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Panagis Galiatsatos,1 Han Woo,1 Laura M Paulin,2 Amy Kind,3,4 Nirupama Putcha,1 Amanda J Gassett,5 Christopher B Cooper,6 Mark T Dransfield,7 Trisha M Parekh,7 Gabriela R Oates,8 R Graham Barr,9 Alejandro P Comellas,10 Meilan K Han,11 Stephen P Peters,12 Jerry A Krishnan,13 Wassim W Labaki,11 Meredith C McCormack,1 Joel D Kaufman,14 Nadia N Hansel1 1Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Pulmonary and Critical Care, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA; 3University of Wisconsin School of Medicine and Public Health, Department of Medicine Health Services and Care Research Program and Division of Geriatrics, Madison, WI, USA; 4Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA; 5Internal Medicine, University of Washington, Seattle, WA, USA; 6Department of Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA, USA; 7Department of Medicine, University of Alabama Birmingham and Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA; 8Department of Medicine, University of Alabama Birmingham, Birmingham, AL, USA; 9Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA; 10Internal Medicine and Pulmonary, University of Iowa, Iowa City, IA, USA; 11Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA; 12Department of Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA; 13Department of Medicine, University of Illinois, Chicago, IL, USA; 14Office of the Dean, University of Washington School of Public Health, Seattle, WA, USACorrespondence: Panagis GaliatsatosJohns Hopkins University School of Medicine, 4940 Eastern Avenue, Asthma and Allergy Building, 4th Floor, Baltimore, MD 21224, USATel +1410 550-0522Fax +1410 550-1094Email panagis@jhmi.eduRationale: Individual socioeconomic status has been shown to influence the outcomes of patients with chronic obstructive pulmonary disease (COPD). However, contextual factors may also play a role. The objective of this study is to evaluate the association between neighborhood socioeconomic disadvantage measured by the area deprivation index (ADI) and COPD-related outcomes.Methods: Residential addresses of SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) subjects with COPD (FEV1/FVC < 0.70) at baseline were geocoded and linked to their respective ADI national ranking score at the census block group level. The associations between the ADI and COPD-related outcomes were evaluated by examining the contrast between participants living in the most-disadvantaged (top quintile) to the least-disadvantaged (bottom quintile) neighborhood. Regression models included adjustment for individual-level demographics, socioeconomic variables (personal income, education), exposures (smoking status, packs per year, occupational exposures), clinical characteristics (FEV1% predicted, body mass index) and neighborhood rural status.Results: A total of 1800 participants were included in the analysis. Participants residing in the most-disadvantaged neighborhoods had 56% higher rate of COPD exacerbation (P< 0.001), 98% higher rate of severe COPD exacerbation (P=0.001), a 1.6 point higher CAT score (P< 0.001), 3.1 points higher SGRQ (P< 0.001), and 24.6 meters less six-minute walk distance (P=0.008) compared with participants who resided in the least disadvantaged neighborhoods.Conclusion: Participants with COPD who reside in more-disadvantaged neighborhoods had worse COPD outcomes compared to those residing in less-disadvantaged neighborhoods. Neighborhood effects were independent of individual-level socioeconomic factors, suggesting that contextual factors could be used to inform intervention strategies targeting high-risk persons with COPD.Keywords: health disparities, COPD, area deprivation index

Rationale: Ambient air pollution has been associated with heart failure morbidity and mortality. The mechanisms responsible for these associations are unknown but may include the effects of traffic-related pollutants on vascular or autonomic function.Objectives: We assessed the cross-sectional relation between long-term air pollution, traffic exposures, and important end-organ measures of alterations in cardiac function-left ventricular mass index (LVMI) and ejection fraction-in the Multi-Ethnic Study of Atherosclerosis, a multicenter study of adults without previous clinical cardiovascular disease.Methods: A total of 3,827 eligible participants (aged 45-84 yr) underwent cardiac magnetic resonance imaging between 2000 and 2002. We estimated air pollution exposures using residential proximity to major roadways and interpolated concentrations of fine particulate matter (less than 2.5 microns in diameter). We examined adjusted associations between these exposures and left ventricular mass and function.Measurements and Main Results: Relative to participants living more than 150 m from a major roadway, participants living within 50 m of a major roadway showed an adjusted 1.4 g/m(2) (95% CI, 0.3-2.5) higher LVMI, a difference in mass corresponding to a 5.6 mm Hg greater systolic blood pressure. Ejection fraction was not associated with proximity to major roadways. Limited variability in estimates of fine particulate matter was observed within cities, and no associations with particulate matter were found for either outcome after adjustment for center.Conclusions: Living in close proximity to major roadways is associated with higher LVMI, suggesting chronic vascular end-organ damage from a traffic-related environmental exposure. Air pollutants or another component of roadway proximity, such as noise, could be responsible. [ABSTRACT FROM AUTHOR]

BACKGROUND: Blood pressure (BP) may be implicated in associations observed between ambient particulate matter and cardiovascular morbidity and mortality. This study examined crosssectional associations between short-term ambient fine particles (particulate matter <= 2.5 [mu]m in aerodynamic diameter; PM2.5) and BP: systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse pressure (PP). METHODS: The study sample included 5,112 persons 45-84 years of age, free of cardiovascular disease at the Multi-Ethnic Study of Atherosclerosis baseline examination (2000-2002). Data from U.S. Environmental Protection Agency monitors were used to estimate ambient PM2.5 exposures for the preceding 1, 2, 7, 30, and 60 days. Roadway data were used to estimate local exposures to traffic-related particles. RESULTS: Results from linear regression found PP and SBP positively associated with PM2.5 For example, a 10-[mu]g/m(3) increase in PM2.5 30-day mean was associated with 1.12 mmHg higher pulse pressure [95% confidence interval (CI), 0.28-1.97] and 0.99 mmHg higher systolic BP (95% CI, -0.15 to 2.13), adjusted for age, sex, race/ethnicity, income, education, body mass index, diabetes, cigarette smoking and environmental tobacco smoke, alcohol use, physical activity, medications, atmospheric pressure, and temperature. Results were much weaker and not statistically significant for MAP and DBP. Although traffic-related variables were not themselves associated with BP, the association between PM2.5 and BP was stronger in the presence of higher traffic exposure. CONCLUSIONS: Higher SBP and PP were associated with ambient levels of PM2.5 and the association was stronger in the presence of roadway traffic, suggesting that impairment of blood pressure regulation may play a role in response to air pollution. [ABSTRACT FROM AUTHOR]

In primary prevention efforts to reduce the incidence of work-related musculoskeletal disease (MSD), many employers will use supervisor or worker assessments for initial evaluation of MSD risk factors. This cross-sectional study examined the ability of supervisors and workers to accurately assess the presence of MSD risk factors at four work sites in four different industries, examining five jobs that represented six primary categories of risk factors: posture, force, repetition, impact, lifting, and vibration. Thirty-seven supervisors and 55 workers assessed the jobs they oversee or perform through the use of a 14-item questionnaire. Their assessments were compared with detailed ergonomist job analyses to determine their accuracy in identifying the presence or absence of MSD risk factors. In assessing the absence or presence of all risk factors, agreement with the ergonomist was found 81% of the time for supervisors and 77% of the time for workers. Overall, supervisors and workers overestimated the presence of risk in assessing the jobs. Supervisors and worker assessments appear promising in recognizing risk in initial ergonomic assessments. [ABSTRACT FROM AUTHOR]

