Clinical and Radiologic Disease in Smokers With Normal Spirometry

Elizabeth A Regan, David A Lynch, Douglas Curran-Everett, Jeffrey L Curtis, John H M Austin, Philippe A Grenier, Hans-Ulrich Kauczor, William C Bailey, Dawn L DeMeo, Richard H Casaburi, Paul Friedman, Edwin J R Van Beek, John E Hokanson, Russell P Bowler, Terri H Beaty, George R Washko, MeiLan K Han, Victor Kim, Song Soo Kim, Kunihiro Yagihashi, Lacey Washington, Charlene E McEvoy, Clint Tanner, David M Mannino, Barry J Make, Edwin K Silverman, James D Crapo, Genetic Epidemiology of COPD (COPDGene) Investigators, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, 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, Adel El-Bouiez, Peter Castaldi, Megan Hardin, Dandi Qiao, Elizabeth Regan, Eitan Halper-Stromberg, Ferdouse Begum, Sungho Won, Brittney Fredericksen, Sharon Lutz, David A Lynch, Harvey O Coxson, MeiLan K Han, Eric A Hoffman, Stephen HumphriesMS, Francine L Jacobson, Philip F Judy, Ella A Kazerooni, John D Newell Jr, Elizabeth Regan, James C Ross, Raul San Jose Estepar, Berend C Stoel, Juerg Tschirren, Eva van Rikxoort, Bramvan 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, Jennifer Black-Shinn, Gregory Kinney, Sharon Lutz, Katherine Pratte, Jeffrey Curtis, Carlos Martinez, Perry G Pernicano, Nicola Hanania, Philip Alapat, Venkata Bandi, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Arun Nachiappan, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, R Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Gregory D N Pearson, Anna Rozenshtein, Neil MacIntyre Jr, Lacey Washington, H Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, Robert Brown, Karen Horton, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Janos Porszasz, Hans Fischer, Matthew Budoff, Dan Cannon, Harry Rossiter, Michael E DeBakey, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Robert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A James Mamary, Nathaniel Marchetti, Aditti Satti, Kartik Shenoy, Robert M Steiner, Alex Swift, Irene Swift, Gloria 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 Jr, Brad Thompson, MeiLan Han, Ella Kazerooni, Fernando 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, Elizabeth A Regan, David A Lynch, Douglas Curran-Everett, Jeffrey L Curtis, John H M Austin, Philippe A Grenier, Hans-Ulrich Kauczor, William C Bailey, Dawn L DeMeo, Richard H Casaburi, Paul Friedman, Edwin J R Van Beek, John E Hokanson, Russell P Bowler, Terri H Beaty, George R Washko, MeiLan K Han, Victor Kim, Song Soo Kim, Kunihiro Yagihashi, Lacey Washington, Charlene E McEvoy, Clint Tanner, David M Mannino, Barry J Make, Edwin K Silverman, James D Crapo, Genetic Epidemiology of COPD (COPDGene) Investigators, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, 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, Adel El-Bouiez, Peter Castaldi, Megan Hardin, Dandi Qiao, Elizabeth Regan, Eitan Halper-Stromberg, Ferdouse Begum, Sungho Won, Brittney Fredericksen, Sharon Lutz, David A Lynch, Harvey O Coxson, MeiLan K Han, Eric A Hoffman, Stephen HumphriesMS, Francine L Jacobson, Philip F Judy, Ella A Kazerooni, John D Newell Jr, Elizabeth Regan, James C Ross, Raul San Jose Estepar, Berend C Stoel, Juerg Tschirren, Eva van Rikxoort, Bramvan 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, Jennifer Black-Shinn, Gregory Kinney, Sharon Lutz, Katherine Pratte, Jeffrey Curtis, Carlos Martinez, Perry G Pernicano, Nicola Hanania, Philip Alapat, Venkata Bandi, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Arun Nachiappan, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, R Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Gregory D N Pearson, Anna Rozenshtein, Neil MacIntyre Jr, Lacey Washington, H Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, Robert Brown, Karen Horton, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Janos Porszasz, Hans Fischer, Matthew Budoff, Dan Cannon, Harry Rossiter, Michael E DeBakey, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Robert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A James Mamary, Nathaniel Marchetti, Aditti Satti, Kartik Shenoy, Robert M Steiner, Alex Swift, Irene Swift, Gloria 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 Jr, Brad Thompson, MeiLan Han, Ella Kazerooni, Fernando 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

Abstract

Importance: Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free.

Objective: To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0.

Design, setting, and participants: Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011.

Main outcomes and measures: Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life.

Results: One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P < .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease.

Conclusions and relevance: Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.

Conflict of interest statement

Conflict of Interest Disclosures: Unrelated to the present work, Dr Kauczor reported receiving grants, personal fees, and nonfinancial support from Siemens; grants and personal fees from Boehringer Ingelheim; personal fees and nonfinancial support from Bayer; and personal fees from Novartis, Almirall, and GlaxoSmithKline. No other disclosures were reported.

Figures

Figure 1. With Advancing Age, Current Smoking…
Figure 1. With Advancing Age, Current Smoking Decreases, and Emphysema and Gas Trapping Increase in the Global Initiative for Obstructive Lung Disease (GOLD) 0 Group
A, Current or former smoking status was assessed in the GOLD 0 group by self-report. The percentage of individuals reporting current or former smoking in each age category is shown and demonstrates steady declines in current smoking with advancing age. Individuals were not surveyed about their reasons for smoking cessation. B, The presence of emphysema and gas trapping was determined for each participant. Individuals with emphysema (>5%) or gas trapping (>20%) were identified by age group. Overall, 20.1% (744 of 3708) of the GOLD 0 group had abnormal emphysema or gas trapping. After age 75 years, 65.3% (382 of 585) of current and former smokers had radiologic evidence of disease. The increase in emphysema or gas trapping by advancing age group (P < .001 for both, Cochran-Armitage test for trend) supports the hypothesis that imaging changes are later manifestations of smoking-related lung disease. The age-related pattern is present in current and former smokers (P < .001 for both, Cochran-Armitage test for trend).
Figure 2. Evidence of Occult Obstructive Disease…
Figure 2. Evidence of Occult Obstructive Disease in the Global Initiative for Obstructive Lung Disease (GOLD)0 Group
Histograms of prebronchodilator forced expiratory volume in the first second of expiration (FEV1) percent predicted values in the Genetic Epidemiology of COPD (COPDGene) cohort and the 2007 to 2010 National Health and Nutrition Examination Survey (NHANES) cohort, segregated by never smokers, GOLD 0 smokers, and GOLD 1 smokers. The black bar in each graph demarcates the mean for that group. For visual clarity, graphs were minimally truncated above 135% of the FEV1 percentage predicted. Individual panels represent the distributions of prebronchodilator FEV1 percent predicted in the 6 groups. COPD indicates chronic obstructive pulmonary disease.

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Source: PubMed

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