Genetic variant rs1205 is associated with COVID-19 outcomes: The Strong Heart Study and Strong Heart Family Study.

BACKGROUND: Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205. METHODOLOGY/PRINCIPAL FINDINGS: The Strong Heart and Strong Heart Family studies have accumulated detailed genetic, cardiovascular risk and event data in geographically dispersed American Indian communities since 1988. Genotypic data and 91 COVID-19 adjudicated deaths or hospitalizations from 2/1/20 through 3/1/23 were identified among 3,780 participants in two subsets. Among 21 candidate variants including genes in the interferon response pathway, APOE, TMPRSS2, TLR3, the HLA complex and the ABO blood group, only rs1205, a 3' untranslated region variant in the CRP gene, showed nominally significant association in T-dominant model analyses (odds ratio 1.859, 95%CI 1.001-3.453, p = 0.049) after adjustment for age, sex, center, body mass index, and a history of cardiovascular disease. Within the younger subset, association with the rs1205 T-Dom genotype was stronger, both in the same adjusted logistic model and in the SOLAR analysis also adjusting for other genetic relatedness. CONCLUSION: A T-dominant genotype of rs1205 in the CRP gene is associated with COVID-19 death or hospitalization, even after adjustment for relevant clinical factors and potential participant relatedness. Additional study of other populations and genetic variants of this gene are warranted.

Preterm Birth and Metal Mixture Exposure among Pregnant Women from the Navajo Birth Cohort Study.

BACKGROUND: Preterm birth (PTB), defined as birth before 37 wk gestation, is associated with hypertension, diabetes, inadequate prenatal care, unemployment or poverty, and metal exposure. Indigenous individuals are more likely to have maternal risk factors associated with PTB compared with other populations in the United States; however, the role of environmental metals on PTB among pregnant Indigenous women remains uncertain. Previous research identified associations between PTB and individual metals, but there is limited investigation on metal mixtures and this birth outcome. OBJECTIVES: We used a mixtures analysis framework to investigate the association between metal mixtures and PTB among pregnant Indigenous women from the Navajo Birth Cohort Study (NBCS). METHODS: Maternal urine and blood samples were collected at the time of study enrollment and analyzed for metals by inductively coupled plasma dynamic reaction cell mass spectrometry. Bayesian Profile Regression was used to identify subgroups (clusters) of individuals with similar patterns of coexposure and to model association with PTB. RESULTS: Results indicated six subgroups of maternal participants with distinct exposure profiles, including one group with low exposure to all metals and one group with total arsenic, cadmium, lead, and uranium concentrations exceeding representative concentrations calculated from the National Health and Nutrition Examination Survey (NHANES). Compared with the reference group (i.e., the lowest exposure subgroup), the subgroup with the highest overall exposure had a relative risk of PTB of 2.9 times (95% credible interval: 1.1, 6.1). Exposures in this subgroup were also higher overall than NHANES median values for women 14-45 years of age. DISCUSSION: Given the wide range of exposures and elevated PTB risk for the most exposed subgroups in a relatively small study, follow-up investigation is recommended to evaluate associations between metal mixture profiles and other birth outcomes and to test hypothesized mechanisms of action for PTB and oxidative stress caused by environmental metals. https://doi.org/10.1289/EHP10361.

Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities.

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.

Metal mixture exposures and multiplexed autoantibody screening in Navajo communities exposed to uranium mine wastes.

