Contributions of neighborhood physical and social environments to racial and ethnic disparities in birth outcomes in California: A mediation analysis.

BACKGROUND: Racially minoritized populations experience higher rates of adverse birth outcomes than White populations in the U.S. We estimated the mediating effect of neighborhood social and physical environments on disparities in adverse birth outcomes in California. METHOD: We used birthing parent's residential address for California live birth records from 2019 to estimate census block group Area Deprivation Index and census tract level measures of ambient fine particulate matter (PM2.5), drinking water contamination, tree canopy coverage, as a measure of greenspace, potential heat vulnerability, and noise. We performed mediation analysis to assess whether neighborhood factors explain racial/ethnic disparities in preterm birth (PTB) and term-birth low birth weight (TLBW) comparing Black, Latinx, and Asian with White births after controlling for individual-level factors. RESULTS: Black, Latinx, and Asian parents had PTB rates that were 67%, 36%, and 11% higher, and TLBW rates that were 150%, 38%, and 81% higher than Whites. Neighborhood deprivation contributed 7% (95% CI: 3%, 11%) to the Black-White and 9% (95% CI: 6%, 12%) to the Latinx-White disparity in PTB, and 8% (95% CI: 3%, 12%) of the Black-White and 9% (95% CI: 5%, 15%) of the Latinx-White disparity in TLBW. Drinking water contamination contributed 2% (95% CI: 1%, 4%) to the Latinx-White disparity in PTB. Lack of greenspace accounted for 7% (95% CI: 2%, 10%) of the Latinx-White PTB disparity and 7% (95% CI: 3%, 12%) of the Asian-White PTB disparity. PM2.5 contributed 11% (95% CI: 5%, 18%), drinking water contamination contributed 3% (95% CI: 1%, 7%), and potential heat vulnerability contributed 2% (95% CI: 1%, 3%) to the Latinx-White TLBW disparity. Lack of green space contributed 3% (95% CI: 1%, 6%) to the Asian-White TLBW disparity. CONCLUSIONS: Our study suggests social environments explain portions of Black/Latinx-White disparities while physical environments explain Latinx/Asian-White disparities in PTB and TLBW.

Pre-Conception And First Trimester Exposure To Pesticides And Associations With Stillbirth.

Associations of pesticide exposures during pre-conception with stillbirth have not been well explored. We linked Arizona pesticide use records with birth certificates from 2006-2020 and estimated associations of living within 500meters of any pyrethroid, organophosphate (OP), or carbamate pesticide applications during a 90 day pre-conception window or the first trimester, with stillbirth. We considered a binary measure of exposure (any exposure), as well as log-pounds and log-acres applied within 500m, in a negative control exposure framework with log-binomial regression. We included 1,237,750 births, 2,290 stillbirths, and 27 pesticides. During pre-conception, any exposure to pesticides were associated with stillbirth, including cyfluthrin (RR=1.97, 95% CI 1.17,3.32), zeta-cypermethrin (RR=1.81, 95%CI 1.20, 2.74), organophosphates as a class (RR=1.60, 95%CI 1.16, 2.19), malathion (RR=2.02, 95%CI 1.26, 3.24), carbaryl (RR=6.39, 95%CI 2.07, 19.74), and propamocarb hydrochloride (RR=7.72, 95%CI 1.10, 54.20) . During the first trimester, fenpropathrin (RR=4.36, 95%CI 1.09, 17.50), permethrin (RR=1.57, 95%CI 1.02, 2.42), organophosphates as a class (RR=1.50, 95%CI 1.11, 2.01), acephate (RR=2.31, 95%CI 1.22, 4.40), and formetanate hydrochloride (RR=7.22, 95%CI 1.03, 50.58) were associated with stillbirth. Interpretations were consistent when using continuous measures of pounds or acres of exposure. Pesticide exposures during pre-conception and first trimester may be associated with stillbirth.

High Traffic Roads and Adverse Birth Outcomes: Comparing Births Upwind and Downwind of the Same Road.

