Non-emphysematous chronic obstructive pulmonary disease is associated with diabetes mellitus

Craig P Hersh, Barry J Make, David A Lynch, R Graham Barr, Russell P Bowler, Peter M A Calverley, Peter J Castaldi, Michael H Cho, Harvey O Coxson, Dawn L DeMeo, Marilyn G Foreman, MeiLan K Han, Benjamin J Harshfield, John E Hokanson, Sharon Lutz, Joe W Ramsdell, Elizabeth A Regan, Stephen I Rennard, Joyce D Schroeder, Frank C Sciurba, Robert M Steiner, Ruth Tal-Singer, Edwin van Beek Jr, Edwin K Silverman, James D Crapo, COPDGene and ECLIPSE Investigators, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Lori Stepp, Sandra Melanson, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John Hokanson, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Jin Zhou, Manuel Mattheisen, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Tanda Murray, David Lynch, Joyce Schroeder, John Newell Jr, John Reilly, Harvey Coxson, Philip Judy, Eric Hoffman, George Washko, Raul San Jose Estepar, James Ross, Mustafa Al Qaisi, Jordan Zach, Alex Kluiber, Jered Sieren, Tanya Mann, Deanna Richert, Alexander McKenzie, Jaleh Akhavan, Douglas Stinson, Robert Jensen, Homayoon Farzadegan, Stacey Meyerer, Shivam Chandan, Samantha Bragan, Douglas Everett, Andre Williams, Carla Wilson, Anna Forssen, Amber Powell, Joe Piccoli, John Hokanson, Marci Sontag, Jennifer Black-Shinn, Gregory Kinney, Sharon Lutz, Jeffrey Curtis, Ella Kazerooni, Nicola Hanania, Philip Alapat, Venkata Bandi, Kalpalatha Guntupalli, Elizabeth Guy, Antara Mallampalli, Charles Trinh, Mustafa Atik, Hasan Al-Azzawi, Marc Willis, Susan Pinero, Linda Fahr, Arun Nachiappan, Collin Bray, L Alexander Frigini, Carlos Farinas, David Katz, Jose Freytes, Anne Marie Marciel, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, Hiroto Hatabu, Peter Clarke, Ritu Gill, Andetta Hunsaker, Beatrice Trotman-Dickenson, Rachna Madan, R Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Neil MacIntyre Jr, Lacey Washington, H Page McAdams, Richard Rosiello, Timothy Bresnahan, Joseph Bradley, Sharon Kuong, Steven Meller, Suzanne Roland, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, Robert Brown, Gregory Diette, Karen Horton, Richard Casaburi, Janos Porszasz, Hans Fischer, Matt Budoff, Michael E DeBakey, Amir Sharafkhaneh, Charles Trinh, Hirani Kamal, Roham Darvishi, Marc Willis, Susan Pinero, Linda Fahr, Arun Nachiappan, Collin Bray, L Alexander Frigini, Carlos Farinas, David Katz, Jose Freytes, Anne Marie Marciel, Dennis Niewoehner, Quentin Anderson, Kathryn Rice, Audrey Caine, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Joyce Schroeder, Valerie Hale, John Armstrong 2nd, Debra Dyer, Jonathan Chung, Gerard Criner, Victor Kim, Nathaniel Marchetti, Aditi Satti, A James Mamary, Robert Steiner, Chandra Dass, Libby Cone, William Bailey, Mark Dransfield, Michael Wells, Surya Bhatt, Hrudaya Nath, Satinder Singh, Joe Ramsdell, Paul Friedman, Alejandro Cornellas, John Newell Jr, Edwin J R van Beek, Fernando Martinez, MeiLan Han, Ella Kazerooni, Christine Wendt, Tadashi Allen, Frank Sciurba, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Danielle Hooper, Sandra Adams, Carlos Orozco, Mario Ruiz, Amy Mumbower, Ariel Kruger, Carlos Restrepo, Michael Lane, Y Ivanov, K Kostov, J Bourbeau, M Fitzgerald, P Hernández, 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, D Lomas, W MacNee, E Silverman, R Tal Singer, J Vestbo, J Yates, A Agusti, P Calverley, B Celli, C Crim, B Miller, W MacNee, S Rennard, R Tal-Singer, E Wouters, J Yates, Craig P Hersh, Barry J Make, David A Lynch, R Graham Barr, Russell P Bowler, Peter M A Calverley, Peter J Castaldi, Michael H Cho, Harvey O Coxson, Dawn L DeMeo, Marilyn G Foreman, MeiLan K Han, Benjamin J Harshfield, John E Hokanson, Sharon Lutz, Joe W Ramsdell, Elizabeth A Regan, Stephen I Rennard, Joyce D Schroeder, Frank C Sciurba, Robert M Steiner, Ruth Tal-Singer, Edwin van Beek Jr, Edwin K Silverman, James D Crapo, COPDGene and ECLIPSE Investigators, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Lori Stepp, Sandra Melanson, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John