Social cohesion as a modifier of joint air pollution exposure and incident dementia.

Social cohesion can reduce stress, increase social interaction, and improve cognitive reserve. These social mechanisms may modify the effects of air pollution on dementia risk. This cohort study examines the potential moderating effect of social cohesion on associations between joint air pollution exposure and incident dementia leveraging data from 5112 community-dwelling adults ≥65 years of age enrolled in the National Health and Aging Trends Study (NHATS). Study participants were enrolled in 2011 and followed through 2018. We assigned 2010 residential census tract-level exposures to five air pollutants, particulate matter (PM) ≤ 10 µm in diameter, PM ≤ 2.5 µm in diameter, carbon monoxide, nitric oxide, and nitrogen dioxide, using the US Environmental Protection Agency's Community Multiscale Air Quality Modeling System. Dementia status was determined based on self- or proxy-reported dementia diagnosis or "probable dementia" according to NHATS cognitive screening tools. Participants' self-rated neighborhood social cohesion was evaluated based on three questions: neighbors knowing each other, being helpful, and being trustworthy. Social cohesion was dichotomized at the median into high vs low social cohesion. Associations between air pollutants and incident dementia were assessed using quantile g-computation Cox proportional hazard models and stratified by high vs low social cohesion, adjusting for age, sex, education, partner status, urbanicity, annual income, race and ethnicity, years lived at current residence, neighborhood disadvantage index, and tract segregation. High social cohesion (HR = 1.20, 95 % CI = 0.98, 1.47) and air pollution (HR = 1.08, 95 % CI = 0.92, 1.28) were not associated with incident dementia alone. However, when stratified, greater joint air pollution exposure increased dementia risk among participants at low (HR = 1.34, 95 % CI = 1.04, 1.72), but not high (HR = 1.00, 95 % CI = 0.93, 1.06) social cohesion. Air pollution was a risk factor for dementia only when reported social cohesion was low, suggesting that social interaction may play a protective role, mitigating dementia risk via air pollution exposure.

Increased Incidence of Vestibular Disorders in Patients With SARS-CoV-2.

Objective: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population. Study Design: Retrospective. Setting: Clinical data in the National COVID Cohort Collaborative database (N3C). Methods: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period. Results: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; P < 0.001), alpha (OR, 3.63; CI, 3.48-3.78; P < 0.001), delta (OR, 3.03; CI, 2.94-3.12; P < 0.001), omicron 21K variant (OR, 2.97; CI, 2.90-3.04; P < 0.001), and omicron 23A variant (OR, 8.80; CI, 8.35-9.27; P < 0.001). Conclusions: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings.

Accelerated aging and altered subclinical response to ozone exposure in young, healthy adults.

Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study (n = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA's effect modification of subclinical responses. For both approaches, we calculated Fisher-exact P-values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, P-value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, P = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the P-values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, P-value = 0.039). In conclusion, EAA is a potential biomarker for individuals with increased susceptibility to ozone exposure even among young, healthy adults.

Associations between long-term exposure to air pollution and kidney function utilizing electronic healthcare records: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) affects more than 38 million people in the United States, predominantly those over 65 years of age. While CKD etiology is complex, recent research suggests associations with environmental exposures. METHODS: Our primary objective is to examine creatinine-based estimated glomerular filtration rate (eGFRcr) and diagnosis of CKD and potential associations with fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) using a random sample of North Carolina electronic healthcare records (EHRs) from 2004 to 2016. We estimated eGFRcr using the serum creatinine-based 2021 CKD-EPI equation. PM2.5 and NO2 data come from a hybrid model using 1 km2 grids and O3 data from 12 km2 CMAQ grids. Exposure concentrations were 1-year averages. We used linear mixed models to estimate eGFRcr per IQR increase of pollutants. We used multiple logistic regression to estimate associations between pollutants and first appearance of CKD. We adjusted for patient sex, race, age, comorbidities, temporality, and 2010 census block group variables. RESULTS: We found 44,872 serum creatinine measurements among 7,722 patients. An IQR increase in PM2.5 was associated with a 1.63 mL/min/1.73m2 (95% CI: -1.96, -1.31) reduction in eGFRcr, with O3 and NO2 showing positive associations. There were 1,015 patients identified with CKD through e-phenotyping and ICD codes. None of the environmental exposures were positively associated with a first-time measure of eGFRcr < 60 mL/min/1.73m2. NO2 was inversely associated with a first-time diagnosis of CKD with aOR of 0.77 (95% CI: 0.66, 0.90). CONCLUSIONS: One-year average PM2.5 was associated with reduced eGFRcr, while O3 and NO2 were inversely associated. Neither PM2.5 or O3 were associated with a first-time identification of CKD, NO2 was inversely associated. We recommend future research examining the relationship between air pollution and impaired renal function.

