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.

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.

Weight Loss through Lifestyle Intervention Improves Mobility in Older Adults.

BACKGROUND AND OBJECTIVES: The high prevalence of overweight or obesity in older adults is a public health concern because obesity affects health, including the risk of mobility disability. RESEARCH DESIGN AND METHODS: The Mobility and Vitality Lifestyle Program, delivered by community health workers (CHWs), enrolled 303 community-dwelling adults to assess the impact of a 32-session behavioral weight management intervention. Participants completed the program at 26 sites led by 22 CHWs. Participation was limited to people aged 60-75 who had a body mass index (BMI) of 27-45 kg/m2. The primary outcome was the performance on the Short Physical Performance Battery (SPPB) over 12 months. RESULTS: Participants were aged 67.7 (SD 4.1) and mostly female (87%); 22.7% were racial minorities. The mean (SD) BMI at baseline was 34.7 (4.7). Participants attended a median of 24 of 32 sessions; 240 (80.3%) completed the 9- or 13-month outcome assessment. Median weight loss in the sample was 5% of baseline body weight. SPPB total scores improved by +0.31 units (p < .006), gait speed by +0.04 m/s (p < .0001), and time to complete chair stands by -0.95 s (p < .0001). Weight loss of at least 5% was associated with a gain of +0.73 in SPPB scores. Increases in activity (by self-report or device) were not independently associated with SPPB outcomes but did reduce the effect of weight loss. DISCUSSION AND IMPLICATIONS: Promoting weight management in a community group setting may be an effective strategy for reducing the risk of disability in older adults.

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.

Lagged Association of Ambient Outdoor Air Pollutants with Asthma-Related Emergency Department Visits within the Pittsburgh Region.

Asthma affects millions of people globally and is especially concerning in populations living with poor air quality. This study examines the association of ambient outdoor air pollutants on asthma-related emergency department (ED) visits in children and adults throughout the Pittsburgh region. A time-stratified case-crossover design is used to analyze the lagged effects of fine particulate matter (PM2.5) and gaseous pollutants, e.g., ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) on asthma-related ED visits (n = 6682). Single-, double-, and multi-pollutant models are adjusted for temperature and analyzed using conditional logistic regression. In children, all models show an association between O3 and increased ED visits at lag day 1 (OR: 1.12, 95% CI, 1.03-1.22, p < 0.05) for the double-pollutant model (OR: 1.10, 95% CI: 1.01-1.20, p < 0.01). In adults, the single-pollutant model shows associations between CO and increased ED visits at lag day 5 (OR: 1.13, 95% CI, 1.00-1.28, p < 0.05) and average lag days 0-5 (OR: 1.22, 95% CI: 1.00-1.49, p < 0.05), and for NO2 at lag day 5 (OR: 1.04, 95% CI: 1.00-1.07, p < 0.05). These results show an association between air pollution and asthma morbidity in the Pittsburgh region and underscore the need for mitigation efforts to improve public health outcomes.

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.

Mobility and Vitality Lifestyle Program (MOVE UP): A Community Health Worker Intervention for Older Adults With Obesity to Improve Weight, Health, and Physical Function.

