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1. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author: Crapo, James D., Silverman, Edwin K., Cummings, Sara, Madden, Kelley, Make, Barry J., Nabbosa, Juliet, Port, Emily, Rashdi, Serine, Regan, Elizabeth A., Stepp, Lori, Watts, Shandi, Weaver, Michael, Beaty, Terri, Bowler, Russell P., Curtis, Jeffrey L., Han, MeiLan K., Hokanson, John E., Lynch, David A., Strand, Matthew J., Anderson, Gary, Bleecker, Eugene R., Coxson, Harvey O., Crystal, Ronald G., Hogg, James C., Province, Michael A., Rennard, Stephen I., Croxton, Thomas, Gan, Weiniu, Postow, Lisa A., Viviano, Lisa M., Costa-Davis, Corinne, Malanga, Elisha, Prieto, Delia, Tal-Singer, Ruth, Farzadegan, Homayoon, Hadji, Akila, Sathe, Leena, Baraghoshi, David, Chen, Grace, Crooks, James, Knowles, Ruthie, Pratte, Katherine, Wilson, Carla, Zelarney, Pearlanne T., Kechris, Katerina J., Leach, Sonia, Austin, Erin E., Czizik, Annika, Kinney, Gregory, Li, Yisha, Lutz, Sharon M., Ragland, Margaret F., Richmond, Nicole, Young, Kendra A., Cho, Michael, Castaldi, Peter J., Glass, Kimberly, Hersh, Craig, Kim, Wonji, Liu, Yang-Yu, Hersh, Craig P., Bidinger, Jacqueline, Cho, Michael H., Conrad, Douglas, DeMeo, Dawn L., El-Boueiz, Adel R., Foreman, Marilyn G., Ghosh, Auyon, Hahn, Georg, Hansel, Nadia N., Hayden, Lystra P., Hobbs, Brian, Kim, Woori, Lange, Christoph, McDonald, Merry- Lynn, McGeachie, Michael, Moll, Matthew, Morris, Melody, Patsopoulos, Nikolaos A., Qiao, Dandi, Ruczinski, Ingo, Wan, Emily S., Dy, Jennifer G., Fain, Sean B., Ginsburg, Shoshana, Hoffman, Eric A., Humphries, Stephen, Judy, Philip F., Stefanie Mason, Alex Kluiber, Oh, Andrea, Poynton, Clare, Reinhardt, Joseph M., Ross, James, San Jose Estepar, Raul, Schroeder, Joyce D., Sitek, Arkadiusz, Steiner, Robert M., van Beek, Edwin, Ginneken, Bram van, van Rikxoort, Eva, Washko, George R., Jensen, Robert, John E. Hokanson, Co-Chair, Bhatt, Surya P., Casaburi, Richard, Kim, Victor, Putcha, Nirupama, Han, MeiLan, Bon, Jessica, Diaz, Alejandro A., Regan, Elizabeth, Anzueto, Antonio, Bailey, William C., Criner, Gerard J., Dransfield, Mark T., Kinney, Greg, Sprenger, Kim, Benos, Takis, Hanania, Nicola A., Hoth, Karin F., Lambert, Allison, Lowe, Katherine, Oates, Gabriela, Parekh, Trisha, Westney, Gloria, Young, Kendra, Balasubramanian, Aparna, Boriek, Aladin, Fawzy, Ashraf, Jacobson, Francine, LaFon, David C., MacIntyre, Neil, Maselli-Caceres, Diego, McCormack, Meredith C., McDonald, Merry-Lynn, Sciurba, Frank, Soler, Xavier, Tejwani, Vickram, van Beek, Edwin JR., Wade, Raymond C., Wells, Mike, Wendt, Chris H., Yun, Jeong H., Zhang, Jingzhou, Gillenwater, Lucas, Lowe, Katherine E., Pratte, Katherine A., Ragland, Margaret, Attaway, Amy, Mason, Stefanie, Rossiter, Harry B., Saha, Punam Kumar, Wilson, Ava, Amaza, Hannatu, Baldomero, Adrienne, Mamary, A. James, O’Brien, James, Wise, Robert A., Eakin, Michelle, Fiedorowicz, Jess G., Henkle, Ben, Holm, Kristen, Iyer, Anand, Kunisaki, Ken M., McEvoy, Charlene, Mkorombindo, Takudzwa, Shinozaki, Gen, Yohannes, Abebaw, Hobbs, Brian D., Miller, Bruce E., Retson, Tara, McCloskey, Lisa, Pernicano, Perry G., Atik, Mustafa, Bertrand, Laura, Monaco, Thomas, Narendra, Dharani, Lenge de Rosen, Veronica V., Badu-Danso, Kwame, Jacobson, Francine L., Kaufman, Laura, Maguire, Cherie, Struble, Sophie, Wilson, Seth, Barr, R. Graham, Almonte, Casandra, Austin, John H.M., Gomez Blum, Maria Lorena, D’Souza, Belinda M., Florez, Emilay, Martinez, Rodney, MacIntyre, Neil, Jr., Curry, Wendy, McAdams, H. Page, Reikofski, Charlotte V., Washington, Lacey, Brown, Robert, Clare, Cheryl, Daniel, Marie, Horton, Karen, Ting “Tony” Lin, Cheng, Mirza, Tahira, Scott, Meagan, Shade, Becky, Budoff, Matt, Calmelat, Robert, Cavanaugh, Deborah, Dailing, Chris, Diaz, Leticia, Fischer, Hans, Indelicato, Renee Love, Porszasz, Janos, Soriano, April, Stringer, William, Urrutia, Miriam, Baldomero, Arianne, Bell, Brian, Deconcini, Miranda, Loes, Linda, Phelan, Jonathan, Robichaux, Camille, Sasse, Cheryl, Tashjian, Joseph H., Flenaugh, Eric L., Abson, Kema, Gebrekristos, Hirut, Johnson, Priscilla, Jordan, Jessica, Ponce, Mario, Terpenning, Silanath, Wilson, Derrick, Broadhurst, Grace, Dyer, Debra, Engel, Elena, Finigan, Jay, Hill, Andrew, Jones, Alex, Jones, Ryan, Owen, Jordan, Rosiello, Richard, Andries, Nicole, Charpentier, Mary, Kirk, Diane, Pace, David, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Davis, Valena, Desai, Parag, Fehrle, Dee, Grabianowski, Carla, Jacobs, Michael, Jameson, Laurie, Jones, Gayle M., Kelsen, Steven, Marchetti, Nathaniel, McGonagle, Francine, Satti, Aditi, Shenoy, Kartik, Sheridan, Regina, Vega-Sanchez, Maria, Wallace, Samantha, Akinseye-kolapo, Samuel, Baker, Matthew, Goggins, Arnissa, McClain, Anny, Nath, Hrudaya, Singh, Satinder P., Sonavane, Sushil K., Westfall, Elizabeth, Gil, Marissa, El Hajjaoui, Tarek, Hsiao, Albert, Martineau, Amber, Mielke, Jenna, Perez, Karl, Querido, Gabriel, Reston, Tara, Yen, Andrew, Comellas, Alejandro, Fortis, Spyridon, Galizia, Mauricio, Garcia, Eric, Keating, Janet, Laroia, Archana, Lee, Changhyun, Meyer, Amber, Mullan, Brian, Nagpal, Prashant, Ofori, Oloigbe, Suiter, Sierra, Mason, Stefanie E., Moreta-Martinez, Rafael, Labaki, Wassim W., San Jose Estepar, Ruben, Make, Barry, and Stringer, Kathleen
Published: 2022
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2. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure

Author: Brigid A. Adviento, Elizabeth A. Regan, Barry J. Make, MeiLan K. Han, Marilyn G. Foreman, Anand S. Iyer, Surya P. Bhatt, Victor Kim, Jessica Bon, Xavier Soler, Gregory L. Kinney, Nicola A. Hanania, Katherine E. Lowe, Kristen E. Holm, Abebaw M. Yohannes, Gen Shinozaki, Karin F. Hoth, Jess G. Fiedorowicz, James D. Crapo, Edwin K. Silverman, Terri H. Beaty, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel El Boueiz, Auyon Ghosh, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Matthew Moll, Jarrett Morrow, Dandi Qiao, Aabida Saferali, Phuwanat Sakornsakolpat, Emily S. Wan, Jeong Yun, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Matthew Strand, Jim Crooks, Katherine Pratte, Aastha Khatiwada, Erin Austin, Gregory Kinney, Kendra A. Young, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh
Subjects: Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published: 2023

3. Development of a Blood-based Transcriptional Risk Score for Chronic Obstructive Pulmonary Disease

Author: Matthew Moll, Adel Boueiz, Auyon J. Ghosh, Aabida Saferali, Sool Lee, Zhonghui Xu, Jeong H. Yun, Brian D. Hobbs, Craig P. Hersh, Don D. Sin, Ruth Tal-Singer, Edwin K. Silverman, Michael H. Cho, Peter J. Castaldi, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Jacqueline Hetmanski, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Diaz, Susan Murray, Xavier Soler, Russell P. Bowler, Katerina Kechris, and Farnoush Banaei-Kashani
Subjects: Pulmonary and Respiratory Medicine, COPD, Framingham Risk Score, business.industry, Pulmonary disease, Critical Care and Intensive Care Medicine, medicine.disease, Bioinformatics, Peripheral blood, respiratory tract diseases, Transcriptome, Gene expression, medicine, Polygenic risk score, business
Abstract: Rationale: The ability of peripheral blood biomarkers to assess COPD risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict...
Published: 2022

4. Clinically Significant and Comorbid Anxiety and Depression Symptoms Predict Severe Respiratory Exacerbations in Smokers: A Post Hoc Analysis of the COPDGene and SPIROMICS Cohorts

Author: Anand S. Iyer, Trisha M. Parekh, Jacqueline O’Toole, Surya P. Bhatt, Michelle N. Eakin, Jerry A. Krishnan, Abebaw M. Yohannes, Prescott G. Woodruff, Christopher B. Cooper, Richard E. Kanner, Nicola A. Hanania, Mark T. Dransfield, Elizabeth A. Regan, Karin F. Hoth, Victor Kim, James D. Crapo, Edwin K. Silverman, Barry J. Make, Terri 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 Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Huries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San José Estépar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A. Young, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Los Angeles, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Comorbid anxiety, business.industry, Internal medicine, Post-hoc analysis, Medicine, Respiratory system, business, Depressive symptoms
Published: 2022

5. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Author: Divay Chandra, Aman Gupta, Gregory L. Kinney, Carl R. Fuhrman, Joseph K. Leader, Alejandro A. Diaz, Jessica Bon, R. Graham Barr, George Washko, Matthew Budoff, John Hokanson, Frank C. Sciurba, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Adel R. Boueiz, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Carla G. Wilson, Robert Jensen, Jim Crooks, Douglas Everett, Camille Moore, null Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Carlos Martinez, Susan Murray, Xavier Soler, Farnoush Banaei-Kashani, Russell P. Bowler, Katerina Kechris, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Michael E. DeBakey, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eugene Berkowitz, Gloria Westney, Russell Bowler, 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, Surya P. Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Carlos H. Martinez, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronary Artery Disease, Critical Care and Intensive Care Medicine, COPD: Original Research, Coronary artery disease, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Functional residual capacity, Risk Factors, Internal medicine, medicine, Humans, Lung volumes, 030212 general & internal medicine, Myocardial infarction, Lung, Subclinical infection, COPD, business.industry, Smoking, Organ Size, Middle Aged, respiratory system, medicine.disease, Coronary Vessels, United States, Respiratory Function Tests, respiratory tract diseases, Airway Obstruction, Plethysmography, Biological Variation, Population, Pulmonary Emphysema, 030228 respiratory system, Asymptomatic Diseases, Cohort, Cardiology, Airway Remodeling, Female, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business
Abstract: BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.
Published: 2021

6. Prevalence of abnormal spirometry in individuals with a smoking history and no known obstructive lung disease

Author: Thuonghien V. Tran, Gregory L. Kinney, Alejandro Comellas, Karin F. Hoth, Arianne K. Baldomero, A. James Mamary, Jeffrey L. Curtis, Nicola Hanania, Richard Casaburi, Kendra A. Young, Victor Kim, Barry Make, Emily S. Wan, Alejandro A. Diaz, John Hokanson, James D. Crapo, Edwin K. Silverman, Surya P. Bhatt, Elizabeth Regan, Spyridon Fortis, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel El Boueiz, Marilyn G. Foreman, Auyon Ghosh, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Matthew Moll, Jarrett Morrow, Dandi Qiao, Aabida Saferali, Phuwanat Sakornsakolpat, Jeong Yun, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Jessica Bon, Susan Murray, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush BanaeiKashani, Perry G. Pernicano, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D'Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh
Subjects: Pulmonary and Respiratory Medicine
Published: 2023

7. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author: Mason, Stefanie E., primary, Moreta-Martinez, Rafael, additional, Labaki, Wassim W., additional, Strand, Matthew J., additional, Regan, Elizabeth A., additional, Bon, Jessica, additional, San Jose Estepar, Ruben, additional, Casaburi, Richard, additional, McDonald, Merry-Lynn, additional, Rossiter, Harry B., additional, Make, Barry, additional, Dransfield, Mark T., additional, Han, MeiLan K., additional, Young, Kendra, additional, Curtis, Jeffrey L., additional, Stringer, Kathleen, additional, Kinney, Greg, additional, Hokanson, John E., additional, San Jose Estepar, Raul, additional, Washko, George R., additional, Crapo, James D., additional, Silverman, Edwin K., additional, Cummings, Sara, additional, Madden, Kelley, additional, Make, Barry J., additional, Nabbosa, Juliet, additional, Port, Emily, additional, Rashdi, Serine, additional, Stepp, Lori, additional, Watts, Shandi, additional, Weaver, Michael, additional, Beaty, Terri, additional, Bowler, Russell P., additional, Lynch, David A., additional, Anderson, Gary, additional, Bleecker, Eugene R., additional, Coxson, Harvey O., additional, Crystal, Ronald G., additional, Hogg, James C., additional, Province, Michael A., additional, Rennard, Stephen I., additional, Croxton, Thomas, additional, Gan, Weiniu, additional, Postow, Lisa A., additional, Viviano, Lisa M., additional, Costa-Davis, Corinne, additional, Malanga, Elisha, additional, Prieto, Delia, additional, Tal-Singer, Ruth, additional, Farzadegan, Homayoon, additional, Hadji, Akila, additional, Sathe, Leena, additional, Baraghoshi, David, additional, Chen, Grace, additional, Crooks, James, additional, Knowles, Ruthie, additional, Pratte, Katherine, additional, Wilson, Carla, additional, Zelarney, Pearlanne T., additional, Kechris, Katerina J., additional, Leach, Sonia, additional, Austin, Erin E., additional, Czizik, Annika, additional, Kinney, Gregory, additional, Li, Yisha, additional, Lutz, Sharon M., additional, Ragland, Margaret F., additional, Richmond, Nicole, additional, Young, Kendra A., additional, Cho, Michael, additional, Castaldi, Peter J., additional, Glass, Kimberly, additional, Hersh, Craig, additional, Kim, Wonji, additional, Liu, Yang-Yu, additional, Hersh, Craig P., additional, Bidinger, Jacqueline, additional, Cho, Michael H., additional, Conrad, Douglas, additional, DeMeo, Dawn L., additional, El-Boueiz, Adel R., additional, Foreman, Marilyn G., additional, Ghosh, Auyon, additional, Hahn, Georg, additional, Hansel, Nadia N., additional, Hayden, Lystra P., additional, Hobbs, Brian, additional, Kim, Woori, additional, Lange, Christoph, additional, McDonald, Merry- Lynn, additional, McGeachie, Michael, additional, Moll, Matthew, additional, Morris, Melody, additional, Patsopoulos, Nikolaos A., additional, Qiao, Dandi, additional, Ruczinski, Ingo, additional, Wan, Emily S., additional, Dy, Jennifer G., additional, Fain, Sean B., additional, Ginsburg, Shoshana, additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Judy, Philip F., additional, Stefanie Mason, Alex Kluiber, additional, Oh, Andrea, additional, Poynton, Clare, additional, Reinhardt, Joseph M., additional, Ross, James, additional, Schroeder, Joyce D., additional, Sitek, Arkadiusz, additional, Steiner, Robert M., additional, van Beek, Edwin, additional, Ginneken, Bram van, additional, van Rikxoort, Eva, additional, Jensen, Robert, additional, John E. Hokanson, Co-Chair:, additional, Bhatt, Surya P., additional, Kim, Victor, additional, Putcha, Nirupama, additional, Han, MeiLan, additional, Diaz, Alejandro A., additional, Regan, Elizabeth, additional, Anzueto, Antonio, additional, Bailey, William C., additional, Criner, Gerard J., additional, Sprenger, Kim, additional, Benos, Takis, additional, Hanania, Nicola A., additional, Hoth, Karin F., additional, Lambert, Allison, additional, Lowe, Katherine, additional, Oates, Gabriela, additional, Parekh, Trisha, additional, Westney, Gloria, additional, Balasubramanian, Aparna, additional, Boriek, Aladin, additional, Fawzy, Ashraf, additional, Jacobson, Francine, additional, LaFon, David C., additional, MacIntyre, Neil, additional, Maselli-Caceres, Diego, additional, McCormack, Meredith C., additional, Sciurba, Frank, additional, Soler, Xavier, additional, Tejwani, Vickram, additional, van Beek, Edwin JR., additional, Wade, Raymond C., additional, Wells, Mike, additional, Wendt, Chris H., additional, Yun, Jeong H., additional, Zhang, Jingzhou, additional, Gillenwater, Lucas, additional, Lowe, Katherine E., additional, Pratte, Katherine A., additional, Ragland, Margaret, additional, Attaway, Amy, additional, Mason, Stefanie, additional, Saha, Punam Kumar, additional, Wilson, Ava, additional, Amaza, Hannatu, additional, Baldomero, Adrienne, additional, Mamary, A. James, additional, O’Brien, James, additional, Wise, Robert A., additional, Eakin, Michelle, additional, Fiedorowicz, Jess G., additional, Henkle, Ben, additional, Holm, Kristen, additional, Iyer, Anand, additional, Kunisaki, Ken M., additional, McEvoy, Charlene, additional, Mkorombindo, Takudzwa, additional, Shinozaki, Gen, additional, Yohannes, Abebaw, additional, Hobbs, Brian D., additional, Miller, Bruce E., additional, Retson, Tara, additional, McCloskey, Lisa, additional, Pernicano, Perry G., additional, Atik, Mustafa, additional, Bertrand, Laura, additional, Monaco, Thomas, additional, Narendra, Dharani, additional, Lenge de Rosen, Veronica V., additional, Badu-Danso, Kwame, additional, Jacobson, Francine L., additional, Kaufman, Laura, additional, Maguire, Cherie, additional, Struble, Sophie, additional, Wilson, Seth, additional, Barr, R. Graham, additional, Almonte, Casandra, additional, Austin, John H.M., additional, Gomez Blum, Maria Lorena, additional, D’Souza, Belinda M., additional, Florez, Emilay, additional, Martinez, Rodney, additional, Curry, Wendy, additional, McAdams, H. Page, additional, Reikofski, Charlotte V., additional, Washington, Lacey, additional, Brown, Robert, additional, Clare, Cheryl, additional, Daniel, Marie, additional, Horton, Karen, additional, Ting “Tony” Lin, Cheng, additional, Mirza, Tahira, additional, Scott, Meagan, additional, Shade, Becky, additional, Budoff, Matt, additional, Calmelat, Robert, additional, Cavanaugh, Deborah, additional, Dailing, Chris, additional, Diaz, Leticia, additional, Fischer, Hans, additional, Indelicato, Renee Love, additional, Porszasz, Janos, additional, Soriano, April, additional, Stringer, William, additional, Urrutia, Miriam, additional, Baldomero, Arianne, additional, Bell, Brian, additional, Deconcini, Miranda, additional, Loes, Linda, additional, Phelan, Jonathan, additional, Robichaux, Camille, additional, Sasse, Cheryl, additional, Tashjian, Joseph H., additional, Flenaugh, Eric L., additional, Abson, Kema, additional, Gebrekristos, Hirut, additional, Johnson, Priscilla, additional, Jordan, Jessica, additional, Ponce, Mario, additional, Terpenning, Silanath, additional, Wilson, Derrick, additional, Broadhurst, Grace, additional, Dyer, Debra, additional, Engel, Elena, additional, Finigan, Jay, additional, Hill, Andrew, additional, Jones, Alex, additional, Jones, Ryan, additional, Owen, Jordan, additional, Rosiello, Richard, additional, Andries, Nicole, additional, Charpentier, Mary, additional, Kirk, Diane, additional, Pace, David, additional, Ciccolella, David, additional, Cordova, Francis, additional, Dass, Chandra, additional, D’Alonzo, Gilbert, additional, Davis, Valena, additional, Desai, Parag, additional, Fehrle, Dee, additional, Grabianowski, Carla, additional, Jacobs, Michael, additional, Jameson, Laurie, additional, Jones, Gayle M., additional, Kelsen, Steven, additional, Marchetti, Nathaniel, additional, McGonagle, Francine, additional, Satti, Aditi, additional, Shenoy, Kartik, additional, Sheridan, Regina, additional, Vega-Sanchez, Maria, additional, Wallace, Samantha, additional, Akinseye-kolapo, Samuel, additional, Baker, Matthew, additional, Goggins, Arnissa, additional, McClain, Anny, additional, Nath, Hrudaya, additional, Singh, Satinder P., additional, Sonavane, Sushil K., additional, Westfall, Elizabeth, additional, Gil, Marissa, additional, El Hajjaoui, Tarek, additional, Hsiao, Albert, additional, Martineau, Amber, additional, Mielke, Jenna, additional, Perez, Karl, additional, Querido, Gabriel, additional, Reston, Tara, additional, Yen, Andrew, additional, Comellas, Alejandro, additional, Fortis, Spyridon, additional, Galizia, Mauricio, additional, Garcia, Eric, additional, Keating, Janet, additional, Laroia, Archana, additional, Lee, Changhyun, additional, Meyer, Amber, additional, Mullan, Brian, additional, Nagpal, Prashant, additional, Ofori, Oloigbe, additional, and Suiter, Sierra, additional
Published: 2022
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8. Machine Learning Characterization of COPD Subtypes

