Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use.

Cannabis is widely used worldwide, yet its links to health outcomes are not fully understood. DNA methylation can serve as a mediator to link environmental exposures to health outcomes. We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and lifetime cannabis use (ever vs. never) in a meta-analysis including 9436 participants (7795 European and 1641 African ancestry) from seven cohorts. Accounting for effects of cigarette smoking, our trans-ancestry EWAS meta-analysis revealed four CpG sites significantly associated with lifetime cannabis use at a false discovery rate of 0.05 [Formula: see text]: cg22572071 near gene ADGRF1, cg15280358 in ADAM12, cg00813162 in ACTN1, and cg01101459 near LINC01132. Additionally, our EWAS analysis in participants who never smoked cigarettes identified another epigenome-wide significant CpG site, cg14237301 annotated to APOBR. We used a leave-one-out approach to evaluate methylation scores constructed as a weighted sum of the significant CpGs. The best model can explain 3.79% of the variance in lifetime cannabis use. These findings unravel the DNA methylation changes associated with lifetime cannabis use that are independent of cigarette smoking and may serve as a starting point for further research on the mechanisms through which cannabis exposure impacts health outcomes.

Residential proximity to toxic metal-emitting industrial sites and toenail metal concentrations in a United States-wide prospective cohort.

BACKGROUND: Industrial facilities across the United States (US) release millions of pounds of toxic chemicals, including metals. Exposure to toxic metals has been associated with adverse health outcomes, but there is limited evidence on the association between living near metal-releasing facilities and the body burden of emitted compounds. OBJECTIVE: To investigate the association between residential proximity to toxic metal-emitting industrial facilities and toenail metal concentrations and to evaluate whether associations differed by race. METHODS: In a sample of 1556 non-Hispanic Black (32.5%) and non-Hispanic White (67.5%) women from the Sister Study, we used the US Environmental Protection Agency Toxics Release Inventory to identify metal-emitting facilities within 3, 5, and 10 km of participants' baseline residences. We measured toenail concentrations (µg/g) of arsenic, cadmium, cobalt, chromium, and lead. Using multivariable linear regression, we examined associations between residential proximity to and emissions from metal-emitting facilities and toenail metal concentrations, stratifying by race. We explored modification of race-stratified associations by neighborhood deprivation, using the Area Deprivation Index (ADI). RESULTS: Black participants were more likely to reside within 3 km of chromium-releasing facilities and 5 and 10 km of all observed metal-emitting sites. Living near metal-releasing facilities was not associated with higher toenail metal concentrations overall. Among Black women, higher chromium emissions exposure was associated with higher toenail chromium levels (ßTertile3vs.non-exposed = 2.36 µg/g, 95% CI = 0.63, 4.10). An association with lead was observed among Black women residing in the most deprived areas (≥75th ADI percentile: ß = 3.08 µg/g, 95% CI = 1.46, 4.71). No associations were observed for White participants. CONCLUSIONS: Despite low exposure prevalence, our findings suggest that living near chromium- and lead-releasing facilities, especially at shorter distances, may be associated with higher corresponding toenail metal levels among Black women, particularly those residing in the most disadvantaged areas.

Nontraditional Occupational Exposures to Crude Oil Combustion Disasters and Respiratory Disease Risk: A Narrative Review of Literature.

PURPOSE OF REVIEW: Burning of petroleum products has been consistently associated with adverse respiratory health effects. Combustion of crude oil, specifically, produces toxic byproducts, but there have been relatively few studies of health effects. Burning of crude oil is increasingly employed as a means of mitigating environmental disasters despite the potential health risks to workers involved in clean-up efforts. Here, we review epidemiological studies of respiratory effects following unique crude oil burning events to (1) characterize respiratory health effects from this nontraditional occupational exposure and (2) identify approaches used to characterize exposures that could be applied to future disaster-related studies. RECENT FINDINGS: We searched PubMed and EMBASE for references from inception to January 30, 2023. We also manually screened references cited in eligible articles. We identified 14 eligible publications. Our review suggests that exposure to crude oil combustion has adverse respiratory effects, including reduced lung function and increased occurrence of respiratory symptoms and disease. However, the evidence is inconsistent, and quality of data varied across studies. While some studies used quantitative, modeled exposure estimates, most used self-reported proxies of exposure. Although disasters involving crude oil combustion are relatively rare, limited evidence suggests that some worker populations may be at risk for respiratory effects from burning exposures in disaster settings. Future studies that use improved exposure assessment methods (e.g., personal monitors, remote sensing data) may help further quantify the respiratory risk from crude oil burning exposures.

