Disparities in the adverse health effects due to ambient environmental exposures have long been documented in the environmental epidemiology literature. A growing body of environmental epidemiology literature has focused on how detrimental aspects of the physical environment (e.g., poor housing quality) and social environment (e.g., chronic social stressors) can exacerbate the adverse health effects of environmental exposures (e.g., air pollution, heat). However, the literature on protective factors which might mitigate adverse health effects of environmental exposure is more limited. We borrow from the climate resilience and disaster preparedness literature to discuss how protective community assets may be identified, operationalized, and understood in environmental epidemiologic research. We outline two major pathways through which community assets may protect environmental health: by reducing overall exposure (mediation) and by reducing susceptibility (effect modification). This framework can help environmental epidemiologists and other public health researchers select and understand appropriate community assets to test as effect modifiers or mediators of associations between environmental exposures and adverse health outcomes. We present examples of community assets organized into five domains and highlight pragmatic challenges that may arise when considering assets in large-scale epidemiologic research-for example, limitations on availability of publicly available data at meaningful spatial scales, and challenges interpreting available community asset data. Finally, we posit that research focused on community assets can inform scalable, impactful health-promoting interventions.
The American College of Epidemiology (ACE) Ethics and Policy Committee was newly formed in 2023 through the merger of separate Ethics and Policy Committees, and over the last three years has been involved with sponsored symposia, collaborations, policy consultations, education, mentoring, and capacity building. The purpose of this reflection paper is to highlight the achievements of the Committee and further highlight its ethics and policy work and presentations. Speakers with diverse expertise were invited to present at consecutive ACE Annual Meetings. Invited symposia speakers presented along the themes of climate change (PT, CH, JH), causal inference in epidemiology (JH, SW, DW, WL), and integrity in epidemiologic research (IB, DS, WA), aligning with the overall theme of each Annual Meeting. At the same time, the Committee's work involved: (i) consultation on policy and position statements developed by the International Network for Epidemiology in Policy (INEP); (ii) education on ethics in epidemiology and public health through the Ethics Syllabi Collection Project; (iii) mentoring graduate-level epidemiology students as part of the ACE Scholars Program; and (iv) developing and strengthening ethics guidance and resources. The sociopolitical landscape and ongoing global health crises have challenged the foundations of epidemiology and its credibility as a scientific discipline to serve public health and maintain the public's trust. Using a principle-based approach, we examined the ethical considerations in each of the themed symposia and highlight the key principles, values, and professional virtues including justice, respect for persons and their communities, beneficence, transparency, accountability, veracity, excellence, and integrity, among others. We provide recommendations on how to focus research efforts and ethically engage with interdisciplinary colleagues and varied audiences while under pressure to be an advocate or policy expert, and counter misinformation. Our reflection paper demonstrates contemporary ethical reflection through the collective work of the Committee with symposia presenters who together represent expertise in epidemiology, public health, bioethics, health disparities, law, bioinformatics, medicine, and occupational and environmental health. Other work of the Committee involved developing more formalized approaches to policy consultations and furthering our efforts in education, mentoring, and capacity building. The ethical intersections of epidemiology and public health remind us of their shared goal which is to improve population health. Despite the attacks on science and the ongoing public scrutiny of these disciplines, the Committee is committed to ongoing collaborations, policy consultations, education, mentoring, and capacity building in broad and specialized areas of epidemiology and public health and supports the ethical analysis of contemporary issues using established and emerging ethical principles, approaches, and frameworks.
The relationship between exposure to perfluoroalkyl substances (PFAS) and birthweight remains unclear. Pooling data across multiple cohorts can increase power, leading to more representative populations and exposure distributions, but confounding by cohort can be a major source of bias. To understand this potential bias, we assessed the relationship between exposure to five PFAS and birthweight utilizing data from 5480 mother-infant dyads across 17 Environmental influences on Child Health Outcomes (ECHO) Cohort sites. The relationship was assessed in several ways: covariate-adjusted models without cohort adjustment as well as adjustment via fixed and random effects. Findings from analysis with cohort adjustment resulted in significantly inverse relationships for four of the five PFAS considered. Adjustment via fixed and random effects produced similar findings. Failure to adjust for cohort resulted in bias of varying direction and magnitude depending on the PFAS considered. Results were supported in simulated data. In this study, we saw evidence of confounding bias by cohort even after adjustment for covariates, while adjustment by both fixed and random effects for cohort resulted in comparable results.
Exposure to extreme temperatures and fine particulate matter is hazardous to human health, especially among children. With growing evidence on the impact of these environmental hazards on child health-including increased risks of respiratory illnesses, heat-related illnesses, and developmental challenges-there is a substantial need to identify high-risk areas for potential adverse pediatric health outcomes. In this study, we developed pediatric vulnerability indices at the census tract scale across the contiguous United States (CONUS) using five dimensionality reduction methods, including unsupervised machine learning and deep learning approaches. We integrated these indices with data on extreme temperature (2012-2024), PM2.5, and black carbon exposures from 2010 to 2020, enabling spatial analysis of environmental hazards and pediatric vulnerability. Among the five methods tested, principal component analysis (PCA) was selected for its balanced representation of 12 vulnerability factors, which explained 23% of the variance in the data. We observed that co-exposure to extreme temperature and air pollutant exposures were highest in the West, Southwest, and certain parts of the South and Northeast. Approximately 36% of the CONUS showed statistically significant hotspots of co-exposures to higher temperatures and air pollutants, concentrated in the West, Northwest, and Southwest. High-risk areas for pediatric vulnerability and co-exposure to environmental hazards were identified in both urban and rural communities, including indigenous lands and agricultural regions. These findings can aid policymakers and public health officials as a preliminary resource in developing heat action plans and allocating cooling centers to protect children living in the most affected communities. Children are particularly vulnerable to health issues associated with high temperatures and air pollution. In this study, we sought to identify the areas in the United States that pose the greatest risk to children from both extreme heat and air pollution. We created an index to measure children's vulnerability across neighborhoods, using data on family income, access to healthcare, and other social factors. We also looked at data on high temperatures and air pollution from 2012 to 2024. The results of this work indicate that children living in the West, Southwest, and certain parts of the South and Northeast are at a higher risk of adverse health outcomes due to extreme temperatures and air pollution. Approximately one‐third of the country's area experienced both high temperatures and high air pollution simultaneously. These areas included both cities and rural places, as well as indigenous lands and farming communities. Our results help decision‐makers and health officials as a preliminary resource for allocating resources, such as cooling centers, and for developing plans to protect children during periods of extreme heat and high air pollution.
The inaugural Pennsylvania One Health Consortium Annual Meeting brought together partners from universities, state agencies, public health, veterinary, agriculture, industry, and community organizations to align around a shared One Health agenda. The program highlighted zoonotic threats, antimicrobial stewardship, wildlife and ecosystem health, invasive species, and climate-sensitive hazards. Participants affirmed privacy-preserving data exchange, projects integrating genomic epidemiology with field and environmental surveillance, cross-disciplinary education, and transparent governance, concluding with a phased roadmap for an integrated statewide One Health framework.
BackgroundSystemic lupus erythematous (SLE) shares many common epidemiologic features with other autoimmune diseases or diseases associated with an underlying Epstein-Barr virus (EBV) infection. It was hypothesized that the geographic variation of mortality from SLE would reveal a similar pattern as Hodgkin lymphoma (HL), multiple sclerosis (MS), Crohn's disease (CD), and ulcerative colitis (UC).MethodsUsing the vital statistics of 21 countries from 1951-2022, overall and age-specific death rates from the 5 diseases were calculated for each individual country. The death rates of different countries were compared using linear regression analysis.ResultsWhereas other autoimmune diseases or diseases associated with an underlying EBV infection, such as HL, MS, CD, and UC, showed remarkably similar geographic variations, the geographic distribution of SLE did not fit this overall pattern. High death rates from SLE were not clearly associated with developing versus developed countries, northern versus southern latitude, or any specific continent. However, similar geographic distributions of SLE were consistently found among consecutive age groups, ranging from 0-4 to 85+ years.ConclusionsThe similarities in the geographic distributions of death rates from HL, MS, CD, and UC suggest that these 4 diseases share a set of one or more common environmental risk factors. Other environmental risk factors besides EBV infection must contribute to the varying occurrence of SLE across the globe. These risk factors start exerting their influence at a very young age of less than 5 years.
