title: Early-onset chronic obstructive pulmonary disease is associated with female sex, maternal factors, and African American race in the COPDGene Study.
abstract: BACKGROUND
  The characterization of young adults who develop late-onset diseases may augment the detection of novel genes and promote new pathogenic insights.
  
  
  METHODS
  We analyzed data from 2,500 individuals of African and European ancestry in the COPDGene Study. Subjects with severe, early-onset chronic obstructive pulmonary disease (COPD) (n=70, age < 55 yr, FEV1 < 50% predicted) were compared with older subjects with COPD (n =306, age >64 yr, FEV1 <50% predicted).
  
  
  RESULTS
  Subjects with severe, early-onset COPD were predominantly females (66%), P =0.0004. Proportionally,early-onset COPD was seen in 42% (25 of 59) of African Americans versus 14% (45 of 317) of non-Hispanic whites, P <0.0001. Other risk factors included current smoking (56 vs. 17%, P < 0.0001) and self-report of asthma (39 vs. 25%, P =0.008). Maternal smoking (70 vs. 44%, P=0.0001) and maternal COPD (23 vs.12%, P=0.03) were reported more commonly in subjects with early-onset COPD. Multivariable regression analysis found association with African American race, odds ratio (OR), 7.5 (95% confidence interval [CI], 2.3–24; P ¼=0.0007); maternal COPD, OR, 4.7 (95% CI,1.3–17; P=0.02); female sex, OR, 3.1 (95% CI, 1.1–8.7; P=0.03); and each pack-year of smoking, OR, 0.98 (95% CI, 0.96–1.0; P ¼ 0.03).
  
  
  CONCLUSIONS
  These observations support the hypothesis that severe, early-onset COPD is prevalent in females and is influenced by maternal factors. Future genetic studies should evaluate (1) gene-by-sex interactions to address sex-specific genetic contributions and (2) gene-by-race interactions.
authors.affiliation: Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Foreman
authors.forename: Lening
authors.initials: L
authors.lastname: Zhang
authors.forename: James
authors.initials: J
authors.lastname: Murphy
authors.forename: Nadia N
authors.initials: NN
authors.lastname: Hansel
authors.forename: Barry
authors.initials: B
authors.lastname: Make
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: George
authors.initials: G
authors.lastname: Washko
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Regan
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Dawn L
authors.initials: DL
authors.lastname: DeMeo
mesh_terms: D001741:Black or African American; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009035:Mothers; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D012720:Severity of Illness Index; D017678:Sex Distribution; D012907:Smoking