Background Long-term exposure to ambient air pollution has been associated with premature mortality, but associations at concentrations lower than current annual limit values are uncertain. We analysed associations between low-level air pollution and mortality within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE). Methods In this multicentre longitudinal study, we analysed seven population-based cohorts of adults (age >= 30 years) within ELAPSE, from Belgium, Denmark, England, the Netherlands, Norway, Rome (Italy), and Switzerland (enrolled in 2000-11; follow-up until 2011-17). Mortality registries were used to extract the underlying cause of death for deceased individuals. Annual average concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon, and tropospheric warm-season ozone (O-3) from Europe-wide land use regression models at 100 m spatial resolution were assigned to baseline residential addresses. We applied cohort-specific Cox proportional hazard models with adjustment for area-level and individual-level covariates to evaluate associations with non-accidental mortality, as the main outcome, and with cardiovascular, non-malignant respiratory, and lung cancer mortality. Subset analyses of participants living at low pollutant concentrations (as per predefined values) and natural splines were used to investigate the concentration-response function. Cohort-specific effect estimates were pooled in a random-effects meta-analysis. Findings We analysed 28 153 138 participants contributing 257 859 621 person-years of observation, during which 3 593 741 deaths from non-accidental causes occurred. We found significant positive associations between non-accidental mortality and PM2.5, NO2, and black carbon, with a hazard ratio (HR) of 1.053 (95% CI 1.021-1.085) per 5 mu g/m(3) increment in PM2.5, 1.044 (1.019-1.069) per 10 mu g/m(3) NO2, and 1.039 (1.018-1.059) per 0.5 x 10(-5)/m black carbon. Associations with PM2.5, NO2, and black carbon were slightly weaker for cardiovascular mortality, similar for non-malignant respiratory mortality, and stronger for lung cancer mortality. Warm-season O-3 was negatively associated with both non-accidental and cause-specific mortality. Associations were stronger at low concentrations: HRs for non-accidental mortality at concentrations lower than the WHO 2005 air quality guideline values for PM2.5 (10 mu g/m(3)) and NO2 (40 mu g/m(3)) were 1.078 (1.046-1.111) per 5 mu g/m(3) PM2.5 and 1.049 (1.024-1.075) per 10 mu g/m(3) NO2. Similarly, the association between black carbon and non-accidental mortality was highest at low concentrations, with a HR of 1.061 (1.032-1.092) for exposure lower than 1.5x 10(-5)/m, and 1.081 (0.966-1.210) for exposure lower than 1.0x 10(-5)/m. Interpretation Long-term exposure to concentrations of PM2.5, and NO2 lower than current annual limit values was associated with non-accidental, cardiovascular, non-malignant respiratory, and lung cancer mortality in seven large European cohorts. Continuing research on the effects of low concentrations of air pollutants is expected to further inform the process of setting air quality standards in Europe and other global regions. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

The Tobacco Products Directive (TPD) defines enhanced reporting obligations applying to 15 priority additives added to cigarettes and roll-your-own tobacco. A consortium of 12 international tobacco companies submitted 14 reports that were reviewed by an independent scientific body within the Joint Action on Tobacco Control (JATC). The reports were evaluated in accordance with the TPD with regard to their comprehensiveness, methodology and conclusions. Here we present their significant identified methodological limitations. The toxicological and chemical evaluation in the industry reports was mainly based on comparative testing, which lacks discriminative power for products with high toxicity and variability, like cigarettes. The literature reviews were biased, the comparative chemical studies did not assess previously identified pyrolysis products, the toxicological evaluation did not include the assessment of inhalation toxicity, and pyrolysis products were not assessed in terms of toxicity, including their genotoxic and carcinogenic potential. For both chemistry and toxicity testing, the statistical approach applied to test the difference between test and additive-free control cigarettes resulted in a high chance of false negatives. The clinical study for inhalation facilitation and nicotine uptake had limitations concerning study design and statistical analysis, while addictiveness was not assessed. Finally, the methodology used to assess characterizing flavors was flawed. In conclusion, there are significant limitations in the methodology applied by the industry. Therefore, the provided reports are of insufficient quality and are clearly not suitable to decide whether a priority additive should be banned in tobacco products according to the TPD.