Author: Peter J. Castaldi, Adel Boueiz, Jeong Yun, Raul San Jose Estepar, James C. Ross, George Washko, Michael H. Cho, Craig P. Hersh, Gregory L. Kinney, Kendra A. Young, Elizabeth A. Regan, David A. Lynch, Gerald J. Criner, Jennifer G. Dy, Stephen I. Rennard, Richard Casaburi, Barry J. Make, James Crapo, Edwin K. Silverman, John E. Hokanson, James D. Crapo, Terri Beaty, Ferdouse Begum, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Jacqueline Hetmanski, Brian D. Hobbs, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Surya P. Bhatt, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, and Farnoush Banaei-Kashani
Subjects: Pulmonary and Respiratory Medicine, Spirometry, COPD, medicine.diagnostic_test, business.industry, Context (language use), Disease, Critical Care and Intensive Care Medicine, medicine.disease, Machine learning, computer.software_genre, Subtyping, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Genetic epidemiology, medicine, Clinical significance, 030212 general & internal medicine, Artificial intelligence, Genetic risk, Cardiology and Cardiovascular Medicine, business, computer
Abstract: COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.
Published: 2020

9. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease

Author: Auyon J. Ghosh, Brian D. Hobbs, Matthew Moll, Aabida Saferali, Adel Boueiz, Jeong H. Yun, Frank Sciurba, Lucas Barwick, Andrew H. Limper, Kevin Flaherty, Gerard Criner, Kevin K. Brown, Robert Wise, Fernando J. Martinez, David Lomas, Peter J. Castaldi, Vincent J. Carey, Dawn L. DeMeo, Michael H. Cho, Edwin K. Silverman, Craig P. Hersh, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Adel El-Boueiz, Marilyn G. Foreman, Lystra P. Hayden, Jacqueline Hetmanski, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Jarrett Morrow, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Richard Rosiello, David Pace, 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, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh
Subjects: Male, Endotype, Respiratory System, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Gastroenterology, Loss of heterozygosity, Pulmonary Disease, Chronic Obstructive, Genotype, 80 and over, 2.1 Biological and endogenous factors, Medicine, Longitudinal Studies, Aetiology, Lung, Aged, 80 and over, COPD, RNA sequencing, Middle Aged, Respiratory Function Tests, medicine.anatomical_structure, Phenotype, Meta-analysis, Respiratory, Female, alpha-1 antitrypsin, Genetic Markers, Adult, Pulmonary and Respiratory Medicine, Chronic Obstructive, Heterozygote, medicine.medical_specialty, Chronic Obstructive Pulmonary Disease, Pulmonary disease, Pulmonary Disease, Clinical Research, Internal medicine, alpha 1-Antitrypsin Deficiency, Humans, Allele, Aged, Emphysema, COPDGene Investigators, Whole Genome Sequencing, business.industry, Original Articles, medicine.disease, Survival Analysis, respiratory tract diseases, meta-analysis, alpha 1-Antitrypsin, Case-Control Studies, business
Abstract: RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas
Published: 2021

10. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author: Stefanie E. Mason, Rafael Moreta-Martinez, Wassim W. Labaki, Matthew J. Strand, Elizabeth A. Regan, Jessica Bon, Ruben San Jose Estepar, Richard Casaburi, Merry-Lynn McDonald, Harry B. Rossiter, Barry Make, Mark T. Dransfield, MeiLan K. Han, Kendra Young, Jeffrey L. Curtis, Kathleen Stringer, Greg Kinney, John E. Hokanson, Raul San Jose Estepar, George R. Washko, James D. Crapo, Edwin K. Silverman, Sara Cummings, Kelley Madden, Barry J. Make, Juliet Nabbosa, Emily Port, Serine Rashdi, Lori Stepp, Shandi Watts, Michael Weaver, Terri Beaty, Russell P. Bowler, David A. Lynch, Gary Anderson, Eugene R. Bleecker, Harvey O. Coxson, Ronald G. Crystal, James C. Hogg, Michael A. Province, Stephen I. Rennard, Thomas Croxton, Weiniu Gan, Lisa A. Postow, Lisa M. Viviano, Corinne Costa-Davis, Elisha Malanga, Delia Prieto, Ruth Tal-Singer, Homayoon Farzadegan, Akila Hadji, Leena Sathe, David Baraghoshi, Grace Chen, James Crooks, Ruthie Knowles, Katherine Pratte, Carla Wilson, Pearlanne T. Zelarney, Katerina J. Kechris, Sonia Leach, Erin E. Austin, Annika Czizik, Gregory Kinney, Yisha Li, Sharon M. Lutz, Margaret F. Ragland, Nicole Richmond, Kendra A. Young, Michael Cho, Peter J. Castaldi, Kimberly Glass, Craig Hersh, Wonji Kim, Yang-Yu Liu, Craig P. Hersh, Jacqueline Bidinger, Michael H. Cho, Douglas Conrad, Dawn L. DeMeo, Adel R. El-Boueiz, Marilyn G. Foreman, Auyon Ghosh, Georg Hahn, Nadia N. Hansel, Lystra P. Hayden, Brian Hobbs, Woori Kim, Christoph Lange, Merry- Lynn McDonald, Michael McGeachie, Matthew Moll, Melody Morris, Nikolaos A. Patsopoulos, Dandi Qiao, Ingo Ruczinski, Emily S. Wan, Jennifer G. Dy, Sean B. Fain, Shoshana Ginsburg, Eric A. Hoffman, Stephen Humphries, Philip F. Judy, Alex Kluiber Stefanie Mason, Andrea Oh, Clare Poynton, Joseph M. Reinhardt, James Ross, Joyce D. Schroeder, Arkadiusz Sitek, Robert M. Steiner, Edwin van Beek, Bram van Ginneken, Eva van Rikxoort, Robert Jensen, Co-Chair: John E. Hokanson, Surya P. Bhatt, Victor Kim, Nirupama Putcha, MeiLan Han, Alejandro A. Diaz, Elizabeth Regan, Antonio Anzueto, William C. Bailey, Gerard J. Criner, Kim Sprenger, Takis Benos, Nicola A. Hanania, Karin F. Hoth, Allison Lambert, Katherine Lowe, Gabriela Oates, Trisha Parekh, Gloria Westney, Aparna Balasubramanian, Aladin Boriek, Ashraf Fawzy, Francine Jacobson, David C. LaFon, Neil MacIntyre, Diego Maselli-Caceres, Meredith C. McCormack, Frank Sciurba, Xavier Soler, Vickram Tejwani, Edwin JR. van Beek, Raymond C. Wade, Mike Wells, Chris H. Wendt, Jeong H. Yun, Jingzhou Zhang, Lucas Gillenwater, Katherine E. Lowe, Katherine A. Pratte, Margaret Ragland, Amy Attaway, Stefanie Mason, Punam Kumar Saha, Ava Wilson, Hannatu Amaza, Adrienne Baldomero, A. James Mamary, James O’Brien, Robert A. Wise, Michelle Eakin, Jess G. Fiedorowicz, Ben Henkle, Kristen Holm, Anand Iyer, Ken M. Kunisaki, Charlene McEvoy, Takudzwa Mkorombindo, Gen Shinozaki, Abebaw Yohannes, Brian D. Hobbs, Bruce E. Miller, Tara Retson, Lisa McCloskey, Perry G. Pernicano, Mustafa Atik, Laura Bertrand, Thomas Monaco, Dharani Narendra, Veronica V. Lenge de Rosen, Kwame Badu-Danso, Francine L. Jacobson, Laura Kaufman, Cherie Maguire, Sophie Struble, Seth Wilson, R. Graham Barr, Casandra Almonte, John H.M. Austin, Maria Lorena Gomez Blum, Belinda M. D’Souza, Emilay Florez, Rodney Martinez, Wendy Curry, H. Page McAdams, Charlotte V. Reikofski, Lacey Washington, Robert Brown, Cheryl Clare, Marie Daniel, Karen Horton, Cheng Ting 'Tony' Lin, Tahira Mirza, Meagan Scott, Becky Shade, Matt Budoff, Robert Calmelat, Deborah Cavanaugh, Chris Dailing, Leticia Diaz, Hans Fischer, Renee Love Indelicato, Janos Porszasz, April Soriano, William Stringer, Miriam Urrutia, Arianne Baldomero, Brian Bell, Miranda Deconcini, Linda Loes, Jonathan Phelan, Camille Robichaux, Cheryl Sasse, Joseph H. Tashjian, Eric L. Flenaugh, Kema Abson, Hirut Gebrekristos, Priscilla Johnson, Jessica Jordan, Mario Ponce, Silanath Terpenning, Derrick Wilson, Grace Broadhurst, Debra Dyer, Elena Engel, Jay Finigan, Andrew Hill, Alex Jones, Ryan Jones, Jordan Owen, Richard Rosiello, Nicole Andries, Mary Charpentier, Diane Kirk, David Pace, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Valena Davis, Parag Desai, Dee Fehrle, Carla Grabianowski, Michael Jacobs, Laurie Jameson, Gayle M. Jones, Steven Kelsen, Nathaniel Marchetti, Francine McGonagle, Aditi Satti, Kartik Shenoy, Regina Sheridan, Maria Vega-Sanchez, Samantha Wallace, Samuel Akinseye-kolapo, Matthew Baker, Arnissa Goggins, Anny McClain, Hrudaya Nath, Satinder P. Singh, Sushil K. Sonavane, Elizabeth Westfall, Marissa Gil, Tarek El Hajjaoui, Albert Hsiao, Amber Martineau, Jenna Mielke, Karl Perez, Gabriel Querido, Tara Reston, Andrew Yen, Alejandro Comellas, Spyridon Fortis, Mauricio Galizia, Eric Garcia, Janet Keating, Archana Laroia, Changhyun Lee, Amber Meyer, Brian Mullan, Prashant Nagpal, Oloigbe Ofori, and Sierra Suiter
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Chronic Obstructive, Clinical Sciences, Respiratory System, Critical Care and Intensive Care Medicine, COPD: Original Research, Body Mass Index, Pectoralis Muscles, Pulmonary Disease, sarcopenia, Pulmonary Disease, Chronic Obstructive, Interquartile range, Clinical Research, Internal medicine, medicine, Tobacco Smoking, COPD, 2.1 Biological and endogenous factors, Humans, Longitudinal Studies, Aetiology, Pectoralis Muscle, Lung, Nutrition, Smokers, COPDGene Investigators, Proportional hazards model, business.industry, Prevention, Smoking, muscle wasting, medicine.disease, mortality, Confidence interval, Good Health and Well Being, Sarcopenia, Cardiology, Body Composition, Cardiology and Cardiovascular Medicine, business, Body mass index, Bioelectrical impedance analysis, Biomarkers
Abstract: BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n= 9,268) and the ECLIPSE study (n= 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1%(95%CI, 2.4%-3.7%; P< .001) in COPDGene, and 2.4%(95%CI, 0.9%-4.0%; P< .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.
Published: 2021

11. Integrative Genomics Analysis Identifies ACVR1B as a Candidate Causal Gene of Emphysema Distribution

Author: Adel Boueiz, Betty Pham, Robert Chase, Andrew Lamb, Sool Lee, Zun Zar Chi Naing, Michael H. Cho, Margaret M. Parker, Phuwanat Sakornsakolpat, Craig P. Hersh, James D. Crapo, Andrew B. Stergachis, Ruth Tal-Singer, Dawn L. DeMeo, Edwin K. Silverman, Xiaobo Zhou, Peter J. Castaldi, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Michael Cho, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dandi Qiao, Emily S. Wan, Sungho Won, Dmitry Prokopenko, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Jessica Bon, Barry Make, Carlos Martinez, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O’Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, Y. Feschenko, V. Gavrisyuk, L. Yashina, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, Rancho Mirage, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, R. Tal-Singer, J. Yates, B. Miller, Per Bakke, Amund Gulsvik, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, and MUMC+: MA Longziekten (3)
Subjects: EXPRESSION, 0301 basic medicine, Pulmonary and Respiratory Medicine, Quantitative Trait Loci, Clinical Biochemistry, Genome-wide association study, Computational biology, Biology, Polymorphism, Single Nucleotide, Proof of Concept Study, OBSTRUCTIVE PULMONARY-DISEASE, chronic obstructive pulmonary disease, Transforming Growth Factor beta1, Jurkat Cells, Pulmonary Disease, Chronic Obstructive, integrative genomics, 03 medical and health sciences, 0302 clinical medicine, T-Lymphocyte Subsets, Cell Line, Tumor, Humans, WIDE ASSOCIATION, GWAS, Distribution (pharmacology), Genetic Predisposition to Disease, LUNG-VOLUME-REDUCTION, Lung, Molecular Biology, Gene, ACVR1B, Original Research, ACVR1B gene, Genetic association, Emphysema, emphysema distribution, LANDSCAPE, transforming growth factor-beta signaling, Editorials, DNA, Genomics, Cell Biology, Integrative genomics, Causal gene, ACVR1B Gene, 030104 developmental biology, Pulmonary Emphysema, 030228 respiratory system, Activin Receptors, Type I, Genome-Wide Association Study
Abstract: Genome-wide association studies (GWAS) have identified multiple associations with emphysema apicobasal distribution (EABD), but the biological functions of these variants are unknown. To characterize the functions of EABD-associated variants, we integrated GWAS results with 1) expression quantitative trait loci (eQTL) from the Genotype Tissue Expression (GTEx) project and subjects in the COPDGene (Genetic Epidemiology of COPD) study and 2) cell type epigenomic marks from the Roadmap Epigenomics project. On the basis of these analyses, we selected a variant near ACVR1B (activin A receptor type 1B) for functional validation. SNPs from 168 loci with P values less than 5 × 10(−5) in the largest GWAS meta-analysis of EABD were analyzed. Eighty-four loci overlapped eQTL, with 12 of these loci showing greater than 80% likelihood of harboring a single, shared GWAS and eQTL causal variant. Seventeen cell types were enriched for overlap between EABD loci and Roadmap Epigenomics marks (permutation P
Published: 2019

12. Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Author: Emily S. Wan, Spyridon Fortis, Elizabeth A. Regan, John Hokanson, MeiLan K. Han, Richard Casaburi, Barry J. Make, James D. Crapo, Dawn L. DeMeo, Edwin K. Silverman, Terri Beaty, Ferdouse Begum, Peter J. Castaldi, Michael Cho, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Sungho Won, Phuwanat Sakornsakolpat, Dmitry Prokopenko, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Jessica Bon, Barry Make, Carlos Martinez, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D. N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, 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, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz
Subjects: Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Follow up studies, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Cardiology, medicine, 030212 general & internal medicine, Prism, business
Abstract: Rationale: Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lu...
Published: 2018

13. Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Author: Vickram Tejwani, Ashraf Fawzy, Nirupama Putcha, Peter J. Castaldi, Michael H. Cho, Katherine A. Pratte, Surya P. Bhatt, David A. Lynch, Stephen M. Humphries, Gregory L. Kinney, Franco R. D’Alessio, Nadia N. Hansel, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bramvan Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A. Young, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Eric Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, KenM. Kunisaki, Russell Bowler, 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, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, and Joel Weissfeld
Subjects: Pulmonary and Respiratory Medicine, Male, Angiotensin receptor, medicine.medical_specialty, Population, Vital Capacity, Angiotensin-Converting Enzyme Inhibitors, Walk Test, Critical Care and Intensive Care Medicine, Cohort Studies, 03 medical and health sciences, Angiotensin Receptor Antagonists, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Forced Expiratory Volume, Medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Prospective Studies, education, Aged, COPD, education.field_of_study, Lung, biology, business.industry, Angiotensin-converting enzyme, respiratory system, Middle Aged, Protective Factors, medicine.disease, Angiotensin II, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Genetic epidemiology, Pulmonary Emphysema, Spirometry, Cohort, biology.protein, Cardiology, Disease Progression, Female, Cardiology and Cardiovascular Medicine, business, Lung Volume Measurements, Tomography, X-Ray Computed
Abstract: Background Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume Results Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry ClinicalTrials.gov ; No.: NCT00608764; URL: www.clinicaltrials.gov
Published: 2020

14. Disease Progression Modeling in Chronic Obstructive Pulmonary Disease

Author: Barry J. Make, Venkata Bandi, Douglas Stinson, Ella A. Kazerooni, Harry B. Rossiter, Farnoush Banaei-Kashani, Xavier Soler, Arun C. Nachiappan, Paul J. Friedman, Karen M. Horton, Terri H. Beaty, Christine H. Wendt, Andrew Yen, Philip F. Judy, Ferdouse Begum, Jeffrey L. Curtis, Lystra P. Hayden, Joe W. Ramsdell, Peter J. Castaldi, Alejandro P. Comellas, Emily S. Wan, Susan Murray, Aladin M. Boriek, David Pace, Jessica Bon, Nadia N. Hansel, Chandra Dass, Marilyn G. Foreman, Neil R. MacIntyre, Kartik Shenoy, David A. Lynch, Brian D. Hobbs, Raúl San José Estépar, John D. Newell, Philip Alapat, Karin F. Hoth, Stephen M. Humphries, Robert M. Steiner, Alessandra Adami, R.P. Bowler, Parag Desai, Mustafa Al Qaisi, Anna Rozenshtein, Joel L. Weissfeld, Robert A. Wise, Nan M. Laird, Margaret M. Parker, Felix J. S. Bragman, Camille M. Moore, Abbie Begnaud, Allison A. Lambert, Elizabeth Guy, Michael R. Jacobs, Mario E. Ruiz, Dawn L. DeMeo, Sungho Won, Alex Kluiber, Amit D. Parulekar, John H. M. Austin, Nathaniel Marchetti, Dandi Qiao, Douglas Everett, Joseph H. Tashjian, Juerg Tschirren, Kendra A. Young, Adel Boueiz, James D. Crapo, Gregory L. Kinney, Richard Casaburi, Russell P. Bowler, Daniel C. Alexander, Francis Cordova, Craig P. Hersh, George R. Washko, H. Page McAdams, Amir Sharafkhaneh, A. James Mamary, J. Michael Wells, Lacey Washington, MeiLan K. Han, Mark T. Dransfield, Nirupama Putcha, Craig J. Galbán, Dmitry Prokopenko, Eric A. Hoffman, Gloria Westney, Katerina Kechris, Bojidar Rangelov, Carla Wilson, Charlene McEvoy, Divay Chandra, Edwin J R van Beek, Carlos H. Martinez, Kalpatha Guntupalli, Gregory D.N. Pearson, Diego Maselli-Caceres, James C. Ross, Katherine A. Pratte, Christoph Lange, David Ciccolella, Charlie Lan, R. Graham Barr, Phuwanat Sakornsakolpat, Aditi Satti, Irene Swift, Robert H. Brown, Hans Fischer, Victor Kim, Maria Elena Vega-Sanchez, Sandra G. Adams, Belinda D’Souza, Perry G. Pernicano, Bram van Ginneken, Hrudaya Nath, Byron Thomashow, Jim Crooks, Joanne Billings, Jered Sieren, Eitan Halper-Stromberg, Matthew J. Budoff, William C. Bailey, Eva M. van Rikxoort, Merry-Lynn McDonald, Francine L. Jacobson, Edwin K. Silverman, John E. Hokanson, Robert L. Jensen, John Hughes, Michael H. Cho, Alexandra L. Young, Steven G. Kelsen, Janos Porszasz, Jacqueline B. Hetmanski, Alex Swift, John R. Hurst, Elizabeth A. Regan, Anand S Iyer, Frank C. Sciurba, Mustafa A. Atik, Gerard J. Criner, Antonio Anzueto, Sharon M. Lutz, David J. Hawkes, Carl R. Fuhrman, William W. Stringer, Harvey O. Coxson, Berend C. Stoel, Eugene Berkowitz, Joyce D. Schroeder, Tadashi Allen, Surya P. Bhatt, Matthew Strand, Brad H. Thompson, Nicola A. Hanania, Brian Bell, Teresa Gray, Gilbert E. D'Alonzo, and Richard Rosiello
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Pulmonary disease, Critical Care and Intensive Care Medicine, Machine Learning, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, COPD, business.industry, Disease progression, Editorials, Original Articles, Middle Aged, Models, Theoretical, respiratory system, medicine.disease, respiratory tract diseases, 030228 respiratory system, Disease Progression, Bronchitis, Female, Ct imaging, business, Tomography, X-Ray Computed, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract: Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) 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."
Published: 2020

15. Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline

Author: Lystra P. Hayden, Megan E. Hardin, Weiliang Qiu, David A. Lynch, Matthew J. Strand, Edwin J. van Beek, James D. Crapo, Edwin K. Silverman, Craig P. Hersh, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Adel R. Boueiz, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Jim Crooks, Douglas Everett, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, and Kendra A. Young
Subjects: Pulmonary and Respiratory Medicine, COPD, medicine.medical_specialty, Exacerbation, business.industry, Respiratory disease, Critical Care and Intensive Care Medicine, medicine.disease, respiratory tract diseases, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, 030228 respiratory system, Internal medicine, medicine, 030212 general & internal medicine, Risk factor, Respiratory system, Cardiology and Cardiovascular Medicine, business, Airway, Asthma
Abstract: Background Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. Methods Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at Results Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. Conclusions Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. Trial Registry ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov.
Published: 2018

16. 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

17. Combined Forced Expiratory Volume in 1 Second and Forced Vital Capacity Bronchodilator Response, Exacerbations, and Mortality in Chronic Obstructive Pulmonary Disease

