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Background:Urinary lead (Pb) is generally considered to have limited use in biomonitoring environmental ex-posure to lead. Carbon load in airway macrophages (AM BC) is an internal marker to assess long-term exposureto combustion-derived aerosol particles. In urban environments, atmospheric Pb and black carbon may havecommon sources. We aimed to study the temporal change of urinary Pb (U-Pb) when exposure to outdoor airpollution changes, and the relationship between U-Pb and AM BC.Methods:A panel of 50 young healthy adults [mean (SD) 26.7 (5.2) years], including 17 long-term (> 1 year)residents in Leuven, Belgium (BE), 15 and 18 newcomers (arrived < 3 weeks) from low- and middle-incomecountries (LMIC) and high-income countries (HIC), respectively, underwent 8 repeated measurements at 6 weeksintervals. In urine spot samples obtained at 5 time points (T1, T2, T4, T6, T8), 24 trace elements were quantifiedby inductively coupled plasma-mass spectrometry. At each time point, AM BC was quantified as the mediansurface of black inclusions (inμm2) by means of image analysis of 25 macrophages obtained by induced sputum.Changes in urinary metal concentrations (with and without creatinine correction) and the relationship betweenU-Pb and AM BC were estimated using linear mixed models adjusted for covariates and potential confounders.Results:Only U-Pb differed between groups and exhibited significant time trends. Participants from the LMICgroup had significantly higher initial U-Pb (1.18μg/g creat) than the HIC group (0.44μg/g creat) and BE group(0.45μg/g creat). In the LMIC group, U-Pb decreased significantly with time by 0.061μg/g creatinine per30 days [95% confidence interval (CI): 0.034, 0.088]. U-Pb remained unchanged in the other two groups. Anincrease in AM BC of 1μm2was associated with an increase in U-Pb of 0.369μg/g creat (95% CI: 0.145, 0.593).Conclusion:This panel study demonstrates that U-Pb may be a valid alternative to blood Pb for biomonitoringchanges in exposure to lead, at least at group level. In addition, we identified a positive association between U-Pband AM BC, a biomarker of exposure to traffic-related air pollution, suggesting the existence of common sourcesof Pb and black carbon in urban environments. ; We thank the study participants. We thank Dr. Lidia Casas for hersuggestions and help with the statistical analysis. We thank GladysDeumer for performing the ICP-MS measurements. This study was partofthe doctoral project of Yang Bai under supervision of ProfessorBenoit Nemery and Professor Tim Nawrot. This study was funded inpart by the Flemish Government, Contract LNE/OL201100023/13034/M&G.

Background: Urinary lead (Pb) is generally considered to have limited use in biomonitoring environmental exposure to lead. Carbon load in airway macrophages (AM BC) is an internal marker to assess long-term exposure to combustion-derived aerosol particles. In urban environments, atmospheric Pb and black carbon may have common sources. We aimed to study the temporal change of urinary Pb (U-Pb) when exposure to outdoor air pollution changes, and the relationship between U-Pb and AM BC. Methods: A panel of 50 young healthy adults [mean (SD) 26.7 (5.2) years], including 17 long-term (> 1 year) residents in Leuven, Belgium (BE), 15 and 18 newcomers (arrived < 3 weeks) from low-and middle-income countries (LMIC) and high-income countries (HIC), respectively, underwent 8 repeated measurements at 6 weeks intervals. In urine spot samples obtained at 5 time points (T1, T2, T4, T6, T8), 24 trace elements were quantified by inductively coupled plasma-mass spectrometry. At each time point, AM BC was quantified as the median surface of black inclusions (in mu m(2)) by means of image analysis of 25 macrophages obtained by induced sputum. Changes in urinary metal concentrations (with and without creatinine correction) and the relationship between U-Pb and AM BC were estimated using linear mixed models adjusted for covariates and potential confounders. Results: Only U-Pb differed between groups and exhibited significant time trends. Participants from the LMIC group had significantly higher initial U-Pb (1.18 mu g/g creat) than the HIC group (0.44 mu g/g creat) and BE group (0.45 mu g/g creat). In the LMIC group, U-Pb decreased significantly with time by 0.061 mu g/g creatinine per 30 days [95% confidence interval (CI): 0.034, 0.088]. U-Pb remained unchanged in the other two groups. An increase in AM BC of 1 mu m(2) was associated with an increase in U-Pb of 0.369 mu g/g creat (95% CI: 0.145, 0.593). Conclusion: This panel study demonstrates that U-Pb may be a valid alternative to blood Pb for biomonitoring changes in exposure to lead, at least at group level. In addition, we identified a positive association between U-Pb and AM BC, a biomarker of exposure to traffic-related air pollution, suggesting the existence of common sources of Pb and black carbon in urban environments. ; We thank the study participants. We thank Dr. Lidia Casas for her suggestions and help with the statistical analysis. We thank Gladys Deumer for performing the ICP-MS measurements. This study was part of the doctoral project of Yang Bai under supervision of Professor Benoit Nemery and Professor Tim Nawrot. This study was funded in part by the Flemish Government, Contract LNE/OL201100023/13034/M&G.

Objective To investigate the incidence of preterm delivery in the Belgian population after implementation of smoke-free legislation in three phases (in public places and most workplaces January 2006, in restaurants January 2007, and in bars serving food January 2010). Design Logistic regression analyses on routinely collected birth data from January 2002 to December 2011. Setting Flanders, Belgium. Population All live born singleton births delivered at 24-44 weeks of gestation (n=606 877, with n=448 520 spontaneous deliveries). Main outcome measures Preterm birth (gestational age <37 weeks). Results We found reductions in the risk of preterm birth after the introduction of each phase of the smoking ban. No decreasing trend was evident in the years or months before the bans. We observed a step change in the risk of spontaneous preterm delivery of -3.13% (95% CI -4.37% to -1.87%; P<0.01) on 1 January 2007 (ban on smoking in restaurants), and an annual slope change of -2.65% (-5.11% to -0.13%; P=0.04) after 1 January 2010 (ban on smoking in bars serving food). The analysis for all births gave similar results: a step change of -3.18% (-5.38% to -0.94%; P<0.01) on 1 January 2007, and an annual slope change of -3.50% (-6.35% to -0.57%; P=0.02) after 1 January 2010. These changes could not be explained by personal factors (infant sex, maternal age, parity, socioeconomic status, national origin, level of urbanisation); time related factors (underlying trends, month of the year, day of the week); or population related factors (public holidays, influenza epidemics, and short term changes in apparent temperature and particulate air pollution). Conclusion Our study shows a consistent pattern of reduction in the risk of preterm delivery with successive population interventions to restrict smoking. This finding is not definitive but it supports the notion that smoking bans have public health benefits from early life.

Objective To investigate the incidence of preterm delivery in the Belgian population after implementation of smoke-free legislation in three phases (in public places and most workplaces January 2006, in restaurants January 2007, and in bars serving food January 2010).

BACKGROUND: Numerous studies show associations between fine particulate air pollutants [particulate matter with an aerodynamic diameter <= 10 mu m (PM(10))] and mortality in adults. OBJECTIVES: We investigated short-term effects of elevated PM(10) levels on infant mortality in Flanders, Belgium, and studied whether the European Union (EU) limit value protects infants from the air pollution trigger. METHODS: In a case-crossover analysis, we estimated the risk of dying from nontraumatic causes before 1 year of age in relation to outdoor PM(10) concentrations on the day of death. We matched control days on temperature to exclude confounding by variations in daily temperature. RESULTS: During the study period (1998-2006), PM(10) concentration averaged 31.9 +/- 13.8 mu g/m(3). In the entire study population (n = 2,382), the risk of death increased by 4% [95% confidence interval (CI), 0-8%; p = 0.045] for a 10-mu g/m(3) increase in daily mean PM(10). However, this association was significant only for late neonates (2-4 weeks of age; n = 372), in whom the risk of death increased by 11% (95% CI, 1-22%; p = 0.028) per 10-mu g/m(3) increase in PM(10). In this age class, infants were 1.74 (95% CI, 1.18-2.58; p = 0.006) times more likely to die on days with a mean PM(10) above the EU limit value of 50 mu g/m(3) than on days below this cutoff. CONCLUSIONS: Even in an affluent region in Western Europe, where infant mortality is low, days with higher PM air pollution are associated with an increased risk of infant mortality. Assuming causality, the current EU limit value for PM(10), which may be exceeded on 35 days/year, does not prevent PM(10) from triggering mortality in late neonates.

Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5-71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05-1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. Pulmonary tuberculosis (PTB) kills almost 2 million individuals every year and is thus a leading cause of death among adults worldwide. Mycobacterium tuberculosis (Mtb) infects more than 10 million people each year 1-3. Mtb potently induces cytokines and chemokines from polymorphonuclear cells and monocytes, thus resulting in intense local inflammation in the lungs 4. Alveolar macrophages are anti-inflammatory in nature, but their function can be impaired by pollutants, including mineral dusts, thereby diminishing the body's ability to clear infections 5-8. This is probably why mineworkers are more susceptible to develop PTB. Telomere length (TL) reflects the history of oxidative stress and chronic inflammation, and is a marker for age-related disease susceptibility 9-12. In normal physiology, mitochondria are important in the cell as they generate most of the adenosine triphosphate (ATP) through the oxidative phosphorylation mechanism (OXPHOS), which is a critical energy supply for cellular processes and partially encoded with mitochondrial DNA (mtDNA). The OXPHOS mechanism uses dietary intake to produce ATP, but it also produces ROS which can destroy mitochon-drial DNA, impairs respiratory chain function and cause nuclear DNA damage 12-14. Further, Mitochondrial DNA (mtDNA) damage can result in genomic instability, cellular senescence and altered intercellular communication. Hallmarks of aging genomic instability and deregulated nutrient sensing can contribute to reduced mitochondrial OPEN ; Funding P.D.M.C.K was fellow of the Fonds Marc Vervenne of the KU Leuven (Belgium) and he is supported by the US National Institutes of Health (NIH)-Fogarty Postdoctoral Fellowship: Grant no. 1D43TW010937-01A1. D.S.M is a FWO postdoc, with funding number: FWO Grant 12X9620N. Fieldwork has been supported by the KU Leuven Alumni Association and the University of Antwerp-USOS via the CEGEMI of the Catholic University of Bukavu. The costs of measuring Telomere length and mtDNA were covered by a grant of the European Research Council (ENVIRONAGE). The funders had no role in the study design, data collection, analysis, interpretation, or writing of the report. The corresponding author had full access to all the study data and had final responsibility for the decision to submit for publication. Acknowledgements We thank Profs J. Balmes (UCSF), N. Lorent, E. André (KU Leuven), and C. Tonne (ISGlobal) for their critical appraisal of the manuscript. We are grateful to the study participants and their relatives, the TB clinics, and the DRC's National/Provincial TB and HIV programs for their collaboration.