Fine particulate matter and incident coronary heart disease events up to 10 years of follow-up among Deepwater Horizon oil spill workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, in-situ burning and flaring were conducted to remove oil from the water. Workers near combustion sites were potentially exposed to burning-related fine particulate matter (PM2.5). Exposure to PM2.5 has been linked to increased risk of coronary heart disease (CHD), but no study has examined the relationship among oil spill workers. OBJECTIVES: To investigate the association between estimated PM2.5 from burning/flaring of oil/gas and CHD risk among the DWH oil spill workers. METHODS: We included workers who participated in response and cleanup activities on the water during the DWH disaster (N = 9091). PM2.5 exposures were estimated using a job-exposure matrix that linked modelled PM2.5 concentrations to detailed DWH spill work histories provided by participants. We ascertained CHD events as the first self-reported physician-diagnosed CHD or a fatal CHD event that occurred after each worker's last day of burning exposure. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for the associations between categories of average or cumulative daily maximum PM2.5 exposure (versus a referent category of water workers not near controlled burning) and subsequent CHD. We assessed exposure-response trends by examining continuous exposure parameters in models. RESULTS: We observed increased CHD hazard among workers with higher levels of average daily maximum exposure (low vs. referent: HR = 1.26, 95% CI: 0.93, 1.70; high vs. referent: HR = 2.11, 95% CI: 1.08, 4.12; per 10 µg/m3 increase: HR = 1.10, 95% CI: 1.02, 1.19). We also observed suggestively elevated HRs among workers with higher cumulative daily maximum exposure (low vs. referent: HR = 1.19, 95% CI: 0.68, 2.08; medium vs. referent: HR = 1.38, 95% CI: 0.88, 2.16; high vs. referent: HR = 1.44, 95% CI: 0.96, 2.14; per 100 µg/m3-d increase: HR = 1.03, 95% CI: 1.00, 1.05). CONCLUSIONS: Among oil spill workers, exposure to PM2.5 from flaring/burning of oil/gas was associated with increased risk of CHD.

Exposure to volatile hydrocarbons and neurologic function among oil spill workers up to 6 years after the Deepwater Horizon disaster.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, oil spill response and cleanup (OSRC) workers were exposed to toxic volatile components of crude oil. Few studies have examined exposure to individual volatile hydrocarbon chemicals below occupational exposure limits in relation to neurologic function among OSRC workers. OBJECTIVES: To investigate the association of several spill-related chemicals (benzene, toluene, ethylbenzene, xylene, n-hexane, i.e., BTEX-H) and total petroleum hydrocarbons (THC) with neurologic function among DWH spill workers enrolled in the Gulf Long-term Follow-up Study. METHODS: Cumulative exposure to THC and BTEX-H across the oil spill cleanup period were estimated using a job-exposure matrix that linked air measurement data to detailed self-reported DWH OSRC work histories. We ascertained quantitative neurologic function data via a comprehensive test battery at a clinical examination that occurred 4-6 years after the DWH disaster. We used multivariable linear regression and modified Poisson regression to evaluate relationships of exposures (quartiles (Q)) with 4 neurologic function measures. We examined modification of the associations by age at enrollment (<50 vs. ≥50 years). RESULTS: We did not find evidence of adverse neurologic effects from crude oil exposures among the overall study population. However, among workers ≥50 years of age, several individual chemical exposures were associated with poorer vibrotactile acuity of the great toe, with statistically significant effects observed in Q3 or Q4 of exposures (range of log mean difference in Q4 across exposures: 0.13-0.26 µm). We also observed suggestive adverse associations among those ≥ age 50 years for tests of postural stability and single-leg stance, although most effect estimates did not reach thresholds of statistical significance (p < 0.05). CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest deficits in neurologic function among OSRC workers who were age 50 years or older at study enrollment.

