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In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.

The global use of pesticides is increasing; however, few studies have examined the exposure of current-use pesticide exposure in Inuit populations. Some current use pesticides are also capable of long-range transport, potentially increasing exposures to northern populations. The study aim was to analyse pesticide (chlorophenoxy, organophosphates, and pyrethroid pesticide) biomarker levels in pooled samples from an Inuit population in Nunavik, Quebec. Thirty pooled samples from the Qanuilirpitaa? 2017 survey (Q2017) from individuals aged 16–80 years were included. Creatinine-adjusted arithmetic (AM) were compared by sex, age, and region sub-groups, and geometric mean concentrations (GM) were compared to those in the Canadian Health Measures Survey (CHMS). Most analysed pesticide biomarkers were detected, and PNP (a metabolite of methyl and ethyl parathion), trans-DCCA (a metabolite of pyrethroids), and 3,5,6-TCP (a metabolite of chlorpyrifos) had the highest concentrations. Concentrations in Q2017 were largely similar to or less than CHMS concentrations. Although not significant, there was a general increase in 2,4-D (a chlorophenoxy biomarker), 3,5,6-TCP, 3-PBA (a metabolite of pyrethroids), and trans-DCCA with increasing age. Concentrations were also somewhat higher in females versus males, but these were not significant. Environmental exposures to current use pesticides were detected in Nunavik and concentrations were similar to or less than those in the general Canadian population. Regular monitoring of current use pesticide exposures is recommended given the increasing global use of pesticides. [ABSTRACT FROM AUTHOR]

Background: Whether including additional environmental risk factors improves cardiovascular disease (CVD) prediction is unclear. We attempted to improve CVD mortality prediction performance beyond traditional CVD risk factors by additionally using metals measured in the urine and blood and with statistical machine learning methods. Methods: Our sample included 7,085 U.S. adults aged 40 years or older from the National Health and Nutrition Examination Survey 2003–2004 through 2015–2016, linked with the National Death Index through December 31, 2019. Data were randomly split into a 50/50 training dataset used to construct CVD mortality prediction models (n = 3542) and testing dataset used as validation to assess prediction performance (n = 3543). Relative to the traditional risk factors (age, sex, race/ethnicity, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, hypertension, and diabetes), we compared models with an additional 17 blood and urinary metal concentrations. To build the prediction models, we used Cox proportional hazards, elastic-net (ENET) penalized Cox, and random survival forest methods. Results: 420 participants died from CVD with 8.8 mean years of follow-up. Blood lead, cadmium, and mercury were associated (p < 0.005) with CVD mortality. Including these blood metals in a Cox model, initially containing only traditional risk factors, raised the C-index from 0.845 to 0.847. Additionally, the Net Reclassification Index showed that 23% of participants received a more accurate risk prediction. Further inclusion of urinary metals improved risk reclassification but not risk discrimination. Conclusions: Incorporating blood metals slightly improved CVD mortality risk discrimination, while blood and urinary metals enhanced risk reclassification, highlighting their potential utility in improving cardiovascular risk assessments. [ABSTRACT FROM AUTHOR]

Background: The indoor home environment plays a crucial role in determining the outcome of respiratory diseases, including asthma. Researchers, clinicians, and patients would benefit from self-reported questionnaires to assess indoor home environmental exposures that may impact on respiratory health. Objective: To review self-reported instruments for assessing indoor home environmental exposures in asthma patients and to characterise their content, development, and psychometric properties. Design: A scoping review was conducted with content assessment. Methods: A literature search was conducted in Embase and PubMed using the key words housing quality, questionnaire and asthma and their index terms, covering articles published in English between January 2000 to July 2023. Articles in which questionnaires or single item questions were used to assess indoor home environmental exposures in asthma patients in middle- and high-income countries were included. We excluded articles in which the questionnaire required an interviewer or onsite observations and those conducted in low-income countries. Results: We screened 1584 articles to identify 44 studies containing self-reported questionnaires measuring indoor home environmental exposures. 36 studies (82%) were cross sectional, 35 (80%) had a sample size of greater than 1000 participants, and 29 (66%) were conducted in children. Most studies (86%, n = 38) had binary (yes/no) or multiple-choice responses. 25 studies (57%) included a recall period of 12 months. 32 studies (73%) had a response rate of greater than 50%. Dampness, biological exposures (e.g. mould), and second-hand tobacco smoke were the most assessed indoor home environmental exposures. Childhood asthma (54%, n = 24) and asthma symptoms (36%, n = 16) were the most examined asthma related outcomes. The exposure most associated with adverse asthma outcomes was exposure to damp (79%, n = 35). 13 studies (29%) had developed a self-reported instrument by adapting questions from previous studies and almost all instruments (n = 42 studies, 95%) had not been validated. Conclusions: The scoping review did not identify a comprehensive, validated self-reported questionnaire for assessing indoor home environmental exposures in patients with asthma. There is need to develop and validate a robust but pragmatic self-reported instrument, incorporating the findings from this review. Lay summary: Background: The home environment significantly affects respiratory diseases like asthma. To help researchers, doctors, and patients, there is a need for instruments that people can use to report environmental factors at home that might influence their asthma. Objective: The aim was to review self-reported instruments that asthma patients use to assess their home environments. The review looked at what these instruments measured, how they were developed, and how reliable they were. Design: The study used a scoping review, which provides an overview of the available evidence, and assessed the content of existing questionnaires. Methods: Researchers searched scientific articles in two major databases, Embase and PubMed. They looked for articles in English published since 2000. They included studies from middle- and high-income countries where people filled out questionnaires about their home environment's impact on asthma. They excluded studies needing an interviewer or on-site visits and those from low-income countries. Results: From 1584 articles, 44 studies were selected. Most studies (82%) were cross-sectional, meaning they looked at data from a single point in time. Four out of five studies included more than 1000 participants, and two thirds involved children. The questionnaires often had yes/no or multiple-choice questions and usually asked about conditions over the past year or more. Common topics were dampness, exposure to mould, and second-hand smoke. Almost three quarters of studies received a response from more than half of the participants they asked. Dampness was the factor most linked to worsening asthma. While many studies adapted questions from previous research, only one in 20 reported how they validated their questionnaires. Conclusions: The review did not find a single, well-validated questionnaire for assessing home environments in asthma patients. There is a need to develop a reliable and practical instrument based on these findings. [ABSTRACT FROM AUTHOR]