From 1990 until 2017, global air-pollution related mortality increased by 40%. Few studies addressed the renal responses to ultrafine particulate [3.5/>2.5 mg per mmol creatinine in women/men) were correlated in individual participants via their residential address with PM2.5 [median 13.1 (range 0.3-2.9) mu g/m(3)] and BC [1.1 (0.3-18) mu g/m(3)], using mixed models accounting for address clusters. Cross-sectional and longitudinally, no renal outcome was associated with PM2.5 or BC in models adjusted for sex and baseline or time varying covariables, including age, blood pressure, heart rate, body mass index, plasma glucose, the total-to-HDL serum cholesterol ratio, alcohol intake, smoking, physical activity, socioeconomic class, and antihypertensive treatment. The subject-level geocorrelations of eGFR change with to BC and PM2.5 were 0.13 and 0.02, respectively (P >= 0.68). In conclusion, in a population with moderate exposure, renal function was unrelated to ultrafine particulate. ; FLEMENGHO was supported by the European Union (Grants IC15-CT98-0329-EPOGH, LSHM CT 037093-InGenious HyperCare, HEALTH-201550-HyperGenes, HEALTH-278249-EU-MASCARA, HEALTH-305507 HOMAGE), the European Research Council (Advanced Researcher Grant-2011–294713-EPLORE and Proof-of-Concept Grant-713601 uPROPHET), the European Research Area Net for Cardiovascular Diseases (JTC2017-046-PROACT), and the Research Foundation Flanders, Ministry of the Flemish Community, Brussels, Belgium. APPREMED (URL: http://www.appremed.org) received a non-binding grant from OMRON Healthcare Co., Ltd., Kyoto, Japan. Te National Science Fund in China (Grant Numbers: 81470566 and 81670765) supported collaboration between Youan Hospital, Beijing, China and the Research Unit Hypertension and Cardiovascular Epidemiology, Leuven, Belgium. Bram Janssen is a postdoctoral fellow supported by the Research Foundation Flanders (Grant Number: 12W3218). Te authors gratefully acknowledge the expert clerical assistance of Vera De Leebeeck and Renilde Wolfs, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.

Abstract
Airborne pollution particles have been shown to translocate from the mother's lung to the fetal circulation but their placental-fetal distribution and internal tissue load remain poorly explored. Here, we investigated the placental-fetal distribution of diesel engine exhaust particles during gestation under controlled exposure conditions using a pregnant rabbit model. Pregnant dams were exposed by nose-only inhalation to either clean air (controls) or diluted and filtered diesel engine exhaust (1 mg/m3) for 2h/day, 5 days/week, from gestational day (GD) 3 to GD27. At GD28, placental and fetal tissues (i.e., heart, kidney, liver, lung and gonads) were collected for biometry and to study the accumulation of carbon particles (CPs) using white light generation by carbon particles under femtosecond pulsed laser illumination. CPs were detected in the placenta, fetal heart, kidney, liver, lung and gonads in significantly higher amounts compared with controls. By using multiple factor analysis, we were able to discriminate the diesel engine-exposed pregnant rabbits from the control group taking all variables related to fetoplacental biometry and CP load into consideration. Although our findings did not reveal a sex effect, a potential interaction effect might be present between exposure and fetal sex. The results confirm the translocation of maternally inhaled CPs from diesel engine exhaust to the placenta and the ability to reach fetal organs during late-stage pregnancy. The differential particle load in the fetal organs may contribute to the disruption of blood flow in the placenta with possible effects on fetoplacental biometry and placental function.

Retinal arteriolar narrowing increases with age and predict adverse cardiovascular outcomes. Telomere length keeps track of the division of somatic cells and is a biomarker of biological age. We investigated to what extent retinal arteriolar diameters are associated with biological age, as captured by leukocyte telomere length (LTL). In 168 randomly selected Flemish participants from the family-based population study FLEMENGHO (mean age, 46.2 years) at baseline, of whom 85 underwent a follow-up examination (median, 4.1 years), we post-processed nonmydriatic retinal photographs and measured LTL. In men only, central retinal arteriolar equivalents (CRAE) and arteriole-to-venule ratio (AVR) were associated with LTL with stronger associations at higher age and body mass index. In men aged 57.6 years (75th percentile) a 20% shorter LTL was associated with a decrease in CRAE of 4.57µm. A 20% shorter LTL was associated with a decrease of 5.88µm in CRAE at a BMI of 29.9kg/m2 (75th percentile). Similar associations were observed between AVR and LTL. In women, no retinal microvascular traits were associated with LTL. Retinal arteriolar narrowing in men but not in women is associated with biological age. Our fndings support the idea that avoiding overweight contributes to maintaining a healthier microcirculation. ; The European Union [HEALTH-F7-305507 HOMAGE] and the European Research Council, Advanced Researcher Grant [2011-294713-EPLORE] and Proof-of-Concept Grant [713601-uPROPHET] and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium [G.0881.13 and G.088013] currently support the Studies Coordinating Centre in Leuven. Telomere measurements were funded by the European Research Council [ERC-2012-StG.310898] and by the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium [G073315N and G073409N]. Dr Cox is a postdoctoral fellow of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium supported by grant 12Q0517N. The authors gratefully acknowledge the contribution of the nurses working at the examination center (Linda Custers, Marie-Jeanne Jehoul, Daisy Thijs, and Hanne Truyens) and the clerical staff at the Studies Coordinating Centre (Vera De Leebeeck, Yvette Piccart, and Renilde Wolfs).