BACKGROUND AND OBJECTIVES: Obesity rates in adults ≥65 years have increased more than other age groups in the last decade, elevating risk for chronic disease and poor physical function, particularly in underserved racial and ethnic minorities. Effective, sustainable lifestyle interventions are needed to help community-based older adults prevent or delay mobility disability. Design, baseline recruitment, and implementation features of the Mobility and Vitality Lifestyle Program (MOVE UP) study are reported. RESEARCH DESIGN AND METHODS: MOVE UP aimed to recruit 26 intervention sites in underserved areas around Allegheny County, Pennsylvania and train a similar number of community health workers to deliver a manualized intervention to groups of approximately 12 participants in each location. We adapted a 13-month healthy aging/weight management intervention aligned with several evidence-based lifestyle modification programs. A nonrandomized, pre-post design was used to measure intervention impact on physical function performance, the primary study endpoint. Secondary outcomes included weight, self-reported physical activity and dietary changes, exercise self-efficacy, health status, health-related quality of life, and accelerometry in a subsample. RESULTS: Of 58 community-based organizations approached, nearly half engaged with MOVE UP. Facilities included neighborhood community centers (25%), YMCAs (25%), senior service centers (20%), libraries (18%), senior living residences (6%), and churches (6%). Of 24 site-based cohorts with baseline data completed through November 2017, 21 community health workers were recruited and trained to implement the standardized intervention, and 287 participants were enrolled (mean age 68 years, 89% female, 33% African American, other, or more than one race). DISCUSSION AND IMPLICATIONS: The MOVE UP translational recruitment, training, and intervention approach is feasible and could be generalizable to diverse aging individuals with obesity and a variety of baseline medical conditions. Additional data regarding strategies for program sustainability considering program cost, organizational capacity, and other adaptations will inform public health dissemination efforts.

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.

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.

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.

Association of exposure to particulate matter (PM2.5) air pollution and biomarkers of cardiovascular disease risk in adult NHANES participants (2001-2008).

BACKGROUND AND OBJECTIVES: Exposure to particulate matter (PM2.5) has been associated with increased cardiovascular outcomes, mediated by a hypothesized biological mechanism of systemic inflammation and oxidation. Although PM10 has been linked to inflammatory markers in a nationally representative sample (NHANES) using data from earlier cycles (1989-1994); no study has considered these relationships for PM2.5 in more recent time periods. We examined the association of ambient PM2.5 exposure and inflammatory markers in adult NHANES participants for cycles 2001-2008. METHODS: We linked each of the adult NHANES participant's address with meteorological and modeled air pollution data for each census tract in conterminous United States. The effects of short and long term PM2.5 on C-reactive protein, white blood cells, fibrinogen and homocysteine were analyzed using multiple linear regression, adjusting for cardiovascular risk factors, temperature and ozone. SAS SURVEYREG was used to account for the complex survey design of NHANES. RESULTS: In the overall population, no significant positive associations were noted for either short or long term PM2.5 exposures for any of the biomarkers after controlling for confounders. However, stronger associations were found among obese, diabetics, hypertensive and smokers. For every 10µg/m(3) increase in PM2.5, there was an increase of (a) 36.9% (95% CI: 0.1%, 87.2%) in CRP at annual average PM2.5 (adjusting for short term exposure) among diabetics (b) 2.6% (95% CI: 0.1%, 5.1%) in homocysteine at lag 0 among smokers. CONCLUSIONS: In a nationally representative sample of individuals we noted no overall association between PM2.5 and biomarkers of cardiovascular risk. However, sensitive subgroups manifested increases in these markers to PM2.5 exposure. Further studies should concentrate on the impact of PM2.5 on these biomarkers in those with multiple cardiovascular risk factors.

Air toxics and the risk of autism spectrum disorder: the results of a population based case-control study in southwestern Pennsylvania.