The European Union Tobacco Products Directive (EU TPD) mandates enhanced reporting obligations for tobacco manufacturers regarding 15 priority additives. Within the Joint Action on Tobacco Control (JATC), a review panel of independent experts was appointed for the scientific evaluation of the additive reports submitted by a consortium of 12 tobacco manufacturers. As required by the TPD, the reports were evaluated based on their comprehensiveness, methodology and conclusions. In addition, we evaluated the chemical, toxicological, addictive, inhalation facilitating and flavoring properties of the priority additives based on the submitted reports, supplemented by the panel's expert knowledge and some independent literature. The industry concluded that none of the additives is associated with concern. Due to significant methodological limitations, we question the scientific validity of these conclusions and conclude that they are not warranted. Our review demonstrates that many issues regarding toxicity, addictiveness and attractiveness of the additives have not been sufficiently addressed, and therefore concerns remain. For example, menthol facilitates inhalation by activation of the cooling receptor TRPM8. The addition of sorbitol and guar gum leads to a significant increase of aldehydes that may contribute to toxicity and addictiveness. Titanium dioxide particles (aerodynamic diameter <10 µm) are legally classified as carcinogenic when inhaled. For diacetyl no report was provided. Overall, the industry reports were not comprehensive, and the information presented provides an insufficient basis for the regulation of most additives. We, therefore, advise MS to consider alternative approaches such as the precautionary principle.

Background and aim: Short-term health effects of air temperature have been extensively investigated at the population level. However, such effects have rarely been assessed using individual-level data. This time-stratified case-crossover study examined short-term associations of air temperature with cause-specific mortality and potential effect modification by individual characteristics in the Cohort of Norway (CONOR) cohort. Methods: CONOR recruited ~173,000 participants from 1994 to 2003. Participants' vital status and cause of death were collected from the Cause of Death Registry of Norway. Daily mean air temperatures estimated by a spatial-temporal model were assigned to participants' residences. We applied conditional logistic regression models with the distributed lag non-linear model approach to assess cold and heat effects on cause-specific mortality up to a lag of 10 days. Effect modification was examined by an interaction term between air temperature and potential modifiers. Results: We identified 40,040 cases of natural-cause deaths through December 31, 2018, including 14,457 deaths from cardiovascular diseases and 3,699 deaths from respiratory diseases. The mean air temperature during the study period was 5.0 °C (SD: 7.5 °C). We observed an increased risk of natural-cause mortality (OR: 1.12, 95% CI: 0.99, 1.27) for a decrease in temperature from the 25th (0 °C) to the 1st (-13.3 °C) percentile. This was accompanied by a trend for increased risks of cardiopulmonary, cardiovascular, ischemic heart disease, and cerebrovascular mortality associated with decreasing air temperature. The cold effect on natural-cause mortality was more pronounced among participants who were female, had lower socioeconomic status, lived in sparsely populated areas, and had no history of CVD. We did not find adverse heat effects on mortality. Conclusions: We find evidence for adverse short-term cold effects on mortality at the individual level in Norway and identify the sub-populations that are potentially most vulnerable. Keywords: Air temperature, mortality, cardiovascular, respiratory, susceptibility

This study explores the risk for cancer by level of antibodies to the anaerobe oral bacteria of periodontitis Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all three collectively termed the red complex, and the facultative anaerobe bacterium Aggregatibacter actinomycetemcomitans (AA). The prospective cohort, the Oslo II-study from 2000, the second screening of the Oslo study of 1972/73, has been followed for 17 ½ years with regard to cancer incidence and mortality. A random sample of 697 elderly men comprised the study cohort. The antibody results measured by enzyme linked immunosorbent assay (ELISA) were used in the Cox proportional hazards analyses, and quartile risk on cancer incidence in a 17 ½ years follow-up. Among the 621 participants with no prior cancer diagnoses, 221 men developed cancer. The incidence trend was inverse, and the results are shown as 1st quartile of highest value and 4th as lowest of antibody levels. The results of the Cox proportional regression analyses showed that TF inversely predicts bladder cancer (n = 22) by Hazard Ratio (HR) = 1.71 (95% CI: 1.12, 2.61). TD inversely predicts colon cancer (n = 26) by HR = 1.52 (95% CI: 1.06, 2.19) and bladder cancer (n = 22) by HR = 1.60 (95% CI: 1.05, 2.43). Antibodies to two oral bacteria, TF and TD, showed an inverse risk relationship with incidence of specific cancers: TF bladder cancer, TD bladder and colon cancer. Lowered immunological response to the oral infection, periodontitis, is shown to be a risk factor in terms of cancer aetiology.

INTRODUCTION Epidemiological cohort studies have consistently found associations between long-term exposure to outdoor air pollution and a range of morbidity and mortality endpoints. Recent evaluations by the World Health Organization and the Global Burden of Disease study have suggested that these associations may be nonlinear and may persist at very low concentrations. Studies conducted in North America in particular have suggested that associations with mortality persisted at concentrations of particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) well below current air quality standards and guidelines. The uncertainty about the shape of the concentration-response function at the low end of the concentration distribution, related to the scarcity of observations in the lowest range, was the basis of the current project. Previous studies have focused on PM2.5, but increasingly associations with nitrogen dioxide (NO2) are being reported, particularly in studies that accounted for the fine spatial scale variation of NO2. Very few studies have evaluated the effects of long-term exposure to low concentrations of ozone (O3). Health effects of black carbon (BC), representing primary combustion particles, have not been studied in most large cohort studies of PM2.5. Cohort studies assessing health effects of particle composition, including elements from nontailpipe traffic emissions (iron, copper, and zinc) and secondary aerosol (sulfur) have been few in number and reported inconsistent results. The overall objective of our study was to investigate the shape of the relationship between long-term exposure to four pollutants (PM2.5, NO2, BC, and O3) and four broad health effect categories using a number of different methods to characterize the concentration-response function (i.e., linear, nonlinear, or threshold). The four health effect categories were (1) natural- and cause-specific mortality including cardiovascular and nonmalignant as well as malignant respiratory and diabetes mortality; and morbidity measured as (2) coronary and cerebrovascular events; (3) lung cancer incidence; and (4) asthma and chronic obstructive pulmonary disease (COPD) incidence. We additionally assessed health effects of PM2.5 composition, specifically the copper, iron, zinc, and sulfur content of PM2,5. METHODS We focused on analyses of health effects of air pollutants at low concentrations, defined as less than current European Union (EU) Limit Values, U.S. Environmental Protection Agency (U.S. EPA), National Ambient Air Quality Standards (NAAQS), and/or World Health Organization (WHO) Air Quality Guideline values for PM2.5, NO2, and O3. We address the health effects at low air pollution levels by performing new analyses within selected cohorts of the ESCAPE study (European Study of Cohorts for Air Pollution Effects; Beelen et al. 2014a) and within seven very large European administrative cohorts. By combining well-characterized ESCAPE cohorts and large administrative cohorts in one study the strengths and weaknesses of each approach can be addressed. The large administrative cohorts are more representative of national or citywide populations, have higher statistical power, and can efficiently control for area-level confounders, but have fewer possibilities to control for individual-level confounders. The ESCAPE cohorts have detailed information on individual confounders, as well as country-specific information on area-level confounding. The data from the seven included ESCAPE cohorts and one additional non-ESCAPE cohort have been pooled and analyzed centrally. More than 300,000 adults were included in the pooled cohort from existing cohorts in Sweden, Denmark, Germany, the Netherlands, Austria, France, and Italy. Data from the administrative cohorts have been analyzed locally, without transfer to a central database. Privacy regulations prevented transfer of data from administrative cohorts to a central database. More than 28 million adults were included from national administrative cohorts in Belgium, Denmark, England, the Netherlands, Norway, and Switzerland as well as an administrative cohort in Rome, Italy. We developed central exposure assessment using Europewide hybrid land use regression (LUR) models, which incorporated European routine monitoring data for PM2.5, NO2, and O3, and ESCAPE monitoring data for BC and PM2.5 composition, land use, and traffic data supplemented with satellite observations and chemical transport model estimates. For all pollutants, we assessed exposure at a fine spatial scale, 100 × 100 m grids. These models have been applied to individual addresses of all cohorts including the administrative cohorts. In sensitivity analyses, we applied the PM2.5 models developed within the companion HEI-funded Canadian MAPLE study (Brauer et al. 2019) and O3 exposures on a larger spatial scale for comparison with previous studies. Identification of outcomes included linkage with mortality, cancer