Publications by authors named "Joel Schwartz"

840 Publications

Long-term effect of exposure to lower concentrations of air pollution on mortality among US Medicare participants and vulnerable subgroups: a doubly-robust approach.

Lancet Planet Health 2021 Oct;5(10):e689-e697

Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA. Electronic address:

Background: Long-term exposure to air pollution has been linked with an increase in risk of mortality. Whether existing US Environmental Protection Agency standards are sufficient to protect health is unclear. Our study aimed to examine the relationship between exposure to lower concentrations of air pollution and the risk of mortality.

Methods: Our nationwide cohort study investigated the effect of annual average exposure to air pollutants on all-cause mortality among Medicare enrolees from the beginning of 2000 to the end of 2016. Patients entered the cohort in the month of January following enrolment and were followed up until the end of the study period in 2016 or death. We restricted our analyses to participants who had only been exposed to lower concentrations of pollutants over the study period, specifically particulate matter less than 2·5 μg/m in diameter (PM) at a concentration of up to 12 μg/m, nitrogen dioxide (NO) at a concentration of up to 53 parts per billion (ppb), and summer ozone (O) at concentrations of up to 50 ppb. We adjusted for two types of covariates, which were individual level and postal code-level variables. We used a doubly-robust additive model to estimate the change in risk. We further looked at effect-measure modification by stratification on the basis of demographic and socioeconomic characteristics.

Findings: We found an increased risk of mortality with all three pollutants. Each 1 μg/m increase in annual PM concentrations increased the absolute annual risk of death by 0·073% (95% CI 0·071-0·076). Each 1 ppb increase in annual NO concentrations increased the annual risk of death by 0·003% (0·003-0·004), and each 1 ppb increase in summer O concentrations increased the annual risk of death by 0·081% (0·080-0·083). This increase translated to approximately 11 540 attributable deaths (95% CI 11 087-11 992) for PM, 1176 attributable deaths (998-1353) for NO, and 15 115 attributable deaths (14 896-15 333) for O per year for each unit increase in pollution concentrations. The effects were higher in certain subgroups, including individuals living in areas of low socioeconomic status. Long-term exposure to permissible concentrations of air pollutants increases the risk of mortality.

Funding: The US Environmental Protection Agency, National Institute of Environmental Health Services, and Health Effects Institute.
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http://dx.doi.org/10.1016/S2542-5196(21)00204-7DOI Listing
October 2021

In utero exposure to near-roadway air pollution and autism spectrum disorder in children.

Environ Int 2021 Oct 6;158:106898. Epub 2021 Oct 6.

Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA. Electronic address:

Importance: Previous studies have reported associations between in utero exposure to regional air pollution and autism spectrum disorders (ASD). In utero exposure to components of near-roadway air pollution (NRAP) has been linked to adverse neurodevelopment in animal models, but few studies have investigated NRAP association with ASD risk.

Objective: To identify ASD risk associated with in utero exposure to NRAP in a large, representative birth cohort.

Design, Setting, And Participants: This retrospective pregnancy cohort study included 314,391 mother-child pairs of singletons born between 2001 and 2014 at Kaiser Permanente Southern California (KPSC) hospitals. Maternal and child data were extracted from KPSC electronic medical records. Children were followed until: clinical diagnosis of ASD, non-KPSC membership, death, or December 31, 2019, whichever came first. Exposure to the complex NRAP mixture during pregnancy was assessed using line-source dispersion models to estimate fresh vehicle emissions from freeway and non-freeway sources at maternal addresses during pregnancy. Vehicular traffic load exposure was characterized using advanced telematic models combining traditional traffic counts and travel-demand models with cell phone and vehicle GPS data. Cox proportional-hazard models estimated hazard ratios (HR) of ASD associated with near-roadway traffic load and dispersion-modeled NRAP during pregnancy, adjusted for covariates. Non-freeway NRAP was analyzed using quintile distribution due to nonlinear associations with ASD.

Exposures: Average NRAP and traffic load exposure during pregnancy at maternal residential addresses.

Main Outcomes: Clinical diagnosis of ASD.

Results: A total of 6,291 children (5,114 boys, 1,177 girls) were diagnosed with ASD. The risk of ASD was associated with pregnancy-average exposure to total NRAP [HR(95% CI): 1.03(1.00,1.05) per 5 ppb increase in dispersion-modeled NOx] and to non-freeway NRAP [HR(95% CI) comparing the highest to the lowest quintile: 1.19(1.11, 1.27)]. Total NRAP had a stronger association in boys than in girls, but the association with non-freeway NRAP did not differ by sex. The association of freeway NRAP with ASD risk was not statistically significant. Non-freeway traffic load exposure demonstrated associations with ASD consistent with those of NRAP and ASD.

Conclusions: In utero exposure to near-roadway air pollution, particularly from non-freeway sources, may increase ASD risk in children.
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http://dx.doi.org/10.1016/j.envint.2021.106898DOI Listing
October 2021

Old age and other factors associated with salivary microbiome variation.

BMC Oral Health 2021 Oct 4;21(1):490. Epub 2021 Oct 4.

Department of Oral Medicine and Diagnostics, College of Dentistry, University of Illinois at Chicago, 801 South Paulina Street, Chicago, IL, 60612, USA.

Background: Many factors can contribute to the exact makeup of the salivary microbiome. Differences in the oral microbiome occur with old age, which may be due to oral conditions and diseases associated with old age, such as edentulism, as well as other unknown causes.

Methods: The salivary microbiome was sampled in patients from a large urban clinic. For all subjects age, gender, periodontal status, caries status, presence of edentulism, medications, and tobacco usage were recorded. Multifactor analysis was used to study variation in salivary microbiome profiles linked to these factors.

Results: In the population sampled, there were significantly higher numbers of edentulous subjects, and increased levels of polypharmacy found with aging. Large differences in alpha diversity and beta diversity of the salivary microbiome in the old age group were largely linked to edentulism. However, multivariable analysis revealed, even after adjusting for differences in edentulism, polypharmacy, tobacco usage, periodontal disease, caries level, and gender, that old age itself was associated with lower levels of taxa Porphyromonas endodontalis, Alloprevotella tannerae, Filifactor alocis, Treponema, Lautropia Mirabilis and Pseudopropionibacterium sp._HMT_194. Surprisingly, of these taxa, most were ones known to reside on or near tooth surfaces.

Conclusions: Another factor or factors beyond edentulism, polypharmacy and periodontal disease play a role in the differences seen in oral microbiome with old age. The nature of this factor(s) is not known.
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http://dx.doi.org/10.1186/s12903-021-01828-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489047PMC
October 2021

Associations between solar and geomagnetic activity and peripheral white blood cells in the Normative Aging Study.

