title: Chronic obstructive pulmonary disease exacerbations in the COPDGene study: associated radiologic phenotypes.
abstract: OBJECTIVE
  To test the hypothesis-given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)-that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease.
  
  
  METHODS
  This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a -950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements.
  
  
  RESULTS
  In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047).
  
  
  CONCLUSIONS
  Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes.
authors.affiliation: Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA. mrking@umich.edu
authors.forename: Meilan K
authors.initials: MK
authors.lastname: Han
authors.forename: Ella A
authors.initials: EA
authors.lastname: Kazerooni
authors.forename: David A
authors.initials: DA
authors.lastname: Lynch
authors.forename: Lyrica X
authors.initials: LX
authors.lastname: Liu
authors.forename: Susan
authors.initials: S
authors.lastname: Murray
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Curtis
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Criner
authors.forename: Victor
authors.initials: V
authors.lastname: Kim
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Anzueto
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Make
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed