Early-onset chronic obstructive pulmonary disease is associated with female sex, maternal factors, and African American race in the COPDGene Study.

RATIONALE 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). MEASUREMENTS AND MAIN 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.