The majority of brachial plexus birth injuries (BPBI) occur without prenatally identifiable risk factors. This meta-analysis mapped BPBI incidence worldwide as a preliminary step toward investigating population-level predictors. This systematic review searched PubMed, Embase, Cochrane, and Web of Science. Eligible studies provided cross-sectional data on BPBI incidence without inclusion criteria predicated on known risk factors. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, two reviewers screened studies, extracted data, and assessed risk of bias. Meta-analyses of proportions were conducted using random-effects models to estimate composite international incidence; covariates were incorporated with meta-regressions to compare population-based differences. Reviewers screened 1,245 studies; 116 were included, and 91 were eligible for meta-analyses. The review identified gaps in the literature regarding Central American, South American, African, and Northeast Asian epidemiology. Acknowledging these limitations, 71.5 million live births across 30 countries in all 6 populated continents were pooled for meta-analyses to estimate composite international incidence and population-level variation. Composite BPBI incidence was 1.4 per thousand births (95% confidence interval, 1.3-1.6), yet estimates from individual countries ranged from 0.4 to 4.6 per thousand births. Meta-regression confirmed significant international differences in BPBI incidence; country of birth explained 34.2% of between-study variance. From studies that tracked permanent BPBI, 18.4% (95% confidence interval, 15.3% to 22.0%) of cases persisted beyond a year. These findings encourage the formulation of new research questions that may allow us to address the remaining unpredictability in BPBI incidence. Significant regional variation warrants exploration of population-level influences, including health-systems-level, environmental, or sociodemographic factors, along with unexplored individual-level factors such as genetic contributions. Symptom prevalence study 2a.
Lung cancer remains one of the leading causes of cancer-related mortality in Africa, with survival rates starkly lagging behind global benchmarks because of systemic inequities in prevention, diagnosis, and treatment access. Despite representing only 6% of global smokers, the continent faces a disproportionate burden driven by environmental and occupational carcinogens, aggressive tobacco marketing, and fragmented health care infrastructure. Key challenges include prohibitive delays in accessing targeted therapies like epidermal growth factor receptor inhibitors and immunotherapies, a dire shortage of radiotherapy infrastructure-0.12 megavoltage units per million people versus the International Atomic Energy Agency's recommended five megavoltage units per million, and a dearth of thoracic surgeons (0.03 thoracic surgeons per 100,000 people). These barriers contribute to over 90% of patients presenting with advanced-stage disease and 5-year survival rates below 10%. Multifaceted strategies are essential to bridge these gaps: regional pooled procurement and compulsory licensing to lower drug costs, telemedicine platforms like the African Radiation Oncology Network to expand radiotherapy access, and task-shifting surgical training programs through institutions such as The College of Surgeons of East, Central, and Southern Africa, which graduates 15 cardiothoracic specialists annually and partnerships such as that between the West African College of Surgeons and Global Oncology Group at Queens University, Canada. Investments in critical care infrastructure, exemplified by dedicated thoracic intensive care units in Ghana and Kenya, alongside harmonized guidelines from the African Cancer Coalition, are pivotal. The Lancet Oncology Commission underscores the urgency of political commitment and sustainable investment in diagnostics, workforce training, and technology transfer to align Africa's cancer care with global standards. Addressing these inequities is a clinical imperative and a moral obligation to ensure life-saving innovations benefit all populations equitably.
Air pollution and socioeconomic deprivation have been independently associated with multiple negative health outcomes, such as depression and increased pain frequency and duration. This study examined the joint influences of air pollution and individual- and neighborhood-level deprivation on depression and pain. A total of 1113 adults (aged 18-88 years) completed a series of surveys about their mental and physical health and living environment. Participants' geocoded addresses were used to obtain their long-term average exposure to PM2.5 and their neighborhood's socioeconomic status and resource access via the Area Deprivation Index (ADI). We found significant age interactions with PM2.5 and several socioeconomic deprivation indicators. Individual-level and neighborhood-level deprivation on their own significantly predicted levels of depression and pain. We also found that relative deprivation, the measure of an individual's socioeconomic deprivation compared to their neighborhood, was significantly associated with experiences of both depression and pain. These findings are important to understanding the impacts of environmental stressors, particularly on the aging population, which may contribute to improved interventions and public policy targeting the detrimental associations of environmental stressors with human health.
