Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 184, Issue 4, Pages 414-420Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.201011-1928OC
Keywords
chronic obstructive pulmonary disease; female; African Americans
Categories
Funding
- Alpha-1 Foundation [U01HL089897, U01HL089856, K01 HL092601]
- National Heart, Lung, and Blood Institute [R01 HL089438]
- Doris Duke Clinical Scientist Development Award
- COPD Foundation
- National Jewish Health
- GlaxoSmithKline (GSK)
- Doris Duke Charitable Foundation
- AZ
- Pfizer
- NABI Biopharmaceuticals
- BI
- Sunovion
- MedImmune
- MRC [G0701127] Funding Source: UKRI
- Medical Research Council [G0701127] Funding Source: researchfish
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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 = 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 = 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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