Dynamic assessment of exposure to air pollution using mobile phone data

Background: Exposure to air pollution can have major health impacts, such as respiratory and cardiovascular diseases. Traditionally, only the air pollution concentration at the home location is taken into account in health impact assessments and epidemiological studies. Neglecting individual travel patterns can lead to a bias in air pollution exposure assessments. Methods: In this work, we present a novel approach to calculate the daily exposure to air pollution using mobile phone data of approximately 5 million mobile phone users living in Belgium. At present, this data is collected and stored by telecom operators mainly for management of the mobile network. Yet it represents a major source of information in the study of human mobility. We calculate the exposure to NO2 using two approaches: assuming people stay at home the entire day (traditional static approach), and incorporating individual travel patterns using their location inferred from their use of the mobile phone network (dynamic approach). Results: The mean exposure to NO2 increases with 1.27 mu g/m(3) (4.3 %) during the week and with 0.12 mu g/m(3) (0.4 %) during the weekend when incorporating individual travel patterns. During the week, mostly people living in municipalities surrounding larger cities experience the highest increase in NO2 exposure when incorporating their travel patterns, probably because most of them work in these larger cities with higher NO2 concentrations. Conclusions: It is relevant for health impact assessments and epidemiological studies to incorporate individual travel patterns in estimating air pollution exposure. Mobile phone data is a promising data source to determine individual travel patterns, because of the advantages (e.g. low costs, large sample size, passive data collection) compared to travel surveys, GPS, and smartphone data (i.e. data captured by applications on smartphones)

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

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. The work is supported by the European Research Council (ERC-2012-StG.310898 and ERC-2011-StG. 282413) and by the Flemish Scientific Fund (FWO,G073315N/G082317N)

Prenatal Air Pollution and Newborns' Predisposition to Accelerated Biological Aging.

Importance: Telomere length is a marker of biological aging that may provide a cellular memory of exposures to oxidative stress and inflammation. Telomere length at birth has been related to life expectancy. An association between prenatal air pollution exposure and telomere length at birth could provide new insights in the environmental influence on molecular longevity. Objective: To assess the association of prenatal exposure to particulate matter (PM) with newborn telomere length as reflected by cord blood and placental telomere length. Design, Setting, and Participants: In a prospective birth cohort (ENVIRONAGE [Environmental Influence on Ageing in Early Life]), a total of 730 mother-newborn pairs were recruited in Flanders, Belgium between February 2010 and December 2014, all with a singleton full-term birth (≥37 weeks of gestation). For statistical analysis, participants with full data on both cord blood and placental telomere lengths were included, resulting in a final study sample size of 641. Exposures: Maternal residential PM2.5 (particles with an aerodynamic diameter ≤2.5 μm) exposure during pregnancy. Main Outcomes and Measures: In the newborns, cord blood and placental tissue relative telomere length were measured. Maternal residential PM2.5 exposure during pregnancy was estimated using a high-resolution spatial-temporal interpolation method. In distributed lag models, both cord blood and placental telomere length were associated with average weekly exposures to PM2.5 during pregnancy, allowing the identification of critical sensitive exposure windows. Results: In 641 newborns, cord blood and placental telomere length were significantly and inversely associated with PM2.5 exposure during midgestation (weeks 12-25 for cord blood and weeks 15-27 for placenta). A 5-µg/m3 increment in PM2.5 exposure during the entire pregnancy was associated with 8.8% (95% CI, -14.1% to -3.1%) shorter cord blood leukocyte telomeres and 13.2% (95% CI, -19.3% to -6.7%) shorter placental telomere length. These associations were controlled for date of delivery, gestational age, maternal body mass index, maternal age, paternal age, newborn sex, newborn ethnicity, season of delivery, parity, maternal smoking status, maternal educational level, pregnancy complications, and ambient temperature. Conclusions and Relevance: Mothers who were exposed to higher levels of PM2.5 gave birth to newborns with shorter telomere length. The observed telomere loss in newborns by prenatal air pollution exposure indicates less buffer for postnatal influences of factors decreasing telomere length during life. Therefore, improvements in air quality may promote molecular longevity from birth onward

Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women

BACKGROUND: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases. OBJECTIVES: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population. METHODS: Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM(10) in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM(2.5) and PM(10) exposures over 2-years were estimated for each participant’s residential address using spatiotemporal interpolation in combination with a dispersion model. RESULTS: Average long-term PM(10) was 25.9 (± 5.4) and 23.7 (± 2.3) μg/m(3) in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM(10) and the expression of individual genes differed by sex. In the validation cohort, long-term PM(10) was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM(10) in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM(10) exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women). CONCLUSIONS: Expression of the sex-specific candidate genes identified in the discovery population predicted PM(10) exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects. CITATION: Vrijens K, Winckelmans E, Tsamou M, Baeyens W, De Boever P, Jennen D, de Kok TM, Den Hond E, Lefebvre W, Plusquin M, Reynders H, Schoeters G, Van Larebeke N, Vanpoucke C, Kleinjans J, Nawrot TS. 2017. Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women. Environ Health Perspect 125:660–669; http://dx.doi.org/10.1289/EHP37

Long-term exposure to residential green spaces and site-specific cancer mortality in urban Belgium : a 13-year follow-up cohort study