The Case for Case-Cohort: An Applied Epidemiologist's Guide to Reframing Case-Cohort Studies to Improve Usability and Flexibility.

When research questions require the use of precious samples, expensive assays or equipment, or labor-intensive data collection or analysis, nested case-control or case-cohort sampling of observational cohort study participants can often reduce costs. These study designs have similar statistical precision for addressing a singular research question, but case-cohort studies have broader efficiency and superior flexibility. Despite this, case-cohort designs are comparatively underutilized in the epidemiologic literature. Recent advances in statistical methods and software have made analyses of case-cohort data easier to implement, and advances from casual inference, such as inverse probability of sampling weights, have allowed the case-cohort design to be used with a variety of target parameters and populations. To provide an accessible link to this technical literature, we give a conceptual overview of case-cohort study analysis with inverse probability of sampling weights. We show how this general analytic approach can be leveraged to more efficiently study subgroups of interest or disease subtypes or to examine associations independent of case status. A brief discussion of how this framework could be extended to incorporate other related methodologic applications further demonstrates the broad cost-effectiveness and adaptability of case-cohort methods for a variety of modern epidemiologic applications in resource-limited settings.

Neighborhood Deprivation, Obesity, and Diabetes in Residents of the US Gulf Coast.

Socioeconomic status has been associated with cardiovascular disease risk factors. However, few studies have examined this relationship among populations in the US Gulf Coast region. We assessed neighborhood deprivation in relation to obesity and diabetes in 9,626 residents participating in the Gulf Long-Term Follow-Up Study (2011-present) who completed a home visit (2011-2013) with height, weight, waist, and hip measurements. Obesity was categorized as body mass index of at least 30, and diabetes was defined by doctor's diagnosis or prescription medication. Participant home addresses were linked to an established Area Deprivation Index and categorized into 4 levels (1 = least deprived). In adjusted, modified Poisson regression models, participants with greatest deprivation were more likely to have obesity compared with those with least deprivation (adjusted prevalence ratio (aPR) = 1.21, 95% confidence interval (CI): 1.08, 1.35), central obesity (aPR = 1.11, 95% CI: 1.04, 1.19), and diabetes (aPR = 1.49, 95% CI: 1.03, 2.14). Repeated analyses among a subgroup of participants (n = 3,016) whose hemoglobin A1C values were measured 3 years later indicated the association with diabetes (defined as diagnosis, medications, or hemoglobin A1C ≥ 6.5) was similar (aPR = 1.46, 95% CI: 1.14, 1.86). Results suggest neighborhood deprivation is associated with obesity and diabetes in a US region with high baseline prevalence.

Association of neighborhood deprivation with pulmonary function measures among participants in the Gulf Long-Term Follow-up Study.

INTRODUCTION: Individual-level socioeconomic status (SES) has been shown to be an important determinant of lung function. Neighborhood level SES factors may increase psychological and physiologic stress and may also reflect other exposures that can adversely affect lung function, but few studies have considered neighborhood factors. OBJECTIVE: Our aim was to assess the association between neighborhood-level SES and lung function. METHODS: We cross-sectionally analyzed 6168 spirometry test results from participants in the Gulf long-term Follow-up Study, a large cohort of adults enrolled following the largest maritime oil spill in US history. Outcomes of interest included the forced expiratory volume in 1 s (FEV1; mL), the forced vital capacity (FVC; mL), and the FEV1/FVC ratio (%). Neighborhood deprivation was measured by linking participant home addresses to an existing Area Deprivation Index (ADI) and categorized into quartiles. Individual-level SES measures were collected at enrollment using a structured questionnaire and included income, educational attainment, and financial strain. We used multilevel regression to estimate associations between ADI quartiles and each lung function measure. RESULTS: Greater neighborhood deprivation was associated with lower FEV1: ßQ2vsQ1: -30 mL (95% CI: -97, 36), ßQ3vsQ1: -70 mL (95% CI: -135, -4) and ßQ4vsQ1: -104 mL (95% CI: -171, -36). FVC showed similar patterns of associations with neighborhood deprivation. No associations with the FEV1/FVC ratio were observed. CONCLUSION: Neighborhood deprivation, a measure incorporating economic and other stressors, was associated with lower FEV1 and FVC, with magnitudes of associations reaching clinically meaningful levels. The impact of this neighborhood SES measure persisted even after adjustment for individual-level SES factors.