incidence, hospital discharge registries, and physician-based adjudication of cases. We analyzed natural-cause, cardiovascular, ischemic heart disease, stroke, diabetes, cardiometabolic, respiratory, and COPD mortality. We also analyzed lung cancer incidence, incidence of coronary and cerebrovascular events, and incidence of asthma and COPD (pooled cohort only). We applied the Cox proportional hazard model with increasing control for individual- and area-level covariates to analyze the associations between air pollution and mortality and/or morbidity for both the pooled cohort and the individual administrative cohorts. Age was used as the timescale because of evidence that this results in better adjustment for potential confounding by age. Censoring occurred at the time of the event of interest, death from other causes, emigration, loss to follow-up for other reasons, or at the end of follow-up, whichever came first. A priori we specified three confounder models, following the modeling methods of the ESCAPE study. Model 1 included only age (time axis), sex (as strata), and calendar year of enrollment. Model 2 added individual-level variables that were consistently available in the cohorts contributing to the pooled cohort or all variables available in the administrative cohorts, respectively. Model 3 further added area-level socioeconomic status (SES) variables. A priori model 3 was selected as the main model. All analyses in the pooled cohort were stratified by subcohort. All analyses in the administrative cohorts accounted for clustering of the data in neighborhoods by adjusting the variance of the effect estimates. The main exposure variable we analyzed was derived from the Europewide hybrid models based on 2010 monitoring data. Sensitivity analyses were conducted using earlier time periods, time-varying exposure analyses, local exposure models, and the PM2.5 models from the Canadian MAPLE project. We first specified linear single-pollutant models. Two-pollutant models were specified for all combinations of the four main pollutants. Two-pollutant models for particle composition were analyzed with PM2.5 and NO2 as the second pollutant. We then investigated the shape of the concentration-response function using natural splines with two, three, and four degrees of freedom; penalized splines with the degrees of freedom determined by the algorithm and shape-constrained health impact functions (SCHIF) using confounder model 3. Additionally, we specified linear models in subsets of the concentration range, defined by removing concentrations above a certain value from the analysis, such as for PM2.5 25 μg/m3 (EU limit value), 20, 15, 12 μg/m3 (U.S. EPA National Ambient Air Quality Standard), and 10 μg/m3 (WHO Air Quality Guideline value). Finally, threshold models were evaluated to investigate whether the associations persisted below specific concentration values. For PM2.5, we evaluated 10, 7.5, and 5 μg/m3 as potential thresholds. Performance of threshold models versus the corresponding no-threshold linear model were evaluated using the Akaike information criterion (AIC). RESULTS In the pooled cohort, virtually all subjects in 2010 had PM2.5 and NO2 annual average exposures below the EU limit values (25 μg/m3 and 40 μg/m3, respectively). More than 50,000 had a residential PM2.5 exposure below the U.S. EPA NAAQS (12 μg/m3). More than 25,000 subjects had a residential PM2.5 exposure below the WHO guideline (10 μg/m3). We found significant positive associations between PM2.5, NO2, and BC and natural-cause, respiratory, cardiovascular, and diabetes mortality. In our main model, the hazard ratios (HRs) (95% [confidence interval] CI) were 1.13 (CI = 1.11, 1.16) for an increase of 5 μg/m3 PM2.5, 1.09 (CI = 1.07, 1.10) for an increase of 10 μg/m3 NO2, and 1.08 (CI = 1.06, 1.10) for an increase of 0.5 × 10-5/m BC for natural-cause mortality. The highest HRs were found for diabetes mortality. Associations with O3 were negative, both in the fine spatial scale of the main ELAPSE model and in large spatial scale exposure models. For PM2.5, NO2, and BC, we generally observed a supralinear association with steeper slopes at low exposures and no evidence of a concentration below which no association was found. Subset analyses further confirmed that these associations remained at low levels: below 10 μg/m3 for PM2.5 and 20 μg/m3 for NO2. HRs were similar to the full cohort HRs for subjects with exposures below the EU limit values for PM2.5 and NO2, the U.S. NAAQS values for PM2.5, and the WHO guidelines for PM2.5 and NO2. The mortality associations were robust to alternative specifications of exposure, including different time periods, PM2.5 from the MAPLE project, and estimates from the local ESCAPE model. Time-varying exposure natural spline analyses confirmed associations at low pollution levels. HRs in two-pollutant models were attenuated but remained elevated and statistically significant for PM2.5 and NO2. In two-poll

