title: Clinical and Radiologic Disease in Smokers With Normal Spirometry.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: National Jewish Health, Denver, Colorado2Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Regan
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: David A
authors.initials: DA
authors.lastname: Lynch
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: Douglas
authors.initials: D
authors.lastname: Curran-Everett
authors.affiliation: 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.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Curtis
authors.affiliation: Department of Radiology, Columbia University Medical Center, New York, New York.
authors.forename: John H M
authors.initials: JH
authors.lastname: Austin
authors.affiliation: Department of Diagnostic Radiology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Grenier
authors.affiliation: Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Kauczor
authors.affiliation: Translational Lung Research Center Heidelberg, German Center of Lung Research, University of Alabama, Birmingham.
authors.forename: William C
authors.initials: WC
authors.lastname: Bailey
authors.affiliation: Pulmonary and Critical Care, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: DeMeo
authors.affiliation: Division of Respiratory and Critical Care Physiology and Medicine, Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles, Medical Center, Torrance.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Casaburi
authors.affiliation: Department of Radiology, University of California, San Diego.
authors.forename: Paul
authors.initials: P
authors.lastname: Friedman
authors.affiliation: Department of Radiology, University of Edinburgh, Edinburgh, Scotland.
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: Van Beek
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora.
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.affiliation: Pulmonary and Critical Care, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor.
authors.forename: MeiLan K
authors.initials: MK
authors.lastname: Han
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University, Philadelphia, Pennsylvania.
authors.forename: Victor
authors.initials: V
authors.lastname: Kim
authors.affiliation: Department of Radiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Song Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Radiology, St Marianna University School of Medicine, Sugao, Miyamaeku, Kawasaki, Kanagawa, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yagihashi
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Lacey
authors.initials: L
authors.lastname: Washington
authors.affiliation: Pulmonary Medicine, HealthPartners, Minneapolis-St Paul, Minnesota.
authors.forename: Charlene E
authors.initials: CE
authors.lastname: McEvoy
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: Clint
authors.initials: C
authors.lastname: Tanner
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Preventive Medicine and Environmental Health, College of Public Health, University of Kentucky, Lexington.
authors.forename: David M
authors.initials: DM
authors.lastname: Mannino
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Make
authors.affiliation: Pulmonary and Critical Care, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000209:etiology; D011788:Quality of Life; D013902:Radiography, Thoracic; D012907:Smoking / Q000009:adverse effects*; D013147:Spirometry; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology