An algorithm for quantitatively estimating occupational endotoxin exposure in the biomarkers of exposure and effect in agriculture study: II. Application to the study population.

BACKGROUND: We developed an algorithm to quantitatively estimate endotoxin exposure for farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) Study. METHODS: The algorithm combined task intensity estimates derived from published data with questionnaire responses on activity duration to estimate task-specific cumulative endotoxin exposures for 13 tasks during four time windows, ranging from "past 12 months" to "yesterday/today." We applied the algorithm to 1681 participants in Iowa and North Carolina. We examined correlations in endotoxin metrics within- and between-task. We also compared these metrics to prior day full-shift inhalable endotoxin concentrations from 32 farmers. RESULTS: The highest median task-specific cumulative exposures were observed for swine confinement, poultry confinement, and grind feed. Inter-quartile ranges showed substantial between-subject variability for most tasks. Time window-specific metrics of the same task were moderately-highly correlated. Between-task correlation was variable, with moderately-high correlations observed for similar tasks (e.g., between animal-related tasks). Prior day endotoxin concentration increased with the total metric and with task metrics for swine confinement, clean other animal facilities, and clean grain bins. SIGNIFICANCE: This study provides insight into the variability and sources of endotoxin exposure among farmers in the BEEA study and summarizes exposure estimates for future investigations in this population.

An algorithm for quantitatively estimating occupational endotoxin exposure in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study: I. Development of task-specific exposure levels from published data.

BACKGROUND/OBJECTIVE: Farmers conduct numerous tasks with potential for endotoxin exposure. As a first step to characterize endotoxin exposure for farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) Study, we used published data to estimate task-specific endotoxin concentrations. METHODS: We extracted published data on task-specific, personal, inhalable endotoxin concentrations for agricultural tasks queried in the study questionnaire. The data, usually abstracted as summary measures, were evaluated using meta-regression models that weighted each geometric mean (GM, natural-log transformed) by the inverse of its within-study variance to obtain task-specific predicted GMs. RESULTS: We extracted 90 endotoxin summary statistics from 26 studies for 9 animal-related tasks, 30 summary statistics from 6 studies for 3 crop-related tasks, and 10 summary statistics from 5 studies for 4 stored grain-related tasks. Work in poultry and swine confinement facilities, grinding feed, veterinarian services, and cleaning grain bins had predicted GMs > 1000 EU/m3 . In contrast, harvesting or hauling grain and other crop-related tasks had predicted GMs below 100 EU/m3 . SIGNIFICANCE: These task-specific endotoxin GMs demonstrated exposure variability across common agricultural tasks. These estimates will be used in conjunction with questionnaire responses on task duration to quantitatively estimate endotoxin exposure for study participants, described in a companion paper.

Human Health Exposure Analysis Resource (HHEAR): A model for incorporating the exposome into health studies.

BACKGROUND: Characterizing the complexity of environmental exposures in relation to human health is critical to advancing our understanding of health and disease throughout the life span. Extant cohort studies open the door for such investigations more rapidly and inexpensively than launching new cohort studies and the Human Health Exposure Analysis Resource (HHEAR) provides a resource for implementing life-stage exposure studies within existing study populations. Primary challenges to incorporation of environmental exposure assessment in health studies include: (1) lack of widespread knowledge of biospecimen and environmental sampling and storage requirements for environmental exposure assessment among investigators; (2) lack of availability of and access to laboratories capable of analyzing multiple environmental exposures throughout the life-course; and (3) studies lacking sufficient power to assess associations across life-stages. HHEAR includes a consortium of researchers with expertise in laboratory analyses, statistics and logistics to overcome these limitations and enable inclusion of exposomics in human health studies. OBJECTIVE: This manuscript describes the structure and strengths of implementing the harmonized HHEAR resource model, and our approaches to addressing challenges. We describe how HHEAR incorporates analyses of biospecimens and environmental samples and human health studies across the life span - serving as a model for incorporating environmental exposures into national and international research. We also present program successes to date. DISCUSSION: HHEAR provides a full-service laboratory and data analysis exposure assessment resource, linking scientific, life span, and toxicological consultation with both laboratory and data analysis expertise. HHEAR services are provided without cost but require NIH, NCI, NHLBI, or ECHO funding of the original cohort; internal HHEAR scientific review and approval of a brief application; and adherence to data sharing and publication policies. We describe the benefits of HHEAR's structure, collaborative framework and coordination across project investigators, analytical laboratories, biostatisticians and bioinformatics specialists; quality assurance/quality control (QA/QC) including integrated sample management; and tools that have been developed to support the research (exposure information pages, ontology, new analytical methods, common QA/QC approach across laboratories, etc.). This foundation supports HHEAR's inclusion of new laboratory and statistical analysis methods and studies that are enhanced by including targeted analysis of specific exposures and untargeted analysis of chemicals associated with phenotypic endpoints in biological and environmental samples. CONCLUSION: HHEAR is an interdisciplinary team of toxicologists, epidemiologists, laboratory scientists, and data scientists across multiple institutions to address broad and complex questions that benefit from integrated laboratory and data analyses. HHEAR's processes, features, and tools include all life stages and analysis of biospecimens and environmental samples. They are available to the wider scientific community to augment studies by adding state of the art environmental analyses to be linked to human health outcomes.

Recommendations for Assessment of Environmental Exposures in Longitudinal Life Course Studies Such as the National Children's Study.

