Polystyrene Microplastics of Varying Sizes and Shapes Induce Distinct Redox and Mitochondrial Stress Responses in a Caco-2 Monolayer.

Currently, we lack crucial knowledge on how the physicochemical properties of particles affect cellular health, resulting in an important gap in our understanding of the human toxicity of microplastics (MPs). Our aim was to evaluate the impact of the size and the shape of MPs on uptake and the intracellular effects in a human epithelial colorectal adenocarcinoma (Caco-2) cell line. Spherical (200 nm and 2 µm) and fibre-/fragment-shaped (8.9 ± 10.1 µm by 1.14 ± 0.97 µm) polystyrene microplastics (PS-MPs) were used to study their uptake and the potential to induce redox and mitochondrial stress responses after 24 h of exposure. We demonstrated the cellular uptake of both spherical and fibre-/fragment-shaped MPs in a size-dependent manner. In response to 2 µm spheres, we observed differential expressions of redox-related genes, including HMOX1, CAT, and GPX1. All PS-MPs decreased the intracellular H2O2 levels, which can be attributed to mitochondrial stress responses, such as increased mitochondrial DNA content, footprint, and morphology. Altogether, we demonstrated uptakes and changes in redox and mitochondrial parameters for all PS-MPs, with the 200 nm spheres showing the most profound effects. This suggests that the induction of defensive responses in Caco-2 cells mainly correlates with the number of particles taken up.

A healthy lifestyle is positively associated with mental health and well-being and core markers in ageing.

BACKGROUND: Studies often evaluate mental health and well-being in association with individual health behaviours although evaluating multiple health behaviours that co-occur in real life may reveal important insights into the overall association. Also, the underlying pathways of how lifestyle might affect our health are still under debate. Here, we studied the mediation of different health behaviours or lifestyle factors on mental health and its effect on core markers of ageing: telomere length (TL) and mitochondrial DNA content (mtDNAc). METHODS: In this study, 6054 adults from the 2018 Belgian Health Interview Survey (BHIS) were included. Mental health and well-being outcomes included psychological and severe psychological distress, vitality, life satisfaction, self-perceived health, depressive and generalised anxiety disorder and suicidal ideation. A lifestyle score integrating diet, physical activity, smoking status, alcohol consumption and BMI was created and validated. On a subset of 739 participants, leucocyte TL and mtDNAc were assessed using qPCR. Generalised linear mixed models were used while adjusting for a priori chosen covariates. RESULTS: The average age (SD) of the study population was 49.9 (17.5) years, and 48.8% were men. A one-point increment in the lifestyle score was associated with lower odds (ranging from 0.56 to 0.74) for all studied mental health outcomes and with a 1.74% (95% CI: 0.11, 3.40%) longer TL and 4.07% (95% CI: 2.01, 6.17%) higher mtDNAc. Psychological distress and suicidal ideation were associated with a lower mtDNAc of - 4.62% (95% CI: - 8.85, - 0.20%) and - 7.83% (95% CI: - 14.77, - 0.34%), respectively. No associations were found between mental health and TL. CONCLUSIONS: In this large-scale study, we showed the positive association between a healthy lifestyle and both biological ageing and different dimensions of mental health and well-being. We also indicated that living a healthy lifestyle contributes to more favourable biological ageing.

Air pollution in association with mental and self-rated health and the mediating effect of physical activity.