Background: Residing in greener areas may decrease the burden of chronic diseases, but the association with cancer is unclear. We studied the associations between residential green spaces and site-specific cancer mortality in urban Belgium. Methodology: We linked the 2001 Belgian census, register mortality data for 2001–2014, and environmental information (green spaces and air pollution) at baseline residence (2001). We included residents from the largest Belgian urban areas aged ≥ 30 years at baseline. Exposure to residential green spaces was assessed using the Normalized Difference Vegetation Index (NDVI), Urban Atlas, and perceived neighbourhood greenness (from the census). We used Cox proportional hazards models to obtain hazard ratios (HR) and their 95 % confidence intervals (95 %CI) of the mortality risk from lung, colorectal, breast (in women) and prostate cancer (in men) per interquartile range increment in residential green spaces. We further analyzed the role of outdoor air pollution and effect modification by age and socioeconomic position (SEP) in main associations. Results: 2,441,566 individuals were included at baseline. During follow-up, 1.2 % died from lung cancer, 0.6 % from colorectal cancer, 0.8 % from breast cancer, and 0.6 % from prostate cancer. After adjustment, higher exposure to green spaces was associated with a reduced mortality risk from lung cancer and breast cancer [e.g., for NDVI within 300 m, HR:0.946 (95 %CI:0.924,0.970), and HR:0.927 (95 %CI:0.892,0.963), respectively], but not with colorectal or prostate cancer mortality. For the latter, a suggestive hazardous effect of green spaces was found. Air pollution seemed to have only a marginal role. Beneficial effects of greenspace were generally stronger in < 65-year-old, but no clear trend by SEP was found. Conclusions: Our findings suggest that residing in green areas could decrease mortality risk from lung and breast cancer, potentially independent from air pollution. Future studies should consider different indicators of greenspace exposure and investigate potential pathways underlying the associations

Long-term exposure to residential green spaces and site-specific cancer mortality in urban Belgium: A 13-year follow-up cohort study

Background: Residing in greener areas may decrease the burden of chronic diseases, but the association with cancer is unclear. We studied the associations between residential green spaces and site-specific cancer mortality in urban Belgium. Methodology: We linked the 2001 Belgian census, register mortality data for 2001–2014, and environmental information (green spaces and air pollution) at baseline residence (2001). We included residents from the largest Belgian urban areas aged ≥ 30 years at baseline. Exposure to residential green spaces was assessed using the Normalized Difference Vegetation Index (NDVI), Urban Atlas, and perceived neighbourhood greenness (from the census). We used Cox proportional hazards models to obtain hazard ratios (HR) and their 95 % confidence intervals (95 %CI) of the mortality risk from lung, colorectal, breast (in women) and prostate cancer (in men) per interquartile range increment in residential green spaces. We further analyzed the role of outdoor air pollution and effect modification by age and socioeconomic position (SEP) in main associations. Results: 2,441,566 individuals were included at baseline. During follow-up, 1.2 % died from lung cancer, 0.6 % from colorectal cancer, 0.8 % from breast cancer, and 0.6 % from prostate cancer. After adjustment, higher exposure to green spaces was associated with a reduced mortality risk from lung cancer and breast cancer [e.g., for NDVI within 300 m, HR:0.946 (95 %CI:0.924,0.970), and HR:0.927 (95 %CI:0.892,0.963), respectively], but not with colorectal or prostate cancer mortality. For the latter, a suggestive hazardous effect of green spaces was found. Air pollution seemed to have only a marginal role. Beneficial effects of greenspace were generally stronger in < 65-year-old, but no clear trend by SEP was found. Conclusions: Our findings suggest that residing in green areas could decrease mortality risk from lung and breast cancer, potentially independent from air pollution. Future studies should consider different indicators of greenspace exposure and investigate potential pathways underlying the associations

Long-term exposure to residential greenness and neurodegenerative disease mortality among older adults : a 13-year follow-up cohort study

BACKGROUND: Living in greener areas is associated with slower cognitive decline and reduced dementia risk among older adults, but the evidence with neurodegenerative disease mortality is scarce. We studied the association between residential surrounding greenness and neurodegenerative disease mortality in older adults. METHODS: We used data from the 2001 Belgian census linked to mortality register data during 2001–2014. We included individuals aged 60 years or older and residing in the five largest Belgian urban areas at baseline (2001). Exposure to residential surrounding greenness was assessed using the 2006 Normalized Difference Vegetation Index (NDVI) within 500-m from residence. We considered all neurodegenerative diseases and four specific outcomes: Alzheimer’s disease, vascular dementia, unspecified dementia, and Parkinson’s disease. We fitted Cox proportional hazard models to obtain hazard ratios (HR) and 95% confidence intervals (CI) of the associations between one interquartile range (IQR) increment in surrounding greenness and neurodegenerative disease mortality outcomes, adjusted for census-based covariates. Furthermore, we evaluated the potential role of 2010 air pollution (PM(2.5) and NO(2)) concentrations, and we explored effect modification by sociodemographic characteristics. RESULTS: From 1,134,502 individuals included at baseline, 6.1% died from neurodegenerative diseases during follow-up. After full adjustment, one IQR (0.22) increment of surrounding greenness was associated with a 4–5% reduction in premature mortality from all neurodegenerative diseases, Alzheimer’s disease, vascular and unspecified dementia [e.g., for Alzheimer’s disease mortality: HR 0.95 (95%CI: 0.93, 0.98)]. No association was found with Parkinson’s disease mortality. Main associations remained for all neurodegenerative disease mortality when accounting for air pollution, but not for the majority of specific mortality outcomes. Associations were strongest in the lower educated and residents from most deprived neighbourhoods. CONCLUSIONS: Living near greener spaces may reduce the risk of neurodegenerative disease mortality among older adults, potentially independent from air pollution. Socioeconomically disadvantaged groups may experience the greatest beneficial effect. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12940-022-00863-x