Associations of periodontal disease and tooth loss with all-cause and cause-specific mortality in the Sister Study.

AIM: Studies have found that periodontal disease and tooth loss are associated with increased mortality; however, associations with cause-specific mortality and all-cause mortality within specific subgroups have not been thoroughly investigated. MATERIALS AND METHODS: We examined the association of self-reported periodontal disease and disease/decay-related tooth loss with subsequent all-cause and cause-specific mortality in the Sister Study, a prospective cohort study of 50,884 women aged 35-74 years at baseline, whose sister was diagnosed with breast cancer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations were calculated with adjustment for relevant confounders. RESULTS: With a mean follow-up of 10.9 years (range 0.1-14.3), 2058 women died. Participants with periodontal disease had a slightly higher rate of all-cause mortality (HR = 1.08, 95% CI 0.98-1.19), while participants with tooth loss had an increased rate of all-cause mortality (HR = 1.15, 95% CI 1.05-1.26). For cause-specific mortality, women with tooth loss had increased rates of death from circulatory system diseases, respiratory system diseases, and endocrine/metabolic diseases. Results varied in stratified models, but no heterogeneity across strata was found. CONCLUSIONS: In this large prospective study, periodontal disease and tooth loss were associated with all-cause and certain specific cause-specific mortality outcomes.

Lung function in oil spill responders 4-6 years after the Deepwater Horizon disaster.

Oil spill response and clean-up (OSRC) workers were exposed to hazardous airborne chemicals following the 2010 Deepwater Horizon disaster. The aim of this study was to evaluate lung function in workers 4-6 years following the disaster using a prospective cohort. Participants who completed two spirometry test sessions 1-3 years, and 4-6 years after the spill (N = 1,838) were included and forced expiratory volume in 1 s (FEV1; ml), forced vital capacity (FVC; ml), and ratio (FEV1/FVC; %) determined. Linear mixed models were utilized to estimate relationships between OSRC exposures and lung function 4-6 years after the spill and changes since the prior measurement. Despite suggestive reduced lung function at 1-3 years, at the  4-6-year exam workers with total hydrocarbon (THC) exposure 1-2.99 ppm and ≥3 ppm compared to those with ≤0.29 ppm exhibited higher FEV1 (ß: 108 ml, 95% CI: 17, 198) and (ß: 118 ml, 95% CI: 5, 232), respectively. Compared with support workers, those in higher exposed jobs displayed greater improvement in FEV1 between visits: cleanup on water (ß: 143 ml, 95% CI: 35, 250), operations (ß: 132 ml, 95% CI: 30, 234) and response (ß: 149 ml, 95% CI: 43, 256). Greater FEV1 improvement was also associated with higher versus the lowest level THC exposure: 1-2.99 ppm (ß: 134 ml, 95% CI: 57, 210) and ≥3 ppm (ß: 205 ml, 95% CI: 109, 301). Lung function decrements seen shortly after the spill were no longer apparent 4-6 years later, with the greatest improvement among those with the highest exposures.

Childhood and adolescent residential and farm pesticide exposures and inflammatory bowel disease incidence in a U.S. cohort of women.