An important step toward understanding the relationship between the environment and child health and development is the comprehensive cataloging of external environmental factors that may modify health and development over the life course. Our understanding of the environmental influences on health is growing increasingly complex. Significant key questions exist as to what genes, environment, and life stage mean to defining normal variations and altered developmental trajectories throughout the life course and also across generations. With the rapid advances in genetic technology came large-scale genomic studies to search for the genetic etiology of complex diseases. While genome-wide association studies (GWAS) have revealed genetic factors and networks that advance our understanding to some extent, it is increasingly recognized that disease causation is largely non-genetic and reflects interactions between an individual's genetic susceptibility and his or her environment. Thus, the full promise of the human genome project to prevent or treat disease and promote good health arguably depends on a commitment to understanding the interactions between our environment and our genetic makeup and requires a design with prospective environmental data collection that considers critical windows of susceptibility that likely correspond to the expression of specific genes and gene pathways. Unlike the genome, which is static, relevant exposures as well as our response to exposures, change over time. This has fostered the complementary concept of the exposome ideally defined as the measure of all exposures of an individual over a lifetime and how those exposures relate to health. The exposome framework considers multiple external exposures (e.g., chemical, social) and behaviors that may modify exposures (e.g., diet), as well as consequences of environmental exposures indexed via biomarkers of physiological response or measures of behavioral response throughout the lifespan. The exposome concept can be applied in prospective developmental studies such as the National Children's Study (NCS) with the practical understanding that even a partial characterization will bring major advances to health. Lessons learned from the NCS provide an important opportunity to inform future studies that can leverage these evolving paradigms in elucidating the role of environment on health across the life course.

Pilot study of methods and equipment for in-home noise level measurements.

Knowledge of the auditory and non-auditory effects of noise has increased dramatically over the past decade, but indoor noise exposure measurement methods have not advanced appreciably, despite the introduction of applicable new technologies. This study evaluated various conventional and smart devices for exposure assessment in the National Children's Study. Three devices were tested: a sound level meter (SLM), a dosimeter, and a smart device with a noise measurement application installed. Instrument performance was evaluated in a series of semi-controlled tests in office environments over 96-hour periods, followed by measurements made continuously in two rooms (a child's bedroom and a most used room) in nine participating homes over a 7-day period with subsequent computation of a range of noise metrics. The SLMs and dosimeters yielded similar A-weighted average noise levels. Levels measured by the smart devices often differed substantially (showing both positive and negative bias, depending on the metric) from those measured via SLM and dosimeter, and demonstrated attenuation in some frequency bands in spectral analysis compared to SLM results. Virtually all measurements exceeded the Environmental Protection Agency's 45 dBA day-night limit for indoor residential exposures. The measurement protocol developed here can be employed in homes, demonstrates the possibility of measuring long-term noise exposures in homes with technologies beyond traditional SLMs, and highlights potential pitfalls associated with measurements made by smart devices.

Assessment of Noise Exposure to Children: Considerations for the National Children's Study.

Evidence has been accruing to indicate that young children are vulnerable to noise in their physical environment. A literature review identified that, in addition to hearing loss, noise exposure is associated with negative birth outcomes, reduced cognitive function, inability to concentrate, increased psychosocial activation, nervousness, feeling of helplessness, and increased blood pressure in children. While increasing attention has been given to the health effects of noise in children, research about noise exposure is sparse and often the measure of exposure is simply proximity to a noise source. The U.S. National Children's Study (NCS) provides a unique opportunity to investigate noise exposures to pregnant women and children using a number of assessment modalities at different life stages. Measurement of noise levels in homes and other environments, personal dosimetry measurements made over a period of days, and questionnaires addressing sources of noise in the environment, annoyance to noise, perceived noise level, use of head phones and ear buds, noisy activity exposures, and occupational exposures, are planned for evaluation within the NCS Vanguard pilot study. We describe the NCS planned approach to addressing noise exposure assessment in study visits over a child's lifetime.

Lead, allergen, and pesticide levels in licensed child care centers in the United States.

The First National Environmental Health Survey of Child Care Centers was conducted to provide information about lead, allergen, and pesticide levels in licensed U.S. child care centers. Lead levels were measured in settled dust, paint, and play area soil; indoor allergen levels were measured in settled dust; and pesticide residues were measured on indoor surfaces and in play area soil. Fourteen percent of centers had significant lead hazards, suggesting that an estimated 470,000 children under age six (approximately 10% of all children in licensed centers) attend centers with significant lead hazards. Approximately 5% of centers had levels of allergens associated with asthma and allergic conditions. Three-quarters of centers had pesticides applied (either indoors or outdoors) during the previous year. Although most centers did not appear to present risks from lead and allergens, some centers did have unsafe levels of these contaminants. These conclusions cannot be generalized to unlicensed child care arrangements.

Comparable measures of cognitive function in human infants and laboratory animals to identify environmental health risks to children.

The importance of including neurodevelopmental end points in environmental studies is clear. A validated measure of cognitive function in human infants that also has a homologous or parallel test in laboratory animal studies will provide a valuable approach for large-scale studies. Such a comparable test will allow researchers to observe the effect of environmental neurotoxicants in animals and relate those findings to humans. In this article, we present the results of a review of post-1990, peer-reviewed literature and current research examining measures of cognitive function that can be applied to both human infants (0-12 months old) and laboratory animals. We begin with a discussion of the definition of cognitive function and important considerations in cross-species research. We then describe identified comparable measures, providing a description of the test in human infants and animal subjects. Available information on test reliability, validity, and population norms, as well as test limitations and constraints, is also presented.