Search

Background: Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults., Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up., Results: Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI}, .86-1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI, .28-1.30]). Statistical power to assess effect modification in other subgroups was limited., Conclusions: In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259., Competing Interests: Potential conflicts of interest. C. A. C. received support for the present manuscript from the NIH, Pharmavite, Pronova BioPharma/BASF, and Quest Diagnostics paid to their institution. R. J. G. reported receipt of grants from Amarin, Kowa, Novartis, and Pfizer; participation on a data safety monitoring board or advisory board for National Heart, Lung, and Blood Institute trials of blood disorders, HI-PRO Trial of venous thromboembolism prevention, and the CANARY trial of cannabidiol. D. R. G. has received grants or contracts from the NIH. S. M. reports consulting for Quest Diagnostics and Pfizer. J. E. B. reports that her spouse is a member of the scientific advisory board of Pharmavite, which provided the vitamin D pills and packaging for the trial. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Human endogenous retroviruses (HERVs) are transposable genomic elements generally repressed through DNA methylation. HERVs can be demethylated and expressed in response to environmental stimuli. Therefore, more research is needed to understand the influence of environmental exposures on HERV methylation. Air pollutants are commonly linked with global hypomethylation, and as HERVs comprise of nearly 8% of repetitive elements in the human genome, our objective was to examine the association between air pollutant exposure and HERV methylation. We investigated 180 students with asthma participating in the School Inner-City Asthma Intervention Study, which evaluated the efficacy of classroom air filters and school-wide pest management on air pollutant/allergen exposure and asthma. Both air pollutants measured in classrooms and asthma outcomes assessed by surveys were collected pre- and post-intervention. Buccal swabs were also collected pre- and post-intervention, and methylation levels from 9 transposable genomic elements (HERV-E, -FRD, -K, -L, -R, -W, -9, and HRES and LINE1) were measured. Adjusting for relevant covariates, the overall air pollutant mixture was cross-sectionally associated with higher HERV-W and lower HERV-L and LINE1 methylation. Coarse PM was cross-sectionally associated with higher HERV-K methylation and CO2 with lower LINE1 methylation. These results suggest that exposure to air pollutants is associated with HERV-W and HERV-K hypermethylation and HERV-L and LINE1 hypomethylation in children with asthma. Future studies are needed to characterize the links between HERV methylation and possible adverse outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Cardiac arrhythmias have been associated with intense solar and geomagnetic activity (SGA) and exposures to air pollution., Methods and Results: We examined whether oscillations of SGA can modify the effect of hourly exposures to air pollutants on atrial fibrillation ≥30 s (AF) risk in patients with dual-chamber implantable cardioverter-defibrillators. The effects of SGA on ambient particulate matter <2.5 µm (PM2.5), black carbon (BC), ultrafine particles (PN), and associations with AF were assessed. Measures of SGA included solar wind proton density (SW), total interplanetary magnetic field strength (IMF), and Kp index, a measure of global geomagnetic activity. Overall time lags between 0 and 24 h, periods of increased SGA (>50th percentile in IMF, SW, and Kp index) enhanced the effects of all three air pollutants on AF, while during periods of reduced SGA the associations were considerably weaker or absent. During periods of intense SW 6 h prior to an AF event, the odds ratio (OR) for PM2.5 exposure per interquartile range (IQR) of 5.6 µg/m3 was 1.7 [95% confident interval (CI) 1.3-2.3, P = 0.0001]. For periods of reduced SW, the OR for PM2.5 exposure per IQR was 1.2 (95% CI 0.9-1.5; P = 0.27). There were similar effects for PN and BC exposures. In patients with multiple AF events per hour, the associations with air pollutants during intense SGA were even greater., Conclusion: The effects of air pollutants up to 24 h before AF events were enhanced during periods of increased SGA. Our results suggest that these effects may account for variation in AF risk., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Our study adds to the sparse literature on the effect of multiple fine particulate matter (PM2.5) components on QT interval length, an outcome with high clinical relevance in vulnerable populations. To our knowledge, this is the first study to examine the association between spatiotemporally resolved exposures to PM2.5 components and QT interval length., Methods and Results: Among 578 men living in Eastern Massachusetts between 2000 and 2011, we utilized time-varying linear mixed-effects regressions with a random intercept to examine associations between acute (0-3 days), intermediate (4-28 days), and long-term (1 year) exposure to PM2.5 components, temperature, and heart-rate corrected QT interval (QTc). Each of the PM2.5 components and temperature was geocoded to the participant's residential address using validated ensemble and hybrid exposure models and gridMET predictions. We also evaluated whether diabetic status modified the association between PM2.5 components and QTc interval. We found consistent results that higher sulfate levels and colder temperatures were associated with significant longer QTc across all moving averages except the day of exposure. The greatest effect of sulfate and temperature was detected for the 28-day moving average. In the multi-pollutant model, each 1.5 µg/m3 IQR increase in daily sulfate was associated with a 15.1 ms [95% confidence interval (CI): 10.2-20.0] increase in QTc interval and in the single-pollutant models a 15.3 ms (95% CI: 11.6-19.1) increase in QTc interval. Other secondary particles, such as nitrate and organic carbon, also prolonged QT interval, while elemental carbon decreased QT interval. We found that diabetic status did not modify the association between PM2.5 components and QTc interval., Conclusion: Acute and long-term exposure to PM2.5 components and temperature are associated with changes in ventricular repolarization as measured by QT interval., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Context: Per- and polyfluoroalkyl substances (PFAS) may alter body composition by lowering anabolic hormones and increasing inflammation, but data are limited, particularly in adolescence when body composition is rapidly changing., Objective: To evaluate associations of PFAS plasma concentrations in childhood with change in body composition through early adolescence., Methods: A total of 537 children in the Boston-area Project Viva cohort participated in this study. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to examine associations of plasma concentrations of 6 PFAS, quantified by mass spectrometry, in mid-childhood (mean age, 7.9 years; 2007-2010) with change in body composition measured by dual-energy x-ray absorptiometry from mid-childhood to early adolescence (mean age, 13.1 years)., Results: In single-PFAS linear regression models, children with higher concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoate (PFDA), and perfluorohexane sulfonate (PFHxS) had less accrual of lean mass (eg, -0.33 [95% CI: -0.52, -0.13] kg/m2 per doubling of PFOA). Children with higher PFOS and PFHxS had less accrual of total and truncal fat mass (eg, -0.32 [95% CI: -0.54, -0.11] kg/m2 total fat mass per doubling of PFOS), particularly subcutaneous fat mass (eg, -17.26 [95% CI -32.25, -2.27] g/m2 per doubling of PFOS). Children with higher PFDA and perfluorononanoate (PFNA) had greater accrual of visceral fat mass (eg, 0.44 [95% CI: 0.13, 0.75] g/m2 per doubling of PFDA). Results from BKMR mixture models were consistent with linear regression analyses., Conclusion: Early life exposure to some but not all PFAS may be associated with adverse changes in body composition., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

