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1.
Article in English | MEDLINE | ID: mdl-38708410

ABSTRACT

Aim: Increasing evidence suggests that the inclusion of self-identified race in clinical decision algorithms may perpetuate longstanding inequities. Until recently, most pulmonary function tests utilized separate reference equations that are race/ethnicity based. Purpose: We assess the magnitude and scope of the available literature on the negative impact of race-based pulmonary function prediction equations on relevant outcomes in African Americans with COPD. Methods: We performed a scoping review utilizing an English language search on PubMed/Medline, Embase, Scopus, and Web of Science in September 2022 and updated it in December 2023. We searched for publications regarding the effect of race-specific vs race-neutral, race-free, or race-reversed lung function testing algorithms on the diagnosis of COPD and COPD-related physiologic and functional measures. Joanna Briggs Institute (JBI) guidelines were utilized for this scoping review. Eligibility criteria: The search was restricted to adults with COPD. We excluded publications on other lung disorders, non-English language publications, or studies that did not include African Americans. The search identified publications. Ultimately, six peer-reviewed publications and four conference abstracts were selected for this review. Results: Removal of race from lung function prediction equations often had opposite effects in African Americans and Whites, specifically regarding the severity of lung function impairment. Symptoms and objective findings were better aligned when race-specific reference values were not used. Race-neutral prediction algorithms uniformly resulted in reclassifying severity in the African Americans studied. Conclusion: The limited literature does not support the use of race-based lung function prediction equations. However, this assertion does not provide guidance for every specific clinical situation. For African Americans with COPD, the use of race-based prediction equations appears to fall short in enhancing diagnostic accuracy, classifying severity of impairment, or predicting subsequent clinical events. We do not have information comparing race-neutral vs race-based algorithms on prediction of progression of COPD. We conclude that the elimination of race-based reference values potentially reduces underestimation of disease severity in African Americans with COPD.


Subject(s)
Black or African American , Lung , Pulmonary Disease, Chronic Obstructive , Respiratory Function Tests , Humans , Algorithms , Health Status Disparities , Healthcare Disparities/ethnology , Lung/physiopathology , Predictive Value of Tests , Prognosis , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/ethnology , Race Factors , Adult
5.
Am J Respir Crit Care Med ; 209(1): 59-69, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37611073

ABSTRACT

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.


Subject(s)
Airway Obstruction , Pulmonary Disease, Chronic Obstructive , Humans , Nutrition Surveys , Cross-Sectional Studies , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Dyspnea/diagnosis , Spirometry , Forced Expiratory Volume
6.
J Gen Intern Med ; 38(13): 2988-2997, 2023 10.
Article in English | MEDLINE | ID: mdl-37072532

ABSTRACT

BACKGROUND: COPD diagnosis is tightly linked to the fixed-ratio spirometry criteria of FEV1/FVC < 0.7. African-Americans are less often diagnosed with COPD. OBJECTIVE: Compare COPD diagnosis by fixed-ratio with findings and outcomes by race. DESIGN: Genetic Epidemiology of COPD (COPDGene) (2007-present), cross-sectional comparing non-Hispanic white (NHW) and African-American (AA) participants for COPD diagnosis, manifestations, and outcomes. SETTING: Multicenter, longitudinal US cohort study. PARTICIPANTS: Current or former smokers with ≥ 10-pack-year smoking history enrolled at 21 clinical centers including over-sampling of participants with known COPD and AA. Exclusions were pre-existing non-COPD lung disease, except for a history of asthma. MEASUREMENTS: Subject diagnosis by conventional criteria. Mortality, imaging, respiratory symptoms, function, and socioeconomic characteristics, including area deprivation index (ADI). Matched analysis (age, sex, and smoking status) of AA vs. NHW within participants without diagnosed COPD (GOLD 0; FEV1 ≥ 80% predicted and FEV1/FVC ≥ 0.7). RESULTS: Using the fixed ratio, 70% of AA (n = 3366) were classified as non-COPD, versus 49% of NHW (n = 6766). AA smokers were younger (55 vs. 62 years), more often current smoking (80% vs. 39%), with fewer pack-years but similar 12-year mortality. Density distribution plots for FEV1 and FVC raw spirometry values showed disproportionate reductions in FVC relative to FEV1 in AA that systematically led to higher ratios. The matched analysis demonstrated GOLD 0 AA had greater symptoms, worse DLCO, spirometry, BODE scores (1.03 vs 0.54, p < 0.0001), and greater deprivation than NHW. LIMITATIONS: Lack of an alternative diagnostic metric for comparison. CONCLUSIONS: The fixed-ratio spirometric criteria for COPD underdiagnosed potential COPD in AA participants when compared to broader diagnostic criteria. Disproportionate reductions in FVC relative to FEV1 leading to higher FEV1/FVC were identified in these participants and associated with deprivation. Broader diagnostic criteria for COPD are needed to identify the disease across all populations.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Black or African American , Cohort Studies , Cross-Sectional Studies , Forced Expiratory Volume , Longitudinal Studies , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Spirometry , Vital Capacity , Middle Aged , White , Smoking/adverse effects
7.
Chest ; 163(2): 292-302, 2023 02.
Article in English | MEDLINE | ID: mdl-36167120