BACKGROUND: Recent studies showed that air pollution might play a role in the etiology of mental disorders. In this study we evaluated the association between air pollution and mental and self-rated health and the possible mediating effect of physical activity in this association. METHODS: In 2008, 2013 and 2018 the Belgian Health Interview Survey (BHIS) enrolled 16,455 participants who completed following mental health dimensions: psychological distress, suboptimal vitality, suicidal ideation, and depressive and generalized anxiety disorder and self-rated health. Annual exposure to nitrogen dioxide (NO2), particulate matter ≤ 2.5 µm (PM2.5) and black carbon (BC) were estimated at the participants' residence by a high resolution spatiotemporal model. Multivariate logistic regressions were carried out taking into account a priori selected covariates. RESULTS: Long-term exposure to PM2.5, BC and NO2 averaged 14.5, 1.4, and 21.8 µg/m3, respectively. An interquartile range (IQR) increment in PM2.5 exposure was associated with higher odds of suboptimal vitality (OR = 1.27; 95% CI: 1.13, 1.42), poor self-rated health (OR = 1.20; 95% CI: 1.09, 1.32) and depressive disorder (OR = 1.19; 95% CI: 1.00, 1.41). Secondly, an association was found between BC exposure and higher odds of poor self-rated health and depressive and generalized anxiety disorder and between NO2 exposure and higher odds of psychological distress, suboptimal vitality and poor self-rated health. No association was found between long-term ambient air pollution and suicidal ideation or severe psychological distress. The mediation analysis suggested that between 15.2% (PM2.5-generalized anxiety disorder) and 40.1% (NO2-poor self-rated health) of the association may be mediated by a difference in physical activity. CONCLUSIONS: Long-term exposure to PM2.5, BC or NO2 was adversely associated with multiple mental health dimensions and self-rated health and part of the association was mediated by physical activity. Our results suggest that policies aiming to reduce air pollution levels could also reduce the burden of mental health disorders in Belgium.

Gestational acrylamide exposure and biomarkers of fetal growth: Probing the mechanism underlying the association between acrylamide and reduced fetal growth.

INTRODUCTION: Four epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth. METHODS: In newborns of the ENVIRONAGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes. RESULTS: We observed lower cord plasma TSH (-10.2% [95% CI: -15.0, -4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of -2.9% (95% CI: -5.7, -0.1) and -3.9% (95% CI: -6.2, -1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (-11.2% [95% CI: -19.5, -0.1]). Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight. CONCLUSIONS: A decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study.

Two-year neurocognitive responses to first occupational lead exposure.

Objectives Lead exposure causes neurocognitive dysfunction in children, but its association with neurocognition in adults at current occupational exposure levels is uncertain mainly due to the lack of longitudinal studies. In the Study for Promotion of Health in Recycling Lead (NCT02243904), we assessed the two-year responses of neurocognitive function among workers without previous known occupational exposure newly hired at lead recycling plants. Methods Workers completed the digit-symbol test (DST) and Stroop test (ST) at baseline and annual follow-up visits. Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). Statistical methods included multivariable-adjusted mixed models with participants modelled as random effect. Results DST was administered to 260 participants (11.9% women; 46.9%/45.0% whites/Hispanics; mean age 29.4 years) and ST to 168 participants. Geometric means were 3.97 and 4.13 µg/dL for baseline BL, and 3.30 and 3.44 for the last-follow-up-to-baseline BL ratio in DST and ST cohorts, respectively. In partially adjusted models, a doubling of the BL ratio was associated with a 0.66% [95% confidence interval (CI) 0.03-1.30; P=0.040] increase in latency time (DST) and a 0.35% (95% CI ­1.63-1.63; P=0.59) decrease in the inference effect (ST). In fully adjusted models, none of the associations of the changes in the DST and ST test results with the blood lead changes reached statistical significance (P≥0.12). Conclusions An over 3-fold increase in blood lead over two years of occupational exposure was not associated with a relevant decline in cognitive performance.

Environmental exposures and health behavior in association with mental health: a study design.

