Diesel exhaust and respiratory dust exposure in miners and chronic obstructive pulmonary disease (COPD) mortality in DEMS II.

BACKGROUND: Diesel exhaust and respirable dust exposures in the mining industry have not been studied in depth with respect to non-malignant respiratory disease including chronic obstructive pulmonary disease (COPD), with most available evidence coming from other settings. OBJECTIVES: To assess the relationship between occupational diesel exhaust and respirable dust exposures and COPD mortality, while addressing issues of survivor bias in exposed miners. METHODS: The study population consisted of 11,817 male workers from the Diesel Exhaust in Miners Study II, followed from 1947 to 2015, with 279 observed COPD deaths. We fit Cox proportional hazards models for the relationship between respirable elemental carbon (REC) and respirable dust (RD) exposure and COPD mortality. To address healthy worker survivor bias, we leveraged the parametric g-formula to assess effects of hypothetical interventions on both exposures. RESULTS: Cox models yielded elevated estimates for the associations between average intensity of REC and RD and COPD mortality, with hazard ratios (HR) corresponding to an interquartile range width increase in exposure of 1.46 (95 % confidence interval (CI): 1.12, 1.91) and 1.20 (95 % CI: 0.96, 1.49), respectively for each exposure. HRs for cumulative exposures were negative for both REC and RD. Based on results from the parametric g-formula, the risk ratio (RR) for COPD mortality comparing risk under an intervention eliminating REC to the observed risk was 0.85 (95 % CI: 0.55, 1.06), equivalent to an attributable risk of 15 %. The corresponding RR comparing risk under an intervention eliminating RD to the observed risk was 0.93 (95 % CI: 0.56, 1.31). CONCLUSIONS: Our findings, based on data from a cohort of nonmetal miners, are suggestive of an increased risk of COPD mortality associated with REC and RD, as well as evidence of survivor bias in this population leading to negative associations between cumulative exposures and COPD mortality in traditional regression analysis.

Measuring long-term exposure to wildfire PM2.5 in California: Time-varying inequities in environmental burden.

Wildfires have become more frequent and intense due to climate change and outdoor wildfire fine particulate matter (PM2.5) concentrations differ from relatively smoothly varying total PM2.5. Thus, we introduced a conceptual model for computing long-term wildfire PM2.5 and assessed disproportionate exposures among marginalized communities. We used monitoring data and statistical techniques to characterize annual wildfire PM2.5 exposure based on intermittent and extreme daily wildfire PM2.5 concentrations in California census tracts (2006 to 2020). Metrics included: 1) weeks with wildfire PM2.5 < 5 µg/m3; 2) days with non-zero wildfire PM2.5; 3) mean wildfire PM2.5 during peak exposure week; 4) smoke waves (≥2 consecutive days with <15 µg/m3 wildfire PM2.5); and 5) mean annual wildfire PM2.5 concentration. We classified tracts by their racial/ethnic composition and CalEnviroScreen (CES) score, an environmental and social vulnerability composite measure. We examined associations of CES and racial/ethnic composition with the wildfire PM2.5 metrics using mixed-effects models. Averaged 2006 to 2020, we detected little difference in exposure by CES score or racial/ethnic composition, except for non-Hispanic American Indian and Alaska Native populations, where a 1-SD increase was associated with higher exposure for 4/5 metrics. CES or racial/ethnic × year interaction term models revealed exposure disparities in some years. Compared to their California-wide representation, the exposed populations of non-Hispanic American Indian and Alaska Native (1.68×, 95% CI: 1.01 to 2.81), white (1.13×, 95% CI: 0.99 to 1.32), and multiracial (1.06×, 95% CI: 0.97 to 1.23) people were over-represented from 2006 to 2020. In conclusion, during our study period in California, we detected disproportionate long-term wildfire PM2.5 exposure for several racial/ethnic groups.

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.

Distribution of working hour characteristics by race, age, gender, and shift schedule among U.S. manufacturing workers.

Shift work is a common occupational exposure, however, few studies have examined aspects of shift work beyond night work and long hours, such as rotational patterns or weekend work, which may contribute to poor health through disruption of the body's circadian rhythms. In this manuscript, we calculated the prevalence of working hour characteristics using algorithms for type (e.g., day), duration, intensity, rotational direction, and social aspects (e.g., weekend work) in a nationwide cohort of American manufacturing workers (N = 23,044) between 2003 and 2014. Distributions of working hour characteristics were examined by schedules (e.g., permanent day, day/night) and demographics, and were cross-classified in a matrix to examine co-occurrence. Approximately 55% of shifts may cause circadian rhythm disruption as they were non-day shifts or day shifts with a quick return or rotation, or were 13 h or longer. Older workers, female workers, and White workers worked permanent day shifts most often, while workers of color worked more day/night schedules. Night and evening shifts had more frequent shift rotations, quick returns, and longer hours than day shifts. Yet, day shifts, which are presumed to have little negative circadian impact, may cause circadian rhythm disruption as long hours, quick returns and rotations also occurred within day shifts.

