Epidemiological studies have identified associations between air pollution and green space access with type 2 diabetes in adults. However, it remains unclear to what extent associations with ...greenness are attributable to air pollution exposure.
We aimed to investigate associations between long-term exposure to air pollution and satellite-derived greenness with insulin resistance in adolescents.
A total of 837 participants of two German birth cohorts (LISAplus and GINIplus) were included in the analysis. Generalized additive models were used to determine the association of individual satellite-derived greenness defined by the Normalized Difference Vegetation Index (NDVI), long-term air pollution exposure estimated by land-use regression (LUR) models with insulin resistance (HOMA-IR) in 15-year-old adolescents. Models were adjusted for study area, cohort, socioeconomic, and individual characteristics such as body mass index, physical activity, and smoking.
Increases of 2 SDs in nitrogen dioxide (NO2; 8.9 μg/m3) and particulate matter ≤ 10 μm in diameter (PM10; 6.7 μg/m3) were significantly associated with 11.4% (95% CI: 4.4, 18.9) and 11.4% (95% CI: 0.4, 23.7) higher HOMA-IR. A 2-SD increase in NDVI in a 1,000-m buffer (0.2 units) was significantly associated with a lower HOMA-IR (-7.4%; 95% CI: -13.3, -1.1). Associations tended to be stronger in adolescents who spent more time outside and in those with lower socioeconomic status. In combined models including both air pollution and greenness, only NO2 remained significantly associated with HOMA-IR, whereas effect estimates for all other exposures attenuated after adjustment for NO2.
NO2, often considered as a marker of traffic, was independently associated with insulin resistance. The observed association between higher greenness exposure and lower HOMA-IR in adolescents might thus be attributable mainly to the lower co-exposure to traffic-related air pollution.
Thiering E, Markevych I, Brüske I, Fuertes E, Kratzsch J, Sugiri D, Hoffmann B, von Berg A, Bauer CP, Koletzko S, Berdel D, Heinrich J. 2016. Associations of residential long-term air pollution exposures and satellite-derived greenness with insulin resistance in German adolescents. Environ Health Perspect 124:1291-1298; http://dx.doi.org/10.1289/ehp.1509967.
Asthma is caused by a combination of poorly understood genetic and environmental factors. We have systematically mapped the effects of single nucleotide polymorphisms (SNPs) on the presence of ...childhood onset asthma by genome-wide association. We characterized more than 317,000 SNPs in DNA from 994 patients with childhood onset asthma and 1,243 non-asthmatics, using family and case-referent panels. Here we show multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P value of P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P < 10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encodes transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.
Background
Allergic diseases often develop jointly during early childhood but differ in timing of onset, remission, and progression. Their disease course over time is often difficult to predict and ...determinants are not well understood.
Objectives
We aimed to identify trajectories of allergic diseases up to adolescence and to investigate their association with early‐life and genetic determinants and clinical characteristics.
Methods
Longitudinal k‐means clustering was used to derive trajectories of allergic diseases (asthma, atopic dermatitis, and rhinitis) in two German birth cohorts (GINIplus/LISA). Associations with early‐life determinants, polygenic risk scores, food and aeroallergen sensitization, and lung function were estimated by multinomial models. The results were replicated in the independent Swedish BAMSE cohort.
Results
Seven allergic disease trajectories were identified: “Intermittently allergic,” “rhinitis,” “early‐resolving dermatitis,” “mid‐persisting dermatitis,” “multimorbid,” “persisting dermatitis plus rhinitis,” and “early‐transient asthma.” Family history of allergies was more prevalent in all allergic disease trajectories compared the non‐allergic controls with stronger effect sizes for clusters comprising more than one allergic disease (e.g., RRR = 5.0, 95% CI = 3.1–8.0 in the multimorbid versus 1.8 1.4–2.4 in the mild intermittently allergic cluster). Specific polygenic risk scores for single allergic diseases were significantly associated with their relevant trajectories. The derived trajectories and their association with genetic effects and clinical characteristics showed similar results in BAMSE.
Conclusion
Seven robust allergic clusters were identified and showed associations with early life and genetic factors as well as clinical characteristics.
We identified seven allergic disease trajectories up to adolescence, which are corresponding to clinical observation in the German GINIplus and LISA studies and replicated the results in the Swedish BAMSE cohort. The clusters can be characterized using polygenic risk scores and early‐life determinants, which support the hygiene hypothesis. The clusters also pose clinical implications for allergic sensitization, increasing with number of present allergic diseases, and lung function.Abbreviations: BAMSE, Barn/Child Allergy Milieu Stockholm Epidemiology; GINIplus, German Infant Study on the Influence of Nutrition Intervention plus Air pollution and Genetics on Allergy Development; LISA, Influence of Life‐style factors on Development of the Immune System and Allergies in East and West Germany study; PRS, polygenic risk score.
