Search

BackgroundEvidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases.ObjectiveWe hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs.MethodsWe recruited 256 subjects from Fresno, CA. Ambient PAH concentrations (ng/m(3) ) were measured using a spatial-temporal regression model over multiple time periods. Asthma diagnosis was determined by current NHLBI criteria. Phenotyping and functional immune measurements were performed from isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced.ResultsWe show that higher average PAH exposure was significantly associated with impaired Treg function and increased methylation in the forkhead box protein 3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic modifications were significantly linked to differential protein expression of FOXP3 (P < 0.001). Methylation was associated with cellular functional changes, specifically Treg dysfunction, and an increase in total plasma IgE levels. Protein expression of IL-10 decreased and IFN-γ increased as the extent of PAH exposure increased. The strength of the associations generally increased as the time window for average PAH exposure increased from 24 hr to 1 year, suggesting more of a chronic response. Significant associations with chronic PAH exposure and immune outcomes were also observed in subjects with allergic rhinitis.Conclusions and clinical relevanceCollectively, these results demonstrate that increased ambient PAH exposure is associated with impaired systemic immunity and epigenetic modifications in a key locus involved in atopy: FOXP3, with a higher impact on atopic children. The results suggest that increased atopic clinical symptoms in children could be linked to increased PAH exposure in air pollution.

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 (PM 2.5 ) and ozone (O 3 ) 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 (FEV 1 ), adjusted for covariates., Results: PM 2.5 exposure during the prenatal period and the first 3-years of life was associated with lower FVC and FEV 1 assessed at ages 6-9. Specifically, an increase from the 5th percentile of the observed monthly average exposure (7.55 μg/m 3 ) to the median observed exposure (12.69 μg/m 3 ) 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 FEV 1 (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 PM 2.5 are associated with decreased lung function later in childhood. Exposures during the latter months of pregnancy may be especially influential., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andreas Neophytou reports financial support was provided by National Institute of Environmental Health Sciences. John R. Balmes, Liza Lutzker, Stephanie Holm, Elizabeth M. Noth, Sadie Costello, Tim Tyner, Ellen Eisen, Kari C. Nadeau, S Katharine Hammond reports financial support was provided by National Institute of Environmental Health Sciences. John R. Balmes reports a relationship with California Air Resources Board that includes: board membership., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 ( β =-0.073, 95% CI -0.13 to -0.02; p=0.006) and diffusion capacity of the lung for carbon monoxide ( β =-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., Competing Interests: Competing interests: SDN is a consultant and is on the speakers bureau for Roche-Genentech and Boehringer-Ingelheim. He is also a consultant for Bellerophon, United Therapeutics and Galapagos. KAJ reports grants, personal fees and other from Boehringer-Ingelheim, personal fees and other from Hoffman La Roche, personal fees and other from Theravance, personal fees and other from Blade Therapeutics, grants from Chest Foundation, grants from University of Calgary School of Medicine, grants from Pulmonary Fibrosis Society of Calgary, grants and personal fees from Three Lakes Foundation, personal fees from Pliant Therapeutic, outside the submitted work., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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 (NO 2 ), nitrogen oxides (NO x ), elemental carbon, polycyclic aromatic hydrocarbons, carbon monoxide (CO), fine particulates (PM 2.5 )) 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 NO 2 and NO x , with the strongest relationship between HDL and 3-month exposure to NO 2 (-15.4 mg/dL per IQR increase in 3-month NO 2 , 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., (© 2021. The Author(s).)

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), NO 2 , elemental carbon, and fine particulate matter (PM 2.5 ) - 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/m 3 increase in 6-month average PAH456 was associated with a 0.07% increase (95% CI: 0.01, 0.14) and a 3.62 μg/m 3 increase in 6-month average PM 2.5 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 NO 2 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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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/m 3 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., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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 (PM 2.5 ) 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/m 3 was associated with an improvement in forced expiratory volume in one second (FEV 1 ) 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 FEV 1 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 PM 2.5 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., Competing Interests: Competing interests: KH has received compensation as a member of the scientific advisory board for Alcoa, Inc. (Pittsburgh, Pennsylvania) and for consulting for Alcoa, Inc. in the past. MRC has received salary support from Alcoa, Inc. through contracts with Stanford University (Stanford, California)., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Wildland firefighters engaged in fire suppression activities are often exposed to hazardous air pollutants such as polycyclic aromatic hydrocarbons (PAHs) and particulate matter (PM 2.5 ) 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 PM 2.5 near an ICP during a wildfire event in California. We collected area air samples for PAHs and PM 2.5, 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 PM 2.5 concentrations were measured with an Environmental Beta Attenuation Monitor. Most PAH concentrations generally had similar concentrations during the day and night. PM 2.5 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.

Traditional methods for measuring personal exposure to fine particulate matter (PM 2.5 ) 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 PM 2.5 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 PM 2.5 black carbon (BC) using light transmissometry and aerosol oxidative potential (OP) using the dithiothreitol (DTT) assay. The amount of inhaled PM 2.5 was calculated for each microenvironment to evaluate the health risks associated with exposure. On average, the estimated amount of inhaled PM 2.5 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 PM 2.5 species within distinct microenvironments.

Background: Air pollution exposure is associated with acute exacerbation, disease progression, and mortality in patients with idiopathic pulmonary fibrosis (IPF). The objective of this study was to describe the impact of air pollution exposures on disease severity, as well as changes in lung function, in patients with IPF., Methods: Using home spirometers and symptom diaries, 25 patients with IPF prospectively recorded FVC weekly for up to 40 weeks. Residential addresses were geocoded to estimate weekly mean air pollution exposures for ground-level ozone (O 3 ), nitrogen dioxide (NO 2 ), and particulate matter < 2.5 or 10 μm in aerodynamic diameter (PM 2.5 and PM 10 , respectively). The dependence of weekly clinical measurements on preceding levels of each pollutant was assessed with the use of linear mixed models, yielding beta-coefficients with 95% CIs, using varying lag times., Results: Lower mean FVC % predicted was consistently associated with increased mean exposures to PM 10 in the 2 to 5 weeks preceding clinical measurements (range, -0.46 to -0.39 [95% CI, -0.73 to -0.13]; P < .005). Lower mean FVC % predicted over the study period was inversely related to mean levels of NO 2 (-0.45 [95% CI, -0.85 to -0.05]; P = .03), PM 2.5 (-0.45 [95% CI, -0.84 to -0.07]; P = .02), and PM 10 (-0.57 [95% CI, -0.92 to -0.21]; P = .003), averaged over the study. Weekly changes in FVC and changes over 40 weeks were independent of pollution exposures., Conclusions: Higher air pollution exposures were associated with lower lung function, but not changes in lung function, in patients with IPF. Further studies are needed to characterize the mechanisms underlying this relationship., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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.

Objective: The main objective of this pilot study was to gather preliminary information about how telomere length (TL) varies in relation to exposure to polycyclic aromatic hydrocarbons (PAHs) in children living in a highly polluted city., Methods: We conducted a cross-sectional study of children living in Fresno, California (n = 14). Subjects with and without asthma were selected based on their annual average PAH level in the 12-months prior to their blood draw. We measured relative telomere length from peripheral blood mononuclear cells (PBMC)., Results: We found an inverse linear relationship between average PAH level and TL (R = 0.69), as well as between age and TL (R = 0.21). Asthmatics had shorter mean telomere length than non-asthmatics (TLasthmatic = 1.13, TLnon-asthmatic = 1.29)., Conclusions: These preliminary findings suggest that exposure to ambient PAH may play a role in telomere shortening.Become familiar with previous evidence suggesting that telomere length may be a biomarker of air pollution-induced cytotoxicity.Summarize the new findings on the association between polycyclic aromatic hydrocarbon (PAH) exposure and telomere length in adolescents, including those with asthma.Discuss the implications for recommendations and policies to mitigate the health and respiratory effects of traffic-related air pollution.

Despite increasing evidence that airborne polycyclic aromatic hydrocarbon (PAH) exposures contribute to adverse health outcomes for sensitive populations, limited data are available on short-term intraurban spatial distributions for use in epidemiologic research. Exposure assessments for airborne PAHs are uncommon because air sampling for PAHs is a labor-, equipment-, and time-intensive task. To address this gap we measured wintertime PAH concentrations during 2010-2011 in Bakersfield, California, USA, a major city in the Southern San Joaquin Valley. Specifically, 58 96-hour integrated PAH samples were collected during 4 time periods at 14 locations from November 2010 to January 2011; duplicates were collected at two sites. We also collected elemental carbon (EC) at the same 14 sites and analyzed the two time periods with the highest ambient PAH pollution. We used linear regression models to quantify the relationship between potential spatial and temporal predictors of PAH concentrations. We found that wintertime PAH concentrations in Bakersfield, CA, are best predicted by meteorological variables and traffic proximity. Our model explains a moderate amount of the variability in the data (R 2 =0.58), likely reflecting the major sources of PAHs in Bakersfield. We also observed that PAH concentrations were more spatially variable than EC concentrations. Comparing our data to historical monitoring data at one location in Bakersfield showed that the relatively low PAH concentrations during the 2010-2011 winter in Bakersfield is part of a long-term trend in decreasing PAH concentrations.

Ischemic heart disease (IHD) has been linked to exposures to airborne particles with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient environment and in occupational settings. Routine industrial exposure monitoring, however, has traditionally focused on total particulate matter (TPM). To assess potential benefits of PM2.5 monitoring, we compared the exposure-response relationships between both PM2.5 and TPM and incidence of IHD in a cohort of active aluminum industry workers. To account for the presence of time varying confounding by health status we applied marginal structural Cox models in a cohort followed with medical claims data for IHD incidence from 1998 to 2012. Analyses were stratified by work process into smelters (n = 6,579) and fabrication (n = 7,432). Binary exposure was defined by the 10th-percentile cut-off from the respective TPM and PM2.5 exposure distributions for each work process. Hazard Ratios (HR) comparing always exposed above the exposure cut-off to always exposed below the cut-off were higher for PM2.5, with HRs of 1.70 (95% confidence interval (CI): 1.11-2.60) and 1.48 (95% CI: 1.02-2.13) in smelters and fabrication, respectively. For TPM, the HRs were 1.25 (95% CI: 0.89-1.77) and 1.25 (95% CI: 0.88-1.77) for smelters and fabrication respectively. Although TPM and PM2.5 were highly correlated in this work environment, results indicate that, consistent with biologic plausibility, PM2.5 is a stronger predictor of IHD risk than TPM. Cardiovascular risk management in the aluminum industry, and other similar work environments, could be better guided by exposure surveillance programs monitoring PM2.5.

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., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

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.

Few studies have examined the relationship between ambient polycyclic aromatic hydrocarbons (PAHs) and pulmonary function in children. Major sources include vehicular emissions, home heating, wildland fires, agricultural burning, and power plants. PAHs are an important component of fine particulate matter that has been linked to respiratory health. This cross-sectional study examines the relationship between estimated individual exposures to the sum of PAHs with 4, 5, or 6 rings (PAH456) and pulmonary function tests (forced expiratory volume in one second (FEV1) and forced expiratory flow between 25% and 75% of vital capacity) in asthmatic and non-asthmatic children. We applied land-use regression to estimate individual exposures to ambient PAHs for averaging periods ranging from 1 week to 1 year. We used linear regression to estimate the relationship between exposure to PAH456 with pre- and postbronchodilator pulmonary function tests in children in Fresno, California (N=297). Among non-asthmatics, there was a statistically significant association between PAH456 during the previous 3 months, 6 months, and 1 year and postbronchodilator FEV1. The magnitude of the association increased with the length of the averaging period ranging from 60 to 110 ml decrease in FEV1 for each 1 ng/m(3) increase in PAH456. There were no associations with PAH456 observed among asthmatic children. We identified an association between annual PAHs and chronic pulmonary function in children without asthma. Additional studies are needed to further explore the association between exposure to PAHs and pulmonary function, especially with regard to differential effects between asthmatic and non-asthmatic children.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

As part of exposure assessment for an ongoing epidemiologic study of heart disease and fine particle exposures in aluminum industry, area particle samples were collected in production facilities to assess instrument reliability and particle size distribution at different process areas. Personal modular impactors (PMI) and Minimicro-orifice uniform deposition impactors (MiniMOUDI) were used. The coefficient of variation (CV) of co-located samples was used to evaluate the reproducibility of the samplers. PM 2.5 measured by PMI was compared to PM 2.5 calculated from MiniMOUDI data. Mass median aerodynamic diameter (MMAD) and concentrations of sub-micrometer (PM 1.0 ) and quasi-ultrafine (PM 0.56) particles were evaluated to characterize particle size distribution. Most of CVs were less than 30%. The slope of the linear regression of PMI&#95;PM 2.5 versus MiniMOUDI&#95;PM 2.5 was 1.03 mg/m 3 per mg/m 3 (± 0.05), with correlation coefficient of 0.97 (± 0.01). Particle size distribution varied substantively in smelters, whereas it was less variable in fabrication units with significantly smaller MMADs (arithmetic mean of MMADs: 2.59 μm in smelters vs. 1.31 μm in fabrication units, p = 0.001). Although the total particle concentration was more than two times higher in the smelters than in the fabrication units, the fraction of PM 10 which was PM 1.0 or PM 0.56 was significantly lower in the smelters than in the fabrication units (p < 0.001). Consequently, the concentrations of sub-micrometer and quasi-ultrafine particles were similar in these two types of facilities. It would appear, studies evaluating ultrafine particle exposure in aluminum industry should focus on not only the smelters, but also the fabrication facilities.

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., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Increasing evidence indicates that exposure to particulate matter (PM) at environmental concentrations increases the risk of cardiovascular disease, particularly PM with an aerodynamic diameter of less than 2.5 μm (PM(2.5)). Despite this, the health impacts of higher occupational exposures to PM(2.5) have rarely been evaluated. In part, this research gap derives from the absence of information on PM(2.5) exposures in the workplace. To address this gap, we have developed a job-exposure matrix (JEM) to estimate exposure to two size fractions of PM in the aluminum industry. Measurements of total PM (TPM) and PM(2.5) were used to develop exposure metrics for an epidemiologic study. TPM exposures for distinct exposure groups (DEGs) in the JEM were calculated using 8385 personal TPM samples collected at 11 facilities (1980-2011). For eight of these facilities, simultaneous PM(2.5) and TPM personal monitoring was conducted from 2010 to 2011 to determine the percent of TPM that is composed of PM(2.5) (%PM(2.5)) in each DEG. The mean TPM from the JEM was then multiplied by %PM(2.5) to calculate PM(2.5) exposure concentrations in each DEG. Exposures in the smelters were substantially higher than in fabrication units; mean TPM concentrations in smelters and fabrication facilities were 3.86 and 0.76 mg/m(3), and the corresponding mean PM(2.5) concentrations were 2.03 and 0.40 mg/m(3). Observed occupational exposures in this study generally exceeded environmental PM(2.5) concentrations by an order of magnitude.

Fine particulate matter (PM(2.5)) in air pollution, primarily from combustion sources, is recognized as an important risk factor for cardiovascular events but studies of workplace PM(2.5) exposure are rare. We conducted a prospective study of exposure to PM(2.5) and incidence of ischemic heart disease (IHD) in a cohort of 11,966 US aluminum workers. Incident IHD was identified from medical claims data from 1998 to 2008. Quantitative metrics were developed for recent exposure (within the last year) and cumulative exposure; however, we emphasize recent exposure in the absence of interpretable work histories before follow-up. IHD was modestly associated with recent PM(2.5) overall. In analysis restricted to recent exposures estimated with the highest confidence, the hazard ratio (HR) increased to 1.78 (95% CI: 1.02, 3.11) in the second quartile and remained elevated. When the analysis was stratified by work process, the HR rose monotonically to 1.5 in both smelter and fabrication facilities, though exposure was almost an order of magnitude higher in smelters. The differential exposure-response may be due to differences in exposure composition or healthy worker survivor effect. These results are consistent with the air pollution and cigarette smoke literature; recent exposure to PM(2.5) in the workplace appears to increase the risk of IHD incidence.

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.

Polycyclic aromatic hydrocarbons (PAHs) are found widely in the ambient air and result from combustion of various fuels and industrial processes. PAHs have been associated with adverse human health effects such as cognitive development, childhood IQ, and respiratory health. The Fresno Asthmatic Children's Environment Study enrolled 315 children aged 6-11 years with asthma in Fresno, CA and followed the cohort from 2000 to 2008. Subjects were evaluated for asthma symptoms in up to three 14-day panels per year. Detailed ambient pollutant concentrations were collected from a central site and outdoor pollutants were measured at 83 homes for at least one 5-day period. Measurements of particle-bound PAHs were used with land-use regression models to estimate individual exposures to PAHs with 4-, 5-, or 6-member rings (PAH456) and phenanthrene for the cohort (approximately 22,000 individual daily estimates). We used a cross-validation-based algorithm for model fitting and a generalized estimated equation approach to account for repeated measures. Multiple lags and moving averages of PAH exposure were associated with increased wheeze for each of the three types of PAH exposure estimates. The odds ratios for asthmatics exposed to PAHs (ng/m(3)) ranged from 1.01 (95% CI, 1.00-1.02) to 1.10 (95% CI, 1.04-1.17). This trend for increased wheeze persisted among all PAHs measured. Phenanthrene was found to have a higher relative impact on wheeze. These data provide further evidence that PAHs contribute to asthma morbidity.

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., (Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Few books about the environment have generated as much heated debate as Bjørn Lomborg's 'The Skeptical Environmentalist: Measuring the Real State of the World', published by Cambridge University Press in 2001. A flavor of the controversy can be gleaned from a series of reviews and rebuttals published in 'Scientific American' (Rennie 2002). In general, most positive reviews appeared in the popular press (e.g., 'The Economist', 'Washington Post Book Review', 'The Wall Street Journal') and most negative reviews appeared in the scientific press (e.g., 'Science', 'Nature', 'Bioscience'). Although 'The Skeptical Environmentalist' (TSE) addresses a number of environmental health issues, voices from the environmental health community have not been prominent among the participants in this debate. Now that the dust from the initial stampede to praise and condemn the book has settled, we will explore lessons to be learned from TSE and the associated debate from an environmental health perspective.