Associations among NMR-measured inflammatory and metabolic biomarkers and accelerated aging in cardiac catheterization patients.

Research into aging has grown substantially with the creation of molecular biomarkers of biological age that can be used to determine age acceleration. Concurrently, nuclear magnetic resonance (NMR) assessment of biomarkers of inflammation and metabolism provides researchers with new ways to examine intermediate risk factors for chronic disease. We used data from a cardiac catheterization cohort to examine associations between biomarkers of cardiometabolic health and accelerated aging assessed using both gene expression (Transcriptomic Age) and DNA methylation (Hannum Age, GrimAge, Horvath Age, and Phenotypic Age). Linear regression models were used to associate accelerated aging with each outcome (cardiometabolic health biomarkers) while adjusting for chronological age, sex, race, and neighborhood socioeconomic status. Our study shows a robust association between GlycA and GrimAge (5.71, 95% CI = 4.36, 7.05, P = 7.94 × 10-16), Hannum Age (1.81, 95% CI = 0.65, 2.98, P = 2.30 × 10-3), and Phenotypic Age (2.88, 95% CI = 1.91, 3.87, P = 1.21 × 10-8). We also saw inverse associations between apolipoprotein A-1 and aging biomarkers. These associations provide insight into the relationship between aging and cardiometabolic health that may be informative for vulnerable populations.

Risk of dementia due to Co-exposure to air pollution and neighborhood disadvantage.

BACKGROUND: Co-exposure to air pollution and neighborhood disadvantage may influence cognition decline. We tested these associations in the context of dementia risk. METHODS: We leveraged a cohort of adults ≥65 years (n = 5397) enrolled from 2011 to 2018 in the National Health and Aging Trends Study (NHATS). Particulate matter (PM) ≤ 10 µm in diameter, PM ≤ 2.5 µm in diameter, carbon monoxide, nitric oxide, and nitrogen dioxide - and neighborhood disadvantage were tested for joint associations with dementia risk. Pollutant concentrations at the 2010 census tract level were assigned using the US Environmental Protection Agency's Community Multiscale Air Quality Modeling System. Neighborhood disadvantage was defined using the tract Social Deprivation Index (SDI). Dementia was determined through self- or proxy-report or scores indicative of "probable dementia" according to NHATS screening tools. Joint effects of air pollutants and SDI were tested using quantile g-computation Cox proportional hazards models. We also stratified joint air pollution effects across SDI tertiles. Analyses adjusted for age at enrollment, sex, education, partner status, urbanicity, income, race and ethnicity, years at residence, census segregation, and census region. RESULTS: SDI score (aHR = 1.08; 95% CI 0.96, 1.22), joint air pollution (aHR = 1.03, 95% CI 0.92, 1.16) and joint SDI with air pollution (aHR = 1.04, 95% CI 0.89, 1.22) were not associated with dementia risk. After accounting for competing risk of death, joint SDI with air pollution was not associated with dementia risk (aHR = 1.06; 95% CI 0.87, 1.29). In stratified models, joint air pollution was associated with greater risk of dementia at high (aHR = 1.19; 95% CI 0.87, 1.63), but not at medium or low SDI. CONCLUSION: Air pollution was associated with greater dementia risk in disadvantaged areas after accounting for competing risks. Air pollution associations with dementia incidence may be attenuated when other risk factors are more prominent in disadvantaged neighborhoods.

Serum metabolite signatures of cardiac function and morphology in individuals from a population-based cohort.

BACKGROUND: Changes in serum metabolites in individuals with altered cardiac function and morphology may exhibit information about cardiovascular disease (CVD) pathway dysregulations and potential CVD risk factors. We aimed to explore associations of cardiac function and morphology, evaluated using magnetic resonance imaging (MRI) with a large panel of serum metabolites. METHODS: Cross-sectional data from CVD-free individuals from the population-based KORA cohort were analyzed. Associations between 3T-MRI-derived left ventricular (LV) function and morphology parameters (e.g., volumes, filling rates, wall thickness) and markers of carotid plaque with metabolite profile clusters and single metabolites as outcomes were assessed by adjusted multinomial logistic regression and linear regression models. RESULTS: In 360 individuals (mean age 56.3 years; 41.9% female), 146 serum metabolites clustered into three distinct profiles that reflected high-, intermediate- and low-CVD risk. Higher stroke volume (relative risk ratio (RRR): 0.53, 95%-CI [0.37; 0.76], p-value < 0.001) and early diastolic filling rate (RRR: 0.51, 95%-CI [0.37; 0.71], p-value < 0.001) were most strongly protectively associated against the high-risk profile compared to the low-risk profile after adjusting for traditional CVD risk factors. Moreover, imaging markers were associated with 10 metabolites in linear regression. Notably, negative associations of stroke volume and early diastolic filling rate with acylcarnitine C5, and positive association of function parameters with lysophosphatidylcholines, diacylphosphatidylcholines, and acylalkylphosphatidylcholines were observed. Furthermore, there was a negative association of LV wall thickness with alanine, creatinine, and symmetric dimethylarginine. We found no significant associations with carotid plaque. CONCLUSIONS: Serum metabolite signatures are associated with cardiac function and morphology even in individuals without a clinical indication of CVD.

Prescribed fires, smoke exposure, and hospital utilization among heart failure patients.

BACKGROUND: Prescribed fires often have ecological benefits, but their environmental health risks have been infrequently studied. We investigated associations between residing near a prescribed fire, wildfire smoke exposure, and heart failure (HF) patients' hospital utilization. METHODS: We used electronic health records from January 2014 to December 2016 in a North Carolina hospital-based cohort to determine HF diagnoses, primary residence, and hospital utilization. Using a cross-sectional study design, we associated the prescribed fire occurrences within 1, 2, and 5 km of the patients' primary residence with the number of hospital visits and 7- and 30-day readmissions. To compare prescribed fire associations with those observed for wildfire smoke, we also associated zip code-level smoke density data designed to capture wildfire smoke emissions with hospital utilization amongst HF patients. Quasi-Poisson regression models were used for the number of hospital visits, while zero-inflated Poisson regression models were used for readmissions. All models were adjusted for age, sex, race, and neighborhood socioeconomic status and included an offset for follow-up time. The results are the percent change and the 95% confidence interval (CI). RESULTS: Associations between prescribed fire occurrences and hospital visits were generally null, with the few associations observed being with prescribed fires within 5 and 2 km of the primary residence in the negative direction but not the more restrictive 1 km radius. However, exposure to medium or heavy smoke (primarily from wildfires) at the zip code level was associated with both 7-day (8.5% increase; 95% CI = 1.5%, 16.0%) and 30-day readmissions (5.4%; 95% CI = 2.3%, 8.5%), and to a lesser degree, hospital visits (1.5%; 95% CI: 0.0%, 3.0%) matching previous studies. CONCLUSIONS: Area-level smoke exposure driven by wildfires is positively associated with hospital utilization but not proximity to prescribed fires.

Associations between medium- and long-term exposure to air temperature and epigenetic age acceleration.

Climate change poses a serious threat to human health worldwide, while aging populations increase. However, no study has ever investigated the effects of air temperature on epigenetic age acceleration. This study involved 1,725 and 1,877 participants from the population-based KORA F4 (2006-2008) and follow-up FF4 (2013-2014) studies, respectively, conducted in Augsburg, Germany. The difference between epigenetic age and chronological age was referred to as epigenetic age acceleration and reflected by Horvath's epigenetic age acceleration (HorvathAA), Hannum's epigenetic age acceleration (HannumAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Epigenetic Skin and Blood Age acceleration (SkinBloodAA). Daily air temperature was estimated using hybrid spatiotemporal regression-based models. To explore the medium- and long-term effects of air temperature modeled in time and space on epigenetic age acceleration, we applied generalized estimating equations (GEE) with distributed lag non-linear models, and GEE, respectively. We found that high temperature exposure based on the 8-week moving average air temperature (97.5th percentile of temperature compared to median temperature) was associated with increased HorvathAA, HannumAA, GrimAA, and SkinBloodAA: 1.83 (95% CI: 0.29-3.37), 11.71 (95% CI: 8.91-14.50), 2.26 (95% CI: 1.03-3.50), and 5.02 (95% CI: 3.42-6.63) years, respectively. Additionally, we found consistent results with high temperature exposure based on the 4-week moving average air temperature was associated with increased HannumAA, GrimAA, and SkinBloodAA: 9.18 (95% CI: 6.60-11.76), 1.78 (95% CI: 0.66-2.90), and 4.07 (95% CI: 2.56-5.57) years, respectively. For the spatial variation in annual average temperature, a 1 °C increase was associated with an increase in all five measures of epigenetic age acceleration (HorvathAA: 0.41 [95% CI: 0.24-0.57], HannumAA: 2.24 [95% CI: 1.95-2.53], PhenoAA: 0.32 [95% CI: 0.05-0.60], GrimAA: 0.24 [95%: 0.11-0.37], and SkinBloodAA: 1.17 [95% CI: 1.00-1.35] years). In conclusion, our results provide first evidence that medium- and long-term exposures to high air temperature affect increases in epigenetic age acceleration.

