Andrea Winquist

Perfluorooctanoic Acid (PFOA) Exposures and Incident Cancers among Adults Living near a Chemical Plant

Background: Perfluorooctanoic acid (PFOA) is a synthetic chemical ubiquitous in the serum of U.S. residents. It causes liver, testicular, and pancreatic tumors in rats. Human studies are sparse. Objective: We examined cancer incidence in Mid-Ohio Valley residents exposed to PFOA in drinking water due to chemical plant emissions. Methods: The cohort consisted of adult community residents who resided in contaminated water districts or worked at a local chemical plant. Most participated in a 2005–2006 baseline survey in which serum PFOA was measured. We interviewed the cohort in 2008–2011 to obtain further medical history. Retrospective yearly PFOA serum concentrations were estimated for each participant from 1952 through 2011. Self-reported cancers were validated through medical records and cancer registry review. We estimated the association between cancer and cumulative PFOA serum concentration using proportional hazards models. Results: Participants (n = 32,254) reported 2,507 validated cancers (21 different cancer types). Estimated cumulative serum PFOA concentrations were positively associated with kidney and testicular cancer [hazard ratio (HR) = 1.10; 95% CI: 0.98, 1.24 and HR = 1.34; 95% CI: 1.00, 1.79, respectively, for 1-unit increases in ln-transformed serum PFOA]. Categorical analyses also indicated positive trends with increasing exposures for both cancers: for kidney cancer HRs for increasing exposure quartiles were 1.0, 1.23, 1.48, and 1.58 (linear trend test p = 0.18) and for testicular cancer, HRs were 1.0, 1.04, 1.91, 3.17 (linear trend test p = 0.04). Conclusions: PFOA exposure was associated with kidney and testicular cancer in this population. Because this is largely a survivor cohort, findings must be interpreted with caution, especially for highly fatal cancers such as pancreatic and lung cancer. Citation: Barry V, Winquist A, Steenland K. 2013. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect 121:1313–1318; http://dx.doi.org/10.1289/ehp.1306615

Higher serum uric acid associated with decreased Parkinson's disease prevalence in a large community-based survey.

A large community‐based cross‐sectional survey provided an opportunity to evaluate a previously reported association between Parkinsons disease (PD) and low serum uric acid (UA) levels in this population. The association between a self‐reported PD diagnosis with treatment (n = 59) and serum UA level was examined using logistic and linear regression models, controlling for key covariates. In adjusted models, participants with UA levels at or above the median had a significantly lower odds of reporting PD with treatment compared with those with lower UA levels (OR 0.33, 95% CI 0.19–0.60, P = 0.0002). This association was observed for both men and women. The mean UA level among participants reporting PD with treatment was 0.78 mg/dl lower than the mean UA level among those not reporting PD (P ≤ 0.0001). These findings concur with several previous longitudinal studies that found an association between higher UA levels and decreased PD risk.

Joint effects of ambient air pollutants on pediatric asthma emergency department visits in Atlanta, 1998-2004.

Background: Because ambient air pollution exposure occurs as mixtures, consideration of joint effects of multiple pollutants may advance our understanding of the health effects of air pollution. Methods: We assessed the joint effect of air pollutants on pediatric asthma emergency department visits in Atlanta during 1998–2004. We selected combinations of pollutants that were representative of oxidant gases and secondary, traffic, power plant, and criteria pollutants, constructed using combinations of criteria pollutants and fine particulate matter (PM2.5) components. Joint effects were assessed using multipollutant Poisson generalized linear models controlling for time trends, meteorology, and daily nonasthma upper respiratory emergency department visit counts. Rate ratios (RRs) were calculated for the combined effect of an interquartile range increment in each pollutant’s concentration. Results: Increases in all of the selected pollutant combinations were associated with increases in warm-season pediatric asthma emergency department visits (eg, joint-effect RR = 1.13 [95% confidence interval = 1.06–1.21] for criteria pollutants, including ozone, carbon monoxide, nitrogen dioxide, sulfur dioxide, and PM2.5). Cold-season joint effects from models without nonlinear effects were generally weaker than warm-season effects. Joint-effect estimates from multipollutant models were often smaller than estimates based on single-pollutant models, due to control for confounding. Compared with models without interactions, joint-effect estimates from models including first-order pollutant interactions were largely similar. There was evidence of nonlinear cold-season effects. Conclusions: Our analyses illustrate how consideration of joint effects can add to our understanding of health effects of multipollutant exposures and also illustrate some of the complexities involved in calculating and interpreting joint effects of multiple pollutants.