Environ Res 2021 Sep 17;204(Pt B):112066. Epub 2021 Sep 17.

Department of Environmental Health, Harvard T.H. Chan School of Public Heath, Boston, MA, United States.

It has been hypothesized that solar and geomagnetic activity can affect the function of the autonomic nervous system (ANS) and melatonin secretion, both of which may influence immune response. We investigated the association between solar geomagnetic activity and white blood cell counts in the Normative Aging Study (NAS) Cohort between 2000 and 2013. Linear mixed effects models with moving day averages ranging from 0 to 28 days were used to evaluate the effects of solar activity measures, interplanetary magnetic field (IMF), and sunspot number (SSN), and a measure of geomagnetic activity, K Index (K), on total white blood cell (WBC), neutrophil, monocytes, lymphocyte, eosinophil, and basophil concentrations. After adjusting for demographic and health-related factors, there were consistently significant associations between IMF, SSN, and K index, with reductions in total WBC, neutrophils, and basophil counts. These associations were stronger with longer moving averages. The associations were similar after adjusting for ambient air particulate pollution and particle radioactivity. Our findings suggest that periods of increased solar and geomagnetic activity result in lower WBC, neutrophil, and basophil counts that may contribute to mil mild immune suppression.
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http://dx.doi.org/10.1016/j.envres.2021.112066DOI Listing
September 2021

COVID-19 and oral diseases: Assessing manifestations of a new pathogen in oral infections.

Int Rev Immunol 2021 Sep 16:1-15. Epub 2021 Sep 16.

Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, USA.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a recently identified virus responsible for life-threatening coronavirus disease 19 (COVID-19). The SARS-CoV-2 infected subjects can be asymptomatic or symptomatic; the later may present a wide spectrum of clinical manifestations. However, the impact of SARS-CoV-2 on oral diseases remain poorly studied. Detection of SARS-CoV-2 in saliva indicates existence of virus in the oral cavity. Recent studies demonstrating the expression of ACE-2, a SARS-CoV-2 entry receptor, in oral tissues further strengthens this observation. Cytokine storm in severe COVID-19 patients and copious secretion of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) in multiple symptomatic oral pathologies including periodontitis and periapical periodontitis suggests that inflammatory microenvironment is a hallmark of both COVID-19 and oral diseases. Hyperinflammation may provide conducive microenvironment for the growth of local oral pathogens or opportunistic microbes and exert detrimental impact on the oral tissue integrity. Multiple case reports have indicated uncharacterized oral lesions, symptomatic irreversible pulpitis, higher plaque index, necrotizing/desquamative gingivitis in COVID-19 patients suggesting that SARS-CoV-2 may worsen the manifestations of oral infections. However, the underlying factors and pathways remain elusive. Here we summarize current literature and suggest mechanisms for viral pathogenesis of oral dental pathology derived from oral microbiome and oral mucosa-dental tissue interactions. Longitudinal studies will reveal how the virus impairs disease progression and resolution post-therapy. Some relationships we suggest provide the basis for novel monitoring and treatment of oral viral disease in the era of SARS-CoV-2 pandemic, promoting evidence-based dentistry guidelines to diagnose virus-infected patients to improve oral health.
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http://dx.doi.org/10.1080/08830185.2021.1967949DOI Listing
September 2021

Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort.

Environ Pollut 2021 Aug 21;290:118024. Epub 2021 Aug 21.

University Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology Applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France.

In utero exposure to environmental chemicals, such as synthetic phenols, may alter DNA methylation in different tissues, including placenta - a critical organ for fetal development. We studied associations between prenatal urinary biomarker concentrations of synthetic phenols and placental DNA methylation. Our study involved 202 mother-son pairs from the French EDEN cohort. Nine phenols were measured in spot urine samples collected between 22 and 29 gestational weeks. We performed DNA methylation analysis of the fetal side of placental tissues using the IlluminaHM450 BeadChips. We evaluated methylation changes of individual CpGs in an adjusted epigenome-wide association study (EWAS) and identified differentially methylated regions (DMRs). We performed mediation analysis to test whether placental tissue heterogeneity mediated the association between urinary phenol concentrations and DNA methylation. We identified 46 significant DMRs (≥5 CpGs) associated with triclosan (37 DMRs), 2,4-dichlorophenol (3), benzophenone-3 (3), methyl- (2) and propylparaben (1). All but 2 DMRs were positively associated with phenol concentrations. Out of the 46 identified DMRs, 7 (6 for triclosan) encompassed imprinted genes (APC, FOXG1, GNAS, GNASAS, MIR886, PEG10, SGCE), which represented a significant enrichment. Other identified DMRs encompassed genes encoding proteins responsible for cell signaling, transmembrane transport, cell adhesion, inflammatory, apoptotic and immunological response, genes encoding transcription factors, histones, tumor suppressors, genes involved in tumorigenesis and several cancer risk biomarkers. Mediation analysis suggested that placental cell heterogeneity may partly explain these associations. This is the first study describing the genome-wide modifications of placental DNA methylation associated with pregnancy exposure to synthetic phenols or their precursors. Our results suggest that cell heterogeneity might mediate the effects of triclosan exposure on placental DNA methylation. Additionally, the enrichment of imprinted genes within the DMRs suggests mechanisms by which certain exposures, mainly to triclosan, could affect fetal development.
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http://dx.doi.org/10.1016/j.envpol.2021.118024DOI Listing
August 2021

Mortality risk attributable to wildfire-related PM pollution: a global time series study in 749 locations.

Lancet Planet Health 2021 09;5(9):e579-e587

Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Background: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM and mortality across various regions of the world.

Methods: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM exposure was calculated.

Findings: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM exposure during the study period.

Interpretation: Short-term exposure to wildfire-related PM was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.

Funding: Australian Research Council, Australian National Health & Medical Research Council.
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http://dx.doi.org/10.1016/S2542-5196(21)00200-XDOI Listing
September 2021

A self-controlled approach to survival analysis, with application to air pollution and mortality.

Environ Int 2021 12 8;157:106861. Epub 2021 Sep 8.

Harvard TH Chan School of Public Health, Department of Epidemiology, United States.

Background: Many studies have reported that long-term air pollution exposure is associated with increased mortality rates. These investigations have been criticized for failure to control for omitted, generally personal, confounders. Study designs that are robust to such confounders can address this issue.

