title: Phenotype of normal spirometry in an aging population.
abstract: BACKGROUND
  In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]).
  
  
  OBJECTIVE
  To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories.
  
  
  METHODS
  Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm).
  
  
  RESULTS
  Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories.
  
  
  CONCLUSIONS
  GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the normal range for multiple phenotypes. These results suggest that among adults with GLI-defined normal spirometry, GOLD may misclassify normal phenotypes as having respiratory impairment.
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: 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: H Klar
authors.initials: HK
authors.lastname: Yaggi
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; D000402:Airway Obstruction / Q000175:diagnosis; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000235:genetics*; D011656:Pulmonary Emphysema / Q000175:diagnosis; D011788:Quality of Life; D013147:Spirometry / Q000592:standards
keywords: COPD; COPDGene; emphysema; normal spirometry; phenotype