E-cigarettes have surged in popularity over the last few years, particularly among youth and young adults. These battery-powered devices aerosolize e-liquids, comprised of propylene glycol and vegetable glycerin, typically with nicotine, flavors, and stabilizers/humectants. Although the use of combustible cigarettes is associated with several adverse health effects including multiple pulmonary and cardiovascular diseases, the effects of e-cigarettes on both short- and long-term health have only begun to be investigated. Given the recent increase in the popularity of e-cigarettes, there is an urgent need for studies to address their potential adverse health effects, particularly as many researchers have suggested that e-cigarettes may pose less of a health risk than traditional combustible cigarettes and should be used as nicotine replacements. This report is prepared for clinicians, researchers, and other health care providers to provide the current state of knowledge on how e-cigarette use might affect cardiopulmonary health, along with research gaps to be addressed in future studies., (Published by Oxford University Press on behalf of American Physiological Society 2021. This work is written by US Government employees and is in the public domain in the US.)

Background: Few studies have examined the independent and combined relationships of body mass index (BMI) peak and rebound with adiposity, insulin resistance and metabolic risk later in life. We used data from Project Viva, a well-characterized birth cohort from Boston with repeated measures of BMI, to help fill this gap., Methods: Among 1681 children with BMI data from birth to mid childhood, we fitted individual BMI trajectories using mixed-effects models with natural cubic splines and estimated age, and magnitude of BMI, at peak (in infancy) and rebound (in early childhood). We obtained cardiometabolic measures of the children in early adolescence (median 12.9 years) and analysed their associations with the BMI parameters., Results: After adjusting for potential confounders, age and magnitude at infancy BMI peak were associated with greater adolescent adiposity, and earlier adiposity rebound was strongly associated with greater adiposity, insulin resistance and metabolic risk score independently of BMI peak. Children with a normal timing of BMI peak plus early rebound had an adverse cardiometabolic profile, characterized by higher fat mass index {β 2.2 kg/m2 [95% confidence interval (CI) 1.6, 2.9]}, trunk fat mass index [1.1 kg/m2 (0.8, 1.5)], insulin resistance [0.2 units (0.04, 0.4)] and metabolic risk score [0.4 units (0.2, 0.5)] compared with children with a normal BMI peak and a normal rebound pattern. Children without a BMI peak (no decline in BMI after the rise in infancy) also had adverse adolescent metabolic profiles., Conclusions: Early age at BMI rebound is a strong risk factor for cardiometabolic risk, independent of BMI peak. Children with a normal peak-early rebound pattern, or without any BMI decline following infancy, are at greatest risk of adverse cardiometabolic profile in adolescence. Routine monitoring of BMI may help to identify children who are at greatest risk of developing an adverse cardiometabolic profile in later life and who may be targeted for preventive interventions., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

We examined associations between ambient air pollution and hepatic steatosis among 2,513 participants from the Framingham (Massachusetts) Offspring Study and Third Generation Cohort who underwent a computed tomography scan (2002-2005), after excluding men who reported >21 drinks/week and women who reported >14 drinks/week. We calculated each participant's residential-based distance to a major roadway and used a spatiotemporal model to estimate the annual mean concentrations of fine particulate matter. Liver attenuation was measured by computed tomography, and liver-to-phantom ratio (LPR) was calculated. Lower values of LPR represent more liver fat. We estimated differences in continuous LPR using linear regression models and prevalence ratios for presence of hepatic steatosis (LPR ≤ 0.33) using generalized linear models, adjusting for demographics, individual and area-level measures of socioeconomic position, and clinical and lifestyle factors. Participants who lived 58 m (25th percentile) from major roadways had lower LPR (β = -0.003, 95% confidence interval: -0.006, -0.001) and higher prevalence of hepatic steatosis (prevalence ratio = 1.16, 95% confidence interval: 1.05, 1.28) than those who lived 416 m (75th percentile) away. The 2003 annual average fine particulate matter concentration was not associated with liver-fat measurements. Our findings suggest that living closer to major roadways was associated with more liver fat., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We established Project Viva to examine prenatal diet and other factors in relation to maternal and child health. We recruited pregnant women at their initial prenatal visit in eastern Massachusetts between 1999 and 2002. Exclusion criteria included multiple gestation, inability to answer questions in English, gestational age ≥22 weeks at recruitment and plans to move away before delivery. We completed in-person visits with mothers during pregnancy in the late first (median 9.9 weeks of gestation) and second (median 27.9 weeks) trimesters. We saw mothers and children in the hospital during the delivery admission and during infancy (median age 6.3 months), early childhood (median 3.2 years) and mid-childhood (median 7.7 years). We collected information from mothers via interviews and questionnaires, performed anthropometric and neurodevelopmental assessments and collected biosamples. We have collected additional information from medical records and from mailed questionnaires sent annually to mothers between in-person visits and to children beginning at age 9 years. From 2341 eligible women, there were 2128 live births; 1279 mother-child pairs provided data at the mid-childhood visit. Primary study outcomes include pregnancy outcomes, maternal mental and cardiometabolic health and child neurodevelopment, asthma/atopy and obesity/cardiometabolic health. Investigators interested in learning more about how to obtain Project Viva data can contact Project&#95;Viva@hphc.org., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

