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.

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

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

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

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

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.

Metalworking fluids and cancer mortality in a US autoworker cohort (1941-2015).

Objectives This report describes the extended follow-up (1941-2015) of a cohort of 38 549 automobile manufacturing workers with potential exposure to metalworking fluids (MWF). The outcomes of interest were mortality from cancers of the esophagus, stomach, intestine, rectum, bladder, liver, pancreas, larynx, lung, skin, prostate, brain, and female breast, as well as leukemia. This report includes 5472 deaths from cancer, more than ten times the numbers of deaths in our last summary report published 20 years ago. Methods Standardized mortality ratios were computed for the entire study period. Adjusted hazard ratios (HR) were estimated in Cox proportional hazard models with categorical variables for cumulative exposure to each type of MWF. Results Exposure-response patterns are consistent with prior mortality reports from this cohort. We found increased risk of skin and female breast cancer with straight fluids. For the first time, we found elevated risk of stomach cancer mortality. Overall, many of the exposure-response results did not suggest an association with MWF. Conclusions Mortality is a poor proxy for cancer diagnosis for treatable cancers and not the optimal outcome measure in etiological studies. Although the HR presented here handle bias from the healthy worker hire effect and left truncation, they do not handle bias from healthy worker survivor effect, which likely results in underestimates of the health impacts of MWF. Although this updated summary provides some information on the risk of cancer from MWF, targeted future analyses will help clarify associations.

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.

Age, period, and cohort effects in adult lifetime asthma prevalence in California: an application of hierarchical age-period-cohort analysis.

PURPOSE: Using 27 years of survey data, the contributions of age, period, and cohort effects on the increase in adult lifetime asthma prevalence in California were examined. METHODS: Lifetime asthma diagnosis for adults was assessed in 1984-1992 and 1995-2011 through the California Behavioral Risk Factor Surveillance System, an annual, cross-sectional, population-based survey (n = 144,100). Using date of survey and date of birth, we classified 18,305 adult respondents with lifetime asthma into 7 age groups, 6 periods, and 17 cohorts. Using hierarchical, cross-classified random effects models, birth cohort, period, and age patterns in adult lifetime asthma prevalence were analyzed. RESULTS: After adjusting for sex, ethnicity, education, and smoking, age effects peak in young adulthood, flatten from 40 to 60 years old, and then decrease in older adulthood. A significant positive trend in asthma prevalence was observed in the two earliest survey periods (1984-1993; P value < .0001). Survey period trends appear to flatten beginning in 2004. Although the overall birth cohort effect was statistically significant, the magnitude of the effect for each birth cohort category was small (P value = .0005). CONCLUSIONS: We observed that strong age and period effects have been driving the increase in lifetime asthma prevalence in California over the past 3 decades.

Prevalence of work-related asthma in Michigan, Minnesota, and Oregon.

INTRODUCTION: Adults who have asthma that is caused or aggravated by triggers at work experience a reduced quality of life. In this study, the authors sought to estimate the proportion of asthma that is associated with work using a state-based survey of adults with asthma. METHODS: In 2005, Michigan, Minnesota, and Oregon piloted the Behavioral Risk Factor Surveillance System Adult Asthma Call-Back Survey, with sample sizes of 867, 469, and 1072, respectively. Six questions addressing work-related asthma (WRA) were analyzed to generate estimates of the proportion of adult asthma that is work-related and compare those with and without WRA. RESULTS: Over half of all adults with asthma (53%) reported that their asthma was caused or made worse by any job they ever had, and among these respondents reporting WRA, only 21.5% to 25.1% reported ever telling or being told by a health professional that their asthma was work-related. Additionally, adults with WRA consistently reported poorer asthma control and higher health care utilization than adults with non-WRA. CONCLUSIONS: WRA is a common but frequently unrecognized health problem, and this lack of recognition might contribute to poorer asthma control among adults with WRA. Because early recognition, treatment, and management of WRA are crucial for improving long-term prognosis, clinicians need to include assessment of workplace triggers in both their diagnostic and treatment plans for adult patients with asthma.