A Narrative Review on the Impact of Air Pollution on Heart Failure Risk and Exacerbation.

Air pollution is a risk factor for many cardiovascular diseases, including heart failure (HF). Although the links between air pollution and HF have been explored, the results are scattered and difficult to piece together into a cohesive story. Therefore, we undertook a narrative review of all aspects of the relationship between HF and air pollution exposure, including risks of developing HF when exposed to air pollution, the exacerbation of HF symptoms by air pollution exposure, and the increased susceptibility that individuals with HF have for air pollution-related health risks. We also examined the literature on environmental justice as well as air pollution interventions for HF. We found substantial evidence linking air pollution exposure to HF incidence. There were a limited number of studies that examined air pollution exposure in clearly defined populations with HF to explore exacerbation of HF or the susceptibility of individuals with HF to air pollution health risks. However, there is substantial evidence that HF-related hospitalisations are increased under air pollution exposure and that the air pollution associated increase in HF-related hospitalisations is greater than hospitalisations for other chronic diseases, supporting links between air pollution and both exacerbation of HF and susceptibility of individuals with HF. There is emerging evidence for interventions that can decrease air pollution health risks for individuals with HF, and more studies are needed, particularly randomised controlled trials. Thus, although the air pollution-related health risks for HF incidence and hospitalisations are clear, further studies specifically targeted at identified data gaps will greatly improve our knowledge of the susceptibility of individuals with HF and interventions to reduce risks.

Effect measure modification of the association between short-term exposures to PM2.5 and hospitalizations by longs-term PM2.5 exposure among a cohort of people with Chronic Obstructive Pulmonary Disease (COPD) in North Carolina, 2002-2015.

BACKGROUND: Approximately nine million adults in the United States are living with chronic obstructive pulmonary disease (COPD), and positive associations between short-term air pollution exposure and increased risk of COPD hospitalizations in older adults are consistently reported. We examined the association between short-term PM2.5 exposure and hospitalizations and assessed if there is modification by long-term exposure in a cohort of individuals with COPD. METHODS: In a time-referent case-crossover design, we used a cohort of randomly selected individuals with electronic health records from the University of North Carolina Healthcare System, restricted to patients with a medical encounter coded with a COPD diagnosis from 2004-2016 (n = 520), and estimated ambient PM2.5 concentrations from an ensemble model. Odds ratios and 95% confidence intervals (OR (95%CI)) were estimated with conditional logistic regression for respiratory-related, cardiovascular (CVD), and all-cause hospitalizations. Exposures examined were 0-2 and 0-3 day lags of PM2.5 concentration, adjusting for daily census-tract temperature and humidity, and models were stratified by long-term (annual average) PM2.5 concentration at the median value. RESULTS: We observed generally null or low-magnitude negative associations with short-term PM2.5 exposure and respiratory-related (OR per 5 µg/m3 increase in 3-day lag PM2.5: 0.971 (0.885, 1.066)), CVD (2-day lag: 0.976 (0.900, 1.058) and all-cause (3 day lag: 1.003 (0.927, 1.086)) hospitalizations. Associations between short-term PM2.5 exposure and hospitalizations were higher among patients residing in areas with higher levels of annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 1.066 (0.958, 1.185)) than those in areas with lower annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 0.914 (0.804, 1.039)). CONCLUISONS: Differences in associations demonstrate that people in areas with higher annual PM2.5 exposure may be associated with higher risk of hospitalization during short-term increases in PM2.5 exposure.

Wildfire smoke exposure and early childhood respiratory health: a study of prescription claims data.

