Clinical and computed tomographic predictors of chronic bronchitis in COPD: A cross sectional analysis of the COPDGene study

Victor Kim, Adam Davey, Alejandro P. Comellas, Meilan K. Han, George Washko, Carlos H. Martinez, David Lynch, Jin H. Lee, Edwin K. Silverman, James D. Crapo, Barry J. Make, Gerard J. Criner, Homayoon Farzadegan, Samantha Bragan, Stacey Cayetano, Jeffrey Curtis, Ella Kazerooni, Nicola Hanania, Philip Alapat, Venkata BandiKalpalatha 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, 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, 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, Mehdi Rambod, Amir Sharafkhaneh, Hirani Kamal, Roham Darvishi, Dennis Niewoehner, Quentin Anderson, Kathryn Rice, Audrey Caine, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, Joyce Schroeder, Valerie Hale, John Armstrong, Debra Dyer, Jonathan Chung, Christian Cox, 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, Edwin J.R. van Beek, Fernando Martinez, Christine Wendt, Tadashi Allen, Frank Sciurba, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Danielle Hooper, Antonio Anzueto, Sandra Adams, Carlos Orozco, Mario Ruiz, Amy Mumbower, Ariel Kruger, Carlos Restrepo, Michael Lane, Jaleh Akhavan, Mustafa Al Qaisi, Terri Beaty, Jennifer Black-Shinn, Eugene R. Bleecker, Russell P. Bowler, Stephanie Bratschie, Peter J. Castaldic, Michael Cho, Christian W. Cox, Harvey O. Coxson, Thomas Croxton, Ronald G. Crystal, Jeffrey L. Curtis, Deanna Cusick, Dawn L. DeMeo, Jennifer G. Dy, Douglas Everett, Marilyn G. Foreman, Weiniu Gan, Shoshana Ginsburg, Nadia N. Hansel, Megan E. Hardin, Jacqueline Hetmanski, Eric A. Hoffman, James C. Hogg, John Hokanson, John E. Hokanson, Robert Jensen, Raul San Jose Estepar, Philip F. Judy, Gregory Kinney, Alex Kluiber, Ruthie Knowles, Nan Laird, Christoph Lange, Rochelle Lantz, Sharon M. Lutz, Manuel Mattheisen, Merry Lynn McDonaldc, Alexander McKenzie, Sandra Melanson, John D. Newell, Margaret M. Parker, Randel Plant, Lisa Postow, Delia Prieto, Michael A. Province, Elizabeth A. Regan, John J. Reilly, Stephen I. Rennard, James Rossc, Stephanie Santorico, Joyce D. Schroeder, Jered Sieren, Arkadiusz Sitek, Lori Stepp, Douglas Stinson, E. Rand Sutherland, Duncan C. Thomas, John W. Walsh, Emily S. Wan, Andre Williams, Carla Wilson, Jordan Zach, Jin Zhou, Edwin van Beek

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Abstract

Background: Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.Methods: We divided 2703 GOLD 1-4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%). Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com). Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org).Results: There were no differences in % emphysema (11.4 ± 12.0 vs. 12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs. 36.3 ± 20.6%, p = 0.272) between groups. Mean segmental WA% (63.0 ± 3.2 vs. 62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs. 3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs. 5.17 ± 0.20, p < 0.0001) were greater in the CB + group. Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group. In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB.Conclusions: Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB. These data provide clinical and radiologic correlations to the clinical phenotype of CB.

Original languageEnglish
Article number52
JournalRespiratory Research
Volume15
Issue number1
DOIs
StatePublished - 27 Apr 2014

Bibliographical note

Funding Information:
This study was supported by the NHLBI R01 HL089856 and R01 HL08989. VK is supported by NHLBI K23HL094696-03. VK has participated in clinical trials sponsored by Boehringer Ingelheim, Glaxo-Smith-Kline, and Roche pharmaceuticals. AD, JC, and CHM report no conflicts. APC has been a consultant for VIDA diagnostics. Also, APC has participated in clinical trials sponsored by Boehringer Ingelheim, Glaxo-Smith-Kline, and Astra-Zeneca, and Forest. MKH has participated in advisory boards for Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Genentech, Novartis, and Medimmune; participated on speaker’s bureaus for Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Forest, Grifols therapeutics, and the National Association for Continuing Education, and WebMD; has consulted for Novartis, Ikaria and United Biosource Corporation; and has received royalties from UpToDate and ePocrates. GW has received grants from the NHLBI to perform quantitative image analysis and have been a paid consultant for MedImmune and Spiration, and his spouse is an employee of Merck Research Laboratories. Over the last three years, BJM has participated in advisory boards, speaker bureaus, consultations and multi-center clinical trials with funding from the National Heart Lung and Blood Institute, Abbott, Astellas, AstraZeneca, Boerhinger-Ingelheim, Coviden, Dey, Forest, GlaxoSmithKline, Merck, MedImmune, NABI, Novartis, Pfizer, Respironics, Sepracor, Sequal and Talecris. EKS received grant support from GlaxoSmithKline for studies of COPD genetics, and he received honoraria and consulting fees from AstraZeneca, Merck, and GlaxoSmithKline. DAL’s institution and laboratory receives research support from the National Heart Lung and Blood Institute, Siemens, Inc, Perceptive Imaging, Inc, and Centocor, Inc, Inc. Dr Lynch is a consultant to Perceptive Imaging, Inc, Boehringer Ingelheim, Inc, Genentech, Inc, Gilead, Inc, Veracyte, Inc and Intermune, Inc. GJC has served on Advisory Committees for Boehringer Ingelheim, CSA, Amirall and Holaira. All of these sums are less than $2,500. GJC has received research grants from: Boehringer Ingelheim, AstraZeneca, MedImmune, Pearl, Actelion, Glaxo-Smith-Kline, Forest, Aeris, Therapeutics, Pulmonx and PneumRx. All research grant monies are deposited and controlled by Temple University.

Keywords

  • Airway thickening
  • Asthma
  • Chronic bronchitis
  • Chronic obstructive pulmonary disease

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