Cohort profile: the ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS).

PURPOSE: Exposures early in life, beginning in utero, have long-term impacts on mental and physical health. The ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS) was established to examine the independent and combined impact of pregnancy and childhood chemical exposures and psychosocial stressors on child neurodevelopment and airway health, as well as the placental mechanisms underlying these associations. PARTICIPANTS: The ECHO-PATHWAYS consortium harmonises extant data from 2684 mother-child dyads in three pregnancy cohort studies (CANDLE [Conditions Affecting Neurocognitive Development and Learning in Early Childhood], TIDES [The Infant Development and Environment Study] and GAPPS [Global Alliance to Prevent Prematurity and Stillbirth]) and collects prospective data under a unified protocol. Study participants are socioeconomically diverse and include a large proportion of Black families (38% Black and 51% White), often under-represented in research. Children are currently 5-15 years old. New data collection includes multimodal assessments of primary outcomes (airway health and neurodevelopment) and exposures (air pollution, phthalates and psychosocial stress) as well as rich covariate characterisation. ECHO-PATHWAYS is compiling extant and new biospecimens in a central biorepository and generating the largest placental transcriptomics data set to date (N=1083). FINDINGS TO DATE: Early analyses demonstrate adverse associations of prenatal exposure to air pollution, phthalates and maternal stress with early childhood airway outcomes and neurodevelopment. Placental transcriptomics work suggests that phthalate exposure alters placental gene expression, pointing to mechanistic pathways for the developmental toxicity of phthalates. We also observe associations between prenatal maternal stress and placental corticotropin releasing hormone, a marker of hormonal activation during pregnancy relevant for child health. Other publications describe novel methods for examining exposure mixtures and the development of a national spatiotemporal model of ambient outdoor air pollution. FUTURE PLANS: The first wave of data from the unified protocol (child age 8-9) is nearly complete. Future work will leverage these data to examine the combined impact of early life social and chemical exposures on middle childhood health outcomes and underlying placental mechanisms.

Deployment, Calibration, and Cross-Validation of Low-Cost Electrochemical Sensors for Carbon Monoxide, Nitrogen Oxides, and Ozone for an Epidemiological Study.

We designed and built a network of monitors for ambient air pollution equipped with low-cost gas sensors to be used to supplement regulatory agency monitoring for exposure assessment within a large epidemiological study. This paper describes the development of a series of hourly and daily field calibration models for Alphasense sensors for carbon monoxide (CO; CO-B4), nitric oxide (NO; NO-B4), nitrogen dioxide (NO2; NO2-B43F), and oxidizing gases (OX-B431)-which refers to ozone (O3) and NO2. The monitor network was deployed in the Puget Sound region of Washington, USA, from May 2017 to March 2019. Monitors were rotated throughout the region, including at two Puget Sound Clean Air Agency monitoring sites for calibration purposes, and over 100 residences, including the homes of epidemiological study participants, with the goal of improving long-term pollutant exposure predictions at participant locations. Calibration models improved when accounting for individual sensor performance, ambient temperature and humidity, and concentrations of co-pollutants as measured by other low-cost sensors in the monitors. Predictions from the final daily models for CO and NO performed the best considering agreement with regulatory monitors in cross-validated root-mean-square error (RMSE) and R2 measures (CO: RMSE = 18 ppb, R2 = 0.97; NO: RMSE = 2 ppb, R2 = 0.97). Performance measures for NO2 and O3 were somewhat lower (NO2: RMSE = 3 ppb, R2 = 0.79; O3: RMSE = 4 ppb, R2 = 0.81). These high levels of calibration performance add confidence that low-cost sensor measurements collected at the homes of epidemiological study participants can be integrated into spatiotemporal models of pollutant concentrations, improving exposure assessment for epidemiological inference.

Calibration of low-cost particulate matter sensors: Model development for a multi-city epidemiological study.

Low-cost air monitoring sensors are an appealing tool for assessing pollutants in environmental studies. Portable low-cost sensors hold promise to expand temporal and spatial coverage of air quality information. However, researchers have reported challenges in these sensors' operational quality. We evaluated the performance characteristics of two widely used sensors, the Plantower PMS A003 and Shinyei PPD42NS, for measuring fine particulate matter compared to reference methods, and developed regional calibration models for the Los Angeles, Chicago, New York, Baltimore, Minneapolis-St. Paul, Winston-Salem and Seattle metropolitan areas. Duplicate Plantower PMS A003 sensors demonstrated a high level of precision (averaged Pearson's r = 0.99), and compared with regulatory instruments, showed good accuracy (cross-validated R2 = 0.96, RMSE = 1.15 µg/m3 for daily averaged PM2.5 estimates in the Seattle region). Shinyei PPD42NS sensor results had lower precision (Pearson's r = 0.84) and accuracy (cross-validated R2 = 0.40, RMSE = 4.49 µg/m3). Region-specific Plantower PMS A003 models, calibrated with regulatory instruments and adjusted for temperature and relative humidity, demonstrated acceptable performance metrics for daily average measurements in the other six regions (R2 = 0.74-0.95, RMSE = 2.46-0.84 µg/m3). Applying the Seattle model to the other regions resulted in decreased performance (R2 = 0.67-0.84, RMSE = 3.41-1.67 µg/m3), likely due to differences in meteorological conditions and particle sources. We describean approach to metropolitan region-specific calibration models for low-cost sensors that can be used with cautionfor exposure measurement in epidemiological studies.

Author Correction: Integrating data from multiple time-location measurement methods for use in exposure assessment: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

In addition to the acknowledgments that were included, the authors wish to add the following: MESA was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute.

Estimating ambient-origin PM2.5 exposure for epidemiology: observations, prediction, and validation using personal sampling in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: We aim to characterize the qualities of estimation approaches for individual exposure to ambient-origin fine particulate matter (PM2.5), for use in epidemiological studies. METHODS: The analysis incorporates personal, home indoor, and home outdoor air monitoring data and spatio-temporal model predictions for 60 participants from the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). We compared measurement-based personal PM2.5 exposure with several measured or predicted estimates of outdoor, indoor, and personal exposures. RESULTS: The mean personal 2-week exposure was 7.6 (standard deviation 3.7) µg/m3. Outdoor model predictions performed far better than outdoor concentrations estimated using a nearest-monitor approach (R = 0.63 versus R = 0.43). Incorporating infiltration indoors of ambient-derived PM2.5 provided better estimates of the measurement-based personal exposures than outdoor concentration predictions (R = 0.81 versus R = 0.63) and better scaling of estimated exposure (mean difference 0.4 versus 5.4 µg/m3 higher than measurements), suggesting there is value to collecting data regarding home infiltration. Incorporating individual-level time-location information into exposure predictions did not increase correlations with measurement-based personal exposures (R = 0.80) in our sample consisting primarily of retired persons. CONCLUSIONS: This analysis demonstrates the importance of incorporating infiltration when estimating individual exposure to ambient air pollution. Spatio-temporal models provide substantial improvement in exposure estimation over a nearest monitor approach.

Contribution of the in-vehicle microenvironment to individual ambient-source nitrogen dioxide exposure: the Multi-Ethnic Study of Atherosclerosis and Air Pollution.

Exposure estimates that do not account for time in-transit may underestimate exposure to traffic-related air pollution, but exact contributions have not been studied directly. We conducted a 2-week monitoring, including novel in-vehicle sampling, in a subset of the Multi-Ethnic Study of Atherosclerosis and Air Pollution cohort in two cities. Participants spent the majority of their time indoors and only 4.4% of their time (63 min/day) in-vehicle, on average. The mean ambient-source NO2 concentration was 5.1 ppb indoors and 32.3 ppb in-vehicle during drives. On average, indoor exposure contributed 69% and in-vehicle exposure contributed 24% of participants' ambient-source NO2 exposure. For participants in the highest quartile of time in-vehicle (≥1.3 h/day), indoor and in-vehicle contributions were 60 and 31%, respectively. Incorporating infiltrated indoor and measured in-vehicle NO2 produced exposure estimates 5.6 ppb lower, on average, than using only outdoor concentrations. The indoor microenvironment accounted for the largest proportion of ambient-source exposure in this older population, despite higher concentrations of NO2 outdoors and in vehicles than indoors. In-vehicle exposure was more influential among participants who drove the most and for participants residing in areas with lower outdoor air pollution. Failure to characterize exposures in these microenvironments may contribute to exposure misclassification in epidemiologic studies.

Integrating data from multiple time-location measurement methods for use in exposure assessment: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

Tools to assess time-location patterns related to environmental exposures have expanded from reliance on time-location diaries (TLDs) and questionnaires to use of geospatial location devices such as data-logging Global Positioning System (GPS) equipment. The Multi-Ethnic Study of Atherosclerosis and Air Pollution obtained typical time-location patterns via questionnaire for 6424 adults in six US cities. At a later time (mean 4.6 years after questionnaire), a subset (n=128) participated in high-resolution data collection for specific 2-week periods resulting in concurrent GPS and detailed TLD data, which were aggregated to estimate time spent in various microenvironments. During these 2-week periods, participants were observed to spend the most time at home indoors (mean of 78%) and a small proportion of time in-vehicle (mean of 4%). Similar overall patterns were reported by these participants on the prior questionnaire (mean home indoors: 75%; mean in-vehicle: 4%). However, individual micro-environmental time estimates measured over specific 2-week periods were not highly correlated with an individual's questionnaire report of typical behavior (Spearman's ρ of 0.43 for home indoors and 0.39 for in-vehicle). Although questionnaire data about typical time-location patterns can inform interpretation of long-term epidemiological analyses and risk assessment, they may not reliably represent an individual's short-term experience.

Advances in Understanding Air Pollution and CVD.

The MESA Air (Multi-Ethnic Study of Atherosclerosis and Air Pollution) leveraged the platform of the MESA cohort into a prospective longitudinal study of relationships between air pollution and cardiovascular health. MESA Air researchers developed fine-scale, state-of-the-art air pollution exposure models for the MESA Air communities, creating individual exposure estimates for each participant. These models combine cohort-specific exposure monitoring, existing monitoring systems, and an extensive database of geographic and meteorological information. Together with extensive phenotyping in MESA-and adding participants and health measurements to the cohort-MESA Air investigated environmental exposures on a wide range of outcomes. Advances by the MESA Air team included not only a new approach to exposure modeling, but also biostatistical advances in addressing exposure measurement error and temporal confounding. The MESA Air study advanced our understanding of the impact of air pollutants on cardiovascular disease and provided a research platform for advances in environmental epidemiology.

Factors influencing time-location patterns and their impact on estimates of exposure: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

We assessed time-location patterns and the role of individual- and residential-level characteristics on these patterns within the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) cohort and also investigated the impact of individual-level time-location patterns on individual-level estimates of exposure to outdoor air pollution. Reported time-location patterns varied significantly by demographic factors such as age, gender, race/ethnicity, income, education, and employment status. On average, Chinese participants reported spending significantly more time indoors and less time outdoors and in transit than White, Black, or Hispanic participants. Using a tiered linear regression approach, we predicted time indoors at home and total time indoors. Our model, developed using forward-selection procedures, explained 43% of the variability in time spent indoors at home, and incorporated demographic, health, lifestyle, and built environment factors. Time-weighted air pollution predictions calculated using recommended time indoors from USEPA overestimated exposures as compared with predictions made with MESA Air participant-specific information. These data fill an important gap in the literature by describing the impact of individual and residential characteristics on time-location patterns and by demonstrating the impact of population-specific data on exposure estimates.

Time-location patterns of a diverse population of older adults: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

The primary aim of this analysis was to present and describe questionnaire data characterizing time-location patterns of an older, multiethnic population from six American cities. We evaluated the consistency of results from repeated administration of this questionnaire and between this questionnaire and other questionnaires collected from participants of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Participants reported spending most of their time inside their homes (average: 121 h/week or 72%). More than 50% of the participants reported spending no time in several of the location options, including at home outdoors, at work/volunteer/school locations indoors or outdoors, or in "other" locations outdoors. We observed consistency between self-reported time-location patterns from repeated administration of the time-location questionnaire and compared with other survey instruments. Comparisons with national cohorts demonstrated the differences in time-location patterns in the MESA Air cohort due to differences in demographics, but the data showed similar trends in patterns by age, gender, season, and employment status. This study was the first to explicitly examine the time-location patterns in an older, multiethnic population and the first to add data on Chinese participants. These data can be used to inform future epidemiological research of MESA Air and other studies that include diverse populations.

Dermal absorption of environmental contaminants from soil and sediment: a critical review.

Risk assessment of hazardous wastes sites may require characterization of the dermal availability of chemical contaminants in soil and/or sediment. Current U.S. Environmental Protection Agency guidance for assessment of dermal exposures to contaminants in water and soil was finalized in 2004 as a supplement (Part E) to the Risk Assessment Guidance for Superfund (RAGS). The soil protocol presented in RAGS Part E is less sophisticated than the water protocol and is supported by less empirical data. Investigations of dermal absorption of soil and sediment-borne contaminants that have been conducted to date include in vitro and in vivo experiments using both human and surrogate skin. A review of that literature was conducted with attention to relevant criteria including consideration of layering effects, degree of chemical saturation of soil, appropriateness of particle size distribution employed, soil-chemical contact time, and continuity of soil-skin contact (in in vivo studies). Most studies published to date are deficient by virtue of execution or reporting on one or more of the selected criteria. In addition the lack of methodological standardization evident in the literature hinders systematic evaluation of results. Since additional experimental work is needed, general agreement on acceptable approaches would be useful. Recommendations for good practice are presented.