Associations between prenatal and early-life air pollution exposure and lung function in young children: Exploring influential windows of exposure on lung development.

BACKGROUND: Evidence in the literature suggests that air pollution exposures experienced prenatally and early in life can be detrimental to normal lung development, however the specific timing of critical windows during development is not fully understood. OBJECTIVES: We evaluated air pollution exposures during the prenatal and early-life period in association with lung function at ages 6-9, in an effort to identify potentially influential windows of exposure for lung development. METHODS: Our study population consisted of 222 children aged 6-9 from the Fresno-Clovis metro area in California with spirometry data collected between May 2015 and May 2017. We used distributed-lag non-linear models to flexibly model the exposure-lag-response for monthly average exposure to fine particulate matter (PM2.5) and ozone (O3) during the prenatal months and first three years of life in association with forced vital capacity (FVC), and forced expiratory volume in the first second (FEV1), adjusted for covariates. RESULTS: PM2.5 exposure during the prenatal period and the first 3-years of life was associated with lower FVC and FEV1 assessed at ages 6-9. Specifically, an increase from the 5th percentile of the observed monthly average exposure (7.55 µg/m3) to the median observed exposure (12.69 µg/m3) for the duration of the window was associated with 0.42 L lower FVC (95% confidence interval (CI): -0.82, -0.03) and 0.38 L lower FEV1 (95% CI: -0.75, -0.02). The shape of the lag-response indicated that the second half of pregnancy may be a particularly influential window of exposure. Associations for ozone were not as strong and typically CIs included the null. CONCLUSIONS: Our findings indicate that prenatal and early-life exposures to PM2.5 are associated with decreased lung function later in childhood. Exposures during the latter months of pregnancy may be especially influential.

Disparities in job characteristics by race and sex in a Southern aluminum smelting facility.

BACKGROUND: Former workers at a Southern aluminum smelting facility raised concerns that the most hazardous jobs were assigned to Black workers, but the role of workplace segregation had not been quantified or examined in the company town. Prior studies discuss race and gender disparities in working conditions, but few have documented them in the aluminum industry. METHODS: We obtained workers' company records for 1985-2007 and characterized four job metrics: prestige (sociologic rankings), worker-defined danger (worker assessments), annual wage (1985 dollars), and estimated total particulate matter (TPM) exposure (job exposure matrix). Characteristics of job at hire and trajectories were compared by race and sex using linear binomial models. RESULTS: Non-White males had the highest percentage of workers in low prestige and high danger jobs at hire and up to 20 years after. After 20 years tenure, 100% of White workers were in higher prestige and lower danger jobs. Most female workers, regardless of race, entered and remained in low-wage jobs, while 50% of all male workers maintained their initial higher-wage jobs. Non-White females had the highest prevalence of workers in low-wage jobs at hire and after 20 years-increasing from 63% (95% CI: 59-67) to 100% (95% CI: 78-100). All female workers were less likely to be in high TPM exposure jobs. Non-White males were most likely to be hired into high TPM exposure jobs, and this exposure prevalence increased as time accrued, while staying constant for other race-sex groups. CONCLUSIONS: There is evidence of job segregation by race and sex in this cohort of aluminum smelting workers. Documentation of disparities in occupational hazards is important for informing health interventions and research.

Relative environmental and social disadvantage in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Air pollution exposure is associated with disease severity, progression and mortality in patients with idiopathic pulmonary fibrosis (IPF). Combined impacts of environmental and socioeconomic factors on outcomes in patients with IPF are unknown. The objectives of this study were to characterise the relationships between relative environmental and social disadvantage with clinical outcomes in patients with IPF. METHODS: Patients with IPF were identified from a longitudinal database at University of California, San Francisco. Residential addresses were geocoded and linked to the CalEnviroScreen 3.0 (CES), a tool that quantifies environmental burden in California communities, combining population, environmental and pollution vulnerability into individual and composite scores (higher scores indicating greater disadvantage). Unadjusted and adjusted linear and logistic regression and Fine and Gray proportional hazards models were used. RESULTS: 603 patients were included. Higher CES was associated with lower baseline forced vital capacity ( ß =-0.073, 95% CI -0.13 to -0.02; p=0.006) and diffusion capacity of the lung for carbon monoxide ( ß =-0.11, 95% CI -0.16 to -0.06; p<0.001). Patients in the highest population vulnerability quartile were less likely to be on antifibrotic therapy (OR=0.33; 95% CI 0.18 to 0.60; p=0.001) at time of enrolment, compared with those in the lowest quartile. An association between CES and mortality was suggested, but sensitivity analyses demonstrated inconsistent results. Relative disadvantage of the study cohort appeared lower compared with the general population. CONCLUSIONS: Higher environmental exposures and vulnerability were associated with lower baseline lung function and lower antifibrotic use, suggesting that relative socioenvironmental disadvantage has meaningful impacts on patients with IPF.

Traffic-related air pollution is associated with glucose dysregulation, blood pressure, and oxidative stress in children.

BACKGROUND: Metabolic syndrome increases the risk of cardiovascular disease in adults. Antecedents likely begin in childhood and whether childhood exposure to air pollution plays a contributory role is not well understood. OBJECTIVES: To assess whether children's exposure to air pollution is associated with markers of risk for metabolic syndrome and oxidative stress, a hypothesized mediator of air pollution-related health effects. METHODS: We studied 299 children (ages 6-8) living in the Fresno, CA area. At a study center visit, questionnaire and biomarker data were collected. Outcomes included hemoglobin A1c (HbA1c), urinary 8-isoprostane, systolic blood pressure (SBP), and BMI. Individual-level exposure estimates for a set of four pollutants that are constituents of traffic-related air pollution (TRAP) - the sum of 4-, 5-, and 6-ring polycyclic aromatic hydrocarbon compounds (PAH456), NO2, elemental carbon, and fine particulate matter (PM2.5) - were modeled at the primary residential location for 1-day lag, and 1-week, 1-month, 3-month, 6-month, and 1-year averages prior to each participant's visit date. Generalized additive models were used to estimate associations between each air pollutant exposure and outcome. RESULTS: The study population was 53% male, 80% Latinx, 11% Black and largely low-income (6% were White and 3% were Asian/Pacific Islander). HbA1c percentage was associated with longer-term increases in TRAP; for example a 4.42 ng/m3 increase in 6-month average PAH456 was associated with a 0.07% increase (95% CI: 0.01, 0.14) and a 3.62 µg/m3 increase in 6-month average PM2.5 was associated with a 0.06% increase (95% CI: 0.01, 0.10). The influence of air pollutants on blood pressure was strongest at 3 months; for example, a 6.2 ppb increase in 3-month average NO2 was associated with a 9.4 mmHg increase in SBP (95% CI: 2.8, 15.9). TRAP concentrations were not significantly associated with anthropometric or adipokine measures. Short-term TRAP exposure averages were significantly associated with creatinine-adjusted urinary 8-isoprostane. DISCUSSION: Our results suggest that both short- and longer-term estimated individual-level outdoor residential exposures to several traffic-related air pollutants, including ambient PAHs, are associated with biomarkers of risk for metabolic syndrome and oxidative stress in children.

Decrease in Ambient Polycyclic Aromatic Hydrocarbon Concentrations in California's San Joaquin Valley 2000-2019.

As part of our ongoing research to understand the impact of polycyclic aromatic hydrocarbon (PAH) exposures on health in the San Joaquin Valley, we evaluated airborne PAH concentration data collected over 19 years (2000-2019) at the central air monitoring site in Fresno, California. We found a dramatic decline in outdoor airborne PAH concentrations between 2000 and 2004 that has been maintained through 2019. This decline was present in both the continuous particle-bound PAHs and the filter-based individual PAHs. The decline was more extreme when restricted to winter concentrations. Annual mean PAHs concentrations in 2017- 2018 of particle-bound PAHs were 6.8 ng/m3 or 62% lower than 2000 - 2001. The decline for winter concentrations of continuous particle-bound PAHs between winter 2019 and winter 2001 was 17.2 ng/m3, a drop of 70%. The 2001 to 2018 decline in average wintertime concentrations for filter-based individual PAHs was 82%. We examined industrial emissions, on-road vehicle emissions, residential wood burning, and agricultural and biomass waste burning as possible explanations. The major decline in PAHs from 2000-2004 was coincident with and most likely due to a similar decline in the amount of agricultural and biomass waste burned in Fresno and Madera Counties. On-road vehicle emissions and residential wood burning did not decline until after 2005. Industrial emissions were too low (2% of total) to explain such large decreases in PAH concentrations.

Accelerated lung function decline in an aluminium manufacturing industry cohort exposed to PM2.5: an application of the parametric g-formula.

OBJECTIVE: Occupational dust exposure has been associated with accelerated lung function decline, which in turn is associated with overall morbidity and mortality. In the current study, we assess potential benefits on lung function of hypothetical interventions that would reduce occupational exposure to fine particulate matter (PM2.5) while adjusting for the healthy worker survivor effect. METHODS: Analyses were performed in a cohort of 6485 hourly male workers in an aluminium manufacturing company in the USA, followed between 1996 and 2013. We used the parametric g-formula to assess lung function decline over time under hypothetical interventions while also addressing time-varying confounding by underlying health status, using a composite risk score based on health insurance claims. RESULTS: A counterfactual scenario envisioning a limit on exposure equivalent to the 10th percentile of the observed exposure distribution of 0.05 mg/m3 was associated with an improvement in forced expiratory volume in one second (FEV1) equivalent to 37.6 mL (95% CI 13.6 to 61.6) after 10 years of follow-up when compared with the observed. Assuming a linear decrease and (from NHANES reference values), a 20 mL decrease per year for a 1.8 m-tall man as they age, this 37.6 mL FEV1 loss over 10 years associated with observed exposure would translate to approximately a 19% increase to the already expected loss per year from age alone. CONCLUSIONS: Our results indicate that occupational PM2.5 exposure in the aluminium industry accelerates lung function decline over age. Reduction in exposure may mitigate accelerated loss of lung function over time in the industry.

Incident command post exposure to polycyclic aromatic hydrocarbons and particulate matter during a wildfire.

Wildland firefighters engaged in fire suppression activities are often exposed to hazardous air pollutants such as polycyclic aromatic hydrocarbons (PAHs) and particulate matter (PM2.5) during wildfires with no respiratory protection. Although the most significant exposures to smoke likely occur on the fireline, wildland firefighters may also be exposed at the incident command post (ICP), an area designated for wildfire suppression support operations. Our objective was to characterize exposures of PAHs and PM2.5 near an ICP during a wildfire event in California. We collected area air samples for PAHs and PM2.5, during the first 12 days of a wildfire event. PAH area air samples were actively collected in 12-hr shifts (day and night) using XAD4-coated quartz fiber filters and XAD2 sorbent tubes and analyzed for 17 individual PAHs. Hourly area PM2.5 concentrations were measured with an Environmental Beta Attenuation Monitor. Most PAH concentrations generally had similar concentrations during the day and night. PM2.5 concentrations were higher during the day, due to increased fire activity, than at night. The highest concentrations of the 17 PAHs measured were for naphthalene, phenanthrene, and retene. The location of an ICP may be a critical factor in reducing these potential exposures to firefighters during wildfire events. Additionally, exposures could be reduced by utilizing clean air tents or sleeping trailers with HEPA filtration or setting up smaller camps in less smokey areas closer to the fireline for firefighters. Although measured exposures to PAHs for firefighters from smoke are lower at an ICP, these exposures still contribute to the overall cumulative work exposures.

Personal Exposure to PM2.5 Black Carbon and Aerosol Oxidative Potential using an Automated Microenvironmental Aerosol Sampler (AMAS).

Traditional methods for measuring personal exposure to fine particulate matter (PM2.5) are cumbersome and lack spatiotemporal resolution; methods that are time-resolved are limited to a single species/component of PM. To address these limitations, we developed an automated microenvironmental aerosol sampler (AMAS), capable of resolving personal exposure by microenvironment. The AMAS is a wearable device that uses a GPS sensor algorithm in conjunction with a custom valve manifold to sample PM2.5 onto distinct filter channels to evaluate home, school, and other (e.g., outdoors, in transit, etc.) exposures. Pilot testing was conducted in Fresno, CA where 25 high-school participants ( n = 37 sampling events) wore an AMAS for 48-h periods in November 2016. Data from 20 (54%) of the 48-h samples collected by participants were deemed valid and the filters were analyzed for PM2.5 black carbon (BC) using light transmissometry and aerosol oxidative potential (OP) using the dithiothreitol (DTT) assay. The amount of inhaled PM2.5 was calculated for each microenvironment to evaluate the health risks associated with exposure. On average, the estimated amount of inhaled PM2.5 BC (µg day-1) and OP [(µM min-1) day-1] was greatest at home, owing to the proportion of time spent within that microenvironment. Validation of the AMAS demonstrated good relative precision (8.7% among collocated instruments) and a mean absolute error of 22% for BC and 33% for OP when compared to a traditional personal sampling instrument. This work demonstrates the feasibility of new technology designed to quantify personal exposure to PM2.5 species within distinct microenvironments.

Occupational Exposure to Polycyclic Aromatic Hydrocarbon of Wildland Firefighters at Prescribed and Wildland Fires.

Wildland firefighters suppressing wildland fires or conducting prescribed fires work long shifts during which they are exposed to high levels of wood smoke with no respiratory protection. Polycyclic aromatic hydrocarbons (PAHs) are hazardous air pollutants formed during incomplete combustion. Exposure to PAHs was measured for 21 wildland firefighters suppressing two wildland fires and 4 wildland firefighters conducting prescribed burns in California. Personal air samples were actively collected using XAD4-coated quartz fiber filters and XAD2 sorbent tubes. Samples were analyzed for 17 individual PAHs through extraction with dichloromethane and gas chromatograph-mass spectrometer analysis. Naphthalene, retene, and phenanthrene were consistently the highest measured PAHs. PAH concentrations were higher at wildland fires compared to prescribed fires and were highest for firefighters during job tasks that involve the most direct contact with smoke near an actively burning wildland fire. Although concentrations did not exceed current occupational exposure limits, wildland firefighters are exposed to PAHs not only on the fire line at wildland fires, but also while working prescribed burns and while off-duty. Characterization of occupational exposures from wildland firefighting is important to understand better any potential long-term health effects.

Incident Ischemic Heart Disease After Long-Term Occupational Exposure to Fine Particulate Matter: Accounting for 2 Forms of Survivor Bias.

Little is known about the heart disease risks associated with occupational, rather than traffic-related, exposure to particulate matter with aerodynamic diameter of 2.5 µm or less (PM2.5). We examined long-term exposure to PM2.5 in cohorts of aluminum smelters and fabrication workers in the United States who were followed for incident ischemic heart disease from 1998 to 2012, and we addressed 2 forms of survivor bias. Left truncation bias was addressed by restricting analyses to the subcohort hired after the start of follow up. Healthy worker survivor bias, which is characterized by time-varying confounding that is affected by prior exposure, was documented only in the smelters and required the use of marginal structural Cox models. When comparing always-exposed participants above the 10th percentile of annual exposure with those below, the hazard ratios were 1.67 (95% confidence interval (CI): 1.11, 2.52) and 3.95 (95% CI: 0.87, 18.00) in the full and restricted subcohorts of smelter workers, respectively. In the fabrication stratum, hazard ratios based on conditional Cox models were 0.98 (95% CI: 0.94, 1.02) and 1.17 (95% CI: 1.00, 1.37) per 1 mg/m(3)-year in the full and restricted subcohorts, respectively. Long-term exposure to occupational PM2.5 was associated with a higher risk of ischemic heart disease among aluminum manufacturing workers, particularly in smelters, after adjustment for survivor bias.

Occupational Exposure to PM2.5 and Incidence of Ischemic Heart Disease: Longitudinal Targeted Minimum Loss-based Estimation.

BACKGROUND: We investigated the incidence of ischemic heart disease (IHD) in relation to accumulated exposure to particulate matter (PM) in a cohort of aluminum workers. We adjusted for time varying confounding characteristic of the healthy worker survivor effect, using a recently introduced method for the estimation of causal target parameters. METHODS: Applying longitudinal targeted minimum loss-based estimation, we estimated the difference in marginal cumulative risk of IHD in the cohort comparing counterfactual outcomes if always exposed above to always exposed below a PM2.5 exposure cut-off. Analyses were stratified by sub-cohort employed in either smelters or fabrication facilities. We selected two exposure cut-offs a priori, at the median and 10th percentile in each sub-cohort. RESULTS: In smelters, the estimated IHD risk difference after 15 years of accumulating PM2.5 exposure during follow-up was 2.9% (0.6%, 5.1%) using the 10th percentile cut-off of 0.10 mg/m. For fabrication workers, the difference was 2.5% (0.8%, 4.1%) at the 10th percentile of 0.06 mg/m. Using the median exposure cut-off, results were similar in direction but smaller in size. We present marginal incidence curves describing the cumulative risk of IHD over the course of follow-up for each sub-cohort under each intervention regimen. CONCLUSIONS: The accumulation of exposure to PM2.5 appears to result in higher risks of IHD in both aluminum smelter and fabrication workers. This represents the first longitudinal application of targeted minimum loss-based estimation, a method for generating doubly robust semi-parametric efficient substitution estimators of causal parameters, in the fields of occupational and environmental epidemiology.

Marginal structural models in occupational epidemiology: application in a study of ischemic heart disease incidence and PM2.5 in the US aluminum industry.

Marginal structural models (MSMs) and inverse probability weighting can be used to estimate risk in a cohort of active workers if there is a time-varying confounder (e.g., health status) affected by prior exposure-a feature of the healthy worker survivor effect. We applied Cox MSMs in a study of incident ischemic heart disease and exposure to particulate matter with aerodynamic diameter of 2.5 µm or less (PM2.5) in a cohort of 12,949 actively employed aluminum workers in the United States. The cohort was stratified by work process into workers in smelting facilities, herein referred to as "smelters" and workers in fabrication facilities, herein referred to as "fabricators." The outcome was assessed by using medical claims data from 1998 to 2012. A composite risk score based on insurance claims was treated as a time-varying measure of health status. Binary PM2.5 exposure was defined by the 10th-percentile cutoff for each work process. Health status was associated with past exposure and predicted the outcome and subsequent exposure in smelters but not in fabricators. In smelters, the Cox MSM hazard ratio comparing those always exposed above the cutoff with those always exposed below the cutoff was 1.98 (95% confidence interval: 1.18, 3.32). In fabricators, the hazard ratio from a traditional Cox model was 1.34 (95% confidence interval: 0.98, 1.83). Results suggest that occupational PM2.5 exposure increases the risk of incident ischemic heart disease in workers in both aluminum smelting and fabrication facilities.

Exposure to airborne polycyclic aromatic hydrocarbons during pregnancy and risk of preterm birth.

BACKGROUND: Preterm birth is an important marker of health and has a prevalence of 12-13% in the U.S. Polycyclic aromatic hydrocarbons (PAHs) are a group of organic contaminants that form during the incomplete combustion of hydrocarbons, such as coal, diesel and gasoline. Studies suggest that exposure to PAHs during pregnancy is related to adverse birth outcomes. The aim of this study is to evaluate the association between exposure to PAHs during the pregnancy and preterm birth. METHODS: The study population included births from years 2001 to 2006 of women whose maternal residence was within 20km of the primary monitoring site in Fresno, California. Data in the Fresno area were used to form a spatio-temporal model to assign daily exposure to PAHs with 4, 5, or 6 rings at the maternal residence throughout pregnancy of all of the births in the study area. Gestational age at birth and relevant covariates were extracted from the birth certificate. RESULTS: We found an association between PAHs during the last 6 weeks of pregnancy and birth at 20-27 weeks (OR=2.74; 95% CI: 2.24-3.34) comparing the highest quartile to the lower three. The association was consistent when each quartile was compared to the lowest (OR2nd=1.49, 95% CI: 1.08-2.06; OR3rd=2.63, 95% CI:1.93-3.59; OR4th=3.94, 95% CI:3.03-5.12). Inverse associations were also observed for exposure to PAHs during the entire pregnancy and the first trimester and birth at 28-31 weeks and 20-27 weeks. CONCLUSION: An association between PAH exposure during the 6 weeks before delivery and early preterm birth was observed. However, the inverse association with early preterm birth offers an unclear, and potentially complex, inference of these associations.

Pregnancy exposure to PM2.5 from wildland fire smoke and preterm birth in California.

BACKGROUND: Wildfires in the Western United States are a growing and significant source of air pollution that is eroding decades of progress in air pollution reduction. The effects on preterm birth during critical periods of pregnancy are unknown. METHODS: We assessed associations between prenatal exposure to wildland fire smoke and risk of preterm birth (gestational age < 37 weeks). We assigned smoke exposure to geocoded residence at birth for all live singleton births in California conceived 2007-2018, using weekly average concentrations of particulate matter ≤ 2.5 µm (PM2.5) attributable to wildland fires from United States Environmental Protection Agency's Community Multiscale Air Quality Model. Logistic regression yielded odds ratio (OR) for preterm birth in relation to increases in average exposure across the whole pregnancy, each trimester, and each week of pregnancy. Models adjusted for season, age, education, race/ethnicity, medical insurance, and smoking of the birthing parent. RESULTS: For the 5,155,026 births, higher wildland fire PM2.5 exposure averaged across pregnancy, or any trimester, was associated with higher odds of preterm birth. The OR for an increase of 1 µg/m3 of average wildland fire PM2.5 during pregnancy was 1.013 (95 % CI:1.008,1.017). Wildland fire PM2.5 during most weeks of pregnancy was associated with higher odds. Strongest estimates were observed in weeks in the second and third trimesters. A 10 µg/m3 increase in average wildland fire PM2·5 in gestational week 23 was associated with OR = 1.034; 95 % CI: 1.019, 1.049 for preterm birth. CONCLUSIONS: Preterm birth is sensitive to wildland fire PM2.5; therefore, we must reduce exposure during pregnancy.

Mapping and modeling airborne urban phenanthrene distribution using vegetation biomonitoring.

To capture the spatial distribution of phenanthrene in an urban setting we used vegetation biomonitoring with Jeffrey pine trees (Pinus jeffreyi). The major challenge in characterizing spatial variation in polycyclic aromatic hydrocarbon (PAH) concentrations within a metropolitan area has been sampling at a fine enough resolution to observe the underlying spatial pattern. However, field and chamber studies show that the primary pathway through which PAHs enter plants is from air into leaves, making vegetation biomonitoring a feasible way to examine the spatial distribution of these compounds. Previous research has shown that phenanthrene has adverse health effects and that it is one of the most abundant PAHs in urban air. We collected 99 pine needle samples from 91 locations in Fresno in the morning on a winter day, and analyzed them for PAHs in the inner needle. All 99 pine needle samples had detectable levels of phenanthrene, with mean concentration of 41.0 ng g-1, median 36.9 ng g-1, and standard deviation of 28.5 ng g-1 fresh weight. The ratio of the 90th:10th percentile concentrations by location was 3.3. The phenanthrene distribution had a statistically significant Moran's I of 0.035, indicating a high degree of spatial clustering. We implemented land use regression to fit a model to our data. Our model was able to explain a moderate amount of the variability in the data (R 2 = 0.56), likely reflecting the major sources of phenanthrene in Fresno. The spatial distribution of modeled airborne phenanthrene shows the influences of highways, railroads, and industrial and commercial zones.

Ventilation conditions during COVID-19 outbreaks in six California state carceral institutions.

Residents of carceral facilities are exposed to poor ventilation conditions which leads to the spread of communicable diseases such as COVID-19. Indoor ventilation conditions are rarely studied within carceral settings and there remains limited capacity to develop solutions to address the impact of poor ventilation on the health of people who are incarcerated. In this study, we empirically measured ventilation rates within housing units of six adult prisons in the California Department of Corrections and Rehabilitation (CDCR) and compare the measured ventilation rates to recommended standards issued by the World Health Organization (WHO). Findings from the empirical assessment include lower ventilation rates than the recommended ventilation standards with particularly low ventilation during winter months when heating systems were in use. Inadvertent airflows from spaces housing potentially infected individuals to shared common spaces was also observed. The methodology used for this work can be leveraged for routine ventilation monitoring, pandemic preparedness, and disaster response.

Traffic-related air pollution, biomarkers of metabolic dysfunction, oxidative stress, and CC16 in children.

BACKGROUND: Previous research has revealed links between air pollution exposure and metabolic syndrome in adults; however, these associations are less explored in children. OBJECTIVE: This study aims to investigate the association between traffic-related air pollutants (TRAP) and biomarkers of metabolic dysregulation, oxidative stress, and lung epithelial damage in children. METHODS: We conducted cross-sectional analyses in a sample of predominantly Latinx, low-income children (n = 218) to examine associations between air pollutants (nitrogen dioxide (NO2), nitrogen oxides (NOx), elemental carbon, polycyclic aromatic hydrocarbons, carbon monoxide (CO), fine particulates (PM2.5)) and biomarkers of metabolic function (high-density lipoprotein (HDL), hemoglobin A1c (HbA1c), oxidative stress (8-isoprostane), and lung epithelial damage (club cell protein 16 (CC16)). RESULTS: HDL cholesterol showed an inverse association with NO2 and NOx, with the strongest relationship between HDL and 3-month exposure to NO2 (-15.4 mg/dL per IQR increase in 3-month NO2, 95% CI = -27.4, -3.4). 8-isoprostane showed a consistent pattern of increasing values with 1-day and 1-week exposure across all pollutants. Non-significant increases in % HbA1c were found during 1-month time frames and decreasing CC16 in 3-month exposure time frames. CONCLUSION: Our results suggest that TRAP is significantly associated with decreased HDL cholesterol in longer-term time frames and elevated 8-isoprostane in shorter-term time frames. TRAP could have the potential to influence lifelong metabolic patterns, through metabolic effects in childhood.

Increases in ambient air pollutants during pregnancy are linked to increases in methylation of IL4, IL10, and IFNγ.

BACKGROUND: Ambient air pollutant (AAP) exposure is associated with adverse pregnancy outcomes, such as preeclampsia, preterm labor, and low birth weight. Previous studies have shown methylation of immune genes associate with exposure to air pollutants in pregnant women, but the cell-mediated response in the context of typical pregnancy cell alterations has not been investigated. Pregnancy causes attenuation in cell-mediated immunity with alterations in the Th1/Th2/Th17/Treg environment, contributing to maternal susceptibility. We recruited women (n = 186) who were 20 weeks pregnant from Fresno, CA, an area with chronically elevated AAP levels. Associations of average pollution concentration estimates for 1 week, 1 month, 3 months, and 6 months prior to blood draw were associated with Th cell subset (Th1, Th2, Th17, and Treg) percentages and methylation of CpG sites (IL4, IL10, IFNγ, and FoxP3). Linear regression models were adjusted for weight, age, season, race, and asthma, using a Q value as the false-discovery-rate-adjusted p-value across all genes. RESULTS: Short-term and mid-term AAP exposures to fine particulate matter (PM2.5), nitrogen dioxide (NO2) carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAH456) were associated with percentages of immune cells. A decrease in Th1 cell percentage was negatively associated with PM2.5 (1 mo/3 mo: Q < 0.05), NO2 (1 mo/3 mo/6 mo: Q < 0.05), and PAH456 (1 week/1 mo/3 mo: Q < 0.05). Th2 cell percentages were negatively associated with PM2.5 (1 week/1 mo/3 mo/6 mo: Q < 0.06), and NO2 (1 week/1 mo/3 mo/6 mo: Q < 0.06). Th17 cell percentage was negatively associated with NO2 (3 mo/6 mo: Q < 0.01), CO (1 week/1 mo: Q < 0.1), PM2.5 (3 mo/6 mo: Q < 0.05), and PAH456 (1 mo/3 mo/6 mo: Q < 0.08). Methylation of the IL10 gene was positively associated with CO (1 week/1 mo/3 mo: Q < 0.01), NO2 (1 mo/3 mo/6 mo: Q < 0.08), PAH456 (1 week/1 mo/3 mo: Q < 0.01), and PM2.5 (3 mo: Q = 0.06) while IL4 gene methylation was positively associated with concentrations of CO (1 week/1 mo/3 mo/6 mo: Q < 0.09). Also, IFNγ gene methylation was positively associated with CO (1 week/1 mo/3 mo: Q < 0.05) and PAH456 (1 week/1 mo/3 mo: Q < 0.06). CONCLUSION: Exposure to several AAPs was negatively associated with T-helper subsets involved in pro-inflammatory and anti-inflammatory responses during pregnancy. Methylation of IL4, IL10, and IFNγ genes with pollution exposure confirms previous research. These results offer insights into the detrimental effects of air pollution during pregnancy, the demand for more epigenetic studies, and mitigation strategies to decrease pollution exposure during pregnancy.

Ambient air pollution impairs regulatory T-cell function in asthma.

BACKGROUND: Asthma is the most frequent chronic disease in children, and children are at high risk for adverse health consequences associated with ambient air pollution (AAP) exposure. Regulatory T (Treg) cells are suppressors of immune responses involved in asthma pathogenesis. Treg-cell impairment is associated with increased DNA methylation of Forkhead box transcription factor 3 (Foxp3), a key transcription factor in Treg-cell activity. Because AAP exposure can induce epigenetic changes, we hypothesized that Treg-cell function would be impaired by AAP, allowing amplification of an inflammatory response. OBJECTIVES: To assess whether exposure to AAP led to hypermethylation of the Foxp3 gene, causing impaired Treg-cell suppression and worsened asthma symptom scores. METHODS: Children with and without asthma from Fresno, Calif (high pollution, Fresno Asthma Group [FA], n = 71, and Fresno Non Asthmatic Group, n = 30, respectively), and from Stanford, Calif (low pollution, Stanford Asthma Group, n = 40, and Stanford Non Asthmatic Group, n = 40), were enrolled in a cross-sectional study. Peripheral blood Treg cells were used in functional and epigenetic studies. Asthma outcomes were assessed by Global Initiative in Asthma score. RESULTS: Fresno Asthma Group Treg-cell suppression was impaired and FA Treg-cell chemotaxis were reduced compared with other groups (P ≤ .05). Treg-cell dysfunction was associated with more pronounced decreases in asthma Global Initiative in Asthma score in FA versus the Stanford Asthma Group. Foxp3 was decreased in FA compared with the Fresno Non Asthmatic Group (P ≤ .05). FA also contained significantly higher levels of methylation at the Foxp3 locus (P ≤ .05). CONCLUSION: Increased exposure to AAP is associated with hypermethylation of the Foxp3 locus, impairing Treg-cell function and increasing asthma morbidity. AAP could play a role in mediating epigenetic changes in Treg cells, which may worsen asthma by an immune mechanism.

Air pollution exposure is linked with methylation of immunoregulatory genes, altered immune cell profiles, and increased blood pressure in children.

Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for clinical intervention prior to actual disease presentation. We therefore determined the associations between exposure to multiple air pollutants and both immunological outcomes (methylation and protein expression of immune cell types associated with immune regulation) and cardiovascular outcomes (blood pressure) in a cohort of school-aged children (6-8 years; n = 221) living in a city with known elevated pollution levels. Exposure to fine particular matter (PM2.5), carbon monoxide (CO), and ozone (O3) was linked to altered methylation of most CpG sites for genes Foxp3, IL-4, IL-10 and IFN-g, all involved in immune regulation (e.g. higher PM2.5 exposure 1 month prior to the study visit was independently associated with methylation of the IL-4 CpG24 site (est = 0.16; P = 0.0095). Also, immune T helper cell types (Th1, Th2 and Th17) were associated with short-term exposure to PM2.5, O3 and CO (e.g. Th1 cells associated with PM2.5 at 30 days: est = - 0.34, P < 0.0001). Both B cells (est = - 0.19) and CD4+ cells (est = 0.16) were associated with 1 day NO2 exposure (P ≤ 0.031), whereas CD4+ and CD8+ cells were associated with chronic exposure to PAH456, NOx and/or NO2 (P ≤ 0.038 for all). Finally, diastolic BP (DBP) was inversely associated with long-term exposures to both CO and PAH456, and both systolic and pulse pressure were associated with short-term NO2 and chronic NOx exposure. Our findings demonstrate links between air pollution exposure and methylation of immunoregulatory genes, immune cell profiles and blood pressure, suggesting that even at a young age, the immune and cardiovascular systems are negatively impacted by exposure to air pollution.