Traffic related air pollution is a major concern for perinatal health. Determining causal associations, however, is difficult since high-traffic areas tend to correspond with lower socioeconomic neighborhoods and other environmental exposures. To overcome confounding, we compared pregnant individuals living downwind and upwind of the same high-traffic road. We leveraged vital statistics data for Texas from 2007-2016 (n=3,570,272 births) and computed hourly wind estimates for residential addresses within 500 m of high-traffic roads (i.e., annual average daily traffic greater than 25,000) (10.9% of births). We matched pregnant individuals predominantly upwind to pregnant neighbors downwind of the same road segment (n=37,631 pairs). Living downwind was associated with an 11.6 gram (95% CI: -18.01, -5.21) decrease in term birth weight. No associations were observed with low term birth weight, preterm birth, or very preterm birth. In distance-stratified models, living downwind within 50 m was associated with a -36.3 gram (95% CI: -67.74, -4.93) decrease in term birth weight and living 51-100m downwind was associated with an odds ratio of 3.68 (95% CI: 1.71, 7.90) for very preterm birth. These results suggest traffic air pollution is associated with adverse birth outcomes, with steep distance decay gradients around major roads.

Ambient exposure to fine particulate matter with oxidative potential affects oxidative stress biomarkers in pregnancy.

Prenatal exposures to ambient particulate matter (PM2.5) from traffic may generate oxidative stress, and thus contribute to adverse birth outcomes. We investigated whether PM2.5 constituents from brake and tire wear affect levels of oxidative stress biomarkers (malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG)) using urine samples collected up to three times during pregnancy in 156 women recruited from antenatal clinics at the University of California Los Angeles. Land use regression models with co-kriging were employed to estimate average residential outdoor concentrations of black carbon (BC), PM2.5 mass, PM2.5 metal components, and three PM2.5 oxidative potential metrics during the 4-weeks prior to urine sample collection. 8-OHdG concentrations in mid-pregnancy increased by 24.8% (95% CI: 9.0, 42.8) and 14.3% (95% CI: 0.4%, 30.0%) per interquartile range (IQR) increase in PM2.5 mass and BC, respectively. The brake wear marker (barium) and the oxidative potential metrics were associated with increased MDA concentration in the 1st sample collected (10-17 gestational week), but 95% CIs included the null. Traffic-related air pollution contributed in early to mid-pregnancy to oxidative stress generation previously linked to adverse birth outcomes.

A call from 40 public health scientists for an end to the continuing humanitarian and environmental catastrophe in Gaza.

An under-recognised aspect of the current humanitarian catastrophe in Gaza is the impact of the war on the environment and the associated risks for human health. This commentary contextualises these impacts against the background of human suffering produced by the overwhelming violence associated with the use of military force against the general population of Gaza. In calling for an immediate cessation to the violence, the authors draw attention to the urgent need to rebuild the health care system and restore the physical and human infrastructure that makes a liveable environment possible and promotes human health and well-being, especially for the most vulnerable in the population. Environmental remediation should therefore form one of the most important parts of international efforts to assist reconstruction, through which we hope Palestinians and Israelis will achieve lasting peace, health, and sustainable development, all as part of accepted international human rights obligations.

Genome-wide meta-analysis of short-tandem repeats for Parkinson's disease risk using genotype imputation.

Idiopathic Parkinson's disease is determined by a combination of genetic and environmental factors. Recently, the first genome-wide association study on short-tandem repeats in Parkinson's disease reported on eight suggestive short-tandem repeat-based risk loci (α = 5.3 × 10-6), of which four were novel, i.e. they had not been implicated in Parkinson's disease risk by genome-wide association analyses of single-nucleotide polymorphisms before. Here, we tested these eight candidate short-tandem repeats in a large, independent Parkinson's disease case-control dataset (n = 4757). Furthermore, we combined the results from both studies by meta-analysis resulting in the largest Parkinson's disease genome-wide association study of short-tandem repeats to date (n = 43 844). Lastly, we investigated whether leading short-tandem repeat risk variants exert functional effects on gene expression regulation based on methylation quantitative trait locus data in human 'post-mortem' brain (n = 142). None of the eight previously reported short-tandem repeats were significantly associated with Parkinson's disease in our independent dataset after multiple testing correction (α = 6.25 × 10-3). However, we observed modest support for short-tandem repeats near CCAR2 and NCOR1 in the updated meta-analyses of all available data. While the genome-wide meta-analysis did not reveal additional study-wide significant (α = 6.3 × 10-7) short-tandem repeat signals, we identified seven novel suggestive Parkinson's disease short-tandem repeat risk loci (α = 5.3 × 10-6). Of these, especially a short-tandem repeat near MEIOSIN showed consistent evidence for association across datasets. CCAR2, NCOR1 and one novel suggestive locus identified here (LINC01012) emerged from colocalization analyses showing evidence for a shared causal short-tandem repeat variant affecting both Parkinson's disease risk and cis DNA methylation in brain. Larger studies, ideally using short-tandem repeats called from whole-sequencing data, are needed to more fully investigate their role in Parkinson's disease.

Untargeted serum metabolic profiling of diabetes mellitus among Parkinson's disease patients.

Type 2 diabetes mellitus (T2DM) is a common comorbidity among Parkinson's disease (PD) patients. Yet, little is known about dysregulated pathways that are unique in PD patients with T2DM. We applied high-resolution metabolomic profiling in serum samples of 636 PD and 253 non-PD participants recruited from Central California. We conducted an initial discovery metabolome-wide association and pathway enrichment analysis. After adjusting for multiple testing, in positive (or negative) ion mode, 30 (25) metabolic features were associated with T2DM in both PD and non-PD participants, 162 (108) only in PD participants, and 32 (7) only in non-PD participants. Pathway enrichment analysis identified 17 enriched pathways associated with T2DM in both the PD and non-PD participants, 26 pathways only in PD participants, and 5 pathways only in non-PD participants. Several amino acid, nucleic acids, and fatty acid metabolisms were associated with T2DM only in the PD patient group suggesting a possible link between PD and T2DM.

Trends in the Prevalence of Autism Spectrum Disorder in California: Disparities by Sociodemographic Factors and Region Between 1990-2018.

Autism Spectrum Disorders (ASD) prevalence has risen globally, with regional variation and sociodemographic disparities affecting diagnosis and intervention. This study examines ASD trends from 1990 to 2018 in California (CA), focusing on sociodemographic factors that may inform policy/interventions. Using CA Department of Public Health birth records (1990-2018) and Developmental Services ASD cases (1994-2022), we analyzed diagnosis incidence by age 4 or 8, stratified by sociodemographic and regional factors. From 1990 to 2018, for each birth year the cumulative incidence of ASD by 4 and 8 years of age in CA increased while the diagnosis age decreased. Distinct patterns emerged over these three decades. Children born to White and Asian and Pacific Islander (API) mothers, or to mothers with higher education or living in high socioeconomic status (SES) neighborhoods exhibited higher ASD cumulative incidences throughout the 1990s and early 2000s. However, in the mid-2000s, ASD incidence in children born to Black or Hispanic mothers, with low education, or living in low SES neighborhoods surpassed that of White/API children or those living in high SES neighborhoods. Black or Hispanic children now have the highest ASD cumulative incidence, even though age at first diagnosis remains lowest in high SES regions, for the highly educated, and for White/API children. ASD cumulative incidence in CA from 1990 to 2018 exhibited demographic reversals with higher rates in children born to Black or Hispanic mothers or lower SES neighborhoods. Black and Hispanic children still have delayed age at diagnosis compared to White/API children.

Effects of hypertension and use of antihypertensive drugs in pregnancy on the risks of childhood cancers in Taiwan.

BACKGROUND: Childhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks. OBJECTIVE: This population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring. METHODS: Data on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers. RESULTS: Offspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth. CONCLUSIONS: In this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

Diet and the gut microbiome in patients with Parkinson's disease.

It has been suggested that gut microbiota influence Parkinson's disease (PD) via the gut-brain axis. Here, we examine associations between diet and gut microbiome composition and its predicted functional pathways in patients with PD. We assessed gut microbiota in fecal samples from 85 PD patients in central California using 16S rRNA gene sequencing. Diet quality was assessed by calculating the Healthy Eating Index 2015 (HEI-2015) based on the Diet History Questionnaire II. We examined associations of diet quality, fiber, and added sugar intake with microbial diversity, composition, taxon abundance, and predicted metagenomic profiles, adjusting for age, sex, race/ethnicity, and sequencing platform. Higher HEI scores and fiber intake were associated with an increase in putative anti-inflammatory butyrate-producing bacteria, such as the genera Butyricicoccus and Coprococcus 1. Conversely, higher added sugar intake was associated with an increase in putative pro-inflammatory bacteria, such as the genera Klebsiella. Predictive metagenomics suggested that bacterial genes involved in the biosynthesis of lipopolysaccharide decreased with higher HEI scores, whereas a simultaneous decrease in genes involved in taurine degradation indicates less neuroinflammation. We found that a healthy diet, fiber, and added sugar intake affect the gut microbiome composition and its predicted metagenomic function in PD patients. This suggests that a healthy diet may support gut microbiome that has a positive influence on PD risk and progression.

