Elevated serum chemokines are independently associated with both endometriosis and uranium exposure.

Endometriosis is a complex disease impacted by the hormonal and immune systems. Cytokines and chemokines are serum biomarkers that maybe useful to develop a noninvasive disease diagnosis. Individuals in the Fernald Community Cohort were exposed to uranium, a heavy metal with radioactive properties and estrogenic potential; therefore, serum samples from women in this cohort with or without uranium and with or without endometriosis were compared for alterations in chemokine, cytokine, and matrix metalloproteinase (MMP) levels. Control women were matched to endometriosis cases by uranium exposure, age, and body mass index. MMP levels were not altered. Five chemokines and one cytokine significantly increased in endometriosis cases versus controls irrespective of uranium exposure. Uranium exposure alone was associated with an increase in inflammatory chemokines. The majority of the elevated chemokines in endometriosis cases play important roles in attracting T helper-2 cells, which may be vital to understanding the immune response in endometriosis.

Comprehension and perceptions of study participants upon receiving perfluoroalkyl substance exposure biomarker results.

BACKGROUND: Measurement of environmental biomarkers in biomedia is increasingly used as a method of exposure characterization in human population studies. Reporting the results of biomarker measurements back to study participants has been controversial, including questions of ethics and whether the study participants would want to receive and would understand the results. METHODS: Recently we mailed individual measurements of two serum biomarkers, perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) to participants in three exposure studies of persons living in the Ohio River Valley, of whom 60 were parents of children who had been sampled. Many had serum concentrations of PFOA above the US population 95th percentile value. Reporting forms used in the three studies were somewhat different (either tables or charts for comparison to US population values) and varied in complexity. With all reports, we included information about concentrations of PFOA and PFOS in the general population, and a survey designed to ascertain the opinions of the study participants about the information they received. RESULTS: Approximately 33% (273/821) returned the survey, and of those, 96% reported that they were pleased that we had sent them the report. Most (86%) responded that the results were easy to understand and the enclosed fact sheet was helpful in answering questions (87%). Regarding the amount of information, most felt that we provided the "right amount" (78%) but some "too much" (7%) and some "too little" (15%). The majority (53%) were surprised at their serum concentrations. Of those with serum values > 13.0 ng/mL, 74% responded that they thought their serum concentration was "high", but only 22% of those with serum concentrations ≤5.6 responded that their concentration was "low". Surprisingly, many talked to no one about their levels; those who did were most likely to discuss the report with family members. CONCLUSIONS: Reporting back individual environmental biomarker results is generally well received by study participants, and those with high concentrations perceived them to be high. Questions remain as to why study participants did not discuss their results with others.

Polyfluoroalkyl substance exposure in the Mid-Ohio River Valley, 1991-2012.

BACKGROUND: Industrial discharges of perfluorooctanoic acid (PFOA) to the Ohio River, contaminating water systems near Parkersburg, WV, were previously associated with nearby residents' serum PFOA concentrations above US general population medians. Ohio River PFOA concentrations downstream are elevated, suggesting Mid-Ohio River Valley residents are exposed through drinking water. OBJECTIVES: Quantify PFOA and 10 other per- and polyfluoroalkyl substances (PFAS) in Mid-Ohio River Valley resident sera collected between 1991 and 2013 and determine whether the Ohio River and Ohio River Aquifer are exposure sources. METHODS: We measured eleven PFAS in 1608 sera from 931 participants. Serum PFOA concentration and water source associations were assessed using linear mixed-effects models. We estimated between-sample serum PFOA using one-compartment pharmacokinetics for participants with multiple samples. RESULTS: In serum samples collected as early as 1991, PFOA (median = 7.6 ng/mL) was detected in 99.9% of sera; 47% had concentrations greater than US population 95th percentiles. Five other PFAS were detected in greater than 82% of samples; median other PFAS concentrations were similar to the US general population. Serum PFOA was significantly associated with water source, sampling year, age at sampling, tap water consumption, pregnancy, gravidity and breastfeeding. Serum PFOA was 40-60% lower with granular activated carbon (GAC) use. Repeated measurements and pharmacokinetics suggest serum PFOA peaked 2000-2006 for participants using water without GAC treatment; where GAC was used, serum PFOA concentrations decreased from 1991 to 2012. CONCLUSIONS: Mid-Ohio River Valley residents appear to have PFOA, but not other PFAS, serum concentrations above US population levels. Drinking water from the Ohio River and Ohio River Aquifer, primarily contaminated by industrial discharges 209-666 km upstream, is likely the primary exposure source. GAC treatment of drinking water mitigates, but does not eliminate, PFOA exposure.

Headache Disorders May Be a Risk Factor for the Development of New Onset Hypothyroidism.