ABSTRACT

BACKGROUND: Studies have shown that COPD and smoking are associated with increased suicide risk. To date, there are no prospective studies examining suicide risk among individuals with smoking exposure along a spectrum of pulmonary diseases ranging from normal spirometry to severe COPD. RESEARCH QUESTION: Which clinical variables predict death by suicide or overdose of indeterminate intent in a large cohort of individuals with smoking exposure within the Genetic Epidemiology of COPD (COPDGene) study? STUDY DESIGN AND METHODS: We studied data from 9,930 participants involved in COPDGene, a multisite, prospective cohort study of individuals with smoking exposure. Primary cause of adjudicated deaths was identified by using death certificates, family reports, and medical records. Time to death by suicide/overdose was examined as the primary outcome in Cox regression models including age, sex, race, BMI, pack-years, current smoking status, airflow limitation (FEV1 % predicted), dyspnea (modified Medical Research Council scale score ≥ 2), 6-min walk distance, supplemental oxygen use, and severe exacerbations in the prior year with time-varying covariates and other causes of death as a competing risk. RESULTS: The cohort was 47% female and 33% Black (67% White); they had a mean ± SD age of 59.6 ± 9.0 years and a mean FEV1 % predicted of 76.1 ± 25.5. Sixty-three individuals died by suicide/overdose. Factors associated with risk of suicide/overdose were current smoking (hazard ratio [HR], 6.44; 95% CI, 2.64-15.67), use of sedative/hypnotics (HR, 2.33; 95% CI, 1.24-4.38), and dyspnea (HR, 2.23; 95% CI, 1.34-3.70). Lower risk was associated with older age (per-decade HR, 0.45; 95% CI, 0.31-0.67), higher BMI (HR, 0.95; 95% CI, 0.91-0.99), and African-American race (HR, 0.41; 95% CI, 0.23-0.74). Severity of airflow limitation (FEV % predicted) was not associated with suicide risk. INTERPRETATION: In this well-characterized cohort of individuals with smoking exposure with and without COPD, risk factors for suicide/overdose were identified that emphasize the subjective experience of illness over objective assessments of lung function.


Subject(s)
Drug Overdose , Pulmonary Disease, Chronic Obstructive , Humans , Female , Middle Aged , Aged , Male , Follow-Up Studies , Prospective Studies , Smoking/adverse effects , Smoking/epidemiology , Risk Factors , Dyspnea , Biomarkers , Forced Expiratory Volume
8.
Thorax ; 77(4): 351-356, 2022 04.
Article in English | MEDLINE | ID: mdl-34417353

ABSTRACT

INTRODUCTION: COPD is a heterogeneous disorder with varied phenotypes. We aimed to determine the prevalence of asthma history, peripheral eosinophilia and elevated FeNO levels along with the diagnostic utility of peripheral eosinophilia in identifying airway eosinophilic inflammation. METHODS: National Health and Nutrition Examination Survey data were analysed for the study period 2007-2010. Subjects aged ≥40 years with postbronchodilator FEV1/FVC ratio <0.70 were included. Receiver operator curve analysis was performed for sensitivity analysis. A p value of <0.001 is considered statistically significant. RESULTS: A total of 3 110 617 weighted COPD cases were identified; predominantly male (64.4%) and non-Hispanic whites (86.1%). Among our COPD subjects, 14.6% had a history of doctor diagnosed asthma, highest among females and other race Americans. The overall prevalence of peripheral eosinophilia is 36%, 38.3% among COPD subjects with asthma history, and 35.6% among COPD without asthma history. The overall prevalence of elevated FeNO ≥25 ppb is 14.3%; 28.7% among COPD subjects with asthma history and 13.0% among COPD without asthma history. DISCUSSION: The prevalence of FeNO levels ≥25 ppb and peripheral eosinophilia was significantly higher among COPD subjects with asthma compared with COPD without asthma history. Not all COPD subjects with peripheral eosinophilia and elevated FeNO levels have a reported history of asthma. Our study supports clinically phenotyping COPD subjects with eosinophilic inflammation be independent of their asthma history and peripheral eosinophilia can be used as a surrogate marker in resource-limited settings.