We investigated associations between ambient air pollution and microvessel function measured by peripheral arterial tonometry between 2003 and 2008 in the Framingham Heart Study Offspring and Third Generation Cohorts. We measured particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), black carbon, sulfates, particle number, nitrogen oxides, and ozone by using fixed monitors, and we determined moving averages for 1-7 days preceding vascular testing. We examined associations between these exposures and hyperemic response to ischemia and baseline pulse amplitude, a measure of arterial tone (n = 2,369). Higher short-term exposure to air pollutants, including PM2.5, black carbon, and particle number was associated with higher baseline pulse amplitude. For example, higher 3-day average PM2.5 exposure was associated with 6.3% higher baseline pulse amplitude (95% confidence interval: 2.0, 10.9). However, there were no consistent associations between the air pollution exposures assessed and hyperemic response. Our findings in a community-based sample exposed to relatively low pollution levels suggest that short-term exposure to ambient particulate pollution is not associated with vasodilator response, but that particulate air pollution is associated with baseline pulse amplitude, suggesting potentially adverse alterations in baseline vascular tone or compliance., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is increasing interest in evaluating the association between specific fine-particle (particles with aerodynamic diameters less than 2.5 µm; PM2.5) constituents and adverse health outcomes rather than focusing solely on the impact of total PM2.5. Because PM2.5 may be related to both constituent concentration and health outcomes, constituents that are more strongly correlated with PM2.5 may appear more closely related to adverse health outcomes than other constituents even if they are not inherently more toxic. Therefore, it is important to properly account for potential confounding by PM2.5 in these analyses. Usually, confounding is due to a factor that is distinct from the exposure and outcome. However, because constituents are a component of PM2.5, standard covariate adjustment is not appropriate. Similar considerations apply to source-apportioned concentrations and studies assessing either short-term or long-term impacts of constituents. Using data on 18 constituents and data from 1,060 patients admitted to a Boston medical center with ischemic stroke in 2003-2008, the authors illustrate several options for modeling the association between constituents and health outcomes that account for the impact of PM2.5. Although the different methods yield results with different interpretations, the relative rankings of the association between constituents and ischemic stroke were fairly consistent across models.

Frequently, exposure data are measured over time on a grid of discrete values that collectively define a functional observation. In many applications, researchers are interested in using these measurements as covariates to predict a scalar response in a regression setting, with interest focusing on the most biologically relevant time window of exposure. One example is in panel studies of the health effects of particulate matter (PM), where particle levels are measured over time. In such studies, there are many more values of the functional data than observations in the data set so that regularization of the corresponding functional regression coefficient is necessary for estimation. Additional issues in this setting are the possibility of exposure measurement error and the need to incorporate additional potential confounders, such as meteorological or co-pollutant measures, that themselves may have effects that vary over time. To accommodate all these features, we develop wavelet-based linear mixed distributed lag models that incorporate repeated measures of functional data as covariates into a linear mixed model. A Bayesian approach to model fitting uses wavelet shrinkage to regularize functional coefficients. We show that, as long as the exposure error induces fine-scale variability in the functional exposure profile and the distributed lag function representing the exposure effect varies smoothly in time, the model corrects for the exposure measurement error without further adjustment. Both these conditions are likely to hold in the environmental applications we consider. We examine properties of the method using simulations and apply the method to data from a study examining the association between PM, measured as hourly averages for 1-7 days, and markers of acute systemic inflammation. We use the method to fully control for the effects of confounding by other time-varying predictors, such as temperature and co-pollutants.