Wildfire smoke is associated with short-term respiratory outcomes including asthma exacerbation in children. As investigations into developmental wildfire smoke exposure on children's longer-term respiratory health are sparse, we investigated associations between developmental wildfire smoke exposure and first use of respiratory medications. Prescription claims from IBM MarketScan Commercial Claims and Encounters database were linked with wildfire smoke plume data from NASA satellites based on Metropolitan Statistical Area (MSA). A retrospective cohort of live infants (2010-2016) born into MSAs in six western states (U.S.A.), having prescription insurance, and whose birthdate was estimable from claims data was constructed (N = 184,703); of these, gestational age was estimated for 113,154 infants. The residential MSA, gestational age, and birthdate were used to estimate average weekly smoke exposure days (smoke-day) for each developmental period: three trimesters, and two sequential 12-week periods post-birth. Medications treating respiratory tract inflammation were classified using active ingredient and mode of administration into three categories:: 'upper respiratory', 'lower respiratory', 'systemic anti-inflammatory'. To evaluate associations between wildfire smoke exposure and medication usage, Cox models associating smoke-days with first observed prescription of each medication category were adjusted for infant sex, birth-season, and birthyear with a random intercept for MSA. Smoke exposure during postnatal periods was associated with earlier first use of upper respiratory medications (1-12 weeks: hazard ratio (HR) = 1.094 per 1-day increase in average weekly smoke-day, 95%CI: (1.005,1.191); 13-24 weeks: HR = 1.108, 95%CI: (1.016,1.209)). Protective associations were observed during gestational windows for both lower respiratory and systemic anti-inflammatory medications; it is possible that these associations may be a consequence of live-birth bias. These findings suggest wildfire smoke exposure during early postnatal developmental periods impact subsequent early life respiratory health.

Associations between long-term fine particulate matter exposure and hospital procedures in heart failure patients.

BACKGROUND: Ambient fine particulate matter (PM2.5) contributes to global morbidity and mortality. One way to understand the health effects of PM2.5 is by examining its impact on performed hospital procedures, particularly among those with existing chronic disease. However, such studies are rare. Here, we investigated the associations between annual average PM2.5 and hospital procedures among individuals with heart failure. METHODS: Using electronic health records from the University of North Carolina Healthcare System, we created a retrospective cohort of 15,979 heart failure patients who had at least one of 53 common (frequency > 10%) procedures. We used daily modeled PM2.5 at 1x1 km resolution to estimate the annual average PM2.5 at the time of heart failure diagnosis. We used quasi-Poisson models to estimate associations between PM2.5 and the number of performed hospital procedures over the follow-up period (12/31/2016 or date of death) while adjusting for age at heart failure diagnosis, race, sex, year of visit, and socioeconomic status. RESULTS: A 1 µg/m3 increase in annual average PM2.5 was associated with increased glycosylated hemoglobin tests (10.8%; 95% confidence interval = 6.56%, 15.1%), prothrombin time tests (15.8%; 95% confidence interval = 9.07%, 22.9%), and stress tests (6.84%; 95% confidence interval = 3.65%, 10.1%). Results were stable under multiple sensitivity analyses. CONCLUSIONS: These results suggest that long-term PM2.5 exposure is associated with an increased need for diagnostic testing on heart failure patients. Overall, these associations give a unique lens into patient morbidity and potential drivers of healthcare costs linked to PM2.5 exposure.

Associations between source-apportioned PM2.5 and 30-day readmissions in heart failure patients.

BACKGROUND: Air pollution exposure is a significant risk factor for morbidity and mortality, especially for those with pre-existing chronic disease. Previous studies highlighted the risks that long-term particulate matter exposure has for readmissions. However, few studies have evaluated source and component specific associations particularly among vulnerable patient populations. OBJECTIVES: Use electronic health records from 5556 heart failure (HF) patients diagnosed between July 5, 2004 and December 31, 2010 that were part of the EPA CARES resource in conjunction with modeled source-specific fine particulate matter (PM2.5) to estimate the association between exposure to source and component apportioned PM2.5 at the time of HF diagnosis and 30-day readmissions. METHODS: We used zero-inflated mixed effects Poisson models with a random intercept for zip code to model associations while adjusting for age at diagnosis, year of diagnosis, race, sex, smoking status, and neighborhood socioeconomic status. We undertook several sensitivity analyses to explore the impact of geocoding precision and other factors on associations and expressed associations per interquartile range increase in exposures. RESULTS: We observed associations between 30-day readmissions and an interquartile range increase in gasoline- (16.9% increase; 95% confidence interval = 4.8%, 30.4%) and diesel-derived PM2.5 (9.9% increase; 95% confidence interval = 1.7%, 18.7%), and the secondary organic carbon component of PM2.5 (SOC; 20.4% increase; 95% confidence interval = 8.3%, 33.9%). Associations were stable in sensitivity analyses, and most consistently observed among Black study participants, those in lower income areas, and those diagnosed with HF at an earlier age. Concentration-response curves indicated a linear association for diesel and SOC. While there was some non-linearity in the gasoline concentration-response curve, only the linear component was associated with 30-day readmissions. DISCUSSION: There appear to be source specific associations between PM2.5 and 30-day readmissions particularly for traffic-related sources, potentially indicating unique toxicity of some sources for readmission risks that should be further explored.