Urinary polycyclic aromatic hydrocarbon metabolites and their association with oxidative stress among pregnant women in Los Angeles.

Background: Polycyclic aromatic hydrocarbons (PAHs) have been linked to adverse birth outcomes, but few epidemiological studies to date have evaluated associations between urinary PAH metabolites and oxidative stress biomarkers in pregnancy. Methods: We measured a total of 7 PAH metabolites and 2 oxidative stress biomarkers (malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG)) in urine samples collected up to three times during pregnancy in 159 women enrolled at antenatal clinics at the University of California Los Angeles during 2016-2019. Using multiple linear regression models, we estimated the percentage change (%) and 95% confidence interval (CI) in 8-OHdG and MDA measured at each sample collection time per doubling of PAH metabolite concentrations. Results: Most PAH metabolites were positively associated with both urinary oxidative stress biomarkers, MDA and 8-OHdG, with stronger associations in early and late pregnancy. Women pregnant with male fetuses exhibited slightly larger increases in both MDA and 8-OHdG in association with PAH exposures in early and late pregnancy. Conclusion: Urinary OH-PAH biomarkers are associated with increases in oxidative stress during pregnancy, especially in early and late pregnancy. Sex differences in associations between PAH exposures and oxidative stress need to be further explored in the future.

Exposure to outdoor ambient air toxics and risk of breast cancer: The multiethnic cohort.

BACKGROUND: A growing literature has reported associations between traffic-related air pollution and breast cancer, however there are fewer investigations into specific ambient agents and any putative risk of breast cancer development, particularly studies occurring in populations residing in higher pollution areas such as Los Angeles. OBJECTIVES: To estimate breast cancer risks related to ambient air toxics exposure at residential addresses. METHODS: We examined the relationships between ambient air toxics and breast cancer risk in the Multiethnic Cohort among 48,665 California female participants followed for cancer from 2003 through 2013. We obtained exposure data on chemicals acting as endocrine disruptors or mammary gland carcinogens from the National-Scale Air Toxics Assessment. Cox proportional hazards models were used to estimate breast cancer risk per one interquartile range (IQR) increase in air toxics exposure lagged by 5-years. Stratified analyses were conducted by race, ethnicity, and hormone receptor types. RESULTS: Among all women, increased risks of invasive breast cancer were observed with toxicants related to industries [1,1,2,2-tetrachloroethane (hazard ratio [HR] = 4.22, 95% confidence interval [95% CI] 3.18-5.60), ethylene dichloride (HR = 2.81, 95% CI 2.20-3.59), and vinyl chloride (HR = 2.27, 95% CI 1.81, 2.85); these 3 agents were correlated (r2 = 0.45-0.77)]. Agents related to gasoline production or combustion were related to increased breast cancer risk [benzene (HR = 1.32, 95% CI 1.24, 1.41), ethylbenzene (HR = 1.20, 95% CI 1.13-1.28), toluene (HR = 1.29, 95% CI 1.20-1.38), naphthalene (HR = 1.11, 95% CI 1.02-2.22), acrolein (HR = 2.26, 95% CI 1.92, 2.65)]. Higher hazard ratios were observed in African Americans and Whites compared to other racial and ethnic groups (p-heterogeneity <0.05 for traffic-related air toxics, acrolein, and vinyl acetate). CONCLUSIONS: Our findings suggest that specific toxic air pollutants may be associated with increase breast cancer risk.

Ambient long-term exposure to organophosphorus pesticides and the human gut microbiome: an observational study.

