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JAMA Intern Med. 2015 Sep;175(9):1539-49. doi: 10.1001/jamainternmed.2015.2735.

Clinical and Radiologic Disease in Smokers With Normal Spirometry.

Collaborators (162)

Crapo J, Silverman E, Make B, Regan E, Beaty T, Laird N, Lange C, Cho M, Santorico S, Hokanson J, DeMeo D, Hansel N, Hersh C, Castaldi P, McDonald ML, Wan E, Hardin M, Hetmanski J, Parker M, Foreman M, Hobbs B, Busch R, El-Bouiez A, Castaldi P, Hardin M, Qiao D, Regan E, Halper-Stromberg E, Begum F, Won S, Fredericksen B, Lutz S, Lynch DA, Coxson HO, Han MK, Hoffman EA, HumphriesMS S, Jacobson FL, Judy PF, Kazerooni EA, Newell JD Jr, Regan E, Ross JC, Estepar RS, Stoel BC, Tschirren J, van Rikxoort E, Ginneken B, Washko G, Wilson CG, Qaisi MA, Gray T, Kluiber A, Mann T, Sieren J, Stinson D, Schroeder J, Van Beek E, Jensen R, Everett D, Faino A, Strand M, Wilson C, Hokanson JE, Black-Shinn J, Kinney G, Lutz S, Pratte K, Curtis J, Martinez C, Pernicano PG, Hanania N, Alapat P, Bandi V, Atik M, Boriek A, Guntupalli K, Guy E, Parulekar A, Nachiappan A, DeMeo D, Hersh C, Washko G, Jacobson F, Barr R, Thomashow B, Austin J, D'Souza B, Pearson GD, Rozenshtein A, MacIntyre N Jr, Washington L, McAdams H, McEvoy C, Tashjian J, Wise R, Hansel N, Brown R, Horton K, Putcha N, Casaburi R, Adami A, Porszasz J, Fischer H, Budoff M, Cannon D, Rossiter H, DeBakey ME, Sharafkhaneh A, Lan C, Wendt C, Bell B, Foreman M, Westney G, Berkowitz E, Bowler R, Lynch D, Rosiello R, Pace D, Criner G, Ciccolella D, Cordova F, Dass C, D'Alonzo R, Desai P, Jacobs M, Kelsen S, Kim V, Mamary A, Marchetti N, Satti A, Shenoy K, Steiner RM, Swift A, Swift I, Vega-Sanchez G, Dransfield M, Bailey W, Wells JM, Bhatt S, Nath H, Ramsdell J, Friedman P, Soler X, Yen A, Cornellas A, Newell J Jr, Thompson B, Han M, Kazerooni E, Martinez F, Billings J, Allen T, Sciurba F, Chandra D, Weissfeld J, Fuhrman C, Bon J, Anzueto A, Adams S, Maselli-Caceres D, Ruiz ME.

Author information

National Jewish Health, Denver, Colorado2Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora.
National Jewish Health, Denver, Colorado.
Section of Pulmonary and Critical Care Medicine, Medical Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, An.
Department of Radiology, Columbia University Medical Center, New York, New York.
Department of Diagnostic Radiology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.
Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany.
Translational Lung Research Center Heidelberg, German Center of Lung Research, University of Alabama, Birmingham.
Pulmonary and Critical Care, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Respiratory and Critical Care Physiology and Medicine, Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles, Medical Center, Torrance.
Department of Radiology, University of California, San Diego.
Department of Radiology, University of Edinburgh, Edinburgh, Scotland.
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor.
Section of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University, Philadelphia, Pennsylvania.
Department of Radiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea.
Department of Radiology, St Marianna University School of Medicine, Sugao, Miyamaeku, Kawasaki, Kanagawa, Japan.
Department of Radiology, Duke University Medical Center, Durham, North Carolina.
Pulmonary Medicine, HealthPartners, Minneapolis-St Paul, Minnesota.
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Preventive Medicine and Environmental Health, College of Public Health, University of Kentucky, Lexington.



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.


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.


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.


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


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.


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.

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