Epidemiology, radiology, and genetics of nicotine dependence in COPD

Deog Kyeom Kim, Craig P Hersh, George R Washko, John E Hokanson, David A Lynch, John D Newell, James R Murphy, James D Crapo, Edwin K Silverman, COPD Gene Investigators, Jeffrey Curtis, Ella Kazerooni, Nicola Hanania, Philip Alapat, Venkata Bandi, Kalpalatha Guntupalli, Elizabeth Guy, Antara Mallampalli, Charles Trinh, Mustafa Atik, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, R Graham Barr, Byron Thomashow, John Austin, Neil MacIntyre Jr, Lacey Washington, H Page McAdams, Richard Rosiello, Timothy Bresnahan, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, Robert Brown, Gregory Diette, Richard Casaburi, Janos Porszasz, Hans Fischer, Matt Budoff, Amir Sharafkhaneh, Charles Trinh, Hirani Kamal, Roham Darvishi, Dennis Niewoehner, Tadashi Allen, Quentin Anderson, Kathryn Rice, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, Adam Friedlander, David Lynch, Joyce Schroeder, John Newell Jr, Gerard Criner, Victor Kim, Nathaniel Marchetti, Aditi Satti, A James Mamary, Robert Steiner, Chandra Dass, William Bailey, Mark Dransfield, Hrudaya Nath, Joe Ramsdell, Paul Friedman, Geoffrey McLennan, Edwin J R van Beek, Brad Thompson, Dwight Look, Fernando Martinez, MeiLan Han, Ella Kazerooni, Christine Wendt, Tadashi Allen, Frank Sciurba, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Antonio Anzueto, Sandra Adams, Carlos Orozco, Mario Ruiz, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Jonathan Samet, Sarah Moyle, Douglas Stinson, Terri Beaty, Barbara Klanderman, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John Hokanson, Dawn DeMeo, Nadia Hansel, Jacqueline Hetmanski, Tanda Murray, Edwin Silverman, David Lynch, Joyce Schroeder, John Newell Jr, John Reilly, Harvey Coxson, Philip Judy, Eric Hoffman, Raul San Jose Estepar, James Ross, Rebecca Leek, Jordan Zach, Alex Kluiber, Jered Sieren, Heather Baumhauer, Verity McArthur, Dzimitry Kazlouski, Andrew Allen, Tanya Mann, Robert Jensen, Homayoon Farzadegan, Stacey Meyerer, Shivam Chandan, Samantha Bragan, James Murphy, Douglas Everett, Ruthie Knowles, Amber Powell, Carla Wilson, John Hokanson, Jennifer Black-Shinn, Gregory Kinney, Deog Kyeom Kim, Craig P Hersh, George R Washko, John E Hokanson, David A Lynch, John D Newell, James R Murphy, James D Crapo, Edwin K Silverman, COPD Gene Investigators, Jeffrey Curtis, Ella Kazerooni, Nicola Hanania, Philip Alapat, Venkata Bandi, Kalpalatha Guntupalli, Elizabeth Guy, Antara Mallampalli, Charles Trinh, Mustafa Atik, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, R Graham Barr, Byron Thomashow, John Austin, Neil MacIntyre Jr, Lacey Washington, H Page McAdams, Richard Rosiello, Timothy Bresnahan, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, Robert Brown, Gregory Diette, Richard Casaburi, Janos Porszasz, Hans Fischer, Matt Budoff, Amir Sharafkhaneh, Charles Trinh, Hirani Kamal, Roham Darvishi, Dennis Niewoehner, Tadashi Allen, Quentin Anderson, Kathryn Rice, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, Adam Friedlander, David Lynch, Joyce Schroeder, John Newell Jr, Gerard Criner, Victor Kim, Nathaniel Marchetti, Aditi Satti, A James Mamary, Robert Steiner, Chandra Dass, William Bailey, Mark Dransfield, Hrudaya Nath, Joe Ramsdell, Paul Friedman, Geoffrey McLennan, Edwin J R van Beek, Brad Thompson, Dwight Look, Fernando Martinez, MeiLan Han, Ella Kazerooni, Christine Wendt, Tadashi Allen, Frank Sciurba, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Antonio Anzueto, Sandra Adams, Carlos Orozco, Mario Ruiz, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Jonathan Samet, Sarah Moyle, Douglas Stinson, Terri Beaty, Barbara Klanderman, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John Hokanson, Dawn DeMeo, Nadia Hansel, Jacqueline Hetmanski, Tanda Murray, Edwin Silverman, David Lynch, Joyce Schroeder, John Newell Jr, John Reilly, Harvey Coxson, Philip Judy, Eric Hoffman, Raul San Jose Estepar, James Ross, Rebecca Leek, Jordan Zach, Alex Kluiber, Jered Sieren, Heather Baumhauer, Verity McArthur, Dzimitry Kazlouski, Andrew Allen, Tanya Mann, Robert Jensen, Homayoon Farzadegan, Stacey Meyerer, Shivam Chandan, Samantha Bragan, James Murphy, Douglas Everett, Ruthie Knowles, Amber Powell, Carla Wilson, John Hokanson, Jennifer Black-Shinn, Gregory Kinney

Abstract

Background: Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers.

Methods: Current smokers with COPD (GOLD stage ≥ 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes.

Results: Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p < .0001) as well as in COPD cases (ρ = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers.

Conclusions: Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.

Trial registration: ClinicalTrials.gov NCT00608764.

Figures

Figure 1
Figure 1
The correlation of FTND score with emphysema severity on chest CT in controls (left; log (%emphysema) = 4.33-(0.09 × FTND score), p < .0001) and COPD subjects (right; log (%emphysema) = 5.87-(0.10 × FTND score), p = 0.0008).

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