title: Airflow Limitation and Histology Shift in the National Lung Screening Trial. The NLST-ACRIN Cohort Substudy.
abstract: BACKGROUND
  Annual computed tomography (CT) is now widely recommended for lung cancer screening in the United States, although concerns remain regarding the potential harms, including those from overdiagnosis.
  
  
  OBJECTIVE
  To examine the effect of airflow limitation on overdiagnosis by comparing lung cancer incidence, histology, and stage shift in a subgroup of the National Lung Screening Trial (NLST).
  
  
  METHODS
  In an NLST subgroup (n = 18,714), screening participants were randomized to annual computed tomography (CT, n = 9,357) or chest radiograph (n = 9,357) screening and monitored for a mean of 6.1 years. After baseline prebronchodilator spirometry, to identify the presence of airflow limitation, 18,475 subjects (99%) were assigned as having chronic obstructive pulmonary disease (COPD) or no COPD. Lung cancer prevalence, incidence, histology, and stage shift were compared after stratification by COPD.
  
  
  RESULTS
  For screening participants with spirometric COPD (n = 6,436), there was a twofold increase in lung cancer incidence (incident rate ratio, 2.15; P < 0.001) and, when compared according to screening arm, no excess lung cancers and comparable histology. Compared with chest radiography, there was also a trend favoring reduced late-stage and increased early-stage cancers in the CT arm (P = 0.054). For those with normal baseline spirometry (n = 12,039), we found an excess of lung cancers during screening in the CT arm, almost exclusively early-stage adenocarcinoma-related cancers (histology shift and overdiagnosis). After correction for these excess cancers, stage shift was marginal (P = 0.077).
  
  
  CONCLUSIONS
  In the CT arm of the NLST-ACRIN (American College of Radiology Imaging Network) cohort, COPD status was associated with a doubling of lung cancer incidence, no apparent overdiagnosis, and a more favorable stage shift.
authors.affiliation: 1 School of Biological Sciences and.|2 Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Young
authors.affiliation: 3 Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors.forename: Fenghai
authors.initials: F
authors.lastname: Duan
authors.affiliation: 4 Department of Radiology, Comprehensive Cancer Center, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina; and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chiles
authors.affiliation: 2 Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Raewyn J
authors.initials: RJ
authors.lastname: Hopkins
authors.affiliation: 2 Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gamble
authors.affiliation: 3 Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Greco
authors.affiliation: 3 Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors.forename: Constantine
authors.initials: C
authors.lastname: Gatsonis
authors.affiliation: 5 Department of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
authors.forename: Denise
authors.initials: D
authors.lastname: Aberle
mesh_terms: D015331:Cohort Studies; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000453:epidemiology*; D008297:Male; D008403:Mass Screening / Q000379:methods* / Q000706:statistics & numerical data*; D008875:Middle Aged; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology
keywords: National Lung Screening Trial; airflow limitation; chronic obstructive pulmonary disease; overdiagnosis; stage shift