title: Phenotype of Spirometric Impairment in an Aging Population.
abstract: BACKGROUND
  The Global Lung Initiative (GLI) provides age-appropriate criteria for establishing spirometric impairment, including mild, moderate, and severe chronic obstructive pulmonary disease (COPD) and restrictive pattern, but its association with respiratory-related phenotypes has not been evaluated.
  
  
  OBJECTIVE
  To evaluate respiratory-related phenotypes in GLI-defined spirometric impairment.
  
  
  METHODS
  In COPDGene (N = 10,131 patients; age range, 45-81 yr; average smoking history, 44.3 pack-years), we evaluated spirometry, dyspnea (modified Medical Research Council grade, ≥2), poor respiratory health-related quality of life (St. George's Respiratory Questionnaire total score, ≥25), poor exercise performance (6-minute-walk distance, <391 m), bronchodilator reversibility (FEV1 change, >12% and ≥200 ml), and computed tomography-diagnosed emphysema and gas trapping (>5% and >15% of lung, respectively).
  
  
  RESULTS
  GLI established normal spirometry in 5,100 patients (50.3%), mild COPD in 669 (6.6%), moderate COPD in 865 (8.5%), severe COPD in 2,522 (24.9%), and restrictive pattern in 975 (9.6%). Relative to normal spirometry, graded associations with respiratory-related phenotypes were found for mild, moderate, and severe COPD, with respective adjusted odds ratios (95% confidence intervals) as follows: dyspnea-1.31 (1.10-1.56), 2.20 (1.81-2.68), and 10.73 (8.04-14.33); poor respiratory health-related quality of life-1.49 (1.28-1.75), 2.69 (2.08-3.47), and 14.61 (10.09-21.17); poor exercise performance-1.11 (0.94-1.31), 1.58 (1.33-1.88), and 4.58 (3.42-6.12); bronchodilator reversibility-2.76 (2.24-3.40), 5.18 (4.29-6.27), and 6.21 (5.06-7.62); emphysema-4.86 (3.16-7.47), 6.41 (4.09-10.05), and 17.79 (10.79-29.32); and gas trapping-3.92 (3.12-4.93), 5.20 (3.82-7.07), and 16.28 (9.71-27.30). Restrictive pattern was also associated with multiple respiratory-related phenotypes at a level similar to moderate COPD, but it was otherwise not associated with emphysema (0.89 [0.60-1.32]) or gas trapping (1.15 [0.92-1.42]).
  
  
  CONCLUSIONS
  GLI-defined spirometric impairment establishes clinically meaningful respiratory disease, as validated by graded associations with respiratory-related phenotypes.
authors.affiliation: 1 Veterans Affairs Clinical Epidemiology Research Center, West Haven, Connecticut.|2 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Vaz Fragoso
authors.affiliation: 2 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Gail
authors.initials: G
authors.lastname: McAvay
authors.affiliation: 2 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Van Ness
authors.affiliation: 3 Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Casaburi
authors.affiliation: 4 LDS Hospital and University of Utah, Salt Lake City, Utah; and.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jensen
authors.affiliation: 5 Division of Pulmonary and Critical Care Medicine, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Neil
authors.initials: N
authors.lastname: MacIntyre
authors.affiliation: 1 Veterans Affairs Clinical Epidemiology Research Center, West Haven, Connecticut.|2 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: H Klar
authors.initials: HK
authors.lastname: Yaggi
authors.affiliation: 2 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Gill
authors.affiliation: 1 Veterans Affairs Clinical Epidemiology Research Center, West Haven, Connecticut.|2 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: John
authors.initials: J
authors.lastname: Concato
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D015897:Comorbidity; D004417:Dyspnea / Q000175:diagnosis / Q000209:etiology*; D004646:Emphysema / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000209:etiology*; D005080:Exercise Test; D005260:Female; D005540:Forced Expiratory Flow Rates; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000145:classification / Q000150:complications / Q000235:genetics*; D011788:Quality of Life; D012015:Reference Standards; D012720:Severity of Illness Index; D012907:Smoking; D013147:Spirometry / Q000592:standards; D014057:Tomography, X-Ray Computed; D014481:United States
keywords: chronic obstructive pulmonary disease; emphysema; restriction