BACKGROUND: Organophosphorus pesticides (OP) have been associated with various human health conditions. Animal experiments and in-vitro models suggested that OP may also affect the gut microbiota. We examined associations between ambient chronic exposure to OP and gut microbial changes in humans. METHODS: We recruited 190 participants from a community-based epidemiologic study of Parkinson's disease living in a region known for heavy agricultural pesticide use in California. Of these, 61% of participants had Parkinson's disease and their mean age was 72 years. Microbiome and predicted metagenome data were generated by 16S rRNA gene sequencing of fecal samples. Ambient long-term OP exposures were assessed using pesticide application records combined with residential addresses in a geographic information system. We examined gut microbiome differences due to OP exposures, specifically differences in microbial diversity based on the Shannon index and Bray-Curtis dissimilarities, and differential taxa abundance and predicted Metacyc pathway expression relying on regression models and adjusting for potential confounders. RESULTS: OP exposure was not associated with alpha or beta diversity of the gut microbiome. However, the predicted metagenome was sparser and less evenly expressed among those highly exposed to OP (p = 0.04). Additionally, we found that the abundance of two bacterial families, 22 genera, and the predicted expression of 34 Metacyc pathways were associated with long-term OP exposure. These pathways included perturbed processes related to cellular respiration, increased biosynthesis and degradation of compounds related to bacterial wall structure, increased biosynthesis of RNA/DNA precursors, and decreased synthesis of Vitamin B1 and B6. CONCLUSION: In support of previous animal studies and in-vitro findings, our results suggest that ambient chronic OP pesticide exposure alters gut microbiome composition and its predicted metabolism in humans.

Lysosomal genes contribute to Parkinson's disease near agriculture with high intensity pesticide use.

Parkinson's disease (PD), the second most common neurodegenerative disorder, develops sporadically, likely through a combination of polygenic and environmental factors. Previous studies associate pesticide exposure and genes involved in lysosomal function with PD risk. We evaluated the frequency of variants in lysosomal function genes among patients from the Parkinson's, Environment, and Genes (PEG) study with ambient pesticide exposure from agricultural sources. 757 PD patients, primarily of White European/non-Hispanic ancestry (75%), were screened for variants in 85 genes using a custom amplicon panel. Variant enrichment was calculated against the Genome Aggregation Database (gnomAD). Enriched exonic variants were prioritized by exposure to a cluster of pesticides used on cotton and severity of disease progression in a subset of 386 patients subdivided by race/ethnicity. Gene enrichment analysis identified 36 variants in 26 genes in PEG PD patients. Twelve of the identified genes (12/26, 46%) had multiple enriched variants and/or a single enriched variant present in multiple individuals, representing 61% (22/36) of the observed variation in the cohort. The majority of enriched variants (26/36, 72%) were found in genes contributing to lysosomal function, particularly autophagy, and were bioinformatically deemed functionally deleterious (31/36, 86%). We conclude that, in this study, variants in genes associated with lysosomal function, notably autophagy, were enriched in PD patients exposed to agricultural pesticides suggesting that altered lysosomal function may generate an underlying susceptibility for developing PD with pesticide exposure. Further study of gene-environment interactions targeting lysosomal function may improve understanding of PD risk in individuals exposed to pesticides.

Roadway construction as a natural experiment to examine air pollution impacts on infant health.

Traffic-related air pollution (TRAP) poses a significant public health risk that is associated with adverse birth outcomes. Large roadway infrastructure projects present a natural experiment to examine how resulting congestion change is associated with adverse birth outcomes for nearby populations. This study is designed to examine the influence of living close to a roadway before, during, and after a construction project using a difference-in-differences design. We integrated data on all large roadway construction projects (defined as widening of existing roads, building new roads, improving bridges, installing intelligent transportation systems, improving intersections, and installing or upgrading traffic signals) in Texas from 2007 to 2016 with Vital Statistic data for all births with residential addresses within 1 km of construction projects. Our outcomes included term low birth weight, term birth weight, preterm birth, and very preterm birth. Using a difference-in-differences design, we included births within 3 years of construction start and 2 years of construction end. In our main model, the exposed group is limited to pregnant individuals residing within 300 m of a construction project, and the control group includes those living within 300-1000 m from a project. We used regression models to estimate the influence of construction on infant health. We included 1,360 large roadway construction projects linked to 408,979 births. During construction, we found that the odds of term low birth weight increased by 19% (95% CI: 1.05, 1.36). However, we saw little evidence of an association for other birth outcomes. Contrary to our hypothesis of decreased TRAP after construction ends, we did not observe consistent improvements post-construction for pregnant individuals living within 300 m. Continued consideration of the influence of traffic congestion programs on birth outcomes is necessary to inform future policy decisions.