OBJECTIVE: To determine whether headache disorders are a risk factor for the development of new onset hypothyroidism. BACKGROUND: Past studies have reported associations between headache disorders and hypothyroidism, but the directionality of the association is unknown. METHODS: This was a longitudinal retrospective cohort study using data from the Fernald Medical Monitoring Program (FMMP). Residents received physical examinations and thyroid function testing every 3 years during the 20 year program. Residents were excluded from the cohort if there was evidence of past thyroid disease or abnormal thyroid function tests at the first office visit. A diagnosis of a headache disorder was established by self-report of "frequent headaches," use of any headache-specific medication, or a physician diagnosis of a headache disorder. The primary outcome measure was new onset hypothyroidism defined as the initiation of thyroid replacement therapy or TSH ≥ 10 without thyroid medication. A Cox survival analysis with time dependent variables were used for the model. Headache disorders, age, sex, body mass index, income, smoking, narcotic use, and hypothyroidism-producing medications were independent variables in the model. RESULTS: Data from 8412 residents enrolled in the FMMP were used in the current study. Headache disorders were present in about 26% of the residents and new onset hypothyroidism developed in ∼7%. The hazard ratio for the development of new onset hypothyroidism was 1.21 (95% CI = 1.001, 1.462) for those with headache disorders. CONCLUSIONS: Headache disorders may be associated with an increased risk for the development of new onset hypothyroidism.

Association of systemic lupus erythematosus with uranium exposure in a community living near a uranium-processing plant: a nested case-control study.

OBJECTIVE: To explore the hypothesis that cases of systemic lupus erythematosus (SLE) would be found more frequently in community members with high prior uranium exposure in the Fernald Community Cohort (FCC). METHODS: A nested case-control study was performed using data from the FCC, a volunteer population of individuals who had resided near a uranium ore-processing plant in Fernald, Ohio during the years of plant operation; uranium plant workers were excluded. Members of the FCC were monitored for 18 years. SLE cases were identified using the American College of Rheumatology 1997 revised classification criteria, laboratory testing, and medical record review. Each case was matched to 4 controls by age, race, and sex. Sera from potential cases and controls were screened for autoantibodies. Cumulative exposure to uranium particulates was calculated using a dosimetry model. Logistic regression with covariates was used to calculate the odds ratios (ORs) with 95% confidence intervals (95% CIs) for the probability of an association between uranium exposure and SLE. RESULTS: The FCC comprised 4,187 individuals with minimal levels of uranium exposure, 1,273 with moderate exposure, and 2,756 with high exposure. The diagnosis of SLE was confirmed in 23 of 31 individuals who had been assigned International Classification of Diseases, Ninth Revision codes for lupus, and was also confirmed in 2 of 43 individuals who had been prescribed hydroxychloroquine. The female to male ratio was 5.25:1. Of the 25 confirmed SLE cases, 12 were in the high exposure group. The presence of SLE was associated with higher levels of uranium exposure (OR 3.92, 95% CI 1.13-13.59; P = 0.031). CONCLUSION: High uranium exposure is associated with SLE, as compared to matched controls, in this sample of uranium-exposed individuals. Potential explanations for this relationship include possible autoimmune or estrogen effects of uranium, somatic mutation, epigenetic effects, or effects of some other unidentified accompanying exposure.

Medical monitoring: a beneficial remedy for residents living near an environmental hazard site.

OBJECTIVE: People living close to an environmental hazard site may suffer health harms from real or perceived contaminant exposures. In class-action litigation, medical monitoring is a potential remedy that has been allowed in some jurisdictions but not others. From 1952 to 1989, a US Department of Energy uranium metal plant near Fernald, Ohio, released ionizing radiation and uranium particulates into the surrounding community. METHODS: Settlement of litigation between nearby residents and the Department of Energy resulted in an 18-year medical monitoring program (N = 9775), which focused on general health promotion rather than effects of uranium. RESULTS: Participation was higher than projected; decreases in common risk factors (cholesterol and blood pressure) and deaths from cancer have been observed. CONCLUSIONS: These data support the appropriateness of comprehensive medical monitoring as a remedy for people affected by defined sources of environmental contaminants.

Health effects in community residents near a uranium plant at Fernald, Ohio, USA.

OBJECTIVES: Health outcomes in persons who lived in the area surrounding a U.S. Department of Energy (DOE) uranium processing plant near Fernald, Ohio were evaluated using data of Fernald Medical Monitoring Program (FMMP) participants. METHODS: Residential history information was used to identify participants who lived in close proximity to the plant (less than 2 miles), in the direction of groundwater runoff (south of the plant), or used a well or cistern as a drinking water source. Standardized prevalence ratios (SPRs) for certain disease endpoints were calculated using the U.S. National Health Interview Survey(NHIS) and the National Health and Nutrition Examination Survey (NHANES) data files for comparison rates. RESULTS: Findings suggest that prior living within the Fernald exposure domain is related to increased prevalence of urinary system disease. Statistically significant elevations of bladder disease (standardized prevalence ratio or SPR = 1.32) and kidney disease (SPR = 2.15), including sub-categories, kidney stones (SPR = 3.98) and chronic nephritis (SPR = 2.03) were noted, as well as increased rates for hematuria and urethral stricture. In regression analyses with adjustment forage and sex, serum creatinine levels were increased in those who had lived close to the plant. Increased white blood cell count and hemoglobin levels, and decreased mean corpuscular volume were also found in those living less than 2 miles from the plant. Those who used a well or cistern for drinking water were found to have increased urinary microalbumin, red blood cell count and hematocrit. CONCLUSIONS: These preliminary findings will provide the basis for future hypothesis testing incorporating important determinants of exposure not included in this study, such as duration and calendar year of exposure, location relevant to prevailing wind direction, and age at exposure.