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Harnessing electronic health records to study emerging environmental disasters: a proof of concept with perfluoroalkyl substances (PFAS).

ABSTRACT: Environmental disasters are anthropogenic catastrophic events that affect health. Famous disasters include the Seveso disaster and the Fukushima-Daiichi nuclear meltdown, which had disastrous health consequences. Traditional methods for studying environmental disasters are costly and time-intensive. We propose the use of electronic health records (EHR) and informatics methods to study the health effects of emergent environmental disasters in a cost-effective manner. An emergent environmental disaster is exposure to perfluoroalkyl substances (PFAS) in the Philadelphia area. Penn Medicine (PennMed) comprises multiple hospitals and facilities within the Philadelphia Metropolitan area, including over three thousand PFAS-exposed women living in one of the highest PFAS exposure areas nationwide. We developed a high-throughput method that utilizes only EHR data to evaluate the disease risk in this heavily exposed population. We replicated all five disease/conditions implicated by PFAS exposure, including hypercholesterolemia, thyroid disease, proteinuria, kidney disease and colitis, either directly or via closely related diagnoses. Using EHRs coupled with informatics enables the health impacts of environmental disasters to be more easily studied in large cohorts versus traditional methods that rely on interviews and expensive serum-based testing. By reducing cost and increasing the diversity of individuals included in studies, we can overcome many of the hurdles faced by previous studies, including a lack of racial and ethnic diversity. This proof-of-concept study confirms that EHRs can be used to study human health and disease impacts of environmental disasters and produces equivalent disease-exposure knowledge to prospective epidemiology studies while remaining cost-effective.

SUBMITTER: Boland MR

PROVIDER: S-EPMC8357930 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children.MethodsForty overweight and obese Hispanic children (8-14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1-3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry. Multiple linear regression models were used to assess the association between baseline PFASs and changes in glucose homeostasis over follow-up. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with plasma PFASs concentrations. We performed a structural integrated analysis aiming to characterize the joint impact of all factors and to identify latent clusters of children with alterations in glucose homeostasis, based on their exposure and metabolomics profile.ResultsEach ln (ng/ml) increase in PFOA and PFHxS concentrations was associated with a 30.6 mg/dL (95% CI: 8.8-52.4) and 10.2 mg/dL (95% CI: 2.7-17.7) increase in 2-hour glucose levels, respectively. A ln (ng/ml) increase in PFHxS concentrations was also associated with 17.8 mg/dL increase in the glucose area under the curve (95% CI: 1.5-34.1). Pathway enrichment analysis showed significant alterations of lipids (e.g., glycosphingolipids, linoleic acid, and de novo lipogenesis), and amino acids (e.g., aspartate and asparagine, tyrosine, arginine and proline) in association to PFASs exposure. The integrated analysis identified a cluster of children with increased 2-h glucose levels over follow up, characterized by increased PFAS levels and altered metabolite patterns.ConclusionsThis proof-of-concept analysis shows that higher PFAS exposure was associated with dysregulation of several lipid and amino acid pathways and longitudinal alterations in glucose homeostasis in Hispanic youth. Larger studies are needed to confirm these findings and fully elucidate the underlying biological mechanisms.

