Olena Gruzieva

Ambient air pollution and low birthweight: a European cohort study (ESCAPE)

BACKGROUND Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight. METHODS We pooled data from 14 population-based mother-child cohort studies in 12 European countries. Overall, the study population included 74 178 women who had singleton deliveries between Feb 11, 1994, and June 2, 2011, and for whom information about infant birthweight, gestational age, and sex was available. The primary outcome of interest was low birthweight at term (weight <2500 g at birth after 37 weeks of gestation). Mean concentrations of particulate matter with an aerodynamic diameter of less than 2·5 μm (PM2·5), less than 10 μm (PM10), and between 2·5 μm and 10 μm during pregnancy were estimated at maternal home addresses with temporally adjusted land-use regression models, as was PM2·5 absorbance and concentrations of nitrogen dioxide (NO2) and nitrogen oxides. We also investigated traffic density on the nearest road and total traffic load. We calculated pooled effect estimates with random-effects models. FINDINGS A 5 μg/m(3) increase in concentration of PM2·5 during pregnancy was associated with an increased risk of low birthweight at term (adjusted odds ratio [OR] 1·18, 95% CI 1·06-1·33). An increased risk was also recorded for pregnancy concentrations lower than the present European Union annual PM2·5 limit of 25 μg/m(3) (OR for 5 μg/m(3) increase in participants exposed to concentrations of less than 20 μg/m(3) 1·41, 95% CI 1·20-1·65). PM10 (OR for 10 μg/m(3) increase 1·16, 95% CI 1·00-1·35), NO2 (OR for 10 μg/m(3) increase 1·09, 1·00-1·19), and traffic density on nearest street (OR for increase of 5000 vehicles per day 1·06, 1·01-1·11) were also associated with increased risk of low birthweight at term. The population attributable risk estimated for a reduction in PM2·5 concentration to 10 μg/m(3) during pregnancy corresponded to a decrease of 22% (95% CI 8-33%) in cases of low birthweight at term. INTERPRETATION Exposure to ambient air pollutants and traffic during pregnancy is associated with restricted fetal growth. A substantial proportion of cases of low birthweight at term could be prevented in Europe if urban air pollution was reduced. FUNDING The European Union.

Air Pollution Exposure and Lung Function in Children: The ESCAPE Project.

Background: There is evidence for adverse effects of outdoor air pollution on lung function of children. Quantitative summaries of the effects of air pollution on lung function, however, are lacking due to large differences among studies. Objectives: We aimed to study the association between residential exposure to air pollution and lung function in five European birth cohorts with a standardized exposure assessment following a common protocol. Methods: As part of the European Study of Cohorts for Air Pollution Effects (ESCAPE) we analyzed data from birth cohort studies situated in Germany, Sweden, the Netherlands, and the United Kingdom that measured lung function at 6–8 years of age (n = 5,921). Annual average exposure to air pollution [nitrogen oxides (NO2, NOx), mass concentrations of particulate matter with diameters < 2.5, < 10, and 2.5–10 μm (PM2.5, PM10, and PMcoarse), and PM2.5 absorbance] at the birth address and current address was estimated by land-use regression models. Associations of lung function with estimated air pollution levels and traffic indicators were estimated for each cohort using linear regression analysis, and then combined by random effects meta-analysis. Results: Estimated levels of NO2, NOx, PM2.5 absorbance, and PM2.5 at the current address, but not at the birth address, were associated with small decreases in lung function. For example, changes in forced expiratory volume in 1 sec (FEV1) ranged from –0.86% (95% CI: –1.48, –0.24%) for a 20-μg/m3 increase in NOx to –1.77% (95% CI: –3.34, –0.18%) for a 5-μg/m3 increase in PM2.5. Conclusions: Exposure to air pollution may result in reduced lung function in schoolchildren. Citation: Gehring U, Gruzieva O, Agius RM, Beelen R, Custovic A, Cyrys J, Eeftens M, Flexeder C, Fuertes E, Heinrich J, Hoffmann B, de Jongste JC, Kerkhof M, Klümper C, Korek M, Mölter A, Schultz ES, Simpson A, Sugiri D, Svartengren M, von Berg A, Wijga AH, Pershagen G, Brunekreef B. 2013. Air pollution exposure and lung function in children: the ESCAPE project. Environ Health Perspect 121:1357–1364; http://dx.doi.org/10.1289/ehp.1306770

Air Pollution and Respiratory Infections during Early Childhood: An Analysis of 10 European Birth Cohorts within the ESCAPE Project