BACKGROUND AND AIMS: There are few known risk factors for inflammatory bowel disease (IBD), an autoimmune disease characterized by chronic intestinal inflammation. Use of specific pesticides has been associated with higher incidence of IBD among pesticide applicators and their spouses, but no study has examined pesticide exposure in early life, a period where the human immune system undergoes rapid changes. We evaluated pesticide use during childhood and adolescence and incidence of IBD among US women enrolled in the Sister Study. METHODS: Incident IBD diagnoses between enrollment (2003-2009) and 2021 were identified and validated with medication use and colectomy/colostomy surgery. We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for the relationship of childhood/adolescent residential and farm pesticide exposures with IBD incidence using Cox models, accounting for age, race and ethnicity, education, smoking, and birth year. RESULTS: We identified 277 incident IBD cases among 48,382 eligible participants. IBD hazard was elevated among those whose childhood residence was regularly treated with pesticides, especially among those who ever personally applied pesticides (HR: 1.39, 95%CI: 0.65, 2.99). We observed a positive association between IBD and exposure to broadcast pesticide sprays before DDT was banned (>6 times vs. never HR: 1.56, 95%CI: 1.06, 2.31). Among participants who lived on a farm during childhood/adolescence for ≥1 year (N = 9162), IBD hazards were higher among those who were in crop fields during pesticide application (HR: 2.06, 95%CI: 0.94, 4.51) and who ever personally applied pesticides on crops (HR: 1.85, 95%CI: 0.81, 4.18) or livestock (HR: 2.58, 95%CI: 1.14, 5.83). CONCLUSION: Early-life pesticide exposure may be a novel risk factor for IBD. Practices that reduce pesticide exposure during early life may help reduce the burden of this disease.

Association between solar radiation and mood disorders among Gulf Coast residents.

BACKGROUND: Climate factors such as solar radiation could contribute to mood disorders, but evidence of associations between exposure to solar radiation and mood disorders is mixed and varies by region. OBJECTIVE: To evaluate the association of solar radiation with depression and distress among residents living in U.S. Gulf states. METHODS: We enrolled home-visit participants in the Gulf Long-Term Follow-up Study who completed validated screening questionnaires for depression (Patient Health Questionnaire-9, N = 10,217) and distress (Kessler Psychological Distress Questionnaire, N = 8,765) for the previous 2 weeks. Solar radiation estimates from the Daymet database (1-km grid) were linked to residential addresses. Average solar radiation exposures in the seven (SRAD7), 14 (SRAD14), and 30 days (SRAD30) before the home visit were calculated and categorized into quartiles (Q1-Q4). We used generalized linear mixed models to estimate prevalence ratios (PR) and 95% confidence intervals (CI) for associations between solar radiation and depression/distress. RESULTS: Higher levels of SRAD7 were non-monotonically inversely associated with depression [PRVs.Q1 (95%CI): Q2 = 0.81 (0.68, 0.97), Q3 = 0.80 (0.65, 0.99), Q4 = 0.88 (0.69, 1.15)] and distress [PRVs.Q1 (95%CI): Q2 = 0.76 (0.58, 0.99), Q3 = 0.77 (0.57, 1.06), Q4 = 0.84 (0.58, 1.22)]. Elevated SRAD14 and SRAD30 appeared to be associated with decreasing PRs of distress. For example, for SRAD14, PRs were 0.86 (0.63-1.19), 0.80 (0.55-1.18), and 0.75 (0.48-1.17) for Q2-4 versus Q1. Associations with SRAD7 varied somewhat, though not significantly, by season with increasing PRs of distress in spring and summer and decreasing PRs of depression and distress in fall. IMPACT STATEMENT: Previous research suffered from exposure misclassification, which impacts the validity of their conclusions. By leveraging high-resolution datasets and Gulf Long-term Follow-up Cohort, our findings support an association between increased solar radiation and fewer symptoms of mood disorders.

Associations of a toenail metal mixture with attention and memory in the Gulf long-term follow-up (GuLF) study.

BACKGROUND: Research on metal-associated neurodegeneration has largely focused on single metals. Since metal exposures typically co-occur as combinations of both toxic and essential elements, a mixtures framework is important for identifying risk and protective factors. This study examined associations between toenail levels of an eight-metal mixture and attention and memory in men living in US Gulf states. METHODS: We measured toenail concentrations of toxic (arsenic, chromium, lead, and mercury) and essential (copper, manganese, selenium, and zinc) metals in 413 non-smoking men (23-69 years, 46 % Black) from the Gulf Long-Term Follow-Up (GuLF) Study. Sustained attention and working memory were assessed at the time of toenail sample collection using the continuous performance test (CPT) and digit span test (DST), respectively. Associations between toenail metal concentrations and performance on neurobehavioral tests were characterized using co-pollutant adjusted general linear models and Bayesian Kernel Machine Regression. RESULTS: Adjusting for other metals, one interquartile range (IQR) increase in toenail chromium was associated with a 0.19 (95 % CI: -0.31, -0.07) point reduction in CPT D Prime score (poorer ability to discriminate test signals from noise). One IQR increase in toenail manganese was associated with a 0.20 (95 % CI, -0.41, 0.01) point reduction on the DST Reverse Count (fewer numbers recalled). Attention deficits were greater among Black participants compared to White participants for the same increase in toenail chromium concentrations. No evidence of synergistic interaction between metals or adverse effect of the overall metal mixture was observed for either outcome. CONCLUSIONS: Our findings support existing studies of manganese-related memory deficits and are some of the first to show chromium related attention deficits in adults. Longitudinal study of cognitive decline is needed to verify chromium findings. Research into social and chemical co-exposures is also needed to explain racial differences in metal-associated neurobehavioral deficits observed in this study.

