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Original Investigation |

Clinical and Radiologic Disease in Smokers With Normal Spirometry

Elizabeth A. Regan, MD1,2; David A. Lynch, MD1; Douglas Curran-Everett, PhD1; Jeffrey L. Curtis, MD3,4; John H. M. Austin, MD5; Philippe A. Grenier, MD6; Hans-Ulrich Kauczor, MD7; William C. Bailey, MD8; Dawn L. DeMeo, MD9; Richard H. Casaburi, PhD, MD10; Paul Friedman, MD11; Edwin J. R. Van Beek, MD12; John E. Hokanson, PhD2; Russell P. Bowler, MD1; Terri H. Beaty, PhD13; George R. Washko, MD9; MeiLan K. Han, MD4; Victor Kim, MD14; Song Soo Kim, MD15; Kunihiro Yagihashi, MD16; Lacey Washington, MD17; Charlene E. McEvoy, MD18; Clint Tanner, MD1; David M. Mannino, MD19; Barry J. Make, MD1; Edwin K. Silverman, MD9; James D. Crapo, MD1 ; for the Genetic Epidemiology of COPD (COPDGene) Investigators
[+] Author Affiliations
1National Jewish Health, Denver, Colorado
2Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora
3Section of Pulmonary and Critical Care Medicine, Medical Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan
4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor
5Department of Radiology, Columbia University Medical Center, New York, New York
6Department of Diagnostic Radiology, Hôpital Pitié-Salpêtrière, Assistance Publique–Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France
7Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
8Translational Lung Research Center Heidelberg, German Center of Lung Research, University of Alabama, Birmingham
9Pulmonary and Critical Care, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
10Division of Respiratory and Critical Care Physiology and Medicine, Los Angeles Biomedical Research Institute, Harbor–University of California, Los Angeles, Medical Center, Torrance
11Department of Radiology, University of California, San Diego
12Department of Radiology, University of Edinburgh, Edinburgh, Scotland
13Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
14Section of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University, Philadelphia, Pennsylvania
15Department of Radiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea
16Department of Radiology, St Marianna University School of Medicine, Sugao, Miyamaeku, Kawasaki, Kanagawa, Japan
17Department of Radiology, Duke University Medical Center, Durham, North Carolina
18Pulmonary Medicine, HealthPartners, Minneapolis–St Paul, Minnesota
19Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Preventive Medicine and Environmental Health, College of Public Health, University of Kentucky, Lexington
JAMA Intern Med. 2015;175(9):1539-1549. doi:10.1001/jamainternmed.2015.2735.
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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.

Figures in this Article


Place holder to copy figure label and caption
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).

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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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