Information concerning the impact of environmental factors on cystic fibrosis (CF) is limited. We conducted a cohort study to assess the impact of air pollutants in CF. The study included patients over the age of 6 years enrolled in the Cystic Fibrosis Foundation National Patient Registry in 1999 and 2000. Exposure was assessed by linking air pollution values from the Aerometric Information Retrieval System with the patients' home zip code. After adjusting for confounders, a 10 microg/m(3) rise in particulate matter (both with a median aerodynamic diameter of 10 microm (PM(10)) or less and with an aerodynamic diameter of 2.5 microm or less (PM(2.5)) was associated with an 8% (95% confidence interval [CI], 2-15%) and 21% (95% CI, 7-33%) increase in the odds of two or more exacerbations, respectively; a 10-ppb rise in ozone was associated with a 10% (95% CI, 3-17%) increase in odds of two or more exacerbations. For every increase in PM(2.5) of 10 microg/m(3), there was an associated fall in FEV(1) of 24 ml (7-40) (95% CI) after adjusting for confounders. PM(2.5)'s association with mortality did not achieve statistical significance (adjusted RR = 1.32 per 10 microg/m(3) 0.91-1.93; 95% CI). Annual average exposures to particulate air pollution was associated with an increased risk of pulmonary exacerbations and a decline in lung function, suggesting a role of environmental exposures on prognosis in CF. [ABSTRACT FROM AUTHOR]

Background: Fine particulate air pollution has been linked to cardiovascular disease, but previous studies have assessed only mortality and differences in exposure between cities. We examined the association of long-term exposure to particulate matter of less than 2.5 microm in aerodynamic diameter (PM2.5) with cardiovascular events.Methods: We studied 65,893 postmenopausal women without previous cardiovascular disease in 36 U.S. metropolitan areas from 1994 to 1998, with a median follow-up of 6 years. We assessed the women's exposure to air pollutants using the monitor located nearest to each woman's residence. Hazard ratios were estimated for the first cardiovascular event, adjusting for age, race or ethnic group, smoking status, educational level, household income, body-mass index, and presence or absence of diabetes, hypertension, or hypercholesterolemia.Results: A total of 1816 women had one or more fatal or nonfatal cardiovascular events, as confirmed by a review of medical records, including death from coronary heart disease or cerebrovascular disease, coronary revascularization, myocardial infarction, and stroke. In 2000, levels of PM2.5 exposure varied from 3.4 to 28.3 microg per cubic meter (mean, 13.5). Each increase of 10 microg per cubic meter was associated with a 24% increase in the risk of a cardiovascular event (hazard ratio, 1.24; 95% confidence interval [CI], 1.09 to 1.41) and a 76% increase in the risk of death from cardiovascular disease (hazard ratio, 1.76; 95% CI, 1.25 to 2.47). For cardiovascular events, the between-city effect appeared to be smaller than the within-city effect. The risk of cerebrovascular events was also associated with increased levels of PM2.5 (hazard ratio, 1.35; 95% CI, 1.08 to 1.68).Conclusions: Long-term exposure to fine particulate air pollution is associated with the incidence of cardiovascular disease and death among postmenopausal women. Exposure differences within cities are associated with the risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

There is growing interest in cardiometabolic outcomes associated with nighttime noise, given that noise can disturb sleep and sleep disturbance can increase cardiometabolic risk such as hypertension. However, there is little empirical research evaluating the association between nighttime aircraft noise and hypertension risk. In this study, we expand on previous work to evaluate associations between nighttime aircraft noise exposure and self-reported hypertension incidence in the Nurses' Health Studies (NHS/NHSII), two US-wide cohorts of female nurses. Annual nighttime average aircraft sound levels (L night ) surrounding 90 airports for 1995-2015 (in 5-year intervals) were modeled using the Aviation Environmental Design Tool and assigned to participants' geocoded addresses over time. Hypertension risk was estimated for each cohort using time-varying Cox proportional-hazards models for L night dichotomized at 45 dB (dB), adjusting for individual-level hypertension risk factors, area-level socioeconomic status, region, and air pollution. Random effects meta-analysis was used to combine cohort results. Among 63,229 NHS and 98,880 NHSII participants free of hypertension at study baseline (1994/1995), we observed 33,190 and 28,255 new hypertension cases by 2014/2013, respectively. Although ∼1% of participants were exposed to L night ≥45 dB, we observed an adjusted hazard ratio (HR) of 1.10 (95% CI: 0.96, 1.27) in NHS and adjusted HR of 1.12 (95% CI: 0.98, 1.28) in NHSII, comparing exposure to L night ≥45 versus <45 dB(A). In meta-analysis, we observed an adjusted HR of 1.11 (95% CI: 1.01, 1.23). These results were attenuated with adjustment for additional variables such as body mass index. Our findings support a modest positive association between nighttime aircraft noise and hypertension risk across NHS/NHSII, which may reinforce the concept that sleep disturbance contributes to noise-related disease burden., Competing Interests: Declaration of competing interest Susan Redline reports a relationship with Jazz Pharmaceuticals Inc., Ireland that includes grant and consulting. All other authors declare they have no actual or potential competing financial interests., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Exposure to metals has been associated with cardiovascular disease (CVD) end points and mortality, yet prospective evidence is limited beyond arsenic, cadmium, and lead. In this study, we assessed the prospective association of urinary metals with incident CVD and all-cause mortality in a racially diverse population of US adults from MESA (the Multi-Ethnic Study of Atherosclerosis)., Methods: We included 6599 participants (mean [SD] age, 62.1 [10.2] years; 53% female) with urinary metals available at baseline (2000 to 2001) and followed through December 2019. We used Cox proportional hazards models to estimate the adjusted hazard ratio and 95% CI of CVD and all-cause mortality by baseline urinary levels of cadmium, tungsten, and uranium (nonessential metals), and cobalt, copper, and zinc (essential metals). The joint association of the 6 metals as a mixture and the corresponding 10-year survival probability was calculated using Cox Elastic-Net., Results: During follow-up, 1162 participants developed CVD, and 1844 participants died. In models adjusted by behavioral and clinical indicators, the hazard ratios (95% CI) for incident CVD and all-cause mortality comparing the highest with the lowest quartile were, respectively: 1.25 (1.03, 1.53) and 1.68 (1.43, 1.96) for cadmium; 1.20 (1.01, 1.42) and 1.16 (1.01, 1.33) for tungsten; 1.32 (1.08, 1.62) and 1.32 (1.12, 1.56) for uranium; 1.24 (1.03, 1.48) and 1.37 (1.19, 1.58) for cobalt; 1.42 (1.18, 1.70) and 1.50 (1.29, 1.74) for copper; and 1.21 (1.01, 1.45) and 1.38 (1.20, 1.59) for zinc. A positive linear dose-response was identified for cadmium and copper with both end points. The adjusted hazard ratios (95% CI) for an interquartile range (IQR) increase in the mixture of these 6 urinary metals and the corresponding 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56) and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91) and -2.0% (-2.6, -1.5) for all-cause mortality., Conclusions: This epidemiological study in US adults indicates that urinary metal levels are associated with increased CVD risk and mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health., Competing Interests: None.