Subject(s)
Eosinophilia , Pulmonary Disease, Chronic Obstructive , Breath Tests , Eosinophilia/epidemiology , Eosinophils , Female , Fractional Exhaled Nitric Oxide Testing , Humans , Male , Nitric Oxide/analysis , Nutrition Surveys
9.
Chronic Obstr Pulm Dis ; 6(5): 384-399, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31710793

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. METHODS: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. RESULTS: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. CONCLUSIONS: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

10.
Chest ; 156(2): 228-238, 2019 08.
Article in English | MEDLINE | ID: mdl-31154041

ABSTRACT

The Genetic Epidemiology of COPD (COPDGene) study is a noninterventional, multicenter, longitudinal analysis of > 10,000 subjects, including smokers with a ≥ 10 pack-year history with and without COPD and healthy never smokers. The goal was to characterize disease-related phenotypes and explore associations with susceptibility genes. The subjects were extensively phenotyped with the use of comprehensive symptom and comorbidity questionnaires, spirometry, CT scans of the chest, and genetic and biomarker profiling. The objective of this review was to summarize the major advances in the clinical epidemiology of COPD from the first 10 years of the COPDGene study. We highlight the influence of age, sex, and race on the natural history of COPD, and the impact of comorbid conditions, chronic bronchitis, exacerbations, and asthma/COPD overlap.


Subject(s)
Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/genetics , Smoking/epidemiology , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications
11.
Article in English | MEDLINE | ID: mdl-31083298

ABSTRACT

African Americans, other minorities and underserved populations are consistently under- represented in clinical trials. Such underrepresentation results in a gap in the evidence base, and health disparities. The ABC Cardiovascular Implementation Study (CVIS) is a comprehensive prospective cohort registry that integrates social determinants of health. ABC CVIS uses real world clinical practice data to address critical gaps in care by facilitating robust participation of African Americans and other minorities in clinical trials. ABC CVIS will include diverse patients from collaborating ABC member private practices, as well as patients from academic health centers and Federally Qualified Health Centers (FQHCs). This paper describes the rationale and design of the ABC CVIS Registry. The registry will: (1) prospectively collect socio-demographic, clinical and biospecimen data from enrolled adults, adolescents and children with prioritized cardiovascular diseases; (2) Evaluate the safety and clinical outcomes of new therapeutic agents, including post marketing surveillance and pharmacovigilance; (3) Support National Institutes of Health (NIH) and industry sponsored research; (4) Support Quality Measures standards from the Center for Medicare and Medicaid Services (CMS) and Commercial Health Plans. The registry will utilize novel data and technology tools to facilitate mobile health technology application programming interface (API) to health system or practice electronic health records (EHR). Long term, CVIS will become the most comprehensive patient registry for underserved diverse patients with cardiovascular disease (CVD) and co morbid conditions, providing real world data to address health disparities. At least 10,000 patients will be enrolled from 50 sites across the United States.


Subject(s)
Black or African American/statistics & numerical data , Social Determinants of Health/statistics & numerical data , Vulnerable Populations/statistics & numerical data , Georgia , Humans , Prospective Studies , Registries
12.
Crit Care Med ; 47(8): e630-e638, 2019 08.
Article in English | MEDLINE | ID: mdl-31094740