BACKGROUND: Air pollution, green space and smoking are known to affect human health. However, less is known about their underlying biological mechanisms. One of these mechanisms could be biological aging. In this study, we explore the mediation of biomarkers of exposure and biological aging to explain the associations between environmental exposures, health behavior and mental health. METHODS: The study population of this cross-sectional study (n = 1168) is a subsample of the Belgian 2018 Health Interview Survey (BHIS). Mental health indicators including psychological and severe psychological distress, life satisfaction, vitality, eating disorders, suicidal ideation, subjective health and depressive and anxiety disorders, demographics and health behavior such as smoking are derived from the BHIS. Urine and blood samples are collected to measure respectively the biomarkers of exposure (urinary black carbon (BC) and (hydroxy)cotinine) and the biomarkers of biological aging (mitochondrial DNA content (mtDNAc) and telomere length (TL)). Recent and chronic exposure (µg/m3) to nitrogen dioxide (NO2), particulate matter ≤2.5 µm (PM2.5) and ≤ 10 µm (PM10) and BC at the participants' residence are modelled using a high resolution spatial temporal interpolation model. Residential green space is defined in buffers of different size (50 m - 5000 m) using land cover data in ArcGIS 10 software. For the statistical analysis multivariate linear and logistic regressions as well as mediation analyses are used taking into account a priori selected covariates and confounders. RESULTS: As this study combined data of BHIS and laboratory analyses, not all data is available for all participants. Therefore, data analyses will be conducted on different subsets. Data on air pollution and green space exposure is available for all BHIS participants. Questions on smoking and mental health were answered by respectively 7829 and 7213 BHIS participants. For biomarker assessment, (hydroxy) cotinine, urinary BC and the biomarkers of biological aging are measured for respectively 1130, 1120 and 985 participants. CONCLUSION: By use of personal markers of air pollution and smoking, as well as biological aging, we will gain knowledge about the association between environmental exposures, health behavior, and the mental health status. The results of the study can provide insights on the health of the Belgian population, making it a nationwide interesting study.

Residential green space and seasonal distress in a cohort of tree pollen allergy patients.

BACKGROUND: Residential green space may improve human health, for example by promoting physical activity and by reducing stress. Conversely, residential green space may increase stress by emitting aeroallergens and exacerbating allergic disease. Here we examine impacts of exposure to residential green space on distress in the susceptible subpopulation of adults sensitized to tree pollen allergens. METHODS: In a panel study of 88 tree pollen allergy patients we analyzed self-reported mental health (GHQ-12), perceived presence of allergenic trees (hazel, alder, birch) near the residence and residential green space area within 1 km distance [high (≥3 m) and low (<3 m) green]. Results were adjusted for patients' background data (gender, age, BMI, smoking status, physical activity, commuting distance, education level, allergy medication use and chronic respiratory problems) and compared with distress in the general population (N = 2467). RESULTS: Short-term distress [mean GHQ-12 score 2.1 (95% confidence interval 1.5-2.7)] was higher in the study population than in the general population [1.5 (1.4-1.7)]. Residential green space had protective effects against short-term distress [high green, per combined surface area of 10 ha: adjusted odds ratio OR = 0.94 (95% confidence interval 0.90-0.99); low green, per 10 ha: OR = 0.85 (0.78-0.93)]. However, distress was higher in patients who reported perceived presence of allergenic trees near their residence [present vs. absent: OR = 2.04 (1.36-3.07)]. CONCLUSIONS: Perceived presence of allergenic tree species in the neighbourhood of the residence of tree pollen allergy patients modulates the protective effect of residential green space against distress during the airborne tree pollen season.

Ambient black carbon particles reach the fetal side of human placenta.

Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 104 (0.66 × 104) and 2.09 × 104 (0.9 × 104) particles per mm3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers' residential BC exposure during pregnancy (0.63-2.42 µg per m3). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards.

Neurocognitive function in relation to blood lead among young men prior to chronic occupational exposure.

Objectives Higher than contemporary exposure levels and advanced age of study participants have limited the interpretation of previous studies relating neurocognitive function to lead exposure. We reassessed this association in young American men prior to chronic occupational exposure at lead recycling plants, using baseline measurements of the Study for Promotion of Health in Recycling Lead (NCT02243904). Methods We administered the Stroop test (ST) and the digit-symbol test (DST) to 339 men (mean age, 28.6 years; participation rate 82.7%). Whole blood lead (BL) was determined by inductively coupled plasma mass spectrometry and related ST and DST test results using multivariable-adjusted regression. Results Average values were 4.26 µg/dL for BL, 1624 ms and 1474 ms for mean reaction time in incongruent and congruent ST trials, and 109 sec for mean total latency in DST. The number of participants with fully correct answers amounted to 281 (82.9%) and 334 (98.5%) in incongruent and congruent ST trials, respectively, and to 198 (58.4%) in the DST. In multivariable-adjusted analyses, there was no association between cognitive performance and BL except for a weak but opposite association in DST; for a 10-fold BL increment, mean total latency was 5.4% (95% confidence interval, -0.4‒11.5%; P=0.066) higher, whereas the error score was 42% (-10‒69%; P=0.096) lower. To exclude an effect of the cumulative lead dose, sensitivity analyses restricted to workers <40, 35 and 30 years were confirmatory. Conclusions At the exposure levels in our current study, we failed to demonstrate a consistent inverse association of BL with neurocognitive performance in young American men.

