Elizabeth M. Noth

Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells

Evidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases.

Polycyclic aromatic hydrocarbon exposure and wheeze in a cohort of children with asthma in Fresno, CA

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 Childrens 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/m3) 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.

Ambient polycyclic aromatic hydrocarbons and pulmonary function in children

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/m3 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.

Incident ischemic heart disease and recent occupational exposure to particulate matter in an aluminum cohort

Fine particulate matter (PM2.5) in air pollution, primarily from combustion sources, is recognized as an important risk factor for cardiovascular events but studies of workplace PM2.5 exposure are rare. We conducted a prospective study of exposure to PM2.5 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 PM2.5 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 PM2.5 in the workplace appears to increase the risk of IHD incidence.

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/m3. For fabrication workers, the difference was 2.5% (0.8%, 4.1%) at the 10th percentile of 0.06 mg/m3. 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.

Development of a job-exposure matrix for exposure to total and fine particulate matter in the aluminum industry

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 (PM2.5). Despite this, the health impacts of higher occupational exposures to PM2.5 have rarely been evaluated. In part, this research gap derives from the absence of information on PM2.5 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 PM2.5 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 PM2.5 and TPM personal monitoring was conducted from 2010 to 2011 to determine the percent of TPM that is composed of PM2.5 (%PM2.5) in each DEG. The mean TPM from the JEM was then multiplied by %PM2.5 to calculate PM2.5 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/m3, and the corresponding mean PM2.5 concentrations were 2.03 and 0.40 mg/m3. Observed occupational exposures in this study generally exceeded environmental PM2.5 concentrations by an order of magnitude.

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/m3-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.

Traffic-Related Air Pollution and Telomere Length in Children and Adolescents Living in Fresno, CA: A Pilot Study.

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 (R2 = 0.69), as well as between age and TL (R2 = 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. Learning Objectives 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.

Ischemic Heart Disease Incidence in Relation to Fine versus Total Particulate Matter Exposure in a U.S. Aluminum Industry Cohort

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.

Spatial and temporal distribution of polycyclic aromatic hydrocarbons and elemental carbon in Bakersfield, California

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 four 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 (R2 = 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.