Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

Objective: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. Methods: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. Results: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). Conclusion: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

Risk of longer-term neurological conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort Study - Five years of follow-up.

BACKGROUND: Long-term neurological health risks associated with oil spill cleanup exposures are largely unknown. We aimed to investigate risks of longer-term neurological conditions among U.S. Coast Guard (USCG) responders to the 2010 Deepwater Horizon (DWH) oil spill. METHODS: We used data from active duty members of the DWH Oil Spill Coast Guard Cohort Study (N=45224). Self-reported oil spill exposures were ascertained from post-deployment surveys. Incident neurological outcomes were classified using International Classification of Diseases, 9th Revision, codes from military health encounter records up to 5.5 years post-DWH. We used Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for various incident neurological diagnoses (2010-2015). Oil spill responder (n=5964) vs. non-responder (n= 39260) comparisons were adjusted for age, sex, and race, while within-responder comparisons were additionally adjusted for smoking. RESULTS: Compared to those not responding to the spill, spill responders had reduced risks for headache (aHR=0.84, 95% CI: 0.74-0.96), syncope and collapse (aHR=0.74, 95% CI: 0.56-0.97), and disturbance of skin sensation (aHR=0.81, 95% CI: 0.68-0.96). Responders reporting ever (n=1068) vs. never (n=2424) crude oil inhalation exposure were at increased risk for several individual and grouped outcomes related to headaches and migraines (aHR range: 1.39-1.83). Crude oil inhalation exposure was also associated with elevated risks for an inflammatory nerve condition, mononeuritis of upper limb and mononeuritis multiplex (aHR=1.71, 95% CI: 1.04-2.83), and tinnitus (aHR=1.91, 95% CI: 1.23-2.96), a condition defined by ringing in one or both ears. Risk estimates for those neurological conditions were higher in magnitude among responders reporting exposure to both crude oil and oil dispersants than among those reporting crude oil only. CONCLUSION: In this large study of active duty USCG responders to the DWH disaster, self-reported spill cleanup exposures were associated with elevated risks for longer-term neurological conditions.

Long-term air pollution and risk of amyotrophic lateral sclerosis mortality in the Women's Health Initiative cohort.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure. Although the etiology of sporadic ALS is largely unknown, environmental exposures may affect ALS risk. OBJECTIVE: We investigated relationships between exposure to long-term ambient particulate matter (PM) and gaseous air pollution (AP) and ALS mortality. METHODS: Within the Women's Health Initiative (WHI) cohort of 161,808 postmenopausal women aged 50-79 years at baseline (1993-1998), we performed a nested case-control study of 256 ALS deaths and 2486 matched controls with emphasis on PM constituents (PM2.5, PM10, and coarse PM [PM10-2.5]) and gaseous pollutants (NOx, NO2, SO2, and ozone). Time-varying AP exposures estimates were averaged 5, 7.5, and 10 years prior to ALS death using both a GIS-based spatiotemporal generalized additive mixed model and ordinary kriging (empirical and multiple imputation, MI). Conditional logistic regression was used to estimate the relative risk of ALS death. RESULTS: In general, PM2.5 and PM10-related risks were not significantly elevated using either method. However, for PM10-2.5, odds ratios (ORs) were >1.0 for both methods at all time periods using MI and empirical data for PM10-2.5 (coarse) except for 5 and 7.5 years using the kriging method with covariate adjustment. CONCLUSION: This investigation adds to the body of information on long-term ambient AP exposure and ALS mortality. Specifically, the 2019 US Environmental Protection Agency (EPA) Integrated Science Assessment summarized the neurotoxic effects of PM2.5, PM10, and PM10-2.5. The conclusion was that evidence of an effect of coarse PM is suggestive but the data is presently not sufficient to infer a causal relationship. Further research on AP and ALS is warranted. As time from symptom onset to death in ALS is ∼2-4 years, earlier AP measures may also be of interest to ALS development. This is the first study of ALS and AP in postmenopausal women controlling for individual-level confounders.

Recruitment of population-based controls for ALS cases from the National ALS Registry.