High temperatures and air pollution exposure are individually known risks to human health, with amplifying adverse health effects during periods of co-exposure. This study compared co-occurring individual-level exposures to particulate matter (PM5, aerodynamic diameter of ≤5 μm) and heat among women in residential and agricultural settings in Guatemala. We measured personal and ambient exposure to PM5, temperature, and humidity among 21 female sugarcane workers in the fields and on their off days. We measured similar exposures among a group of 30 community members not involved in sugarcane work. We collected 171 personal PM5 measurements across 18 sampling days. The median workday personal PM5 concentration was 271 µg/m3, which was 3.6-fold higher than ambient area levels in the fields. The median personal PM5 concentration was 95.8 µg/m3 for off-work days and 83.5 µg/m3 for community days. The average workday individual-level temperature and humidity were 39.4 °C and 82.4%, respectively, with significantly lower temperatures on off-work and community days. The women workers and community members were exposed to high levels of PM5 and heat in both occupational and residential settings. Research needs to consider individual-level exposures at both work and home to help tailor more effective comprehensive prevention efforts to reduce risks. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify environmental risk factors associated with asthmatic fixed airflow obstruction (FAO) and assess the relationship between small airway abnormalities defined by forced expiratory flow at 25– 75% (FEF25-75%) and FAO. Patients and Methods: We analyzed data from 312 han Chinese patients with stable asthma on standard treatment. Low FEF25-75% was defined as post-bronchodilator FEF25-75% z-score <− 0.8435, and FAO as post-bronchodilator FEV1/FVC z-score <− 1.645. Exposure levels were retrospectively analyzed in relation to FAO risk in asthmatics. Asthmatics were grouped by low FEF25-75% and FAO, and lung function, environmental exposure, daily symptoms, and exacerbations in the previous year were compared cross-sectionally across groups. Results: In retrospective analyses, pack-years of smoking in male patients (adjusted odd ratio [95% confidence interval] 1.05 [1.03– 1.07], P< 0.001), biomass exposure for > 20 years (2.65 [1.13– 6.43], P=0.027), occupational exposure for > 10 years (2.01 [1.06– 3.86], P=0.035) and occupational exposure for > 20 years (2.67 [1.24– 5.91], P=0.013) were associated with asthmatic FAO. In cross-sectional analyses, compared with the normal FEF25-75%/ asthmatics without FAO (NON-FAO) group, the low FEF25-75%/ asthmatics with FAO (FAO) group had lower FEV1 z-scores and FEV1/FVC z-scores, more pack-years and years of biomass and occupational exposure, higher Asthma Control Questionnaire-5 and Chronic Obstructive Pulmonary Disease Assessment Test scores, and more frequent exacerbations. The low FEF25-75%/NON-FAO group showed the same trend, but to a lesser extent. Conclusion: Chronic airway inflammation is not the only driver of asthmatic FAO, and management and treatment targeting environmental risk factors (smoking and biomass and occupational exposures) may slow FAO progression in asthmatics. The FEF25-75% determined by the z-score is a reliable marker of small airway abnormalities, and patients with low FEF25-75% are at greater risk for FAO, requiring more frequent follow-up. [ABSTRACT FROM AUTHOR]

Abstract Background Whether including additional environmental risk factors improves cardiovascular disease (CVD) prediction is unclear. We attempted to improve CVD mortality prediction performance beyond traditional CVD risk factors by additionally using metals measured in the urine and blood and with statistical machine learning methods. Methods Our sample included 7,085 U.S. adults aged 40 years or older from the National Health and Nutrition Examination Survey 2003–2004 through 2015–2016, linked with the National Death Index through December 31, 2019. Data were randomly split into a 50/50 training dataset used to construct CVD mortality prediction models (n = 3542) and testing dataset used as validation to assess prediction performance (n = 3543). Relative to the traditional risk factors (age, sex, race/ethnicity, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, hypertension, and diabetes), we compared models with an additional 17 blood and urinary metal concentrations. To build the prediction models, we used Cox proportional hazards, elastic-net (ENET) penalized Cox, and random survival forest methods. Results 420 participants died from CVD with 8.8 mean years of follow-up. Blood lead, cadmium, and mercury were associated (p

Abstract Background The indoor home environment plays a crucial role in determining the outcome of respiratory diseases, including asthma. Researchers, clinicians, and patients would benefit from self-reported questionnaires to assess indoor home environmental exposures that may impact on respiratory health. Objective To review self-reported instruments for assessing indoor home environmental exposures in asthma patients and to characterise their content, development, and psychometric properties. Design A scoping review was conducted with content assessment. Methods A literature search was conducted in Embase and PubMed using the key words housing quality, questionnaire and asthma and their index terms, covering articles published in English between January 2000 to July 2023. Articles in which questionnaires or single item questions were used to assess indoor home environmental exposures in asthma patients in middle- and high-income countries were included. We excluded articles in which the questionnaire required an interviewer or onsite observations and those conducted in low-income countries. Results We screened 1584 articles to identify 44 studies containing self-reported questionnaires measuring indoor home environmental exposures. 36 studies (82%) were cross sectional, 35 (80%) had a sample size of greater than 1000 participants, and 29 (66%) were conducted in children. Most studies (86%, n = 38) had binary (yes/no) or multiple-choice responses. 25 studies (57%) included a recall period of 12 months. 32 studies (73%) had a response rate of greater than 50%. Dampness, biological exposures (e.g. mould), and second-hand tobacco smoke were the most assessed indoor home environmental exposures. Childhood asthma (54%, n = 24) and asthma symptoms (36%, n = 16) were the most examined asthma related outcomes. The exposure most associated with adverse asthma outcomes was exposure to damp (79%, n = 35). 13 studies (29%) had developed a self-reported instrument by adapting questions from previous studies and almost all instruments (n = 42 studies, 95%) had not been validated. Conclusions The scoping review did not identify a comprehensive, validated self-reported questionnaire for assessing indoor home environmental exposures in patients with asthma. There is need to develop and validate a robust but pragmatic self-reported instrument, incorporating the findings from this review.

Idiopathic pulmonary fibrosis (IPF), the most common and severe of the idiopathic interstitial pneumonias, is a chronic and relentlessly progressive disease, which occurs mostly in middle-aged and elderly males. Although IPF is by definition idiopathic, multiple factors have been reported to increase disease risk, aging being the most prominent one. Several occupational and environmental exposures, including metal dust, wood dust and air pollution, as well as various lifestyle variables, including smoking and diet, have also been associated with an increased risk of IPF, probably through interaction with genetic factors. Many of the predisposing factors appear to act also as trigger for acute exacerbations of the disease, which herald a poor prognosis. The more recent literature on inhalation injuries has focused on the first responders in the World Trade Center attacks and military exposure. In this review, we present an overview of the environmental and occupational causes of IPF and its pathogenesis. While our list is not comprehensive, we have selected specific exposures to highlight based on their overall disease burden.

Abstract Sex and gender differences play a crucial role in health and disease outcomes. This study used data from the National Health and Nutrition Examination Survey to explore how environmental exposures affect health-related traits differently in males and females. We utilized a sex-stratified phenomic environment-wide association study (PheEWAS), which allowed the identification of associations across a wide range of phenotypes and environmental exposures. We examined associations between 272 environmental exposures, including smoking-related exposures such as cotinine levels and smoking habits, and 58 clinically relevant blood phenotypes, such as serum albumin and homocysteine levels. Our analysis identified 119 sex-specific associations. For example, smoking-related exposures had a stronger impact on increasing homocysteine, hemoglobin, and hematocrit levels in females while reducing serum albumin and bilirubin levels and increasing c-reactive protein levels more significantly in males. These findings suggest mechanisms by which smoking exposure may pose higher cardiovascular risks and greater induced hypoxia for women, and greater inflammatory and immune responses in men. The results highlight the importance of considering sex differences in biomedical research. Understanding these differences can help develop more personalized and effective health interventions and improve clinical outcomes for both men and women.

This study aims to evaluate the association between social determinants, environmental exposure metrics, and the risk of asthma emergency department (ED) visits in the New York State (NYS) Medicaid population using small-area analysis. Traffic densities for each census tract in NYS were calculated using the length of road segments within each tract and total area of the tract to produce a measure of average number of vehicles per square meter per day. Data on social determinants of health including internal and external environments and other demographic factors were obtained from various sources. Poisson regression analyses were conducted to identify significant factors associated with asthma ED visits in Medicaid claim and encounter data for years 2005–2015. High traffic density in NYS excluding New York City (NYC) correlated with increased risk of asthma ED visits (RR 1.69; 95% CI: 1.42, 2.00), mitigated by adjusting for environmental and social determinants (RR 1.00; 95% CI: 0.85, 1.19). Similar trends were observed in NYC only (RR 1.19; 95% CI: 1.00, 1.41), with the adjusted risk remaining elevated (RR 1.14; 95% CI: 0.98, 1.33) albeit not statistically significant. Living in census tracts with high concentrated disadvantage index, high proportions of minorities, and less green space predicted higher asthma ED visits. We mapped predicted rates and model residuals to identify areas of high risk. Our results support previous findings that environmental and social risk factors in poor and urban areas contribute to asthma exacerbations in the NYS Medicaid population, even if they may not necessarily contribute to its development.

Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015–2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25–2.60) for the Weng Park plant and 1.39 (1.12–1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission.

Sex and gender differences play a crucial role in health and disease outcomes. This study used data from the National Health and Nutrition Examination Survey to explore how environmental exposures affect health-related traits differently in males and females. We utilized a sex-stratified phenomic environment-wide association study (PheEWAS), which allowed the identification of associations across a wide range of phenotypes and environmental exposures. We examined associations between 272 environmental exposures, including smoking-related exposures such as cotinine levels and smoking habits, and 58 clinically relevant blood phenotypes, such as serum albumin and homocysteine levels. Our analysis identified 119 sex-specific associations. For example, smoking-related exposures had a stronger impact on increasing homocysteine, hemoglobin, and hematocrit levels in females while reducing serum albumin and bilirubin levels and increasing c-reactive protein levels more significantly in males. These findings suggest mechanisms by which smoking exposure may pose higher cardiovascular risks and greater induced hypoxia for women, and greater inflammatory and immune responses in men. The results highlight the importance of considering sex differences in biomedical research. Understanding these differences can help develop more personalized and effective health interventions and improve clinical outcomes for both men and women. [ABSTRACT FROM AUTHOR]

Thyroid cancer rates have risen globally over the past four decades, with Puerto Rico experiencing a particularly pronounced increase. This may be linked to higher metal exposure, as some metals are endocrine disruptors and carcinogens. Currently, certain regions of Puerto Rico have Superfund programs because of high concentrations of metals in the soil. Therefore, we investigated the association between thyroid cancer incidence and three metals (lead, cadmium, and mercury) with known endocrine-disrupting properties and increased levels in soil samples in Puerto Rico. We used the National Health and Nutrition Examination Survey (NHANES) data for heavy metal levels and the thyroglobulin antibody (TgAb) as a thyroid cancer marker. Additionally, we performed an ecological study using data from the Environmental Protection Agency (EPA) report on Metals from Natural and Anthropogenic Sources in Puerto Rico Soils and data from the Puerto Rico Central Cancer Registry on age-adjusted thyroid cancer incidence rates from 2015 to 2019. Through NHANES analysis, we found a significant negative association between mercury and TgAb. Through our ecological study, we observed higher thyroid cancer incidence rates and increased metal levels in the soil in the northern parts of Puerto Rico. Our heterogenous results necessitate further research on this topic. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) exposure is a potential risk factor for thyroid cancer and may be a contributor to the increasing thyroid cancer incidence rates. A systematic review and meta-analysis was performed to summarize all human studies to date investigating the association between PFAS exposure and thyroid cancer. A search of the National Library of Medicine and National Institutes of Health PubMed and Scopus databases was done to identify relevant articles published in English through January 2024. Studies reporting the association between PFAS exposure and thyroid cancer using odds ratios (OR) were included in the meta-analysis with summary estimate calculated using a random effects model (n=5). Perfluorooctanoic acid (PFOA) was the most investigated PFAS. Results of the included studies varied, ranging from significant positive to significant negative associations with thyroid cancer incidence for different PFAS. Meta-analyses of PFOA, Perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS) were not significant. This comprehensive review of the current literature highlights the limited knowledge and inconsistent results of this association. Large longitudinal cohort studies with varying time between sample collection and thyroid cancer diagnosis are needed to better understand the role of PFAS exposure on thyroid carcinogenesis. • Limited number of human studies on PFAS exposure and thyroid cancer. • Inconsistent results of PFAS exposure and thyroid cancer associations in humans. • No significant results in meta-analyses for 4 PFAS and thyroid cancer. • Urgent need for longitudinal cohort studies on PFAS exposure and (thyroid) cancer. [ABSTRACT FROM AUTHOR]

Objectives: Prevention methods for carbon monoxide (CO) poisoning in Wisconsin address occupational and nonoccupational exposures together, but differences between the settings could inform new approaches to preventing occupational CO poisonings. We described occupational CO poisonings in Wisconsin from July 1, 2018, through July 1, 2021, using surveillance data from the Wisconsin Electronic Disease Surveillance System and Wisconsin Poison Center. Methods: We identified cases of CO poisoning from the Wisconsin Electronic Disease Surveillance System and Wisconsin Poison Center. Occupational CO poisonings were records where "workplace" was recorded as the location of exposure. We excluded records classified as suspect/not a case, those missing laboratory results or information on exposure source/location, and intentional poisonings. We compared characteristics between occupational and nonoccupational settings using odds ratios (ORs), and we estimated crude incidence rates of occupational exposures by occupation. Results: We identified 614 cases of CO poisoning, of which 168 (27.4%) were occupational exposures. When compared with patients with nonoccupational exposures, patients with occupational exposures were more likely to be male (OR = 3.8; 95% CI, 2.4-6.1), Hispanic (OR = 2.4; 95% CI, 1.4-4.2), and younger (mean difference [SD] = 6.6 [20.9]). Several CO sources were significantly associated with occupational poisonings: forklifts (OR = 58.4; 95% CI, 13.9-246.1; P <.001), pressure sprayers (OR = 2.4; 95% CI, 1.3-4.4; P =.003), and other gasoline-powered tools (OR = 3.8; 95% CI, 2.3-6.3; P <.001). The natural resources, construction, and maintenance occupation group had the highest crude incidence rate—45.0 poisonings per 100 000 full-time equivalent employees. Conclusions: Incorporating data from the Wisconsin Poison Center improved data quality, but surveillance is limited by underreporting. Creating strategies to increase reporting would allow for a more comprehensive understanding of occupational CO poisoning. [ABSTRACT FROM AUTHOR]

The association between PM2.5 and cardiovascular and respiratory mortality from a gender perspective is scarce in the literature, despite the fifth sustainable development goal (SDG 5) related to gender equality. This study aims to assess whether gender analysis in the association of PM2.5 on respiratory and cardiovascular mortality shows a different impact on women than men around diverse regions of the world. We conducted a scoping review of the Web of Science database citations for epidemiological studies published between June 2020 and October 2021. The articles that met our inclusion criteria were grouped into three categories based on gender-induced effects to compare the registered risks between men and women. Of 956 articles identified, 36 published were eligible. The regions with the most gender analysis studies were Asia (n = 15), North America (n = 15), and Europe (n = 6). Irrespective of the gender-induced effect category, 7 articles reported a higher risk for women than men, and 14 declared the contrary. The magnitude of the impact of PM2.5 on cardiovascular and respiratory mortality in women is unclear. Differences in covariates, methods of analysis, and regional characteristics of each country could influence the results. All studies lacked indoor PM2.5 measurements, which may bias mortality estimates for the female population. The use of indoor PM2.5 measurements would more accurately reflect the air quality that women and girls typically breathe. [ABSTRACT FROM AUTHOR]

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The longitudinal collection of biological samples from over 7000 birthing parents and their children within the HBCD study enables research on pre- and postnatal exposures (e.g., substance use, toxicants, nutrition), and biological processes (e.g., genetics, epigenetic signatures, proteins, metabolites) on neurobehavioral developmental outcomes. The following biosamples are collected from the birthing parent: 1) blood (i.e., whole blood, serum, plasma, buffy coat, and dried blood spots) during pregnancy, 2) nail clippings during pregnancy and one month postpartum, 3) urine during pregnancy, and 4) saliva during pregnancy and at in-person postnatal assessments. The following samples are collected from the child at in-person study assessments: 1) saliva, 2) stool, and 3) urine. Additionally, placenta tissue, cord blood, and cord tissue are collected by a subset of HBCD sites. Here, we describe the rationale for the collection of these biospecimens, their current and potential future uses, the collection protocol, and collection success rates during piloting. This information will assist research teams in the planning of future studies utilizing this collection of biological samples.