Healthcare facilities may be major reservoirs for antimicrobial resistance, particularly in low- and middle-income countries, yet data are limited on factors influencing acquisition in these settings. In this cohort study, we followed up participants who screened negative for colonisation with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) on admission and assessed the incidence and risk factors for hospital acquisition of ESCrE and CRE colonisation in this population. In this 12-month cohort study, we enrolled patients upon admission to a tertiary referral hospital Emergency Department in Botswana. A rectal swab was collected within 24 h of admission, and on days 3-6, 7-10, and 11-14 of hospitalisation, if still admitted. Acquisition of ESCrE and CRE was defined as a new positive swab culture in a study subject with a negative swab culture on admission. ESCrE and CRE colonisation were determined by growth on selective culture media and confirmed using automated phenotypic identification and antibiotic susceptibility testing. Associations between acquisition of ESCrE/CRE colonisation and clinical and demographic variables were analysed. Among patients with no detected colonisation at admission who remained hospitalised for ≥3 days, 81 (34.3%) and 29 (9.4%) had newly acquired ESCrE and CRE colonisation, respectively. Patients were at higher risk of ESCrE acquisition if they were hospitalised in the summer/rainy months (adjusted risk ratio, 1.49 [95% confidence interval [CI]: 1.05-2.12]). The risk of CRE acquisition was higher among patients aged <12 months (crude risk ratio, 2.58 [95% CI: 1.09-6.08]). High rates of hospital ESCrE and CRE acquisition in this cohort highlight the urgent need for strengthening hospital infection prevention and control programmes to mitigate transmission. Observed seasonal variation in hospital acquisition suggests that future analyses should consider seasonality as a potential confounder and investigate environmental drivers that may influence antimicrobial resistance transmission in healthcare facilities.
Police violence is increasingly recognized as a public health crisis, disproportionately affecting Black, Indigenous, and other communities of color due to long-standing patterns of racialized surveillance and disinvestment. Environmental stressors such as heat have also been linked to increased aggression, stress reactivity, and violence, suggesting that as climate change drives more frequent and intense extremes in temperature, these conditions may amplify existing risks of fatal police encounters. This study evaluated whether extreme ambient temperatures were associated with fatal police violence and whether structural neighborhood deprivation modified this relationship. Our nationwide case-crossover analysis examined daily maximum temperature and fatal police violence in the United States (2013-2024) using data from Mapping Police Violence. We estimated odds ratios across percentiles of the temperature distribution and analyses were stratified by neighborhood-level measures of deprivation, using Index of Concentration at the Extremes metrics for education, income, racialized income, and homeownership. Our main analysis revealed that compared to the median temperature (23.5 °C), the odds of fatal police violence at the 5th temperature percentile were reduced by 12% (95 percent CI: 0.806 to 0.955), while the odds at the 99th percentile were increased by 11% (CI: 1.037 to 1.185). While there was limited evidence of effect modification by neighborhood deprivation metrics, we found neighborhoods with higher levels of deprivation were disproportionately burdened by fatal police violence. These findings highlight the importance of temperature as a determinant of fatal police violence, suggesting that policies that address neighborhood deprivation and fatal policing may be needed on a warming planet.