Exposure to Metalworking Fluids and Cancer Incidence in the United Auto Workers-General Motors Cohort.

In previous studies, investigators have reported increased risks of specific cancers associated with exposure to metalworking fluids (MWFs). In this report we broadly examine the incidence of 14 types of cancer, with a focus on digestive, respiratory, and hormonal cancers, in the United Auto Workers-General Motors (UAW-GM) cohort, a cohort of workers exposed to MWFs (1973-2015). The cohort included 39,132 workers followed for cancer incidence. Cox models yielded estimates of adjusted hazard ratios, with categorical variables for lagged cumulative exposure to 3 types of MWF (straight, soluble, and synthetic). We fitted penalized splines to examine the shape of the exposure-response relationships. There were 7,809 incident cancer cases of interest. Oil-based straight and soluble MWFs were each modestly associated with all cancers combined. Exposure-response patterns were consistent with prior reports from this cohort, and results for splined exposures generally reflected their categorically modeled counterparts. We found significantly increased incidence of stomach and kidney cancer with higher levels of straight MWF exposure and increased rectal and prostate cancer with increasing water-based synthetic MWF exposure. Only non-Hodgkin lymphoma and prostate cancer were associated with soluble MWF. All results for colon and lung cancers were null. Our results provide updated evidence for associations between MWF exposure and incidence of several types of cancer.

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.

Occupational risk factors for work disability following carpal tunnel syndrome: a pooled prospective study.

BACKGROUND: Although recent studies have identified important risk factors associated with incident carpal tunnel syndrome (CTS), risk factors associated with its severity have not been well explored. OBJECTIVE: To examine the associations between personal, workplace psychosocial and biomechanical factors and incident work disability among workers with CTS. METHODS: Between 2001 and 2010 five research groups conducted coordinated prospective studies of CTS and related work disability among US workers from various industries. Workers with prevalent or incident CTS (N=372) were followed for up to 6.4 years. Incident work disability was measured as: (1) change in work pace or work quality, (2) lost time or (3) job change following the development of CTS. Psychosocial factors were assessed by questionnaire. Biomechanical exposures were assessed by observation and measurements and included force, repetition, duty cycle and posture. HRs were estimated using Cox models. RESULTS: Disability incidence rates per 100 person-years were 33.2 for changes in work pace or quality, 16.3 for lost time and 20.0 for job change. There was a near doubling of risk for job change among those in the upper tertile of the Hand Activity Level Scale (HR 2.17; 95% CI 1.17 to 4.01), total repetition rate (HR 1.75; 95% CI 1.02 to 3.02), % time spent in all hand exertions (HR 2.20; 95% CI 1.21 to 4.01) and a sixfold increase for high job strain. Sensitivity analyses indicated attenuation due to inclusion of the prevalent CTS cases. CONCLUSION: Personal, biomechanical and psychosocial job factors predicted CTS-related disability. Results suggest that prevention of severe disability requires a reduction of both biomechanical and organisational work stressors.

Metalworking Fluid Exposure and Stroke Mortality Among US Autoworkers.

Although air pollution is an important risk factor for stroke, few studies have considered the impact of workplace exposure to particulate matter (PM). We examined implications of exposure to PM composed of metalworking fluids (MWFs) for stroke mortality in the United Autoworkers-General Motors cohort. Cox proportional hazards models with age as the timescale were used to estimate the association of cumulative straight, soluble, and synthetic MWF exposure with stroke mortality, controlling for sex, race, plant, calendar year, and hire year. Among 38,553 autoworkers followed during 1941-1995, we identified 114 ischemic stroke deaths and 113 hemorrhagic stroke deaths. Overall stroke mortality risk was increased among workers in the middle exposure category for straight MWF (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 0.87, 1.98) and workers in the highest exposure category for synthetic MWF (HR = 1.94, 95% CI: 1.13, 3.16) compared with workers who had no direct exposure. Ischemic stroke mortality risk was increased among workers in the highest exposure categories for straight MWF (HR = 1.45, 95% CI: 0.83, 2.52) and synthetic MWF (HR = 2.39, 95% CI: 1.39, 4.50). We observed no clear relationship between MWF exposure and hemorrhagic stroke mortality. Our results support a potentially important role for occupational PM exposures in stroke mortality and indicate the need for further studies of PM exposure and stroke in varied occupational settings.