Author: Spyridon Fortis, Alejandro Comellas, Barry J. Make, Craig P. Hersh, Sandeep Bodduluri, Dimitris Georgopoulos, Victor Kim, Gerard J. Criner, Mark T. Dransfield, Surya P. Bhatt, James D. Crapo, Edwin K. Silverman, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D.N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz
Subjects: Pulmonary and Respiratory Medicine, Spirometry, Male, Vital capacity, medicine.medical_specialty, medicine.drug_class, Vital Capacity, Pulmonary disease, Risk Assessment, Severity of Illness Index, Cohort Studies, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Bronchodilator, Forced Expiratory Volume, medicine, Humans, 030212 general & internal medicine, Respiratory system, Asthma, Aged, Proportional Hazards Models, Retrospective Studies, Original Research, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Survival Analysis, respiratory tract diseases, Bronchodilator Agents, Respiratory Function Tests, Logistic Models, Treatment Outcome, 030228 respiratory system, Volume (thermodynamics), Multivariate Analysis, Cardiology, Disease Progression, Female, business, Tomography, X-Ray Computed
Abstract: Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV(1)) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV(1) or FVC; 2) FEV(1)-BDR, BDR in FEV(1) but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV(1); and 4) Combined-BDR, BDR in both FEV(1) and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV(1) over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV(1)-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV(1) decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, −1.67; 95% confidence interval [CI], −2.68 to −0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03–1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05–1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58–0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV(1) and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.
Published: 2019

18. The St. George's Respiratory Questionnaire Definition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic Definition

Author: Victor Kim, Huaqing Zhao, Elizabeth Regan, MeiLan K. Han, Barry J. Make, James D. Crapo, Paul W. Jones, Jeffrey L. Curtis, Edwin K. Silverman, Gerard J. Criner, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Jean-Paul Charbonnier, Harvey O. Coxson, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D.N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Eric L. Flenaugh, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, Gabriela Oates, Sushil Sonavane, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Chronic bronchitis, Exacerbation, Critical Care and Intensive Care Medicine, Severity of Illness Index, 03 medical and health sciences, Diagnostic Self Evaluation, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Medicine, Humans, Per patient per year, 030212 general & internal medicine, Respiratory system, Aged, COPD, Normal spirometry, business.industry, Severe exacerbation, Middle Aged, medicine.disease, Prognosis, humanities, Obstructive lung disease, respiratory tract diseases, Bronchitis, Chronic, 030228 respiratory system, Disease Progression, Female, Cardiology and Cardiovascular Medicine, business, human activities
Abstract: Background Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. Methods We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB+ or classic CB–, using the classic definition. In addition, subjects were divided into SGRQ CB+ or SGRQ CB–. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. Results There were 1,434 classic CB+ subjects and 2,290 SGRQ CB+ subjects. The classic CB+ group had a greater exacerbation frequency compared with the classic CB– group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P Conclusions The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.
Published: 2018

19. Spirometric Volumes and Breathlessness across Levels of Airflow Limitation: The COPDGene Study

Author: Magnus Ekström, Anna Bornefalk-Hermansson, Nicholas Wysham, David C. Currow, Neil MacIntyre, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D. N. Pearson, Anna Rozenshtein, Byron Thomashow, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs Pharm.D, 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, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, business.industry, Airflow, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Correspondence, Cardiology, Medicine, business, Lung function
Abstract: Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.
Published: 2018

20. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Author: Jeong H. Yun, Andrew Lamb, Robert Chase, Dave Singh, Margaret M. Parker, Aabida Saferali, Jørgen Vestbo, Ruth Tal-Singer, Peter J. Castaldi, Edwin K. Silverman, Craig P. Hersh, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D'Souza, Gregory D.N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, 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, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, P. de Mallorca, Y. Feschenko, V. Gavrisyuk, L. Yashina Kiev, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, R. Tal Singer, J. Yates, B. Miller, R. Tal-Singer, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, and MUMC+: MA Longziekten (3)
Subjects: Male, Exacerbation, Allergy, AIRWAY INFLAMMATION, INHALED CORTICOSTEROIDS, Rate ratio, Leukocyte Count, 0302 clinical medicine, exacerbation, CLINICAL CHARACTERISTICS, Immunology and Allergy, 030212 general & internal medicine, Longitudinal Studies, Lung, COPD, medicine.diagnostic_test, Chronic obstructive pulmonary disease, Complete blood count, Middle Aged, RANDOMIZED CONTROLLED-TRIAL, Observational Studies as Topic, medicine.anatomical_structure, Disease Progression, Respiratory, Female, SHORT-TERM RESPONSE, medicine.medical_specialty, Chronic Obstructive, Chronic Obstructive Pulmonary Disease, Immunology, Pulmonary Disease, 03 medical and health sciences, FEV1/FVC ratio, Clinical Research, Internal medicine, White blood cell, medicine, Humans, eosinophil, Asthma, Aged, business.industry, COPDGene and ECLIPSE Investigators, Eosinophil, asthma, medicine.disease, Eosinophils, 030228 respiratory system, SPUTUM-EOSINOPHILIA, OVERLAP SYNDROME, business, COPENHAGEN GENERAL-POPULATION
Abstract: BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). Asubset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.
Published: 2018

21. Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

Author: Robert Busch, Brian D. Hobbs, Jin Zhou, Peter J. Castaldi, Michael J. McGeachie, Megan E. Hardin, Iwona Hawrylkiewicz, Pawel Sliwinski, Jae-Joon Yim, Woo Jin Kim, Deog K. Kim, Alvar Agusti, Barry J. Make, James D. Crapo, Peter M. Calverley, Claudio F. Donner, David A. Lomas, Emiel F. Wouters, Jørgen Vestbo, Ruth Tal-Singer, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David Sparrow, Peter D. Paré, Robert D. Levy, Stephen I. Rennard, Terri H. Beaty, John Hokanson, Edwin K. Silverman, Michael H. Cho, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Marilyn Foreman, Brian Hobbs, Adel El-Bouiez, 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 San Jose Estepar, Berend C. Stoel, Juerg Tschirren, Eva van Rikxoort, Bram van Ginneken, George Washko, 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 Comellas, 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, Mario E. Ruiz, Jaume Sauleda, Peter M. A. Calverley, Stephen Rennard, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, Y. Feschenko, V. Gavrisyuk, L. Yashina, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, R. Tal Singer, J. Yates, B. Miller, R. Tal-Singer, J. Benditt, G. Criner, M. DeCamp, P. Diaz, M. Ginsburg, L. Kaiser, M. Katz, M. Krasna, N. MacIntyre, R. McKenna, F. Martinez, Z. Mosenifar, J. Reilly, A. Ries, J. Utz, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, MUMC+: MA Longziekten (3), and RS: NUTRIM - R3 - Chronic inflammatory disease and wasting
Subjects: 0301 basic medicine, Male, Clinical Biochemistry, EMPHYSEMA, SUSCEPTIBILITY, AIR-FLOW OBSTRUCTION, Pulmonary Disease, Chronic Obstructive, Risk Factors, Medicine, EPIDEMIOLOGY, Genetic epidemiology, Original Research, COPD, COMPLEX DISEASE, RECLASSIFICATION, Chronic obstructive pulmonary disease, Middle Aged, Genetic risk score, Respiratory Function Tests, LUNG-FUNCTION, Genetic risk factors, alpha-1 antitrypsin, Meta-analysis, Female, SMOKING, Pulmonary and Respiratory Medicine, medicine.medical_specialty, genetic epidemiology, Pulmonary disease, Single-nucleotide polymorphism, genetic risk score, chronic obstructive pulmonary disease, 03 medical and health sciences, Internal medicine, Genetic variation, genetic risk factors, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Molecular Biology, Genotyping, Genetic association, Aged, business.industry, Cell Biology, Heritability, medicine.disease, respiratory tract diseases, 030104 developmental biology, Physical therapy, business, Genome-Wide Association Study
Abstract: The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10(-8)) and PPP4R4/SERPINA1 (P = 1.01 X 10(-8)) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, similar to 0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.
Published: 2017