Background: Environmental exposures to metals in uranium mining wastes and drinking water were documented in more than half of the 1304 Navajo community members of the Diné Network for Environmental Health (DiNEH) Project, the first comprehensive assessment of exposures to these metals and community health on the Navajo Nation. Objective: Evaluate environmental exposures among participants who provided blood and urine samples using multiplexed autoantibody positivity as an early effect biomarker. Methods: Survey and geospatial location data, well water quality, and metals biomonitoring were used to assess exposures to mixed-metal wastes from 100 abandoned uranium waste sites. Results: We observed that the prevalence of multiplexed autoantibody positivity in 239 participants was more than double that reported for the U.S. population (27.2% v. 13.8%) even though the national prevalence was generated using a different assay, the HEp-2 cell-based antinuclear antibody test. Increased risk of multiplexed autoantibody screening positivity (OR = 3.07,95%CI 1.15-8.22) was found among DiNEH study people who lived close to uranium mine and milling wastes and consumed metals in drinking water. Associations for females were even stronger when they lived closed to contaminated uranium mining and milling sites. Anti-U1-RNP antibodies were associated with water consumption of nickel. Conclusion: Proximity to waste sites and consumption of metals in water even below current drinking water standards were associated with perturbations of immune tolerance. These findings are consistent with previous studies of autoimmunity in the local population and demonstrate that multiplexed autoantibody screening method has a potential as sentinel indicator of exposures to environmental metals. Impact statement: This is the first, community-engaged environmental health study in exposed Navajo communities that applied clinical multiplexed testing in risk assessment of environmental metals associated with abandoned, unremediated uranium mining and milling waste sites. Routine clinical autoimmunity measures could be used as early effect biomarkers of environmental metal exposures.

Serum autoantibodies and exploratory molecular pathways in rural miners: A pilot study.

Introduction: The Southwestern United States (SWUS) has an extensive history of coal and metal mining, including uranium (U) mining. Lung diseases, including but not limited to, lung cancer and pulmonary fibrosis, have been studied extensively in miners due to occupational, dust-related exposures. However, high-throughput autoimmune biomarkers are largely understudied in miners, despite the fact that ore miners, such as U-miners, are at an increased risk for the development of autoimmune diseases such as systemic sclerosis and systemic lupus erythematosus (SLE). Additionally, there are current gaps in knowledge regarding which signaling pathways may play a role in occupational exposure-associated autoimmunity. Methods: Most current and former miners in the SWUS live close to their previous workplaces, in remote areas, with limited access to healthcare. In this pilot study, by leveraging a mobile clinical platform for patient care and clinical outreach, we recruited 44 miners who self-identified as either U (n = 10) or non-U miners (n = 34) and received health screenings. Serum IgG and IgM autoantibodies against 128 antigens were assessed using a high-throughput molecular technique, as a preliminary health screening opportunity. Results: Even when adjusting for age as a covariate, there was a significant (p < 0.05) association between self-reported U-mining exposure and biomarkers including IgM alpha-actinin, histones H2B, and H4, myeloperoxidase (MPO) and myelin basic protein. However, adjusting for age did not result in significant associations for IgG autoantibody production in U-miners. Bioinformatic pathway analysis revealed several altered signaling pathways between IgM and IgG autoantibodies among both U and non-U miners. Conclusions: Further research is warranted regarding the mechanistic connection between U-exposure and autoantibody development, especially regarding histone-related alterations and IgM autoantibody production.

Environmental uranium exposures and cytokine profiles among mother-newborn baby pairs from the Navajo Βirth Cohort Study.

The Navajo Nation was heavily mined for uranium (U) during the cold-war leading to a legacy of >1100 abandoned U mining, milling and associated waste sites. The Navajo Birth Cohort Study was initiated to assess the effect of non-occupational legacy exposure to U during pregnancy on birth outcomes and child development. We report that 92% of babies with detectable urine U at birth were born from mothers who had urine U concentrations greater than national norms during pregnancy, indicative of prenatal exposure to U. To assess immune alterations associated with U exposure on both mothers and babies, we investigated associations between cytokine profiles and maternal U and associations of these measures with cytokine profiles in babies. Effect sizes for the differences in cytokine profiles were more evident among babies than mothers. Overall, there were seven cytokines (IFN-γ, IL-1ß, IL-2, IL-4, IL-10, GM-CSF, and TNF-α), for which the effect size for babies with higher than the national U concentrations was medium to large (ORs of 2.21 (1.08-4.52) through 1.71(0.76-3.83). In contrast, only three cytokines (IL-8, IL-12p70, and TNF-α) had effect sizes which almost reached medium strength (ORs of 1.64 (0.74-4.05) through 1.36 (0.65-2.87) in mothers with U above national norms. The effects of prenatal exposures to uranium and associated alterations in systemic immune responses resulting from U exposure could impact both maternal health as well as healthy child development through induction of inflammation, autoimmunity or other chronic diseases related to immune dysfunction that may affect long-term health.