The childhood environment is critical for brain development. However, most neuroimaging studies examine individual environmental measures (e.g., socioeconomic status) or a limited set of exposures, obscuring how the combination of complex, real-world exposures jointly influence brain development. Here we investigated how white matter shape and tissue properties are linked to the childhood exposome, a multidimensional measure capturing over 300 environmental exposures. Using multi-shell diffusion MRI from 8,183 children (ages 9-10) in the ABCD study, we quantified microstructural and macrostructural properties across 62 person-specific white matter tracts. The exposome showed widespread and highly replicable associations with both white matter microstructure and macrostructure: more advantaged environments were associated with larger tract macrostructure and lower orientation dispersion. Principal component analysis revealed that the dominant axis of exposome-white matter covariation aligns with the cortical sensorimotor-association hierarchy, such that tracts spanning this hierarchy exhibit the strongest associations with the exposome. Multivariate models demonstrated that patterns of white matter features explained 25% of the variance in the exposome in unseen individuals. Notably, white matter-based prediction of cognition was markedly reduced after accounting for the exposome (~82% reduction in explained variance), indicating that brain-cognition associations overlap substantially with variance captured by the exposome. These findings generalized to independent data from the Healthy Brain Network (n=869), which differs substantially from ABCD in MRI acquisition, participant selection, and childhood environments. Together, these results suggest that white matter architecture strongly reflects the childhood environment.
Residential segregation is associated with differential exposure to air pollution. Hippocampus structure and function are highly susceptible to pollutants and associated with posttraumatic stress disorder (PTSD) development. Therefore, we investigated associations between residential segregation, air pollutants, hippocampal neurobiology, and PTSD in recent trauma survivors. Participants (N = 278; 34% non-Hispanic white, 46% Non-Hispanic Black, 16% Hispanic) completed multimodal neuroimaging two weeks after trauma. Yearly averages of air pollutants (PM2.5 and NO2) and racial/economic segregation (Index of Concentration at the Extremes) were derived from each participant's address. Linear models assessed if air pollutants mediated associations between segregation and hippocampal volume, threat reactivity, or parahippocampal cingulum fractional anisotropy (FA) after covarying for age, sex, income, and 2-week PTSD symptoms. Further models evaluated if pollutants or segregation prospectively predicted PTSD symptoms six months post-trauma. We found that non-Hispanic Black participants lived in neighborhoods with significantly greater segregation and air pollution compared to Hispanic and non-Hispanic white participants (ps < 0.001). PM2.5 concentration was positively correlated with threat reactivity (r(276) = 0.16, p < 0.006), while NO2 concentration was positively correlated with hippocampus volume (r(276) = 0.17, p < 0.005) and negatively correlated with white matter tract FA (r(276) = -0.18, p < 0.003). There was a significant indirect effect of NO2 between segregation and FA values (β = 0.08, 95% CI[0.01, 0.15]), and an indirect effect of PM2.5 between segregation and threat reactivity (β = -0.08, 95% CI[-0.14, -0.01]). There was no direct effect of segregation on hippocampal features. Pollutants and segregation were not associated with PTSD symptoms. In conclusion, residential segregation is associated with greater air pollution exposure, which is in turn associated with variability in hippocampal features among recent trauma survivors. Further research is needed to assess relationships between other environmental factors and trauma and stress-related disorders.
Climate change intensifies temperature extremes, increasing daily variations between high and low temperatures (intraday temperature variation). These variations can influence environmental exposures, such as ambient air pollution and pollen, and indoor behaviors, including heating use, potentially elevating asthma exacerbation risk. Neighborhood context may modify these effects, particularly in disinvested or racially segregated areas where adaptive capacity is limited. We conducted a case-crossover study using conditional logistic regressions to estimate associations between intraday temperature variation and asthma exacerbations among children in Philadelphia, PA (2011-2016). Cases were identified from electronic health records at the Children's Hospital of Philadelphia. Analyses were stratified by season: Spring/Summer (March-August) and Fall/Winter (October-February). We assessed nonlinear and lagged (up to 7 days) effects, defining reference thresholds as 4 °F for Spring/Summer and 3 °F for Fall/Winter. Models were further stratified by present-day racialized economic segregation and historical redlining. In Spring/Summer, greater intraday temperature variation on lag day 4 was associated with increased odds of asthma exacerbation (OR = 1.20, 95% CI: 1.08-1.34). In Fall/Winter, greater variation was associated with decreased odds (OR = 0.81, 95% CI: 0.68-0.98). No statistically significant effect modification was observed by segregation or redlining. Intraday temperature variation was associated with pediatric asthma exacerbations, with stronger adverse effects during warmer months. These findings highlight the importance of addressing temperature variation in public health and clinical strategies aimed at protecting children with asthma in a changing climate.