Comparison of emergency department and hospital admissions data for air pollution time-series studies

BackgroundEmergency department (ED) visit and hospital admissions (HA) data have been an indispensible resource for assessing acute morbidity impacts of air pollution. ED visits and HAs are types of health care visits with similarities, but also potentially important differences. Little previous information is available regarding the impact of health care visit type on observed acute air pollution-health associations from studies conducted for the same location, time period, outcome definitions and model specifications.MethodsAs part of a broader study of air pollution and health in St. Louis, individual-level ED and HA data were obtained for a 6.5 year period for acute care hospitals in the eight Missouri counties of the St. Louis metropolitan area. Patient demographic characteristics and diagnostic code distributions were compared for four visit types including ED visits, HAs, HAs that came through the ED, and non-elective HAs. Time-series analyses of the relationship between daily ambient ozone and PM2.5 and selected cardiorespiratory outcomes were conducted for each visit type.ResultsOur results indicate that, compared with ED patients, HA patients tended to be older, had evidence of greater severity for some outcomes, and had a different mix of specific outcomes. Consideration of ‘HA through ED’ appeared to more effectively select acute visits than consideration of ‘non-elective HA’. While outcomes with the strongest observed temporal associations with air pollutants tended to show strong associations for all visit types, we found some differences in observed associations for ED visits and HAs. For example, risk ratios for the respiratory disease-ozone association were 1.020 for ED visits and 1.004 for ‘HA through ED’; risk ratios for the asthma/wheeze-ozone association were 1.069 for ED visits and 1.106 for ‘HA through ED’. Several factors (e.g. age) were identified that may be responsible, in part, for the differences in observed associations.ConclusionsDemographic and diagnostic differences between visit types may lead to preference for one visit type over another for some questions and populations. The strengths of observed associations with air pollutants sometimes varied between different health care visit types, but the relative strengths of association generally were specific to the pollutant-outcome combination.

Ulcerative Colitis and Perfluorooctanoic Acid (PFOA) in a Highly Exposed Population of Community Residents and Workers in the Mid-Ohio Valley

Background: Little is known about environmental determinants of autoimmune diseases. Objectives: We studied autoimmune diseases in relation to level of exposure to perfluorooctanoic acid (PFOA), which was introduced in the late 1940s and is now ubiquitous in the serum of residents of industrialized countries. Methods: In 2008–2011 we interviewed 32,254 U.S. adults with high serum PFOA serum levels (median, 28 ng/mL) associated with drinking contaminated water near a chemical plant. Disease history was assessed retrospectively from 1952 or birth (if later than 1952) until interview. Self-reported history of autoimmune disease was validated via medical records. Cumulative exposure to PFOA was derived from estimates of annual mean serum PFOA levels during follow-up, which were based on plant emissions, residential and work history, and a fate-transport model. Cox regression models were used to estimate associations between quartiles of cumulative PFOA serum levels and the incidence of autoimmune diseases with ≥ 50 validated cases, including ulcerative colitis (n = 151), Crohn’s disease (n = 96), rheumatoid arthritis (n = 346), insulin-dependent diabetes (presumed to be type 1) (n = 160), lupus (n = 75), and multiple sclerosis (n = 98). Results: The incidence of ulcerative colitis was significantly increased in association with PFOA exposure, with adjusted rate ratios by quartile of exposure of 1.00 (referent), 1.76 (95% CI: 1.04, 2.99), 2.63 (95% CI: 1.56, 4.43), and 2.86 (95% CI: 1.65, 4.96) (ptrend < 0.0001). A prospective analysis of ulcerative colitis diagnosed after the baseline 2005–2006 survey (n = 29 cases) suggested a positive but non-monotonic trend (ptrend = 0.21). Discussion: To our knowledge, this is the first study of associations between this common environmental exposure and autoimmune diseases in humans. We found evidence that PFOA is associated with ulcerative colitis.

