Children's microvascular traits and ambient air pollution exposure during pregnancy and early childhood: prospective evidence to elucidate the developmental origin of particle-induced disease.

BACKGROUND: Particulate matter exposure during in utero life may entail adverse health outcomes later in life. The microvasculature undergoes extensive, organ-specific prenatal maturation. A growing body of evidence shows that cardiovascular disease in adulthood is rooted in a dysfunctional fetal and perinatal development, in particular that of the microcirculation. We investigate whether prenatal or postnatal exposure to PM2.5 (particulate matter with a diameter ≤ 2.5 µm) or NO2 is related to microvascular traits in children between the age of four and six. METHODS: We measured the retinal microvascular diameters, the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), and the vessel curvature by means of the tortuosity index (TI) in young children (mean [SD] age 4.6 [0.4] years), followed longitudinally within the ENVIRONAGE birth cohort. We modeled daily prenatal and postnatal PM2.5 and NO2 exposure levels for each participant's home address using a high-resolution spatiotemporal model. RESULTS: An interquartile range (IQR) increase in PM2.5 exposure during the entire pregnancy was associated with a 3.85-µm (95% CI, 0.10 to 7.60; p = 0.04) widening of the CRVE and a 2.87-µm (95% CI, 0.12 to 5.62; p = 0.04) widening of the CRAE. For prenatal NO2 exposure, an IQR increase was found to widen the CRVE with 4.03 µm (95% CI, 0.44 to 7.63; p = 0.03) and the CRAE with 2.92 µm (95% CI, 0.29 to 5.56; p = 0.03). Furthermore, a higher TI score was associated with higher prenatal NO2 exposure. We observed a postnatal effect of short-term PM2.5 exposure on the CRAE and a childhood NO2 exposure effect on both the CRVE and CRAE. CONCLUSIONS: Our results link prenatal and postnatal air pollution exposure with changes in a child's microvascular traits as a fundamental novel mechanism to explain the developmental origin of cardiovascular disease.

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.

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 ≤ 2.5µm (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 child's 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 10µg/m³ increment in same-day exposure to PM2.5 measured at school was associated with 0.35µm (95% CI: 0.09-0.61µm) narrower retinal arterioles and 0.35µm (-0.03 to 0.73µm) wider venules. Children living 100m closer to a major road had 0.30µm (0.05-0.54µm) 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.

Short-term air pollution exposure decreases lung function: a repeated measures study in healthy adults.

BACKGROUND: Daily changes in ambient concentrations of particulate matter, nitrogen oxides and ozone are associated with increased cardiopulmonary morbidity and mortality, with the lungs and their function being a vulnerable target. METHODS: To evaluate the association between daily changes in air pollution and lung function in healthy adults we obtained annual lung function measurements from a routine worker health surveillance program not designed for research purposes. Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), FEV1/FVC and Peak Expiratory flow (PEF) from a cohort of 2449 employees were associated with daily measurements of PM10, NO2 and ozone at a nearby monitoring station in the North of Belgium. Repeated measures were available for the period 2011-2015. RESULTS: The mean (SD) PM10 concentration on the day of the lung function test was 24.9 (15.5) µg/m3. A 10 µg PM10/m3 increase on the day of the clinical examination was associated with a 18.9 ml lower FVC (95% CI: -27.5 to -10.3, p < 0.0001), 12.8 ml lower FEV1 (-19.1 to -6.5; p < 0.0001), and a 51.4 ml/s lower PEF (-75.0 to -27.0; p < 0.0001). The FEV1/FVC-ratio showed no associations. An increase of 10 µgNO2/m3 was associated with a reduction in PEF (-66.1 ml/s (-106.6 to -25.6; p < 0.001)) on the day of the examination. CONCLUSIONS: We found negative associations between daily variations in ambient air pollution and FVC, FEV1 and PEF in healthy adults.

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.

Denser Retinal Microvascular Network Is Inversely Associated With Behavioral Outcomes and Sustained Attention in Children.

Changes in geometry of the retinal microvascular network, including vessel width, vessel density, and tortuosity, have been associated with neurological disorders in adults. We investigated metrics of the retinal microvasculature in association with behavior and cognition in 8- to 12-year-old children. Digital fundus images of 190 children (48.2% girls, mean age 9.9 years) were used to calculate retinal vessel diameters, fractal dimension, lacunarity, and tortuosity. Parents filled out a Strengths and Difficulties Questionnaire (SDQ) for behavioral screening. Cognitive performance testing included a computerized version of the Stroop test (selective attention), the Continuous Performance (sustained attention), the Digit-Symbol (visual scanning and information-processing speed) and the Pattern Comparison (visuospatial analytic ability) tests from the Neurobehavioral Evaluation System (NES3) battery. Retinal vessel geometry was significantly associated with the SDQ problem score, which increased with 1.1 points (95% CI: 0.3 to 1.9 points) per interquartile (IQR) increment in retinal fractal dimension, and decreased 1.4 points (95% CI: -2.4 to -0.4 points) or decreased 1.0 points (95% CI: -2.1 to 0.1 points) per IQR increment in retinal vascular lacunarity or tortuosity, respectively. Sensitivity analyses showed that results were driven by the hyperactivity/inattention and conduct problem scales of the SDQ. Correspondingly, mean reaction time on the Continuous Performance test increased by 11 ms (95% CI: 4.4 to 17.6 ms) with an IQR increase in fractal dimension. The results indicate that a denser retinal microvascular network, exemplified by a higher fractal dimension and lower lacunarity, are inversely associated with behavioral outcomes and sustained attention in children.

Association of Retinal Microvascular Characteristics With Short-term Memory Performance in Children Aged 4 to 5 Years.

Importance: Neurocognitive functions develop rapidly in early childhood and depend on the intrinsic cooperation between cerebral structures and the circulatory system. The retinal microvasculature can be regarded as a mirror image of the cerebrovascular circulation. Objective: To investigate the association between retinal vessel characteristics and neurological functioning in children aged 4 to 5 years. Design, Setting, and Participants: In this cohort study, mother-child pairs were recruited at birth from February 10, 2010, to June 24, 2014, and renewed consent at their follow-up visit from December 10, 2014, to July 13, 2018. Participants were followed up longitudinally within the prospective Environmental Influence on Aging in Early Life birth cohort. A total of 251 children underwent assessment for this study. Data were analyzed from July 17 to October 30, 2019. Main Outcomes and Measures: Retinal vascular diameters, the central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), vessel tortuosity, and fractal dimensions were determined. Attention and psychomotor speed, visuospatial working memory, and short-term visual recognition memory were assessed by the Cambridge Neuropsychological Test Automated Battery, including the following tasks: Motor Screening (MOT), Big/Little Circle (BLC), Spatial Span (SSP), and Delayed Matching to Sample (DMS). Results: Among the 251 children included in the assessment (135 girls [53.8%]; mean [SD] age, 4.5 [0.4] years), for every 1-SD widening in CRVE, the children performed relatively 2.74% (95% CI, -0.12 to 5.49; P = .06) slower on the MOT test, had 1.76% (95% CI, -3.53% to -0.04%; P = .04) fewer correct DMS assessments in total, and made 2.94% (95% CI, 0.39 to 5.29; P = .02) more errors given a previous correct answer in the DMS task on multiple linear regression modeling. For every 1-SD widening in CRAE, the total percentage of errors and errors given previous correct answers in the DMS task increased 1.44% (95% CI, -3.25% to 0.29%; P = .09) and 2.30% (95% CI, -0.14% to 4.61%; P = .07), respectively. A 1-SD higher vessel tortuosity showed a 4.32% relative increase in latency in DMS task performance (95% CI, -0.48% to 9.12%; P = .07). Retinal vessel characteristics were not associated with BLC and SSP test outcomes. Conclusions and Relevance: These findings suggest that children's microvascular phenotypes are associated with short-term memory and that changes in the retinal microvasculature may reflect neurological development during early childhood.

Establishing reference values for macro- and microvascular measurements in 4-to-5 year-old children of the ENVIRONAGE prospective birth cohort.