Background: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood. Objectives: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts—BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)—and to derive combined effect estimates using meta-analysis. Methods: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, PM10, PM2.5–10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates. Results: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR = 1.30; 95% CI: 1.02, 1.65 per 10-μg/m3 increase in NO2 and OR = 1.76; 95% CI: 1.00, 3.09 per 10-μg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR = 1.09; 95% CI: 1.02, 1.16 per 10-μg/m3). Conclusion: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media. Citation: MacIntyre EA, Gehring U, Mölter A, Fuertes E, Klümper C, Krämer U, Quass U, Hoffmann B, Gascon M, Brunekreef B, Koppelman GH, Beelen R, Hoek G, Birk M, de Jongste JC, Smit HA, Cyrys J, Gruzieva O, Korek M, Bergström A, Agius RM, de Vocht F, Simpson A, Porta D, Forastiere F, Badaloni C, Cesaroni G, Esplugues A, Fernández-Somoano A, Lerxundi A, Sunyer J, Cirach M, Nieuwenhuijsen MJ, Pershagen G, Heinrich J. 2014. Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE project. Environ Health Perspect 122:107–113; http://dx.doi.org/10.1289/ehp.1306755

Traffic-related air pollution and lung function in children at 8 years of age: a birth cohort study

RATIONALE Long-term exposure to air pollution has been related to lung function decrements in children, but the role of timing of exposure remains unknown. OBJECTIVES To assess the role of long-term exposure to air pollution on lung function in school-age children. METHODS More than 1,900 children in the Swedish birth cohort BAMSE were followed with repeated questionnaires, dynamic spirometry, and IgE measurements until 8 years of age. Outdoor concentrations of particulate matter with an aerodynamic diameter less than 10 μm (PM(10)) from road traffic were estimated for residential, day care, and school addresses from birth and onward using dispersion modeling. The relationship between time-weighted average exposure during different time windows and FEV at 8 years was analyzed by linear regression, adjusting for potential confounding factors, including short-term exposure to air pollution. MEASUREMENTS AND MAIN RESULTS A 5th to 95th percentile difference in time-weighted average particulate matter less than 10 μm in aerodynamic diameter exposure during the first year of life was associated with a reduced FEV(1) of -59.3 ml (95% confidence interval, -113 to -5.6) at 8 years of age. The negative association was particularly pronounced in children concomitantly sensitized to common inhalant or food allergens (-136.9 ml; 95% confidence interval, -224.1 to -49.7). Exposure after the first year of life seemed to have less impact on lung function at 8 years. CONCLUSIONS Our results indicate that exposure to traffic-related air pollution during infancy affects lung function in children up to 8 years of age and particularly in those sensitized to common inhalant or food allergens.

Traffic-related air pollution and development of allergic sensitization in children during the first 8 years of life

BACKGROUND The role of exposure to air pollution in the development of allergic sensitization remains unclear. OBJECTIVE We sought to assess the development of sensitization until school age related to longitudinal exposure to air pollution from road traffic. METHODS More than 2500 children in the birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) from Stockholm, Sweden, were followed with repeated questionnaires and blood sampling until 8 years of age. Outdoor concentrations of nitrogen oxides, as a marker of exhaust particles, and particles with an aerodynamic diameter of less than 10 μm (PM(10)), mainly representing road dust, were assigned to residential, day care, and school addresses by using dispersion models. Time-weighted average exposures were linked to levels of IgE against common inhalant and food allergens at 4 and 8 years of age. RESULTS Air pollution exposure during the first year of life was associated with an increased risk of pollen sensitization at 4 years of age (odds ratio, 1.83; 95% confidence interval, 1.02-3.28) for a 5th to 95th difference in exposure to nitrogen oxides. At 8 years, there was no general increase in the risk of sensitization; however, the risk of food sensitization was increased, particularly among children free of sensitization at 4 years of age (odds ratio, 2.30; 95% confidence interval, 1.10-4.82). Results were similar by using PM(10). No associations between air pollution exposure after the first year of life and sensitization were seen. CONCLUSION Traffic-related air pollution exposure does not seem to increase the overall risk of sensitization to common inhalant and food allergens up to school age, but sensitization to certain allergens might be related to exposure during infancy.

Exposure to Air Pollution from Traffic and Childhood Asthma Until 12 Years of Age.

Background: There are limited prospective data on long-term exposure to air pollution and effects on childhood respiratory morbidity. We investigated the development of asthma and related symptoms longitudinally over the first 12 years of life in relation to air pollution from road traffic. Methods: The Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) includes 4089 children who were followed up with repeated questionnaires and blood samples for up to 12 years of age. Residential, daycare, and school addresses, time-activity patterns, emission databases, and dispersion models were used to estimate individual exposure to particulate matter with aerodynamic diameter <10 &mgr;m (PM10) and nitrogen oxides (NOx) from traffic. Results: Overall, the data suggested possible associations between exposure to air pollution during the first year of life and asthma and wheezing in children up to 12 years of age. Asthma risks seemed to be particularly increased in children age 8 to 12 years; the overall odds ratio was 2.0 (95% confidence interval = 1.1–3.5), and for nonallergic asthma, the odds ratio was 3.8 (0.9–16.2) for a 5th to 95th percentile increase in time-weighted average exposure to PM10 (corresponding to 7.2 µg/m3). Results were similar using exposure to traffic-NOx. Conclusions: We found modest positive associations between air pollution exposure from traffic during infancy and asthma in children during the first 12 years of life, with stronger effects suggested for nonallergic asthma.

