title: Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial-American College of Radiology Imaging Network Cohort.
abstract: BACKGROUND
  Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk.
  
  
  OBJECTIVE
  We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4.
  
  
  METHODS
  In the National Lung Screening Trial-ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group).
  
  
  RESULTS
  Compared with those with no airflow limitation, where lung cancer incidence was 3.78/1,000 person years, incidence rates increased in a simple linear relationship: GOLD 1 (6.27/1,000 person yr); GOLD 2 (7.86/1,000 person yr); GOLD 3 (10.71/1,000 person yr); and GOLD 4 (13.25/1,000 person yr). All relationships were significant versus the reference group at a P value of 0.0001 or less.
  
  
  CONCLUSIONS
  In a large prospective study of high-risk cigarette smokers, we report a strong linear relationship between increasing severity of airflow limitation and risk of lung cancer.
authors.affiliation: 1 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 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: 3 Department of Radiology, Comprehensive Cancer Center, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chiles
authors.affiliation: 2 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: 1 Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gamble
authors.affiliation: 4 Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and.
authors.forename: Denise
authors.initials: D
authors.lastname: Aberle
authors.affiliation: 1 Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.|5 School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Young
mesh_terms: D000368:Aged; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000503:physiopathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology*; D013147:Spirometry; D014481:United States / Q000453:epidemiology; D014797:Vital Capacity
keywords: National Lung Screening Trial; airflow limitation; chronic obstructive pulmonary disease; lung cancer; risk