The immunotoxicity of natural and depleted uranium: From cells to people.

Uranium is a naturally occurring element found in the environment as a mixture of isotopes with differing radioactive properties. Enrichment of mined material results in depleted uranium waste with substantially reduced radioactivity but retains the capacity for chemical toxicity. Uranium mine and milling waste are dispersed by wind and rain leading to environmental exposures through soil, air, and water contamination. Uranium exposure is associated with numerous adverse health outcomes in humans, yet there is limited understanding of the effects of depleted uranium on the immune system. The purpose of this review is to summarize findings on uranium immunotoxicity obtained from cell, rodent and human population studies. We also highlight how each model contributes to an understanding of mechanisms that lead to immunotoxicity and limitations inherent within each system. Information from population, animal, and laboratory studies will be needed to significantly expand our knowledge of the contributions of depleted uranium to immune dysregulation, which may then inform prevention or intervention measures for exposed communities.

Efficacy of Air Filtration and Education Interventions on Indoor Fine Particulate Matter and Child Lower Respiratory Tract Infections among Rural U.S. Homes Heated with Wood Stoves: Results from the KidsAIR Randomized Trial.

BACKGROUND: Millions of rural U.S. households are heated with wood stoves. Wood stove use can lead to high indoor concentrations of fine particulate matter [airborne particles ≤2.5µm in aerodynamic diameter (PM2.5)] and is associated with lower respiratory tract infection (LRTI) in children. OBJECTIVES: We assessed the impact of low-cost educational and air filtration interventions on childhood LRTI and indoor PM2.5 in rural U.S. homes with wood stoves. METHODS: The Kids Air Quality Interventions for Reducing Respiratory Infections (KidsAIR) study was a parallel three-arm (education, portable air filtration unit, control), post-only randomized trial in households from Alaska, Montana, and Navajo Nation (Arizona and New Mexico) with a wood stove and one or more children <5 years of age. We tracked LRTI cases for two consecutive winter seasons and measured indoor PM2.5 over a 6-d period during the first winter. We assessed results using two analytical frameworks: a) intervention efficacy on LRTI and PM2.5 (intent-to-treat), and b) association between PM2.5 and LRTI (exposure-response). RESULTS: There were 61 LRTI cases from 14,636 child-weeks of follow-up among 461 children. In the intent-to-treat analysis, children in the education arm [odds ratio (OR)=0.98; 95% confidence interval (CI): 0.35, 2.72] and the filtration arm (OR=1.23; 95% CI: 0.46, 3.32) had similar odds of LRTI vs. control. Geometric mean PM2.5 concentrations were similar to control in the education arm (11.77% higher; 95% CI: -16.57, 49.72) and air filtration arm (6.96% lower; 95% CI: -30.50, 24.55). In the exposure-response analysis, odds of LRTI were 1.45 times higher (95% CI: 1.02, 2.05) per interquartile range (25 µg/m3) increase in mean indoor PM2.5. DISCUSSION: We did not observe meaningful differences in LRTI or indoor PM2.5 in the air filtration or education arms compared with the control arm. Results from the exposure-response analysis provide further evidence that biomass air pollution adversely impacts childhood LRTI. Our results highlight the need for novel, effective intervention strategies in households heated with wood stoves. https://doi.org/10.1289/EHP9932.

Building Environmental Health and Genomics Literacy among Healthcare Providers Serving Vulnerable Communities: An Innovative Educational Framework.