A multicentre study of air pollution exposure and childhood asthma prevalence: the ESCAPE project

The aim of this study was to determine the effect of six traffic-related air pollution metrics (nitrogen dioxide, nitrogen oxides, particulate matter with an aerodynamic diameter <10 μm (PM10), PM2.5, coarse particulate matter and PM2.5 absorbance) on childhood asthma and wheeze prevalence in five European birth cohorts: MAAS (England, UK), BAMSE (Sweden), PIAMA (the Netherlands), GINI and LISA (both Germany, divided into north and south areas). Land-use regression models were developed for each study area and used to estimate outdoor air pollution exposure at the home address of each child. Information on asthma and current wheeze prevalence at the ages of 4–5 and 8–10 years was collected using validated questionnaires. Multiple logistic regression was used to analyse the association between pollutant exposure and asthma within each cohort. Random-effects meta-analyses were used to combine effect estimates from individual cohorts. The meta-analyses showed no significant association between asthma prevalence and air pollution exposure (e.g. adjusted OR (95%CI) for asthma at age 8–10 years and exposure at the birth address (n=10377): 1.10 (0.81–1.49) per 10 μg·m-3 nitrogen dioxide; 0.88 (0.63–1.24) per 10 μg·m-3 PM10; 1.23 (0.78–1.95) per 5 μg·m-3 PM2.5). This result was consistently found in initial crude models, adjusted models and further sensitivity analyses. This study found no significant association between air pollution exposure and childhood asthma prevalence in five European birth cohorts. No significant association between air pollution and childhood asthma prevalence in five European birth cohorts http://ow.ly/Cdbba

Pre- and Postnatal Exposure to Parental Smoking and Allergic Disease Through Adolescence

OBJECTIVES: To examine the role of prenatal and postnatal second-hand tobacco smoke (SHS) exposure on asthma, rhinitis, and eczema development up to 16 years of age. METHODS: A birth cohort of 4089 children was followed for 16 years. Information on parental smoking habits, lifestyle factors, and symptoms of allergic disease was gathered using repeated parental questionnaires. Generalized estimating equations assessed the overall and age-specific associations between SHS exposure and allergic disease at ages 1 to 16 years. RESULTS: Exposure to SHS in utero was associated with an overall elevated risk of developing asthma up to 16 years (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.15–1.83) but not for rhinitis or eczema. After additional adjustment for parental smoking throughout childhood, excess overall risks for asthma remained statistically significant. Moreover, a dose-dependent pattern with SHS was observed. Exposure to SHS during infancy was associated with an overall elevated risk of asthma (OR = 1.23; 95% CI, 1.01–1.51), rhinitis (OR = 1.18; 95% CI, 1.01–1.39), and eczema (OR = 1.26; 95% CI, 1.09–1.45) up to 16 years. When age-specific associations were examined, the elevated risks related to SHS exposure in utero or during infancy were mostly confined to early childhood for asthma and rhinitis, whereas the excess risk of eczema appeared greatest at later ages. CONCLUSIONS: Our findings indicate that early SHS exposure, in utero or during infancy, influences the development of allergic disease up to adolescence. Excess risks for asthma and rhinitis were seen primarily in early childhood, whereas those for eczema occurred at later ages.

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure

Background: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation. Objectives: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation. Methods: We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239). Results: We found epigenome-wide significant associations [false discovery rate (FDR) p < 0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p < 0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression. Conclusions: NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways. Citation: Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. 2017. Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environ Health Perspect 125:104–110; http://dx.doi.org/10.1289/EHP36

Elemental composition of particulate matter and the association with lung function.

Background: Negative effects of long-term exposure to particulate matter (PM) on lung function have been shown repeatedly. Spatial differences in the composition and toxicity of PM may explain differences in observed effect sizes between studies. Methods: We conducted a multicenter study in 5 European birth cohorts—BAMSE (Sweden), GINIplus and LISAplus (Germany), MAAS (United Kingdom), and PIAMA (The Netherlands)—for which lung function measurements were available for study subjects at the age of 6 or 8 years. Individual annual average residential exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM smaller than 2.5 &mgr;m (PM2.5) and smaller than 10 &mgr;m (PM10) was estimated using land-use regression models. Associations between air pollution and lung function were analyzed by linear regression within cohorts, adjusting for potential confounders, and then combined by random effects meta-analysis. Results: We observed small reductions in forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow related to exposure to most elemental pollutants, with the most substantial negative associations found for nickel and sulfur. PM10 nickel and PM10 sulfur were associated with decreases in forced expiratory volume in the first second of 1.6% (95% confidence interval = 0.4% to 2.7%) and 2.3% (−0.1% to 4.6%) per increase in exposure of 2 and 200 ng/m3, respectively. Associations remained after adjusting for PM mass. However, associations with these elements were not evident in all cohorts, and heterogeneity of associations with exposure to various components was larger than for exposure to PM mass. Conclusions: Although we detected small adverse effects on lung function associated with annual average levels of some of the evaluated elements (particularly nickel and sulfur), lower lung function was more consistently associated with increased PM mass.