Eline B. Provost

Carotid Intima-Media Thickness, a Marker of Subclinical Atherosclerosis, and Particulate Air Pollution Exposure: the Meta-Analytical Evidence

Introduction Studies on the association between atherosclerosis and long-term exposure to ambient air pollution suggest that carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, is positively associated with particulate matter (PM) exposure. However, there is heterogeneity between the different studies concerning the magnitude of this association. We performed a meta-analysis to determine the strength of the association between CIMT and particulate air pollution. Methods We queried PubMed citation database and Web of Knowledge up to March 2015 in order to identify studies on CIMT and particulate air pollution. Two investigators selected and computerized all relevant information, independently. Eight of the reviewed epidemiological publications provided sufficient details and met our inclusion criteria. Descriptive and quantitative information was extracted from each selected study. The meta-analysis included 18,349 participants from eight cohorts for the cross-sectional association between CIMT and PM and 7,268 participants from three cohorts for the longitudinal analysis on CIMT progression and PM exposure. Results The average exposure to PM2.5 in the different study populations ranged from 4.1 to 20.8 µg/m3 and CIMT averaged (SD) 0.73 (0.14) mm. We computed a pooled estimate from a random-effects model. In the combined cross-sectional studies, an increase of 5 µg/m3 PM2.5 was associated with a 1.66% (95% CI: 0.86 to 2.46; P<0.0001) thicker CIMT, which corresponds to an average increase of 12.1 µm. None of the studies moved the combined estimate outside the confidence interval of the overall estimate. A funnel plot suggested absence of publication bias. The combined longitudinal estimate showed for each 5 µg/m3 higher PM2.5 exposure, a 1.04 µm per year (95% CI: 0.01 to 2.07; P=0.048) greater CIMT progression. Conclusion Our meta-analysis supports the evidence of a positive association between CIMT, a marker of subclinical atherosclerosis, and long-term exposure to particulate air pollution.

Serum levels of club cell secretory protein (Clara) and short- and long-term exposure to particulate air pollution in adolescents.

BACKGROUND Studies in populations have shown that particulate air pollution is associated with changes in lung function in adolescents. OBJECTIVE We investigated the effect of short- and long-term exposure to particulate matter (PM10) on the pulmonary health of adolescents, using serum lung club cell secretory protein (Clara) (CC16) as a biomarker for respiratory epithelium integrity. METHODS We measured serum CC16 in 825 adolescents (57% girls, mean age: 15 years). Short-term and long-term exposure to ambient PM10 was estimated for each participants home address using a kriging interpolation method. To explore the association between PM10 and serum CC16 we applied restricted cubic splines with 5 knots located at the 5th, 25th, 50th, 75th and 95th percentiles of the PM10 distribution. The explorative analyses showed a change in the slope of this association, after which a change-point analysis was performed. RESULTS After adjustment for potential covariates, the analysis showed strong associations between PM10 concentrations, averaged over the week preceding the clinical examination, and serum CC16 levels. Each 5 μg/m(3) increase in mean PM10 concentration in the week before the clinical examination was associated with a substantial increase of 0.52 μg/l (95% confidence interval: 0.31 to 0.73; p<0.0001) in serum CC16 levels. The association appears nonlinear with a flattening out of the slope at mean week PM10 levels above 37 μg/m(3). There was no evidence of an association between long-term exposure to PM10 and serum CC16 concentrations. CONCLUSIONS Our findings suggest that short-term exposure to particulate air pollution may compromise the integrity of the lung epithelium and lead to increased epithelial barrier permeability in the lungs of adolescents, even at low concentrations.

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. Childrens 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.

Blood pressure changes in association with black carbon exposure in a panel of healthy adults are independent of retinal microcirculation

Exposure to ambient particulate matter and elevated blood pressure are risk factors for cardiovascular morbidity and mortality. Microvascular changes might be an important pathway in explaining the association between air pollution and blood pressure. The objective of the study was to evaluate the role of the retinal microcirculation in the association between black carbon (BC) exposure and blood pressure. We estimated subchronic BC exposure based on 1-week personal measurements (μ-Aethalometer, AethLabs) in 55 healthy nurses. Blood pressure and retinal microvasculature were measured on four different days (range: 2-4) during this week. Subchronic BC exposure averaged (± SD) 1334±631ng/m(3) and ranged from 338ng/m(3) to 3889ng/m(3). An increased exposure of 631ng/m(3) BC was associated with a 2.77mmHg (95% CI: 0.39 to 5.15, p=0.027) increase in systolic blood pressure, a 2.35mmHg (95% CI: 0.52 to 4.19, p=0.016) increase in diastolic blood pressure and with 5.65μm (95% CI: 1.33 to 9.96, p=0.014) increase in central retinal venular equivalent. Mediation analysis failed to reveal an effect of retinal microvasculature in the association between blood pressure and subchronic BC exposure. In conclusion, we found a positive association between blood pressure and subchronic black carbon exposure in healthy adults. This finding adds evidence to the association between black carbon exposure and cardiovascular health effects, with elevated blood pressure as a plausible intermediate effector. Our results suggest that the changes in a persons blood pressure as a result of subchronic black carbon exposure operate independently of the retinal microcirculation.

Cohort Profile: The ENVIRonmental influence ON early AGEing (ENVIRONAGE): a birth cohort study

The ENVIRONAGE birth cohort is supported by the European Research Council [ERC-2012-StG.310898], and by funds of the Flemish Scientific Research council [FWO, G.0.733.15.N]. Bianca Cox, Janneke Hogervorst and Karen Vrijens have a postdoctoral fellowship from the Research Foundation - Flanders (FWO).

Short-term fluctuations in personal black carbon exposure are associated with rapid changes in carotid arterial stiffening

BACKGROUND Vascular changes may underpin the association between airborne black carbon (BC) and cardiovascular events. Accurate assessment of personal exposure is a major challenge in epidemiological research. BC concentrations are strongly related to time-activity patterns, which is particularly relevant when investigating short-term effects. We investigated associations between arterial stiffness and personal short-term BC exposure. METHODS This panel study included 54 healthy adults (92% women, mean age 40.7years). BC exposure was monitored individually with a micro-aethalometer during one workweek. Functional and structural properties of the carotid artery were examined ultrasonographically on two separate days. The effect of different short-term personal BC exposure windows (1, 2, 4, 6, 8, 24 and 48h before the ultrasound examination) on carotid artery stiffness was estimated using mixed models while adjusting for other known correlates of arterial stiffness. RESULTS Median personal BC exposures within the same day ranged from 599.8 to 728.9ng/m(3) and were associated with carotid arterial stiffness measures. Youngs elastic modulus and pulse wave velocity, both measures of stiffness, were positively associated with BC exposure, while the distensibility and compliance coefficient, measures of elasticity, were negatively associated with BC exposure. The strongest associations were observed with BC exposure 8h before the clinical examination. For each 100ng/m(3) increase in exposure within this time window, Youngs elastic modulus increased by 2.38% (95% CI: 0.81 to 3.97; P=0.0033), while the distensibility coefficient decreased by 2.27% (95% CI: -3.62 to -0.92; P=0.0008). CONCLUSIONS Short-term elevations in personal BC exposure, even within hours, are associated with increased arterial stiffness. This response may reflect a pathway by which air pollution triggers cardiovascular events.

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

Childrens 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 childs 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.

Fundus Photography as a Convenient Tool to Study Microvascular Responses to Cardiovascular Disease Risk Factors in Epidemiological Studies