This study addresses healthcare providers' knowledge deficits in environmental health and genetics, and primarily focuses on student nurses and nurses serving marginalized, low-income communities frequently exposed to environmental toxicants. Our approach to improve public health is unique, combining hands-on modeling exercises with case-based lessons in addition to three targeted 40 min lectures on toxicology. These lectures included the team's community-based environmental health research among Indigenous peoples of the U.S. The hands-on approach employed DNA and protein molecular models designed to demonstrate normal and dysfunctional molecules, as well as genetic variants in world populations. The models provided learners with visuals and an experience of "learning by doing." Increased awareness of the effects of environmental toxicants is the first step toward improving health care for exposed communities. We measured knowledge gains by pre- and post-tests among student nurses and nurses serving Native Americans living both in urban and rural areas of the U.S. (n = 116). The modeling lessons illustrated genetic variants in liver proteins common in Native peoples and their resulting health vulnerabilities. Participants were engaged and enthusiastic; and pre- and post-test results reported substantial knowledge gains and a greater understanding of genetic susceptibility (p < 0.0001). Our study demonstrates the utility of this framework across diverse populations and remote communities.

Prognostic Values of Serum Ferritin and D-Dimer Trajectory in Patients with COVID-19.

Cytokine storm syndrome in patients with COVID-19 is mediated by pro-inflammatory cytokines resulting in acute lung injury and multiorgan failure. Elevation in serum ferritin and D-dimer is observed in COVID-19 patients. To determine prognostic values of optimal serum cutoff with trajectory plots for both serum ferritin and D-dimer in COVID-19 patients with invasive ventilator dependence and in-hospital mortality. We used retrospective longitudinal data from the Cerner COVID-19 de-identified cohort. COVID-19 infected patients with valid repeated values of serum ferritin and D-dimer during hospitalization were used in mixed-effects logistic-regression models. Among 52,411 patients, 28.5% (14,958) had valid serum ferritin and 28.6% (15,005) D-dimer laboratory results. Optimal cutoffs of ferritin (714 ng/mL) and D-dimer (2.1 mg/L) revealed AUCs ≥ 0.99 for in-hospital mortality. Optimal cutoffs for ferritin (502 ng/mL) and D-dimer (2.0 mg/L) revealed AUCs ≥ 0.99 for invasive ventilator dependence. Optimal cutoffs for in-house mortality, among females, were lower in serum ferritin (433 ng/mL) and D-dimer (1.9 mg/L) compared to males (740 ng/mL and 2.5 mg/L, respectively). Optimal cutoffs for invasive ventilator dependence, among females, were lower in ferritin (270 ng/mL) and D-dimer (1.3 mg/L) compared to males (860 ng/mL and 2.3 mg/L, respectively). Optimal prognostic cutoffs for serum ferritin and D-dimer require considering the entire trajectory of laboratory values during the disease course. Females have an overall lower optimal cutoff for both serum ferritin and D-dimer. The presented research allows health professionals to predict clinical outcomes and appropriate allocation of resources during the COVID-19 pandemic, especially early recognition of COVID-19 patients needing higher levels of care.

Indoor fine particulate matter and demographic, household, and wood stove characteristics among rural US homes heated with wood fuel.

Household heating using wood stoves is common practice in many rural areas of the United States (US) and can lead to elevated concentrations of indoor fine particulate matter (PM2.5 ). We collected 6-day measures of indoor PM2.5 during the winter and evaluated household and stove-use characteristics in homes at three rural and diverse study sites. The median indoor PM2.5 concentration across all homes was 19 µg/m3 , with higher concentrations in Alaska (median = 30, minimum = 4, maximum = 200, n = 10) and Navajo Nation homes (median = 29, minimum = 3, maximum = 105, n = 23) compared with Montana homes (median = 16, minimum = 2, maximum = 139, n = 59). Households that had not cleaned the chimney within the past year had 65% higher geometric mean PM2.5 compared to those with chimney cleaned within 6 months (95% confidence interval [CI]: -1, 170). Based on a novel wood stove grading method, homes with low-quality and medium-quality stoves had substantially higher PM2.5 compared to homes with higher-quality stoves (186% higher [95% CI: 32, 519] and 161% higher; [95% CI:27, 434], respectively). Our findings highlight the need for, and complex nature of, regionally appropriate interventions to reduce indoor air pollution in rural wood-burning regions. Higher-quality stoves and behavioral practices such as regular chimney cleaning may help improve indoor air quality in such homes.