Background: Reported associations between particulate matter with aerodynamic diameter ≤2.5 μm (PM 2.5 ) and cognitive outcomes remain mixed. Differences in exposure estimation method may contribute to this heterogeneity., Objectives: To assess agreement between PM 2.5 exposure concentrations across 11 exposure estimation methods and to compare resulting associations between PM 2.5 and cognitive or MRI outcomes., Methods: We used Visit 5 (2011-2013) cognitive testing and brain MRI data from the Atherosclerosis Risk in Communities (ARIC) Study. We derived address-linked average 2000-2007 PM 2.5 exposure concentrations in areas immediately surrounding the four ARIC recruitment sites (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; Washington County, MD) using 11 estimation methods. We assessed agreement between method-specific PM 2.5 concentrations using descriptive statistics and plots, overall and by site. We used adjusted linear regression to estimate associations of method-specific PM 2.5 exposure estimates with cognitive scores (n = 4678) and MRI outcomes (n = 1518) stratified by study site and combined site-specific estimates using meta-analyses to derive overall estimates. We explored the potential impact of unmeasured confounding by spatially patterned factors., Results: Exposure estimates from most methods had high agreement across sites, but low agreement within sites. Within-site exposure variation was limited for some methods. Consistently null findings for the PM 2.5 -cognitive outcome associations regardless of method precluded empirical conclusions about the potential impact of method on study findings in contexts where positive associations are observed. Not accounting for study site led to consistent, adverse associations, regardless of exposure estimation method, suggesting the potential for substantial bias due to residual confounding by spatially patterned factors., Discussion: PM 2.5 estimation methods agreed across sites but not within sites. Choice of estimation method may impact findings when participants are concentrated in small geographic areas. Understanding unmeasured confounding by factors that are spatially patterned may be particularly important in studies of air pollution and cognitive or brain health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Melinda Power reports financial support was provided by National Institutes of Health.Melinda Power reports a relationship with National Institutes of Health that includes: funding grants. Melinda Power reports a relationship with U.S. Department of Defense that includes: funding grants. Melinda Power reports a relationship with DC DEPARTMENT OF HEALTH that includes: funding grants. Melinda Power reports a relationship with Biogen that includes: consulting or advisory. Erin Bennett reports a relationship with Massachusetts General Hospital that includes: consulting or advisory. Eun Sug Park reports a relationship with National Institutes of Health that includes: funding grants. Jeff D. Yanosky reports a relationship with National Institutes of Health that includes: funding grants. Duanping Liao reports a relationship with National Institutes of Health that includes: funding grants. Joel D. Kaufman reports a relationship with National Institutes of Health that includes: funding grants. Joel D. Kaufman reports a relationship with U.S. Environmental Protection Agency that includes: funding grants. Lianne Sheppard reports a relationship with National Institutes of Health that includes: funding grants. Lianne Sheppard reports a relationship with Health Effects Institute that includes: funding grants. Adam Szpiro reports a relationship with National Institutes of Health that includes: funding grants. Adam Szpiro reports a relationship with Health Effects Institute that includes: funding grants. Adam Szpiro reports a relationship with Health Effects Institute that includes: consulting or advisory. Eric Whitsel reports a relationship with National Institutes of Health that includes: funding grants. Eric Whitsel reports a relationship with USFederal Aviation Administration that includes: funding grants.If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: It is unknown whether air pollution is associated with radiographic features of interstitial lung disease in individuals with chronic obstructive pulmonary disease (COPD). Objectives: To determine whether air pollution increases the prevalence of interstitial lung abnormalities (ILA) or percent high-attenuation areas (HAA) on computed tomography (CT) in individuals with a heavy smoking history and COPD. Methods: We performed a cross-sectional study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), focused on current or former smokers with COPD. Ten-year exposure to particulate matter ⩽2.5 μm in aerodynamic diameter (PM 2.5 ), nitrogen oxides (NO x ), nitrogen dioxide (NO 2 ), and ozone before enrollment CT (completed between 2010 and 2015) were estimated with validated spatiotemporal models at residential addresses. We applied adjusted multivariable modified Poisson regression and linear regression to investigate associations between pollution exposure and relative risk (RR) of ILA or increased percent HAA (between -600 and -250 Hounsfield units), respectively. We assessed for effect modification by MUC5B -promoter polymorphism (variant allele carriers GT or TT vs. GG at rs3705950), smoking status, sex, and percent emphysema. Results: Among 1,272 participants with COPD assessed for HAA, 424 were current smokers, and 249 were carriers of the variant MUC5B allele. A total of 519 participants were assessed for ILA. We found no association between pollution exposure and ILA or HAA. Associations between pollutant exposures and risk of ILA were modified by the presence of MUC5B polymorphism ( P value interaction term for NO x  = 0.04 and PM 2.5  = 0.05) and smoking status ( P value interaction term for NO x  = 0.05; NO 2  = 0.01; and ozone = 0.05). With higher exposure to NO x and PM 2.5 , MUC5B variant carriers had an increased risk of ILA (RR per 26 ppb NO x , 2.41; 95% confidence interval [CI], 0.97-6.0; and RR per 4 μg ⋅ m -3 PM 2.5 , 1.43; 95% CI, 0.93-2.2, respectively). With higher exposure to NO 2 , former smokers had an increased risk of ILA (RR per 10 ppb, 1.64; 95% CI, 1.0-2.7). Conclusions: Exposure to ambient air pollution was not associated with interstitial features on CT in this population of heavy smokers with COPD. MUC5B modified the association between pollution and ILA, suggesting that gene-environment interactions may influence prevalence of interstitial lung features in COPD.

Background: Increased exposure to ambient air pollution, especially fine particulate matter ≤ 2.5 μ m ( PM 2.5 ) is associated with poorer brain health and increased risk for Alzheimer's disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants., Objective: Our aim was to investigate if exposure to PM 2.5 was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia., Methods: We examined the relationship between PM 2.5 and in vivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio ( LC CNR ) in 381 men [ mean age = 67.3 ; standard deviation ( SD ) = 2.6 ] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to PM 2.5 was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on LC CNR in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between PM 2.5 exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment., Results: Multiple linear regressions revealed a significant association between PM 2.5 and rostral-middle LC CNR ( β = - 0.16 ; p = 0.02 ), whereby higher exposure to PM 2.5 was associated with lower LC CNR . A co-twin control analysis found that, within monozygotic pairs, individuals with higher PM 2.5 exposure showed lower LC CNR ( β = - 0.11 ; p = 0.02 ), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between PM 2.5 and caudal LC CNR or hippocampal volume, suggesting a degree of specificity to the rostral-middle portion of the LC., Discussion: Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. https://doi.org/10.1289/EHP14344.

Prediabetes is a heterogenous metabolic state with various risks for development of type 2 diabetes (T2D). In this study, we used genetic data on 7,227 US Hispanic/Latino participants without diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and 400,149 non-Hispanic White participants without diabetes from the UK Biobank (UKBB) to calculate five partitioned polygenetic risk scores (pPRSs) representing various pathways related to T2D. Consensus clustering was performed in participants with prediabetes in HCHS/SOL (n = 3,677) and UKBB (n = 16,284) separately based on these pPRSs. Six clusters of individuals with prediabetes with distinctive patterns of pPRSs and corresponding metabolic traits were identified in the HCHS/SOL, five of which were confirmed in the UKBB. Although baseline glycemic traits were similar across clusters, individuals in cluster 5 and cluster 6 showed an elevated risk of T2D during follow-up compared with cluster 1 (risk ratios [RRs] 1.29 [95% CI 1.08, 1.53] and 1.34 [1.13, 1.60], respectively). Inverse associations between a healthy lifestyle score and risk of T2D were observed across different clusters, with a suggestively stronger association observed in cluster 5 compared with cluster 1. Among individuals with a healthy lifestyle, those in cluster 5 had a similar risk of T2D compared with those in cluster 1 (RR 1.03 [0.91, 1.18]). This study identified genetic subtypes of prediabetes that differed in risk of progression to T2D and in benefits from a healthy lifestyle., (© 2024 by the American Diabetes Association.)