Cognitive impairment is a major public health concern among older adults. This study examined the associations of purpose in life (PIL), personal growth (PG), and life satisfaction (LS) with cognitive impairment risk, as well as potential underlying pathways. The study population comprised 1,179 U.S. women (aged 77-93 years) from the Women's Health Initiative Memory Study - Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) cohort who completed psychological well-being assessments in 2012 and were followed until 2021. Cognitive status was evaluated annually using standardized assessments and central adjudication. Over an average of 5.4 years of follow-up, 355 participants were classified with MCI (175) or dementia (180). The association between PIL and cognitive impairment was largely mediated by lower perceived stress and higher physical activity (61%), rendering the direct effect non-significant. Women in the highest PG quartile had a 33% lower risk of impairment (HR = 0.67, 95% CI: 0.46-0.96). Mediation analyses showed both direct and indirect effects of PG. No association was found for LS. PG and PIL were linked to lower cognitive impairment risk, primarily via stress reduction and physical activity. Targeting these factors may promote cognitive health among aging populations.
BACKGROUND: Alzheimer’s disease (AD) remains a major therapeutic challenge, characterized by high clinical trial failure rates and limited efficacy of current treatments. Drug repurposing offers a faster, lower-risk route to new therapies; however, existing computational approaches often prioritize predictive accuracy over mechanistic novelty and interpretability, both of which are critical for clinical translation. RESULTS: We introduce a quality-diversity Automated Machine Learning (AutoML) framework that integrates biologically informed graph neural network (GNN) embeddings with a MAP-Elites-guided search to discover predictive yet mechanistically distinct therapeutic hypotheses. Drugs and genes are embedded using GraphSAGE and variational graph autoencoders trained on the Alzheimer’s Knowledge Base (AlzKB), with a clustering loss used to anchor known AD entities and define dimensions of biological novelty. In an AD case study using matched ADSP GWAS-derived features, our framework successfully recovered known drug–gene relationships and identified robust consensus candidates across independent validation runs. Most notably, the search consistently prioritized Triclosan—a recently identified environmental risk factor for AD neuroinflammation—and the Ketamine/Quazepam pair, suggesting a model-driven preference for restoring synaptic E/I balance. Furthermore, exploratory leads such as Exemestane and Felodipine were identified in underrepresented biological niches, supported by enrichment in oxidative stress and autophagy pathways. The framework demonstrated high stability across multiple random seeds and a 48% reduction in computational cost compared to standard multi-objective evolutionary baselines. CONCLUSIONS: Beyond AD, this framework offers a generalizable strategy for integrating biomedical knowledge graphs with diversity-enhancing AutoML to accelerate the discovery of mechanistically novel drug candidates across complex polygenic diseases.
Direct measurement of in utero phthalate exposure in placental and fetal tissues is generally not possible. Maternal urinary levels serve as proxies and may introduce measurement error, biasing health effect estimates. We adjusted for measurement error when using maternal urinary phthalates as proxies for placental-fetal exposure and to evaluate the impact of this correction on the association between prenatal phthalate exposure and anogenital distance (AGD). We biopsied and analyzed 68 placentas from the TIDES study (San Francisco site: n = 204, 2010-2012). Phthalate metabolite concentrations were measured in three placental tissue types: chorion smooth (CS), chorion frondosum (CF), and basal plate (BP). Phthalate concentrations were standardized to remove pre-processing variation. Regression calibration (RC) and multiple imputation for measurement error (MIME) were used for correction. Associations between phthalates and AGD were estimated by generalized linear models. Bias was quantified by calculating the percent change in the beta coefficient from the gold standard (placental phthalate) to the proxy (urinary phthalate), after correction for measurement error. Phthalate metabolites were detected in over 70% of placental tissues. Monoethylhexyl (MEHP) phthalate was the most abundant metabolite in CF and in CS. Phthalate concentrations were lowest in BP and varied across placental tissues. Weak associations were found between urinary and placental phthalates. MIME outperformed RC, reducing bias in the average phthalate effect on AGD in the male by 30% for AGD-penis and 69% for AGD-scrotum, and in the female by 32% for AGD-clitoris and 45% for AGD-fourchette. Placental phthalate concentrations varied by tissue type and showed poor correlation with maternal urinary levels. MIME outperformed RC in adjusting for measurement error in this setting. Findings suggest maternal and placental exposures are distinct constructs, highlighting the need for direct placental measurement in phthalate toxicity studies. Further research can improve phthalate exposure assessment and knowledge of maternal-placental-fetal transfer. This study highlights a key gap in environmental health research, where maternal urinary phthalates are often used as proxies for placental and fetal exposure. Using two correction methods, we found that maternal urinary and placental phthalates represent distinct exposure constructs and are not interchangeable.