Methods: We used a self-controlled design for survival analysis. We stratified on each person in the Medicare cohort between 2000 and 2015 who died, and examined whether PM, O and NO exposures predicted in which follow-up period the death occurred. We used conditional logistic regression stratified on person and controlled for nonlinear terms in calendar year and age. By design slowly varying covariates such as smoking history, BMI, diabetes and other pre-existing conditions, usual alcohol consumption, sex, race, socioeconomic status, and green space were controlled by matching each person to themselves.

Results: There were 6,452,618 deaths in the study population in the study period. We observed a 5.37% increase in the mortality rate (95% CI 4.67%, 6.08%) for every 5 μg/m increase in PM, a 1.98% (95% CI 1.61%, 2.36%) increase for 5 ppb increment in O, and a 2.10% decrease (95% CI 1.88%, 2.33%) for a 5 ppb increase in NO. When restricted to persons whose PM exposure never exceeded 12 μg/m in any year between 2000 and 2015, the effect size increased for PM (12.71% (11.30, 14.15)), and the signs of O and NO reversed (-0.26% (-0.88, 0.35) for O and 1.77% increase (1.40, 2.13) for NO). Effect sizes were larger for Blacks (e.g. 7.71% (5.46, 10.02) for PM).

Conclusion: There is strong evidence that the association between annual exposure to PM and mortality is not confounded by individual or neighborhood covariates, and continues below the standard. The effects of O and NO are difficult to disentangle.
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http://dx.doi.org/10.1016/j.envint.2021.106861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490318PMC
December 2021

Prenatal exposure to wildfire-related air pollution and birth defects in Brazil.

J Expo Sci Environ Epidemiol 2021 Sep 9. Epub 2021 Sep 9.

Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background: Birth defects are a major cause of poor health outcomes during both childhood and adulthood. A growing body of evidence demonstrated associations between air pollution exposure during pregnancy and birth defects. To date, there is no study looking at birth defects and exposure to wildfire-related air pollution, which is suggested as a type of air pollution source with high toxicity for reproductive health.

Objective: Our study addresses this gap by examining the association between birth defects and wildfire smoke exposure in Brazil between 2001 and 2018. Based on known differences of impacts of wildfires across different regions of Brazil, we hypothesized differences in risks of birth defects for different regions.

Methods: We used a logistic regression model to estimate the odds ratios (ORs) for individual birth defects (12 categories) associated with wildfire exposure during each trimester of pregnancy.

Results: Among the 16,825,497 birth records in our study population, there were a total of 7595 infants born in Brazil between 2001 and 2018 with birth defects in any of the selected categories. After adjusting for several confounders in the primary analysis, we found statistically significant OR for three birth defects, including cleft lip/cleft palate [OR: 1.007 (95% CI: 1.001; 1.013)] during the second trimester of exposure, congenital anomalies of the respiratory system [OR: 1.013 (95% CI: 1.002; 1.023)] in the second trimester of exposure, and congenital anomalies of the nervous system [OR: 1.002 (95% CI: 1.001; 1.003)] during the first trimester of exposure for the regions South, North, and Midwest, respectively.

Significance: Our results suggest that maternal exposure to wildfire smoke during pregnancy may increase the risk of an infant being born with some congenital anomaly. Considering that birth defects are associated with long-term disability, impacting families and the healthcare system (e.g., healthcare costs), our findings should be of great concern to the public health community.

Impact Statement: Our study focused on the association between maternal exposure to wildfire smoke in Brazil during pregnancy and the risk of an infant being born with congenital anomalies, which presents serious public health and environmental challenges.
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http://dx.doi.org/10.1038/s41370-021-00380-yDOI Listing
September 2021

Heat warnings, mortality, and hospital admissions among older adults in the United States.

Environ Int 2021 12 27;157:106834. Epub 2021 Aug 27.

Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA.

Background: Heat warnings are issued in advance of forecast extreme heat events, yet little evidence is available regarding their effectiveness in reducing heat-related illness and death. We estimated the association of heat warnings and advisories (collectively, "alerts") issued by the United States National Weather Service with all-cause mortality and cause-specific hospitalizations among Medicare beneficiaries aged 65 years and older in 2,817 counties, 2006-2016.

Methods: In each county, we compared days with heat alerts to days without heat alerts, matched on daily maximum heat index and month. We used conditional Poisson regression models stratified on county, adjusting for year, day of week, federal holidays, and lagged daily maximum heat index.

Results: We identified a matched non-heat alert day for 92,029 heat alert days in 2,817 counties, or 54.6% of all heat alert days during the study period. Contrary to expectations, heat alerts were not associated with lower risk of mortality (RR: 1.005 [95% CI: 0.997, 1.013]). However, heat alerts were associated with higher risk of hospitalization for fluid and electrolyte disorders (RR: 1.040 [95% CI: 1.015, 1.065]) and heat stroke (RR: 1.094 [95% CI: 1.038, 1.152]). Results were similar in sensitivity analyses additionally adjusting for same-day heat index, ozone, and PM.

Conclusions: Our results suggest that heat alerts are not associated with lower risk of mortality but may be associated with higher rates of hospitalization for fluid and electrolyte disorders and heat stroke, potentially suggesting that heat alerts lead more individuals to seek or access care.
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http://dx.doi.org/10.1016/j.envint.2021.106834DOI Listing
December 2021

Quantifying the short-term effects of air pollution on health in the presence of exposure measurement error: a simulation study of multi-pollutant model results.

Environ Health 2021 08 24;20(1):94. Epub 2021 Aug 24.

Environmental Research Group, School of Public Health, Imperial College London, Michael Uren Biomedical Engineering Hub, White City Campus, Wood Lane, W12 0BZ, London, UK.

Background: Most epidemiological studies estimate associations without considering exposure measurement error. While some studies have estimated the impact of error in single-exposure models we aimed to quantify the effect of measurement error in multi-exposure models, specifically in time-series analysis of PM, NO, and mortality using simulations, under various plausible scenarios for exposure errors. Measurement error in multi-exposure models can lead to effect transfer where the effect estimate is overestimated for the pollutant estimated with more error to the one estimated with less error. This complicates interpretation of the independent effects of different pollutants and thus the relative importance of reducing their concentrations in air pollution policy.

Methods: Measurement error was defined as the difference between ambient concentrations and personal exposure from outdoor sources. Simulation inputs for error magnitude and variability were informed by the literature. Error-free exposures with their consequent health outcome and error-prone exposures of various error types (classical/Berkson) were generated. Bias was quantified as the relative difference in effect estimates of the error-free and error-prone exposures.

Results: Mortality effect estimates were generally underestimated with greater bias observed when low ratios of the true exposure variance over the error variance were assumed (27.4% underestimation for NO). Higher ratios resulted in smaller, but still substantial bias (up to 19% for both pollutants). Effect transfer was observed indicating that less precise measurements for one pollutant (NO) yield more bias, while the co-pollutant (PM) associations were found closer to the true. Interestingly, the sum of single-pollutant model effect estimates was found closer to the summed true associations than those from multi-pollutant models, due to cancelling out of confounding and measurement error bias.

Conclusions: Our simulation study indicated an underestimation of true independent health effects of multiple exposures due to measurement error. Using error parameter information in future epidemiological studies should provide more accurate concentration-response functions.
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http://dx.doi.org/10.1186/s12940-021-00757-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385952PMC
August 2021

Daily nonaccidental mortality associated with short-term PM exposures in Delhi, India.

Environ Epidemiol 2021 Aug 6;5(4):e167. Epub 2021 Aug 6.

Harvard T. H. Chan School of Public Health, Boston, MA.

Ambient particulate matter of aerodynamic diameter less than 2.5 microns PM) levels in Delhi routinely exceed World Health Organization (WHO) guidelines and Indian National Ambient Air Quality Standards (NAAQS) for acceptable levels of daily exposure. Only a handful of studies have examined the short-term mortality effects of PM in India, with none from Delhi examining the contribution of PM.

Objectives: We aimed to analyze the association between short-term PM exposures and daily nonaccidental mortality in Delhi, India.

Methods: Using generalized additive Poisson regression models, we examined the association between daily PM exposures and nonaccidental mortality between June 2010 and December 2016. Daily exposures to PM were estimated using an ensemble averaging technique developed by our research group, and mortality data were obtained from the Municipal Corporations of Delhi and the New Delhi Municipal Council.

Results: Median exposures to PM were 91.1 µg/m (interquartile range = 68.9, 126.2), with minimum and maximum exposures of 21.4 µg/m and 276.7 µg/m, respectively. Total nonaccidental deaths recorded in Delhi during the study period were 700,512. Each 25 µg/m increment in exposure was associated with a 0.8% (95% confidence intervals [CI] = 0.3, 1.3%) increase in daily nonaccidental mortality in the study population and a 1.5% (95% CI = 0.8, 2.2%) increase in mortality among those with 60 years of age or over. The exposure-response relationship was nonlinear in nature, with relative risk rising rapidly before tapering off above 125 µg/m. Meeting WHO guidelines for acceptable levels of exposure over the study period would have likely averted 17,526 (95% CI = 6,837, 25,589) premature deaths, with older and male populations disproportionately affected.

Discussion: This study provides robust evidence of the impact of short-term exposure to PM on nonaccidental mortality with important considerations for various stakeholders including policymakers and physicians. Most importantly, we find that reducing exposures significantly below current levels would substantially decrease the mortality burden associated with PM.
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http://dx.doi.org/10.1097/EE9.0000000000000167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367036PMC
August 2021

Health effects of air pollutant mixtures on overall mortality among the elderly population using Bayesian kernel machine regression (BKMR).

Chemosphere 2021 Jul 17;286(Pt 1):131566. Epub 2021 Jul 17.

Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address:

It is well documented that fine particles matter (PM), ozone (O), and nitrogen dioxide (NO) are associated with a range of adverse health outcomes. However, most epidemiologic studies have focused on understanding their additive effects, despite that individuals are exposed to multiple air pollutants simultaneously that are likely correlated with each other. Therefore, we applied a novel method - Bayesian Kernel machine regression (BKMR) and conducted a population-based cohort study to assess the individual and joint effect of air pollutant mixtures (PM, O, and NO) on all-cause mortality among the Medicare population in 15 cities with 656 different ZIP codes in the southeastern US. The results suggest a strong association between pollutant mixture and all-cause mortality, mainly driven by PM. The positive association of PM with mortality appears stronger at lower percentiles of other pollutants. An interquartile range change in PM concentration was associated with a significant increase in mortality of 1.7 (95% CI: 0.5, 2.9), 1.6 (95% CI: 0.4, 2.7) and 1.4 (95% CI: 0.1, 2.6) standard deviations (SD) when O and NO were set at the 25th, 50th, and 75th percentiles, respectively. BKMR analysis did not identify statistically significant interactions among PM, O, and NO. However, since the small sub-population might weaken the study power, additional studies (in larger sample size and other regions in the US) are in need to reinforce the current finding.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131566DOI Listing
July 2021

Causal mediation analysis with latent subgroups.

Stat Med 2021 Jul 15. Epub 2021 Jul 15.

Department of Statistics and Actuarial Science, University of Hong Kong, Pokfulam, Hong Kong SAR, China.

In biomedical studies, the causal mediation effect might be heterogeneous across individuals in the study population due to each study subject's unique characteristics. While individuals' mediation effects may differ from each other, it is often reasonable and more interpretable to assume that individuals belong to several distinct latent subgroups with similar attributes. In this article, we first show that the subgroup-specific mediation effect can be identified under the group-specific sequential ignorability assumptions. Then, we propose a simple mixture modeling approach to account for the latent subgroup structure where each mixture component corresponds to one latent subgroup in the linear structural equation model framework. Model parameters can be estimated using the standard expectation-maximization (EM) algorithm. Each individual's subgroup membership can be inferred based on the posterior probability. We propose to use the singular Bayesian information criterion to consistently select the number of latent subgroups by recognizing that the Fisher information matrix for mixture models might be singular. We then propose to use nonparametric bootstrap method to compute standard errors and confidence intervals. We conducted simulation studies to evaluate the empirical performance of our proposed method named iMed. Finally, we reanalyzed a DNA methylation data set from the Normative Aging Study and found that the mediation effects of two well-documented DNA methylation CpG sites are heterogeneous across two latent subgroups in the causal pathway from smoking behavior to lung function. We also developed an R package iMed for public use.
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http://dx.doi.org/10.1002/sim.9144DOI Listing
July 2021

Short-term exposure to PM components and renal health: Findings from the Veterans Affairs Normative Aging Study.

J Hazard Mater 2021 Oct 3;420:126557. Epub 2021 Jul 3.

Laboratory of Environmental Precision Health, Mailman School of Public Health, Columbia University, New York, NY, USA.