FLEXiGUT is the first large-scale exposomics study focused on chronic low-grade inflammation. It aims to characterize human life course environmental exposure to assess and validate its impact on gut inflammation and related biological processes and diseases. The cumulative influences of environmental and food contaminants throughout the lifespan on certain biological responses related to chronic gut inflammation will be investigated in two Flemish prospective cohorts, namely the "ENVIRONAGE birth cohort", which provides follow-up from gestation to early childhood, and the "Flemish Gut Flora Project longitudinal cohort", a cohort of adults. The exposome will be characterised through biomonitoring of legacy and emerging contaminants, mycotoxins and markers of air pollution, by analysing the available metadata on nutrition, location and activity, and by applying state-of-the-art-omics techniques, including metagenomics, metabolomics and DNA adductomics, as well as the assessment of telomere length and measurement of inflammatory markers, to encompass both exposure and effect. Associations between exposures and health outcomes will be uncovered using an integrated-omics data analysis framework comprising data exploration, pre-processing, dimensionality reduction and data mining, combined with machine learning-based pathway analysis approaches. This is expected to lead to a more profound insight in mechanisms underlying disease progression (e.g. metabolic disorders, food allergies, gastrointestinal cancers) and/or accelerated biological ageing. ; Interuniversity Special Research Fund (iBOF) from Flanders [BOFIBO2021001102]; European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programEuropean Research council (ERC) [946192]; Exposome Centre of Excellence of the University of Antwerp (BOF grant) [41222]

Background: People from low- and middle-income countries are disproportionately affected by the global burden of adverse health effects caused by ambient air pollution (AAP). However, data from Sub-Saharan Africa (SSA) are still scarce. We systematically reviewed the literature to describe the existing knowledge on AAP and health outcomes in SSA. Methods: We searched PubMed, Medline-OVID, EMBASE and Scopus databases to identify studies of AAP and health outcomes published up to November 15, 2017. We used a systematic review approach to critically analyze and summarize levels of outdoor air pollutants, and data on health effects associated with AAP. We excluded occupational and indoor exposure studies. Results: We identified 60 articles, with 37 only describing levels of AAP and 23 assessing the association between air pollution and health outcomes. Most studies (75%) addressing the relation between AAP and disease were cross-sectional. In general, exposure data were only obtained for selected cities in the framework of temporary international collaborative research initiatives without structural long-term continuation. Measurements of AAP revealed 10-20 fold higher levels than WHO standards. Of the 23 studies reporting health effects, 14 originated from South Africa, and most countries within SSA contributed no data at all. No studies, except from South Africa, were based on reliable morbidity or mortality statistics at regional or country level. The majority of studies investigated self-reported respiratory symptoms. Children and the elderly were found to be more susceptible to AAP. Conclusion: AAP and its negative health effects have been understudied in SSA compared with other continents. The limited direct measurements of air pollutants indicate that AAP in SAA cities is high compared with international standards. Efforts are needed to monitor AAP in African cities, to identify its main sources, and to reduce adverse health effects by enforcing legislation. ; This research did not receive any specific grant from fundingagenciesinthepublic,commercial,ornot-for-profitsectors

Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5–71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05–1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome.