BACKGROUND: Estimating the burden of disease attributable to long-term exposure to fine particulate matter (PM2.5) in ambient air requires knowledge of both the shape and magnitude of the relative risk (RR) function. However, adequate direct evidence to identify the shape of the mortality RR functions at the high ambient concentrations observed in many places in the world is lacking. OBJECTIVE: We developed RR functions over the entire global exposure range for causes of mortality in adults: ischemic heart disease (IHD), cerebrovascular disease (stroke), chronic obstructive pulmonary disease (COPD), and lung cancer (LC). We also developed RR functions for the incidence of acute lower respiratory infection (ALRI) that can be used to estimate mortality and lost-years of healthy life in children < 5 years of age. METHODS: We fit an integrated exposure-response (IER) model by integrating available RR information from studies of ambient air pollution (AAP), second hand tobacco smoke, household solid cooking fuel, and active smoking (AS). AS exposures were converted to estimated annual PM2.5 exposure equivalents using inhaled doses of particle mass. We derived population attributable fractions (PAFs) for every country based on estimated worldwide ambient PM2.5 concentrations. RESULTS: The IER model was a superior predictor of RR compared with seven other forms previously used in burden assessments. The percent PAF attributable to AAP exposure varied among countries from 2 to 41 for IHD, 1 to 43 for stroke, < 1 to 21 for COPD, < 1 to 25 for LC, and < 1 to 38 for ALRI. CONCLUSIONS: We developed a fine particulate mass-based RR model that covered the global range of exposure by integrating RR information from different combustion types that generate emissions of particulate matter. The model can be updated as new RR information becomes available.
BACKGROUND: More than a decade of satellite observations offers global information about the trend and magnitude of human exposure to fine particulate matter (PM2.5). OBJECTIVE: In this study, we developed improved global exposure estimates of ambient PM2.5 mass and trend using PM2.5 concentrations inferred from multiple satellite instruments. METHODS: We combined three satellite-derived PM2.5 sources to produce global PM2.5 estimates at about 10 km x 10 km from 1998 through 2012. For each source, we related total column retrievals of aerosol optical depth to near-ground PM2.5 using the GEOS-Chem chemical transport model to represent local aerosol optical properties and vertical profiles. We collected 210 global ground-based PM2.5 observations from the literature to evaluate our satellite-based estimates with values measured in areas other than North America and Europe. RESULTS: We estimated that global population-weighted ambient PM2.5 concentrations increased 0.55 mu g/m(3)/year (95% CI: 0.43, 0.67) (2.1%/year; 95% CI: 1.6, 2.6) from 1998 through 2012. Increasing PM2.5 in some developing regions drove this global change, despite decreasing PM2.5 in some developed regions. The estimated proportion of the population of East Asia living above the World Health Organization (WHO) Interim Target-1 of 35 mu g/m(3) increased from 51% in 1998-2000 to 70% in 2010-2012. In contrast, the North American proportion above the WHO Air Quality Guideline of 10 mu g/m(3) fell from 62% in 1998-2000 to 19% in 2010-2012. We found significant agreement between satellite-derived estimates and ground-based measurements outside North America and Europe (r = 0.81; n = 210; slope = 0.68). The low bias in satellite-derived estimates suggests that true global concentrations could be even greater. CONCLUSIONS: Satellite observations provide insight into global long-term changes in ambient PM2.5 concentrations. Satellite-derived estimates and ground-based PM2.5 observations from this study are available for public use.
BACKGROUND: Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons. OBJECTIVES: We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life. METHODS: We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications. DISCUSSION: Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U. S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 mu g/L; however, concentrations of > 3,000 mu g/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood. CONCLUSIONS: These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.
BACKGROUND: Three decades of rapid economic development is causing severe and widespread PM2.5 (particulate matter <= 2.5 mu m) pollution in China. However, research on the health impacts of PM2.5 exposure has been hindered by limited historical PM2.5 concentration data. OBJECTIVES: We estimated ambient PM2.5 concentrations from 2004 to 2013 in China at 0.1 degrees resolution using the most recent satellite data and evaluated model performance with available ground observations. METHODS: We developed a two-stage spatial statistical model using the Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 6 aerosol optical depth (AOD) and assimilated meteorology, land use data, and PM2.5 concentrations from China's recently established ground monitoring network. An inverse variance weighting (IVW) approach was developed to combine MODIS Dark Target and Deep Blue AOD to optimize data coverage. We evaluated model-predicted PM2.5 concentrations from 2004 to early 2014 using ground observations. RESULTS: The overall model cross-validation R-2 and relative prediction error were 0.79 and 35.6%, respectively. Validation beyond the model year (2013) indicated that it accurately predicted PM2.5 concentrations with little bias at the monthly (R-2 = 0.73, regression slope = 0.91) and seasonal (R-2 = 0.79, regression slope = 0.92) levels. Seasonal variations revealed that winter was the most polluted season and that summer was the cleanest season. Analysis of predicted PM2.5 levels showed a mean annual increase of 1.97 mu g/m(3) between 2004 and 2007 and a decrease of 0.46 mu g/m(3) between 2008 and 2013. CONCLUSIONS: Our satellite-driven model can provide reliable historical PM2.5 estimates in China at a resolution comparable to those used in epidemiologic studies on the health effects of long-term PM2.5 exposure in North America. This data source can potentially advance research on PM2.5 health effects in China.
Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear. Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy. Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K). Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10-7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke. Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.
Background: Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson's disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans. Objectives: Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans. Methods: We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controlsrone case. Results: In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0-2.8] including rotenone (OR = 2.5; 95% CI, 1.3-4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2-3.6), including paraquat (OR = 2.5; 95% CI, 1.4-4.7). Conclusions: PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.
Background: Epidemiologic studies have reported associations between fine particles (aerodynamic diameter ≤ 2.5 µm; PM₂.₅) and mortality. However, concerns have been raised regarding the sensitivity of the results to model specifications, lower exposures, and averaging time. Objective: We addressed these issues using 11 additional years of follow-up of the Harvard Six Cities study, incorporating recent lower exposures. Methods: We replicated the previously applied Cox regression, and examined different time lags, the shape of the concentration—response relationship using penalized splines, and changes in the slope of the relation over time. We then conducted Poisson survival analysis with time-varying effects for smoking, sex, and education. Results: Since 2001, average PM₂.₅ levels, for all six cities, were < 18 µg/m³. Each increase in PM₂.₅ (10 µg/m³) was associated with an adjusted increased risk of all-cause mortality (PM₂.₅ average on previous year) of 14% [95% confidence interval (CI): 7, 22], and with 26% (95% CI: 14, 40) and 37% (95% CI: 7, 75) increases in cardiovascular and lung-cancer mortality (PM₂.₅ average of three previous years), respectively. The concentration-response relationship was linear down to PM₂.₅ concentrations of 8 µg/m³. Mortality rate ratios for PM₂.₅ fluctuated over time, but without clear trends despite a substantial drop in the sulfate fraction. Poisson models produced similar results. Conclusions: These results suggest that further public policy efforts that reduce fine particulate matter air pollution are likely to have continuing public health benefits.
BACKGROUND: Few studies have investigated effects of air pollution on the incidence of cerebrovascular events. OBJECTIVES: We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts. METHODS: Data from 11 cohorts were collected, and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The exposures were: PM2.5 [particulate matter (PM) = 2.5 m in diameter], coarse PM (PM between 2.5 and 10 m), PM10 (PM = 60 years of age (HR = 1.40, 95% CI: 1.05, 1.87), among neversmokers (HR = 1.74, 95% CI: 1.06, 2.88), and among participants with PM2.5 exposure <25 g/m(3) (HR = 1.33, 95% CI: 1.01, 1.77). CONCLUSIONS: We found suggestive evidence of an association between fine particles and incidence of cerebrovascular events in Europe, even at lower concentrations than set by the current air quality limit value.
BACKGROUND: Epidemiologie and health impact studies of fine particulate matter with diameter < 2.5 um (PM₂.₄) are limited by the lack of monitoring data, especially in developing countries. Satellite observations offer valuable global information about PM₂.₄ concentrations. OBJECTIVE: In this study, we developed a technique for estimating surface PM₂.₄ concentrations from satellite observations. METHODS: We mapped global ground-level PM₂.₄ concentrations using total column aerosol optical depth (AOD) from the MODIS (Moderate Resolution Imaging Spectroradiometer) and MISR (Multiangle Imaging Spectroradiometer) satellite instruments and coincident aerosol vertical profiles from the GEOS-Chem global chemical transport model. RESULTS: We determined that global estimates of long-term average (1 January 2001 to 31 December 2006) PM₂.₄ concentrations at approximately 10 km x 10 km resolution indicate a global population-weighted geometric mean PM2.5 concentration of 20 ug/m³. The World Health Organization Air Quality PM₂.₄ Interim Target-1 (35 Hg/m 3 annual average) is exceeded over central and eastern Asia for 38% and for 50% of the population, respectively. Annual mean PM₂.₄ concentrations exceed 80 ug/m 3 over eastern China. Our evaluation of the satellite-derived estimate with ground-based in situ measurements indicates significant spatial agreement with North American measurements (r = 0.77; slope = 1.07; n= 1057) and with noncoincident measurements elsewhere (r = 0.83; slope = 0.86; n = 244). The 1 SO of uncertainty in the satellite-derived PM₂.₄ is 25%, which is inferred from the AOD retrieval and from aerosol vertical profile errors and sampling.The global population-weighted mean uncertainty is 6.7 ug/m³. CONCLUSIONS: Satellite-derived total-column AOD, when combined with a chemical transport model,provides estimates of global long-term average PM₂.₄ concentrations.
BACKGROUND: Exposure to household air pollution from cooking with solid fuels in simple stoves is a major health risk. Modeling reliable estimates of solid fuel use is needed for monitoring trends and informing policy. OBJECTIVES: In order to revise the disease burden attributed to household air pollution for the Global Burden of Disease 2010 project and for international reporting purposes, we estimated annual trends in the world population using solid fuels. METHODS: We developed a multilevel model based on national survey data on primary cooking fuel. RESULTS: The proportion of households relying mainly on solid fuels for cooking has decreased from 62% (95% CI: 58, 66%) to 41% (95% CI: 37, 44%) between 1980 and 2010. Yet because of population growth, the actual number of persons exposed has remained stable at around 2.8 billion during three decades. Solid fuel use is most prevalent in Africa and Southeast Asia where > 60% of households cook with solid fuels. In other regions, primary solid fuel use ranges from 46% in the Western Pacific, to 35% in the Eastern Mediterranean and < 20% in the Americas and Europe. CONCLUSION: Multilevel modeling is a suitable technique for deriving reliable solid-fuel use estimates. Worldwide, the proportion of households cooking mainly with solid fuels is decreasing. The absolute number of persons using solid fuels, however, has remained steady globally and is increasing in some regions. Surveys require enhancement to better capture the health implications of new technologies and multiple fuel use.
BACKGROUND: Phthalates are ubiquitous environmental contaminants. Because of potential adverse effects on human health, butylbenzyl phthalate [BBzP; metabolite, monobenzyl phthalate (MBzP)], di-n-butyl phthalate [DnBP; metabolite, mono-n-butyl phthalate (MnBP)], and di(2-ethylhexyl) phthalate (DEHP) are being replaced by substitutes including other phthalates; however, little is known about consequent trends in population-level exposures. OBJECTIVE: We examined temporal trends in urinary concentrations of phthalate metabolites in the general U. S. population and whether trends vary by sociodemographic characteristics. METHODS: We combined data on 11 phthalate metabolites for 11,071 participants from five cycles of the National Health and Nutrition Examination Survey (2001-2010). Percent changes and least square geometric means (LSGMs) were calculated from multivariate regression models. RESULTS: LSGM concentrations of monoethyl phthalate, MnBP, MBzP, and SDEHP metabolites decreased between 2001-2002 and 2009-2010 [ percent change (95% CI): -42% (- 49, - 34); -17% (-23, -9); -32% (-39, -23) and -37% (-46, -26), respectively]. In contrast, LSGM concentrations of monoisobutyl phthalate, mono(3-carboxypropyl) phthalate (MCPP), monocarboxyoctyl phthalate, and monocarboxynonyl phthalate (MCNP) increased over the study period [percent change (95% CI): 206% (178, 236); 25% (8, 45); 149% (102, 207); and 15% (1, 30), respectively]. Trends varied by subpopulations for certain phthalates. For example, LSGM concentrations of SDEHP metabolites, MCPP, and MCNP were higher in children than adults, but the gap between groups narrowed over time (P-interaction < 0.01). CONCLUSIONS: Exposure of the U. S. population to phthalates has changed in the last decade. Data gaps make it difficult to explain trends, but legislative activity and advocacy campaigns by non-governmental organizations may play a role in changing trends.
BACKGROUND: There are > 7,000 e-cigarette flavors currently marketed. Flavoring chemicals gained notoriety in the early 2000s when inhalation exposure of the flavoring chemical diacetyl was found to be associated with a disease that became known as "popcorn lung." There has been limited research on flavoring chemicals in e-cigarettes. OBJECTIVE: We aimed to determine if the flavoring chemical diacetyl and two other high-priority flavoring chemicals, 2,3-pentanedione and acetoin, are present in a convenience sample of flavored e-cigarettes. METHODS: We selected 51 types of flavored e-cigarettes sold by leading e-cigarette brands and flavors we deemed were appealing to youth. E-cigarette contents were fully discharged and the air stream was captured and analyzed for total mass of diacetyl, 2,3-pentanedione, and acetoin, according to OSHA method 1012. RESULTS: At least one flavoring chemical was detected in 47 of 51 unique flavors tested. Diacetyl was detected above the laboratory limit of detection in 39 of the 51 flavors tested, ranging from below the limit of quantification to 239 mu g/e-cigarette. 2,3-Pentanedione and acetoin were detected in 23 and 46 of the 51 flavors tested at concentrations up to 64 and 529 mu g/e-cigarette, respectively. CONCLUSION: Because of the associations between diacetyl and bronchiolitis obliterans and other severe respiratory diseases observed in workers, urgent action is recommended to further evaluate this potentially widespread exposure via flavored e-cigarettes.
Background: Exposure to chemicals during fetal development can increase the risk of adverse health effects, and while biomonitoring studies suggest pregnant women are exposed to chemicals, little is known about the extent of multiple chemicals exposures among pregnant women in the United States. Objective: We analyzed biomonitoring data from the National Health and Nutritional Examination Survey (NHANES) to characterize both individual and multiple chemical exposures in U.S. pregnant women. Methods: We analyzed data for 163 chemical analytes in 12 chemical classes for subsamples of 268 pregnant women from NHANES 2003-2004, a nationally representative sample of the U.S. population. For each chemical analyte, we calculated descriptive statistics. We calculated the number of chemicals detected within the following chemical classes: polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), organochlorine pesticides, and phthalates and across multiple chemical classes. We compared chemical analyte concentrations for pregnant and nonpregnant women using least-squares geometric means, adjusting for demographic and physiological covariates. Results: The percentage of pregnant women with detectable levels of an individual chemical ranged from 0 to 100%. Certain polychlorinated biphenyls, organochlorine pesticides, PFCs, phenols, PBDEs, phthalates, polycydic aromatic hydrocarbons, and perchlorate were detected in 99-100% of pregnant women. The median number of detected chemicals by chemical class ranged from 4 of 12 PFCs to 9 of 13 phthalates. Across chemical classes, median number ranged from 8 of 17 chemical analytes to 50 of 71 chemical analytes. We found, generally, that levels in pregnant women were similar to or lower than levels in nonpregnant women; adjustment for covariates tended to increase levels in pregnant women compared with nonpregnant women. Conclusions: Pregnant women in the U.S. are exposed to multiple chemicals. Further efforts are warranted to understand sources of exposure and implications for policy making.
BACKGROUND: Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism. OBJECTIVES: We evaluated whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. METHODS: The CHARGE study is a population-based case-control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997-2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316). RESULTS: Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified. CONCLUSIONS: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates.
Background: Lung cancer and cardiovascular disease (CVD) mortality risks increase with smoking, secondhand smoke (SHS), and exposure to fine paniculate matter 40 among long-term heavy smokers. Excess risks for CVD mortality increased steeply at low exposure levels and leveled off at higher exposures, reaching RRs of approximately 2-3 for cigarette smoking. Conclusions: The exposure-response relationship associated with PM2.5 is qualitatively different for lung cancer versus cardiovascular mortality. At low exposure levels, cardiovascular deaths are projected to account for most of the burden of disease, whereas at high levels of PM2.5, lung cancer becomes proportionately more important.
BACKGROUND: Associations of higher indoor carbon dioxide (CO2) concentrations with impaired work performance, increased health symptoms, and poorer perceived air quality have been attributed to correlation of indoor CO2 with concentrations of other indoor air pollutants that are also influenced by rates of outdoor-air ventilation. OBJECTIVES: We assessed direct effects of increased CO2, within the range of indoor concentrations, on decision making. METHODS: Twenty-two participants were exposed to CO2 at 600, 1,000, and 2,500 ppm in an office-like chamber, in six groups. Each group was exposed to these conditions in three 2.5-hr sessions, all on 1 day, with exposure order balanced across groups. At 600 ppm, CO2 came from outdoor air and participants' respiration. Higher concentrations were achieved by injecting ultrapure CO2. Ventilation rate and temperature were constant. Under each condition, participants completed a computer-based test of decision-making performance as well as questionnaires on health symptoms and perceived air quality. Participants and the person administering the decision-making test were blinded to CO2 level. Data were analyzed with analysis of variance models. RESULTS: Relative to 600 ppm, at 1,000 ppm CO2, moderate and statistically significant decrements occurred in six of nine scales of decision-making performance. At 2,500 ppm, large and statistically significant reductions occurred in seven scales of decision-making performance (raw score ratios, 0.06-0.56), but performance on the focused activity scale increased. CONCLUSIONS: Direct adverse effects of CO2 on human performance may be economically important and may limit energy-saving reductions in outdoor air ventilation per person in buildings. Confirmation of these findings is needed.
BACKGROUND: California children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals. OBJECTIVE: Here we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort. METHODS: We measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children's attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323). RESULTS: Maternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination-particularly in the nondominant-at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels. CONCLUSIONS: Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.
BACKGROUND: The human intestine is host to an enormously complex, diverse, and vast microbial community-the gut microbiota. The gut microbiome plays a profound role in metabolic processing, energy production, immune and cognitive development, epithelial homeostasis, and so forth. However, the composition and diversity of the gut microbiome can be readily affected by external factors, which raises the possibility that exposure to toxic environmental chemicals leads to gut microbiome alteration, or dysbiosis. Arsenic exposure affects large human populations worldwide and has been linked to a number of diseases, including cancer, diabetes, and cardiovascular disorders. OBJECTIVES: We investigated the impact of arsenic exposure on the gut microbiome composition and its metabolic profiles. METHODS: We used an integrated approach combining 16S rRNA gene sequencing and mass spectrometry-based metabolomics profiling to examine the functional impact of arsenic exposure on the gut microbiome. RESULTS: 16S rRNA gene sequencing revealed that arsenic significantly perturbed the gut microbiome composition in C57BL/6 mice after exposure to 10 ppm arsenic for 4 weeks in drinking water. Moreover, metabolomics profiling revealed a concurrent effect, with a number of gut microflora-related metabolites being perturbed in multiple biological matrices. CONCLUSIONS: Arsenic exposure not only alters the gut micro-biome community at the abundance level but also substantially disturbs its metabolic profiles at the function level. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism by which arsenic exposure leads to or exacerbates human diseases.
BACKGROUND: Few European studies have investigated the effects of long-term exposure to both fine particulate matter (= 30 years of age who had been living in Rome for at least 5 years at baseline. Residential exposures included annual NO2 (from a land use regression model) and annual PM2.5 (from a Eulerian dispersion model), as well as distance to roads with > 10,000 vehicles/day and traffic intensity. We used Cox regression models to estimate associations with cause-specific mortality adjusted for individual (sex, age, place of birth, residential history, marital status, education, occupation) and area (socio-economic status, clustering) characteristics. RESULTS: Long-term exposures to both NO2 and PM2.5 were associated with an increase in non-accidental mortality [hazard ratio (HR) = 1.03 (95% CI: 1.02, 1.03) per 10-mu g/m(3) NO2; HR = 1.04 (95% CI: 1.03, 1.05) per 10-mu g/m(3) PM2.5]. The strongest association was found for ischemic heart diseases (IHD) [HR = 1.10 (95% CI: 1.06, 1.13) per 10-mu g/m(3) PM2.5], followed by cardio-vascular diseases and lung cancer. The only association showing some deviation from linearity was that between NO2 and IHD. In a bi-pollutant model, the estimated effect of NO2 on mortality was independent of PM2.5. CONCLUSIONS: This large study strongly supports an effect of long-term exposure to NO2 and PM2.5 on mortality, especially from cardio-vascular causes. The results are relevant for the next European policy decisions regarding air quality.
BACKGROUND: Few cohort studies have evaluated the risk of mortality associated with long-term exposure to fine particulate matter [<= 2.5 mu m in aerodynamic diameter (PM2.5)]. This is the first national-level cohort study to investigate these risks in Canada. OBJECTIVE: We investigated the association between long-term exposure to ambient PM2.5 and cardio vascular mortality in non immigrant Canadian adults. METHODS: We assigned estimates of exposure to ambient PM2.5 derived from satellite observations to a cohort of 2.1 million Canadian adults who in 1991 were among the 20% of the population mandated to provide detailed census data. We identified deaths occurring between 1991 and 2001 through record linkage. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for available individual-level and contextual covariates using both standard Cox proportional survival models and nested, spatial random-effects survival models. RESULTS: Using standard Cox models, we calculated HRs of 1.15 (95% CI: 1.13, 1.16) from non-accidental causes and 1.31 (95% CI: 1.27, 1.35) from ischemic heart disease for each 10-mu g/m(3) increase in concentrations of PM2.5. Using spatial random-effects models controlling for the same variables, we calculated HRs of 1.10 (95% CI: 1.05, 1.15) and 1.30 (95% CI: 1.18, 1.43), respectively. We found similar associations between non accidental mortality and PM2.5 based on satellite-derived estimates and ground-based measurements in a subanalysis of subjects in 11 cities. CONCLUSIONS: In this large national cohort of non immigrant Canadians, mortality was associated with long-term exposure to PM2.5. Associations were observed with exposures to PM2.5 at concentrations that were predominantly lower (mean, 8.7 mu g/m(3); interquartile range, 6.2 mu g/m(3)) than those reported previously.