Background: Valid, high-resolution estimates of population-level exposure to air pollutants are necessary for accurate estimation of the association between air pollution and the occurrence or exacerbation of adverse health outcomes such as Chronic Obstructive Pulmonary Disease (COPD)., Objectives: We produced fine-scale individual-level estimates of ambient concentrations of multiple air pollutants (fine particulate matter [PM 2.5 ], NO X , NO 2 , and O 3 ) at residences of participants in the Subpopulations and Intermediate Outcomes in COPD Air Pollution (SPIROMICS Air) study, located in seven regions in the US. For PM 2.5 , we additionally integrated modeled estimates of particulate infiltration based on home characteristics and measured total indoor concentrations to provide comprehensive estimates of exposure levels., Methods: To estimate ambient concentrations, we used a hierarchical high-resolution spatiotemporal model that integrates hundreds of geographic covariates and pollutant measurements from regulatory and study-specific monitors, including ones located at participant residences. We modeled infiltration efficiency based on data on house characteristics, home heating and cooling practices, indoor smoke and combustion sources, meteorological factors, and paired indoor-outdoor pollutant measurements, among other indicators., Results: Cross-validated prediction accuracy (R 2 ) for models of ambient concentrations was above 0.80 for most regions and pollutants. Particulate matter infiltration efficiency varied by region, from 0.51 in Winston-Salem to 0.72 in Los Angeles, and ambient-source particles constituted a substantial fraction of total indoor PM 2.5 ., Conclusion: Leveraging well-validated fine-scale approaches for estimating outdoor, ambient-source indoor, and total indoor pollutant concentrations, we can provide comprehensive estimates of short and long-term exposure levels for cohorts undergoing follow-up in multiple different regions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Prescott G Woodruff reports a relationship with AstraZeneca, Sanofi, Regeneron, Roche that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Outdoor air pollution is a ubiquitous exposure that includes endocrine-disrupting and carcinogenic compounds that may contribute to the risk of hormone-sensitive outcomes such as uterine cancer. However, there is limited evidence about the relationship between outdoor air pollution and uterine cancer incidence., Methods: We investigated the associations of residential exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2) with uterine cancer among 33 417 Sister Study participants with an intact uterus at baseline (2003-2009). Annual average air pollutant concentrations were estimated at participants' geocoded primary residential addresses using validated spatiotemporal models. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association between time-varying 12-month PM2.5 (µg/m3) and NO2 (parts per billion; ppb) averages and uterine cancer incidence., Results: Over a median follow-up period of 9.8 years, 319 incident uterine cancer cases were identified. A 5-ppb increase in NO2 was associated with a 23% higher incidence of uterine cancer (hazard ratio = 1.23, 95% confidence interval = 1.04 to 1.46), especially among participants living in urban areas (hazard ratio = 1.53, 95% confidence interval = 1.13 to 2.07), but  PM2.5 was not associated with increased uterine cancer incidence., Conclusion: In this large US cohort, NO2, a marker of vehicular traffic exposure, was associated with a higher incidence of uterine cancer. These findings expand the scope of health effects associated with air pollution, supporting the need for policy and other interventions designed to reduce air pollutant exposure., (Published by Oxford University Press 2024.)

Importance: Air pollution is a recognized risk factor associated with chronic diseases, including respiratory and cardiovascular conditions, which can lead to physical and cognitive impairments in later life. Although these losses of function, individually or in combination, reduce individuals' likelihood of living independently, little is known about the association of air pollution with this critical outcome., Objective: To investigate associations between air pollution and loss of independence in later life., Design, Setting, and Participants: This cohort study was conducted as part of the Environmental Predictors Of Cognitive Health and Aging study and used 1998 to 2016 data from the Health and Retirement Study. Participants included respondents from this nationally representative, population-based cohort who were older than 50 years and had not previously reported a loss of independence. Analyses were performed from August 31 to October 15, 2023., Exposures: Mean 10-year pollutant concentrations (particulate matter less than 2.5 μm in diameter [PM2.5] or ranging from 2.5 μm to 10 μm in diameter [PM10-2.5], nitrogen dioxide [NO2], and ozone [O3]) were estimated at respondent addresses using spatiotemporal models along with PM2.5 levels from 9 emission sources., Main Outcomes and Measures: Loss of independence was defined as newly receiving care for at least 1 activity of daily living or instrumental activity of daily living due to health and memory problems or moving to a nursing home. Associations were estimated with generalized estimating equation regression adjusting for potential confounders., Results: Among 25 314 respondents older than 50 years (mean [SD] baseline age, 61.1 [9.4] years; 11 208 male [44.3%]), 9985 individuals (39.4%) experienced lost independence during a mean (SD) follow-up of 10.2 (5.5) years. Higher exposure levels of mean concentration were associated with increased risks of lost independence for total PM2.5 levels (risk ratio [RR] per 1-IQR of 10-year mean, 1.05; 95% CI, 1.01-1.10), PM2.5 levels from road traffic (RR per 1-IQR of 10-year mean, 1.09; 95% CI, 1.03-1.16) and nonroad traffic (RR per 1-IQR of 10-year mean, 1.13; 95% CI, 1.03-1.24), and NO2 levels (RR per 1-IQR of 10-year mean, 1.05; 95% CI, 1.01-1.08). Compared with other sources, traffic-generated pollutants were most consistently and robustly associated with loss of independence; only road traffic-related PM2.5 levels remained associated with increased risk after adjustment for PM2.5 from other sources (RR per 1-IQR increase in 10-year mean concentration, 1.10; 95% CI, 1.00-1.21). Other pollutant-outcome associations were null, except for O3 levels, which were associated with lower risks of lost independence (RR per 1-IQR increase in 10-year mean concentration, 0.94; 95% CI, 0.92-0.97)., Conclusions and Relevance: This study found that long-term exposure to air pollution was associated with the need for help for lost independence in later life, with especially large and consistent increases in risk for pollution generated by traffic-related sources. These findings suggest that controlling air pollution could be associated with diversion or delay of the need for care and prolonged ability to live independently.

Background: Evidence linking gaseous air pollution to late-life brain health is mixed., Objective: We explored associations between exposure to gaseous pollutants and brain magnetic resonance imaging (MRI) markers among Atherosclerosis Risk in Communities (ARIC) Study participants, with attention to the influence of exposure estimation method and confounding by site., Methods: We considered data from 1,665 eligible ARIC participants recruited from four US sites in the period 1987-1989 with valid brain MRI data from Visit 5 (2011-2013). We estimated 10-y (2001-2010) mean carbon monoxide (CO), nitrogen dioxide ( NO 2 ), nitrogen oxides ( NO x ), and 8- and 24-h ozone ( O 3 ) concentrations at participant addresses, using multiple exposure estimation methods. We estimated site-specific associations between pollutant exposures and brain MRI outcomes (total and regional volumes; presence of microhemorrhages, infarcts, lacunes, and severe white matter hyperintensities), using adjusted linear and logistic regression models. We compared meta-analytically combined site-specific associations to analyses that did not account for site., Results: Within-site exposure distributions varied across exposure estimation methods. Meta-analytic associations were generally not statistically significant regardless of exposure, outcome, or exposure estimation method; point estimates often suggested associations between higher NO 2   and   NO x and smaller temporal lobe, deep gray, hippocampal, frontal lobe, and Alzheimer disease signature region of interest volumes and between higher CO and smaller temporal and frontal lobe volumes. Analyses that did not account for study site more often yielded significant associations and sometimes different direction of associations., Discussion: Patterns of local variation in estimated air pollution concentrations differ by estimation method. Although we did not find strong evidence supporting impact of gaseous pollutants on brain changes detectable by MRI, point estimates suggested associations between higher exposure to CO, NO x , and NO 2 and smaller regional brain volumes. Analyses of air pollution and dementia-related outcomes that do not adjust for location likely underestimate uncertainty and may be susceptible to confounding bias. https://doi.org/10.1289/EHP13906.