There is little evidence on the short-term impact of fine particulate matter (PM) on renal health, and the potential interactions and various influences of PM components on renal health have not been examined. We investigated whether short-term (≤28 days) ambient PM and 15 PM components were associated with serum uric acid (SUA), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and odds of incident chronic kidney disease (CKD) using both mixed-effect and Bayesian kernel machine regression (BKMR) models in the Normative Aging Study. This analysis included 2466 study visits from 808 older males enrolled during 1998-2016 with available data. BKMR showed positive relationships of PM mixture with SUA and odds of CKD, and an inverse relationship with eGFR. In the 28-day exposure window, an interquartile range (IQR) increase in vanadium was associated with a 0.244-mg/dL higher SUA. IQR increases in sulfur and lead were associated with a 1.281- and 1.008-mL/min/1.73 m decrease in eGFR, respectively. The same change in sulfur was also associated with a 39% higher odds of CKD. Our findings provide solid evidence supporting short-term adverse effects of PM on renal health and further highlight that components from oil combustion and regional pollution may be major contributors.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126557DOI Listing
October 2021

Global, regional, and national burden of mortality associated with non-optimal ambient temperatures from 2000 to 2019: a three-stage modelling study.

Lancet Planet Health 2021 07;5(7):e415-e425

Department of Earth Sciences, University of Turin, Turin, Italy.

Background: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures.

Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature-mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature-mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division.

Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967-5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58-11·07) of all deaths (8·52% [6·19-10·47] were cold-related and 0·91% [0·56-1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60-87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000-03 to 2016-19, the global cold-related excess death ratio changed by -0·51 percentage points (95% eCI -0·61 to -0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13-0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe.

Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios.

Funding: Australian Research Council and the Australian National Health and Medical Research Council.
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http://dx.doi.org/10.1016/S2542-5196(21)00081-4DOI Listing
July 2021

Predictors of indoor radon levels in the Midwest United States.

J Air Waste Manag Assoc 2021 Sep 23:1-14. Epub 2021 Sep 23.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Radon (Rn) is a natural and toxic radioactive gas that accumulates indoors, mainly in low-ventilated underground floors and basements. Several factors make prediction of indoor Rn exposure in enclosed spaces challenging. In this study, we investigated the influence of soil, geology, topography, atmospheric variables, radiation, urbanization, community economic well-being, and monthly and yearly variations on indoor Rn concentrations. We analyzed 7,515 monthly indoor Rn measurements in 623 zip codes from two U.S. States (Michigan and Minnesota) during 2005-2018 using a random forest model. Using Shapley Additive exPlanations (SHAP) values we investigated the contribution of each factor using variable importance and partial dependence plots. Factors that predict indoor Rn differed between states, with topographical, geological and soil composition being most influential. Cross-validated Pearson correlation between predictions and measurements was 0.68 (RMSE = 47.8 Bq/m) in Minnesota, and 0.67 (RMSE = 52.5 Bq/m) in Michigan. Our results underline the importance of soil structure for radon exposure, presumably due to strapped Rn in soil. The differences across states also suggest that Rn studies performing model development should consider geographical variables, along with other factors. As indoor Rn levels are multifactorial, an understanding of the factors that influence its emanation and build up indoors will help better assess spatial and temporal variations, which will be useful to improve prevention and mitigation control strategies.: Radon exposure has become a year-round problem as people spend most of their time indoors. In North America, radon exposure is increasing over time and awareness related to its health effects remains low in the general population. Several factors make prediction of indoor radon exposure in enclosed spaces challenging. In this study, we used random forest to investigate the influence of factors on indoor radon in the Midwest United States. We found that topography, geology, and soil composition were the most influential factors on indoor radon levels. These results will help better assess spatial and temporal variations, which will further help better prevention and mitigation control strategies.
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http://dx.doi.org/10.1080/10962247.2021.1950074DOI Listing
September 2021

Temporal changes in associations between high temperature and hospitalizations by greenspace: Analysis in the Medicare population in 40 U.S. northeast counties.

Environ Int 2021 11 2;156:106737. Epub 2021 Jul 2.

School of the Environment, Yale University, New Haven, CT, USA. Electronic address:

Although research indicates health and well-being benefits of greenspace, little is known regarding how greenspace may influence adaptation to health risks from heat, particularly how these risks change over time. Using daily hospitalization rates of Medicare beneficiaries ≥65 years for 2000-2016 in 40 U.S. Northeastern urban counties, we assessed how temperature-related hospitalizations from cardiovascular causes (CVD) and heat stroke (HS) changed over time. We analyzed effect modification of those temporal changes by Enhanced Vegetation Index (EVI), approximating greenspace. We used a two-stage analysis including a generalized additive model and meta-analysis. Results showed that relative risk (RR) (per 1 °C increase in lag0-3 temperature) for temperature-HS hospitalization was higher in counties with the lowest quartile EVI (RR = 2.7, 95% CI: 2.0, 3.4) compared to counties with the highest quartile EVI (RR = 0.40, 95% CI: 0.14, 1.13) in the early part of the study period (2000-2004). RR of HS decreased to 0.88 (95% CI: 0.31, 2.53) in 2013-2016 in counties with the lowest quartile EVI. RR for HS changed over time in counties in the highest quartile EVI, with RRs of 0.4 (95% CI: -0.7, 1.4) in 2000-2004 and 2.4 (95% CI: 1.6, 3.2) in 2013-2016. Findings suggest that adaptation to heat-health associations vary by greenness. Greenspace may help lower risks from heat but such health risks warrant continuous local efforts such as heat-health plans.
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http://dx.doi.org/10.1016/j.envint.2021.106737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380720PMC
November 2021

A Co-Twin control study of fine particulate matter and the prevalence of metabolic syndrome risk factors.

Environ Res 2021 10 27;201:111604. Epub 2021 Jun 27.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA. Electronic address:

The relationship between ambient fine particulate matter (PM) and metabolic syndrome (MetS) is understudied. It also remains unknown whether familial factors play a role in this relationship. In a study of 566 middle-aged twins, we examined the association of PM with MetS risk factors, measured by a MetS score as a summation of individual risk factors (range, 0 to 5). High-resolution PM estimates were obtained through previously validated models that incorporated monitor and satellite derived data. We estimated two-year average PM concentrations based on the ZIP code of each twin's residence. We used ordinal response models adapted for twin studies. When treating twins as individuals, the odds ratio of having 1-point higher MetS score was 1.78 for each 10 μg/m-increase in exposure to PM (confidence interval [CI]: 1.01, 3.15), after adjusting for potential confounders. This association was mainly between pairs; the odds ratio was 1.97 (CI: 1.01, 3.84) for each 10 μg/m-increase in the average pairwise exposure level. We found no significant difference in MetS scores within pairs who were discordant for PM exposure. In conclusion, higher PM in residence area is associated with more MetS risk factors. This association, however, is confounded by shared familial factors.
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http://dx.doi.org/10.1016/j.envres.2021.111604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478791PMC
October 2021

Metabolomic signatures of the short-term exposure to air pollution and temperature.

