Gene-environment interactions within a precision environmental health framework.

Understanding the complex interplay of genetic and environmental factors in disease etiology and the role of gene-environment interactions (GEIs) across human development stages is important. We review the state of GEI research, including challenges in measuring environmental factors and advantages of GEI analysis in understanding disease mechanisms. We discuss the evolution of GEI studies from candidate gene-environment studies to genome-wide interaction studies (GWISs) and the role of multi-omics in mediating GEI effects. We review advancements in GEI analysis methods and the importance of large-scale datasets. We also address the translation of GEI findings into precision environmental health (PEH), showcasing real-world applications in healthcare and disease prevention. Additionally, we highlight societal considerations in GEI research, including environmental justice, the return of results to participants, and data privacy. Overall, we underscore the significance of GEI for disease prediction and prevention and advocate for integrating the exposome into PEH omics studies.

Advancing environmental health sciences through implementation science.

BACKGROUND: Environmental health sciences have identified and characterized a range of environmental exposures and their associated risk for disease, as well as informed the development of interventions, including recommendations, guidelines, and policies for mitigating exposure. However, these interventions only serve to mitigate exposures and prevent disease if they are effectively disseminated, adopted, implemented, and sustained. MAIN BODY: Numerous studies have documented the enormous time lag between research and practice, noting that dissemination and implementation are not passive processes but rely on active and intentional strategies. Implementation science seeks to build the knowledge base for understanding strategies to effectively disseminate and implement evidence and evidence-based interventions, and thus, bridge the research-to-practice gap. CONCLUSION: Environmental health researchers are well positioned to advance health promotion and disease prevention by incorporating implementation science into their work. This article describes the rationale for and key components of implementation science and articulates opportunities to build upon existing efforts to advance environmental health supported by the National Institute of Environmental Health Sciences and National Institutes of Health broadly.

Respiratory Impacts of Wildland Fire Smoke: Future Challenges and Policy Opportunities. An Official American Thoracic Society Workshop Report.

Wildland fires are diminishing air quality on a seasonal and regional basis, raising concerns about respiratory health risks to the public and occupational groups. This American Thoracic Society (ATS) workshop was convened in 2019 to meet the growing health threat of wildland fire smoke. The workshop brought together a multidisciplinary group of 19 experts, including wildland fire managers, public health officials, epidemiologists, toxicologists, and pediatric and adult pulmonologists. The workshop examined the following four major topics: 1) the science of wildland fire incidence and fire management, 2) the respiratory and cardiovascular health effects of wildland fire smoke exposure, 3) communication strategies to address these health risks, and 4) actions to address wildland fire health impacts. Through formal presentations followed by group discussion, workshop participants identified top priorities for fire management, research, communication, and public policy to address health risks of wildland fires. The workshop concluded that short-term exposure to wildland smoke causes acute respiratory health effects, especially among those with asthma and chronic obstructive pulmonary disease. Research is needed to understand long-term health effects of repeated smoke exposures across fire seasons for children, adults, and highly exposed occupational groups (especially firefighters). Other research priorities include fire data collection and modeling, toxicology of different fire fuel sources, and the efficacy of health protective measures to prevent respiratory effects of smoke exposure. The workshop committee recommends a unified federal response to the growing problem of wildland fires, including investment in fire behavior and smoke air quality modeling, research on the health impacts of smoke, and development of robust clinical and public health communication tools.

Environmental Factors Involved in Maternal Morbidity and Mortality.

Nongenetic, environmental factors contribute to maternal morbidity and mortality through chemical exposures via air, water, soil, food, and consumer products. Pregnancy represents a particularly sensitive window of susceptibility during which physiological changes to every major organ system increase sensitivity to chemicals that can impact a woman's long-term health. Nonchemical stressors, such as low socioeconomic status, may exacerbate the effects of chemical exposures on maternal health. Racial/ethnic minorities are exposed disproportionately to both chemicals and nonchemical stressors, which likely contribute to the observed health disparities for maternal morbidities and mortality. Epidemiological studies linking exposures to adverse maternal health outcomes underscore the importance of environmental health impacts, and mechanistic studies in model systems reveal how chemicals perturb biological pathways and processes. Environmental stressors are associated with a variety of immediate maternal health impacts, including hypertensive disorders of pregnancy, fibroids, and infertility, as well as long-term maternal health impacts, such as higher risk of breast cancer and metabolic disorders. Identifying and reducing a pregnant woman's environmental exposures is not only beneficial to her offspring but also important to preserve her short- and long-term health.