Objective: In 2010, the United States Agency for Toxic Substances and Disease Registry (ATSDR) created the National ALS Registry (Registry) to examine the epidemiology of ALS and potential risk factors. We are currently recruiting population-based controls for an epidemiologic case-control study to examine ALS environmental risk factors using this Registry. To date, we have recruited 181 non-diseased, population-based controls for comparison to Registry cases (n = 280). Here we report our recruitment methods for controls and the associated response rates and costs. Methods: Eligible ALS cases had complete risk factor survey data, DNA analysis, and blood concentrations of persistent organic pollutants (POPs). Age, sex, and county-matched controls were identified from commercial/consumer databases using a targeted landline phone sample. Eligible controls were consented, surveyed, and mailed the POPs' blood analysis consent form. Once consented, phlebotomy was scheduled. Results: We mailed 3760 recruitment letters for 181 potential case-matches across 42 states between 9/2018 and 3/2020. After making phone contact and determining eligibility, 146 controls agreed to participate (response rate = 11.4%, cooperation rate = 22.8%). To date, 127 controls completed the survey and bloodwork. Though controls were matched to cases on age, sex, and county, unmatched characteristics (e.g. smoking) did not differ statistically. Interviewing and incentive costs are estimated at $211.85 per complete participation. Conclusions: Recruiting matched population-based controls for comparison to cases from the Registry for a study involving completion of a detailed survey and blood specimen provision is relatively feasible and cost effective. This recruitment method could be useful for case-control studies of other rare disorders.

Ambient fine particulate matter exposure and incident mild cognitive impairment and dementia.

BACKGROUND/OBJECTIVE: Poor air quality is implicated as a risk factor for cognitive impairment and dementia. Few studies have examined these associations longitudinally in well-characterized population-based cohorts with standardized annual assessment of both mild cognitive impairment (MCI) and dementia. We investigated the association between estimated ambient fine particulate matter (PM2.5 ) and risk of incident MCI and dementia in a post-industrial region known for historically poor air quality. SETTING/PARTICIPANTS: Adults aged 65+ years in a population-based cohort (n = 1572). MEASUREMENTS: Census tract level PM2.5 from Environmental Protection Agency (EPA) air quality monitors; Clinical Dementia Rating (CDR)®. DESIGN: We estimated ambient PM2.5 exposure (µg/m3 , single-year and 5-year averages) by geocoding participants' residential addresses to census tracts with daily EPA PM2.5 measurements from 2002 to 2014. Using Bayesian spatial regression modeling adjusted for age, sex, education, smoking history, and household income, we examined the association between estimated PM2.5 exposure and risk of incident MCI (CDR = 0.5) and incident dementia (CDR ≥ 1.0). RESULTS: Modeling estimated single-year exposure, each 1 µg/m3 higher ambient PM2.5 was associated with 67% higher adjusted risk of incident dementia (hazard ratio [HR] = 1.669, 95% credible interval [CI]: 1.298, 2.136) and 75% higher adjusted risk of incident MCI (HR = 1.746, 95% CI: 1.518, 2.032). Estimates were higher when modeling 5-year ambient PM2.5 exposure for incident dementia (HR = 2.082, 95% CI: 1.528, 3.015) and incident MCI (HR = 3.419, 95% CI: 2.806, 4.164). CONCLUSIONS: Higher estimated ambient PM2.5 was associated with higher risk of incident MCI and dementia, particularly when considering longer-term exposure, and independent of demographic characteristics and smoking history. Targeting poor air quality may be a reasonable population-wide intervention to reduce the risk of cognitive impairment in older adults, particularly in regions exceeding current recommendations for safe exposure to PM2.5 .

Maternal Obesity, Birth Size, and Risk of Childhood Cancer Development.

Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother's exposures before and during pregnancy could have important consequences for her child's health, including cancer development. We examined whether birth certificate-derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)2) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being <30% below expected size also increased the overall cancer risk (P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth-related factors in childhood cancer development.

Residential Exposure to PM2.5 and Ozone and Progression of Subclinical Atherosclerosis Among Women Transitioning Through Menopause: The Study of Women's Health Across the Nation.

