A Bayesian joint model for compositional mediation effect selection in microbiome data.

Analyzing multivariate count data generated by high-throughput sequencing technology in microbiome research studies is challenging due to the high-dimensional and compositional structure of the data and overdispersion. In practice, researchers are often interested in investigating how the microbiome may mediate the relation between an assigned treatment and an observed phenotypic response. Existing approaches designed for compositional mediation analysis are unable to simultaneously determine the presence of direct effects, relative indirect effects, and overall indirect effects, while quantifying their uncertainty. We propose a formulation of a Bayesian joint model for compositional data that allows for the identification, estimation, and uncertainty quantification of various causal estimands in high-dimensional mediation analysis. We conduct simulation studies and compare our method's mediation effects selection performance with existing methods. Finally, we apply our method to a benchmark data set investigating the sub-therapeutic antibiotic treatment effect on body weight in early-life mice.

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.

The Impact of Job Loss on Self-injury Mortality in a Cohort of Autoworkers: Application of a Novel Causal Approach.

BACKGROUND: Recent increases in national rates of suicide and fatal overdose have been linked to a deterioration of economic and social stability. The American auto industry experienced comparable pressures beginning in the 1980s with the emergence of a competitive global market. METHODS: Using the United Autoworkers-General Motors (GM) cohort as a case study, we examine the impact of employment loss on these self-injury mortality events. For 29,538 autoworkers employed on or after 1 January 1970, we apply incremental propensity score interventions, a novel causal inference approach, to examine how proportional shifts in the odds of leaving active GM employment affect the cumulative incidence of self-injury mortality. RESULTS: Cumulative incidence of self-injury mortality was 0.87% (255 cases) at the observed odds of leaving active GM employment (δ = 1) over a 45-year period. A 10% decrease in the odds of leaving active GM employment (δ = 0.9) results in an estimated 8% drop in self-injury mortality (234 cases) while a 10% increase (δ = 1.1) results in a 19% increase in self-injury mortality (303 cases). CONCLUSIONS: These results are consistent with the hypothesis that leaving active employment at GM increases the risk of death due to suicide or drug overdose.

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.

Chronic obstructive pulmonary disease mortality: The Diesel Exhaust in Miners Study (DEMS).

BACKGROUND: Miners are highly exposed to diesel exhaust emissions from powered equipment. Although biologically plausible, there is little evidence based on quantitative exposure assessment, that long-term diesel exposure increases risk of chronic obstructive pulmonary disease (COPD). To fill this gap, we examined COPD mortality and diesel exhaust exposure in the Diesel Exhaust in Miners Study (DEMS). METHODS: We fit Cox models to estimate hazard ratios (HRs) for COPD mortality and cumulative exposure (µg/m3-years) to respirable elemental carbon (REC), a key metric for diesel exhaust exposure. Separate models were fit for ever-underground and surface-only miners to allow for effect modification. Exposure was lagged by 0, 10 and 15 years. In a secondary analysis, we addressed the healthy worker survivor effect by applying the parametric g-formula to handle time-varying confounding affected by prior exposure among ever-underground workers. RESULTS: Based on 140 cases, the HRs for COPD mortality increased as categories of lagged REC exposure increased for all workers. Among surface-only workers, those in the middle exposure category (0 lag) had a significantly elevated hazard ratio of 2.34 (95% CI: 1.11-4.61) relative to those in the lowest category. Among the ever-underground, that ratio was 1.35, with wide confidence intervals. Using the g-formula, we estimated that the lifetime cumulative risk of COPD mortality would have been reduced from the observed 5.0%-3.1% under a hypothetical intervention where all ever-underground workers were always unexposed. CONCLUSIONS: Our results suggest long term exposure to diesel exhaust may increase risk of COPD in miners, though power was limited.

Comment on "A global-scale ecological niche model to predict SARS-CoV-2 coronavirus infection rate", author Coro.

In this letter we present comments on the article "A global-scale ecological niche model to predict SARS-CoV-2 coronavirus" by Coro published in 2020.

