porszasz, Eric Hoff Man, Andre Williams, Mustafa A. Atik, Gerard J. Criner, Paul A. Friedman, Carl R. Fuhrman, Marilyn G. Foreman, Timothy Bresnahan, Nadia N. Hansel, Amy Willis, Sandra G. Adams, Eleonora Meoni, William C. Bailey, A. James Mamary, Carla Wilson, Christoph Lange, James D. Crapo, Christine H. Wendt, Eugene Berkowitz, Russell P. Bowler, Amy L Mumbower, Charlene McEvoy, Robert A. Wise, Venkata Bandi, Ella A. Kazerooni, Nathaniel Marchetti, Homayoon Farzadegan, Aditi Satti, and Byron Thomashow

Subjects
Male, Pulmonary and Respiratory Medicine, Chronic Obstructive, medicine.medical_specialty, Exacerbation, Chronic Obstructive Pulmonary Disease, Respiratory Tract Diseases, Clinical Sciences, Respiratory System, Critical Care and Intensive Care Medicine, Pulmonary Disease, Pulmonary Disease, Chronic Obstructive, Risk Factors, Clinical Research, Internal medicine, medicine, Humans, Longitudinal Studies, Intensive care medicine, Lung, Original Research, Proportional Hazards Models, Aged, First episode, COPD, Framingham Risk Score, Proportional hazards model, business.industry, Incidence, Smoking, Hazard ratio, Respiratory disease, Middle Aged, medicine.disease, United States, respiratory tract diseases, Hospitalization, Good Health and Well Being, Acute Disease, Cohort, Quality of Life, Respiratory, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

BACKGROUND The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV 1 ), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

Published
2014
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