Objective: This article aims to examine the association between long-term ambient air pollution and progression of subclinical atherosclerosis with 2-year follow-up among midlife women from the Study of Women's Health Across the Nation (SWAN). Materials and Methods: Carotid duplex ultrasonography was performed in participants from a SWAN ancillary study carried out at the Pittsburgh and Chicago sites. Mean and maximum carotid intima-media thickness (CIMT) and plaque burden were assessed throughout the common, bulb, and internal carotid artery. The yearly mean exposure to PM2.5 (particulate matter) and ozone was generated based on monitors within 20 km of the participants' home. The effect of air pollutants during follow-up on progression of CIMT was estimated using linear mixed-effects models, and the effect on progression of plaque presence and plaque index, a measure of extent of plaque, was evaluated using logistic regression. Results: This study included 417 (257 White and 160 Black) women with a mean age of 51 years at baseline. A 1 µg/m3 higher yearly mean exposure to PM2.5 during follow-up was associated with a 4.28 (95% confidence interval [CI]: 0.02-8.54) µm/year increase in maximum CIMT, after adjusting for socioeconomic and traditional cardiovascular disease (CVD) risk factors. Exposure to PM2.5 contributed to a 30% (95% CI: 3%-65%) higher odds of plaque index progression adjusting for socioeconomic factors only. Conclusions: PM2.5 independently contributed to progression of subclinical atherosclerosis, among women transitioning through menopause, a time of increasing CVD risk. Yet no significant associations between ozone and subclinical atherosclerosis were observed.

Healthy Air, Healthy Brains: Advancing Air Pollution Policy to Protect Children's Health.

Evidence is growing on the adverse neurodevelopmental effects of exposure to combustion-related air pollution. Project TENDR (Targeting Environmental Neurodevelopmental Risks), a unique collaboration of leading scientists, health professionals, and children's and environmental health advocates, has identified combustion-related air pollutants as critical targets for action to protect healthy brain development. We present policy recommendations for maintaining and strengthening federal environmental health protections, advancing state and local actions, and supporting scientific research to inform effective strategies for reducing children's exposures to combustion-related air pollution. Such actions not only would improve children's neurological development but also would have the important co-benefit of climate change mitigation and further improvements in other health conditions.

Prediagnostic plasma branched-chain amino acids and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To assess whether prediagnostic levels of plasma branched-chain amino acids (BCAAs) are associated with amyotrophic lateral sclerosis (ALS) risk. METHODS: We included participants from 5 large cohort studies-The Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition, the Multiethnic Cohort Study, and the Women's Health Initiative-and identified 275 individuals who developed ALS during follow-up. Two controls were randomly selected for each case, matched on cohort, age, sex, fasting status, and time of blood draw. We measured metabolites using liquid chromatography-mass spectrometry and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association of individual BCAAs with ALS risk. RESULTS: None of the 3 BCAAs was associated with a higher ALS risk. The risk estimates were similar for leucine (RR top vs bottom quartile: 0.87, 95% CI 0.57-1.33), isoleucine (RR top vs bottom quartile: 0.81, 95% CI 0.52-1.24), and valine (RR top vs bottom quartile: 0.80, 95% CI 0.52-1.23) in a multivariable analysis adjusted for body mass index, smoking, level of education, and physical activity. The estimates did not vary significantly by sex, fasting status, or time interval between blood draw and disease onset. CONCLUSION: The results from this study do not support the hypothesis that BCAAs are risk factors for ALS.

Characterization of the concentration-response curve for ambient ozone and acute respiratory morbidity in 5 US cities.

