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Träfflista för sökning "WFRF:(Koppelman Gerard H.) srt2:(2020-2022);pers:(Melén Erik)"

Sökning: WFRF:(Koppelman Gerard H.) > (2020-2022) > Melén Erik

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1.
  • Wang, Gang, et al. (författare)
  • Spirometric phenotypes from early childhood to young adulthood : a Chronic Airway Disease Early Stratification study
  • 2021
  • Ingår i: ERJ Open Research. - : ERS Publications. - 2312-0541. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.Methods: We studied 49334 participants from 14 population-based cohorts in different age groups (⩽10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ⩾LLN, and FVC z-score Results: The prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio (aOR=2.55, 95% CI 2.14–3.04), preterm birth (aOR=1.84, 1.27–2.66), maternal smoking during pregnancy (aOR=1.16, 95% CI 1.01–1.35) and family history of asthma (aOR=1.44, 95% CI 1.25–1.66) were associated with a higher prevalence of obstructive, but not restrictive, phenotype across ages (5–25 years). A higher current body mass index (BMI was more often observed in those with the obstructive phenotype but less in those with the restrictive phenotype (aOR=1.05, 95% CI 1.03–1.06 and aOR=0.81, 95% CI 0.78–0.85, per kg·m−2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46).Conclusion: Obstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.
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2.
  • Acevedo, Nathalie, et al. (författare)
  • DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life
  • 2021
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:2
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p <= 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.
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3.
  • Lemonnier, Nathanaël, et al. (författare)
  • A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
  • 2020
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:12, s. 3248-3260
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.
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4.
  • Melén, Erik, et al. (författare)
  • Air pollution and IgE sensitization in 4 European birth cohorts : the MeDALL project
  • 2021
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 147:2, s. 713-722
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWhether long-term exposure air to pollution has effects on allergic sensitization is controversial.ObjectiveOur aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years.MethodsA total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 μm, less than 10 μm, and between 2.5 and 10 μm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021).ResultsAir pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-μg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-μg/m3 increase in exposure).ConclusionAir pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.
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5.
  • Melén, Erik, et al. (författare)
  • Allergies to food and airborne allergens in children and adolescents : role of epigenetics in a changing environment
  • 2022
  • Ingår i: The Lancet Child & Adolescent Health. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 2352-4642. ; 6:11, s. 810-819
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic diseases today affect millions of children and adolescents worldwide. In this review, we focus on allergies to food and airborne allergens, and provide examples of prevalence trends during a time when climate change is of increasing concern. Profound environmental changes have affected natural systems in terms of biodiversity loss, air pollution levels and climate change. We discuss potential links between these changes and allergic diseases in children, as well as clinical implications. Several exposures of relevance for allergic disease also correlate with epigenetic changes such as DNA-methylation levels. We propose that epigenetics may offer a promising tool by which exposures and hazards related to a changing environment may be captured. Epigenetics may also provide promising biomarkers and help elucidation of mechanisms related to allergic disease initiation and progress. Key messages: • Allergic diseases affect millions of children and adolescents worldwide; between 5 and 30% of adolescents report rhino-conjunctivitis symptoms and up to 10 % report food allergy. • Links between climate change and allergic diseases are of increasing concern, and these include: extended and altered pollen seasons, spread of allergens to new areas along with changing and warmer climate, air pollution exposures changes, increasing exposure to heat events, and altered biodiversity. • These new climate change aspects of allergic diseases have clinical implications for prevention, diagnostics and treatment. • Epigenetic changes, exemplified by DNA methylation, are associated both with environmental exposures and allergic diseases, although causality needs to be explored further. • There is potential in the use of epigenetic signatures and omics profiles to detect and monitor aspects of environmental exposures of relevance for health and disease in children and adolescents.
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6.
  • Merid, Simon Kebede, et al. (författare)
  • Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
  • 2020
  • Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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7.
  • Merid, Simon Kebede, et al. (författare)
  • Integration of gene expression and DNA methylation identifies epigenetically controlled modules related to PM2.5 exposure
  • 2020
  • Ingår i: Environment International. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 0160-4120 .- 1873-6750.
  • Tidskriftsartikel (refereegranskat)abstract
    • Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.
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