Background The long-term effect of nutritional intervention with hydrolysate infant formulas on allergic manifestations in high-risk children is uncertain. Objective We sought to investigate the ...effect of hydrolysate infant formulas on allergic phenotypes in children with family history of allergies at school age. Methods We analyzed data from participants of the prospective German Infant Nutritional Intervention study after 10 years of follow-up. At birth, children were randomly assigned to receive, for the first 4 months, one of 4 blinded formulas as breast milk substitute, if necessary: partially hydrolyzed whey formula (pHF-W), extensively hydrolyzed whey formula (eHF-W), extensively hydrolyzed casein formula (eHF-C), or standard cow's milk formula. Outcomes were parent-reported, physician-diagnosed allergic diseases. Log-binomial regression models were used for statistical analysis. Results The relative risk for the cumulative incidence of any allergic disease in the intention-to-treat analysis (n = 2252) was 0.87 (95% CI, 0.77-0.99) for pHF-W, 0.94 (95% CI, 0.83-1.07) for eHF-W, and 0.83 (95% CI, 0.72-0.95) for eHF-C compared with standard cow's milk formula. The corresponding figures for atopic eczema/dermatits (AD) were 0.82 (95% CI, 0.68-1.00), 0.91 (95% CI, 0.76-1.10), and 0.72 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis (n = 988) effects were stronger. The period prevalence of AD at 7 to 10 years was significantly reduced with eHF-C in this analysis, but there was no preventive effect on asthma or allergic rhinitis. Conclusion The significant preventive effect on the cumulative incidence of allergic diseases, particularly AD, with pHF-W and eHF-C persisted until 10 years without rebound, whereas eHF-W showed no significant risk reduction. There is insufficient evidence of ongoing preventive activity at 7 to 10 years of age.
Background
Childhood asthma is a result of a complex interaction of genetic and environmental components causing epigenetic and immune dysregulation, airway inflammation and impaired lung function. ...Although different microarray based EWAS studies have been conducted, the impact of epigenetic regulation in asthma development is still widely unknown. We have therefore applied unbiased whole genome bisulfite sequencing (WGBS) to characterize global DNA‐methylation profiles of asthmatic children compared to healthy controls.
Methods
Peripheral blood samples of 40 asthmatic and 42 control children aged 5–15 years from three birth cohorts were sequenced together with paired cord blood samples. Identified differentially methylated regions (DMRs) were categorized in genotype‐associated, cell‐type‐dependent, or prenatally primed. Network analysis and subsequent natural language processing of DMR‐associated genes was complemented by targeted analysis of functional translation of epigenetic regulation on the transcriptional and protein level.
Results
In total, 158 DMRs were identified in asthmatic children compared to controls of which 37% were related to the eosinophil content. A global hypomethylation was identified affecting predominantly enhancer regions and regulating key immune genes such as IL4, IL5RA, and EPX. These DMRs were confirmed in n = 267 samples and could be linked to aberrant gene expression. Out of the 158 DMRs identified in the established phenotype, 56 were perturbed already at birth and linked, at least in part, to prenatal influences such as tobacco smoke exposure or phthalate exposure.
Conclusion
This is the first epigenetic study based on whole genome sequencing to identify marked dysregulation of enhancer regions as a hallmark of childhood asthma.
Whole‐genome bisulfite sequencing in whole blood identifies 158 DMRs related to childhood‐asthma predominantly affecting enhancer regions, including an enhancer for IL‐4. Global DNA‐hypomethylation in the asthma‐phenotype affects key immune genes such as IL5RA or EPX. 35% of the aberrant DNA‐methylation in asthma is already present in cord blood, which is partially related to adverse prenatal influences such as tobacco smoke exposure.Abbreviations: DMR, differentially methylated region, EPX, eosinophil peroxidase; IL5RA, interleukin 5 receptor subunit alpha; LINA, Lifestyle and environmental factors and their influence on newborns allergy risk; LISA, Lifestyle‐related factors on the immune system and the development of allergies in childhood; PASTURE, Protection against allergy: study in rural environments
We investigated the association between surrounding greenness at the mother's residential address at the time of delivery and birth weight in two German birth cohorts and explored potential ...underlying hypotheses.
Complete data on 3203 newborns, recruited in Munich between 1996 and 1999, were available. Surrounding greenness was defined using the mean of the Normalized Difference Vegetation Index, which was derived from Landsat 5TM satellite images.
An interquartile increase of surrounding greenness in a 500-m buffer was associated with an average birth weight increase of 17.6g (95% CI=0.5 to 34.6). The effect strengthened after individual adjustment for NO2, PM2.5, distance to major road and population density. The strongest association was found for mothers with less than 10 years of school education. The results remained robust when additionally adjusted for noise or maternal stress during pregnancy. Neighbourhood green spaces were not associated with birth weight.
Surrounding greenness at the birth address was positively associated with birth weight in two birth cohorts in Munich. The mechanisms driving this association remain unclear and warrant further investigation.
•Surrounding greenness at the mother's residence at the time of delivery was positively associated with the birth weight of newborns•Air pollution, noise, population density and maternal stress during pregnancy do not appear to be influential factors for this association.•Increased accessibility to green spaces does not explain the observed association with greenness.
Atopic dermatitis (AD) primarily affects infants and young children. Although topical corticosteroids (TCSs) are often prescribed, noncorticosteroid treatments are needed because compliance with TCSs ...is poor due to concerns about their side effects. In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD, pimecrolimus 1% cream (PIM) was compared with TCSs.
A total of 2418 infants were enrolled in this 5-year open-label study. Infants were randomized to PIM (n = 1205; with short-term TCSs for disease flares) or TCSs (n = 1213). The primary objective was to compare safety; the secondary objective was to document PIM's long-term efficacy. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear).
Both PIM and TCSs had a rapid onset of action with >50% of patients achieving treatment success by week 3. After 5 years, >85% and 95% of patients in each group achieved overall and facial treatment success, respectively. The PIM group required substantially fewer steroid days than the TCS group (7 vs 178). The profile and frequency of adverse events was similar in the 2 groups; in both groups, there was no evidence for impairment of humoral or cellular immunity.
Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. PIM was steroid-sparing. The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children.
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