Rationale: Airway tree morphology varies in the general population and may modify the distribution and uptake of inhaled pollutants. Objectives: We hypothesized that smaller airway caliber would be associated with emphysema progression and would increase susceptibility to air pollutant-associated emphysema progression. Methods: MESA (Multi-Ethnic Study of Atherosclerosis) is a general population cohort of adults 45-84 years old from six U.S. communities. Airway tree caliber was quantified as the mean of airway lumen diameters measured from baseline cardiac computed tomography (CT) (2000-2002). Percentage emphysema, defined as percentage of lung pixels below -950 Hounsfield units, was assessed up to five times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scan (2010-2018). Long-term outdoor air pollutant concentrations (particulate matter with an aerodynamic diameter ⩽2.5 μm, oxides of nitrogen, and ozone) were estimated at the residential address with validated spatiotemporal models. Linear mixed models estimated the association between airway tree caliber and emphysema progression; modification of pollutant-associated emphysema progression was assessed using multiplicative interaction terms. Measurements and Main Results: Among 6,793 participants (mean ± SD age, 62 ± 10 yr), baseline airway tree caliber was 3.95 ± 1.1 mm and median (interquartile range) of percentage emphysema was 2.88 (1.21-5.68). In adjusted analyses, 10-year emphysema progression rate was 0.75 percentage points (95% confidence interval, 0.54-0.96%) higher in the smallest compared with largest airway tree caliber quartile. Airway tree caliber also modified air pollutant-associated emphysema progression. Conclusions: Smaller airway tree caliber was associated with accelerated emphysema progression and modified air pollutant-associated emphysema progression. A better understanding of the mechanisms of airway-alveolar homeostasis and air pollutant deposition is needed.

Accurately predicting ambient NO 2 concentrations has great public health importance, as traffic-related air pollution is of major concern in urban areas. In this study, we present a novel approach incorporating traffic contribution to NO 2 prediction in a fine-scale spatiotemporal model. We used nationally available traffic estimate dataset in a scalable dispersion model, Research LINE source dispersion model (RLINE). RLINE estimates then served as an additional input for a validated spatiotemporal pollution modeling approach. Our analysis uses measurement data collected by the Multi-Ethnic Study of Atherosclerosis and Air Pollution in the greater Los Angeles area between 2006 and 2009. We predicted road-type-specific annual average daily traffic (AADT) on road segments via national-level spatial regression models with nearest-neighbor Gaussian processes (spNNGP); the spNNGP models were trained based on over half a million point-level traffic volume measurements nationwide. AADT estimates on all highways were combined with meteorological data in RLINE models. We evaluated two strategies to integrate RLINE estimates into spatiotemporal NO 2 models: 1) incorporating RLINE estimates as a space-only covariate and, 2) as a spatiotemporal covariate. The results showed that integrating the RLINE estimates as a space-only covariate improved overall cross-validation R 2 from 0.83 to 0.84, and root mean squared error (RMSE) from 3.58 to 3.48 ppb. Incorporating the estimates as a spatiotemporal covariate resulted in similar model improvement. The improvement of our spatiotemporal model was more profound in roadside monitors alongside highways, with R 2 increasing from 0.56 to 0.66 and RMSE decreasing from 3.52 to 3.11 ppb. The observed improvement indicates that the RLINE estimates enhanced the model's predictive capabilities for roadside NO 2 concentration gradients even after considering a comprehensive list of geographic covariates including the distance to roads. Our proposed modeling framework can be generalized to improve high-resolution prediction of NO 2 exposure - especially near major roads in the U.S., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To examine whether long-term air pollution exposure is associated with central hemodynamic and brachial artery stiffness parameters., Methods: We assessed central hemodynamic parameters including central blood pressure, cardiac parameters, systemic vascular compliance and resistance, and brachial artery stiffness measures [including brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR)] using waveform analysis of the arterial pressure signals obtained from a standard cuff sphygmomanometer (DynaPulse2000A, San Diego, CA). The long-term exposures to particles with an aerodynamic diameter < 2.5 μm (PM2.5) and nitrogen dioxide (NO2) for the 3-year periods prior to enrollment were estimated at residential addresses using fine-scale intra-urban spatiotemporal models. Linear mixed models adjusted for potential confounders were used to examine associations between air pollution exposures and health outcomes., Results: The cross-sectional study included 2,387 Chicago residents (76% African Americans) enrolled in the ChicagO Multiethnic Prevention And Surveillance Study (COMPASS) during 2013-2018 with validated address information, PM2.5 or NO2, key covariates, and hemodynamics measurements. We observed long-term concentrations of PM2.5 and NO2 to be positively associated with central systolic, pulse pressure and BAR, and negatively associated with BAD, and BAC after adjusting for relevant covariates. A 1-µg/m 3 increment in preceding 3-year exposures to PM2.5 was associated with 1.8 mmHg higher central systolic (95% CI: 0.98, 4.16), 1.0 mmHg higher central pulse pressure (95% CI: 0.42, 2.87), a 0.56%mmHg lower BAD (95% CI: -0.81, -0.30), and a 0.009 mL/mmHg lower BAC (95% CI: -0.01, -0.01)., Conclusion: This population-based study provides evidence that long-term exposures to PM2.5 and NO2 is related to central BP and arterial stiffness parameters, especially among African Americans., (© 2024. The Author(s).)

Objective: This study sought to investigate a novel strategy using temperature-controlled delivery of nanosecond pulsed electric fields as an alternative to the 50-100 microsecond pulses used for irreversible electroporation., Methods: INSPIRE treatments were carried out at two temperatures in 3D tumor models using doses between 0.001 s and 0.1 s. The resulting treatment zones were quantified using viability staining and lethal electric field intensities were determined numerically. Computational modeling was then used to determine parameters necessary for INSPIRE treatments to achieve equivalent treatment zones to clinical electroporation treatments and evaluate the potential for these treatments to induce deleterious thermal damage., Results: Lethal thresholds between 1109 and 709 V/cm were found for nominal 0.01 s treatments with pulses between 350 ns and 2000 ns at physiological temperatures. Further increases in dose resulted in significant decreases in lethal thresholds. Given these experimental results, treatment zones comparable to clinical electroporation are possible by increasing the dose and voltage used with nanosecond duration pulses. Temperature-controlled simulations indicate minimal thermal cell death while achieving equivalent treatment volumes to clinical electroporation., Conclusion: Nanosecond electrical pulses can achieve comparable outcomes to traditional electroporation provided sufficient electrical doses or voltages are applied. The use of temperature-controlled delivery may minimize thermal damage during treatment., Significance: Intense muscle stimulation and the need for cardiac gating have limited irreversible electroporation. Nanosecond pulses can alleviate these challenges, but traditionally have produced significantly smaller treatment zones. This study suggests that larger ablation volumes may be possible with the INSPIRE approach and that future in vivo studies are warranted.