Cardiopulmonary Impact of Particulate Air Pollution in High-Risk Populations: JACC State-of-the-Art Review.

Fine particulate air pollution <2.5 µm in diameter (PM2.5) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM2.5 as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM2.5 can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention.

Integrating environmental health and genomics research in Africa: challenges and opportunities identified during a Human Heredity and Health in Africa (H3Africa) Consortium workshop.

Individuals with African ancestry have extensive genomic diversity but have been underrepresented in genomic research. There is also extensive global diversity in the exposome (the totality of human environmental exposures from conception onwards) which should be considered for integrative genomic and environmental health research in Africa. To address current research gaps, we organized a workshop on environmental health research in Africa in conjunction with the H3Africa Consortium and the African Society of Human Genetics meetings in Kigali, Rwanda. The workshop was open to all researchers with an interest in environmental health in Africa and involved presentations from experts within and outside of the Consortium. This workshop highlighted innovative research occurring on the African continent related to environmental health and the interplay between the environment and the human genome. Stories of success, challenges, and collaborative opportunities were discussed through presentations, breakout sessions, poster presentations, and a panel discussion. The workshop informed participants about environmental risk factors that can be incorporated into current or future epidemiology studies and addressed research design considerations, biospecimen collection and storage, biomarkers for measuring chemical exposures, laboratory strategies, and statistical methodologies. Inclusion of environmental exposure measurements with genomic data, including but not limited to H3Africa projects, can offer a strong platform for building gene-environment (G x E) research in Africa. Opportunities to leverage existing resources and add environmental exposure data for ongoing and planned studies were discussed. Future directions include expanding the measurement of both genomic and exposomic risk factors and incorporating sophisticated statistical approaches for analyzing high dimensional G x E data. A better understanding of how environmental and genomic factors interact with nutrition and infection is also needed. Considering that the environment represents many modifiable risk factors, these research findings can inform intervention and prevention efforts towards improving global health.

Expanding the Concept of Translational Research: Making a Place for Environmental Health Sciences.

SUMMARY: The National Institute of Environmental Health Sciences (NIEHS) introduces a new translational research framework that builds upon previous biomedical models to create a more comprehensive and integrated environmental health paradigm. The framework was developed as a graphical construct that illustrates the complexity of designing, implementing, and tracking translational research in environmental health. We conceptualize translational research as a series of concentric rings and nodes, defining "translation" as movement either from one ring to another or between nodes on a ring. A "Fundamental Questions" ring expands upon the research described in other frameworks as "basic" to include three interrelated concepts critical to basic science research: research questions, experimental settings, and organisms. This feature enables us to capture more granularity and thus facilitates an approach for categorizing translational research and its growth over time. We anticipate that the framework will help researchers develop compelling long-term translational research stories and accelerate public health impacts by clearly mapping out opportunities for collaborations. By using this paradigm, researchers everywhere will be better positioned to design research programs, identify research partners based on cross-disciplinary research needs, identify stakeholders who are likely to use the research for environmental decision-making and intervention, and track progress toward common goals. https://doi.org/10.1289/EHP3657.

Yale school of public health symposium on lifetime exposures and human health: the exposome; summary and future reflections.

The exposome is defined as "the totality of environmental exposures encountered from birth to death" and was developed to address the need for comprehensive environmental exposure assessment to better understand disease etiology. Due to the complexity of the exposome, significant efforts have been made to develop technologies for longitudinal, internal and external exposure monitoring, and bioinformatics to integrate and analyze datasets generated. Our objectives were to bring together leaders in the field of exposomics, at a recent Symposium on "Lifetime Exposures and Human Health: The Exposome," held at Yale School of Public Health. Our aim was to highlight the most recent technological advancements for measurement of the exposome, bioinformatics development, current limitations, and future needs in environmental health. In the discussions, an emphasis was placed on moving away from a one-chemical one-health outcome model toward a new paradigm of monitoring the totality of exposures that individuals may experience over their lifetime. This is critical to better understand the underlying biological impact on human health, particularly during windows of susceptibility. Recent advancements in metabolomics and bioinformatics are driving the field forward in biomonitoring and understanding the biological impact, and the technological and logistical challenges involved in the analyses were highlighted. In conclusion, further developments and support are needed for large-scale biomonitoring and management of big data, standardization for exposure and data analyses, bioinformatics tools for co-exposure or mixture analyses, and methods for data sharing.

