Early-Onset Chronic Obstructive Pulmonary Disease Is Associated with Female Sex, Maternal Factors, and African American Race in the COPDGene Study

Abstract

Rationale: The characterization of young adults who develop lateonset 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 ¼ 70, age , 55 yr, FEV 1 , 50% predicted) were compared with older subjects with COPD (n ¼ 306, age . 64 yr, FEV 1 , 50% predicted). Measurements and Main Results: Subjects with severe, early-onset COPD were predominantly females (66%), P ¼ 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 ¼ 0.008). Maternal smoking (70 vs. 44%, P ¼ 0.0001) and maternal COPD (23 vs. 12%, P ¼ 0.03) were reported more commonly in subjects with earlyonset 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 ¼ 0.02); female sex, OR, 3.1 (95% CI, 1.1-8.7; P ¼ 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.Keywords: chronic obstructive pulmonary disease; female; African Americans Chronic obstructive pulmonary disease (COPD) is typically a disease that presents in late adulthood, often associated with cigarette smoking (1, 2). Although the prevalence of COPD has been changing, COPD is more prevalent in individuals older than 65 years of age (3). Previously considered a disease affecting primarily males, the prevalence of COPD in women and the number of women dying from COPD have increased (4). Maturity-onset diseases are complex; they may have multiple causes with contributions from environmental exposures, comorbidities, age-related degenerative changes, and genetic factors. Diseases occurring at an earlier age than traditionally expected may result from the interaction of inherited factors and environmental exposures.In 1998, a family-based cohort composed of 44 probands with severe, early-onset COPD recruited from specialized programs in lung transplantation, lung volume reduction surgery, and local pulmonary clinics and 249 first-or second-degree relatives was reported (5). Eligibility criteria for inclusion as a proband included the following: (1) age not greater than 52 years, (2) the absence of severe a 1 -antitrypsin deficiency, and (3) FEV 1 less than 40% predicted. This first report was notable for the high percentage of female probands (80%). However, whether earlyonset COPD is a specific phenotype and whether it is a ...

Telomerase and the Genetics of Emphysema Susceptibility. Implications for Pathogenesis Paradigms and Patient Care

“…In the vast majority of patients, cigarette smoke is the culprit, highlighting the importance of prevention efforts (1,4). In some cases, even after minimal cigarette smoke exposure, severe emphysema develops at a young age, as early as the fifth decade (5,6). Several pieces of evidence support a genetic etiology for these cases (7).…”

“…For example, in addition to severe, young-onset disease, emphysema may cluster in families (5,6). In familial cases, airspace destruction is frequently the predominant phenotype and occurs in the absence of significant airway obstruction, suggesting that emphysema may be a definable heritable trait that is separable from chronic obstructive pulmonary disease (COPD) (5)(6)(7). This article reviews the emerging role of telomerase and telomere abnormalities in driving emphysema susceptibility.…”

The raising epidemic of COPD in women

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The View of the Turkish Thoracic Society on the Report of the GOLD 2017 Global Strategy for the Diagnosis, Management, and Prevention of COPD

“…The socioeconomic status may be linked to a child's birth weight. Although controversial, some studies have suggested that women are susceptible to tobacco smoke [10][11][12].…”