Background: Fine particulate matter (PM 2.5 ) exposure has been associated with liver cancer incidence and mortality in a limited number of studies. We sought to evaluate this relationship for the first time in a U.S. cohort with historical exposure assessment., Methods: We used spatiotemporal prediction models to estimate annual average historical PM 2.5 concentrations (1980-2015) at residential addresses of 499,729 participants in the NIH-AARP Diet and Health Study, a cohort in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, Georgia, and Detroit, Michigan) enrolled in 1995-1996 and followed up through 2017. We used a time-varying Cox model to estimate the association for liver cancer and the predominant histologic type, hepatocellular carcinoma (HCC), per 5 µg/m 3 increase in estimated outdoor PM 2.5 levels, incorporating a 5-year average, lagged 10 years prior to cancer diagnosis and adjusting for age, sex, race/ethnicity, education level and catchment state. We also evaluated PM 2.5 interactions with hypothesized effect modifiers., Results: We observed a non-significantly increased risk of liver cancer associated with estimated PM 2.5 exposure (Hazard ratio [HR] = 1.05 [0.96-1.14], N = 1,625); associations were slightly stronger for HCC, (84 % of cases; HR = 1.08 [0.98-1.18]). Participants aged 70 or older at enrollment had an increased risk of liver cancer versus other age groups (HR = 1.50 [1.01-2.23]); p-interaction = 0.01) and risk was elevated among participants who did not exercise (HR = 1.81 [1.22-2.70]; p-interaction = 0.01). We found no evidence of effect modification by sex, smoking status, body mass index, diabetes status, or alcohol consumption (p-interaction > 0.05)., Conclusions: Our findings in this large cohort suggest that residential ambient PM 2.5 levels may be associated with liver cancer risk. Further exploration of the variation in associations by age and physical activity are important areas for future research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: Growing evidence links air pollution exposure to the risk of dementia. We hypothesized that hypertension may partially mediate this effect., Methods: We previously documented an association between air pollution and dementia in the Ginkgo Evaluation of Memory Study, a randomized, placebo-controlled trial of 3069 adults ≥75 years across four US sites who were evaluated for dementia every 6 months from 2000-2008. We utilized a two-stage regression approach for causal mediation analysis to decompose the total effect of air pollution on dementia into its natural direct and indirect effect through prevalent hypertension. Exposure to air pollution in the 10 or 20 years before enrollment was assigned using estimates from fine-scale spatial-temporal models for PM 2.5 , PM 10 , and NO 2 . We used Poisson regression models for hypertension and Cox proportional hazard models for time-to-incident all-cause dementia, adjusting for a priori confounders., Results: Participants were free of mild cognitive impairment at baseline (n = 2564 included in analyses); 69% had prevalent hypertension at baseline. During follow-up, 12% developed all-cause dementia (Alzheimer's disease [AD] = 212; vascular dementia with or without AD [VaD/AD mixed] = 97). We did not find an adverse effect of any air pollutant on hypertension. Hypertension was associated with VaD/AD mixed (HR, 1.92 [95% CI = 1.14, 3.24]) but not AD. We did not observe mediation through hypertension for the effect of any pollutant on dementia outcomes., Conclusions: The lack of mediated effect may be due to other mechanistic pathways and the minimal effect of air pollution on hypertension in this cohort of older adults., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Inequities in urban greenspace have been identified, though patterns by race and socioeconomic status vary across US settings. We estimated the magnitude of the relationship between a broad mixture of neighborhood-level factors and residential greenspace using weighted quantile sum (WQS) regression, and compared predictive models of greenspace using only neighborhood-level, only individual-level, or multi-level predictors. Greenspace measures included the Normalized Difference Vegetation Index (NDVI), tree canopy, and proximity of the nearest park, for residential locations in Shelby County, Tennessee of children in the CANDLE cohort. Neighborhood measures include socioeconomic and education resources, as well as racial composition and racial residential segregation. In this sample of 1012 mother-child dyads, neighborhood factors were associated with higher NDVI and tree canopy (0.021 unit higher NDVI [95% CI: 0.014, 0.028] per quintile increase in WQS index); homeownership rate, proximity of and enrollment at early childhood education centers, and racial composition, were highly weighted in the WQS index. In models constrained in the opposite direction (0.028 unit lower NDVI [95% CI: - 0.036, - 0.020]), high school graduation rate and teacher experience were highly weighted. In prediction models, adding individual-level predictors to the suite of neighborhood characteristics did not meaningfully improve prediction accuracy for greenspace measures. Our findings highlight disparities in greenspace for families by neighborhood socioeconomic and early education factors, and by race, suggesting several neighborhood indicators for consideration both as potential confounders in studies of greenspace and pediatric health as well as in the development of policies and programs to improve equity in greenspace access., (© 2024. The Author(s).)

Spontaneous abortion (SAB), defined as a pregnancy loss before 20 weeks of gestation, affects up to 30% of conceptions, yet few modifiable risk factors have been identified. We estimated the effect of ambient air pollution exposure on SAB incidence in Pregnancy Study Online (PRESTO), a preconception cohort study of North American couples who were trying to conceive. Participants completed questionnaires at baseline, every 8 weeks during preconception follow-up, and in early and late pregnancy. We analyzed data on 4643 United States (U.S.) participants and 851 Canadian participants who enrolled during 2013-2019 and conceived during 12 months of follow-up. We used country-specific national spatiotemporal models to estimate concentrations of particulate matter <2.5 μm (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) during the preconception and prenatal periods at each participant's residential address. On follow-up and pregnancy questionnaires, participants reported information on pregnancy status, including SAB incidence and timing. We fit Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying prenatal concentrations of PM 2.5 , NO 2 , and O 3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM 2.5 concentrations were associated with a higher incidence of SAB in Canada, but not in the U.S. (HRs for a 5 μg/m 3 increase = 1.29, 95% CI: 0.99, 1.68 and 0.94, 95% CI: 0.83, 1.08, respectively). NO 2 and O 3 concentrations were not appreciably associated with SAB incidence. Results did not vary substantially by gestational weeks or season at risk. In summary, we found little evidence for an effect of residential ambient PM 2.5 , NO 2 , and O 3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM 2.5 with SAB incidence in Canada., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lauren A. Wise and Elizabeth E. Hatch reports financial support was provided by National Institute of Environmental Health Sciences. Lauren A. Wise reports a relationship with AbbVie Inc that includes: consulting or advisory. Dr. Lauren Wise serves as a consultant for AbbVie, Inc. and the Gates Foundation. She also receives in-kind donations for primary data collection in Pregnancy Study Online (PRESTO) from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility apps). All of these relationships are for work unrelated to this manuscript. The remaining authors report no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rationale: Individuals with COPD have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen., Objectives: Does residence at higher-altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, or mortality?, Methods: From the SPIROMICS cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation (n= 1,367) versus above 4,000 ft (1,219 m) elevation (n= 288). Multivariable regression models were used to evaluate associations of exposure to high altitude with COPD-related outcomes., Measurements and Main Results: Living at higher altitude was associated with reduced functional exercise capacity as defined by 6MWD (-32.3 m, (-55.7 to -28.6)). There were no differences in patient-reported outcomes as defined by symptoms (CAT, mMRC), or health status (SGRQ). Higher altitude was not associated with a different rate of FEV1 decline. Higher altitude was associated with lower odds of severe exacerbations (IRR 0.65, (0.46 to 0.90)). There were no differences in small airway disease, air trapping, or emphysema. In longitudinal analyses, higher altitude was associated with increased mortality (HR 1.25, (1.0 to 1.55)); however, this association was no longer significant when accounting for air pollution., Conclusions: Chronic altitude exposure is associated with reduced functional exercise capacity in individuals with COPD, but this did not translate into differences in symptoms or health status. Additionally, chronic high-altitude exposure did not affect progression of disease as defined by longitudinal changes in spirometry.