Although short-term exposure to ambient ozone (O3) can cause poor respiratory health outcomes, the shape of the concentration-response (C-R) between O3 and respiratory morbidity has not been widely investigated. We estimated the effect of daily O3 on emergency department (ED) visits for selected respiratory outcomes in 5 US cities under various model assumptions and assessed model fit. Population-weighted average 8-h maximum O3 concentrations were estimated in each city. Individual-level data on ED visits were obtained from hospitals or hospital associations. Poisson log-linear models were used to estimate city-specific associations between the daily number of respiratory ED visits and 3-day moving average O3 levels controlling for long-term trends and meteorology. Linear, linear-threshold, quadratic, cubic, categorical, and cubic spline O3 C-R models were considered. Using linear C-R models, O3 was significantly and positively associated with respiratory ED visits in each city with rate ratios of 1.02-1.07 per 25 ppb. Models suggested that O3-ED C-R shapes were linear until O3 concentrations of roughly 60 ppb at which point risk continued to increase linearly in some cities for certain outcomes while risk flattened in others. Assessing C-R shape is necessary to identify the most appropriate form of the exposure for each given study setting.

A multicity study of air pollution and cardiorespiratory emergency department visits: Comparing approaches for combining estimates across cities.

Determining how associations between ambient air pollution and health vary by specific outcome is important for developing public health interventions. We estimated associations between twelve ambient air pollutants of both primary (e.g. nitrogen oxides) and secondary (e.g. ozone and sulfate) origin and cardiorespiratory emergency department (ED) visits for 8 specific outcomes in five U.S. cities including Atlanta, GA; Birmingham, AL; Dallas, TX; Pittsburgh, PA; St. Louis, MO. For each city, we fitted overdispersed Poisson time-series models to estimate associations between each pollutant and specific outcome. To estimate multicity and posterior city-specific associations, we developed a Bayesian multicity multi-outcome (MCM) model that pools information across cities using data from all specific outcomes. We fitted single pollutant models as well as models with multipollutant components using a two-stage chemical mixtures approach. Posterior city-specific associations from the MCM models were somewhat attenuated, with smaller standard errors, compared to associations from time-series regression models. We found positive associations of both primary and secondary pollutants with respiratory disease ED visits. There was some indication that primary pollutants, particularly nitrogen oxides, were also associated with cardiovascular disease ED visits. Bayesian models can help to synthesize findings across multiple outcomes and cities by providing posterior city-specific associations building on variation and similarities across the multiple sources of available information.

Association Between Hypertensive Disorders in Pregnancy and Particulate Matter in the Contiguous United States, 1999-2004.

Hypertensive disorders in pregnancy harm both maternal and infant health and have been linked to ambient particulate matter. However, existing studies are restricted to a local scale and remain inconsistent. A large-scale study is required to enrich the epidemiological evidence and explore the potential sources of the inconsistency. Making use of US birth certificates (1999-2004), and monitoring data from the environmental protection agency air quality networks, we associated hypertensive disorders in pregnancy with maternal exposure to fine particles or coarse particles using logistic regression analysis after adjusting for many covariates among >5 million subjects in the contiguous United States. Additional analyses were conducted to examine variations in the associations according to (1) census divisions; (2) individual-level factors; (3) a socioeconomic indicator, county-level poverty; and (4) the concentration of ambient particles. The results indicated that hypertensive disorders in pregnancy were robustly linked to maternal exposure to fine particles with an adjusted odds ratio of 1.10 (95% confidence intervals, 1.08-1.12) per 5 µg/m3 increment in terms of the entire pregnancy mean. Stronger associations were found among white mothers. There were also considerable variations in the association by census division or poverty level among counties. Nonlinear analysis indicated a sublinear dose-response function with a threshold concentration of 9 µg/m3 Based on the national study, we calculated the population attributable fractions and found that 8.1% (6.8%-9.4%) of hypertensive disorder cases were attributable to an entire pregnancy exposure of fine particles. These findings can help policymakers to plan related interventions.

Systemic inflammatory markers associated with cardiovascular disease and acute and chronic exposure to fine particulate matter air pollution (PM2.5) among US NHANES adults with metabolic syndrome.

BACKGROUND: There has been no investigation to date of adults with metabolic syndrome examining the association of short and long-term exposure to fine particulate matter (PM2.5) air pollution with cardiovascular-disease related inflammatory marker (WBC and CRP) levels in a nationally representative sample. The goal of this study is to assess the susceptibility of adults with metabolic syndrome to PM2.5 exposure as suggested by increased cardiovascular-disease related inflammatory marker levels. METHODS: A cross sectional analysis of adult National Health and Nutrition Examination Survey (NHANES) participants (2000-2008) was carried out with linkage of CDC WONDER meteorological data and downscaler modeled USEPA air pollution data for census tracts in the continental United States. Participants were non-pregnant NHANES adults (2000-2008) with complete data for evaluating presence of metabolic syndrome and laboratory data on WBC and CRP. Exposures studied included short (lags 0-3 days and their averages), long-term (30 and 60 day moving and annual averages) PM2.5 exposure levels at the census tract level in the continental United States. The main outcomes included CRP and WBC levels the day of NHANES study visit analyzed using multiple linear regression, adjusting for age, gender, race, education, smoking status, history of any cardiovascular disease, maximum apparent temperature and ozone level, for participants with and without metabolic syndrome. RESULTS: A total of 7134 NHANES participants (35% with metabolic syndrome) met the inclusion criteria. After adjusting for confounders, we observed a significant effect of PM2.5 acutely at lag day 0 on CRP level; a 10µg/m3 rise in lag day 0 PM2.5 level was associated with a 10.1% increase (95% CI: 2.2-18.6%) in CRP levels for participants with metabolic syndrome. For those without metabolic syndrome, the change in CRP was -1.3% (95% CI -8.8%, 6.8%). There were no significant associations for WBC count. In this first national study of the effect of PM2.5 air pollution on levels of cardiovascular-disease related inflammatory markers in adults with metabolic syndrome, CRP levels were found to be significantly increased in those with this condition with increased fine particulate matter levels at lag day 0. With one third of US adults with metabolic syndrome, the health impact of PM2.5 in this sensitive population may be significant.

Gamma Knife Radiosurgery for Vestibular Schwannomas and Quality of Life Evaluation.

BACKGROUND: Further investigation is needed to look at the impact of vestibular schwannoma (VS) on the health-related quality of life (QOL) of participants who undergo Gamma Knife® radiosurgery (GKRS). OBJECTIVES: Investigators compared the QOL for VS participants to reported US population norms in order to evaluate disease burden and long-term QOL several years after GKRS. METHODS: This cross-sectional study surveyed participants to assess hearing status, tinnitus, imbalance, vertigo, as well as the Short-Form 36-item Health Questionnaire (SF-36). The data were normalized, age adjusted, and functional status was correlated to determine clinically significant differences. RESULTS: A total of 353 participants who underwent GKRS between 1997 and 2007 were included in this study with a median postoperative period of 5 years. SF-36 scores were very similar to population norms, and age-adjusted scores for participants followed the US population curve. Frequent vertigo and balance problems had the largest statistically and clinically significant effect on physical and mental component summary scores followed by nonuseful hearing in the tumor ear. CONCLUSIONS: Participants reported a good long-term QOL that was very similar to the QOL of US population norms. Of the common VS symptoms, vertigo had the greatest impact on QOL followed by imbalance and then hearing loss.

Pesticide exposure and liver cancer: a review.

PURPOSE: To review the epidemiologic literature examining pesticide exposure and liver cancer incidence. METHODS: A search of the MEDLINE and Embase databases was conducted in October 2015. Eligibility criteria included examining hepatocellular carcinoma (HCC) or primary liver cancer, pesticides as an exposure of interest, and individual-level incidence. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Forty-eight papers were assessed for eligibility and 15 studies were included in the review. The majority of studies were conducted in China and Egypt (n = 8), used a case-control design (n = 14), and examined HCC (n = 14). Most studies showed no association between self-reported and/or occupational exposure to pesticides and liver cancer risk. Six studies demonstrated statistically significant positive associations, including three biomarker-based studies (two using pre-diagnostic sera) that reported higher serum levels of dichlorodiphenyltrichloroethane (DDT) were associated with increased HCC risk. Studies indirectly measuring pesticide exposure using self-reported exposure, occupation, job-exposure matrices, or geographic residence demonstrated inconsistent results. These studies were limited by exposure assessment methods, lack of confounder information, minimal case confirmation, selection bias, and/or over-adjustment. CONCLUSIONS: There is mixed evidence suggesting a possible association between specific pesticides and HCC risk, with the strongest evidence observed in biomarker-based studies. In particular, organochlorine pesticides, including DDT, may increase HCC risk. Future research should focus on improved pesticide exposure assessment methods, potentially incorporating multiple approaches including biomonitoring while considering the chemicals of interest, historical exposure to address latency periods, and examining specific chemicals and exposure pathways.