Environ Res 2021 10 24;201:111553. Epub 2021 Jun 24.

Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA; Channing Division of Network Medicine; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02129, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.

Background: Short-term exposures to air pollution and temperature have been reported to be associated with inflammation and oxidative stress. However, mechanistic understanding of the affected metabolic pathways is still lacking and literature on the short-term exposure of air-pollution on the metabolome is limited.

Objectives: We aimed to determine changes in the plasma metabolome and associated metabolic pathways related to short-term exposure to outdoor air pollution and temperature.

Methods: We performed mass-spectrometry based untargeted metabolomic profiling of plasma samples from a large and well-characterized cohort of men (Normative Aging Study) to identify metabolic pathways associated with short-term exposure to PM, NO, O, and temperature (one, seven-, and thirty-day average of address-specific predicted estimates). We used multivariable linear mixed-effect regression and independent component analysis (ICA) while simultaneously adjusting for all exposures and correcting for multiple testing.

Results: Overall, 456 white men provided 648 blood samples, in which 1158 metabolites were quantified, between 2000 and 2016. Average age and body mass index were 75.0 years and 27.7 kg/m, respectively. Only 3% were current smokers. In the adjusted models, NO, and temperature showed statistically significant associations with several metabolites (19 metabolites for NO and 5 metabolites for temperature). We identified six metabolic pathways (sphingolipid, butanoate, pyrimidine, glycolysis/gluconeogenesis, propanoate, and pyruvate metabolisms) perturbed with short-term exposure to air pollution and temperature. These pathways were involved in inflammation and oxidative stress, immunity, and nucleic acid damage and repair.

Conclusions: This is the first study to report an untargeted metabolomic signature of temperature exposure, the largest to report an untargeted metabolomic signature of air pollution, and the first to use ICA. We identified several significant plasma metabolites and metabolic pathways associated with short-term exposure to air pollution and temperature; using an untargeted approach. Those pathways were involved in inflammation and oxidative stress, immunity, and nucleic acid damage and repair. These results need to be confirmed by future research.
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http://dx.doi.org/10.1016/j.envres.2021.111553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478827PMC
October 2021

Impact of ambient temperature on ovarian reserve.

Fertil Steril 2021 Oct 9;116(4):1052-1060. Epub 2021 Jun 9.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Objective: To examine the association between ambient temperature and antral follicle count (AFC), a standard measure of ovarian reserve.

Design: Prospective cohort study.

Setting: Fertility center at an academic hospital in the northeastern United States.

Patient(s): 631 women attending the Massachusetts General Hospital Fertility Center (2005-2015) who participated in the Environment and Reproductive Health Study.

Intervention(s): Daily temperature at the women's residential address was estimated for the 90 days before their antral follicle scan using a spatially refined gridded climate data set. We evaluated the associations between temperature and AFC using Poisson regression with robust standard errors, adjusting for relative humidity, fine particulate matter exposure, age, education, smoking status, year and month of AFC, and diagnosis of diminished ovarian reserve and ovulation disorders.

Main Outcome Measure(s): Antral follicle count as measured with transvaginal ultrasonography.

Result(s): A 1°C increase in average maximum temperature during the 90 days before ovarian reserve testing was associated with a -1.6% (95% confidence interval [CI], -2.8, -0.4) lower AFC. Associations remained negative, but were attenuated, for average maximum temperature exposure in the 30 days (-0.9%, 95% CI, -1.8, 0.1) and 14 days (-0.8%, 95% CI, -1.6, 0.0) before AFC. The negative association between average maximum temperature and AFC was stronger in November through June than during the summer months, suggesting that timing of heat exposure and acclimatization to heat may be important factors to consider in future research.

Conclusion(s): Exposure to higher temperatures was associated with lower ovarian reserve. These results raise concern that rising ambient temperatures worldwide may result in accelerated reproductive aging among women.
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http://dx.doi.org/10.1016/j.fertnstert.2021.05.091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478715PMC
October 2021

Periconception air pollution, metabolomic biomarkers, and fertility among women undergoing assisted reproduction.

Environ Int 2021 10 8;155:106666. Epub 2021 Jun 8.

Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, United States.

Background: Air pollution exposure has been linked with diminished fertility. Identifying the metabolic changes induced by periconception air pollution exposure among women could enhance our understanding of the potential biological pathways underlying air pollution's reproductive toxicity.

Objective: To identify serum metabolites associated with periconception air pollution exposure and evaluate the extent to which these metabolites mediate the association between air pollution and live birth.

Methods: We included 200 women undergoing a fresh assisted reproductive technology (ART) cycle at Massachusetts General Hospital Fertility Center (2005-2015). A serum sample was collected during stimulation, and untargeted metabolic profiling was conducted using liquid chromatography with ultra-high-resolution mass spectrometry. Exposure to nitrogen dioxide (NO), ozone (O), fine particulate matter <2.5 µm (PM), and black carbon (BC) was estimated using validated spatiotemporal models. Multivariable linear regression models were used to evaluate the associations between the air pollutants, live birth, and metabolic feature intensities. A meet in the middle approach was used to identify overlapping features and metabolic pathways.

Results: From the C18 and HILIC chromatography columns, 10,803 and 12,968 metabolic features were extracted. There were 190 metabolic features and 18 pathways that were significantly associated with both air pollution and live birth (P < 0.05) across chromatography columns. Eight features were confirmed metabolites implicated in amino acid and nutrient metabolism with downstream effects on oxidative stress and inflammation. Six confirmed metabolites fell into two intuitive clusters - "antioxidants" and "oxidants"- which could potentially mediate some of the association between air pollution and lower odds of live birth. Tryptophan and vitamin B3 metabolism were common pathways linking air pollution exposure to decreased probability of live birth.

Conclusion: Higher periconception air pollution exposure was associated with metabolites and biologic pathways involved in inflammation and oxidative stress that may mediate the observed associations with lower probability of live birth following ART.
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http://dx.doi.org/10.1016/j.envint.2021.106666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292230PMC
October 2021

Comparison of Postoperative Anatomy Using Anatomic Total Shoulder Arthroplasty Versus Soft-Tissue Balancing Total Shoulder Arthroplasty.

J Am Acad Orthop Surg 2021 Oct;29(19):848-854

From the Department of Orthopaedics, Stanford University Hospitals, Redwood City, CA (Truntzer), the Department of Orthopaedics, University of Kansas Medical Center, Kansas City, KS (Vopat, Barnds), the Department of Orthopaedics, Brown University, Providence, RI (Schwartz, Anavian, Green), and the Department of Orthopaedic Surgery, Yale University, New Haven, CT (Blaine).