Determining the most feasible and cost-effective approaches to improving PM 2.5 exposure assessment with low-cost monitors (LCMs) can considerably enhance the quality of its epidemiological inferences. We investigated features of fixed-site LCM designs that most impact PM 2.5 exposure estimates to be used in long-term epidemiological inference for the Adult Changes in Thought Air Pollution (ACT-AP) study. We used ACT-AP collected and calibrated LCM PM 2.5 measurements at the two-week level from April 2017 to September 2020 (N of monitors [measurements] = 82 [502]). We also acquired reference-grade PM 2.5 measurements from January 2010 to September 2020 (N = 78 [6186]). We used a spatiotemporal modeling approach to predict PM 2.5 exposures with either all LCM measurements or varying subsets with reduced temporal or spatial coverage. We evaluated the models based on a combination of cross-validation and external validation at locations of LCMs included in the models (N = 82), and also based on an independent external validation with a set of LCMs not used for the modeling (N = 30). We found that the model's performance declined substantially when LCM measurements were entirely excluded (spatiotemporal validation R 2 [RMSE] = 0.69 [1.2 μg/m 3 ]) compared to the model with all LCM measurements (0.84 [0.9 μg/m 3 ]). Temporally, using the farthest apart measurements (i.e., the first and last) from each LCM resulted in the closest model's performance (0.79 [1.0 μg/m 3 ]) to the model with all LCM data. The models with only the first or last measurement had decreased performance (0.77 [1.1 μg/m 3 ]). Spatially, the model's performance decreased linearly to 0.74 (1.1 μg/m 3 ) when only 10% of LCMs were included. Our analysis also showed that LCMs located in densely populated, road-proximate areas improved the model more than those placed in moderately populated, road-distant areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Green space exposures may promote child mental health and well-being across multiple domains and stages of development. The aim of this study was to investigate associations between residential green space exposures and child mental and behavioral health at age 4-6 years., Methods: Children's internalizing and externalizing behaviors in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort in Shelby County, Tennessee, were parent-reported on the Child Behavior Checklist (CBCL). We examined three exposures-residential surrounding greenness calculated as the Normalized Difference Vegetation Index (NDVI), tree cover, and park proximity-averaged across the residential history for the year prior to outcome assessment. Linear regression models were adjusted for individual, household, and neighborhood-level confounders across multiple domains. Effect modification by neighborhood socioeconomic conditions was explored using multiplicative interaction terms., Results: Children were on average 4.2 years (range 3.8-6.0) at outcome assessment. Among CANDLE mothers, 65% self-identified as Black, 29% as White, and 6% as another or multiple races; 41% had at least a college degree. Higher residential surrounding greenness was associated with lower internalizing behavior scores (-0.66 per 0.1 unit higher NDVI; 95% CI: -1.26, -0.07) in fully-adjusted models. The association between tree cover and internalizing behavior was in the hypothesized direction but confidence intervals included the null (-0.29 per 10% higher tree cover; 95% CI: -0.62, 0.04). No associations were observed between park proximity and internalizing behavior. We did not find any associations with externalizing behaviors or the attention problems subscale. Estimates were larger in neighborhoods with lower socioeconomic opportunity, but interaction terms were not statistically significant., Conclusions: Our findings add to the accumulating evidence of the importance of residential green space for the prevention of internalizing problems among young children. This research suggests the prioritization of urban green spaces as a resource for child mental health., (© 2024. The Author(s).)

Background: In contrast to fine particles, less is known of the inflammatory and coagulation impacts of coarse particulate matter ( PM 10 - 2.5 , particulate matter with aerodynamic diameter ≤ 10 μ m  and > 2.5 μ m ). Toxicological research suggests that these pathways might be important processes by which PM 10 - 2.5 impacts health, but there are relatively few epidemiological studies due to a lack of a national PM 10 - 2.5 monitoring network., Objectives: We used new spatiotemporal exposure models to examine associations of both 1-y and 1-month average PM 10 - 2.5 concentrations with markers of inflammation and coagulation., Methods: We leveraged data from 7,071 Multi-Ethnic Study of Atherosclerosis and ancillary study participants 45-84 y of age who had repeated plasma measures of inflammatory and coagulation biomarkers. We estimated PM 10 - 2.5 at participant addresses 1 y and 1 month before each of up to four exams (2000-2012) using spatiotemporal models that incorporated satellite, regulatory monitoring, and local geographic data and accounted for spatial correlation. We used random effects models to estimate associations with interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and D-dimer, controlling for potential confounders., Results: Increases in PM 10 - 2.5 were not associated with greater levels of inflammation or coagulation. A 10 - μ g / m 3 increase in annual average PM 10 - 2.5 was associated with a 2.5% decrease in CRP [95% confidence interval (CI): - 5.5 , 0.6]. We saw no association between annual average PM 10 - 2.5 and the other markers (IL-6: - 0.7 % , 95% CI: - 2.6 , 1.2; fibrinogen: - 0.3 % , 95% CI: - 0.9 , 0.3; D-dimer: - 0.2 % , 95% CI: - 2.6 , 2.4). Associations consistently showed that a 1 0 - μ g / m 3 increase in 1-month average PM 10 - 2.5 was associated with reduced inflammation and coagulation, though none were distinguishable from no association (IL-6: - 1.2 % , 95% CI: - 3.0   , 0.5; CRP: - 2.5 % , 95% CI: - 5.3 , 0.4; fibrinogen: - 0.4 % , 95% CI: - 1.0 , 0.1; D-dimer: - 2.0 % , 95% CI: - 4.3 , 0.3)., Discussion: We found no evidence that PM 10 - 2.5 is associated with higher inflammation or coagulation levels. More research is needed to determine whether the inflammation and coagulation pathways are as important in explaining observed PM 10 - 2.5 health impacts in humans as they have been shown to be in toxicology studies or whether PM 10 - 2.5 might impact human health through alternative biological mechanisms. https://doi.org/10.1289/EHP12972.

Rationale: Particulate matter ⩽2.5 μm in aerodynamic diameter (PM 2.5 ) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter < 0.1 μm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged ⩾50 years in southern California at enrollment (1995-1996) followed through 2017 for incident lung cancer ( n  = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM 2.5 . In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm 3 and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99-1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05-1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm 3 , 1.09 [95% CI, 1.00-1.18]), but no increased risk was apparent among women ( P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02-1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with ⩾10 years of residential duration (HR, 1.11 [95% CI, 0.98-1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung.