ABSTRACT

OBJECTIVES: Atrial fibrillation is frequently seen in sepsis-related hospitalizations. However, large-scale contemporary data from the United States comparing outcomes among sepsis-related hospitalizations with versus without atrial fibrillation are limited. The aim of our study was to assess the frequency of atrial fibrillation and its impact on outcomes of sepsis-related hospitalizations. DESIGN: Retrospective cohort study. SETTING: The National Inpatient Sample databases (2010-2014). PATIENTS: Primary discharge diagnosis of sepsis with and without atrial fibrillation were identified using prior validated International Classification of Diseases, 9th Edition, Clinical Modification codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 5,808,166 hospitalizations with the primary diagnosis of sepsis, of which 19.4% (1,126,433) were associated with atrial fibrillation. The sepsis-atrial fibrillation cohort consisted of older (median [interquartile range] age of 79 yr [70-86 yr] vs 67 yr [53-79 yr]; p < 0.001) white (80.9% vs 68.8%; p < 0.001) male (51.1% vs 47.5%; p < 0.001) patients with an extended length of stay (median [interquartile range] 6 d [4-11 d] vs 5 d [3-9 d]; p < 0.001) and higher hospitalization charges (median [interquartile range] $44,765 [$23,234-$88,657] vs $35,737 [$18,767-$72,220]; p < 0.001) as compared with the nonatrial fibrillation cohort. The all-cause mortality rate in the sepsis-atrial fibrillation cohort was significantly higher (18.4% and 11.9%; p = 0.001) as compared with those without atrial fibrillation. Although all-cause mortality (20.4% vs 16.6%) and length of stay (median [interquartile range] 7 d [4-11 d] vs 6 d [4-10 d]) decreased between 2010 and 2014, hospitalization charges increased (median [interquartile range] $41,783 [$21,430-$84,465] vs $46,251 [$24,157-$89,995]) in the sepsis-atrial fibrillation cohort. The greatest predictors of mortality in the atrial fibrillation-sepsis cohort were African American race, female gender, advanced age, and the presence of medical comorbidities. CONCLUSIONS: The presence of atrial fibrillation among sepsis-related hospitalizations is a marker of poor prognosis and increased mortality. Although we observed rising trends in sepsis and sepsis-atrial fibrillation-related hospitalizations during the study period, the rate and odds of mortality progressively decreased.


Subject(s)
Atrial Fibrillation/mortality , Hospital Mortality/trends , Hospitalization/trends , Sepsis/mortality , Aged , Comorbidity , Databases, Factual , Female , Humans , Inpatients/statistics & numerical data , Length of Stay , Male , Middle Aged , Retrospective Studies , United States
13.
J Psychosom Res ; 118: 18-26, 2019 03.
Article in English | MEDLINE | ID: mdl-30782350

ABSTRACT

OBJECTIVES: To compare the frequency of anxiety/depressive symptoms and use of anxiolytic-hypnotics/antidepressants in smokers with and without COPD and to identify characteristics associated with having unmedicated symptoms. METHODS: Cross-sectional analysis of ambulatory, current/former smokers ≥10 pack years enrolled in the COPDGene study. We measured anxiety/depressive symptoms using the Hospital Anxiety and Depression Scale (subscales ≥8), recorded anxiolytic-hypnotic/antidepressant use, and defined unmedicated symptoms as elevated anxiety/depressive symptoms and not on medications. Regression analysis identified characteristics associated with having unmedicated symptoms. KEY RESULTS: Of 5331 current/former smokers (45% with and 55% without COPD), 1332 (25.0%) had anxiety/depressive symptoms. Anxiety symptoms were similar in frequency in smokers with and without COPD (19.7% overall), while depressive symptoms were most frequent in severe-very severe COPD at 20.7% (13.1% overall). In the entire cohort, 1135 (21.2%) were on medications. Anxiolytic-hypnotic use was highest in severe-very severe COPD (range 7.6%-12.0%), while antidepressant use showed no significant variation in smokers with and without COPD (range 14.7%-17.1%). Overall, 881 (66% of those with symptoms) had unmedicated symptoms, which was associated with African American race (adjusted OR 2.95, 95% CI 2.25-3.87), male gender (adjusted OR 1.93, 95% CI 1.57-2.36), no health insurance (adjusted OR 2.38, 95% CI 1.30-4.35), severe-very severe COPD (adjusted OR 1.48, 95% CI 1.04-2.11), and higher respiratory symptoms/exacerbation history (adjusted OR 2.21, 95% CI 1.62-3.02). CONCLUSIONS: Significant unmet mental health care needs exist in current and former smokers with and without COPD. One in five have unmedicated symptoms, identified by key demographic and clinical characteristics. PRIMARY FUNDING SOURCE: National Institutes of Health and The COPD Foundation.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Anxiety/drug therapy , Depression/drug therapy , Hypnotics and Sedatives/therapeutic use , Pulmonary Disease, Chronic Obstructive/psychology , Smokers/psychology , Aged , Anti-Anxiety Agents/pharmacology , Antidepressive Agents/pharmacology , Cohort Studies , Cross-Sectional Studies , Female , Humans , Hypnotics and Sedatives/pharmacology , Male , Risk Factors
14.
15.
Nicotine Tob Res ; 21(6): 714-722, 2019 05 21.
Article in English | MEDLINE | ID: mdl-29767774