Neighborhood disadvantage and immune-related illnesses among residents living in the US Gulf States.

PURPOSE: Neighborhood disadvantage has been associated with increased risk for pneumonia and influenza-associated hospitalizations. Few studies, however, have investigated how neighborhood disadvantage may influence immune-related illnesses. The aim of this study was to examine the association between neighborhooddisadvantage and immune-related illnesses. METHODS: We used data from the Gulf Long-term Follow-up (GuLF) Study (n = 32,608). Our analytic sample included home visit participants (n = 11,193) who had complete information on exposure and covariates (n = 10,543). Neighborhood disadvantage was assessed using the 2013 Area Deprivation Index (ADI), which assigns a ranking of 1 to 100 for lowest to highest disadvantage. We linked ADI to participants' geocoded enrollment addresses at the census block group level. ADI was categorized into quartiles based on the national distribution with the first quartile as the referent. Immune-related illnesses self-reported at the home visit (May 2011-May 2013) included occurrence of shingles, pneumonia, cold sores, flu, and colds since the Deepwater Horizon oil spill (April 2010). Frequent colds and frequent flu were defined as ≥4 colds and ≥2 episodes of flu since the spill. An aggregated outcome, based on occurrence of any pneumonia, cold sores, flu, and ≥4 colds since the spill, was also examined. We assessed the association of each outcome with ADI using multivariable log-binomial regression adjusting for individual-level demographics, behavioral factors, kids at home, and season of interview completion. RESULTS: We found elevated prevalence ratios (PR) and 95% confidence intervals (CI) for pneumonia associated with ADI in the third (PR: 2.04, 95% CI: 1.04, 4.02) and fourth (PR: 2.00; 95% CI: 1.00, 3.98) quartiles. PRs for frequent colds were also elevated for increasing ADI quartiles, but with confidence intervals including the null value. CONCLUSIONS: The observed associations of frequent colds and pneumonia with increasing neighborhood disadvantage may warrant further research on this topic.

Residential proximity to metal emitting industries and toenail metal concentration in the US Gulf States.

Objective: The US Gulf region is heavily reliant on metal-emitting petrochemical and manufacturing industries. We characterized the effect of residential proximity to metal-emitting sites and metal body burden in Gulf states residents with particular attention to potential differential exposure burden by race. Methods: We measured toenail concentrations of arsenic, chromium, lead, manganese, mercury, and selenium using inductively coupled plasma mass spectrometry in 413 non-smoking men from the Gulf Long-term Follow-Up Study. Point sources of industrial metal emissions were identified using the US EPA's National Emissions Inventory (NEI) database and geocoded to participant residential addresses. For each metal, we assessed associations of toenail metal concentrations with the inverse-distance weighted number of emissions sites and volume of air-metal emissions within 30 km radial buffers of participant residences using multivariable linear regression. Results were stratified by race. Results: Compared to self-identified Non-Hispanic (NH) White participants, NH Black participants lived closer to NEI sites but had 23-70% lower toenail metal concentrations adjusting for other personal/behavioral factors. Residential proximity to lead-emitting NEI sites was positively associated with toenail Pb concentration while proximity to mercury-emitting NEI sites was inversely associated with toenail Hg concentration. Findings for lead were significantly attenuated after adjustment for neighborhood-level socioeconomic factors. Conclusion: Residential proximity to lead-emitting NEI sites in the US Gulf region is associated with a higher body burden of lead. However, this relationship may be driven in part by non-NEI factors related to residence in industry-adjacent neighborhoods.