Recent studies indicate that heat stress pathophysiology is associated with intestinal barrier dysfunction, local and systemic inflammation, and gut dysbiosis. However, inconclusive results and a poor description of tissue-specific changes must be addressed to identify potential intervention targets against heat stress illness in growing calves. Therefore, the objective of this study was to evaluate components of the intestinal barrier, pro- and anti-inflammatory signals, and microbiota community composition in Holstein bull calves exposed to heat stress. Animals (mean age = 12 wk old; mean body weight = 122 kg) penned individually in temperature-controlled rooms were assigned to (1) thermoneutral conditions (constant room temperature at 19.5°C) and restricted offer of feed (TNR, n = 8), or (2) heat stress conditions (cycles of room temperatures ranging from 20 to 37.8°C) along with ad libitum offer of feed (HS, n = 8) for 7 d. Upon treatment completion, sections of the jejunum, ileum, and colon were collected and snap-frozen immediately to evaluate gene and protein expression, cytokine concentrations, and myeloperoxidase activity. Digesta aliquots of the ileum, colon, and rectum were collected to assess bacterial communities. Plasma was harvested on d 2, 5, and 7 to determine cytokine concentrations. Overall, results showed a section-specific effect of HS on intestinal integrity. Jejunal mRNA expression of TJP1 was decreased by 70.9% in HS relative to TNR calves. In agreement, jejunal expression of heat shock transcription factor-1 protein, a known tight junction protein expression regulator, decreased by 48% in HS calves. Jejunal analyses showed that HS decreased concentrations of IL-1α by 36.6% and tended to decrease the concentration of IL-17A. Conversely, HS elicited a 3.5-fold increase in jejunal concentration of anti-inflammatory IL-36 receptor antagonist. Plasma analysis of pro-inflammatory cytokines showed that IL-6 decreased by 51% in HS relative to TNR calves. Heat stress alteration of the large intestine bacterial communities was characterized by increased genus Butyrivibrio&#95;3, a known butyrate-producing organism, and changes in bacteria metabolism of energy and AA. A strong positive correlation between the rectal temperature and pro-inflammatory Eggerthii spp. was detected in HS calves. In conclusion, this work indicates that HS impairs the intestinal barrier function of jejunum. The pro- and anti-inflammatory signal changes may be part of a broader response to restore intestinal homeostasis in jejunum. The changes in large intestine bacterial communities favoring butyrate-producing organisms (e.g., Butyrivibrio spp.) may be part of a successful response to maintain the integrity of the colonic mucosa of HS calves. The alteration of intestinal homeostasis should be the target for heat stress therapies to restore biological functions, and, thus highlights the relevance of this work., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Ozone (O 3 ) exposure interrupts normal lung development in animal models. Epidemiologic evidence further suggests impairment with higher long-term O 3 exposure across early and middle childhood, although study findings to date are mixed and few have investigated vulnerable subgroups., Methods: Participants from the CANDLE study, a pregnancy cohort in Shelby County, TN, in the ECHO-PATHWAYS Consortium, were included if children were born at gestational age >32 weeks, completed a spirometry exam at age 8-9, and had a valid residential history from birth to age 8. We estimated lifetime average ambient O 3 exposure based on each child's residential history from birth to age 8, using a validated fine-resolution spatiotemporal model. Spirometry was performed at the age 8-9 year study visit to assess Forced Expiratory Volume in the first second (FEV 1 ) and Forced Vital Capacity (FVC) as primary outcomes; z-scores were calculated using sex-and-age-specific reference equations. Linear regression with robust variance estimators was used to examine associations between O 3 exposure and continuous lung function z-scores, adjusted for child, sociodemographic, and home environmental factors. Potential susceptible subgroups were explored using a product term in the regression model to assess effect modification by child sex, history of bronchiolitis in infancy, and allergic sensitization., Results: In our sample (n = 648), O 3 exposure averaged from birth to age 8 was modest (mean 26.6 [SD 1.1] ppb). No adverse associations between long-term postnatal O 3 exposure were observed with either FEV 1 (β = 0.12, 95% CI: -0.04, 0.29) or FVC (β = 0.03, 95% CI: -0.13, 0.19). No effect modification by child sex, history of bronchiolitis in infancy, or allergic sensitization was detected for associations with 8-year average O 3 ., Conclusions: In this sample with low O 3 concentrations, we did not observe adverse associations between O 3 exposures averaged from birth to age 8 and lung function in middle childhood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fine particulate matter (PM2.5) has been inconsistently associated with breast cancer incidence, however, few studies have considered historic exposure when levels were higher., Methods: Outdoor residential PM2.5 concentrations were estimated using a nationwide spatiotemporal model for women in the National Institutes of Health-AARP Diet and Health Study, a prospective cohort located in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, GA, and Detroit, MI) and enrolled in 1995-1996 (n = 196 905). Annual average PM2.5 concentrations were estimated for a 5-year historical period 10 years prior to enrollment (1980-1984). We used Cox regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between a 10 µg/m3 increase in PM2.5 and breast cancer incidence overall and by estrogen receptor status and catchment area., Results: With follow-up of participants through 2017, a total of 15 870 breast cancer cases were identified. A 10 ug/m3 increase in PM2.5 was statistically significantly associated with overall breast cancer incidence (HR = 1.08, 95% CI = 1.02 to 1.13). The association was evident for estrogen receptor-positive (HR = 1.10, 95% CI = 1.04 to 1.17) but not estrogen receptor-negative tumors (HR = 0.97, 95% CI = 0.84 to 1.13; Pheterogeneity = .3). Overall breast cancer hazard ratios were more than 1 across the catchment areas, ranging from a hazard ratio of 1.26 (95% CI = 0.96 to 1.64) for North Carolina to a hazard ratio of 1.04 (95% CI = 0.68 to 1.57) for Louisiana (Pheterogeneity = .9)., Conclusions: In this large US cohort with historical air pollutant exposure estimates, PM2.5 was associated with risk of estrogen receptor-positive breast cancer. State-specific estimates were imprecise but suggest that future work should consider region-specific associations and the potential contribution of PM2.5 chemical constituency in modifying the observed association., (Published by Oxford University Press 2023.)

Background and Aims: Air pollution has been associated with coronary artery disease. The underlying mechanisms were understudied, especially in relation to coronary stenosis leading to myocardial ischemia. Advances in computed tomography (CT) allow for novel quantification of lesion ischemia. We aim to investigate associations between air pollution exposures and fractional flow reserve on CT (CT-FFR), a measure of coronary artery blood flow., Methods: CT-FFR, which defines a ratio of maximal myocardial blood flow compared to its normal value (range: 0-100%), was characterized in 2017 patients with atherosclerosis between 2015 and 2017. Exposures to ozone (O 3 ), nitrogen dioxide (NO 2 ), and fine particulate matter (PM 2.5 ) were estimated using high-resolution exposure models. Linear and logistic regression models were used to assess the association of each air pollutant with CT-FFR and with the prevalence of clinically relevant myocardial ischemia (CT-FFR <75%)., Results: Participants were on average 60.1 years old. Annual mean O 3 , NO 2 , PM 2.5 were 61, 47 and 60 μg/m 3 , respectively. Mean CT-FFR value was 76.9%. In the main analysis, a higher level of O 3 was associated with a lower CT-FFR value (-1.74%, 95% CI: -2.85, -0.63 per 8 μg/m 3 ) and a higher prevalence of myocardial ischemia (odds ratio: 1.32, 95% CI: 1.05-1.65), adjusting for potential confounders such as risk factors and plaque phenotypes, independent of the effects of exposure to NO 2 and PM 2.5 . No associations were observed for PM 2.5 or NO 2 with CT-FFR., Conclusions: Long-term exposure to O 3 is associated with lower CT-FFR value in atherosclerotic patients, indicating higher risk of lesion ischemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: Air pollutants may contribute to the development of Parkinson's disease (PD), but empirical evidence is limited and inconsistent., Objectives: This study aimed to prospectively investigate the associations of PD with ambient exposures to fine particulate matter with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ) and nitrogen dioxide ( NO 2 )., Methods: We analyzed data from 47,108 US women from the Sister Study, enrolled from 2003-2009 (35-80 years of age) and followed through 2018. Exposures of interest included address-level ambient PM 2.5 and NO 2 in 2009 and their cumulative averages from 2009 to PD diagnosis with varying lag-years. The primary outcome was PD diagnosis between 2009 and 2018 ( n = 163 ). We used multivariable Cox proportional hazards and time-varying Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: NO 2 exposure in 2009 was associated with PD risk in a dose-response manner. The HR and 95% CI were 1.22 (95% CI: 1.03, 1.46) for one interquartile [4.8 parts per billion (ppb)] increment in NO 2 , adjusting for age, race and ethnicity, education, smoking status, alcohol drinking, caffeine intake, body mass index, physical activity, census region, residential area type, area deprivation index (ADI), and self-reported health status. The association was confirmed in secondary analyses with time-varying averaged cumulative exposures. For example, the multivariable adjusted HR for PD per 4.8   ppb increment in NO 2 was 1.25 (95% CI: 1.05, 1.50) in the 2-year lag analysis using cumulative average exposure. Post hoc subgroup analyses overall confirmed the association. However, statistical interaction analyses found that the positive association of NO 2 with PD risk was limited to women in urban, rural, and small town areas and women with ≥ 50 th percentile ADI but not among women from suburban areas or areas with < 50 th percentile ADI. In contrast, PM 2.5 exposure was not associated with PD risk with the possible exception for women from the Midwest region of the US ( HR interquartile -range = 2.49 , 95% CI: 1.20, 5.14) but not in other census regions., Discussion: In this nationwide cohort of US women, higher level exposure to ambient NO 2 is associated with a greater risk of PD. This finding needs to be independently confirmed and the underlying mechanisms warrant further investigation. https://doi.org/10.1289/EHP13009.