Placental promoter methylation of DNA repair genes and prenatal exposure to particulate air pollution: an ENVIRONAGE cohort study.

BACKGROUND: Exposure to particulate air pollution has been linked with risk of carcinogenesis. Damage to repair pathways might have long-term adverse health effects. We aimed to investigate the association of prenatal exposure to air pollution with placental mutation rate and the DNA methylation of key placental DNA repair genes. METHODS: This cohort study used data from the ongoing ENVironmental Influence ON early AGEing (ENVIRONAGE) birth cohort, which enrols pairs of mothers and neonates (singleton births only) at the East-Limburg Hospital (Genk, Belgium). Placental DNA samples were collected after birth. We used bisulfite-PCR-pyrosequencing to investigate the mutation rate of Alu (a marker for overall DNA mutation) and DNA methylation in the promoter genes of key DNA repair and tumour suppressor genes (APEX1, OGG1, PARP1, ERCC1, ERCC4, p53, and DAPK1). We used a high-resolution air pollution model to estimate exposure to particulate matter with a diameter less than 2·5 µm (PM2·5), black carbon, and NO2 over the entire pregnancy on the basis of maternal address. Alu mutation was analysed with a linear regression model, and methylation values of the selected genes were analysed in mixed-effects models. Effect estimates are presented as the relative percentage change in methylation for an ambient air pollution increment of one IQR (ie, the difference between the first and third quartiles of exposure in the entire cohort). FINDINGS: 500 biobanked placental DNA samples were randomly selected from 814 pairs of mothers and neonates who were recruited to the cohort between Feb 1, 2010, and Dec 31, 2014, of which 463 samples met the pyrosequencing quality control criteria. IQR exposure increments were 3·84 µg/m3 for PM2·5, 0·36 µg/m3 for black carbon, and 5·34 µg/m3 for NO2. Among these samples, increased Alu mutation rate was associated with greater exposure to PM2·5 (r=0·26, p<0·0001) and black carbon (r=0·33, p<0·0001), but not NO2. Promoter methylation was positively associated with PM2·5 in APEX1 (7·34%, 95% CI 0·52 to 14·16, p=0·009), OGG1 (13·06, 3·88 to 22·24, p=0·005), ERCC4 (16·31%, 5·43 to 27·18, p=0·01), and p53 (10·60%, 4·46 to 16·74, p=0·01), whereas promoter methylation of DAPK1 (-12·92%, -22·35 to -3·49, p=0·007) was inversely associated with PM2·5 exposure. Black carbon exposure was associated with elevated promoter methylation in APEX1 (9·16%, 4·06 to 14·25, p=0·01) and ERCC4 (27·56%, 17·58 to 37·55, p<0·0001). Promoter methylation was not associated with pollutant exposure in PARP1 and ERCC1, and NO2 exposure was not associated with methylation in any of the genes studied. INTERPRETATION: Transplacental in-utero exposure to particulate matter is associated with an increased overall placental mutation rate (as measured with Alu), which occurred in concert with epigenetic alterations in key DNA repair and tumour suppressor genes. Our results suggest that exposure to air pollution can induce changes to fetal and neonatal DNA repair capacity. Future studies will be essential to elucidate whether these changes persist and have a role in carcinogenic insults later in life. FUNDING: European Research Council and the Flemish Scientific Fund.

Children's Urinary Environmental Carbon Load. A Novel Marker Reflecting Residential Ambient Air Pollution Exposure?

RATIONALE: Ambient air pollution, including black carbon, entails a serious public health risk because of its carcinogenic potential and as climate pollutant. To date, an internal exposure marker for black carbon particles that have cleared from the systemic circulation into the urine does not exist. OBJECTIVES: To develop and validate a novel method to measure black carbon particles in a label-free way in urine. METHODS: We detected urinary carbon load in 289 children (aged 9-12 yr) using white-light generation under femtosecond pulsed laser illumination. Children's residential black carbon concentrations were estimated based on a high-resolution spatial temporal interpolation method. MEASUREMENTS AND MAIN RESULTS: We were able to detect urinary black carbon in all children, with an overall average (SD) of 98.2 × 105 (29.8 × 105) particles/ml. The urinary black carbon load was positively associated with medium-term to chronic (1 mo or more) residential black carbon exposure: +5.33 × 105 particles/ml higher carbon load (95% confidence interval, 1.56 × 105 to 9.10 × 105 particles/ml) for an interquartile range increment in annual residential black carbon exposure. Consistently, children who lived closer to a major road (≤160 m) had higher urinary black carbon load (6.93 × 105 particles/ml; 95% confidence interval, 0.77 × 105 to 13.1 × 105). CONCLUSIONS: Urinary black carbon mirrors the accumulation of medium-term to chronic exposure to combustion-related air pollution. This specific biomarker reflects internal systemic black carbon particles cleared from the circulation into the urine, allowing investigators to unravel the complexity of particulate-related health effects.

Cord plasma insulin and in utero exposure to ambient air pollution.

INTRODUCTION: Cardio-metabolic risk factors including insulin levels are at young age barely perceived as harmful, but over time these risk factors may track and lead to higher risk of metabolic syndrome. Studies showed that exposure to air pollution is associated with an increased risk of insulin resistance in childhood. We determined whether the origin of type 2 diabetes can be found in the early childhood by examining the levels of insulin in the neonatal cord blood and whether this can be considered as a disease marker for later life. METHODS: In the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort, we recruited 620 mother-infant pairs between February 2nd 2010 until August 12th 2014 at the East-Limburg Hospital in Genk, Belgium. We investigated in 590 newborns the association between cord plasma insulin levels and exposure to particulate matter (PM2.5 and PM10) and nitrogen dioxide (NO2) in various exposure windows during pregnancy. Trimester-specific air pollutant exposure levels were estimated for each mother's home address using a spatiotemporal model. RESULTS: Cord plasma insulin levels averaged 33.1pmol/L (25-75th percentile: 20.1-53.5), while PM2.5 exposure during pregnancy averaged (SD) 13.7µg/m3 (2.4). Independent of maternal age, newborn's sex, birth weight, gestational age, parity, early-pregnancy BMI, ethnicity, smoking status, time of the day, maternal education, time of delivery, and season of delivery, cord plasma insulin levels increased with 15.8% (95% CI 7.8 to 24.4, p<0.0001) for each SD increment in PM2.5 levels during the entire pregnancy and was most pronounced in the 2nd trimester (13.1%, 95% CI 3.4 to 23.7, p=0.007) of pregnancy. The results for PM10 exposure were similar with those of PM2.5 exposure but we did not observe an association between cord blood insulin levels and NO2 exposure. CONCLUSIONS: Exposure to particulate air pollution during pregnancy is associated with increased levels of cord plasma insulin at birth. The public health relevance of this association is demonstrated by the fact that a 2.4µg/m3 (SD) increase in PM2.5 during pregnancy on cord plasma insulin levels corresponds to the effect-size of a 9kg/m2 higher early-pregnancy BMI on cord plasma. Particulate air pollution induced changes in cord plasma insulin levels during early life and might be a risk factor in the development of metabolic disease, such as glucose intolerance or type 2 diabetes, later in life.

Placental Nitrosative Stress and Exposure to Ambient Air Pollution During Gestation: A Population Study.

