Early-onset chronic obstructive pulmonary disease is associated with female sex, maternal factors, and African American race in the COPDGene Study
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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 (1/4)=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 (1/4) 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.
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