The microcirculation consists of blood vessels with diameters less than 150 µm. It makes up a large part of the circulatory system and plays an important role in maintaining cardiovascular health. The retina is a tissue that lines the interior of the eye and it is the only tissue that allows for a non-invasive analysis of the microvasculature. Nowadays, high-quality fundus images can be acquired using digital cameras. Retinal images can be collected in 5 min or less, even without dilatation of the pupils. This unobtrusive and fast procedure for visualizing the microcirculation is attractive to apply in epidemiological studies and to monitor cardiovascular health from early age up to old age. Systemic diseases that affect the circulation can result in progressive morphological changes in the retinal vasculature. For example, changes in the vessel calibers of retinal arteries and veins have been associated with hypertension, atherosclerosis, and increased risk of stroke and myocardial infarction. The vessel widths are derived using image analysis software and the width of the six largest arteries and veins are summarized in the Central Retinal Arteriolar Equivalent (CRAE) and the Central Retinal Venular Equivalent (CRVE). The latter features have been shown useful to study the impact of modifiable lifestyle and environmental cardiovascular disease risk factors. The procedures to acquire fundus images and the analysis steps to obtain CRAE and CRVE are described. Coefficients of variation of repeated measures of CRAE and CRVE are less than 2% and within-rater reliability is very high. Using a panel study, the rapid response of the retinal vessel calibers to short-term changes in particulate air pollution, a known risk factor for cardiovascular mortality and morbidity, is reported. In conclusion, retinal imaging is proposed as a convenient and instrumental tool for epidemiological studies to study microvascular responses to cardiovascular disease risk factors.

Recent versus chronic fine particulate air pollution exposure as determinant of the retinal microvasculature in school children

Background: Microvascular changes may represent an underlying mechanism through which exposure to fine particulate matter with a diameter ≤ 2.5 &mgr;m (PM2.5) contributes to age‐related disease development. We investigated the effect of recent and chronic exposure to PM2.5 on the microcirculation, exemplified by retinal vessel diameters, using repeated measurements in 8‐ to 12‐year‐old children. Methods: 221 children (49.1% girls; mean age 9.9 years) were examined repeatedly (25 one, 124 two, and 72 three times) adding up to 489 retinal vessel examinations. Same‐day exposure to PM2.5 was measured at school. In addition, recent (same and previous day) and chronic (yearly mean) exposure was modelled at the childs residence using a high‐resolution interpolation model. Residential proximity to major roads was also assessed. Changes in retinal vessel diameters associated with recent and chronic exposures were estimated using mixed models, while adjusting for other known covariates such as sex, age, BMI, blood pressure and birth weight. Results: Each 10 &mgr;g/m³ increment in same‐day exposure to PM2.5 measured at school was associated with 0.35 &mgr;m (95% CI: 0.09–0.61 &mgr;m) narrower retinal arterioles and 0.35 &mgr;m (−0.03 to 0.73 &mgr;m) wider venules. Children living 100 m closer to a major road had 0.30 &mgr;m (0.05–0.54 &mgr;m) narrower arterioles. Conclusions: Blood vessel diameters of the retinal microcirculation of healthy school‐aged children respond to same‐day PM2.5 exposure. Furthermore, children living closer to major roads had smaller arteriolar diameters. Our results suggest that the microcirculation, with retinal microvasculature as a proxy in this study, is a pathophysiological target for air pollution in children. HighlightsChildrens retinal blood vessel diameters respond to recent PM2.5 exposure.Repeated design with multiple retinal microvascular examinations in each child.Integrative exposure assessment at school and at home.Microvascular changes may be an early phenotypic marker for disease development.

Children’s screen time alters the expression of saliva extracellular miR-222 and miR-146a

An imbalance between energy uptake and energy expenditure is the most important reason for increasing trends in obesity starting from early in life. Extracellular miRNAs are expressed in all bodily fluids and their expression is influenced by a broad range of stimuli. We examined whether screen time, physical activity and BMI are associated with children’s salivary extracellular miR-222 and miR-146a expression. In 80 children 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 studied the association between children’s salivary extracellular miRNA expression and screen time, physical activity and BMI using mixed models, while accounting for potential confounders. We found that higher screen time was positively associated with salivary extracellular miR-222 and miR-146a levels. On average, one hour more screen time use per week was associated with a 3.44% higher miR-222 (95% CI: 1.34 to 5.58; p = 0.002) and 1.84% higher miR-146a (95% CI: −0.04 to 3.75; p = 0.055) level in saliva. BMI and physical activity of the child were not significantly associated with either miR-222 or miR-146a. A sedentary behaviour, represented by screen time use in children, is associated with discernible changes in salivary expression of miR-146a and or miR-222. These miRNA targets may emerge attractive candidates to explore the role of these exposures in developmental processes of children’s health.