Diesel Exhaust, Respirable Dust, and Ischemic Heart Disease: An Application of the Parametric g-formula.

BACKGROUND: Although general population studies of air pollution suggest that particulate matter-diesel exhaust emissions in particular-is a potential risk factor for cardiovascular disease, direct evidence from occupational cohorts using quantitative metrics of exposure is limited. In this study, we assess counterfactual risk of ischemic heart disease (IHD) mortality under hypothetical scenarios limiting exposure levels of diesel exhaust and of respirable mine/ore dust in the Diesel Exhaust in Miners Study cohort. METHODS: We analyzed data on 10,779 male miners from 8 nonmetal, noncoal mines-hired after diesel equipment was introduced in the respective facilities-and followed from 1948 to 1997, with 297 observed IHD deaths in this sample. We applied the parametric g-formula to assess risk under hypothetical scenarios with various limits for respirable elemental carbon (a surrogate for diesel exhaust), and respirable dust, separately and jointly. RESULTS: The risk ratio comparing the observed risk to cumulative IHD mortality risk at age 80 under a hypothetical scenario where exposures to elemental carbon and respirable dust are eliminated was 0.79 (95% confidence interval [CI]: 0.64, 0.97). The corresponding risk difference was -3.0% (95% CI: -5.7, -0.3). CONCLUSION: Our findings, based on data from a cohort of nonmetal miners, are consistent with the hypothesis that interventions to eliminate exposures to diesel exhaust and respirable dust would reduce IHD mortality risk.

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.

Exposure-Lag-Response in Longitudinal Studies: Application of Distributed-Lag Nonlinear Models in an Occupational Cohort.

Prolonged exposures can have complex relationships with health outcomes, as timing, duration, and intensity of exposure are all potentially relevant. Summary measures such as cumulative exposure or average intensity of exposure may not fully capture these relationships. We applied penalized and unpenalized distributed-lag nonlinear models (DLNMs) with flexible exposure-response and lag-response functions in order to examine the association between crystalline silica exposure and mortality from lung cancer and nonmalignant respiratory disease in a cohort study of 2,342 California diatomaceous earth workers followed during 1942-2011. We also assessed associations using simple measures of cumulative exposure assuming linear exposure-response and constant lag-response. Measures of association from DLNMs were generally higher than those from simpler models. Rate ratios from penalized DLNMs corresponding to average daily exposures of 0.4 mg/m3 during lag years 31-50 prior to the age of observed cases were 1.47 (95% confidence interval (CI): 0.92, 2.35) for lung cancer mortality and 1.80 (95% CI: 1.14, 2.85) for nonmalignant respiratory disease mortality. Rate ratios from the simpler models for the same exposure scenario were 1.15 (95% CI: 0.89, 1.48) and 1.23 (95% CI: 1.03, 1.46), respectively. Longitudinal cohort studies of prolonged exposures and chronic health outcomes should explore methods allowing for flexibility and nonlinearities in the exposure-lag-response.

Estimating Counterfactual Risk Under Hypothetical Interventions in the Presence of Competing Events: Crystalline Silica Exposure and Mortality From 2 Causes of Death.

Exposure to silica has been linked to excess risk of lung cancer and nonmalignant respiratory disease mortality. In this study we estimated risk for both these outcomes in relation to occupational silica exposure as well as the reduction in risk that would result from hypothetical interventions on exposure in a cohort of exposed workers. Analyses were carried out using data from an all-male study population consisting of 2,342 California diatomaceous earth workers regularly exposed to crystalline silica and followed between 1942 and 2011. We estimated subdistribution risk for each event under the natural course and interventions of interest using the parametric g-formula to adjust for healthy-worker survivor bias. The risk ratio for lung cancer mortality, comparing an intervention in which a theoretical maximum exposure limit was set at 0.05 mg/m3 (the current US regulatory limit) with the observed exposure concentrations, was 0.86 (95% confidence interval: 0.63, 1.22). The corresponding risk ratio for nonmalignant respiratory disease mortality was 0.69 (95% confidence interval: 0.52, 0.93). Our findings suggest that risks from both outcomes would have been considerably lower if historical silica exposures in this cohort had not exceeded current regulatory limits.

Ischemic Heart Disease Mortality and Diesel Exhaust and Respirable Dust Exposure in the Diesel Exhaust in Miners Study.

Diesel exhaust is a suggested risk factor for ischemic heart disease (IHD), but evidence from cohorts using quantitative exposure metrics is limited. We examined the impact of respirable elemental carbon (REC), a key surrogate for diesel exhaust, and respirable dust (RD) on IHD mortality, using data from the Diesel Exhaust in Miners Study in the United States. Using data from a cohort of male workers followed from 1948-1968 until 1997, we fitted Cox proportional hazards models to estimate hazard ratios for IHD mortality for cumulative and average intensity of exposure to REC and RD. Segmented linear regression models allowed for nonmonotonicity. Hazard ratios for cumulative and average REC exposure declined relative to the lowest exposure category before increasing to 0.79 and 1.25, respectively, in the highest category. Relative to the category containing the segmented regression change points, hazard ratios for the highest category were 1.69 and 1.54 for cumulative and average REC exposure, respectively. Hazard ratios for RD exposure increased across the full exposure range to 1.33 and 2.69 for cumulative and average RD exposure, respectively. Tests for trend were statistically significant for cumulative REC exposure (above the change point) and for average RD exposure. Our findings suggest excess risk of IHD mortality in relation to increased exposure to REC and RD.

Secondhand smoke exposure and asthma outcomes among African-American and Latino children with asthma.

BACKGROUND: Secondhand smoke (SHS) exposures have been linked to asthma-related outcomes but quantitative dose-responses using biomarkers of exposure have not been widely reported. OBJECTIVES: Assess dose-response relationships between plasma cotinine-determined SHS exposure and asthma outcomes in minority children, a vulnerable population exposed to higher levels of SHS and under-represented in the literature. METHODS: We performed analyses in 1172 Latino and African-American children with asthma from the mainland USA and Puerto Rico. We used logistic regression to assess relationships of cotinine levels ≥0.05 ng/mL with asthma exacerbations (defined as asthma-related hospitalisations, emergency room visits or oral steroid prescription) in the previous year and asthma control. The shape of dose-response relationships was assessed using a continuous exposure variable in generalised additive logistic models with penalised splines. RESULTS: The OR for experiencing asthma exacerbations in the previous year for cotinine levels ≥0.05 ng/mL, compared with <0.05 ng/mL, was 1.40 (95% CI 1.03 to 1.89), while the OR for poor asthma control was 1.53 (95% CI 1.12 to 2.13). Analyses for dose-response relationships indicated increasing odds of asthma outcomes related with increasing exposure, even at cotinine levels associated with light SHS exposures. CONCLUSIONS: Exposure to SHS was associated with higher odds of asthma exacerbations and having poorly controlled asthma with an increasing dose-response even at low levels of exposure. Our results support the conclusion that there are no safe levels of SHS exposures.

Contrasting Causal Effects of Workplace Interventions.

Occupational exposure guidelines are ideally based on estimated effects of static interventions that assign constant exposure over a working lifetime. Static effects are difficult to estimate when follow-up extends beyond employment because their identifiability requires additional assumptions. Effects of dynamic interventions that assign exposure while at work, allowing subjects to leave and become unexposed thereafter, are more easily identifiable but result in different estimates. Given the practical implications of exposure limits, we explored the drivers of the differences between static and dynamic interventions in a simulation study where workers could terminate employment because of an intermediate adverse health event that functions as a time-varying confounder. The two effect estimates became more similar with increasing strength of the health event and outcome relationship and with increasing time between health event and employment termination. Estimates were most dissimilar when the intermediate health event occurred early in employment, providing an effective screening mechanism.

Ambient Air Pollution and Asthma-Related Outcomes in Children of Color of the USA: a Scoping Review of Literature Published Between 2013 and 2017.

