title: Clinical and radiographic predictors of GOLD-unclassified smokers in the COPDGene study.
abstract: BACKGROUND
  A significant proportion of smokers have lung function impairment characterized by a reduced FEV(1) with a preserved FEV(1)/FVC ratio. These smokers are a poorly characterized group due to their systematic exclusion from chronic obstructive pulmonary disease (COPD) studies.
  
  
  OBJECTIVE
  To characterize the clinical, functional, and radiographic features of Global Initiative for Chronic Obstructive Lung Disease (GOLD)-Unclassified (FEV(1)/FVC ≥ 0.7 and FEV(1) < 80% predicted) and lower limits of normal (LLN)-unclassified (FEV(1)/FVC ≥ LLN and FEV(1) < LLN) subjects compared to smokers with normal lung function and subjects with COPD.
  
  
  METHODS
  Data from the first 2,500 subjects enrolled in the COPDGene study were analyzed. All subjects had 10 or more pack-years of smoking and were between the ages of 45 and 80 years. Multivariate regression models were constructed to determine the clinical and radiological variables associated with GOLD-Unclassified (GOLD-U) and LLN-Unclassified status. Separate multivariate regressions were performed in the subgroups of subjects with complete radiologic measurement variables available.
  
  
  RESULTS
  GOLD-U smokers account for 9% of smokers in COPDGene and have increased body mass index (BMI), a disproportionately reduced total lung capacity, and a higher proportion of nonwhite subjects and subjects with diabetes. GOLD-U subjects exhibit increased airway wall thickness compared to smoking control subjects and decreased gas trapping and bronchodilator responsiveness compared to subjects with COPD. When LLN criteria were used to define the "unclassified" group, African American subjects were no longer overrepresented. Both GOLD-U and LLN-Unclassified subjects demonstrated a wide range of lung function impairment, BMI, and percentage of total lung emphysema.
  
  
  CONCLUSIONS
  Subjects with reduced FEV(1) and a preserved FEV(1)/FVC ratio are a heterogeneous group with significant symptoms and functional limitation who likely have a variety of underlying etiologies beyond increased BMI. Clinical trial registered with www.clinicaltrials.gov (NCT000608764).
authors.affiliation: Channing Laboratory and Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA. reesw@channing.harvard.edu
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wan
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: James R
authors.initials: JR
authors.lastname: Murphy
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Regan
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Make
authors.forename: David A
authors.initials: DA
authors.lastname: Lynch
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000145:classification* / Q000175:diagnosis / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging; D012907:Smoking / Q000503:physiopathology*; D013147:Spirometry; D014057:Tomography, X-Ray Computed; D014109:Total Lung Capacity; D014797:Vital Capacity