The global use of pesticides is increasing; however, few studies have examined the exposure of current-use pesticide exposure in Inuit populations. Some current use pesticides are also capable of long-range transport, potentially increasing exposures to northern populations. The study aim was to analyse pesticide (chlorophenoxy, organophosphates, and pyrethroid pesticide) biomarker levels in pooled samples from an Inuit population in Nunavik, Quebec. Thirty pooled samples from the Qanuilirpitaa? 2017 survey (Q2017) from individuals aged 16–80 years were included. Creatinine-adjusted arithmetic (AM) were compared by sex, age, and region sub-groups, and geometric mean concentrations (GM) were compared to those in the Canadian Health Measures Survey (CHMS). Most analysed pesticide biomarkers were detected, and PNP (a metabolite of methyl and ethyl parathion), trans-DCCA (a metabolite of pyrethroids), and 3,5,6-TCP (a metabolite of chlorpyrifos) had the highest concentrations. Concentrations in Q2017 were largely similar to or less than CHMS concentrations. Although not significant, there was a general increase in 2,4-D (a chlorophenoxy biomarker), 3,5,6-TCP, 3-PBA (a metabolite of pyrethroids), and trans-DCCA with increasing age. Concentrations were also somewhat higher in females versus males, but these were not significant. Environmental exposures to current use pesticides were detected in Nunavik and concentrations were similar to or less than those in the general Canadian population. Regular monitoring of current use pesticide exposures is recommended given the increasing global use of pesticides.

Experiencing a hurricane during pregnancy is associated with increased risk of adverse birth outcomes and poor mental health. Pregnant people from marginalized communities are more susceptible to adverse effects, as they have fewer resources to overcome hardships at a time when shelter and nutrition are essential. When Hurricane Maria (HM) devastated Puerto Rico in September 2017, the archipelago was already burdened with high poverty, health disparities, environmental contamination, and fragile utility infrastructure. We aimed to compare biomarkers of environmental exposures among pregnant participants in the PROTECT cohort before and after HM and to identify hurricane-related sources of exposure. Metals, PAHs, phthalate metabolites, and phenols were measured in urine samples collected from participants at three prenatal visits (2011–2019). Samples were categorized as before, 6 months after HM. Using linear mixed effects models, we found that in the 6 months after HM, participants had higher Co, Ni, and DEHPTP concentrations, indicating increased exposure, and lower concentrations of PAHs, several metals, and phthalates, suggesting decreased exposure, compared to pre-HM levels. Biomarkers were not associated with potential exposure sources assessed through questionnaire or previously measured tap water contaminants. This study provides insight into how extreme weather events may alter environmental exposures among pregnant people in Puerto Rico. As climate change has increased the frequency and magnitude of such events, additional research is needed to clarify the implications for maternal and child health and to identify sources of related environmental exposures within this vulnerable population.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The charge of the HBCD Social and Environmental Determinants (SED) working group is to develop and implement a battery of assessments to broadly characterize the social and physical environment during the prenatal period and early life to characterize risk and resilience exposures that can impact child growth and development. The SED battery consists largely of measures that will be repeated across the course of the HBCD Study with appropriate modifications for the age of the child and include participant demographics, indicators of socioeconomic status, stress and economic hardship, bias and discrimination (e.g., racism), acculturation, neighborhood safety, child and maternal exposures to adversity, environmental toxicants, social support, and other protective factors. Special considerations were paid to reducing participant burden, promoting diversity, equity, and inclusion, and adopting trauma-informed practices for the collection of sensitive information such as domestic violence exposure and adverse childhood experiences. Overall, the SED battery will provide essential data to advance understanding of child development and approaches to advance health equity across infant and child development.

Recent evidence indicates that the human womb is contaminated with a variety of particulate contaminants. Microplastics (MPs, tiny plastic particles, 0.1 – 5000 µm) generated by the breakdown of larger plastic products in the environment) accumulation in human placenta has recently been described. In addition, recent evidence has correlated the number of air pollution particulates in term placentas to the loading of these particles in dust from the gestational parent home. The current study sought to characterize the accumulation of plastic and non-plastic particles (NPP) within the term human placenta. Placenta tissues were collected from healthy, singleton pregnancies following vaginal (n = 5) and caesarean section (n = 5) deliveries at a tertiary care centre located in an urban Canadian city (Ottawa, ON), with particles detected and characterized by Raman micro-spectroscopy. Both plastic and non-plastic particles were identified in all placentas examined, with an average of 1 ± 1.2 MPs /g and 4 ± 2.9 NPP /g of tissue. Similar tissue concentrations of MPs and NNP were identified in all regions of the placenta (basal plate, chorionic villous, chorionic plate), and did not differ according to mode of delivery. MPs ranged in size (2 – 60 μm), with the most abundant MPs being polyethylene (PE), polypropylene (PP), polystyrene (PS) and polyvinyl chloride (PVC). The most abundantly identified NPP were carbon, graphite, and lead oxide. Collectively, these results demonstrate the accumulation of foreign particles, including MPs, throughout the human placenta. Given the vital functions of the placenta in supporting fetal growth and development, and a potential for MPs to induce toxicity, further investigations into the potential harmful effects of these environmental toxicants on maternal and fetal health is warranted.

Abstract Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants with significant adverse effects on human health, particularly concerning fetal development during pregnancy. This study investigates the relationship between maternal exposure to particulate matter-bound (PM-bound) PAHs and potential alterations in fetal renal function. A cross-sectional investigation was conducted on 450 mother-pair newborns from June 2019 to August 2021. Exposure to PM-bound PAHs was estimated at the residential address using spatiotemporal models based on data from 30 monitoring stations across the study area. Umbilical cord blood samples were collected post-delivery for biochemical analysis of renal function markers, including creatinine (Cr), blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR). Multivariable regression models were used to assess the relationship between exposure to each PAHs compound and fetal renal function. Moreover, the mixture effects of exposure to PAHs on fetal renal function were assessed using quantile g-computation analysis. Increased concentrations of various PAH compounds at the residential address correlated with raised levels of umbilical BUN and Cr, suggesting potential renal impairment. Notably, exposure to certain PAHs compounds demonstrated statistically negative significant associations with eGFR levels. An increment of one quartile in exposure to PAHs mixture was correlated with a rise of 1.08 mg/dL (95% CI 0.04, 2.11, p = 0.04) and 0.02 mg/dL (95% CI − 0.00, 0.05, p = 0.05) increase in BUN and Cr, respectively. Moreover, a one-quartile increase in PAHs mixture exposure was associated with − 1.09 mL/min/1.73 m2 (95% CI − 2.03, − 0.14, p = 0.02) decrease in eGFR. These findings highlight the potential impact of PAH exposure on fetal renal function and underscore the importance of considering environmental exposures in assessing neonatal renal health outcomes.