A Method for Detection of Residual Confounding in Time-Series and Other Observational Studies

Background: A difficult issue in observational studies is assessment of whether important confounders are omitted or misspecified. In this study, we present a method for assessing whether residual confounding is present. Our method depends on availability of an indicator with 2 key characteristics: first, it is conditionally independent (given measured exposures and covariates) of the outcome in the absence of confounding, misspecification, and measurement errors; second, it is associated with the exposure and, like the exposure, with any unmeasured confounders. Methods: We demonstrate the method using a time-series study of the effects of ozone on emergency department visits for asthma in Atlanta. We argue that future air pollution may have the characteristics appropriate for an indicator, in part because future ozone cannot have caused yesterdays health events. Using directed acyclic graphs and specific causal relationships, we show that one can identify residual confounding using an indicator with the stated characteristics. We use simulations to assess the discriminatory ability of future ozone as an indicator of residual confounding in the association of ozone with asthma-related emergency department visits. Parameter choices are informed by observed data for ozone, meteorologic factors, and asthma. Results: In simulations, we found that ozone concentrations 1 day after the emergency department visits had excellent discriminatory ability to detect residual confounding by some factors that were intentionally omitted from the model, but weaker ability for others. Although not the primary goal, the indicator can also signal other forms of modeling errors, including substantial measurement error, and does not distinguish between them. Conclusions: The simulations illustrate that the indicator based on future air pollution levels can have excellent discriminatory ability for residual confounding, although performance varied by situation. Application of the method should be evaluated by considering causal relationships for the intended application, and should be accompanied by other approaches, including evaluation of a priori knowledge.

Fine Particulate Matter Components and Emergency Department Visits for Cardiovascular and Respiratory Diseases in the St. Louis, Missouri–Illinois, Metropolitan Area

Background: Given that fine particulate matter (≤ 2.5 μm; PM2.5) is a mixture of multiple components, it has been of high interest to identify its specific health-relevant physical and/or chemical features. Objectives: We conducted a time-series study of PM2.5 and cardiorespiratory emergency department (ED) visits in the St. Louis, Missouri–Illinois metropolitan area, using 2 years of daily PM2.5 and PM2.5 component measurements (including ions, carbon, particle-phase organic compounds, and elements) made at the St. Louis-Midwest Supersite, a monitoring site of the U.S. Environmental Protection Agency Supersites ambient air monitoring research program. Methods: Using Poisson generalized linear models, we assessed short-term associations between daily cardiorespiratory ED visit counts and daily levels of 24 selected pollutants. Associations were estimated for interquartile range changes in each pollutant. To allow comparison of relationships among multiple pollutants and outcomes with potentially different lag structures, we used 3-day unconstrained distributed lag models controlling for time trends and meteorology. Results: Considering results of our primary models, as well as sensitivity analyses and models assessing co-pollutant confounding, we observed robust associations of cardiovascular disease visits with 17α(H),21β(H)-hopane and congestive heart failure visits with elemental carbon. We also observed a robust association of respiratory disease visits with ozone. For asthma/wheeze, associations were strongest with ozone and nitrogen dioxide; observed associations of asthma/wheeze with PM2.5 and its components were attenuated in two-pollutant models with these gases. Differential measurement error due to differential patterns of spatiotemporal variability may have influenced patterns of observed associations across pollutants. Conclusions: Our findings add to the growing field examining the health effects of PM2.5 components. Combustion-related components of the pollutant mix showed particularly strong associations with cardiorespiratory ED visit outcomes. Citation: Sarnat SE, Winquist A, Schauer JJ, Turner JR, Sarnat JA. 2015. Fine particulate matter components and emergency department visits for cardiovascular and respiratory diseases in the St. Louis, Missouri–Illinois, metropolitan area. Environ Health Perspect 123:437–444; http://dx.doi.org/10.1289/ehp.1307776

Perfluorooctanoic acid exposure and thyroid disease in community and worker cohorts.