There is a critical need to identify risk factors of Alzheimer's disease and related dementias (ADRD). We included 1227 participants (mean age [standard deviation]: 74.1 [7.9] years) from the Multi-Ethnic Study of Atherosclerosis with brain MRI scans. We investigated joint associations of 13 natural, social, and built-environment exposures with gray matter volume (GMV) (n = 1219), white matter fractional anisotropy (WM FA) (n = 1102), and white matter hyperintensity volume (n = 1210) using weighted quantile sum regression. A one-decile increase in all harmful exposures was associated with lower GMV and WM FA; however, associations were null when adjusting for study site. Examining the impact of many environmental factors simultaneously may provide insight into important modifiable risk factors for ADRD, capturing concomitant exposures as they are experienced.
Phthalates and bisphenols may contribute to childhood allergies through oxidative stress (OS). We examined OS as a potential pathway using two approaches: maternal OS biomarkers to evaluate mediation, and an OS genetic pathway function score reflecting child-level susceptibility to evaluate gene-environment interactions. In an Australian population-based birth cohort (n = 797), nine phthalate metabolites, three bisphenols, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured from spot urine samples at 36 weeks' gestation, with allergic and lung function outcomes assessed up to age four. Associations were estimated with generalised linear models for single exposures, and mixtures were analysed using weighted quantile sum regression (mediation) and quantile g-computation (interaction). The phthalate mixture (mainly driven by dimethyl and diethyl phthalates) was associated with a 14.6% increase in 8-OHdG (95% confidence interval [CI]: 9.4, 18.8). 8-OHdG mediated the association between the phthalate mixture and ventilation inhomogeneity (LCI2.5), with a mediated effect of 0.051 SD (95% CI: 0.002, 0.100). There were additive interactions between diethyl and dibutyl phthalates and genetic susceptibility for asthma and wheeze. The phthalate mixture was associated with higher LCI2.5 (β = 0.89 SD; 95% CI: 0.33, 1.45) and increased risks of asthma (risk ratio [RR] = 2.47; 95% CI: 1.31, 4.65) and wheeze (RR = 1.89; 95% CI: 1.21, 2.94), only in children genetically susceptible (p for interaction ≤0.002). No associations were observed for bisphenols or for other outcomes. This study suggests that OS may be a pathway through which maternal phthalate exposure impairs respiratory health in early childhood.
The U.S. Air Quality Index (AQI) is the most widely reported tool for public communication of air pollution health risks in the U.S., yet its effectiveness in protecting individuals with respiratory conditions remain poorly understood. The American Thoracic Society (ATS) convened an ad hoc multidisciplinary committee, including participation from relevant officials, to assess the current evidence and define research priorities related to the AQI and respiratory health. The committee conducted a systematic search of the peer-reviewed literature and held a full-day meeting to discuss key topics. Subsequent engagement refined the findings and established consensus on priority research questions. The systematic search indicated significant gaps in the literature, including limited evaluation of AQI effectiveness in changing behavior, few studies assessing health outcomes associated with AQI use, and minimal research on how people with respiratory disease interpret and respond to AQI messaging. Priority research areas span five key domains: AQI structure, sub-daily exposure estimation, communication strategies, clinical and community implementation, and evaluation of health and exposure reductions. Specific research recommendations include evaluating AQI structures that better reflect cumulative and multi-pollutant exposures, developing methods to assess how patients with respiratory conditions interpret and act on AQI messaging, and measuring whether AQI-informed behaviors result in meaningful reductions in exposure and improvements in health outcomes. This research statement outlines a framework for strengthening the scientific foundation of the AQI and improving its effectiveness as a respiratory health protection tool.