The placenta plays a crucial role in fetal growth and development through adaptive responses to perturbations of the maternal environment. We investigated the association between placental 3-nitrotyrosine (3-NTp), a biomarker of oxidative stress, and exposure to air pollutants during various time windows of pregnancy. We measured the placental 3-NTp levels of 330 mother-newborn pairs enrolled in the Environmental Influence on Ageing in Early Life (ENVIRONAGE) Study, a Belgian birth cohort study (2010-2013). Daily concentrations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), black carbon (BC), and nitrogen dioxide were interpolated for each mother's residence using a spatiotemporal interpolation method. Placental 3-NTp levels, adjusted for covariates, increased by 35.0% (95% confidence interval (CI): 13.9, 60.0) for each interquartile-range increment in entire-pregnancy PM2.5 exposure. The corresponding estimate for BC exposure was 13.9% (95% CI: -0.21, 29.9). These results were driven by the first (PM2.5: 29.0% (95% CI: 4.9, 58.6); BC: 23.6% (95% CI: 4.4, 46.4)) and second (PM2.5: 39.3% (95% CI: 12.3, 72.7)) gestational exposure windows. This link between placental nitrosative stress and exposure to fine particle air pollution during gestation is in line with experimental evidence on cigarette smoke and diesel exhaust exposure. Further research is needed to elucidate potential health consequences experienced later in life through particle-mediated nitrosative stress incurred during fetal life.

Recent versus chronic exposure to particulate matter air pollution in association with neurobehavioral performance in a panel study of primary schoolchildren.

Children's neuropsychological abilities are in a developmental stage. Recent air pollution exposure and neurobehavioral performance are scarcely studied. In a panel study, we repeatedly administered to each child the following neurobehavioral tests: Stroop Test (selective attention) and Continuous Performance Test (sustained attention), Digit Span Forward and Backward Tests (short-term memory), and Digit-Symbol and Pattern Comparison Tests (visual information processing speed). At school, recent inside classroom particulate matter ≤2.5 or 10µm exposure (PM2.5, PM10) was monitored on each examination day. At the child's residence, recent (same day up to 2days before) and chronic (365days before examination) exposures to PM2.5, PM10 and black carbon (BC) were modeled. Repeated neurobehavioral test performances (n=894) of the children (n=310) reflected slower Stroop Test (p=0.05) and Digit-Symbol Test (p=0.01) performances with increasing recent inside classroom PM2.5 exposure. An interquartile range (IQR) increment in recent residential outdoor PM2.5 exposure was associated with an increase in average latency of 0.087s (SE: ±0.034; p=0.01) in the Pattern Comparison Test. Regarding chronic exposure at residence, an IQR increment of PM2.5 exposure was associated with slower performances in the Continuous Performance (9.45±3.47msec; p=0.007) and Stroop Tests (59.9±26.5msec; p=0.02). Similar results were obtained for PM10 exposure. In essence, we showed differential neurobehavioral changes robustly and adversely associated with recent or chronic ambient exposure to PM air pollution at residence, i.e., with recent exposure for visual information processing speed (Pattern Comparison Test) and with chronic exposure for sustained and selective attention.

Urinary t,t-muconic acid as a proxy-biomarker of car exhaust and neurobehavioral performance in 15-year olds.

INTRODUCTION: Traffic-related air pollution has been shown to induce neurotoxicity in rodents. Several recent epidemiological studies reported negative associations between residential outdoor air pollution and neurobehavioral performance. We investigated in a population of non-smoker adolescents the associations between the urinary concentration of trans, trans-muconic acid (t,t-MA-U), a metabolite of benzene and used as proxy-biomarker of traffic exposure, and two neurobehavioral domains, i.e. sustained attention and short-term memory. METHODS: In the framework of an environmental health surveillance study in Flanders (Belgium), we examined between 2008 and 2014 grade nine high school students (n=895). We used reaction time, number of omission errors, and number of commission errors in the Continuous Performance Test to evaluate sustained attention, and for the evaluation of short-term memory we used maximum digit span forward and backward of the Digit Span Test. We measured blood lead (PbB) to assess the independent effect of t,t-MA-U on neurobehavioral outcomes. RESULTS: This neurobehavioral examination study showed that a ten-fold increase in t,t-MA-U was associated with a 0.14 SD lower sustained attention (95% Confidence Interval: -0.26 to -0.019; p=0.02) and a 0.17 SD diminished short-term memory (95% CI: -0.31 to -0.030; p=0.02). For the same increment in t,t-MA-U, the Continuous Performance Test showed a 12.2ms higher mean reaction time (95% CI: 4.86-19.5; p=0.001) and 0.51 more numbers of errors of omission (95% CI: 0.057-0.97; p=0.028), while no significant association was found with errors of commission. For the Digit Span Tests, the maximum digit span forward was associated with a 0.20 lower number of digits (95% CI: -0.38 to -0.026; p=0.025) and maximum digit span backward with -0.15 digits (95% CI: -0.32 to 0.022; p=0.088). These associations were independent of PbB, parental education and other important covariates including gender, age, passive smoking, ethnicity, urinary creatinine, time of the day, and examination day of the week. For PbB, an independent association was only found with mean reaction time of the Continuous Performance Test (19.1ms, 95% CI: 2.43-35.8; p=0.025). CONCLUSIONS: In adolescents, a ten-fold increase in the concentration of t,t-MA-U, used as a proxy-biomarker for traffic-related exposure, was associated with a significant deficit in sustained attention and short-term memory. The public health implications of this finding cannot be overlooked as the effect-size for these neurobehavioral domains was about 40% of the effect-size of parental education.