Associations between brake and tire wear-related PM2.5 metal components, particulate oxidative stress potential, and autism spectrum disorder in Southern California.

BACKGROUND: Air pollution is a global health concern, with fine particulate matter (PM2.5) constituents posing potential risks to human health, including children's neurodevelopment. Here we investigated associations between exposure during pregnancy and infancy to specific traffic-related PM2.5 components with Autism Spectrum Disorder (ASD) diagnosis. METHODS: For exposure assessment, we estimated PM2.5 components related to traffic exposure (Barium [Ba] as a marker of brake dust and Zinc [Zn] as a tire wear marker, Black Carbon [BC]) and oxidative stress potential (OSP) markers (Hydroxyl Radical [OPOH] formation, Dithiothreitol activity [OPDTT], reactive oxygen species [ROS]) modeled with land use regression with co-kriging based on an intensive air monitoring campaign. We assigned exposures to a cohort of 444,651 children born in Southern California between 2016 and 2019, among whom 11,466 ASD cases were diagnosed between 2018 and 2022, Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained with logistic regression for single pollutant and PM2.5 mass co-adjusted models, also adjusting for sociodemographic characteristics. RESULTS: Among PM2.5 components, we found the strongest positive association with ASD for our brake wear marker Ba (ORper IQR = 1.29, 95 % CI: 1.24, 1.34). This was followed by an increased risk for all PM2.5 oxidative stress potential markers; the strongest association was with ROS formation (ORper IQR = 1.22, 95 % CI: 1.18, 1.25). PM2.5 mass was linked to ASD in Hispanic and Black children, but not White children, while traffic-related PM2.5 and OSP markers increased ASD risk across all groups. In neighborhoods with the lowest socioeconomic status (SES), associations with ASD were stronger for all examined pollutants compared to higher SES areas. CONCLUSIONS: Our findings suggest that brake wear-related PM2.5 and PM2.5 OSP are associated with ASD diagnosis in Southern California. These results suggest that strategies aimed at reducing the public health impacts of PM2.5 need to consider specific sources.

Association between Airport Ultrafine Particles and Lung Cancer Risk: The Multiethnic Cohort Study.

BACKGROUND: Ultrafine particles (UFP) are unregulated air pollutants abundant in aviation exhaust. Emerging evidence suggests that UFPs may impact lung health due to their high surface area-to-mass ratio and deep penetration into airways. This study aimed to assess long-term exposure to airport-related UFPs and lung cancer incidence in a multiethnic population in Los Angeles County. METHODS: Within the California Multiethnic Cohort, we examined the association between long-term exposure to airport-related UFPs and lung cancer incidence. Multivariable Cox proportional hazards regression models were used to estimate the effect of UFP exposure on lung cancer incidence. Subgroup analyses by demographics, histology and smoking status were conducted. RESULTS: Airport-related UFP exposure was not associated with lung cancer risk [per one IGR HR, 1.01; 95% confidence interval (CI), 0.97-1.05] overall and across race/ethnicity. A suggestive positive association was observed between a one IQR increase in UFP exposure and lung squamous cell carcinoma (SCC) risk (HR, 1.08; 95% CI, 1.00-1.17) with a Phet for histology = 0.05. Positive associations were observed in 5-year lag analysis for SCC (HR, 1.12; 95% CI, CI, 1.02-1.22) and large cell carcinoma risk (HR, 1.23; 95% CI, 1.01-1.49) with a Phet for histology = 0.01. CONCLUSIONS: This large prospective cohort analysis suggests a potential association between airport-related UFP exposure and specific lung histologies. The findings align with research indicating that UFPs found in aviation exhaust may induce inflammatory and oxidative injury leading to SCC. IMPACT: These results highlight the potential role of airport-related UFP exposure in the development of lung SCC.

Maternal autoimmune disease and its association with childhood cancer: A population-based case-control study in Denmark.