The Children's Health Exposure Analysis Resource: enabling research into the environmental influences on children's health outcomes.

PURPOSE OF REVIEW: The Children's Health Exposure Analysis Resource (CHEAR) is a new infrastructure supported by the National Institute of Environmental Health Sciences to expand the ability of children's health researchers to include analysis of environmental exposures in their research and to incorporate the emerging concept of the exposome. RECENT FINDINGS: There is extensive discussion of the potential of the exposome to advance understanding of the totality of environmental influences on human health. Children's health is a logical choice to demonstrate the exposome concept due to the extensive existing knowledge of individual environmental exposures affecting normal health and development and the short latency between exposures and observable phenotypes. Achieving this demonstration will require access to extensive analytical capabilities to measure a suite of exposures through traditional biomonitoring approaches and to cross-validate these with emerging exposomic approaches. SUMMARY: CHEAR is a full-service exposure assessment resource, linking up-front consultation with both laboratory and data analysis. Analyses of biological samples are intended to enhance studies by including targeted analysis of specific exposures and untargeted analysis of small molecules associated with phenotypic endpoints. Services provided by CHEAR are made available without cost but require a brief application and adherence to policies detailed on the CHEAR web page at https://chearprogram.org/.

The Pivotal Role of the Social Sciences in Environmental Health Sciences Research.

Environmental health sciences research seeks to elucidate environmental factors that put human health at risk. A primary aim is to develop strategies to prevent or reduce exposures and disease occurrence. Given this primary focus on prevention, environmental health sciences research focuses on the populations most at risk such as communities of color and/or low socioeconomic status. The National Institute of Environmental Health Sciences research programs incorporate the principles of Community-Based Participatory Research to study health disparities. These programs promote community engagement, culturally appropriate communications with a variety of stakeholders, and consideration of the social determinants of health that interact with environmental factors to increase risk. Multidisciplinary research teams that include social and behavioral scientists are essential to conduct this type of research. This article outlines the history of social and behavioral research funding at National Institute of Environmental Health Sciences and offers examples of National Institute of Environmental Health Sciences-funded projects that exemplify the value of social science to the environmental health sciences.

Environmental exposures, breast development and cancer risk: Through the looking glass of breast cancer prevention.

This review summarizes the report entitled: Breast Cancer and the Environment: Prioritizing Prevention, highlights research gaps and the importance of focusing on early life exposures for breast development and breast cancer risk.

Community-based approaches to environmental health research around the globe.

A community-engaged approach to environmental health research incorporates input and knowledge from members of a community and other stakeholders who are affected by an environmental health issue. Bringing the community voice to public health research and practice can increase the potential for translating research findings into sustainable changes and policies that can reduce exposure to environmental chemicals and other agents in order to protect children's health around the world.

Consortium-based science: the NIEHS's multipronged, collaborative approach to assessing the health effects of bisphenol A.

BACKGROUND: Bisphenol A (BPA) is a high production volume chemical used to make polycarbonate plastic and is found in many consumer products. Some studies using animal models have suggested that BPA exposures may have adverse health effects. However, research gaps have precluded a full understanding of the effects of BPA in humans and engendered controversies surrounding the chemical's potential toxicity. OBJECTIVES: The National Institute of Environmental Health Sciences (NIEHS) and National Toxicology Program (NTP) have developed an integrated, multipronged, consortium-based approach to optimize BPA-focused research investments to more effectively address data gaps and inform decision making. DISCUSSION: NIEHS/NTP BPA research investments made over the past 4 years include extramural research grants, establishment of a BPA Grantee Consortium, intramural research activities on BPA's mechanisms of action, the launch of two clinical studies and an occupational study, development of a round-robin experiment to validate BPA measurements in human serum, and, in collaboration with the Food and Drug Administration (FDA), formation of a consortium to design and execute a chronic toxicity study of BPA in rats. The NIEHS's new consortium-based approach has led to more integrated, collaborative efforts and should improve our ability to resolve controversies over the potential human health effects of exposures to low levels of endocrine-active agents.