BackgroundThe ability to induce chronic inflammation and immunosuppression are two key characteristics of carcinogens and important forms of immunotoxicity. The National Toxicology Program (NTP) evaluated the immunotoxicity of two per- and polyfluoroalkyl substances (PFASs), PFOA (perfluorooctanoic acid) and PFOS (perfluorooctane sulfonate), in 2016. However, the potential pro-inflammatory and immunosuppressive effects of other PFASs remain largely uncharacterized.MethodsWe developed an expanded set of search terms pertaining to the chronic inflammatory and immunosuppressive effects of PFASs based on those of the International Agency for Research on Cancer (IARC) and NTP. To confirm searching effectiveness and scope, we compared our search term results with those of IARC and NTP for both PFASs and two other known carcinogens, chromium (VI) and benzene. Systematic evidence maps (SEMs) were also produced using Tableau to visualize the distribution of study numbers and types reporting immunotoxic effects and specific biomarkers elicited by PFAS exposures.ResultsIn total, 1155 PFAS studies were retrieved, of which 321 qualified for inclusion in our dataset. Using our search terms, we identified a greater number of relevant studies than those obtained using IARC and NTP's search terms. From the SEM findings, increased cytokine production strengthened an association between PFAS exposure and chronic inflammation, and decreased B-cell activation and altered levels of T-cell subtypes and immunoglobulins confirmed PFAS-induced immunosuppression.ConclusionOur SEM findings confirm that several PFASs commonly found in both in the environment, including those that are lesser-known, may induce immunosuppression and chronic inflammation, two key characteristics of carcinogens. This approach, including development of search terms, study screening process, data coding, and evidence mapping visualizations, can be applied to other key characteristics of chemical carcinogens.

BackgroundEvaluating the impact of environmental exposures on organism health is a key goal of modern biomedicine and is critically important in an age of greater pollution and chemicals in our environment. Environmental health utilizes many different research methods and generates a variety of data types. However, to date, no comprehensive database represents the full spectrum of environmental health data. Due to a lack of interoperability between databases, tools for integrating these resources are needed. In this manuscript we present the Environmental Conditions, Treatments, and Exposures Ontology (ECTO), a species-agnostic ontology focused on exposure events that occur as a result of natural and experimental processes, such as diet, work, or research activities. ECTO is intended for use in harmonizing environmental health data resources to support cross-study integration and inference for mechanism discovery.Methods and findingsECTO is an ontology designed for describing organismal exposures such as toxicological research, environmental variables, dietary features, and patient-reported data from surveys. ECTO utilizes the base model established within the Exposure Ontology (ExO). ECTO is developed using a combination of manual curation and Dead Simple OWL Design Patterns (DOSDP), and contains over 2700 environmental exposure terms, and incorporates chemical and environmental ontologies. ECTO is an Open Biological and Biomedical Ontology (OBO) Foundry ontology that is designed for interoperability, reuse, and axiomatization with other ontologies. ECTO terms have been utilized in axioms within the Mondo Disease Ontology to represent diseases caused or influenced by environmental factors, as well as for survey encoding for the Personalized Environment and Genes Study (PEGS).ConclusionsWe constructed ECTO to meet Open Biological and Biomedical Ontology (OBO) Foundry principles to increase translation opportunities between environmental health and other areas of biology. ECTO has a growing community of contributors consisting of toxicologists, public health epidemiologists, and health care providers to provide the necessary expertise for areas that have been identified previously as gaps.

ObjectiveOngoing pediatric cohort studies offer opportunities to investigate the impact of the COVID-19 pandemic on children's health. With well-characterized data from tens of thousands of US children, the Environmental influences on Child Health Outcomes (ECHO) Program offers such an opportunity.MethodsECHO enrolled children and their caregivers from community- and clinic-based pediatric cohort studies. Extant data from each of the cohorts were pooled and harmonized. In 2019, cohorts began collecting data under a common protocol, and data collection is ongoing with a focus on early life environmental exposures and five child health domains: birth outcomes, neurodevelopment, obesity, respiratory, and positive health. In April of 2020, ECHO began collecting a questionnaire designed to assess COVID-19 infection and the pandemic's impact on families. We describe and summarize the characteristics of children who participated in the ECHO Program during the COVID-19 pandemic and novel opportunities for scientific advancement.ResultsThis sample (n = 13,725) was diverse by child age (31% early childhood, 41% middle childhood, and 16% adolescence up to age 21), sex (49% female), race (64% White, 15% Black, 3% Asian, 2% American Indian or Alaska Native,

Urban environmental factors such as air quality, heat islands, and access to greenspaces and community amenities impact public health. Some vulnerable populations such as low-income groups, children, older adults, new immigrants, and visible minorities live in areas with fewer beneficial conditions, and therefore, face greater health risks. Planning and advocating for equitable healthy urban environments requires systematic analysis of reliable spatial data to identify where vulnerable populations intersect with positive or negative urban/environmental characteristics. To facilitate this effort in Canada, we developed HealthyPlan.City (https://healthyplan.city/), a freely available web mapping platform for users to visualize the spatial patterns of built environment indicators, vulnerable populations, and environmental inequity within over 125 Canadian cities. This tool helps users identify areas within Canadian cities where relatively higher proportions of vulnerable populations experience lower than average levels of beneficial environmental conditions, which we refer to as Equity priority areas. Using nationally standardized environmental data from satellite imagery and other large geospatial databases and demographic data from the Canadian Census, HealthyPlan.City provides a block-by-block snapshot of environmental inequities in Canadian cities. The tool aims to support urban planners, public health professionals, policy makers, and community organizers to identify neighborhoods where targeted investments and improvements to the local environment would simultaneously help communities address environmental inequities, promote public health, and adapt to climate change. In this paper, we report on the key considerations that informed our approach to developing this tool and describe the current web-based application. [ABSTRACT FROM AUTHOR]

The exponential increase in global plastic usage has led to the emergence of nano- and microplastic (NMP) pollution as a pressing environmental issue due to its implications for human and other mammalian health. We have developed methodologies to extract solid materials from human tissue samples by saponification and ultracentrifugation, allowing for highly specific and quantitative analysis of plastics by pyrolysis-gas chromatography and mass spectrometry (Py-GC-MS). As a benchmark, placenta tissue samples were analyzed using fluorescence microscopy and automated particle count, which demonstrated the presence of >1-micron particles and fibers, but not nano-sized plastic particles. Analyses of the samples (n  = 10) using attenuated total reflectance-Fourier transform infrared spectroscopy indicated presence of rayon, polystyrene, polyethylene, and unclassified plastic particles. By contrast, among 62 placenta samples, Py-GC-MS revealed that microplastics were present in all participants' placentae, with concentrations ranging widely from 6.5 to 685 µg NMPs per gram of placental tissue, averaging 126.8 ± 147.5 µg/g (mean±SD). Polyethylene was the most prevalent polymer, accounting for 54% of total NMPs and consistently found in nearly all samples (mean 68.8 ± 93.2 µg/g placenta). Polyvinyl chloride and nylon each represented approximately 10% of the NMPs by weight, with the remaining 26% of the composition represented by 9 other polymers. Together, these data demonstrate advancements in the unbiased quantitative resolution of Py-GC-MS applied to the identification and quantification of NMP species at the maternal-fetal interface. This method, paired with clinical metadata, will be pivotal to evaluating potential impacts of NMPs on adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Purpose of Review: Ubiquitous environmental exposures, including ambient air pollutants, are linked to the development and severity of childhood asthma. Advances in our understanding of these links have increasingly led to clinical interventions to reduce asthma morbidity. Recent Findings: We review recent work untangling the complex relationship between air pollutants, including particulate matter, nitrogen dioxide, and ozone and asthma, such as vulnerable windows of pediatric exposure and their interaction with other factors influencing asthma development and severity. These have led to interventions to reduce air pollutant levels in children's homes and schools. We also highlight emerging environmental exposures increasingly associated with childhood asthma. Growing evidence supports the present threat of climate change to children with asthma. Summary: Environmental factors play a large role in the pathogenesis and persistence of pediatric asthma; in turn, this poses an opportunity to intervene to change the course of disease early in life. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants with significant adverse effects on human health, particularly concerning fetal development during pregnancy. This study investigates the relationship between maternal exposure to particulate matter-bound (PM-bound) PAHs and potential alterations in fetal renal function. A cross-sectional investigation was conducted on 450 mother-pair newborns from June 2019 to August 2021. Exposure to PM-bound PAHs was estimated at the residential address using spatiotemporal models based on data from 30 monitoring stations across the study area. Umbilical cord blood samples were collected post-delivery for biochemical analysis of renal function markers, including creatinine (Cr), blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR). Multivariable regression models were used to assess the relationship between exposure to each PAHs compound and fetal renal function. Moreover, the mixture effects of exposure to PAHs on fetal renal function were assessed using quantile g-computation analysis. Increased concentrations of various PAH compounds at the residential address correlated with raised levels of umbilical BUN and Cr, suggesting potential renal impairment. Notably, exposure to certain PAHs compounds demonstrated statistically negative significant associations with eGFR levels. An increment of one quartile in exposure to PAHs mixture was correlated with a rise of 1.08 mg/dL (95% CI 0.04, 2.11, p = 0.04) and 0.02 mg/dL (95% CI − 0.00, 0.05, p = 0.05) increase in BUN and Cr, respectively. Moreover, a one-quartile increase in PAHs mixture exposure was associated with − 1.09 mL/min/1.73 m2 (95% CI − 2.03, − 0.14, p = 0.02) decrease in eGFR. These findings highlight the potential impact of PAH exposure on fetal renal function and underscore the importance of considering environmental exposures in assessing neonatal renal health outcomes. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is exposure to environmental chemicals associated with modifications of placental morphology and function? SUMMARY ANSWER Phthalates, a class of ubiquitous chemicals, showed an association with altered placental weight, placental vascular resistance (PVR), and placental efficiency. WHAT IS KNOWN ALREADY Only a few epidemiological studies have assessed the effects of phenols and phthalates on placental health. Their results were affected by exposure measurement errors linked to the rapid excretion of these compounds and the reliance on a limited number of spot urine samples to assess exposure. STUDY DESIGN, SIZE, DURATION A prospective mother–child cohort, with improved exposure assessment for non-persistent chemicals, recruited participants between 2014 and 2017. Sample size ranged between 355 (placental parameters measured at birth: placental weight and placental-to-fetal weight ratio (PFR): a proxy for placental efficiency) and 426 (placental parameters measured during pregnancy: placental thickness and vascular resistance). PARTICIPANTS/MATERIALS, SETTING, METHODS Phenols (four parabens, two bisphenols, triclosan, and benzophenone-3), 13 phthalate metabolites, and two non-phthalate plasticizer metabolites were measured in within-subject pools of repeated urine samples collected during the second and third trimesters of pregnancy (median = 21 samples/trimester/woman). Placental thickness and PVR were measured during pregnancy. The placenta was weighed at birth and the PFR was computed. Both adjusted linear regression and Bayesian Kernel Machine Regression were used to evaluate associations between phenols and phthalates (alone or as a mixture) and placental parameters. Effect modification by child sex was also investigated. MAIN RESULTS AND THE ROLE OF CHANCE Several phthalate metabolites were negatively associated with placental outcomes. Monobenzyl phthalate (MBzP) concentrations, during the second and third trimesters of pregnancy, were associated with a decrease in both placental weight at birth (β = −20.1 g [95% CI: −37.8; −2.5] and β = −17.4 g [95% CI: −33.2; −1.6], for second and third trimester, respectively) and PFR (β = −0.5 [95% CI: −1, −0.1] and β = −0.5 [95% CI: −0.9, −0.1], for the second and third trimester, respectively). Additionally, MBzP was negatively associated with PVR during the third trimester (β = −0.9 [95% CI: −1.8; 0.1]). Mono-n-butyl phthalate (MnBP), was negatively associated with PVR in both trimesters (β = −1.3, 95% CI: [−2.3, −0.2], and β = −1.2, 95% CI: [−2.4, −0.03], for the second and third trimester, respectively). After stratification for child sex, Σ diisononyl phthalate (DiNP) (either second or third-trimester exposures, depending on the outcomes considered) was associated with decreased PVR in the third trimester, as well as decreased placental weight and PFR in males. No associations were observed for phenol biomarkers. LIMITATIONS, REASONS FOR CAUTION False positives cannot be ruled out. Therefore, chemicals that were associated with multiple outcomes (MnBP and DiNP) or reported in existing literature as associated with placental outcomes (MBzP) should be considered as the main results. WIDER IMPLICATIONS OF THE FINDINGS Our results are consistent with in vitro studies showing that phthalates target peroxisome proliferator-activated receptor γ, in the family of nuclear receptors involved in key placental development processes such as trophoblast proliferation, migration, and invasion. In addition to placental weight at birth, we studied placental parameters during pregnancy, which could provide a broader view of how environmental chemicals affect maternal–fetal exchanges over the course of pregnancy. Our findings contribute to the increasing evidence indicating adverse impacts of phthalate exposure on placental health. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the French Research Agency—ANR (MEMORI project ANR-21-CE34-0022). The SEPAGES cohort was supported by the European Research Council (N°311765-E-DOHaD), the European Community's Seventh Framework Programme (FP7/2007-206—N°308333-892 HELIX), the European Union's Horizon 2020 research and innovation programme (N° 874583 ATHLETE Project, N°825712 OBERON Project), the French Research Agency—ANR (PAPER project ANR-12-PDOC-0029-01, SHALCOH project ANR-14-CE21-0007, ANR-15-IDEX-02 and ANR-15-IDEX5, GUMME project ANR-18-CE36-005, ETAPE project ANR-18-CE36-0005—EDeN project ANR-19-CE36-0003-01), the French Agency for Food, Environmental and Occupational Health & Safety—ANSES (CNAP project EST-2016-121, PENDORE project EST-2016-121, HyPAxE project EST-2019/1/039, PENDALIRE project EST-2022-169), the Plan Cancer (Canc'Air project), the French Cancer Research Foundation Association de Recherche sur le Cancer—ARC, the French Endowment Fund AGIR for chronic diseases—APMC (projects PRENAPAR, LCI-FOT, DysCard), the French Endowment Fund for Respiratory Health, the French Fund—Fondation de France (CLIMATHES—00081169, SEPAGES 5–00099903, ELEMENTUM—00124527). N.J. was supported by a doctoral fellowship from the University Grenoble Alpes. V.M. was supported by a Sara Borrell postdoctoral research contract (CD22/00176), granted by Instituto de Salud Carlos III (Spain) and NextGenerationEU funds. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT02852499. [ABSTRACT FROM AUTHOR]

(1) Background: Volatile organic compounds (VOCs) are indoor pollutants absorbed by inhalation. The association of several VOCs with lung function in children and adolescents is unknown. (2) Methods: We analyzed 505 participants, 6–17-year-olds from the 2011–2012 National Health and Nutrition Examination Survey. Multiple linear regression models were fitted to estimate the associations of VOC metabolites with spirometry outcomes adjusting for covariates. (3) Results: Urinary metabolites of xylene, acrylamide, acrolein, 1,3-butadiene, cyanide, toluene, 1-bromopropane, acrylonitrile, propylene oxide, styrene, ethylbenzene, and crotonaldehyde were all detected in ≥64.5% of participants. Forced expiratory volume in 1 s (FEV1) % predicted was lower in participants with higher levels of metabolites of acrylamide (β: −7.95, 95% CI: −13.69, −2.21) and styrene (β: −6.33, 95% CI: −11.60, −1.07), whereas the FEV1 to forced vital capacity (FVC) ratio % was lower in children with higher propylene oxide metabolite levels (β: −2.05, 95% CI: −3.49, −0.61). FEV1 % predicted was lower with higher crotonaldehyde metabolite levels only in overweight/obese participants (β: −15.42, 95% CI: −26.76, −4.08) (Pinteraction < 0.001) and with higher 1-bromopropane metabolite levels only in those with serum cotinine > 1 ng/mL (β: −6.26, 95% CI: −9.69, −2.82) (Pinteraction < 0.001). (4) Conclusions: We found novel associations of metabolites for acrylamide, propylene oxide, styrene, 1-bromopropane and crotonaldehyde with lower lung function in children and adolescents. [ABSTRACT FROM AUTHOR]

Preterm birth is a leading cause of neonatal mortality and presents significant public health concerns. Environmental chemical exposures during pregnancy may be partially to blame for disrupted delivery timing. Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion, exposure to which occurs via inhalation of cigarette smoke and automobile exhaust, and ingestion of charred meats. Exposure to PAHs in the US population is widespread, and pregnant women represent a susceptible population to adverse effects of PAHs. We aimed to investigate associations between gestational exposure to PAHs and birth outcomes, including timing of delivery and infant birth size. We utilized data from the PROTECT birth cohort where pregnant women provided spot urine samples at up to three study visits (median 16, 20, and 24 weeks gestation). Urine samples were assayed for eight hydroxylated PAH concentrations. Associations between PAHs and birth outcomes were calculated using linear/logistic regression models, with adjustment for maternal age, education, pre-pregnancy BMI, and daily exposure to environmental tobacco smoke. Models accounted for urine dilution using specific gravity. We also explored effect modification by infant sex. Interquartile range (IQR) increases in all averaged PAH exposures during the second trimester were associated with reduced gestational age at delivery and increased odds of overall PTB, although these associations were not statistically significant (p > 0.05). Most PAHs at the second study visit were most strongly associated with earlier delivery and increased odds of overall and spontaneous PTB, with visit 2 2-hydroxynapthalene (2-NAP) being significantly associated with increased odds of overall PTB (OR:1.55; 95 %CI: 1.05,2.29). Some PAHs resulted in earlier timing of delivery among only female fetuses, specifically 2-NAP on overall PTB (female OR:1.52 95 %CI: 1.02,2.27; male OR:0.78, 95 %CI: 0.53,1.15). Future work should more deeply investigate differential physiological impacts of PAH exposure between pregnancies with male and female fetuses, and on varying developmental processes occurring at different points through pregnancy.

Abstract The impact of common environmental exposures in combinations with socioeconomic and lifestyle factors on cancer development, particularly for young adults, remains understudied. Here, we leveraged environmental and cancer incidence data collected in New York State at the county level to examine the association between 31 exposures and 10 common cancers (i.e., lung and bronchus, thyroid, colorectal, kidney and renal pelvis, melanoma, non-Hodgkin lymphoma, and leukemia for both sexes; corpus uteri and female breast cancer; prostate cancer), for three age groups (25–49, 50–69, and 70–84 year-olds). For each cancer, we stratified by age group and sex, and applied regression models to examine the associations with multiple exposures simultaneously. The models included 642,013 incident cancer cases during 2010–2018 and found risk factors consistent with previous reports (e.g., smoking and physical inactivity). Models also found positive associations between ambient air pollutants (ozone and PM2.5) and prostate cancer, female breast cancer, and melanoma of the skin across multiple population strata. Additionally, the models were able to better explain the variation in cancer incidence data among 25–49 year-olds than the two older age groups. These findings support the impact of common environmental exposures on cancer development, particularly for younger age groups.

Abstract Background Climate change has been identified as one of the biggest threats to human health. Despite this claim, there are no standardized tools that assess the rigor of published literature for use in weight of evidence (WOE) reviews. Standardized assessment tools are essential for creating clear and comparable WOE reviews. As such, we developed a standardized tool for evaluating the quality of climate change and health studies focused on evaluating studies that quantify exposure-response relationships and studies that implement and/or evaluate adaptation interventions. Methods The authors explored systematic-review methodology to enhance transparency and increase efficiency in summarizing and synthesizing findings from studies on climate change and health research. The authors adapted and extended existing WOE methods to develop the CHANGE (Climate Health ANalysis Grading Evaluation) tool. The resulting assessment tool has been refined through application and subsequent team input. Results The CHANGE tool is a two-step standardized tool for systematic review of climate change and health studies of exposure-response relationships and adaptation intervention studies. Step one of the CHANGE tool aims to classify studies included in weight-of-evidence reviews and step two assesses the quality and presence of bias in the climate change and health studies. Conclusion The application of the CHANGE tool in WOE reviews of climate change and health will lead to increased comparability, objectivity, and transparency within this research area.

Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers. Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined. The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5. The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent). [ABSTRACT FROM AUTHOR]

This study delves into the complex interrelations among nutrient intake, environmental exposures (particularly to heavy metals), and metabolic syndrome. Utilizing data from the Korea National Health and Nutrition Examination Survey (KNHANES), machine learning techniques were applied to analyze associations in a cohort of 5719 participants, categorized into four distinct nutrient intake phenotypes. Our findings reveal that different nutrient intake patterns are associated with varying levels of heavy metal exposure and metabolic health outcomes. Key findings include significant variations in metal levels (Pb, Hg, Cd, Ni) across the clusters, with certain clusters showing heightened levels of specific metals. These variations were associated with distinct metabolic health profiles, including differences in obesity, diabetes prevalence, hypertension, and cholesterol levels. Notably, Cluster 3, characterized by high-energy and nutrient-rich diets, showed the highest levels of Pb and Hg exposure and had the most concerning metabolic health indicators. Moreover, the study highlights the significant impact of lifestyle habits, such as smoking and eating out, on nutrient intake phenotypes and associated health risks. Physical activity emerged as a critical factor, with its absence linked to imbalanced nutrient intake in certain clusters. In conclusion, our research underscores the intricate connections among diet, environmental factors, and metabolic health. The findings emphasize the need for tailored health interventions and policies that consider these complex interplays, potentially informing future strategies to combat metabolic syndrome and related health issues. [ABSTRACT FROM AUTHOR]

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic pulmonary disorder of unknown etiology that is characterized by a usual interstitial pneumonia pattern. Previous meta-analyses have reported associations between occupational exposures and IPF, but higher-quality studies have been published in recent years, doubling the number of studied patients. Objectives: To provide a contemporary and comprehensive assessment of the relationship between occupational exposures and IPF. Methods: We searched PubMed, Embase, and Web of Science through July 2023 to identify all publications on occupational exposure and IPF. We conducted a meta-analysis of the occupational burden, odds ratio (OR), and population attributable fraction (PAF) of exposures. Five exposure categories were analyzed: vapors, gas, dust, and fumes (VGDF); metal dust; wood dust; silica dust; and agricultural dust. A comprehensive bias assessment was performed. The study protocol was registered in the International Prospective Register of Systematic Reviews (identifier CRD42021267808). Results: Our search identified 23,942 publications. Sixteen publications contained relative risks needed to calculate pooled ORs and PAFs, and 12 additional publications reported an occupational burden within a case series. The proportion of cases with occupational exposures to VGDF was 44% (95% confidence interval [CI], 36–53%), with a range of 8–17% within more specific exposure categories. The pooled OR was increased for VGDF at 1.8 (95% CI, 1.3–2.4), with a pooled PAF of 21% (95% CI, 15–28%). ORs and PAFs, respectively, were found to be 1.6 and 7% for metal dust, 1.6 and 3% for wood dust, 1.8 and 14% for agricultural dust, and 1.8 and 4% for silica dust. The pooled ORs and PAFs within specific exposure categories ranged from 1.6 to 1.8 and from 4% to 14%, respectively. We identified some publication bias, but it was not sufficient to diminish the association between occupational exposures and IPF based on sensitivity analysis and bias assessment. Conclusions: Our findings indicate that 21% of IPF cases (or approximately one in five) could be prevented by removal of occupational exposure (alongside a pooled OR of 1.8). Additionally, 44% of patients with IPF report occupational exposure to VGDF. This meta-analysis suggests that a considerable number of cases of IPF are attributable to inhaled occupational exposures and warrant increased consideration in the clinical care of patients and future prevention efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: Population statistics from recent years have demonstrated that rates of colorectal cancer among younger individuals have been increasing with alarming rates of mortality. This is contradictory to expectations given preventative clinical measures and suggests that there are factors that may cause greater rates of cancer in younger generations that are different than in older populations. Bacteria and other microbial organisms in the gut microbiome are crucial to human health, and research studies are beginning to demonstrate that disruptions to the gut microbiome are tied to recent increasing trends of colorectal cancer in younger populations. Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Hypertension is a chronic cardiovascular disease characterized by elevated blood pressure that can lead to a number of complications. There is evidence that the numerous environmental substances to which humans are exposed facilitate the emergence of diseases. In this work, we sought to investigate the relationship between exposure to environmental contaminants and hypertension as well as the predictive value of such exposures. The National Health and Nutrition Survey (NHANES) provided us with the information we needed (2005–2012). A total of 4492 participants were included in our study, and we incorporated more common environmental chemicals and covariates by feature selection followed by regularized network analysis. Then, we applied various machine learning (ML) methods, such as extreme gradient boosting (XGBoost), random forest classifier (RF), logistic regression (LR), multilayer perceptron (MLP), and support vector machine (SVM), to predict hypertension by chemical exposure. Finally, SHapley Additive exPlanations (SHAP) were further applied to interpret the features. After the initial feature screening, we included a total of 29 variables (including 21 chemicals) for ML. The areas under the curve (AUCs) of the five ML models XGBoost, RF, LR, MLP, and SVM were 0.729, 0.723, 0.721, 0.730, and 0.731, respectively. Butylparaben (BUP), propylparaben (PPB), and 9-hydroxyfluorene (P17) were the three factors in the prediction model with the highest SHAP values. Comparing five ML models, we found that environmental exposure may play an important role in hypertension. The assessment of important chemical exposure parameters lays the groundwork for more targeted therapies, and the optimized ML models are likely to predict hypertension. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease of Uncertain Etiology (CKDu) is a significant health concern affecting specific regions, particularly agricultural communities. This prospective study, conducted over one year at a tertiary care center, aimed to comprehensively investigate CKDu by evaluating demographic, clinical, laboratory, and environmental factors. Methods: A total of 150 CKDu patients and 150 control group participants were enrolled to explore this enigmatic disease. Demographic analysis highlighted the prevalence of CKDu in rural, agriculturally engaged individuals. Clinical characteristics revealed distinct symptoms and clinical markers, while laboratory results unveiled key biochemical differences. Occupational history and environmental exposures were assessed to identify potential risk factors. Results: CKDu patients exhibited elevated proteinuria levels, reduced eGFR, and heightened blood pressure, emphasizing the clinical impact. Laboratory findings confirmed renal dysfunction with elevated serum creatinine, BUN, and albuminuria. Occupational and environmental factors highlighted longer agricultural work durations, pesticide/herbicide exposure, and variations in water sources among CKDu patients. Conclusion: This study underscores the multifaceted nature of CKDu, where demographic, clinical, and environmental factors intersect to contribute to its pathogenesis. A strong association between proteinuria and CKDu was observed, emphasizing its diagnostic relevance. These findings call for targeted interventions and preventive measures in high-risk regions, acknowledging the need for a comprehensive approach to manage and mitigate the impact of CKDu on affected communities. [ABSTRACT FROM AUTHOR]

Legacy and emerging toxicants of concern can modulate B cell lymphoma 2 (BCL-2) family protein expression and function, leading to excessive or insufficient levels of apoptosis and consequent pathogenesis. Apoptosis dysregulation undergirds a host of diseases of great public health concern, including cancer, autoimmune diseases, and neurodegenerative disorders. Recent discoveries show that apoptosis is dynamically regulated in healthy tissues across the lifespan, creating periods of heightened vulnerability to exposure-induced apoptosis such as early childhood. Understanding changes in BCL-2 family regulation and apoptotic sensitivity (priming) caused by environmental exposures can help us better understand potential health risks and mechanisms of disease. Novel agents that can modulate the apoptosis pathway may suppress or promote cell death in response to environmental toxicants, and ultimately prevent disease. Environmental exposures are linked to diseases of high public health concern, including cancer, neurodegenerative disorders, and autoimmunity. These diseases are caused by excessive or insufficient cell death, prompting investigation of mechanistic links between environmental toxicants and dysregulation of cell death pathways, including apoptosis. This review describes how legacy and emerging environmental exposures target the intrinsic apoptosis pathway to potentially drive pathogenesis. Recent discoveries reveal that dynamic regulation of apoptosis may heighten the vulnerability of healthy tissues to exposures in children, and that apoptotic signaling can guide immune responses, tissue repair, and tumorigenesis. Understanding how environmental toxicants dysregulate apoptosis will uncover opportunities to deploy apoptosis-modulating agents for the treatment or prevention of exposure-linked diseases. [ABSTRACT FROM AUTHOR]

Prostate cancer is the leading incident cancer among men in the United States. Firefighters are diagnosed with this disease at a rate 1.21 times higher than the average population. This increased risk may result from occupational exposures to many toxicants, including per‐ and polyfluoroalkyl substances (PFAS). This study assessed the association between firefighting as an occupation in general or PFAS serum levels, with DNA methylation. Only genomic regions previously linked to prostate cancer risk were selected for analysis: GSTP1, Alu repetitive elements, and the 8q24 chromosomal region. There were 444 male firefighters included in this study, with some analyses being conducted on fewer participants due to missingness. Statistical models were used to test associations between exposures and DNA methylation at CpG sites in the selected genomic regions. Exposure variables included proxies of cumulative firefighting exposures (incumbent versus academy status and years of firefighting experience) and biomarkers of PFAS exposures (serum concentrations of 9 PFAS). Proxies of cumulative exposures were associated with DNA methylation at 15 CpG sites and one region located within FAM83A (q‐value <0.1). SbPFOA was associated with 19 CpG sites (q < 0.1), but due to low detection rates, this PFAS was modeled as detected versus not detected in serum. Overall, there is evidence that firefighting experience is associated with differential DNA methylation in prostate cancer risk loci, but this study did not find evidence that these differences are due to PFAS exposures specifically. [ABSTRACT FROM AUTHOR]