Hokanson, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Jin Zhou, Manuel Mattheisen, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Tanda Murray, David Lynch, Joyce Schroeder, John Newell Jr, John Reilly, Harvey Coxson, Philip Judy, Eric Hoffman, George Washko, Raul San Jose Estepar, James Ross, Mustafa Al Qaisi, Jordan Zach, Alex Kluiber, Jered Sieren, Tanya Mann, Deanna Richert, Alexander McKenzie, Jaleh Akhavan, Douglas Stinson, Robert Jensen, Homayoon Farzadegan, Stacey Meyerer, Shivam Chandan, Samantha Bragan, Douglas Everett, Andre Williams, Carla Wilson, Anna Forssen, Amber Powell, Joe Piccoli, John Hokanson, Marci Sontag, Jennifer Black-Shinn, Gregory Kinney, Sharon Lutz, Jeffrey Curtis, Ella Kazerooni, Nicola Hanania, Philip Alapat, Venkata Bandi, Kalpalatha Guntupalli, Elizabeth Guy, Antara Mallampalli, Charles Trinh, Mustafa Atik, Hasan Al-Azzawi, Marc Willis, Susan Pinero, Linda Fahr, Arun Nachiappan, Collin Bray, L Alexander Frigini, Carlos Farinas, David Katz, Jose Freytes, Anne Marie Marciel, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, Hiroto Hatabu, Peter Clarke, Ritu Gill, Andetta Hunsaker, Beatrice Trotman-Dickenson, Rachna Madan, R Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Neil MacIntyre Jr, Lacey Washington, H Page McAdams, Richard Rosiello, Timothy Bresnahan, Joseph Bradley, Sharon Kuong, Steven Meller, Suzanne Roland, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, Robert Brown, Gregory Diette, Karen Horton, Richard Casaburi, Janos Porszasz, Hans Fischer, Matt Budoff, Michael E DeBakey, Amir Sharafkhaneh, Charles Trinh, Hirani Kamal, Roham Darvishi, Marc Willis, Susan Pinero, Linda Fahr, Arun Nachiappan, Collin Bray, L Alexander Frigini, Carlos Farinas, David Katz, Jose Freytes, Anne Marie Marciel, Dennis Niewoehner, Quentin Anderson, Kathryn Rice, Audrey Caine, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Joyce Schroeder, Valerie Hale, John Armstrong 2nd, Debra Dyer, Jonathan Chung, Gerard Criner, Victor Kim, Nathaniel Marchetti, Aditi Satti, A James Mamary, Robert Steiner, Chandra Dass, Libby Cone, William Bailey, Mark Dransfield, Michael Wells, Surya Bhatt, Hrudaya Nath, Satinder Singh, Joe Ramsdell, Paul Friedman, Alejandro Cornellas, John Newell Jr, Edwin J R van Beek, Fernando Martinez, MeiLan Han, Ella Kazerooni, Christine Wendt, Tadashi Allen, Frank Sciurba, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Danielle Hooper, Sandra Adams, Carlos Orozco, Mario Ruiz, Amy Mumbower, Ariel Kruger, Carlos Restrepo, Michael Lane, Y Ivanov, K Kostov, J Bourbeau, M Fitzgerald, P Hernández, 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, D Lomas, W MacNee, E Silverman, R Tal Singer, J Vestbo, J Yates, A Agusti, P Calverley, B Celli, C Crim, B Miller, W MacNee, S Rennard, R Tal-Singer, E Wouters, J Yates

Abstract

Background: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.

Methods: Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%).

Results: Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized. Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St. George's Respiratory Questionnaire score 43 vs 31, p < 0.0001). Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use. The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study.

Conclusions: Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes. COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa.

Trial registration: Clinicaltrials.gov identifiers: COPDGene NCT00608764, ECLIPSE NCT00292552.

Figures

Figure 1
Figure 1
Frequencies of the “pink puffer” and “blue bloater” subtypes of COPD by severity of airflow obstruction. See Methods for definitions.
Figure 2
Figure 2
Chest CT scans from COPDGene subjects demonstrating emphysema-predominant and non-emphysematous COPD. (A) Emphysema-predominant: FEV1 55.8% predicted, 29.0% emphysema. (B) Non-emphysematous: FEV1 55.3% predicted, 4.2% emphysema.

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Pre-publication history
    1. The pre-publication history for this paper can be accessed here:

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