Association between spill-related exposure to fine particulate matter and peripheral motor and sensory nerve function among oil spill response and cleanup workers following the Deepwater Horizon oil spill.

BACKGROUND: Burning/flaring of oil/gas during the Deepwater Horizon oil spill response and cleanup (OSRC) generated high concentrations of fine particulate matter (PM2.5). Personnel working on the water during these activities may have inhaled combustion products. Neurologic effects of PM2.5 have been reported previously but few studies have examined lasting effects following disaster exposures. The association of brief, high exposures and adverse effects on sensory and motor nerve function in the years following exposure have not been examined for OSRC workers. OBJECTIVES: We assessed the relationship between exposure to burning/flaring-related PM2.5 and measures of sensory and motor nerve function among OSRC workers. METHODS: PM2.5 concentrations were estimated from Gaussian plume dispersion models and linked to self-reported work histories. Quantitative measures of sensory and motor nerve function were obtained 4-6 years after the disaster during a clinical exam restricted to those living close to two clinics in Mobile, AL or New Orleans, LA (n = 3401). We obtained covariate data from a baseline enrollment survey and a home visit, both in 2011-2013. The analytic sample included 1186 participants. RESULTS: We did not find strong evidence of associations between exposure to PM2.5 and sensory or motor nerve function, although there was a suggestion of impairment based on single leg stance among individuals with high exposure to PM2.5. Results were generally consistent whether we examined average or cumulative maximum exposures or removed individuals with the highest crude oil exposures to account for co-pollutant confounding. There was no evidence of exposure-response trends. IMPACT STATEMENT: Remediating environmental disasters is essential for long-term human and environmental health. During the Deepwater Horizon oil spill disaster, burning and flaring of oil and gas were used to remove these pollutants from the environment, but led to potentially high fine particulate matter exposures for spill response workers working on the water. We investigate the potential adverse effects of these exposures on peripheral nerve function; understanding the potential health harm of remediation tactics is necessary to inform future clean up approaches and protect human health.

Reliability of low mass toenail samples as biomarkers of chronic metal exposure.

BACKGROUND: Toenails are a promising matrix for chronic metal exposure assessment, but there are currently no standard methods for collection and analysis. Questions remain about sample mass requirements and the extent to which metals measured in this matrix are representative of chronic body burden. OBJECTIVE: This study proposes a method to maximize sample conservation for toenail metals analysis using inductively coupled plasma mass spectrometry (ICP-MS). We demonstrate the reliability of an ~25 mg toenail sample (typically 1-2 clippings) for metals analysis and evaluate the intra-individual variability of multiple metals in this matrix over time in men from the Gulf Long-term Follow-up (GuLF) Study. METHODS: Toenail samples from 123 GuLF Study participants were collected at two visits 3 years apart and analyzed for 18 elements using ICP-MS. Participants with samples exceeding 200 mg at the first visit (n = 29) were selected for triplicate sub-sample analysis. Kendall's coefficient of concordance (W) was used to assess sub-sample reliability and Spearman's correlation coefficients (ρ) were used to evaluate fluctuations in elemental concentrations over time. RESULTS: Results were not reported for Cd, Co, Mo, Sb, and V (detected in <60% of the samples). There was strong agreement among triplicate samples (Kendall's W: 0.72 (Cu)-0.90 (Cu)) across all elements evaluated, moderate correlations of elemental concentrations (Spearman's ρ: 0.21-0.42) over 3 years for As, Ca, Cr, Fe, Pb, Mn, and Zn, and strong correlations (>0.50) for Se, Cu, and Hg. IMPACT STATEMENT: This toenail reliability study found that a low-mass (~25 mg) toenail sample (1-2 clippings) is suitable for the determination of most elements using ICP-MS and helps to increase the analytical capacity of limited toenail biospecimens collected in cohort studies. The results highlight differences in the suitability of toenails for chronic metal exposure assessment by element and underscore the need to consider intra-person variability, especially when comparing results across studies. We also provide recommendations for analytical standardization and the partitioning of the total collected toenail sample into multiple analytic sub-samples for future studies using toenail biospecimen for multiple assays.