Background Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O-3) with the incidence of stroke and acute coronary heart disease. Methods We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. Findings From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17.2 years (IQR 13.8-19.5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2.5 (hazard ratio 1.10 [95% CI 1.01-1.21] per 5 mu g/m(3) increase), NO2 (1.08 [1.04-1.12] per 10 mu g/m(3) increase), and black carbon (1.06 [1.02-1.10] per 0.5 10(-5)/m increase), whereas coronary heart disease incidence was only associated with NO2 (1.04 [1.01-1.07]). Warm-season O-3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2.5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 mu g/m(3) for PM2.5 and 40 mu g/m(3) for NO2. Interpretation Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

BACKGROUND:Inconsistent associations between long-term exposure to particles with an aerodynamic diameter ≤2.5 μm [fine particulate matter (PM2.5)] components and mortality have been reported, partly related to challenges in exposure assessment. OBJECTIVES:We investigated the associations between long-term exposure to PM2.5 elemental components and mortality in a large pooled European cohort; to compare health effects of PM2.5 components estimated with two exposure modeling approaches, namely, supervised linear regression (SLR) and random forest (RF) algorithms. METHODS:We pooled data from eight European cohorts with 323,782 participants, average age 49 y at baseline (1985-2005). Residential exposure to 2010 annual average concentration of eight PM2.5 components [copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V), and zinc (Zn)] was estimated with Europe-wide SLR and RF models at a 100×100 m scale. We applied Cox proportional hazards models to investigate the associations between components and natural and cause-specific mortality. In addition, two-pollutant analyses were conducted by adjusting each component for PM2.5 mass and nitrogen dioxide (NO2) separately. RESULTS:We observed 46,640 natural-cause deaths with 6,317,235 person-years and an average follow-up of 19.5 y. All SLR-modeled components were statistically significantly associated with natural-cause mortality in single-pollutant models with hazard ratios (HRs) from 1.05 to 1.27. Similar HRs were observed for RF-modeled Cu, Fe, K, S, V, and Zn with wider confidence intervals (CIs). HRs for SLR-modeled Ni, S, Si, V, and Zn remained above unity and (almost) significant after adjustment for both PM2.5 and NO2. HRs only remained (almost) significant for RF-modeled K and V in two-pollutant models. The HRs for V were 1.03 (95% CI: 1.02, 1.05) and 1.06 (95% CI: 1.02, 1.10) for SLR- and RF-modeled exposures, respectively, per 2 ng/m3, adjusting for PM2.5 mass. Associations with cause-specific mortality were less consistent in two-pollutant models. CONCLUSION:Long-term exposure to V in PM2.5 was most consistently associated with increased mortality. Associations for the other components were weaker for exposure modeled with RF than SLR in two-pollutant models. https://doi.org/10.1289/EHP8368.

BACKGROUND:Chemical and nonchemical environmental exposures are increasingly suspected to influence the development of obesity, especially during early life, but studies mostly consider single exposure groups. OBJECTIVES:Our study aimed to systematically assess the association between a wide array of early-life environmental exposures and childhood obesity, using an exposome-wide approach. METHODS:The HELIX (Human Early Life Exposome) study measured child body mass index (BMI), waist circumference, skinfold thickness, and body fat mass in 1,301 children from six European birth cohorts age 6-11 y. We estimated 77 prenatal exposures and 96 childhood exposures (cross-sectionally), including indoor and outdoor air pollutants, built environment, green spaces, tobacco smoking, and biomarkers of chemical pollutants (persistent organic pollutants, metals, phthalates, phenols, and pesticides). We used an exposure-wide association study (ExWAS) to screen all exposure-outcome associations independently and used the deletion-substitution-addition (DSA) variable selection algorithm to build a final multiexposure model. RESULTS:The prevalence of overweight and obesity combined was 28.8%. Maternal smoking was the only prenatal exposure variable associated with higher child BMI (z-score increase of 0.28, 95% confidence interval: 0.09, 0.48, for active vs. no smoking). For childhood exposures, the multiexposure model identified particulate and nitrogen dioxide air pollution inside the home, urine cotinine levels indicative of secondhand smoke exposure, and residence in more densely populated areas and in areas with fewer facilities to be associated with increased child BMI. Child blood levels of copper and cesium were associated with higher BMI, and levels of organochlorine pollutants, cobalt, and molybdenum were associated with lower BMI. Similar results were found for the other adiposity outcomes. DISCUSSION:This first comprehensive and systematic analysis of many suspected environmental obesogens strengthens evidence for an association of smoking, air pollution exposure, and characteristics of the built environment with childhood obesity risk. Cross-sectional biomarker results may suffer from reverse causality bias, whereby obesity status influenced the biomarker concentration. https://doi.org/10.1289/EHP5975.

Background: Stroke mortality comprises different specific diagnoses as cerebral infarction, different haemorrhagic conditions and unspecified stroke. This study seeks to explore the prediction of oral health indicators versus known cardiovascular disease risk factors for stroke mortality. Methods: Altogether, 12,764 men aged 58 to 77 years were invited to the health screening Oslo II in the year 2000. It included general medical measurements and questionnaire information. Mortality data were supplied by Statistics Norway for the 6530 attending men. Cox proportional hazards regression analyses were used to establish prediction models for mortality. Results: Oral health by number of tooth extractions >10 was found to be an independent predictor for cerebral infarction hazard ratio = 2.92, 95% confidence interval (1.24–6.89). This was independent of HDL-Cholesterol (inversely) hazard ratio = 0.21, 95% confidence interval (0.06–0.76), frequent alcohol consumption (drinking 4–7 times per week) hazard ratio = 3.58, 95% confidence interval (1.40–9.13) and diabetes hazard ratio = 4.28, 95% confidence interval (1.68–10.89). Predictors for cerebral haemorrhage were age, hs-C-reactive protein and body mass index (inversely). Age and total cholesterol (inversely) were predictors for unspecified stroke. Conclusions: Oral health measured by number of tooth extractions >10 was an independent predictor for cerebral infarction in addition to age, HDL-C, hs-C-reactive protein and diabetes. The pattern of risk factors varied between the specific stroke diagnoses.

Den norske tannlegeforenings Tidende – Lavt nivå av antistoffer mot Tannerella forsythia, en av hovedbakteriene i kronisk periodontitt, predikerer død av hjerte-karsykdom blant menn som har hatt et hjerteinfarkt

Antibody levels to periodontal pathogens in prediction of cardiovascular disease (CVD) mortality were explored using data from a health survey in Oslo in 2000 (Oslo II-study) with 12 1/2 years follow-up. IgG antibodies to four common periodontal pathogens; Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all termed collectively the "red complex", and Aggregatibacter actinomycetemcomitans (AA) were analysed. The study sample consisted of 1172 men drawn from a cohort of 6,530 men who participated in the Oslo II-study, where they provided information on medical and dental history. Of the study sample, 548 men had reported prior myocardial infarction (MI) at baseline whereas the remaining 624 men were randomly drawn from the ostensibly healthy participants for comparative analyses. Dental anamnestic information included tooth extractions and oral infections. An inverse relation was found for trend by the quartile risk level of TF predicting CVD mortality, p-value for trend = 0.017. Comparison of the first to fourth quartile of TF antibodies resulted in hazard ratio (HR) = 1.82, 95% confidence interval 1.12-2.94, p = 0.015, adjusted for age, education, diabetes, daily smoking, and systolic blood pressure. Specificity comparing decile 1 to deciles 2-10 of TF predicting mortality was 92.3%. We found an increased HR by low levels of antibodies to the bacterium T. forsythia predicting CVD mortality in a 12 1/2 years follow-up in persons who had experienced an MI but not among non-MI men. This novel finding constitutes a plausible causal link between oral infections and CVD mortality.