PURPOSE OF REVIEW: Given racial disparities in ambient air pollution (AAP) exposure and asthma risk, this review offers an overview of the literature investigating the ambient air pollution-asthma relationship in children of color between 2013 and 2017. RECENT FINDINGS: AAP is likely a key contributor to the excess burden of asthma in children of color due to pervasive exposure before birth, at home, and in school. Recent findings suggest that psychosocial stressors may modify the relationship between AAP and asthma. The effect of AAP on asthma in children of color is likely modulated by multiple unique psychosocial stressors and gene-environment interactions. Although children of color are being included in asthma studies, more research is still needed on impacts of specific criteria pollutants throughout the life course. Additionally, future studies should consider historical factors when analyzing current exposure profiles.

Lung cancer mortality and exposure to synthetic metalworking fluid and biocides: controlling for the healthy worker survivor effect.

OBJECTIVES: Synthetic metalworking fluids (MWFs), widely used to cool and lubricate industrial machining and grinding operations, have been linked with increased risk of several cancers. Estimates of their relation with lung cancer, however, are inconsistent. Controlling for the healthy worker survivor effect, we examined the relations between lung cancer mortality and exposure to synthetic MWF, as well as to biocides added to water-based fluids to control microbial growth, in a cohort of autoworkers. Biocides served as a marker for endotoxin, which has reported antitumour effects, and were hypothesised to be the reason prior studies found reduced lung cancer risk associated with exposure to synthetic fluids. METHODS: Using the parametric g-formula, we estimated risk ratios (RRs) comparing cumulative lung cancer mortality under no intervention with what would have occurred under hypothetical interventions reducing exposure to zero (ie, a ban) separately for two exposures: synthetic fluids and biocides. We also specified an intervention on synthetic MWF and biocides simultaneously to estimate joint effects. RESULTS: Under a synthetic MWF ban, we observed decreased lung cancer mortality risk at age 86, RR=0.96 (0.91-1.01), but when we also intervened to ban biocides, the RR increased to 1.03 (0.95-1.11). A biocide-only ban increased lung cancer mortality (RR=1.07 (1.00-1.16)), with slightly larger RR in younger ages. CONCLUSIONS: Findings suggest a modest positive association for synthetic MWF with lung cancer mortality, contrary to the negative associations reported in earlier studies. Biocide exposure, however, was inversely associated with risk of lung cancer mortality.

Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes-Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies.

RATIONALE: Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking. OBJECTIVES: To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry. METHODS: The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 µm and ≤2.5 µm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry. MEASUREMENTS AND MAIN RESULTS: A 5 µg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 µm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function. CONCLUSIONS: Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

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 Diesel Exposure, Duration of Employment, and Lung Cancer: An Application of the Parametric G-Formula.

BACKGROUND: If less healthy workers terminate employment earlier, thus accumulating less exposure, yet remain at greater risk of the health outcome, estimated health effects of cumulative exposure will be biased downward. If exposure also affects termination of employment, then the bias cannot be addressed using conventional methods. We examined these conditions as a prelude to a reanalysis of lung cancer mortality in the Diesel Exhaust in Miners Study. METHODS: We applied an accelerated failure time model to assess the effect of exposures to respirable elemental carbon (a surrogate for diesel) on time to termination of employment among nonmetal miners who ever worked underground (n = 8,307). We then applied the parametric g-formula to assess how possible interventions setting respirable elemental carbon exposure limits would have changed lifetime risk of lung cancer, adjusting for time-varying employment status. RESULTS: Median time to termination was 36% shorter (95% confidence interval = 33%, 39%), per interquartile range width increase in respirable elemental carbon exposure. Lung cancer risk decreased with more stringent interventions, with a risk ratio of 0.8 (95% confidence interval = 0.5, 1.1) comparing a limit of ≤25 µg/m respirable elemental carbon to no intervention. The fraction of cases attributable to diesel exposure was 27% in this population. CONCLUSIONS: The g-formula controlled for time-varying confounding by employment status, the signature of healthy worker survivor bias, which was also affected by diesel exposure. It also offers an alternative approach to risk assessment for estimating excess cumulative risk, and the impact of interventions based entirely on an observed population.

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.