Long-term exposure to ambient O3 and PM2.5 is associated with reduced cognitive performance in young adults: A retrospective longitudinal repeated measures study in adults aged 18-90 years.

A growing body of evidence indicates that exposure to air pollution affects cognitive performance; however, few studies have assessed this in the context of repeated measures within a large group of individuals or in a population with a large age range. In this study, we evaluated the associations between long-term exposure to fine particulate matter (PM2.5) and ozone (O3) in large cohort of adults aged 18-90 years. The study cohort included 29,091 Lumosity users in the contiguous US who completed 20 repetitions of the Lost in Migration game between 2017 and 2018. Game scores reflect the ability to filter information and avoid distracting information. Long-term air pollution data included ambient PM2.5 and O3 averaged for the 365-day period before each gameplay date. Generalized linear models were used to examine the associations between long-term PM2.5 and O3 and game score percentile. Co-pollutant models were adjusted for meteorology, time trend, age, gender, device, education, local socioeconomic factors, and urbanicity. Results represent the change in attention game score percentile per 1 µg/m3 increase in PM2.5 or 0.01 ppm increase in O3. In the entire cohort, a -0.10 (95% CI: -0.16, -0.04) change in score percentile was associated with PM2.5, while no significant association was observed with O3. Modification of these associations by age was observed for both PM2.5 and O3, with stronger associations observed in younger users. In users aged 18-29, a -0.25 (-0.45, -0.05) change in score percentile was associated with PM2.5, while no associations were observed in other age groups. With O3, there was a -2.92 (-4.63, -1.19) and -2.81 (-4.29, -1.25) change in score percentile for users aged 18-29 and 30-39, respectively. We observed that elevated long-term PM2.5 and O3 were associated with decreased focus scores in young adults, but follow-up research is necessary to further illuminate these associations.

Objectively measured external building quality, Census housing vacancies and age, and serum metals in an adult cohort in Detroit, Michigan.

BACKGROUND: Residentially derived lead pollution remains a significant problem in urban areas across the country and globe. The risks of childhood residence in housing contaminated with lead-based paint are well-established, but less is known about the effects of housing quality on adult lead exposure. OBJECTIVE: To evaluate the effects of residential-area housing age, vacancy status, and building quality on adult lead exposures. METHODS: We evaluated the effect of Census block group housing vacancy proportion, block group housing age, and in-person survey evaluated neighborhood building quality on serum levels of lead, mercury, manganese, and copper among a representative cohort of adults in Detroit, Michigan, from 2008-2013 using generalized estimating equations. RESULTS: Participants in Census block groups with higher proportions of vacant and aged housing had non-significantly elevated serum lead levels. We identified similar positive associations between residence in neighborhoods with poorer objectively measured building quality and serum lead. Associations between Census vacancies, housing age, objectively measured building quality, and serum lead were stronger among participants with a more stable residential history. SIGNIFICANCE: Vacant, aged, and poorly maintained housing may contribute to widespread, low-level lead exposure among adult residents of older cities like Detroit, Michigan. US Census and neighborhood quality data may be a useful tool to identify population-level lead exposures among US adults. IMPACT: Using longitudinal data from a representative cohort of adults in Detroit, Michigan, we demonstrate that Census data regarding housing vacancies and age and neighborhood survey data regarding housing quality are associated with increasing serum lead levels. Previous research has primarily focused on housing quality and lead exposures among children. Here, we demonstrate that area-level metrics of housing quality are associated with lead exposures among adults.

The association of accelerated epigenetic age with all-cause mortality in cardiac catheterization patients as mediated by vascular and cardiometabolic outcomes.

BACKGROUND: Epigenetic age is a DNA methylation-based biomarker of aging that is accurate across the lifespan and a range of cell types. The difference between epigenetic age and chronological age, termed age acceleration (AA), is a strong predictor of lifespan and healthspan. The predictive capabilities of AA for all-cause mortality have been evaluated in the general population; however, its utility is less well evaluated in those with chronic conditions. Additionally, the pathophysiologic pathways whereby AA predicts mortality are unclear. We hypothesized that AA predicts mortality in individuals with underlying cardiovascular disease; and the association between AA and mortality is mediated, in part, by vascular and cardiometabolic measures. METHODS: We evaluated 562 participants in an urban, three-county area of central North Carolina from the CATHGEN cohort, all of whom received a cardiac catheterization procedure. We analyzed three AA biomarkers, Horvath epigenetic age acceleration (HAA), phenotypic age acceleration (PhenoAA), and Grim age acceleration (GrimAA), by Cox regression models, to assess whether AAs were associated with all-cause mortality. We also evaluated if these associations were mediated by vascular and cardiometabolic outcomes, including left ventricular ejection fraction (LVEF), blood cholesterol concentrations, angiopoietin-2 (ANG2) protein concentration, peripheral artery disease, coronary artery disease, diabetes, and hypertension. The total effect, direct effect, indirect effect, and percentage mediated were estimated using pathway mediation tests with a regression adjustment approach. RESULTS: PhenoAA (HR = 1.05, P < 0.0001), GrimAA (HR = 1.10, P < 0.0001) and HAA (HR = 1.03, P = 0.01) were all associated with all-cause mortality. The association of mortality and PhenoAA was partially mediated by ANG2, a marker of vascular function (19.8%, P = 0.016), and by diabetes (8.2%, P = 0.043). The GrimAA-mortality association was mediated by ANG2 (12.3%, P = 0.014), and showed weaker evidence for mediation by LVEF (5.3%, P = 0.065). CONCLUSIONS: Epigenetic age acceleration remains strongly predictive of mortality even in individuals already burdened with cardiovascular disease. Mortality associations were mediated by ANG2, which regulates endothelial permeability and angiogenic functions, suggesting that specific vascular pathophysiology may link accelerated epigenetic aging with increased mortality risks.

Stress Drivers of Glucose Dynamics during Ozone Exposure Measured Using Radiotelemetry in Rats.

BACKGROUND: Inhaled irritant air pollutants may trigger stress-related metabolic dysfunction associated with altered circulating adrenal-derived hormones. OBJECTIVES: We used implantable telemetry in rats to assess real-time changes in circulating glucose during and after exposure to ozone and mechanistically linked responses to neuroendocrine stress hormones. METHODS: First, using a cross-over design, we monitored glucose during ozone exposures (0.0, 0.2, 0.4, and 0.8 ppm) and nonexposure periods in male Wistar Kyoto rats implanted with glucose telemeters. A second cohort of unimplanted rats was exposed to ozone (0.0, 0.4 or 0.8 ppm) for 30 min, 1 h, 2 h, or 4 h with hormones measured immediately post exposure. We assessed glucose metabolism in sham and adrenalectomized rats, with or without supplementation of adrenergic/glucocorticoid receptor agonists, and in a separate cohort, antagonists. RESULTS: Ozone (0.8 ppm) was associated with significantly higher blood glucose and lower core body temperature beginning 90 min into exposure, with reversal of effects 4-6 h post exposure. Glucose monitoring during four daily 4-h ozone exposures revealed duration of glucose increases, adaptation, and diurnal variations. Ozone-induced glucose changes were preceded by higher levels of adrenocorticotropic hormone, corticosterone, and epinephrine but lower levels of thyroid-stimulating hormone, prolactin, and luteinizing hormones. Higher glucose and glucose intolerance were inhibited in rats that were adrenalectomized or treated with adrenergic plus glucocorticoid receptor antagonists but exacerbated by agonists. DISCUSSION: We demonstrated the temporality of neuroendocrine-stress-mediated biological sequalae responsible for ozone-induced glucose metabolic dysfunction and mechanism in a rodent model. Stress hormones assessment with real-time glucose monitoring may be useful in identifying interactions among irritant pollutants and stress-related illnesses. https://doi.org/10.1289/EHP11088.