Background: The importance of anatomic reconstruction of the proximal humerus on shoulder biomechanics and kinematics after anatomic total shoulder replacement (aTSR) has been highlighted by a number of investigations. The humeral head designs of current-generation shoulder arthroplasty emphasize either anatomic or soft-tissue balancing total shoulder arthroplasty (sbTSR) philosophies. The purpose of this study was to compare the postoperative anatomy of TSR systems used to treat primary glenohumeral osteoarthritis.

Methods: This was a matched cohort study of 60 patients treated with either press-fit aTSR or sbTSR by two shoulder surgeons. The analysis of postoperative true AP radiographs was performed to calculate multiple representative anatomic parameters of the TSR.

Results: A significant difference was observed in the average measurements between the sbTSR and aTSR designs about the humeral head center offset (5.2 ± 0.4 mm versus 3.9 ± 0.3 mm; P = 0.02), implant-humeral shaft angle (0.3 ± 0.3 varus versus 1.7 ± 0.3 valgus, P < 0.001), and humeral head to tuberosity height (8.8 ± 0.4 mm versus 6.2 ± 0.4, P < 0.001), respectively. No significant difference was observed in the average measurements between the two systems' designs regarding the head-shaft angle (133.4° ± 0.8° versus 135.0° ± 1.0°, P = 0.16) and the relation of humeral head to lateral humeral cortex (0.15 ± 0.6 mm inside the lateral cortex versus 0.19 ± 0.6 outside the lateral cortex; P = 0.69), respectively.

Conclusions: Despite differing design philosophies of these systems, and some notable differences, the absolute differences between the measured anatomic parameters were small and not likely clinically relevant. Anatomic and soft-tissue balancing humeral arthroplasty implants can both reliably reconstruct proximal humeral anatomy.
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http://dx.doi.org/10.5435/JAAOS-D-20-00782DOI Listing
October 2021

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function.

Clin Epigenetics 2021 Jun 2;13(1):121. Epub 2021 Jun 2.

Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies.

Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β =  - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E-06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria.

Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.
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http://dx.doi.org/10.1186/s13148-021-01082-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170969PMC
June 2021

Maternal Ambient Exposure to Atmospheric Pollutants during Pregnancy and Offspring Term Birth Weight in the Nationwide ELFE Cohort.

Int J Environ Res Public Health 2021 05 28;18(11). Epub 2021 May 28.

Univ. Grenoble Alpes, Inserm, CNRS, IAB, 38000 Grenoble, France.

Background: Studies have reported associations between maternal exposure to atmospheric pollution and lower birth weight. However, the evidence is not consistent and uncertainties remain. We used advanced statistical approaches to robustly estimate the association of atmospheric pollutant exposure during specific pregnancy time windows with term birth weight (TBW) in a nationwide study.

Methods: Among 13,334 women from the French Longitudinal Study of Children (ELFE) cohort, exposures to PM, PM (particles < 2.5 µm and <10 µm) and NO (nitrogen dioxide) were estimated using a fine spatio-temporal exposure model. We used inverse probability scores and doubly robust methods in generalized additive models accounting for spatial autocorrelation to study the association of such exposures with TBW.

Results: First trimester exposures were associated with an increased TBW. Second trimester exposures were associated with a decreased TBW by 17.1 g (95% CI, -26.8, -7.3) and by 18.0 g (-26.6, -9.4) for each 5 µg/m increase in PM and PM, respectively, and by 15.9 g (-27.6, -4.2) for each 10 µg/m increase in NO. Third trimester exposures (truncated at 37 gestational weeks) were associated with a decreased TBW by 48.1 g (-58.1, -38.0) for PM, 38.1 g (-46.7, -29.6) for PM and 14.7 g (-25.3, -4.0) for NO. Effects of pollutants on TBW were larger in rural areas.

Conclusions: Our results support an adverse effect of air pollutant exposure on TBW. We highlighted a larger effect of air pollutants on TBW among women living in rural areas compared to women living in urban areas.
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http://dx.doi.org/10.3390/ijerph18115806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198942PMC
May 2021

A Direct Estimate of the Impact of PM2.5, NO2, and O3 Exposure on Life Expectancy Using Propensity Scores.

Epidemiology 2021 07;32(4):469-476

From the Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA.

Background: Many studies have reported associations of air pollutants and death, but fewer examined multiple pollutants, or used causal methods. We present a method for directly estimating changes in the distribution of age at death using propensity scores.

Methods: We included all participants in Medicare from 2000 to 2016 (637,207,589 person-years of follow-up). We fit separate logistic regressions modeling the probability of death at each year of age from 65 to 98 or older as a function of exposure to particulate matter less tha 2.5 µM in diameter (PM2.5), NO2, and O3, using separate propensity scores for each age. We estimated the propensity score using gradient boosting. We estimated the distribution of life expectancy at three counterfactual exposures for each pollutant.

Results: The estimated increase in mean life expectancy had the population been exposed to 7 versus 12 µg/m3 PM2.5 was 0.29 years (95% CI = 0.28, 0.30). The change in life expectancy had the population been exposed to 10 versus 20 ppb of NO2 was -0.01 years (95% CI = -0.015, -0.006). The increase in mean life expectancy had the population been exposed to 35 versus 45 ppb of O3 was 0.15 years (95% CI = 0.14, 0.16). Each of these effects was independent and additive.

Conclusions: We estimated that reducing PM2.5 and O3 concentrations to levels below current standards would increase life expectancy by substantial amounts compared with the recent increase of life expectancy at age 65 of 0.7 years in a decade. Our results are not consistent with the hypothesis that exposure to NO2 decreases life expectancy.
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http://dx.doi.org/10.1097/EDE.0000000000001354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162225PMC
July 2021

City-level vulnerability to temperature-related mortality in the USA and future projections: a geographically clustered meta-regression.

Lancet Planet Health 2021 06 20;5(6):e338-e346. Epub 2021 May 20.

Boston University School of Public Health, Boston, MA, USA.

Background: Extreme heat exposure can lead to premature death. Climate change is expected to increase the frequency, intensity, and duration of extreme heat events, resulting in many additional heat-related deaths globally, as well as changing the nature of extreme cold events. At the same time, vulnerability to extreme heat has decreased over time, probably due to a combination of physiological, behavioural, infrastructural, and technological adaptations. We aimed to account for these changes in vulnerability and avoid overstated projections for temperature-related mortality. We used the historical observed decrease in vulnerability to improve future mortality estimates.

Methods: We used historical mortality and temperature data from 208 US cities to quantify how observed changes in vulnerability from 1973 to 2013 affected projections of temperature-related mortality under various climate scenarios. We used geographically structured meta-regression to characterise the relationship between temperature and mortality for these urban populations over the specified time period. We then used the fitted relationships to project mortality under future climate conditions.

Findings: Between Oct 26, 2018, and March 9, 2020, we established that differences in vulnerability to temperature were geographically structured. Vulnerability decreased over time in most areas. US mortalities projected from a 2°C increase in mean temperature decreased by more than 97% when using 2003-13 data compared with 1973-82 data. However, these benefits declined with increasing temperatures, with a 6°C increase showing only an 84% decline in projected mortality based on 2003-13 data.

Interpretation: Even after accounting for adaptation, the projected effects of climate change on premature mortality constitute a substantial public health risk. Our work suggests large increases in temperature will require additional mitigation to avoid excess mortality from heat events, even in areas with high air conditioning coverage in place.

Funding: The US Environmental Protection Agency and Abt Associates.
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http://dx.doi.org/10.1016/S2542-5196(21)00058-9DOI Listing
June 2021

Prenatal Ambient Ultrafine Particle Exposure and Childhood Asthma in the Northeastern United States.

Am J Respir Crit Care Med 2021 10;204(7):788-796

Department of Civil and Environmental Engineering, Tufts University, Medford, Massachusetts.

Ambient ultrafine particles (UFPs; with an aerodynamic diameter < 0.1 μm) may exert greater toxicity than other pollution components because of their enhanced oxidative capacity and ability to translocate systemically. Studies examining associations between prenatal UFP exposure and childhood asthma remain sparse. We used daily UFP exposure estimates to identify windows of susceptibility of prenatal UFP exposure related to asthma in children, accounting for sex-specific effects. Analyses included 376 mother-child dyads followed since pregnancy. Daily UFP exposure during pregnancy was estimated by using a spatiotemporally resolved particle number concentration prediction model. Bayesian distributed lag interaction models were used to identify windows of susceptibility for UFP exposure and examine whether effect estimates varied by sex. Incident asthma was determined at the first report of asthma (3.6 ± 3.2 yr). Covariates included maternal age, education, race, and obesity; child sex; nitrogen dioxide (NO) and temperature averaged over gestation; and postnatal UFP exposure. Women were 37.8% Black and 43.9% Hispanic, with 52.9% reporting having an education at the high school level or lower; 18.4% of children developed asthma. The cumulative odds ratio (95% confidence interval) for incident asthma per doubling of the UFP exposure concentration across pregnancy was 4.28 (1.41-15.7), impacting males and females similarly. Bayesian distributed lag interaction models indicated sex differences in the windows of susceptibility, with the highest risk of asthma seen in females exposed to higher UFP concentrations during late pregnancy. Prenatal UFP exposure was associated with asthma development in children, independent of correlated ambient NO and temperature. Findings will benefit future research and policy-makers who are considering appropriate regulations to reduce the adverse effects of UFPs on child respiratory health.
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http://dx.doi.org/10.1164/rccm.202010-3743OCDOI Listing
October 2021

Placental gene networks at the interface between maternal PM exposure early in gestation and reduced infant birthweight.

Environ Res 2021 08 18;199:111342. Epub 2021 May 18.

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Background: A growing body of evidence links maternal exposure to particulate matter <2.5 μM in diameter (PM) and deviations in fetal growth. Several studies suggest that the placenta plays a critical role in conveying the effects of maternal PM exposure to the developing fetus. These include observed associations between air pollutants and candidate placental features, such as mitochondrial DNA content, DNA methylation and telomere length. However, gaps remain in delineating the pathways linking the placenta to air pollution-related health effects, including a comprehensive profiling of placental processes impacted by maternal PM exposure. In this study, we examined alterations in a placental transcriptome-wide network in relation to maternal PM exposure prior to and during pregnancy and infant birthweight.

Methods: We evaluated PM exposure and placental RNA-sequencing data among study participants enrolled in the Rhode Island Child Health Study (RICHS). Daily residential PM levels were estimated using a hybrid model incorporating land-use regression and satellite remote sensing data. Distributed lag models were implemented to assess the impact on infant birthweight due to PM weekly averages ranging from 12 weeks prior to gestation until birth. Correlations were assessed between PM levels averaged across the identified window of susceptibility and a placental transcriptome-wide gene coexpression network previously generated using the WGCNA R package.

Results: We identified a sensitive window spanning 12 weeks prior to and 13 weeks into gestation during which maternal PM exposure is significantly associated with reduced infant birthweight. Two placental coexpression modules enriched for genes involved in amino acid transport and cellular respiration were correlated with infant birthweight as well as maternal PM exposure levels averaged across the identified growth restriction window.

Conclusion: Our findings suggest that maternal PM exposure may alter placental programming of fetal growth, with potential implications for downstream health effects, including susceptibility to cardiometabolic health outcomes and viral infections.
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http://dx.doi.org/10.1016/j.envres.2021.111342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195860PMC
August 2021

Assessing mortality risk attributable to high ambient temperatures in Ahmedabad, 1987 to 2017.

Environ Res 2021 07 11;198:111232. Epub 2021 May 11.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Studies on high temperatures and mortality have not focused on underdeveloped tropical regions and have reported the associations of different temperature metrics without conducting model selection.

Methods: We collected daily mortality and meteorological data including ambient temperatures and humidity in Ahmedabad during summer, 1987-2017. We proposed two cross-validation (CV) approaches to compare semiparametric quasi-Poisson models with different temperature metrics and heat wave definitions. Using the fittest model, we estimated heat-mortality associations among general population and subpopulations. We also conducted separate analyses for 1987-2002 and 2003-2017 to evaluate temporal heterogeneity.

Findings: The model with maximum and minimum temperatures and without heat wave indicator gave the best performance. With this model, we found a substantial and significant increase in mortality rate starting from maximum temperature at 42 °C and from minimum temperature at 28 °C: 1 °C increase in maximum and minimum temperatures at lag 0 were associated with 9.56% (95% confidence interval [CI]: 6.64%, 12.56%) and 9.82% (95% CI: 6.33%, 13.42%) increase in mortality risk, respectively. People aged ≥65 years and lived in South residential zone where most slums were located, were more vulnerable. We observed flatter increases in mortality risk associated with high temperatures comparing the period of 2003-2017 to 1987-2002.

Interpretation: The analyses provided better understanding of the relationship of high temperatures with mortality in underdeveloped tropical regions and important implications in developing heat warning system for local government. The proposed CV approaches will benefit future scientific work.
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Source
http://dx.doi.org/10.1016/j.envres.2021.111232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169607PMC
July 2021
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