Background: Perfluorooctanoic acid (PFOA) was released from a mid-Ohio River Valley chemical plant, exposing the surrounding community to PFOA for >50 years, primarily through drinking water. Toxicological studies and some previous human studies have suggested that PFOA can disrupt thyroid homeostasis. We examined the association between PFOA and thyroid disease among community members and plant workers. Methods: Participants completed health surveys during 2008–2011. Yearly serum PFOA concentrations were estimated for each participant starting at birth or in 1952, whichever came later. We used Cox proportional hazard models, stratified by birth year, to assess adult thyroid disease hazard in relation to time-varying yearly or cumulative (sum of yearly estimates) estimated PFOA serum concentration, controlling for sex, race, education, smoking, and alcohol use. Results: Of 32,254 participants, 3,633 reported functional thyroid disease (excluding neoplasms, congenital disease, nodules without functional changes, cysts, and unspecified type). Analyses were restricted to 2109 cases of functional thyroid disease with thyroid prescription medication use and validation through medical record review. In analyses starting at age 20 years or in 1952, thyroid disease hazard ratios across cumulative exposure quintiles were 1.00, 1.24, 1.27, 1.36, and 1.37 among women and 1.00, 1.12, 0.83, 1.01, and 1.05 among men (log-linear trend tests: P = 0.03 and P = 0.85, respectively); similar results were observed for yearly exposure. Associations were observed for hyperthyroidism and hypothyroidism among women. Some subanalyses also suggested an increased hazard of hypothyroidism among men. Conclusions: Higher PFOA exposure was associated with incident functional thyroid disease in this large cohort with high exposure.

Effectiveness of a patient- and practice-level colorectal cancer screening intervention in health plan members: design and baseline findings of the CHOICE trial.

Evidence‐based interventions have been found effective in increasing colorectal cancer (CRC) screening. Translating these successful interventions into real world settings, such as health plans, can be challenging.

Early life perfluorooctanoic acid (PFOA) exposure and overweight and obesity risk in adulthood in a community with elevated exposure.

BACKGROUND Infants and young children may be susceptible to developmental effects of perfluorooctanoic acid (PFOA) exposure. Two previous studies, one that examined a general population exposed to environmental PFOA levels and one conducted in mice exposed to experimental PFOA levels, found that early life exposure was associated with higher body mass index (BMI) in adulthood and effects may be stronger in women than in men. OBJECTIVES Examine whether elevated early life PFOA exposure was associated with adult BMI among a group of mid-Ohio valley residents exposed to a wide range of early life PFOA levels due to emissions from a chemical plant. METHODS The cohort consisted of 8764 adults aged 20-40 years who reported height and weight on a survey between 2008 and 2011. Annual retrospective early life PFOA serum concentrations were estimated for each participant based on residential history and nearby chemical plant emissions as well as background exposure not originating from the facility. We defined early life exposure as the estimated average PFOA serum concentration over the first three years of life. We examined the association between early life PFOA exposure and adult overweight (BMI ≥ 25 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)) risk using logistic and linear regression models. RESULTS Nearly half the participants (45%) had early life PFOA exposure serum concentration estimates above background levels. Using participants who were exposed only to background PFOA levels as the referent category with quintiles of exposure above background, adjusted odds ratios (and 95% confidence intervals) for overweight risk by increasing exposure category for women were 1.0 (ref), 1.0 (0.8, 1.3), 1.0 (0.8, 1.2), 1.0 (0.8, 1.2), 0.9 (0.7, 1.1), and 0.9 (0.7, 1.1) and for men were 1.0 (ref), 0.9 (0.6, 1.1), 1.0 (0.7, 1.3), 1.0 (0.8, 1.4), 0.7 (0.5, 0.9), and 0.9 (0.7, 1.1). Odds ratios for adult obesity risk were similar. Regression coefficients from linear models using BMI as a continuous outcome showed no association between early life PFOA exposure and adult BMI. CONCLUSIONS Elevated levels of PFOA exposure in early life were not associated with overweight and obesity risk in adulthood and results did not vary by sex.