Recent exposure to ultrafine particles in school children alters miR-222 expression in the extracellular fraction of saliva.

BACKGROUND: Ultrafine particles (<100 nm) are ubiquitous present in the air and may contribute to adverse cardiovascular effects. Exposure to air pollutants can alter miRNA expression, which can affect downstream signaling pathways. miRNAs are present both in the intracellular and extracellular environment. In adults, miR-222 and miR-146a were identified as associated with particulate matter exposure. However, there is little evidence of molecular effects of ambient air pollution in children. This study examined whether exposure to fine and ultrafine particulate matter (PM) is associated with changes in the extracellular content of miR-222 and miR-146a of children. METHODS: Saliva was collected from 80 children at two different time points, circa 11 weeks apart and stabilized for RNA preservation. The extracellular fraction of saliva was obtained by means of differential centrifugation and ultracentrifugation. Expression levels of miR-222 and miR-146a were profiled by qPCR. We regressed the extracellular miRNA expression against recent exposure to ultrafine and fine particles measured at the school site using mixed models, while accounting for sex, age, BMI, passive smoking, maternal education, hours of television use, time of the day and day of the week. RESULTS: Exposure to ultrafine particles (UFP) at the school site was positively associated with miR-222 expression in the extracellular fraction in saliva. For each IQR increase in particles in the class room (+8504 particles/cm(3)) or playground (+28776 particles/cm(3)), miR-222 was, respectively 23.5 % (95 % CI: 3.5 %-41.1 %; p = 0.021) or 29.9 % (95 % CI:10.6 %-49.1 %; p = 0.0027) higher. No associations were found between miR-146a and recent exposure to fine and ultrafine particles. CONCLUSIONS: Our results suggest a possible epigenetic mechanism via which cells respond rapidly to small particles, as exemplified by miR-222 changes in the extracellular fraction of saliva.

Host and environmental predictors of exhaled breath temperature in the elderly.

BACKGROUND: Exhaled breath temperature has been suggested as a new method to detect and monitor pathological processes in the respiratory system. The putative mechanism of this approach is based upon changes in the blood flow. So far potential factors that influence breath temperature have not been studied in the general population. METHODS: The exhaled breath temperature was measured in 151 healthy non-smoking elderly (aged: 60-80 years) at room temperature with the X-halo device with an accuracy of 0.03°C. We related exhaled breath temperature by use of regression models with potential predictors including: host factors (sex, age) and environmental factors (BMI, physical activity, and traffic indicators). RESULTS: Exhaled breath temperature was lower in women than in men and was inversely associated with age, physical activity. BMI and daily average ambient temperature were positively associated with exhaled breath temperature. Independent of the aforementioned covariates, exhaled breath temperature was significantly associated with several traffic indicators. Residential proximity to major road was inversely associated with exhaled breath temperature: doubling the distance to the nearest major intense road was observed a decrease of 0.17°C (95% CI: -0.33 to -0.01; p=0.036). CONCLUSIONS: Exhaled breath temperature has been suggested as a noninvasive method for the evaluation of airway inflammation. We provide evidence that several factors known to be involved in proinflammatory conditions including BMI, physical activity and residential proximity to traffic affect exhaled breath temperature. In addition, we identified potential confounders that should be taken into account in clinical and epidemiological studies on exhaled breath temperature including sex, age, and ambient temperature.