Environmental lead and childhood blood lead levels in US children: NHANES, 1999-2006.

Although blood lead levels in the United States have fallen dramatically since 1980, there remain subgroups of children with high blood lead levels. We assessed the relationship between environmental lead sources and blood lead levels in children ages 1 to 5 years from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Modeled ambient air lead levels and industrial lead releases at the census-tract level were assigned to each child's residence with adjustment for confounding factors. Of 3,223 children, 272 (8.4%) had blood lead levels ≥ 5 ug/dL. Industrial releases (2,252 vs 1,696 lbs/mi2) and ambient air lead levels (2.28 vs 1.75 ng/m3) were greater in exposed versus unexposed children. For every 10,000 lb/mi2 increase in inverse distance squared weighted exposure, there was a 1.13% increase (95% CI: 0.45%, 1.81%) in blood lead (p = .001).

Using spatio-temporal modeling for exposure assessment in an investigation of fine particulate air pollution and cardiovascular mortality.

BACKGROUND: U.S. urban air quality has improved dramatically over the past decades. We evaluated acute effects of fine particulate matter (PM2.5) on cardiovascular (CVD) mortality among residents of Allegheny County in SW Pennsylvania (1999-2011) using spatio-temporal modeling of air pollutants (AP) to reduce misclassification error in exposure assessment. METHODS: Spatio-temporal kriging of daily PM2.5 and ozone (O3) was used to produce daily exposure estimates at the residence ZIP code. Time-stratified case-crossover analysis was conducted to examine short-term effects of PM2.5 on CVD mortality, adjusting for O3 and apparent mean temperature. We studied both single and distributed lags for days 0-5. All CVD mortality and subcategories of ischemic heart disease (IHD), acute myocardial infarction, cerebrovascular disease, peripheral vascular disease (PVD), heart failure and cardiac arrhythmia were examined. RESULTS: A total of 62,135 deaths were identified. We found significant associations of PM2.5 with IHD and PVD mortality at lag day 5: (2.1% (95% CI, 0.2-4.1%) and (7.6%, 95% CI, 0.05-15.7%) per 10µg/m3 increase of PM2.5 in single lag models and for IHD in distributed lag models. There were no statistically significant associations with PM2.5 for any of the other outcomes. CONCLUSIONS: The application of finer scale geographically resolved AP exposures made it possible to study acute effects of PM2.5 on CVD mortality in a large metropolitan area. Our study results demonstrated the continued presence of a dose response relationship of increased risk of CVD mortality within this lower range of PM2.5 exposure.

Revisiting Nonresidential Environmental Exposures and Childhood Lead Poisoning in the US: Findings from Kansas, 2000-2005.

Although blood lead levels (BLLs) in US children have dramatically declined over the past 40 years, there remain pockets of children living in areas with elevated BLLs. While some increases (≥ 10 µg/dL) may be associated with legacy lead paint, ambient air lead may be contributing to the problem. A deidentified dataset of information on over 60,000 Kansas children under 3 years of age who were tested for BLL was provided through the Kansas Environmental Public Health Tracking Network for the period 2000-2005. Using ArcGIS, we calculated distance (in miles) from a lead-emitting industry referred to as a toxic release inventory (TRI) site. The USEPA TRI database tracks the management of certain toxic chemicals that may pose a threat to human health. US facilities in different industry sectors must report annually amount of substances like lead into the environment including their exact location. Distance from a TRI site was inversely related to BLL after controlling for area-level poverty and pre-1950 housing. The results of our evaluation indicate there is a significant relationship between proximity to lead industry and childhood BLLs. Proximity to sources of lead emissions should be evaluated as a possible factor when identifying children for targeted BLL testing.