A New Hybrid Spatio-temporal Model for Estimating Daily Multi-year PM2.5 Concentrations Across Northeastern USA Using High Resolution Aerosol Optical Depth Data

The use of satellite-based aerosol optical depth (AOD) to estimate fine particulate matter PM(sub 2.5) for epidemiology studies has increased substantially over the past few years. These recent studies often report moderate predictive power, which can generate downward bias in effect estimates. In addition, AOD measurements have only moderate spatial resolution, and have substantial missing data. We make use of recent advances in MODIS satellite data processing algorithms (Multi-Angle Implementation of Atmospheric Correction (MAIAC), which allow us to use 1 km (versus currently available 10 km) resolution AOD data.We developed and cross validated models to predict daily PM(sub 2.5) at a 1X 1 km resolution across the northeastern USA (New England, New York and New Jersey) for the years 2003-2011, allowing us to better differentiate daily and long term exposure between urban, suburban, and rural areas. Additionally, we developed an approach that allows us to generate daily high-resolution 200 m localized predictions representing deviations from the area 1 X 1 km grid predictions. We used mixed models regressing PM(sub 2.5) measurements against day-specific random intercepts, and fixed and random AOD and temperature slopes. We then use generalized additive mixed models with spatial smoothing to generate grid cell predictions when AOD was missing. Finally, to get 200 m localized predictions, we regressed the residuals from the final model for each monitor against the local spatial and temporal variables at each monitoring site. Our model performance was excellent (mean out-of-sample R(sup 2) = 0.88). The spatial and temporal components of the out-of-sample results also presented very good fits to the withheld data (R(sup 2) = 0.87, R(sup)2 = 0.87). In addition, our results revealed very little bias in the predicted concentrations (Slope of predictions versus withheld observations = 0.99). Our daily model results show high predictive accuracy at high spatial resolutions and will be useful in reconstructing exposure histories for epidemiological studies across this region

Asthma in Inner-City Children at 5–11 Years of Age and Prenatal Exposure to Phthalates: The Columbia Center for Children’s Environmental Health Cohort

Background: Studies suggest that phthalate exposures may adversely affect child respiratory health. Objectives: We evaluated associations between asthma diagnosed in children between 5 and 11 years of age and prenatal exposures to butylbenzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), and diethyl phthalate (DEP). Methods: Phthalate metabolites were measured in spot urine collected from 300 pregnant inner-city women. Children were examined by an allergist or pulmonologist based on the first parental report of wheeze, other respiratory symptoms, and/or use of asthma rescue/controller medication in the preceding 12 months on repeat follow-up questionnaires. Standardized diagnostic criteria were used to classify these children as either having or not having current asthma at the time of the physician examination. Children without any report of wheeze or the other asthma-like symptoms were classified as nonasthmatics at the time of the last negative questionnaire. Modified Poisson regression analyses were used to estimate relative risks (RR) controlling for specific gravity and potential confounders. Results: Of 300 children, 154 (51%) were examined by a physician because of reports of wheeze, other asthma-like symptoms, and/or medication use; 94 were diagnosed with current asthma and 60 without current asthma. The remaining 146 children were classified as nonasthmatic. Compared with levels in nonasthmatics, prenatal metabolites of BBzP and DnBP were associated with a history of asthma-like symptoms (p 70% higher among children with maternal prenatal BBzP and DnBP metabolite concentrations in the third versus the first tertile. Conclusion: Prenatal exposure to BBzP and DnBP may increase the risk of asthma among inner-city children. However, because this is the first such finding, results require replication. Citation: Whyatt RM, Perzanowski MS, Just AC, Rundle AG, Donohue KM, Calafat AM, Hoepner LA, Perera FP, Miller RL. 2014. Asthma in inner-city children at 5–11 years of age and prenatal exposure to phthalates: the Columbia Center for Children’s Environmental Health Cohort. Environ Health Perspect 122:1141–1146; http://dx.doi.org/10.1289/ehp.130767

Prenatal phthalate and early childhood bisphenol A exposures increase asthma risk in inner-city children

To the Editor: We previously reported that inner-city childhood asthma was independently associated with measures of early childhood exposure to bisphenol A (BPA)1 and prenatal, but not childhood, exposures to di-n-butyl phthalate and butylbenzyl phthalate (BBzP). 2 Here, we evaluate whether these 2 classes of endocrine-disrupting chemicals interact to increase the risk of asthma. We evaluated 292 inner-city women and their children aged 5 to 11 years from the Columbia Center for Children's Environmental Health birth cohort of pregnant women who delivered between 1998 and 2006. Enrollment, exclusion criteria, and a description of the cohort have been reported previously.3 Subjects were selected for the present study on the basis of the availability of (1) measurements of phthalates in spot urine collected from the mother during pregnancy (33.9 ± 3.1 weeks' gestation) and BPA in child urine at ages 3 (n = 237), 5 (259), and/or 7 (n = 161) years; (2) data on child asthma and wheeze-related outcomes; and (3) availability of model covariates. Demographic characteristics of Columbia Center for Children's Environmental Health subjects are provided in Table E1 in this article's Online Repository at www.jacionline.org. All participants gave written informed consent

Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children

Background Bisphenol A (BPA) is used widely to manufacture food container linings. Mouse models suggest exposure to BPA might increase allergic inflammation. Objectives We hypothesized that BPA exposure, as assessed based on urinary BPA concentrations, would be associated with increased odds of wheeze and asthma and increased fraction of exhaled nitric oxide (Feno) values in children. Methods The Columbia Center for Children's Environmental Health recruited pregnant women for a prospective birth cohort study (n = 568). Mothers during the third trimester and children at ages 3, 5, and 7 years provided spot urine samples. Total urinary BPA concentrations were measured by using online solid-phase extraction, high-performance liquid chromatography, isotope-dilution tandem mass spectrometry. Wheeze in the last 12 months was measured by using questionnaires at ages 5, 6, and 7 years. Asthma was determined by a physician once between ages 5 and 12 years. Feno values were measured at ages 7 to 11 years. Results Prenatal urinary BPA concentrations were associated inversely with wheeze at age 5 years (odds ratio [OR], 0.7; 95% CI, 0.5-0.9; P = .02). Urinary BPA concentrations at age 3 years were associated positively with wheeze at ages 5 years (OR, 1.4; 95% CI, 1.1-1.8; P = .02) and 6 years (OR, 1.4; 95% CI, 1.0-1.9; P = .03). BPA concentrations at age 7 years were associated with wheeze at age 7 years (OR, 1.4; 95% CI, 1.0-1.9; P = .04) and Feno values (β = 0.1; 95% CI, 0.02-0.2; P = .02). BPA concentrations at ages 3, 5, and 7 years were associated with asthma (OR, 1.5 [95% CI, 1.1-2.0], P = .005; OR, 1.4 [95% CI, 1.0-1.9], P = .03; and OR, 1.5 [95% CI, 1.0-2.1], P = .04, respectively). Conclusions This is the first report of an association between postnatal urinary BPA concentrations and asthma in children

Maternal Prenatal Urinary Phthalate Metabolite Concentrations and Child Mental, Psychomotor, and Behavioral Development at 3 Years of Age

Background: Research suggests that prenatal phthalate exposures affect child executive function and behavior

Genome-Wide Analysis of DNA Methylation and Fine Particulate Matter Air Pollution in Three Study Populations: KORA F3, KORA F4, and the Normative Aging Study

BACKGROUND: Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites. OBJECTIVES: We studied the association between DNA methylation and short-and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for-additional investigation. METHODS: We collected whole blood samples from three independent studies-KORA F3 (2004-2005) and F4 (2006-2008) in Germany, and the Normative Aging Study (1999-2007) in the United States-and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results. RESULTS: Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p 0.05 and I-2< 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively. CONCLUSION: The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation

Intermediate- and long-term associations between air pollution and ambient temperature and glycated hemoglobin levels in women of child bearing age

Background: Air pollution has been linked to obesity while higher ambient temperatures typically reduce metabolic demand in a compensatory manner. Both relationships may impact glucose metabolism, thus we examined the association between intermediate- and long-term exposure to fine particulate matter (PM2.5) and ambient temperature and glycated hemoglobin (HbA1c), a longer-term marker of glucose control. Methods: We assessed 3-month, 6-month, and 12-month average air pollution and ambient temperature at 1-km2 spatial resolution via satellite remote sensing models (2013–2019), and assessed HbA1c at four, six, and eight years postpartum in women enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City. PM2.5 and ambient temperature were matched to participants’ addresses and confirmed by GPS tracker. Using linear mixed-effects models, we examined the association between 3-month, 6-month, and 12-month average PM2.5 and ambient temperature with repeated log-transformed HbA1c values. All models included a random intercept for each woman and were adjusted for calendar year, season, and individual-level confounders (age, marital status, smoking, alcohol consumption level, and education level). Results: We analyzed 1,265 HbA1c measurements of 484 women. Per 1 µg/m3 increase in 3-month and 6-month PM2.5, HbA1c levels increased by 0.28% (95% confidence interval (95 %CI): 0.14, 0.42%) and 0.28% (95 %CI: 0.04, 0.52%) respectively. No association was seen for 12-month average PM2.5. Per 1 °C increase in ambient temperature, HbA1c levels decreased by 0.63% (95 %CI: −1.06, −0.21%) and 0.61% (95 %CI: −1.08, −0.13%), while the 12-month average again is not associated with HbA1c. Conclusions: Intermediate-term exposure to PM2.5 and ambient temperature are associated with opposing changes in HbA1c levels, in this region of high PM2.5 and moderate temperature fluctuation. These effects, measurable in mid-adult life, may portend future risk of type 2 diabetes and possible heart disease

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Empirical comparison of reduced representation bisulfite sequencing and Infinium BeadChip reproducibility and coverage of DNA methylation in humans

We empirically examined the strengths and weaknesses of two human genome-wide DNA methylation platforms: rapid multiplexed reduced representation bisulfite sequencing and Illumina’s Infinium BeadChip. Rapid multiplexed reduced representation bisulfite sequencing required less input DNA, offered more flexibility in coverage, and interrogated more CpG loci at a higher regional density. The Infinium covered slightly more protein coding, cancer-associated and mitochondrial-related genes, both platforms covered all known imprinting clusters, and rapid multiplexed reduced representation bisulfite sequencing covered more microRNA genes than the HumanMethylation450, but fewer than the MethylationEPIC. Rapid multiplexed reduced representation bisulfite sequencing did not always interrogate exactly the same CpG loci, but genomic tiling improved overlap between different libraries. Reproducibility of rapid multiplexed reduced representation bisulfite sequencing and concordance between the platforms increased with CpG density. Only rapid multiplexed reduced representation bisulfite sequencing could genotype samples and measure allele-specific methylation, and we confirmed that Infinium measurements are influenced by nearby single-nucleotide polymorphisms. The respective strengths and weaknesses of these two genome-wide DNA methylation platforms need to be considered when conducting human epigenetic studies