End-stage renal disease and metalworking fluid exposure.

OBJECTIVE: Despite increasing prevalence of end-stage renal disease (ESRD), little attention has been directed to how occupational exposures may contribute to risk. Our objective was to investigate the relationship between metalworking fluids (MWF) and ESRD in a cohort of 36 703 male autoworkers. METHODS: We accounted for competing risk of death, using the subdistribution hazard approach to estimate subhazard ratios (sHRs) and 95% CIs in models with cubic splines for cumulative exposure to MWF (straight, soluble or synthetic). RESULTS: Based on 501 ESRD cases and 13 434 deaths, we did not observe an association between MWF and ESRD overall. We observed modest associations between MWF and ESRD classification of glomerulonephritis and diabetic nephropathy. For glomerulonephritis, the 60th percentile of straight MWF was associated with an 18% increased subhazard (sHR=1.18, 95% CI: 0.99 to 1.41). For diabetic nephropathy, the subhazard increased 28% at the 60th percentile of soluble MWF (sHR=1.28, 95% CI: 1.00 to 1.64). Differences by race suggest that black males may have higher disease rates following MWF exposure. CONCLUSIONS: Exposure to straight and soluble MWF may be related to ESRD classification, though this relationship should be further examined.

Working: The Role of Occupational Epidemiology.

The coronavirus disease 2019 (COVID-19) pandemic has redemonstrated the importance of work as a determinant of health. During the pandemic, extant disparities were accentuated as the workforce was divided into the roughly 50% who could safely work from home and those who could not. With the spotlight on work, one might wonder where all the occupational epidemiologists have gone. To answer, we point to diminished research support and more limited workplace access that have led many epidemiologists to shift away from a focus on workers toward other vulnerable populations. Here we build on the renewed interest in work as a driver of health and inequality during the pandemic to highlight contributions of occupational epidemiology to public health. We consider: 1) etiological studies of chronic disease based on employment records to define cohorts and reconstruct long-term exposure; 2) studies of hypothetical interventions that are particularly appropriate for evaluating potential regulations to reduce workplace exposures; and 3) studies of disparities that take advantage of work as a potential source of social stratification and economic opportunity. As we have learned during the COVID-19 pandemic, workplaces can become venues for public health messaging and delivering interventions to enumerated populations of adults. By starting with COVID-19 prevention policies for the workplace, we have a chance to better protect public health.

Racial disparities in alcohol-related liver disease mortality in a 75 year follow-up study of Michigan autoworkers.

BACKGROUND: Suicide, drug overdose, and alcohol-related liver disease (ALD) mortality have been rising in the United States. While suicide and overdose have received a great deal of attention, far less public health concern has focused on chronic ALD. To address this gap, we examine ALD mortality rates, by race, in a cohort of autoworkers to describe trends over the past 75 years, from the peak in automobile manufacturing employment through its decline. METHODS: Based on the United Autoworkers-General Motors (UAW-GM) cohort we estimated temporal trends in age-adjusted ALD mortality rates from 1941 through 2015 at three automobile manufacturing plants in Michigan. We compared these rates to county, state, and U.S. rates, directly standardized to the 2000 U.S. census, to assess the roles of race and employment on ALD mortality. RESULTS: The overall age-adjusted ALD mortality rate among 41,097 male autoworkers peaked at 46.1 per 100,000 in the 1970s, followed by a gradual decline and a recent rise. Rates were slightly higher for black than white men until early 2000s, when rates increased only for white men. ALD mortality rates in the study cohort tracked national, state, and county rates for white men until the most recent time period, but were lower throughout the study period for black men, especially in the 1970s and 1980s. CONCLUSIONS: Employment in automobile manufacturing may have offered some protection against death from ALD for black men, and loss of those manufacturing jobs may have impacted white men without a college degree more in recent decades.

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.

Suicide, overdose and worker exit in a cohort of Michigan autoworkers.

BACKGROUND: In recent decades, suicide and fatal overdose rates have increased in the US, particularly for working-age adults with no college education. The coincident decline in manufacturing has limited stable employment options for this population. Erosion of the Michigan automobile industry provides a striking case study. METHODS: We used individual-level data from a retrospective cohort study of 26 804 autoworkers in the United Autoworkers-General Motors cohort, using employment records from 1970 to 1994 and mortality follow-up from 1970 to 2015. We estimated HRs for suicide or fatal overdose in relation to leaving work, measured as active or inactive employment status and age at worker exit. RESULTS: There were 257 deaths due to either suicide (n=202) or overdose (n=55); all but 21 events occurred after leaving work. The hazard rate for suicide was 16.1 times higher for inactive versus active workers (95% CI 9.8 to 26.5). HRs for suicide were elevated for all younger age groups relative to those leaving work after age 55. Those 30-39 years old at exit had the highest HR for suicide, 1.9 (95% CI 1.2 to 3.0). When overdose was included, the rate increased by twofold for both 19- to 29-year-olds and 30- to 39-year-olds at exit. Risks remained elevated when follow-up was restricted to 5 years after exit. CONCLUSIONS: Autoworkers who left work had a higher risk of suicide or overdose than active employees. Those who left before retirement age had higher rates than those who left after, suggesting that leaving work early may increase the risk.

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.

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.

Layoffs and the mental health and safety of remaining workers: a difference-in-differences analysis of the US aluminium industry.

BACKGROUND: Relatively few studies have examined the effects of layoffs on remaining workers, although the effects of layoffs and downsizing events may extend beyond those employees who lose their jobs. METHODS: We examined the effects of layoffs on mental healthcare utilisation and injury risk among workers at 30 US plants between 2003 and 2013. We defined layoffs as reductions in the hourly workforce of 20% or more at each plant. Using a difference-in-differences approach, we compared the change in outcomes during layoffs versus the same 3-month period 1 year previously, accounting for secular trends with control plants. RESULTS: Our study population included 15 502 workers and 7 layoff events between 2003 and 2013. Layoffs were associated with only minor decreases in injuries (-0.006, 95% CI -0.013 to 0.001). The probability of outpatient visits related to mental health increased by 1% during layoffs (0.010, 95% CI 0.003 to 0.017), and the probability of mental health-related prescriptions increased by 1.4% (0.014, 95% CI -0.0006 to 0.027). Among women, the increase in outpatient visits was more pronounced (0.017, 95% CI 0.003 to 0.031). Increased prescription utilisation appeared attributable primarily to opioid use (0.016, 95% CI 0.005 to 0.027). CONCLUSION: Our results indicate an association between layoffs and remaining workers' mental health and safety, although changes mental healthcare utilisation may reflect both changes in underlying mental health and changes in care-seeking. Future research on concordance of service utilisation and underlying health may yield valuable insight into the experiences employed workers in the wake of layoffs.

Hexane exposure and persistent peripheral neuropathy in automotive technicians.

Automotive technicians are commonly exposed to organic and chlorinated solvents, particularly through use of cleaning products. Mainly during the period 1989-2002, n-hexane was a component of some of these products. In other occupational contexts, n-hexane has been shown to be a cause of peripheral neuropathy. The purpose of the present study was to investigate whether previous exposures to low concentrations of n-hexane were a cause of persistent peripheral neuropathy in automotive technicians. Enrolled in the study were 830 San Francisco Bay Area automotive technicians. Each participant underwent a battery of tests to investigate peripheral nervous system impairment. Test results regressed against estimated hexane and total solvent exposures showed only limited evidence of association with solvent exposures. Exposures to both hexane and general solvents were well below their occupational exposure limits. Generally, our results provide reassurance about persistent peripheral neuropathic effects in automotive technicians who previously used hexane-containing automotive cleaning products. This may reflect repair processes, since the exposures occurred some years previous to the study. However, we cannot exclude the possibility that the absence of observed effect in this study may be attributable to low exposures, exposure misclassification and/or the healthy worker survivor effect.

In utero tobacco smoke exposure, DNA methylation, and asthma in Latino children.

BACKGROUND: Maternal smoking during pregnancy is a risk factor for chronic disease later in life and has been associated with variability of DNA methylation at specific cytosine-phosphate-guanine (CpG) loci. We assessed the role of DNA methylation as a potential mediator of adverse effects of in utero tobacco smoke exposures on asthma outcomes in Latino children from the US mainland and Puerto Rico. METHODS: Relationships between self-reported exposure and DNA methylation at CpG loci previously reported to be associated with maternal smoking were assessed in a subsample consisting of 572 children aged 8-21 years (310 cases with asthma, 262 healthy controls), sampled from a larger asthma case-control study. Subsequently, we assessed associations between top loci and asthma-related outcomes, followed by mediation analysis for loci for which associations with outcomes were observed. RESULTS: Self-reported maternal smoking was associated with a -1.5% (95% confidence interval (CI) = -2.4%, -0.6%) lower methylation at CpG locus cg05575921 on the AHRR gene; a 1% increase in DNA methylation at the same locus resulted in an odds ratio (OR) of 0.90 (95% CI = 0.83, 0.96) for the odds of asthma. The OR for the indirect effect of maternal smoking on asthma mediated through methylation at the cg05575921 locus was 1.18 (95% CI = 1.07, 1.68), compared to the OR for the total effect of exposure in the parent study of 1.48 (95% CI = 1.03, 2.11). CONCLUSIONS: Our findings suggest potential mediation by DNA methylation in the association between maternal smoking during pregnancy and asthma status.

Unconventional natural gas development and adverse birth outcomes in Pennsylvania: The potential mediating role of antenatal anxiety and depression.

BACKGROUND: Studies have reported associations between unconventional natural gas development (UNGD) and adverse birth outcomes. None have evaluated potential mediating mechanisms. OBJECTIVES: To evaluate associations between (1) UNGD and antenatal anxiety and depression and (2) antenatal anxiety and depression and preterm birth (<37 weeks gestation) and reduced term birth weight, (3) stochastic direct and indirect effects of UNGD on preterm birth and term birth weight operating through antenatal anxiety and depression, and (4) effect modification by family-level socioeconomic status. METHODS: This retrospective cohort study included mothers without prevalent anxiety or depression at time of conception, who delivered at Geisinger in Pennsylvania between January 2009-January 2013. We assembled phase-specific UNGD activity data from public sources. Mothers were categorized as exposed (quartile 4) or unexposed (quartiles 1-3) based on average daily inverse distance-squared UNGD activity metric between conception and the week prior to anxiety or depression (cases) or the pregnancy-average daily metric (non-cases). We estimated associations with a doubly robust estimator (targeted minimum loss-based estimation) and adjusted for potential individual- and community-level confounding variables. RESULTS: Analyses included 8,371 births to 7,715 mothers, 12.2% of whom had antenatal anxiety or depression. We found 4.3 additional cases of antenatal anxiety or depression per 100 women (95% CI: 1.5, 7.0) under the scenario where all mothers lived in the highest quartile of UNGD activity versus quartiles 1-3. The risk difference appeared larger among mothers receiving Medical Assistance (indicator of low family income) compared to those who did not, 5.6 (95% CI: 0.5, 10.6) versus 2.9 (95% CI: -0.7, 6.5) additional cases of antenatal anxiety or depression per 100 women. We found no relationship between antenatal anxiety or depression and adverse birth outcomes and no mediation effect either overall or when stratifying by Medical Assistance. CONCLUSION: We observed a relationship between UNGD activity and antenatal anxiety and depression, which did not mediate the overall association between UNGD activity and adverse birth outcomes.

Ambient air pollution, asthma drug response, and telomere length in African American youth.

BACKGROUND: Telomere length (TL) can serve as a potential biomarker for conditions associated with chronic oxidative stress and inflammation, such as asthma. Air pollution can induce oxidative stress. Understanding the relationship between TL, asthma, and air pollution is important for identifying risk factors contributing to unhealthy aging in children. OBJECTIVES: We sought to investigate associations between exposures to ambient air pollutants and TL in African American children and adolescents and to examine whether African ancestry, asthma status, and steroid medication use alter the association. METHODS: Linear regression was used to examine associations between absolute telomere length (aTL) and estimated annual average residential ozone (O3) and fine particulate matter with a diameter of 2.5 µm or less (PM2.5) exposures in a cross-sectional analysis of 1072 children in an existing asthma case-control study. African ancestry, asthma status, and use of steroid medications were examined as effect modifiers. RESULTS: Participants' aTLs were measured by using quantitative PCR. A 1-ppb and 1 µg/m3 increase in annual average exposure to O3 and PM2.5 were associated with a decrease in aTL of 37.1 kilo-base pair (kb; 95% CI, -66.7 to -7.4 kb) and 57.1 kb (95% CI, -118.1 to 3.9 kb), respectively. African ancestry and asthma were not effect modifiers; however, exposure to steroid medications modified the relationships between TL and pollutants. Past-year exposure to O3 and PM2.5 was associated with shorter TLs in patients without steroid use. CONCLUSION: Exposure to air pollution was associated with shorter TLs in nonasthmatic children and adolescents. This was not the case for asthmatic children as a group, but those receiving steroid medication had less shortening than those not using steroids. Reduced exposure to air pollution in childhood might help to preserve TL.