22. 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

23. Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease

Author: James Murphy, Edwin J. R. van Beek, Eugene Berkowitz, Carlos Orozco, Venkata Bandi, Robert M. Steiner, Shivam Chandan, Stephanie A. Santorico, Joel L. Weissfeld, Kalpalatha K. Guntupalli, Matthew J. Budoff, Robert H. Brown, Charles Trinh, Ya Hong Chen, Phillip M. Westgate, John D. Newell, Gloria Westney, Raúl San José Estépar, Russell P. Bowler, Geoffrey McLennan, Robert A. Wise, Ella A. Kazerooni, Nathaniel Marchetti, John H. M. Austin, Harvey O. Coxson, Douglas Everett, Joseph H. Tashjian, Antonio Anzueto, Joe Piccoli, Homayoon Farzadegan, Richard Casaburi, Michael H. Cho, Philip Alapat, Charlene McEvoy, Sandra G. Adams, Marilyn G. Foreman, R. Graham Barr, Jessica Bon, Fernando J. Martinez, Susan Murray, Nadia N. Hansel, Paul J. Friedman, Francine L. Jacobson, Ruthie Knowles, Verity McArthur, Jennifer L. Black-Shinn, Joe W. Ramsdell, Janos Porszasz, Martina Wamboldt, Chandra Dass, Terri H. Beaty, John J. Reilly, Timothy Bresnahan, Hans Fischer, Jordan A. Zach, Victor Kim, Jacqueline B. Hetmanski, Elizabeth Guy, Dzimitry Kazlouski, Stacey Meyerer, Eric A. Hoffman, Philip F. Judy, Sarah Moyle, Adam L. Friedlander, Frank C. Sciurba, Brad H. Thompson, Mark T. Dransfield, Tanda Murray, Michael E. DeBakey, Margaret Forbes, Nicola A. Hanania, Gregory L. Kinney, Barbara J. Klanderman, Mustafa A. Atik, Gerard J. Criner, Christine H. Wendt, Dwight C. Look, James D. Crapo, Elizabeth A. Regan, Hirani Kamal, Andrew Allen, Anastasia Rodionova, Amber Powell, Heather Baumhauer, Quentin Anderson, Aditi Satti, Dennis E. Niewoehner, John E. Hokanson, Marci K. Sontag, William C. Bailey, Lyrica X. Liu, Hrudaya Nath, Neil R. MacIntyre, David A. Lynch, Kathryn L. Rice, Samantha Bragan, Barry J. Make, Byron Thomashow, Douglas Stinson, Jered Sieren, Richard Rosiello, Roham Darvishi, Robert L. Jensen, Tanya Mann, Lacey Washington, Gregory B. Diette, Christoph Lange, Mario E. Ruiz, Jeffrey L. Curtis, Joyce D. Schroeder, Antara Mallampalli, Tadashi Allen, Rebecca Leek, Nan M. Laird, Craig P. Hersh, George R. Washko, H. Page McAdams, Amir Sharafkhaneh, Alex Kluiber, MeiLan K. Han, Carl R. Fuhrman, A. James Mamary, Carla Wilson, James C. Ross, Carlos H. Martinez, Edwin K. Silverman, Dawn L. DeMeo, and Maura Robinson
Subjects: Male, Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, Health Status, Body Mass Index, Pulmonary Disease, Chronic Obstructive, Surveys and Questionnaires, Internal medicine, Hounsfield scale, medicine, Humans, Lung emphysema, Lung, Aged, Aged, 80 and over, Emphysema, COPD, medicine.diagnostic_test, business.industry, Middle Aged, respiratory system, medicine.disease, humanities, Obstructive lung disease, respiratory tract diseases, Dyspnea, medicine.anatomical_structure, Multivariate Analysis, Cardiology, Physical therapy, Regression Analysis, Female, Tomography, X-Ray Computed, Airway, business, Body mass index
Abstract: The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George's Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE).1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a -950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p0.001; for WA%, 1.20-fold increase, p0.001; for pi10, 1.16-fold increase, p0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26-fold increase, p0.001).Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.
Published: 2012

24. Vorticity for the assessment of right ventricular diastolic dysfunction using 4D flow CMR

Author: Christopher Glielmi, Jamey Browning, Jean Hertzberg, Joyce D. Schroeder, Lori J. Silveira, Brett E. Fenster, Aurélien F. Stalder, Alex Kluiber, and J. Kern Buckner
Subjects: medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Right ventricular diastolic dysfunction, Diastole, Internal medicine, Medicine, Radiology, Nuclear Medicine and imaging, Diastolic function, cardiovascular diseases, Simulation, Angiology, Medicine(all), Tricuspid valve, Radiological and Ultrasound Technology, business.industry, Vorticity, medicine.disease, Pulmonary hypertension, medicine.anatomical_structure, lcsh:RC666-701, Right heart, Poster Presentation, Cardiology, cardiovascular system, Cardiology and Cardiovascular Medicine, business
Abstract: Background 4D flow CMR analysis of right ventricular (RV) diastolic inflow has demonstrated vortical formations at tips of the tricuspid valve during the deceleration phase of early filling (E wave) (Figure 1). Vorticity can measure the rotation of these vortices and may represent a novel way to assess RV diastolic function. We aimed to determine if right heart vorticity identified right ventricular diastolic dysfunction (RVDD) in pulmonary hypertension (PH) subjects when compared to controls using 4D flow CMR. Methods
Published: 2013

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24 results on '"Alex Kluiber"'

1. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

2. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure

3. Development of a Blood-based Transcriptional Risk Score for Chronic Obstructive Pulmonary Disease

4. Clinically Significant and Comorbid Anxiety and Depression Symptoms Predict Severe Respiratory Exacerbations in Smokers: A Post Hoc Analysis of the COPDGene and SPIROMICS Cohorts

5. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

6. Prevalence of abnormal spirometry in individuals with a smoking history and no known obstructive lung disease

7. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

8. Machine Learning Characterization of COPD Subtypes

9. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease

10. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

11. Integrative Genomics Analysis Identifies ACVR1B as a Candidate Causal Gene of Emphysema Distribution

12. Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

13. Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

14. Disease Progression Modeling in Chronic Obstructive Pulmonary Disease

15. Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline

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

17. Combined Forced Expiratory Volume in 1 Second and Forced Vital Capacity Bronchodilator Response, Exacerbations, and Mortality in Chronic Obstructive Pulmonary Disease

18. The St. George's Respiratory Questionnaire Definition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic Definition

19. Spirometric Volumes and Breathlessness across Levels of Airflow Limitation: The COPDGene Study

20. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

21. Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

22. Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD

23. Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease

24. Vorticity for the assessment of right ventricular diastolic dysfunction using 4D flow CMR

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24 results on '"Alex Kluiber"'

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