BACKGROUND: Autism spectrum disorders (ASD) constitute a major public health problem affecting one in 68 children. There is little understanding of the causes of ASD despite its serious social impact. Air pollution contains many toxicants known to have adverse effects on the fetus. We conducted a population based case-control study in southwestern Pennsylvania to estimate the association between ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30 neurotoxicants. METHODS: A total of 217 ASD cases born between 2005 and 2009 were recruited from local ASD diagnostic and treatment centers. There were two different control groups: 1) interviewed controls (N = 224) frequency matched by child's year of birth, sex and race with complete residential histories from prior to pregnancy through the child's second birthday, and 2) 5,007 controls generated from a random sample of birth certificates (BC controls) using residence at birth. We used logistic regression analysis comparing higher to first quartile of exposure to estimate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for mother's age, education, race, smoking status, child's year of birth and sex. RESULTS: Comparing fourth to first quartile exposures for all births, the adjusted OR for styrene was 2.04 (95% CI = 1.17-3.58, p = 0.013) for the interviewed case-control analysis and 1.61 (95% CI = 1.08-2.40, p = 0.018) for the BC analysis. In the BC comparison, chromium also exhibited an elevated OR of 1.60 (95% CI = 1.08-2.38, p = 0.020), which was similarly elevated in the interviewed analysis (OR = 1.52, 95% CI = 0.87-2.66). There were borderline significant ORs for the BC comparison for methylene chloride (OR = 1.41, 95% CI = 0.96-2.07, p = 0.082) and PAHs (OR = 1.44, 95% CI = 0.98-2.11, p = 0.064). CONCLUSIONS: Living in areas with higher levels of styrene and chromium during pregnancy was associated with increased risk of ASD, with borderline effects for PAHs and methylene chloride. These results are consistent with other studies. It is unclear, however, whether these chemicals are risk factors themselves or if they reflect the effect of a mixture of pollutants. Future work should include improved spatiotemporal estimates of exposure to air toxics, taking into account the dynamic movement of individuals during daily life.

Fine particulate matter and the risk of autism spectrum disorder.

The causes of autism spectrum disorder (ASD) are not well known. Recent investigations have suggested that air pollution, including PM2.5, may play a role in the onset of this condition. The objective of the present work was to investigate the association between prenatal and early childhood exposure to fine particulate matter (PM2.5) and risk for childhood ASD. A population-based case-control study was conducted in children born between January 1, 2005 and December 31, 2009 in six counties in Southwestern Pennsylvania. ASD cases were recruited from specialty autism clinics, local pediatric practices, and school-based special needs services. ASD cases were children who scored 15 or above on the Social Communication Questionnaire (SCQ) and had written documentation of an ASD diagnosis. Controls were children without ASD recruited from a random sample of births from the Pennsylvania state birth registry and frequency matched to cases on birth year, gender, and race. A total of 217 cases and 226 controls were interviewed. A land use regression (LUR) model was used to create person- and time-specific PM2.5 estimates for individual (pre-pregnancy, trimesters one through three, pregnancy, years one and two of life) and cumulative (starting from pre-pregnancy) key developmental time periods. Logistic regression was used to investigate the association between estimated exposure to PM2.5 during key developmental time periods and risk of ASD, adjusting for mother's age, education, race, and smoking. Adjusted odds ratios (AOR) were elevated for specific pregnancy and postnatal intervals (pre-pregnancy, pregnancy, and year one), and postnatal year two was significant, (AOR=1.45, 95% CI=1.01-2.08). We also examined the effect of cumulative pregnancy periods; noting that starting with pre-pregnancy through pregnancy, the adjusted odds ratios are in the 1.46-1.51 range and significant for pre-pregnancy through year 2 (OR=1.51, 95% CI=1.01-2.26). Our data indicate that both prenatal and postnatal exposures to PM2.5 are associated with increased risk of ASD. Future research should include multiple pollutant models and the elucidation of the biological mechanism for PM2.5 and ASD.

A case-crossover analysis of the impact of PM(2.5) on cardiovascular disease hospitalizations for selected CDC tracking states.

BACKGROUND: Information is currently being collected by the CDC Environmental Public Health Tracking (EPHT) network on hospitalizations due to Acute Myocardial Infarction (AMI) and there is interest by CDC in exploring the relationship between fine particulate matter (PM2.5) and other cardiovascular (CVD) outcomes in the context of the EPHT program. The goal of this study was to assess the short term effects of daily PM(2.5) air pollution levels on hospitalizations for CVD for seven states within the CDC EPHT network (Florida, Massachusetts, New Hampshire, New Jersey, New Mexico, New York, and Washington). METHODS: Hospitalization data was obtained for 2001-2008 admissions for circulatory disease (primary discharge diagnosis of ICD-9 codes 390-459) from data stewards in those states and included admission date, age, gender, and zip code of residence. We used CMAQ-derived predicted daily PM2.5 data as estimated by EPA at the centroid of each Census Bureau Zip Code Tabulation Area (ZCTA) and linked to zip code of patient residence. A time-stratified case-crossover study design with conditional logistic regression was used to evaluate the short-term association of PM2.5 on risk of non-elective hospitalizations for CVD. Specifically, we considered all circulatory disease, ischemic heart disease, acute myocardial infarction, heart failure, cardiac arrhythmia, cerebrovascular disease and peripheral vascular disease endpoints. RESULTS: Data were obtained on over 7,500,000 hospitalizations for this time period. Mean annual PM2.5 exposure levels were lowest for New Mexico and Washington (6.5 µg/m3 PM2.5 and 8.4 µg/m3 PM2.5). New Jersey, New York and Massachusetts exhibited the highest annual averages for PM2.5, (12.8 µg/m3, 11.1 µg/m3 and 10.8 µg/m3), respectively. The Northeast states (Massachusetts, New Jersey, New Hampshire and New York) exhibited significant effects of PM2.5 during the cooler months across most disease categories after adjustment for ozone and maximum apparent temperature. Ischemic heart disease risk per 10 µg/m3 increase in PM2.5 varied from 1.02 to 1.05 for the cooler months. The largest lag effect was noted on lag days 0 and 1. New Mexico and Washington exhibited no cool or warm month significant effects. Although Florida showed no cooler month effects, significant increases were noted in odds ratios for the warm weather months for all outcomes except peripheral vascular disease. This study is one of the first large scale applications of linkage of hospitalization data by state with national US EPA statistically modeled air pollution data. The results demonstrate that state-wide, there are multiple cardiovascular outcomes in addition to AMI which may be impacted by particulate air pollution.

Do US ambient air lead levels have a significant impact on childhood blood lead levels: results of a national study.

INTRODUCTION: Although lead paint and leaded gasoline have not been used in the US for thirty years, thousands of US children continue to have blood lead levels (BLLs) of concern. METHODS: We investigated the potential association of modeled air lead levels and BLLs ≥ 10 µ g/dL using a large CDC database with BLLs on children aged 0-3 years. Percent of children with BLLs ≥ 10 µ g/dL (2000-2007) by county and proportion of pre-50 housing and SES variables were merged with the US EPA's National Air Toxics Assessment (NATA) modeled air lead data. RESULTS: The proportion with BLL ≥ 10 µ g/dL was 1.24% in the highest air lead counties, and the proportion with BLL ≥ 10 µ g/dL was 0.36% in the lowest air lead counties, resulting in a crude prevalence ratio of 3.4. Further analysis using multivariate negative binomial regression revealed that NATA lead was a significant predictor of % BLL ≥ 10 µ g/dL after controlling for percent pre-l950 housing, percent rural, and percent black. A geospatial regression revealed that air lead, percent older housing, and poverty were all significant predictors of % BLL ≥ 10 µ g/dL. CONCLUSIONS: More emphasis should be given to potential sources of ambient air lead near residential areas.

Trends in acute myocardial infarction hospitalization rates for US States in the CDC tracking network.

OBJECTIVES: We examined temporal trends, spatial variation, and gender differences in rates of hospitalization due to acute myocardial infarction. METHODS: We used data from the Centers for Disease Control National Environmental Public Health Tracking Network to evaluate temporal trends, geographic variation, and gender differences in 20 Environmental Public Health Tracking Network states from 2000 to 2008. A longitudinal linear mixed effects model was fitted to the acute myocardial infarction hospitalization rates for the states and counties within each state to examine the overall temporal trend. RESULTS: There was a significant overall decrease in age-adjusted acute myocardial infarction hospitalization rates between 2000 and 2008, with most states showing over a 20% decline during the period. The ratio of male/female rates for acute myocardial infarction hospitalization rates remained relatively consistent over time, approximately two-fold higher in men compared to women. A large geographic variability was found for age-adjusted acute myocardial infarction hospitalization rates, with the highest rates found in the Northeastern states. Results of two ecological analyses revealed that the NE region remained significantly associated with increased AMI hospitalization rates after adjustment for socio-demographic factors. CONCLUSIONS: This investigation is one of the first to explore geographic differences in AMI age adjusted hospital rates in individuals 35+ years of age for 2000-2008. We showed a decreasing trend in AMI hospitalization rates in men and women. A large geographic variability in rates was found with particularly higher rates in the New England/Mid-Atlantic region of the US and lower rates in the mountain and Pacific states of the tracking network. It appeared that over time this disparity in rates became less notable.

The relationship of ambient ozone and PM(2.5) levels and asthma emergency department visits: possible influence of gender and ethnicity.

ABSTRACT An investigation of the relationship of air pollution and emergency department (ED) visits for asthma was an opportunity to assess environmental risks for asthma exacerbations in an urban population. A total of 6,979 individuals with a primary discharge diagnosis of asthma presented to 1 of 6 EDs in the Pittsburgh, Pennsylvania, area between 2002 and 2005. Using a case-crossover methodology, which controls for the effects of subject-specific covariates such as gender and race, a 2.5% increase was observed in asthma ED visits for each 10 ppb increase in the 1-hour maximum ozone level on day 2 (odds ratio [OR] = 1.025, p < .05). Particulate matter with an aerodynamic diameter ≤2.5 µm (PM(2.5)) had an effect both on the total population on day 1 after exposure (1.036, p < .05), and on African Americans on days 1, 2, and 3. PM(2.5) had no significant effect on Caucasian Americans alone. The disparity in risk estimates by race may reflect differences in residential characteristics, exposure to ambient air pollution, or a differential effect of pollution by race.

Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women.

BACKGROUND: Given the high prevalence of polycystic ovarian syndrome (PCOS) in the population, the increased risk for the development of type 2 diabetes in these women, and the role of type 2 diabetes in mediating adverse long-term sequelae, the objective of this analysis was to quantify the contribution of this early-life exposure (e.g., PCOS) to the burden of type 2 diabetes in the total population of middle-aged women. METHODS: The cumulative incidence and relative risk (RR) of type 2 diabetes were examined in a group of women with PCOS (n = 149) and unaffected women (n = 166), aged 35-64, who were part of an ongoing investigation of cardiovascular risk factors in women with PCOS. The population attributable risk percent (PAR%) was calculated using Levin's formula to estimate the percentage of type 2 diabetes in the total population among middle-aged women that can be attributed to the presence of PCOS at young adulthood. RESULTS: When the RR of type 2 diabetes among women with PCOS observed in our current study and others (4.0-6.0) was applied to an estimated 6%-10% prevalence of PCOS in the female population, 15.0%-35.6% of all incident cases of type 2 diabetes in white women were estimated to be attributable to PCOS. Moreover, other investigators have noted this proportion of undiagnosed PCOS in populations of women with type 2 diabetes. CONCLUSIONS: These results support the recommendation that all women with PCOS should be periodically rescreened for diabetes and underscores the importance of the early identification of young women with PCOS and the need for early lifestyle intervention.

Cigarette smoking and the risk of adult leukemia: results from the Three Mile Island cohort study.

Smoking is an unconfirmed risk factor for the development of leukemia. The authors examined the potential link using data from the Three Mile Island cohort for the period 1979-1995. Eligible for analysis were 24,539 individuals aged 14 years or older who were followed up over 16 years from the Three Mile Island cohort. The authors identified all incident leukemia cases through the Pennsylvania Department of Health Cancer Registry. They used the Cox proportional hazards model to evaluate the relationships and observed 42 incident leukemia cases, including 15 acute myeloid leukemia (AML) cases, in the cohort. After controlling for other confounding factors, the authors found current smoking to be associated with an increased risk of adult AML (relative risk = 3.47; 95% confidence interval = 1.002-11.99). The authors also observed a marginally significant linear trend of risk of AML associated with the number of years smoked (p = .06). The results from this study suggested that cigarette smoking was associated with an increased risk of adult AML. Further investigation is required to confirm these findings.