Prenatal Metal Exposures and Infants' Developmental Outcomes in a Navajo Population.

Early-life exposure to environmental toxicants can have detrimental effects on children's neurodevelopment. In the current study, we employed a causal modeling framework to examine the direct effect of specific maternal prenatal exposures on infants' neurodevelopment in the context of co-occurring metals. Maternal metal exposure and select micronutrients' concentrations were assessed using samples collected at the time of delivery from mothers living across Navajo Nation with community exposure to metal mixtures originating from abandoned uranium mines. Infants' development across five domains was measured at ages 10 to 13 months using the Ages and Stages Questionnaire Inventory (ASQ:I), an early developmental screener. After adjusting for effects of other confounding metals and demographic variables, prenatal exposure to lead, arsenic, antimony, barium, copper, and molybdenum predicted deficits in at least one of the ASQ:I domain scores. Strontium, tungsten, and thallium were positively associated with several aspects of infants' development. Mothers with lower socioeconomic status (SES) had higher lead, cesium, and thallium exposures compared to mothers from high SES backgrounds. These mothers also had infants with lower scores across various developmental domains. The current study has many strengths including its focus on neurodevelopmental outcomes during infancy, an understudied developmental period, and the use of a novel analytical method to control for the effects of co-occurring metals while examining the effect of each metal on neurodevelopmental outcomes. Yet, future examination of how the effects of prenatal exposure on neurodevelopmental outcomes unfold over time while considering all potential interactions among metals and micronutrients is warranted.

Identifying Issues and Priorities in Reporting Back Environmental Health Data.

Experts recommend reporting environmental exposure results back to research participants and communities, yet environmental health researchers need further guidance to improve the practice of reporting back. We present the results of a workshop developed to identify pertinent issues and areas for action in reporting back environmental health research results. Thirty-five attendees participated, brainstorming responses to the prompt: "What are some specific issues that are relevant to reporting back research results to individuals or the larger community?", and then grouping responses by similarity and rating their importance. Based on a combined theoretical foundation of grounded theory and qualitative content analysis, we used concept mapping to develop a collective understanding of the issues. Visual maps of the participants' responses were created using nonmetric multidimensional scaling and hierarchical cluster analysis. The resulting concept map provided a spatial depiction of five issue areas: Effective Communication Strategies, Community Knowledge and Concerns, Uncertainty, Empowering Action, and Institutional Review and Oversight (listed from highest to lowest rating). Through these efforts, we disentangled the complex issues affecting how and whether environmental health research results are reported back to participants and communities, by identifying five distinct themes to guide recommendations and action. Engaging community partners in the process of reporting back emerged as a unifying global theme, which could improve how researchers report back research results by understanding community context to develop effective communication methods and address uncertainty, the ability to act, and institutional concerns about beneficence and justice.

Exposure to uranium and co-occurring metals among pregnant Navajo women.

Navajo Nation residents are at risk for exposure to uranium and other co-occurring metals found in abandoned mine waste. The Navajo Birth Cohort Study (NBCS) was initiated in 2010 to address community concerns regarding the impact of chronic environmental exposure to metals on pregnancy and birth outcomes. The objectives of this paper were to 1) evaluate maternal urine concentrations of key metals at enrollment and delivery from a pregnancy cohort; and 2) compare the NBCS to the US general population by comparing representative summary statistical values. Pregnant Navajo women (N = 783, age range 14-45 years) were recruited from hospital facilities on the Navajo Nation during prenatal visits and urine samples were collected by trained staff in pre-screened containers. The U.S. Centers for Disease Control and Prevention (CDC), National Center for Environmental Health's (NCEH) Division of Laboratory Sciences (DLS) analyzed urine samples for metals. Creatinine-corrected urine concentrations of cadmium decreased between enrollment (1st or 2nd trimester) and delivery (3rd trimester) while urine uranium concentrations were not observed to change. Median and 95th percentile values of maternal NBCS urine concentrations of uranium, manganese, cadmium, and lead exceeded respective percentiles for National Health and Nutrition Evaluation Survey (NHANES) percentiles for women (ages 14-45 either pregnant or not pregnant.) Median NBCS maternal urine uranium concentrations were 2.67 (enrollment) and 2.8 (delivery) times greater than the NHANES median concentration, indicating that pregnant Navajo women are exposed to metal mixtures and have higher uranium exposure compared to NHANES data for women. This demonstrates support for community concerns about uranium exposure and suggests a need for additional analyses to evaluate the impact of maternal metal mixtures exposure on birth outcomes.