ABSTRACT

INTRODUCTION: Cigarette smoking is a major environmental risk factor for many diseases, including chronic obstructive pulmonary disease (COPD). There are shared genetic influences on cigarette smoking and COPD. Genetic risk factors for cigarette smoking in cohorts enriched for COPD are largely unknown. METHODS: We performed genome-wide association analyses for average cigarettes per day (CPD) across the Genetic Epidemiology of COPD (COPDGene) non-Hispanic white (NHW) (n = 6659) and African American (AA) (n = 3260), GenKOLS (the Genetics of Chronic Obstructive Lung Disease) (n = 1671), and ECLIPSE (the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) (n = 1942) cohorts. In addition, we performed exome array association analyses across the COPDGene NHW and AA cohorts. We considered analyses across the entire cohort and stratified by COPD case-control status. RESULTS: We identified genome-wide significant associations for CPD on chromosome 15q25 across all cohorts (lowest p = 1.78 × 10-15), except in the COPDGene AA cohort alone. Previously reported associations on chromosome 19 had suggestive and directionally consistent associations (RAB4, p = 1.95 × 10-6; CYP2A7, p = 7.50 × 10-5; CYP2B6, p = 4.04 × 10-4). When we stratified by COPD case-control status, single nucleotide polymorphisms on chromosome 15q25 were nominally associated with both NHW COPD cases (ß = 0.11, p = 5.58 × 10-4) and controls (ß = 0.12, p = 3.86 × 10-5) For the gene-based exome array association analysis of rare variants, there were no exome-wide significant associations. For these previously replicated associations, the most significant results were among COPDGene NHW subjects for CYP2A7 (p = 5.2 × 10-4). CONCLUSIONS: In a large genome-wide association study of both common variants and a gene-based association of rare coding variants in ever-smokers, we found genome-wide significant associations on chromosome 15q25 with CPD for common variants, but not for rare coding variants. These results were directionally consistent among COPD cases and controls. IMPLICATIONS: We examined both common and rare coding variants associated with CPD in a large population of heavy smokers with and without COPD of NHW and AA descent. We replicated genome-wide significant associations on chromosome 15q25 with CPD for common variants among NHW subjects, but not for rare variants. We demonstrated for the first time that common variants on chromosome 15q25 associated with CPD are similar among COPD cases and controls. Previously reported associations on chromosome 19 showed suggestive and directionally consistent associations among common variants (RAB4, CYP2A7, and CYP2B6) and for rare variants (CYP2A7) among COPDGene NHW subjects. Although the genetic effect sizes for these single nucleotide polymorphisms on chromosome 15q25 are modest, we show that this creates a substantial smoking burden over the lifetime of a smoker.


Subject(s)
Ethnicity/genetics , Genetic Markers , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive/etiology , Smokers/statistics & numerical data , Smoking/genetics , Adult , Aged , Aged, 80 and over , Aryl Hydrocarbon Hydroxylases/genetics , Case-Control Studies , Cytochrome P-450 CYP2B6/genetics , Cytochrome P450 Family 2/genetics , Europe/epidemiology , Female , Genome-Wide Association Study/methods , Humans , Longitudinal Studies , Male , Middle Aged , Prevalence , Prognosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/pathology , Smoking/adverse effects , Smoking/epidemiology , United States/epidemiology , rab4 GTP-Binding Proteins/genetics
16.
J Racial Ethn Health Disparities ; 6(1): 22-26, 2019 02.
Article in English | MEDLINE | ID: mdl-29729002