Cardiovascular risk factors are usually better tolerated, and can therefore be perceived as less harmful, at a young age. However, over time the effects of these adverse factors may persist or accumulate and lead to excess morbidity and mortality from cardiovascular diseases later in life. Until now, reference values for the basic cardiovascular health characteristics of 4-to-6 year-old children are lacking. Within a follow-up study of the ENVIRONAGE (ENVIRonmental influence ON early AGE) birth cohort we assessed various cardiovascular measurements in 288 children aged 4-5 years. For the macrovasculature, we measured their blood pressure and examined the intima-media thickness of the carotid artery (CIMT), the arterial elasticity (including the pulse-wave velocity (PWV), carotid distensibility (DC) and compliance (CC) coefficients), the carotid ß stiffness index (SIß) and Young's Elastic Modulus (YEM). Retinal microvascular traits included the Central Retinal Arteriolar Equivalent (CRAE) and Central Retinal Venular Equivalent (CRVE). Age of the study population averaged (±SD) 4.2 (±0.4 years. Mean systolic and diastolic blood pressure were 97.9 (±8.1) mmHg and 54.7(±7.6) mmHg, respectively. CIMT for the total population averaged 487.1 (±68.1) µm. The average stiffness values for DC, CC, SIß, and PWV were 78.7 (±34.2) 10-³/kPa, 1.61 (±0.59) mm2/kPa and 4.4 (±2.4), and 3.7 m/s (±0.9) respectively. The mean determined for YEM was 163.2 kPa (±79.9). Concerning the microvasculature, the average CRAE was 180.9 (±14.2) µm and the corresponding value for CRVE was 251.0 (±19.7) µm. In contrast to the macrovasculature, a significant gender-related difference existed for the microvasculature: in boys, both the CRAE (178.8 µm vs 182.6 µm; p = 0.03) and CRVE (247.9 µm vs 254.0 µm; p = 0.01) were narrower than in girls. We have provided reference values for young children to understand changes in the early cardiovascular health trajectory. Establishing these reference values of cardiovascular phenotypes at this young age is necessary to develop targeted health promotion strategies as well as for better understanding of the life course changes of both small and large blood vessels.

Child's buccal cell mitochondrial DNA content modifies the association between heart rate variability and recent air pollution exposure at school.

BACKGROUND: Studies investigating short-term exposure to ambient air pollution and heart rate variability (HRV) suggest that particulate matter (PM) exposure is associated with reductions in measures of HRV. Mitochondria are sensitive to PM exposure and may represent a biologically relevant underlying mechanism. However, evidence in children is lacking. OBJECTIVES: Here we examine whether PM has an influence on children's HRV and evaluate whether mitochondrial DNA content (mtDNAc) reflects individual susceptibility. METHODS: Within a panel study in primary school children (aged 9-12 years), we measured HRV in a subset of 60 children on three different days during school-time using four indicators: normal-to-normal intervals (SDNN), square root of mean squared difference of normal-to-normal intervals (rMSSD), high frequency (HF), and low frequency (LF). This resulted in a total number of 150 visits (median number of visits per child: 2.5/child). MtDNAc was measured using qPCR in buccal cells. We measured recent PM exposure at the school. Residential 24-hour mean exposure to PM was modelled with a high resolution spatial temporal model. Mixed-effects models were used to estimate the association between HRV and recent PM exposure and potential effect-modification by mtDNAc. RESULTS: Children were on average [SD] 9.9 [1.2] years and comprised 39 girls. Median [25th-75th] recent outdoor PM2.5 and PM10 exposure at school was 6.20 [2.8-12.8] µg/m3 and 29.3 [24.7-42.0] µg/m3, respectively. In children with low mtDNAc (25th percentile), we observed for each 10 µg/m3 increment in recent PM2.5 exposure a lowering in the LF parameter with 9.76% (95% CI: -16.9 to -1.99%, p = 0.02; pint = 0.007). Children with high mtDNAc did not show this association. For PM10 exposure, we observed an inverse association with three HRV indicators in children with low mtDNAc: -2.24% (95% CI: -4.27 to -0.16%; p = 0.04; pint = 0.02) for SDNN, -5.67% (95% CI: -10.5 to -0.59%; p = 0.03; pint = 0.04) for HF and -6.64% (95% CI: -10.7 to -2.38%; p = 0.003; pint = 0.005) for LF. CONCLUSIONS: HRV is inversely associated with recent PM air pollution, especially in children with low mtDNAc. Our data revealed that mtDNAc determines susceptibility to adverse autonomic effects of recent PM exposure in children.

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.

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. Young's 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, Young's 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.

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.

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 participant's 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.