Ander Wilson

Wildfire-specific Fine Particulate Matter and Risk of Hospital Admissions in Urban and Rural Counties.

Background: The health impacts of wildfire smoke, including fine particles (PM2.5), are not well understood and may differ from those of PM2.5 from other sources due to differences in concentrations and chemical composition. Methods: First, for the entire Western United States (561 counties) for 2004–2009, we estimated daily PM2.5 concentrations directly attributable to wildfires (wildfires-specific PM2.5), using a global chemical transport model. Second, we defined smoke wave as ≥2 consecutive days with daily wildfire-specific PM2.5 > 20 &mgr;g/m3, with sensitivity analysis considering 23, 28, and 37 &mgr;g/m3. Third, we estimated the risk of cardiovascular and respiratory hospital admissions associated with smoke waves for Medicare enrollees. We used a generalized linear mixed model to estimate the relative risk of hospital admissions on smoke wave days compared with matched comparison days without wildfire smoke. Results: We estimated that about 46 million people of all ages were exposed to at least one smoke wave during 2004 to 2009 in the Western United States. Of these, 5 million are Medicare enrollees (≥65 years). We found a 7.2% (95% confidence interval: 0.25%, 15%) increase in risk of respiratory admissions during smoke wave days with high wildfire-specific PM2.5 (>37 &mgr;g/m3) compared with matched non smoke wave days. We did not observe an association between smoke wave days with wildfire-specific PM2.5 ⩽ 37 &mgr;g/m3and respiratory or cardiovascular admissions. Respiratory effects of wildfire-specific PM2.5 may be stronger than that of PM2.5 from other sources. Conclusion: Short-term exposure to wildfire-specific PM2.5was associated with risk of respiratory diseases in the elderly population in the Western United States during severe smoke days. See video abstract at, http://links.lww.com/EDE/B137.

Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex

Rationale: Impact of ambient pollution upon childrens asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure. Objectives: We implemented Bayesian‐distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO3−) on child asthma, accounting for effect modification by sex and stress. Methods: Analyses included 752 mother‐child dyads. Daily ambient NO3− exposure during pregnancy was derived using a hybrid chemical transport (Geos‐Chem)/land‐use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician‐diagnosed asthma by age 6 years. Measurements and Main Results: Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7‐19 and 33‐40 wk gestation), during which increased NO3− was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO3− across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27‐5.39; per interquartile range increase in ln NO3−). Conclusions: Prenatal NO3− exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.

Potential for Bias When Estimating Critical Windows for Air Pollution in Children’s Health

Evidence supports an association between maternal exposure to air pollution during pregnancy and childrens health outcomes. Recent interest has focused on identifying critical windows of vulnerability. An analysis based on a distributed lag model (DLM) can yield estimates of a critical window that are different from those from an analysis that regresses the outcome on each of the 3 trimester-average exposures (TAEs). Using a simulation study, we assessed bias in estimates of critical windows obtained using 3 regression approaches: 1) 3 separate models to estimate the association with each of the 3 TAEs; 2) a single model to jointly estimate the association between the outcome and all 3 TAEs; and 3) a DLM. We used weekly fine-particulate-matter exposure data for 238 births in a birth cohort in and around Boston, Massachusetts, and a simulated outcome and time-varying exposure effect. Estimates using separate models for each TAE were biased and identified incorrect windows. This bias arose from seasonal trends in particulate matter that induced correlation between TAEs. Including all TAEs in a single model reduced bias. DLM produced unbiased estimates and added flexibility to identify windows. Analysis of body mass index z score and fat mass in the same cohort highlighted inconsistent estimates from the 3 methods.

Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex

Background The impact of prenatal ambient air pollution on child asthma may be modified by maternal stress, child sex, and exposure dose and timing. Objective We prospectively examined associations between coexposure to prenatal particulate matter with an aerodynamic diameter of less than 2.5 microns (PM2.5) and maternal stress and childhood asthma (n = 736). Methods Daily PM2.5 exposure during pregnancy was estimated using a validated satellite‐based spatiotemporally resolved prediction model. Prenatal maternal negative life events (NLEs) were dichotomized around the median (high: NLE ≥ 3; low: NLE < 3). We used Bayesian distributed lag interaction models to identify sensitive windows for prenatal PM2.5 exposure on childrens asthma by age 6 years, and determine effect modification by maternal stress and child sex. Results Bayesian distributed lag interaction models identified a critical window of exposure (19‐23 weeks’ gestation, cumulative odds ratio, 1.15; 95% CI, 1.03‐1.26; per interquartile range [1.7 &mgr;g/m3] increase in prenatal PM2.5 level) during which children concomitantly exposed to prenatal PM2.5 and maternal stress had increased risk of asthma. No significant association was seen in children born to women reporting low prenatal stress. When examining modifying effects of prenatal stress and fetal sex, we found that boys born to mothers with higher prenatal stress were most vulnerable (19‐21 weeks’ gestation; cumulative odds ratio, 1.28; 95% CI, 1.15‐1.41; per interquartile range increase in PM2.5). Conclusions Prenatal PM2.5 exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress.

Bayesian distributed lag interaction models to identify perinatal windows of vulnerability in children’s health

Epidemiological research supports an association between maternal exposure to air pollution during pregnancy and adverse childrens health outcomes. Advances in exposure assessment and statistics allow for estimation of both critical windows of vulnerability and exposure effect heterogeneity. Simultaneous estimation of windows of vulnerability and effect heterogeneity can be accomplished by fitting a distributed lag model (DLM) stratified by subgroup. However, this can provide an incomplete picture of how effects vary across subgroups because it does not allow for subgroups to have the same window but different within-window effects or to have different windows but the same within-window effect. Because the timing of some developmental processes are common across subpopulations of infants while for others the timing differs across subgroups, both scenarios are important to consider when evaluating health risks of prenatal exposures. We propose a new approach that partitions the DLM into a constrained functional predictor that estimates windows of vulnerability and a scalar effect representing the within-window effect directly. The proposed method allows for heterogeneity in only the window, only the within-window effect, or both. In a simulation study we show that a model assuming a shared component across groups results in lower bias and mean squared error for the estimated windows and effects when that component is in fact constant across groups. We apply the proposed method to estimate windows of vulnerability in the association between prenatal exposures to fine particulate matter and each of birth weight and asthma incidence, and estimate how these associations vary by sex and maternal obesity status in a Boston-area prospective pre-birth cohort study.

Telomere length, long-term black carbon exposure, and cognitive function in a cohort of older men: The VA normative aging study

Background: Long-term air pollution exposure has been associated with age-related cognitive impairment, possibly because of enhanced inflammation. Leukocytes with longer telomere length (TL) are more responsive to inflammatory stimuli, yet TL has not been evaluated in relation to air pollution and cognition. Objectives: We assessed whether TL modifies the association of 1-year exposure to black carbon (BC), a marker of traffic-related air pollution, with cognitive function in older men, and we examined whether this modification is independent of age and of C-reactive protein (CRP), a marker of inflammation. Methods: Between 1999 and 2007, we conducted 1–3 cognitive examinations of 428 older men in the Veterans Affairs (VA) Normative Aging Study. We used covariate-adjusted repeated-measure logistic regression to estimate associations of 1-year BC exposure with relative odds of being a low scorer (≤ 25) on the Mini-Mental State Examination (MMSE), which is a proxy of poor cognition. Confounders included age, CRP, and lifestyle and sociodemographic factors. Results: Each doubling in BC level was associated with 1.57 (95% CI: 1.20, 2.05) times higher odds of low MMSE scores. The BC-MMSE association was greater only among individuals with longer blood TL (5th quintile) (OR = 3.23; 95% CI: 1.37, 7.59; p = 0.04 for BC-by-TL-interaction). TL and CRP were associated neither with each other nor with MMSE. However, CRP modified the BC-MMSE relationship, with stronger associations only at higher CRP (5th quintile) and reference TL level (1st quintile) (OR = 2.68; 95% CI: 1.06, 6.79; p = 0.04 for BC-by-CRP-interaction). Conclusions: TL and CRP levels may help predict the impact of BC exposure on cognitive function in older men. Citation: Colicino E, Wilson A, Frisardi MC, Prada D, Power MC, Hoxha M, Dioni L, Spiro A III, Vokonas PS, Weisskopf MG, Schwartz JD, Baccarelli AA. 2017. Telomere length, long-term black carbon exposure, and cognitive function in a cohort of older men: the VA Normative Aging Study. Environ Health Perspect 125:76–81; http://dx.doi.org/10.1289/EHP241

B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial

Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5–induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation.

Prenatal stress, methylation in inflammation-related genes, and adiposity measures in early childhood: the Progress cohort study

Objective Maternal stress during pregnancy may influence childhood growth and adiposity, possibly through immune/inflammatory programming. We investigated whether exposure to prenatal stress and methylation in inflammation-related genes were associated with childhood adiposity in 424 mother-child pairs in Mexico City, Mexico. Methods A stress index was created based on four prenatally administered stress-related scales (Exposure to Violence, Crisis in Family Systems, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale). We measured weight, height, body fat mass (BFM), percentage body fat (PBF), and waist circumference in early childhood (age range, 4–6 years). Body mass index (BMI) z scores were calculated according to World Health Organization standards. DNA methylation in gene promoters of tumor necrosis factor &agr;, interleukin 8, and interleukin 6 (IL6) in umbilical cord blood were determined by pyrosequencing. Results An interquartile range increase in stress index (27.3) was associated with decreases of 0.14 unit in BMI z score (95% confidence interval [CI] = −0.28 to −0.005), 5.6% in BFM (95% CI = −9.7 to −1.4), 3.5% in PBF (95% CI = −6.3 to −0.5), and 1.2% in waist circumference (95% CI = −2.4 to −0.04) in multivariable-adjusted models. An interquartile range increase in IL6 methylation (3.9%) was associated with increases of 0.23 unit in BMI z score (95% CI = 0.06–0.40), 8.1% (95% CI = 2.3–14.3) in BFM, 5.5% (95% CI = 1.7–9.5) in PBF, and 1.7% (95% CI = 0.2–3.3) in waist circumference. Conclusions Prenatal stress was associated with decreased childhood adiposity, whereas cord blood IL6 methylation was associated with increased childhood adiposity in Mexican children.

Associations of Annual Ambient Fine Particulate Matter Mass and Components with Mitochondrial DNA Abundance

Background: Fine particulate matter (PM2.5) represents a mixture of components with potentially different toxicities. However, little is known about the relative effects of PM2.5 mass and PM2.5 components on mitochondrial DNA (mtDNA) abundance, which may lie on the pathway of PM2.5-associated disease. Methods: We studied 646 elderly male participants in the Normative Aging Study from Greater Boston to investigate associations of long-term exposure to PM2.5 mass and PM2.5 components with mtDNA abundance. We estimated concentrations of pollutants for the 365-day preceding examination at each participant’s address using spatial- and temporal-resolved chemical transport models. We measured blood mtDNA abundance using RT-PCR. We applied a shrinkage and selection method (adaptive LASSO) to identify components most predictive of mtDNA abundance, and fit multipollutant linear mixed-effects models with subject-specific intercept to estimate the relative effects of individual PM component. Results: MtDNA abundance was negatively associated with PM2.5 mass in the previous year and—after adjusting for PM2.5 mass—several PM2.5 components, including organic carbon, sulfate (marginally), and nitrate. In multipollutant models including as independent variables PM2.5 mass and PM2.5 components selected by LASSO, nitrate was associated with mtDNA abundance. An SD increase in annual PM2.5-associated nitrate was associated with a 0.12 SD (95% confidence intervals [CI] = −0.18, −0.07) decrease in mtDNA abundance. Analyses restricted to PM2.5 annual concentration below the current 1-year U.S. Environmental Protection Agency standard produced similar results. Conclusions: Long-term exposures to PM2.5-associated nitrate were related to decreased mtDNA abundance independent of PM2.5 mass. Mass alone may not fully capture the potential of PM2.5 to oxidize the mitochondrial genome. See video abstract at, http://links.lww.com/EDE/B274.

Prenatal particulate air pollution exposure and body composition in urban preschool children: Examining sensitive windows and sex-specific associations

Background Evolving animal studies and limited epidemiological data show that prenatal air pollution exposure is associated with childhood obesity. Timing of exposure and child sex may play an important role in these associations. We applied an innovative method to examine sex‐specific sensitive prenatal windows of exposure to PM2.5 on anthropometric measures in preschool‐aged children. Methods Analyses included 239 children born ≥ 37 weeks gestation in an ethnically‐mixed lower‐income urban birth cohort. Prenatal daily PM2.5 exposure was estimated using a validated satellite‐based spatio‐temporal model. Body mass index z‐score (BMI‐z), fat mass, % body fat, subscapular and triceps skinfold thickness, waist and hip circumferences and waist‐to‐hip ratio (WHR) were assessed at age 4.0 ± 0.7 years. Using Bayesian distributed lag interaction models (BDLIMs), we examined sex differences in sensitive windows of weekly averaged PM2.5 levels on these measures, adjusting for child age, maternal age, education, race/ethnicity, and pre‐pregnancy BMI. Results Mothers were primarily Hispanic (55%) or Black (26%), had ≤ 12 years of education (66%) and never smoked (80%). Increased PM2.5 exposure 8–17 and 15–22 weeks gestation was significantly associated with increased BMI z‐scores and fat mass in boys, but not in girls. Higher PM2.5 exposure 10–29 weeks gestation was significantly associated with increased WHR in girls, but not in boys. Prenatal PM2.5 was not significantly associated with other measures of body composition. Estimated cumulative effects across pregnancy, accounting for sensitive windows and within‐window effects, were 0.21 (95%CI = 0.01–0.37) for BMI‐z and 0.36 (95%CI = 0.12–0.68) for fat mass (kg) in boys, and 0.02 (95%CI = 0.01–0.03) for WHR in girls, all per &mgr;g/m3 increase in PM2.5. Conclusions Increased prenatal PM2.5 exposure was more strongly associated with indices of increased whole body size in boys and with an indicator of body shape in girls. Methods to better characterize vulnerable windows may provide insight into underlying mechanisms contributing to sex‐specific associations. HighlightsData‐driven method to identify sensitive windows of prenatal PM2.5 on anthropometry.Findings suggested time‐dependent associations and effect modification by sex.Sex‐specific temporal associations may provide insights into underlying mechanisms.