Background The adverse health effects of early life exposure to tobacco smoking have been widely reported. In spite of this, the underlying molecular mechanisms of in utero and postnatal exposure to tobacco smoke are only partially understood. Here, we aimed to identify multi-layer molecular signatures associated with exposure to tobacco smoke in these two exposure windows. Methods We investigated the associations of maternal smoking during pregnancy and childhood secondhand smoke (SHS) exposure with molecular features measured in 1203 European children (mean age 8.1 years) from the Human Early Life Exposome (HELIX) project. Molecular features, covering 4 layers, included blood DNA methylation and gene and miRNA transcription, plasma proteins, and sera and urinary metabolites. Results Maternal smoking during pregnancy was associated with DNA methylation changes at 18 loci in child blood. DNA methylation at 5 of these loci was related to expression of the nearby genes. However, the expression of these genes themselves was only weakly associated with maternal smoking. Conversely, childhood SHS was not associated with blood DNA methylation or transcription patterns, but with reduced levels of several serum metabolites and with increased plasma PAI1 (plasminogen activator inhibitor-1), a protein that inhibits fibrinolysis. Some of the in utero and childhood smoking-related molecular marks showed dose-response trends, with stronger effects with higher dose or longer duration of the exposure. Conclusion In this first study covering multi-layer molecular features, pregnancy and childhood exposure to tobacco smoke were associated with distinct molecular phenotypes in children. The persistent and dose-dependent changes in the methylome make CpGs good candidates to develop biomarkers of past exposure. Moreover, compared to methylation, the weak association of maternal smoking in pregnancy with gene expression suggests different reversal rates and a methylation-based memory to past exposures. Finally, certain metabolites and protein markers evidenced potential early biological effects of postnatal SHS, such as fibrinolysis.

The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of >= 150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of >= 60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended >= 25 mu g/m(3)). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of >= 30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho < 0.30). The levels of personal external exposures in both pregnant women and children are above the health recommendations, and there is little correlation between the different exposures. The assessment of the personal external exposome is feasible but sampling requires from one day to more than one year depending on exposure due to high variability between and within cities and participants.

Background: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical periods of life. Objective: We evaluated the association of the urban exposome with birth weight. Methods: We estimated exposure to the urban exposome, including the built environment, air pollution, road traffic noise, meteorology, natural space, and road traffic (corresponding to 24 environmental indicators and 60 exposures) for nearly 32,000 pregnant women from six European birth cohorts. To evaluate associations with either continuous birth weight or term low birth weight (TLBW) risk, we primarily relied on the Deletion-Substitution-Addition (DSA) algorithm, which is an extension of the stepwise variable selection method. Second, we used an exposure-by-exposure exposome-wide association studies (ExWAS) method accounting for multiple hypotheses testing to report associations not adjusted for coexposures. Results: The most consistent statistically significant associations were observed between increasing green space exposure estimated as Normalized Difference Vegetation Index (NDVI) and increased birth weight and decreased TLBW risk. Furthermore, we observed statistically significant associations among presence of public bus line, land use Shannon's Evenness Index, and traffic density and birth weight in our DSA analysis. Conclusion: This investigation is the first large urban exposome study of birth weight that tests many environmental urban exposures. It confirmed previously reported associations for NDVI and generated new hypotheses for a number of built-environment exposures. https://doi.org/10.1289/EHP3971

Asbestos (Mg-hydrosilicate; chrysotile) is known to cause pleural diseases, pulmonary fibrosis and lung cancers, via mechanisms strongly depending on diameter-length ratio and possibly metal content. A critical question is whether synthetic hydrosilicate nanotubes (NTs) of short length possess little toxic potential compared to chrysotile. Five Mg- and two NiNTs of different lengths were assessed for cytotoxicity and pro-inflammatory responses in THP-1 macrophages and human bronchial epithelial lung cells (HBEC3-KT), in comparison with chrysotile. NT lengths/diameters were characterized by TEM, surface areas by BET- and BJH analysis, and chemical composition by XRD. The different Mg- and NiNTs induced little cytotoxicity in both cell models, in contrast to chrysotile that induced marked cytotoxicity. The two longest synthetic MgNTs, with median lengths of 3 and 5 µm, induced increased levels of pro-inflammatory cytokines in THP-1 macrophages, but much less than chrysotile (median length 15 µm) and silica nanoparticles (Si10). The shortest NTs did not induce any increase in cytokines. In HBEC3-KT cells, all synthetic NTs induced no or only small changes in cytokine responses, in contrast to chrysotile and Si10. The synthetic NTs induced lower TGF-β responses than chrysotile in both cell models. In conclusion, the pro-inflammatory responses were associated with the length of synthetic hydrosilicate NTs in THP-1 macrophages, but not in HBEC3-KT cells. Notably, the shortest NTs showed no or little pro-inflammatory activity or cytotoxicity in both cell models. Such a safety by design approach is important for development of new materials being candidates for various new products.