Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

The association of COVID-19 incidence with temperature, humidity, and UV radiation - A global multi-city analysis.

BACKGROUND AND AIM: The associations between COVID-19 transmission and meteorological factors are scientifically debated. Several studies have been conducted worldwide, with inconsistent findings. However, often these studies had methodological issues, e.g., did not exclude important confounding factors, or had limited geographic or temporal resolution. Our aim was to quantify associations between temporal variations in COVID-19 incidence and meteorological variables globally. METHODS: We analysed data from 455 cities across 20 countries from 3 February to 31 October 2020. We used a time-series analysis that assumes a quasi-Poisson distribution of the cases and incorporates distributed lag non-linear modelling for the exposure associations at the city-level while considering effects of autocorrelation, long-term trends, and day of the week. The confounding by governmental measures was accounted for by incorporating the Oxford Governmental Stringency Index. The effects of daily mean air temperature, relative and absolute humidity, and UV radiation were estimated by applying a meta-regression of local estimates with multi-level random effects for location, country, and climatic zone. RESULTS: We found that air temperature and absolute humidity influenced the spread of COVID-19 over a lag period of 15 days. Pooling the estimates globally showed that overall low temperatures (7.5 °C compared to 17.0 °C) and low absolute humidity (6.0 g/m3 compared to 11.0 g/m3) were associated with higher COVID-19 incidence (RR temp =1.33 with 95%CI: 1.08; 1.64 and RR AH =1.33 with 95%CI: 1.12; 1.57). RH revealed no significant trend and for UV some evidence of a positive association was found. These results were robust to sensitivity analysis. However, the study results also emphasise the heterogeneity of these associations in different countries. CONCLUSION: Globally, our results suggest that comparatively low temperatures and low absolute humidity were associated with increased risks of COVID-19 incidence. However, this study underlines regional heterogeneity of weather-related effects on COVID-19 transmission.

Childhood Asthma Incidence, Early and Persistent Wheeze, and Neighborhood Socioeconomic Factors in the ECHO/CREW Consortium.

Importance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. Design, Setting, and Participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. Main Outcomes and Measures: Prevalence of early and persistent childhood wheeze and asthma incidence. Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. Conclusions and Relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

A self-controlled approach to survival analysis, with application to air pollution and mortality.

BACKGROUND: Many studies have reported that long-term air pollution exposure is associated with increased mortality rates. These investigations have been criticized for failure to control for omitted, generally personal, confounders. Study designs that are robust to such confounders can address this issue. METHODS: We used a self-controlled design for survival analysis. We stratified on each person in the Medicare cohort between 2000 and 2015 who died, and examined whether PM2.5, O3 and NO2 exposures predicted in which follow-up period the death occurred. We used conditional logistic regression stratified on person and controlled for nonlinear terms in calendar year and age. By design slowly varying covariates such as smoking history, BMI, diabetes and other pre-existing conditions, usual alcohol consumption, sex, race, socioeconomic status, and green space were controlled by matching each person to themselves. RESULTS: There were 6,452,618 deaths in the study population in the study period. We observed a 5.37% increase in the mortality rate (95% CI 4.67%, 6.08%) for every 5 µg/m3 increase in PM2.5, a 1.98% (95% CI 1.61%, 2.36%) increase for 5 ppb increment in O3, and a 2.10% decrease (95% CI 1.88%, 2.33%) for a 5 ppb increase in NO2. When restricted to persons whose PM2.5 exposure never exceeded 12 µg/m3 in any year between 2000 and 2015, the effect size increased for PM2.5 (12.71% (11.30, 14.15)), and the signs of O3 and NO2 reversed (-0.26% (-0.88, 0.35) for O3 and 1.77% increase (1.40, 2.13) for NO2). Effect sizes were larger for Blacks (e.g. 7.71% (5.46, 10.02) for PM2.5). CONCLUSION: There is strong evidence that the association between annual exposure to PM2.5 and mortality is not confounded by individual or neighborhood covariates, and continues below the standard. The effects of O3 and NO2 are difficult to disentangle.

Modeling the impact of exposure reductions using multi-stressor epidemiology, exposure models, and synthetic microdata: an application to birthweight in two environmental justice communities.

BACKGROUND: Many vulnerable populations experience elevated exposures to environmental and social stressors, with deleterious effects on health. Multi-stressor epidemiological models can be used to assess benefits of exposure reductions. However, requisite individual-level risk factor data are often unavailable at adequate spatial resolution. OBJECTIVE: To leverage public data and novel simulation methods to estimate birthweight changes following simulated environmental interventions in two environmental justice communities in Massachusetts, USA. METHODS: We gathered risk factor data from public sources (US Census, Behavioral Risk Factor Surveillance System, and Massachusetts Department of Health). We then created synthetic individual-level data sets using combinatorial optimization, and probabilistic and logistic modeling. Finally, we used coefficients from a multi-stressor epidemiological model to estimate birthweight and birthweight improvement associated with simulated environmental interventions. RESULTS: We created geographically resolved synthetic microdata. Mothers with the lowest predicted birthweight were those identifying as Black or Hispanic, with parity > 1, utilization of government prenatal support, and lower educational attainment. Birthweight improvements following greenness and temperature improvements were similar for all high-risk groups and were larger than benefits from smoking cessation. SIGNIFICANCE: Absent private health data, this methodology allows for assessment of cumulative risk and health inequities, and comparison of individual-level impacts of localized health interventions.

County-level radon exposure and all-cause mortality risk among Medicare beneficiaries.

BACKGROUND: Radon is an inert gas formed from the decay of naturally-occurring materials in the earth's crust. It infiltrates into homes from soil, water, and construction materials. Its decay products are radionuclides, which attach to ambient particles. Residential radon is one of the leading risk factors for lung cancer. The scarce evidence for associations with other mortality causes originates mostly from occupational studies. METHODS: In a cohort study with 14 years of follow-up (2000-2013), we evaluated the association between chronic radon exposure and all-cause mortality, and explored whether there are subpopulations who are more vulnerable to radon effects. We included 87,296,195 person-years of follow-up from all Medicare beneficiaries in the Mid-Atlantic and Northeastern U.S. states. We examined the association between the logarithm of county-averaged radon (ln(Rn)) and mortality and assessed effect modification by chronic conditions. RESULTS: An interquartile range increase in the ln(Rn) was associated with a 2·62% increase (95% CI 2·52%; 2·73%) in mortality, independent of PM2.5 exposure. Larger mortality risks were observed among individuals with respiratory, cardiovascular and metabolic diseases, with the highest associations observed among those with diabetes (4·98% increase), heart failure (4·58% increase), and chronic obstructive pulmonary disease (4·49% increase). CONCLUSION: We found an increased risk for all-cause mortality associated with increased radon exposure. The risk was enhanced among susceptible individuals with chronic conditions. We believe this is the first cohort study to identify populations at higher risk for non-malignant health consequences of radon exposure. Due to the limitations in exposure assessment and availability of individual confounders, these findings should be interpreted with caution.

Long-term exposure to PM2.5 and ozone and hospital admissions of Medicare participants in the Southeast USA.

We examined the association between average annual fine particulate matter (PM2.5) and ozone and first hospital admissions of Medicare participants for stroke, chronic obstructive pulmonary disease (COPD), pneumonia, myocardial infarction (MI), lung cancer, and heart failure (HF). Annual average PM2.5 and ozone levels were estimated using high-resolution spatio-temporal models. We fit a marginal structural Cox proportional hazards model, using stabilized inverse probability weights (IPWs) to account for the competing risk of death and confounding. Analyses were then repeated after restricting to exposure levels below the current U.S. standards. The results showed that PM2.5 was significantly associated with an increased hazard of admissions for all studied outcomes; the highest observed being a 6.1% (95% CI: 5.9%-6.2%) increase in the hazard of admissions with pneumonia for each µg/m3 increase in particulate levels. Ozone was also significantly associated with an increase in the risk of first hospital admissions of all outcomes. The hazard of pneumonia increased by 3.0% (95% CI: 2.9%-3.1%) for each ppb increase in the ozone level. Our results reveal a need to regulate long-term ozone exposure, and that associations persist below current PM2.5 standards.

Impact of Long-Term Exposures to Ambient PM2.5 and Ozone on ARDS Risk for Older Adults in the United States.

BACKGROUND: Chronic exposures to particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5) and ozone pollution can affect respiratory function. ARDS, an often lethal respiratory failure, is most common among older adults. However, few epidemiology studies have investigated an association between air pollution and the risk of ARDS. METHODS: This observational study was conducted to estimate air pollution exposures at the ZIP code level and hospital admissions with ARDS among US Medicare beneficiaries aged ≥ 65 years from 2000 to 2012. A two-pollutant generalized linear mixed model, adjusting for sex, age, race, median household income, smoking, and weather, was applied. RESULTS: There were a total of 1,164,784 hospital admissions with ARDS in the cohort. Increases of 1 µg/m3 in annual average PM2.5 and of 1 parts per billion in annual average ozone were associated with increases in annual hospital admission rates for ARDS of 0.72% (95% CI, 0.62-0.82) and 0.15% (95% CI, 0.08-0.22), respectively. In low-pollution regions (annual average PM2.5 level < 12 µg/m3 and annual average ozone level < 45 parts per billion), the same annual increase in PM2.5 and ozone were associated with increases in annual hospital admission rates for ARDS of 1.50% (95% CI, 1.27-1.72) and 0.27% (95% CI, 0.16-0.38). CONCLUSIONS: Long-term exposures to PM2.5 and ozone were associated with increased risk of ARDS among older adults in the United States, including exposures below current annual US National Ambient Air Quality Standards.

Effect modification of ambient particle mortality by radon: A time series analysis in 108 U.S. cities.

Numerous studies have reported a positive association between ambient fine particles and daily mortality, but little is known about the particle properties or environmental factors that may contribute to these effects. This study assessed potential modification of radon on PM2.5 (particulate matter with an aerodynamic diameter <2.5 µm)-associated daily mortality in 108 U.S. cities using a two-stage statistical approach. First, city- and season-specific PM2.5 mortality risks were estimated using over-dispersed Poisson regression models. These PM2.5 effect estimates were then regressed against mean city-level residential radon concentrations to estimate overall PM2.5 effects and potential modification by radon. Radon exposure estimates based on measured short-term basement concentrations and modeled long-term living-area concentrations were both assessed. Exposure to PM2.5 was associated with total, cardiovascular, and respiratory mortality in both the spring and the fall. In addition, higher mean city-level radon concentrations increased PM2.5-associated mortality in the spring and fall. For example, a 10 µg/m3 increase in PM2.5 in the spring at the 10th percentile of city-averaged short-term radon concentrations (21.1 Bq/m3) was associated with a 1.92% increase in total mortality (95% CI: 1.29, 2.55), whereas the same PM2.5 exposure at the 90th radon percentile (234.2 Bq/m3) was associated with a 3.73% increase in total mortality (95% CI: 2.87, 4.59). Results were robust to adjustment for spatial confounders, including average planetary boundary height, population age, percent poverty and tobacco use. While additional research is necessary, this study suggests that radon enhances PM2.5 mortality. This is of significant regulatory importance, as effective regulation should consider the increased risk for particle mortality in cities with higher radon levels. Implications: In this large national study, city-averaged indoor radon concentration was a significant effect modifier of PM2.5-associated total, cardiovascular, and respiratory mortality risk in the spring and fall. These results suggest that radon may enhance PM2.5-associated mortality. In addition, local radon concentrations partially explain the significant variability in PM2.5 effect estimates across U.S. cities, noted in this and previous studies. Although the concept of PM as a vector for radon progeny is feasible, additional research is needed on the noncancer health effects of radon and its potential interaction with PM. Future air quality regulations may need to consider the increased risk for particle mortality in cities with higher radon levels.

The association between air pollution and the incidence of idiopathic pulmonary fibrosis in Northern Italy.

Acute exacerbations and worsening of idiopathic pulmonary fibrosis (IPF) have been associated with exposure to ozone (O3), nitrogen dioxide (NO2) and particulate matter, but chronic exposure to air pollution might also affect the incidence of IPF. We investigated the association between chronic exposure to NO2, O3 and particulate matter with an aerodynamic diameter <10 µm (PM10) and IPF incidence in Northern Italy between 2005 and 2010.Daily predictions of PM10 concentrations were obtained from spatiotemporal models, and NO2 and O3 hourly concentrations from fixed monitoring stations. We identified areas with homogenous exposure to each pollutant. We built negative binomial models to assess the association between area-specific IPF incidence rate, estimated through administrative databases, and average overall and seasonal PM10, NO2, and 8-hour maximum O3 concentrations.Using unadjusted models, an increment of 10 µg·m-3 in NO2 concentration was associated with an increase between 7.93% (95% CI 0.36-16.08%) and 8.41% (95% CI -0.23-17.80%) in IPF incidence rate, depending on the season. After adjustment for potential confounders, estimated effects were similar in magnitude, but with larger confidence intervals.Although confirmatory studies are needed, our results trace a potential association between exposure to traffic pollution and the development of IPF.

Fine-scale spatial and temporal variation in temperature and arrhythmia episodes in the VA Normative Aging Study.

Many studies have demonstrated that cold and hot temperatures are associated with increased deaths and hospitalization rates; new findings indicate also an association with more specific cardiac risk factors. Most of these existing studies have relied on few weather stations to characterize exposures; few have used residence-specific estimates of temperature, or examined the exposure-response function. We investigated the association of arrhythmia episodes with spatial and temporal variation in temperature. We also evaluated the association btween monitored ambient temperature (central) and the same outcome. This longitudinal analysis included 701 older men participating in the VA Normative Aging Study. Arrhythmia episodes were measured as ventricular ectopy (VE) (bigeminy, trigeminy, or couplets episodes) by 4-min electrocardiogram (ECG) monitoring in repeated visits during 2000-2010. The outcome was defined as having or not VE episodes during a study visit. We applied a mixed-effect logistic regression model with a random intercept for subject, controlling for seasonality, weekday, medication use, smoking, diabetes status, body mass index, and age. We also examined effect modification by personal characteristics, confounding by air pollution, and the exposure-response function. For 1°C increase in the same day residence-specific temperature, the odds of having VE episodes was 1.10 (95% confidence interval [CI]: 1.04-1.17). The odds associated with 1°C increase in central temperature was 1.05 (95% CI: 1.02-1.09). The exposure-response function was nonlinear for averages of temperature, presenting a J-shaped pattern, suggesting greater risk at lower and higher temperatures. Increased warm temperature and decreased cold temperature may increase the risk of ventricular arrhythmias. IMPLICATIONS: This is the first study to provide evidence that residence-specific temperature exposure is associated with increased risk of ventricular arrhythmias in cohort of elderly subjects without known chronic medical conditions; that the delayed effect of temperature has a nonlinear relationship; and therefore that both warm and cold temperature increase the risk of having ventricular arrhythmias. Moreover, we show that the use of residence-specific temperature data reduces downward bias due to exposure error, by comparing the estimated health effect based on our spatiotemporal exposure prediction model to those based on a single local weather monitor.

PM2.5 and Mortality in 207 US Cities: Modification by Temperature and City Characteristics.

BACKGROUND: The reported estimated effects between long-term PM2.5 exposures and mortality vary spatially. We assessed whether community-level variables, including socioeconomic status indicators and temperature, modify this association. METHODS: We used data from >35 million Medicare enrollees from 207 US cities (2000-2010). For each city, we calculated annual PM2.5 averages, measured at ambient central monitoring sites. We used a variation of a causal modeling approach and fitted city-specific Cox models, which we then pooled using a random effects meta-regression. In this second stage, we assessed whether temperature and city-level variables, including smoking and obesity rates, poverty, education and greenness, modify the long-term PM2.5-mortality association. RESULTS: We found an association between long-term PM2.5 and survival (hazard ratio = 1.2; 95% confidence interval [CI]: 1.1, 1.3 per 10 µg/m increase in the annual PM2.5 average concentrations). We observed elevated estimates in the Southeastern, South and Northwestern US (hazard ratio = 1.9; 95% CI: 1.7, 2.2, and 1.4; 95% CI: 1.2, 1.7, and 1.4; 95% CI: 1.1, 1.9, respectively). We observed a higher association between long-term PM2.5 exposure and mortality in warmer cities. Furthermore, we observed increasing estimates with increasing obesity rates, %residents and families in poverty, %black residents and %population without a high school degree, and lower effects with increasing median household income and %white residents. CONCLUSIONS: To the best of our knowledge, this is the first study to assess modification by temperature and community-level characteristics on the long-term PM2.5-survival association. Our findings suggest that living in cities with high temperatures and low socio economic status (SES) is associated with higher effect estimates.

Air pollution and children's health: sickle cell disease / Poluição do ar e a saúde das crianças: a doença falciforme / Contaminación atmosférica y salud de los niños: la enfermedad de células falciformes

The hallmarks of sickle cell disease are anemia and vasculopathy. The aim of this study was to assess the association between air pollution and children's emergency room visits of sickle cell patients. We adopted a case-crossover design. Daily counts of children's and adolescents' sickle cell disease emergency room visits from the pediatric emergency unit in São Paulo, Brazil, were evaluated from September 1999 to December 2004, matching by temperature, humidity and controlling for day of the week. Interquartile range increases of the four-day moving averages of PM10, NO2, SO2, CO, and O3 were associated with increases of 18.9% (95%CI: 11.2-26.5), 19% (95%CI: 8.3-29.6), 14.4% (95%CI: 6.5-22.4), 16,5% (95%CI: 8.9-24.0), and 9.8% (95%CI: 1.1-18.6) in total sickle cell emergency room visits, respectively. When the analyses were stratified by pain, PM10 was found to be 40.3% higher than in sickle cell patients without pain symptoms. Exposure to air pollution can affect the cardiovascular health of children and may promote a significant health burden in a sensitive group.

O objetivo deste estudo foi avaliar a associação entre a poluição do ar e atendimentos de emergência pediátrica de pacientes portadores de anemia falciforme. Adotamos um estudo de case-crossover. Visitas de crianças e adolescentes portadores de anemia falciforme ao pronto-socorro pediátrico, em São Paulo, Brasil, foram avaliadas a partir de setembro de 1999 até dezembro de 2004, controlando a temperatura, umidade e dia da semana. Variações interquartis das médias móveis de quatro dias de PM10, NO2, SO2, CO e O3 foram associadas com aumentos de 18,9% (IC95%: 11,2-26,5), 19% (IC95%: 8,3-29,6), 14,4% (IC95%: 6,5-22,4), 16,5% (IC95%: 8,9-24,0) e 9,8% (IC95%: 1,1-18,6) nos atendimentos totais, respectivamente. Quando as análises foram estratificadas por dor, verificou-se que PM10 apresentou correlação 40,3% maior do que a observada em pacientes falciformes sem sintomas de dor. A exposição à poluição do ar pode afetar a saúde cardiovascular de crianças e promover um fardo significativo para a saúde em um grupo suscetível, como o de pacientes com anemia falciforme.

El objetivo de este estudio fue evaluar la asociación entre la contaminación atmosférica y las visitas de emergencia de los pacientes pediátricos con anemia de células falciformes. Hemos adoptado un estudio de casos cruzados. Visitas de niños y adolescentes con anemia de células falciformes en urgencias pediátricas, en São Paulo, Brasil, se evaluaron entre 1999 y 2004 con un control de la temperatura, humedad y día de la semana. El rango intercuartil de los promedios móviles de 4 días de PM10, NO2, SO2, CO y O3 se asociaron con un aumento del 18,9% (IC95%: 11,2-26,5), 19,0% (IC95%: 8,3-29,6), 14,4% (IC95%: 6,5-22,4), 16,5% (IC95%: 8,9-24,0), y 9,8% (IC95%: 1,1-18,6) en el total de visitas, respectivamente. Cuando los análisis se estratificaron por el dolor, se encontró que el PM10 mostró una correlación un 40,3% mayor que la observada en pacientes sin síntomas de dolor. La exposición a la contaminación del aire puede afectar la salud cardiovascular de los niños y puede promover una importante carga para la salud en pacientes con anemia de células falciformes.

Prenatal air pollution exposure and newborn blood pressure.

BACKGROUND: Air pollution exposure has been associated with increased blood pressure in adults. OBJECTIVE: We examined associations of antenatal exposure to ambient air pollution with newborn systolic blood pressure (SBP). METHODS: We studied 1,131 mother-infant pairs in a Boston, Massachusetts, area pre-birth cohort. We calculated average exposures by trimester and during the 2 to 90 days before birth for temporally resolved fine particulate matter (≤ 2.5 µm; PM2.5), black carbon (BC), nitrogen oxides, nitrogen dioxide, ozone (O3), and carbon monoxide measured at stationary monitoring sites, and for spatiotemporally resolved estimates of PM2.5 and BC at the residence level. We measured SBP at a mean age of 30 ± 18 hr with an automated device. We used mixed-effects models to examine associations between air pollutant exposures and SBP, taking into account measurement circumstances; child's birth weight; mother's age, race/ethnicity, socioeconomic position, and third-trimester BP; and time trend. Estimates represent differences in SBP associated with an interquartile range (IQR) increase in each pollutant. RESULTS: Higher mean PM2.5 and BC exposures during the third trimester were associated with higher SBP (e.g., 1.0 mmHg; 95% CI: 0.1, 1.8 for a 0.32-µg/m3 increase in mean 90-day residential BC). In contrast, O3 was negatively associated with SBP (e.g., -2.3 mmHg; 95% CI: -4.4, -0.2 for a 13.5-ppb increase during the 90 days before birth). CONCLUSIONS: Exposures to PM2.5 and BC in late pregnancy were positively associated with newborn SBP, whereas O3 was negatively associated with SBP. Longitudinal follow-up will enable us to assess the implications of these findings for health during later childhood and adulthood.

Isolated and synergistic effects of PM10 and average temperature on cardiovascular and respiratory mortality / Efeitos isolados e sinérgicos do MP10 e da temperatura média na mortalidade por doenças cardiovasculares e respiratórias

OBJECTIVE To analyze the effect of air pollution and temperature on mortality due to cardiovascular and respiratory diseases. METHODS We evaluated the isolated and synergistic effects of temperature and particulate matter with aerodynamic diameter < 10 µm (PM10) on the mortality of individuals > 40 years old due to cardiovascular disease and that of individuals > 60 years old due to respiratory diseases in Sao Paulo, SP, Southeastern Brazil, between 1998 and 2008. Three methodologies were used to evaluate the isolated association: time-series analysis using Poisson regression model, bidirectional case-crossover analysis matched by period, and case-crossover analysis matched by the confounding factor, i.e., average temperature or pollutant concentration. The graphical representation of the response surface, generated by the interaction term between these factors added to the Poisson regression model, was interpreted to evaluate the synergistic effect of the risk factors. RESULTS No differences were observed between the results of the case-crossover and time-series analyses. The percentage change in the relative risk of cardiovascular and respiratory mortality was 0.85% (0.45;1.25) and 1.60% (0.74;2.46), respectively, due to an increase of 10 μg/m3 in the PM10 concentration. The pattern of correlation of the temperature with cardiovascular mortality was U-shaped and that with respiratory mortality was J-shaped, indicating an increased relative risk at high temperatures. The values for the interaction term indicated a higher relative risk for cardiovascular and respiratory mortalities at low temperatures and high temperatures, respectively, when the pollution levels reached approximately 60 μg/m3. CONCLUSIONS The positive association standardized in the Poisson regression model for pollutant concentration is not confounded by temperature, and the effect of temperature is not confounded by the pollutant levels ...

OBJETIVO Analisar o efeito da poluição do ar e da temperatura na mortalidade por doenças cardiovasculares e respiratórias. MÉTODOS Foram analisados os efeitos da temperatura e do material particulado com diâmetro aerodinâmico < 10 micrômetros (MP10), isolado e sinérgico, na mortalidade de indivíduos > 40 anos por doenças cardiovasculares e na mortalidade de indivíduos > 60 anos por doenças respiratórias em São Paulo, SP, entre 1998 e 2008. Três tipos de metodologias foram aplicadas para avaliar a associação isolada: análise de séries temporais com regressão de Poisson, análise case-crossover com pareamento temporal bidirecional e análise case-crossover com pareamento pelo fator confundidor, i.e., temperatura média ou poluente. Foi interpretada a representação gráfica da superfície resposta, gerada por termo de interação entre tais fatores adicionado à regressão de Poisson, para avaliar o efeito sinérgico entre os fatores de risco. RESULTADOS Não foram observadas diferenças entre os resultados das análises case-crossover e de séries temporais. Estimou-se mudança percentual no risco relativo para mortalidade cardiovascular e respiratória de 0,85% (0,45;1,25) e 1,60% (0,74;2,46), respectivamente, devido ao aumento de 10 μg/m3 na concentração do MP10. O padrão de associação da temperatura para mortalidade cardiovascular foi de U-shape e para mortalidade respiratória foi de J-shape, representando maior risco relativo em temperaturas altas. As figuras do termo de interação indicaram maior risco relativo em baixas temperaturas para mortalidade cardiovascular e em altas temperaturas para mortalidade respiratória em níveis de poluição em torno de 60 μg/m3. CONCLUSÕES ...

Associations of fine particulate matter species with mortality in the United States: a multicity time-series analysis.

BACKGROUND: Epidemiological studies have examined the association between PM2.5 and mortality, but uncertainty remains about the seasonal variations in PM2.5-related effects and the relative importance of species. OBJECTIVES: We estimated the effects of PM2.5 species on mortality and how infiltration rates may modify the association. METHODS: Using city-season specific Poisson regression, we estimated PM2.5 effects on approximately 4.5 million deaths for all causes, cardiovascular disease (CVD), myocardial infarction (MI), stroke, and respiratory diseases in 75 U.S. cities for 2000-2006. We added interaction terms between PM2.5 and monthly average species-to-PM2.5 proportions of individual species to determine the relative toxicity of each species. We combined results across cities using multivariate meta-regression, and controlled for infiltration. RESULTS: We estimated a 1.18% (95% CI: 0.93, 1.44%) increase in all-cause mortality, a 1.03% (95% CI: 0.65, 1.41%) increase in CVD, a 1.22% (95% CI: 0.62, 1.82%) increase in MI, a 1.76% (95% CI: 1.01, 2.52%) increase in stroke, and a 1.71% (95% CI: 1.06, 2.35%) increase in respiratory deaths in association with a 10-µg/m3 increase in 2-day averaged PM2.5 concentration. The associations were largest in the spring. Silicon, calcium, and sulfur were associated with more all-cause mortality, whereas sulfur was related to more respiratory deaths. County-level smoking and alcohol were associated with larger estimated PM2.5 effects. CONCLUSIONS: Our study showed an increased risk of mortality associated with PM2.5, which varied with seasons and species. The results suggest that mass alone might not be sufficient to evaluate the health effects of particles.

Air pollution and gene-specific methylation in the Normative Aging Study: association, effect modification, and mediation analysis.

The mechanisms by which air pollution has multiple systemic effects in humans are not fully elucidated, but appear to include inflammation and thrombosis. This study examines whether concentrations of ozone and components of fine particle mass are associated with changes in methylation on tissue factor (F3), interferon gamma (IFN-γ), interleukin 6 (IL-6), toll-like receptor 2 (TLR-2), and intercellular adhesion molecule 1 (ICAM-1). We investigated associations between air pollution exposure and gene-specific methylation in 777 elderly men participating in the Normative Aging Study (1999-2009). We repeatedly measured methylation at multiple CpG sites within each gene's promoter region and calculated the mean of the position-specific measurements. We examined intermediate-term associations between primary and secondary air pollutants and mean methylation and methylation at each position with distributed-lag models. Increase in air pollutants concentrations was significantly associated with F3, ICAM-1, and TLR-2 hypomethylation, and IFN-γ and IL-6 hypermethylation. An interquartile range increase in black carbon concentration averaged over the four weeks prior to assessment was associated with a 12% reduction in F3 methylation (95% CI: -17% to -6%). For some genes, the change in methylation was observed only at specific locations within the promoter region. DNA methylation may reflect biological impact of air pollution. We found some significant mediated effects of black carbon on fibrinogen through a decrease in F3 methylation, and of sulfate and ozone on ICAM-1 protein through a decrease in ICAM-1 methylation.

Associations between arrhythmia episodes and temporally and spatially resolved black carbon and particulate matter in elderly patients.

OBJECTIVES: Ambient air pollution has been associated with sudden deaths, some of which are likely due to ventricular arrhythmias. Defibrillator discharge studies have examined the association of air pollution with arrhythmias in sensitive populations. No studies have assessed this association using residence-specific estimates of air pollution exposure. METHODS: In the Normative Aging Study, we investigated the association between temporally resolved and spatially resolved black carbon (BC) and PM2.5 and arrhythmia episodes (bigeminy, trigeminy or couplets episodes) measured as ventricular ectopy (VE) by 4 min ECG monitoring in repeated measures of 701 subjects, during the years 2000-2010. We used a binomial distribution (having or not a VE episode) in a mixed effect model with a random intercept for subject, controlling for seasonality, temperature, day of the week, medication use, smoking, having diabetes, body mass index and age. We also examined whether these associations were modified by genotype or phenotype. RESULTS: We found significant increases in VE with both pollutants and lags; for the estimated concentration averaged over the 3 days prior to the health assessment, we found increases in the odds of having VE with an OR of 1.52 (95% CI 1.19 to 1.94) for an IQR (0.30 µg/m(3)) increase in BC and an OR of 1.39 (95% CI 1.12 to 1.71) for an IQR (5.63 µg/m(3)) increase in PM2.5. We also found higher effects in subjects with the glutathione S-transferase theta-1 and glutathione S-transferase mu-1 variants and in obese (p<0.05). CONCLUSIONS: Increased levels of short-term traffic-related pollutants may increase the risk of ventricular arrhythmia in elderly subjects.

Ambient particulate air pollution and microRNAs in elderly men.

BACKGROUND: Ambient particulate matter (PM) has been associated with mortality and morbidity for cardiovascular disease. MicroRNAs control gene expression at a posttranscriptional level. Altered microRNA expression has been reported in processes related to cardiovascular disease and PM exposure, such as systemic inflammation, endothelial dysfunction, and atherosclerosis. Polymorphisms in microRNA-related genes could influence response to PM. METHODS: We investigated the association of exposure to ambient particles in several time windows (4-hour to 28-day moving averages) and blood leukocyte expression changes in 14 candidate microRNAs in 153 elderly males from the Normative Aging Study (examined 2005-2009). Potential effect modification by six single nucleotide polymorphisms (SNPs) in three microRNA-related genes was investigated. Fine PM (PM2.5), black carbon, organic carbon, and sulfates were measured at a stationary ambient monitoring site. Linear regression models, adjusted for potential confounders, were used to assess effects of particles and SNP-by-pollutant interaction. An in silico pathway analysis was performed on target genes of microRNAs associated with the pollutants. RESULTS: We found a negative association for pollutants in all moving averages and miR-1, -126, -135a, -146a, -155, -21, -222, and -9. The strongest associations were observed with the 7-day moving averages for PM2.5 and black carbon and with the 48-hour moving averages for organic carbon. The association with sulfates was stable across the moving averages. The in silico pathway analysis identified 18 pathways related to immune response shared by at least two microRNAs; in particular, the "high-mobility group protein B1/advanced glycosylation end product-specific receptor signaling pathway" was shared by miR-126, -146a, -155, -21, and -222. No important associations were observed for miR-125a-5p, -125b, -128, -147, -218, and -96. We found significant SNP-by-pollutant interactions for rs7813, rs910925, and rs1062923 in GEMIN4 and black carbon and PM2.5 for miR-1, -126, -146a, -222, and -9, and for rs1640299 in DGCR8 and SO4 for miR-1 and -135a. CONCLUSIONS: Exposure to ambient particles could cause a downregulation of microRNAs involved in processes related to PM exposure. Polymorphisms in GEMIN4 and DGCR8 could modify these associations.

Allergen sensitization is associated with increased DNA methylation in older men.

BACKGROUND: Variation in epigenetic modifications, arising from either environmental exposures or internal physiological changes, can influence gene expression and may ultimately contribute to complex diseases such as asthma and allergies. We examined the association of asthma and allergic phenotypes with DNA methylation levels of retrotransposon-derived elements. METHODS: We used data from 704 men (mean age 73 years) in the longitudinal Normative Aging Study to assess the relationship between asthma, allergic phenotypes and DNA methylation levels of the retrotransposon-derived elements Alu and long interspersed nuclear element (LINE)-1. Retrotransposons represent a large fraction of the genome (>30%) and are heavily methylated to prevent expression. Percent methylation of Alu and LINE-1 elements in peripheral white blood cells was quantified using PCR pyrosequencing. Data on sensitization to common allergens from skin prick testing, asthma and methacholine responsiveness were gathered approximately 8 years prior to DNA methylation analysis. RESULTS: Prior allergen sensitization was associated with increased methylation of Alu (ß = 0.32 for sensitized vs. nonsensitized patients; p = 0.003) in models adjusted for pack-years of smoking, body mass index, current smoking, air pollutants, percentage of eosinophils, white blood cell count and age. Of the men interviewed, 5% of subjects reported a diagnosis of asthma. Neither Alu nor LINE-1 methylation was associated with asthma. CONCLUSIONS: These data suggest that increased DNA methylation of repetitive elements may be associated with allergen sensitization but does not appear to be associated with asthma. Future work is needed to identify potential underlying mechanisms for these relationships.