Project description:BackgroundEnvironmental exposures to industrial chemicals, including perfluoroalkyl substances (PFAS), may play a role in bone development and future risk of osteoporosis. However, as prospective evidence is limited, the role of developmental PFAS exposures in bone density changes in childhood is unclear. The objective of this study was to estimate associations between serum-PFAS concentrations measured in infancy and early childhood and areal bone mineral density (aBMD) measured at age 9 years in a birth cohort of children from the Faroe Islands.MethodsWe prospectively measured concentrations of five PFAS in cord serum and serum collected at 18 months, 5 years and 9 years, and conducted whole-body DXA scans at the 9-year clinical visit. Our study included 366 mother-child pairs with DXA scans and at least one PFAS measurement. We estimated covariate-adjusted associations of individual PFAS concentrations with age-, sex- and height-adjusted aBMD z-scores using multivariable regression models and applied formal mediation analysis to estimate the possible impact of by several measures of body composition. We also evaluated whether associations were modified by child sex.ResultsWe found PFAS exposures in childhood to be negatively associated with aBMD z-scores, with the strongest association seen for perfluorononanoic acid (PFNA) at age 5 years. A doubling in age-5 PFNA was associated with a 0.15 decrease in aBMD z-score (95% CI: - 0.26, - 0.039). The PFNA-aBMD association was significantly stronger in males than females, although effect modification by sex was not significant for other PFAS exposures. Results from the mediation analysis suggested that any potential associations between aBMD and 18-month PFAS concentrations may be mediated by total body fat and BMI, although most estimated total effects for PFAS exposures at age 18 months were non-significant. PFAS exposures at age 9 were not associated with age-9 aBMD z-scores.ConclusionsThe PFAS-aBMD associations identified in this and previous studies suggest that bone may be a target tissue for PFAS. Pediatric bone density has been demonstrated to strongly track through young adulthood and possibly beyond; therefore, these prospective results may have important public health implications.

Project description:BackgroundHuman exposure to per- and polyfluoroalkyl substances (PFAS) has been primarily attributed to contaminated food and drinking water. However, additional PFAS exposure pathways have been raised by a limited number of studies reporting correlations between commercial and industrial products and PFAS levels in human media and biomonitoring. Systematic review (SR) methodologies have been widely used to evaluate similar questions using an unbiased approach in the fields of clinical medicine, epidemiology, and toxicology, but the deployment in exposure science is ongoing. Here we present a systematic review protocol that adapts existing systematic review methodologies and study evaluation tools to exposure science studies in order to investigate evidence for important PFAS exposure pathways from indoor media including consumer products, household articles, cleaning products, personal care products, plus indoor air and dust.ObjectivesWe will systematically review exposure science studies that present both PFAS concentrations from indoor exposure media and PFAS concentrations in blood serum or plasma. Exposure estimates will be synthesized from the evidence to answer the question, "For the general population, what effect does exposure from PFAS chemicals via indoor media have on blood, serum or plasma concentrations of PFAS?" We adapt existing systematic review methodologies and study evaluation tools from the U.S. EPA's Systematic Review Protocol for the PFBA, PFHxA, PFHxS, PFNA, and PFDA IRIS Assessments and the Navigation Guide for exposure science studies, as well as present innovative developments of exposure pathway-specific search strings for use in artificial intelligence screening software.Data sourcesWe will search electronic databases for potentially relevant literature, including Web of Science, PubMed, and ProQuest. Literature search results will be stored in EPA's Health and Environmental Research Online (HERO) database.Study eligibility and criteriaIncluded studies will present exposure measures from indoor media including consumer products, household articles, cleaning products, personal care products, plus indoor air and dust, paired with PFAS concentrations in blood, serum or plasma from adults and/or children in the general population. We focus on a subset of PFAS chemicals including perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), perfluorobutanoic acid (PFBA), perfluorobutane sulfonate (PFBS), perfluorodecanoic acid (PFDA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonate (PFHxS), and perfluorononanoic acid (PFNA).Study appraisal and synthesis methodsStudies will be prefiltered at the title and abstract level using computationally intelligent search strings to expedite the screening process for reviewers. Two independent reviewers will screen the prefiltered studies against inclusion criteria at the title/abstract level and then full-text level, after which the reviewers will assess the studies' risk of bias using an approach modified from established systematic review tools for exposure studies. Exposure estimates will be calculated to investigate the proportion of blood, serum or plasma) PFAS concentrations that can be explained by exposure to PFAS in indoor media.

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Harnessing electronic health records to study emerging environmental disasters: a proof of concept with perfluoroalkyl substances (PFAS).

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