Urinary Metals Concentrations and Biomarkers of Autoimmunity among Navajo and Nicaraguan Men.

Metals are suspected contributors of autoimmune disease among indigenous Americans. However, the association between metals exposure and biomarkers of autoimmunity is under-studied. In Nicaragua, environmental exposure to metals is also largely unexamined with regard to autoimmunity. We analyzed pooled and stratified exposure and outcome data from Navajo (n = 68) and Nicaraguan (n = 47) men of similar age and health status in order to characterize urinary concentrations of metals, compare concentrations with the US National Health and Nutrition Examination Survey (NHANES) male population, and examine the associations with biomarkers of autoimmunity. Urine samples were analyzed for metals via inductively coupled plasma mass spectrometry (ICP-MS) at the US Centers for Disease Control and Prevention. Serum samples were examined for antinuclear antibodies (ANA) at 1:160 and 1:40 dilutions, using an indirect immunofluorescence assay and for specific autoantibodies using enzyme-linked immunosorbent assay (ELISA). Logistic regression analyses evaluated associations of urinary metals with autoimmune biomarkers, adjusted for group (Navajo or Nicaraguan), age, and seafood consumption. The Nicaraguan men had higher urinary metal concentrations compared with both NHANES and the Navajo for most metals; however, tin was highest among the Navajo, and uranium was much higher in both populations compared with NHANES. Upper tertile associations with ANA positivity at the 1:160 dilution were observed for barium, cesium, lead, strontium and tungsten.

Environmental risk mapping of potential abandoned uranium mine contamination on the Navajo Nation, USA, using a GIS-based multi-criteria decision analysis approach.

The Navajo Nation (NN), a sovereign indigenous tribal nation in the Southwestern United States, is home to 523 abandoned uranium mines (AUMs). Previous health studies have articulated numerous human health hazards associated with AUMs and multiple environmental mechanisms/pathways (e.g., air, water, and soil) for contaminant transport. Despite this evidence, the limited modeling of AUM contamination that exists relies solely on proximity to mines and only considers single rather than combined pathways from which the contamination is a product. In order to better understand the spatial dynamics of contaminant exposure across the NN, we adopted the following established geospatial and computational methods to develop a more sophisticated environmental risk map illustrating the potential for AUM contamination: GIS-based multi-criteria decision analysis (GIS-MCDA), fuzzy logic, and analytic hierarchy process (AHP). Eight criteria layers were selected for the GIS-MCDA model: proximity to AUMs, roadway proximity, drainage proximity, topographic landforms, wind index, topographic wind exposure, vegetation index, and groundwater contamination. Model sensitivity was evaluated using the one-at-a-time method, and statistical validation analysis was conducted using two separate environmental datasets. The sensitivity analysis indicated consistency and reliability of the model. Model results were strongly associated with environmental uranium concentrations. The model classifies 20.2% of the NN as high potential for AUM contamination while 65.7% and 14.1% of the region are at medium and low risk, respectively. This study is entirely a novel application and a crucial first step toward informing future epidemiologic studies and ongoing remediation efforts to reduce human exposure to AUM waste.

Active smoking, secondhand smoke exposure and serum cotinine levels among Cheyenne River Sioux communities in context of a Tribal Public Health Policy.