Background: Autoimmune diseases have been linked to an increased risk of pregnancy-related complications. A family history of autoimmune diseases may be related to the risk of childhood cancer based on similar histocompatibility antigens. We utilized data from national registries in Denmark to examine associations between maternal autoimmune disease and cancer in their offspring. Methods: We linked data from several national registries in Denmark to identify childhood cancer cases in children <20 years diagnosed between 1977 to 2016. Controls were selected from the Central Population Register and matched to cases by birth year and sex (25:1). Mothers with autoimmune disease diagnosed in pregnancy or prior were identified from the National Patient Register. Multivariable conditional logistic regression analyses were used to estimate associations between maternal autoimmune diseases and childhood cancer in offspring. Results: Autoimmune diseases (all types) were positively associated with all childhood cancers combined (Odds Ratio (OR) = 1.25, 95% CI 1.06, 1.47), acute lymphoblastic leukemia (OR =1.52, 95% CI 1.09, 2.13), Burkitt lymphoma (OR = 2.69, 95% CI 1.04, 6.97), and central nervous system tumors (OR = 1.45, 95% CI 1.06, 1.99), especially astrocytoma (OR = 2.27, 95% CI 1.36, 3.77) and glioma (OR = 1.75, 95% CI 1.13, 2.73). When we examined mothers with rheumatoid arthritis, we observed an increased association for all cancers (OR = 2.15, 95% CI 1.40, 3.30), acute lymphoblastic leukemia (OR = 3.55, 95% CI 1.69, 7.47), and central nervous system tumors (OR = 2.91, 95% CI 1.46, 5.82), especially glioma (OR = 3.58, 95% CI 1.40, 9.18) in offspring. Conclusion: There is a positive association between maternal autoimmune disease and childhood cancer. This association is especially prominent in the offspring of women with rheumatoid arthritis.

Agricultural paraquat dichloride use and Parkinson's disease in California's Central Valley.

BACKGROUND: Paraquat dichloride is currently among the most widely used commercial herbicides in the USA. In the present study, we provide epidemiological assessment of ambient paraquat exposure and Parkinson's disease (PD) risk in a population-based study of PD in agricultural regions of Central California. METHODS: Based on 829 PD patients and 824 community controls, we assessed associations between ambient paraquat dichloride exposure and PD. We estimated residential and workplace proximity to commercial agricultural applications in three California counties since 1974 using the CA pesticide use reporting (PUR) data and land use maps. We evaluated any, duration and average intensity [pounds (0.45 kilograms) per acre per year] of exposure for paraquat in four time windows. RESULTS: Ambient paraquat exposure assessed at both residence and workplace was associated with PD, based on several different exposure measures. The PD patients both lived and worked near agricultural facilities applying greater amounts of the herbicide than community controls. For workplace proximity to commercial applications since 1974, working near paraquat applications every year in the window [odds ratio (OR) = 2.15, 95% confidence interval (CI) = 1.46, 3.19] and a higher average intensity of exposure [per 10 pounds (4.54 kilograms), OR = 2.08, 95% CI = 1.31, 3.38] were both associated with an increased odds of PD. Similar associations were observed for residential proximity (duration: OR = 1.91, 95% CI = 1.30, 2.83; average intensity: OR = 1.72, 95% CI = 0.99, 3.04). Risk estimates were comparable for men and women, and the strongest odds were observed for those diagnosed at ≤60 years of age. CONCLUSION: This study provides further indication that paraquat dichloride exposure increases the risk of Parkinson's disease.

Association between ambient exposure to PM2.5 and upper aerodigestive tract cancer in Los Angeles.

Fine particulate matter (PM2.5 ) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking-related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never-smokers. Therefore, it is imperative to understand the relation between ambient PM2.5 exposure and risk of UADT cancers. A population-based case-control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004. The average residential PM2.5 concentration 1 year before the diagnosis date for cases and the reference date for controls was assessed using a chemical transport model. The association between ambient PM2.5 and the UADT cancers was estimated by unconditional logistic regression, adjusting for confounders at the individual and block-group level. Stratified analyses were conducted by sex, tobacco smoking status and UADT subsites. We also assessed the interaction between PM2.5 and tobacco smoking on UADT cancers. PM2.5 concentrations were associated with an elevated odds of UADT cancers (adjusted odds ratio = 1.21 per interquartile range [4.5 µg/m3 ] increase; 95% confidence interval: 1.02, 1.44). The association between PM2.5 and UADT cancers was similar across UADT subsites, sex and tobacco smoking status. The interaction between PM2.5 and tobacco smoking on UADT cancers was approximately additive on the odds scale. The effect estimate for PM2.5 and UADT cancers was similar among never smokers. Our findings support the hypothesis that exposure to PM2.5 increases the risk of UADT cancers. Improvements in air quality may reduce the risk of UADT cancers.