ABSTRACT

RATIONALE: The current age threshold for lung cancer screening targets individuals beginning at age 55. These guidelines were developed based on results from the National Lung Cancer Screening Trial where only 4.4% of the enrollees were African American, when they represent 12.3% of US population. African Americans were also found to have higher incidence and younger onset of lung cancer. We hypothesized that implementation of screening at age 55 would not detect a substantial fraction of early onset lung cancer cases in African American population. OBJECTIVES: We used Surveillance, Epidemiology, and End Results (SEER) Program data to determine the frequency of early-onset lung cancers and to assess the stage at diagnosis in a biracial sample. METHODS: Microscopically confirmed lung cancer (primary site code C 34) cases were identified using SEER 18 registry (2004-2014). Early-onset cancers were defined as cancers diagnosed in persons aged 45 to 54 years. Cases were stratified by race and age groups. Comparisons were evaluated with chi-square tests. RESULTS: 468,403 lung cancers were diagnosed during this period. Nearly 9% of all lung cancers were early onset, with increased frequency in African Americans vs. Whites, 14.2 vs. 8.2%, p < 0.05. Age-adjusted incidence rates were significantly higher in African Americans with highest percent difference noted for age group 50-54. African Americans were more likely to be diagnosed at advanced stages of lung cancer compared to Whites. CONCLUSIONS: We conclude that the current age threshold for lung cancer screening may potentially miss a considerable number of lung cancer cases in African Americans. Further studies are needed to determine the appropriateness of screening age criteria for African Americans.


Subject(s)
Black or African American/statistics & numerical data , Healthcare Disparities/ethnology , Lung Neoplasms/ethnology , Mass Screening/statistics & numerical data , Practice Guidelines as Topic , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Lung Neoplasms/diagnosis , Male , Middle Aged , Retrospective Studies , United States/epidemiology , White People/statistics & numerical data
17.
Nat Genet ; 51(1): 30-35, 2019 01.
Article in English | MEDLINE | ID: mdl-30455414

ABSTRACT

We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.


Subject(s)
Black People/genetics , Genome, Human/genetics , High-Throughput Nucleotide Sequencing/methods , Humans , Sequence Analysis, DNA/methods
18.
Chronic Obstr Pulm Dis ; 5(3): 177-184, 2018 Jul 02.
Article in English | MEDLINE | ID: mdl-30584581

ABSTRACT

The COPD Genetic Epidemiology (COPDGene®) study provides a rich cross-sectional dataset of patients with substantial tobacco smoke exposure, varied by race, gender, chronic obstructive pulmonary disease (COPD) diagnosis, and disease. We aimed to determine the influence of race, gender and Global initiative for chronic Obstructive Lung Disease (GOLD) stage on prevalence of prior COPD diagnosis at COPDGene® enrollment. Data from the complete phase 1 cohort of 10,192 participants were analyzed. Participants were non-Hispanic white and African-American, ≥45 years of age with a minimum of 10 pack years of cigarette smoking. Characterization upon enrollment included spirometry, demographics and history of COPD diagnosis determined by questionnaire. We evaluated the effects of race and gender on the likelihood of prior diagnosis of COPD and the interaction of race and GOLD stage, and gender and GOLD stage, as determined at study enrollment, on likelihood of prior diagnosis of COPD. We evaluated the 3-way interaction of race, gender and GOLD stage on prior diagnosis. African-Americans had higher odds of not having a prior COPD diagnosis at all GOLD stages of airflow obstruction versus non-Hispanic whites (p<0.0001). Women had higher odds of having a prior COPD diagnosis at all GOLD stages versus men (p<0.0001). Three-way interaction of race, gender and GOLD stage was not significant. African-Americans were less likely to have prior COPD regardless of the severity of airflow obstruction determined at study enrollment. Women were more likely to have a prior COPD diagnosis regardless of the severity of measured airflow obstruction. Race and gender are associated with significant disparities in COPD diagnosis.

19.
ERJ Open Res ; 4(4)2018 Oct.
Article in English | MEDLINE | ID: mdl-30443555

ABSTRACT

Low socioeconomic status has been associated with chronic obstructive pulmonary disease (COPD) but little is known about its impact on disease progression. We assessed the association of income to symptoms, pulmonary disease severity and progression in smokers with and without COPD. The COPDGene cohort of 4826 smokers who reported annual income in phase 2 was analysed. Those who reported annual income

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