Air pollution and epigenetic aging among Black and White women in the US.

BACKGROUND: DNA methylation-based measures of biological aging have been associated with air pollution and may link pollutant exposures to aging-related health outcomes. However, evidence is inconsistent and there is little information for Black women. OBJECTIVE: We examined associations of ambient particulate matter <2.5 µm and <10 µm in diameter (PM2.5 and PM10) and nitrogen dioxide (NO2) with DNA methylation, including epigenetic aging and individual CpG sites, and evaluated whether associations differ between Black and non-Hispanic White (NHW) women. METHODS: Validated models were used to estimate annual average outdoor residential exposure to PM2.5, PM10, and NO2 in a sample of self-identified Black (n=633) and NHW (n=3493) women residing in the contiguous US. We used sampling-weighted generalized linear regression to examine the effects of pollutants on six epigenetic aging measures (primary: DunedinPACE, GrimAgeAccel, and PhenoAgeAccel; secondary: Horvath intrinsic epigenetic age acceleration [EAA], Hannum extrinsic EAA, and skin & blood EAA) and epigenome-wide associations for individual CpG sites. Wald tests of nested models with and without interaction terms were used to examine effect measure modification by race/ethnicity. RESULTS: Black participants had higher median air pollution exposure than NHW participants. GrimAgeAccel was associated with both PM10 and NO2 among Black participants, (Q4 versus Q1, PM10: ß=1.09, 95% CI: 0.16-2.03; NO2: ß=1.01, 95% CI 0.08-1.94) but not NHW participants (p-for-heterogeneity: PM10=0.10, NO2=0.20). In Black participants, we also observed a monotonic exposure-response relationship between NO2 and DunedinPACE (Q4 versus Q1, NO2: ß=0.029, 95% CI: 0.004-0.055; p-for-trend=0.03), which was not observed in NHW participants (p-for-heterogeneity=0.09). In the EWAS, pollutants were significantly associated with differential methylation at 19 CpG sites in Black women and one in NHW women. CONCLUSIONS: In a US-wide cohort study, our findings suggest that air pollution is associated with DNA methylation alterations consistent with higher epigenetic aging among Black, but not NHW, women.

Volatile Hydrocarbon Exposures and Incident Coronary Heart Disease Events: Up to Ten Years of Follow-up among Deepwater Horizon Oil Spill Workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, response and cleanup workers were potentially exposed to toxic volatile components of crude oil. However, to our knowledge, no study has examined exposure to individual oil spill-related chemicals in relation to cardiovascular outcomes among oil spill workers. OBJECTIVES: Our aim was to investigate the association of several spill-related chemicals [benzene, toluene, ethylbenzene, xylene, n-hexane (BTEX-H)] and total hydrocarbons (THC) with incident coronary heart disease (CHD) events among workers enrolled in a prospective cohort. METHODS: Cumulative exposures to THC and BTEX-H across the cleanup period were estimated via a job-exposure matrix that linked air measurement data with self-reported DWH spill work histories. We ascertained CHD events following each worker's last day of cleanup work as the first self-reported physician-diagnosed myocardial infarction (MI) or a fatal CHD event. We estimated hazard ratios (HR) and 95% confidence intervals for the associations of exposure quintiles (Q) with risk of CHD. We applied inverse probability weights to account for bias due to confounding and loss to follow-up. We used quantile g-computation to assess the joint effect of the BTEX-H mixture. RESULTS: Among 22,655 workers with no previous MI diagnoses, 509 experienced an incident CHD event through December 2019. Workers in higher quintiles of each exposure agent had increased CHD risks in comparison with the referent group (Q1) of that agent, with the strongest associations observed in Q5 (range of HR=1.14-1.44). However, most associations were nonsignificant, and there was no evidence of exposure-response trends. We observed stronger associations among ever smokers, workers with ≤high school education, and workers with body mass index <30 kg/m2. No apparent positive association was observed for the BTEX-H mixture. CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest increases in risk of CHD among oil spill workers, although we did not observe exposure-response trends. https://doi.org/10.1289/EHP11859.