Background: Exposure to environmental tobacco smoke (ETS) has been shown to increase the risk for cardiovascular diseases and death, and autonomic dysfunction (specifically, reduced heart rate variability (HRV)) is a predictor of increased cardiac risk. This study tests the hypothesis that ETS exposure reduces HRV in the general population and discusses possible pathways., Methods: This cross-sectional study was conducted between 2001 and 2003 and is part of the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung Diseases in Adults) study. The analysis included 1218 randomly selected non-smokers aged 50 and above who participated in 24-h electrocardiogram recordings. Other examinations included an interview, investigating health status (especially respiratory and cardiovascular health and health relevant behaviours and exposure to ETS) and measurements of blood pressure, body height and weight., Results: Subjects exposed to ETS at home or at work for more than 2 h/day had a difference of -15% in total power (95%CI: -26 to -3%), low frequency power (-28 to -1%), low/high frequency ratio (-26 to -3%) and -18% (-29 to -4%) in ultralow frequency power of HRV compared with subjects not exposed to ETS at home or work. We also found a 2.7% (-0.01 to 5.34%) higher heart rate during the recording in exposed subjects., Conclusions: Exposure to ETS at home and work is associated with lower HRV and with higher heart rate in an ageing population. Our findings suggest that exposure to ETS increases cardiac risk through disturbances in the autonomic nervous system.

Aims: (i) To report associations between cardiovascular risk factors and heart rate variability (HRV) in a general population and (ii) to provide normal values for various HRV measurements in a healthy European general population sample aged >or=50., Methods and Results: Twenty-four-hour electrocardiograms were recorded in 1742 randomly selected SAPALDIA (Swiss cohort study on Air Pollution and Lung Diseases in Adults) participants aged >or=50. In multivariate regression analyses, women (n=895) had a 6.1% lower standard deviation of all normal RR (NN) intervals (SDNN), a 11.4% lower total power (TP), and a 27.2% lower low-frequency (LF) power than men (n=847). Per unit increase in BMI, SDNN decreased by 0.7% and TP decreased by 1.2%. Persons with high blood pressure had a 9.2% lower LF than normotensive persons and current smokers a 15.5% lower LF than never smokers. Each hour of heavy physical exercise was associated with a 2.0% increase in SDNN, a 3.6% increase in the high frequency (HF) range power and a 4.2% increase in LF power. Higher levels of uric acid, high-sensitive C-reactive protein and non-HDL-cholesterol were associated with lower TP, HF and LF. Percentiles of TP and LF/HF as a function of age were calculated for an asymptomatic subsample of participants (n=499) free of cardioactive medications., Conclusion: Heart rate variability in a general population sample shows expected associations with all known cardiovascular risk factors, although not identically for all HRV domains. Together with our percentile estimates for HRV as a function of age, these findings could assist scientists in interpreting 24 h HRV values and factors influencing them in an ageing population.

In a cohort of 849 infants with an asthmatic sibling, the authors examined the relations of exposure to allergens (dust mite, cockroach, cat, and dog), nitrogen dioxide, and mold with symptoms of wheeze and persistent cough in the first year of life (1998-2000). Among infants whose mothers had physician-diagnosed asthma, neither dust mite allergen nor dog allergen was associated with either symptom. Exposure to cockroach allergen (Bla g 1 at >or=2 U/g) modestly increased the risk for wheeze (odds ratio (OR) = 1.87, 95% confidence interval (CI): 0.94, 3.71), and exposure to cat allergen modestly decreased the risk (OR = 0.60, 95% CI: 0.35, 1.03). Among infants of mothers with no asthma history, exposure to gas stoves (OR = 1.50, 95% CI: 1.05, 2.15) and wood-burning stoves (OR = 2.09, 95% CI: 1.12, 3.91) increased the risk of persistent cough. Similarly, measured nitrogen dioxide concentration was associated with persistent cough (OR = 1.21, 95% CI: 1.05, 1.40). Persistent mold affected both infants of mothers with asthma (for wheeze, OR = 2.27, 95% CI: 1.27, 4.07; for cough, OR = 1.83, 95% CI: 1.04, 3.22) and infants of mothers without asthma (for cough, OR = 1.55, 95% CI: 1.04, 2.31). Reported exposure was confirmed by an association of measured fungi with wheeze (OR = 1.23, 95% CI: 1.01, 1.49). This appears to have been the first study to measure all of these home exposures (indoor allergens, nitrogen dioxide, fungi) and to prospectively measure the frequency of infant wheeze and persistent cough.