INTRODUCTION: American Indians and Alaska Natives face disproportionately high rates of smoking and secondhand smoke (SHS) exposure. The Cheyenne River Sioux Tribe (CRST) is among the few Tribal Nations controlling commercial tobacco exposures in public and work places. We had an opportunity to explore effects of the new commercial tobacco-free policy (implemented in 2015) in an environmental health study (2014-2016) that collected information about commercial tobacco use and SHS prevalence and examined predictor variables of serum cotinine concentrations. METHODS: Self-reported survey data were used in quantile regression statistical modelling to explore changes in cotinine levels, based on smoking status, smokeless tobacco consumption and SHS exposure. RESULTS: From enrolled 225 adults, 51% (N=114) were current smokers. Among 88 non-tobacco users, 35 (40%) reported current SHS exposure. Significant differences in cotinine median concentrations were found among participants with and without current SHS exposure. Extremely high cotinine concentrations (~100 times larger than the median) were detected in some non-tobacco users. After implementing the new smoke-free air Tribal policy, cotinine decreased in participants with intermediate (3-15 ng/mL, non-tobacco users with SHS exposure) and high (>15 ng/mL, mainly tobacco users) cotinine levels showing association with an abatement of opportunities for SHS exposure. Significant predictors of cotinine levels were sampling year, current smoking and tobacco chewing. No gender differences were observed in cotinine. CONCLUSIONS: Our results show decrease in cotinine concentrations in CRST participants since implementation of their 'Smoke-Free Clean Air Act' in 2015.

Wood stove interventions and child respiratory infections in rural communities: KidsAir rationale and methods.

BACKGROUND: Acute lower respiratory tract infections (LRTIs) account for >27% of all hospitalizations among US children under five years of age. Residential burning of biomass for heat leads to elevated indoor levels of fine particulate matter (PM2.5) that often exceed current health based air quality standards. This is concerning as PM2.5 exposure is associated with many adverse health outcomes, including a greater than three-fold increased risk of LRTIs. Evidence-based efforts are warranted in rural and American Indian/Alaska Native (AI/AN) communities in the US that suffer from elevated rates of childhood LRTI and commonly use wood for residential heating. DESIGN: In three rural and underserved settings, we conducted a three-arm randomized controlled, post-only intervention trial in wood stove homes with children less than five years old. Education and household training on best-burn practices were introduced as one intervention arm (Tx1). This intervention was evaluated against an indoor air filtration unit arm (Tx2), as well as a control arm (Tx3). The primary outcome was LRTI incidence among children under five years of age. DISCUSSION: To date, exposure reduction strategies in wood stove homes have been either inconsistently effective or include factors that limit widespread dissemination and continued compliance in rural and economically disadvantaged populations. As part of the "KidsAIR" study described herein, the overall hypothesis was that a low-cost, educational intervention targeting indoor wood smoke PM2.5 exposures would be a sustainable approach for reducing children's risk of LRTI in rural and AI/AN communities.

Comparative United States autoimmune disease rates for 2010-2016 by sex, geographic region, and race.

PURPOSE: AIDs may disproportionately impact specific racial groups, but autoimmune (AID) prevalence information by minority racial group is sparse for many AIDs. The objective of this analysis was to supplement previously published AID prevalence rates by providing information on race rate ratios (minority race populations compared to Caucasian populations) in the United States. Preliminary to estimating race rate ratios, contemporary US-specific, health care utilization-based AID prevalence rates and female-to-male ratios were estimated and compared to previously published AID prevalence rates. METHODS: We used a large national electronic medical record database of 52 million individuals to estimate age-adjusted direct standardized rates for 22 AIDs for 2010 through 2016 by gender, race, and US census division. These were compared to previously published estimates. RESULTS: Female-to-male ratios were comparable with published studies. Almost all observed Multiracial AID rates were significantly higher than Caucasian rates, as well as 9 of 22 AID rates observed among Native Americans and 8 of 22 AID rates estimated among African-American patients. Regional variation was noted: highest African-American systemic lupus erythematosus rates were observed in the West North Central and South Atlantic divisions, highest African-American multiple sclerosis rates in the South Atlantic and Pacific divisions, and highest Native American rheumatoid arthritis rates in the West North Central, Mountain, and Pacific divisions. CONCLUSIONS: Substantial AID heterogeneity exists by race and by geographic area. An important research area is further exploring factors related to heterogeneity such as potential interactions between genetic susceptibility and environmental factors.