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1.
Handb Exp Pharmacol ; 268: 21-27, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34165634

RESUMO

The prevalences of allergic diseases, asthma, atopic dermatitis, allergic rhinitis and lately food allergy have been increasing over the last decades. It has been suggested that the prevalence of allergic diseases has reached a plateau in high income countries, while it is still on the rise in low and middle income countries. Generally, allergic diseases more often set on in childhood than in adulthood and affected children contribute more to the rise in allergic disease prevalence than affected adults. Epidemiological evidence suggests that not all atopic dermatitis and asthma cases are attributable to atopic sensitization. Indeed, mainly genetic association studies have prompted the unravelling of barrier dysfunction as a mainstay in the patho-mechanisms leading to atopic dermatitis and to asthma with atopic sensitization secondary to this dysfunction. Epidemiological research on risk and protective factors for allergic disease, acting against the background of genetic susceptibility, has produced an enormous body of evidence. Prominent observations are the 'sibling effect' and the 'farm effect' which gave rise to the 'hygiene hypothesis' and later the 'biodiversity hypothesis'. Future epidemiological research is required to evaluate and refine these hypotheses in light of the paradigm shift from atopic sensitization to barrier dysfunction with ever increasing options for environmental characterization, currently, e.g., 'omics'-techniques in microbiology and metabolism, and with ever increasing options for phenotyping of allergic techniques, including, e.g., high-resolution time series of symptoms using, e.g., sensing technologies.


Assuntos
Asma , Dermatite Atópica , Hipersensibilidade Alimentar , Adulto , Asma/epidemiologia , Asma/etiologia , Criança , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Humanos , Prevalência , Fatores de Risco
2.
Nat Commun ; 12(1): 6618, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785669

RESUMO

Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34779040

RESUMO

BACKGROUND: Hand eczema is a common inflammatory skin disorder in both adolescence and adulthood. OBJECTIVES: We sought to assess the lifetime prevalence of hand eczema and associated exogenous and endogenous risk factors among adolescents in Germany. METHODS: This was a cross-sectional study embedded into a prospective population-based birth cohort in four regions of Germany, which recruited healthy neonates born between November 1997 and January 1999. We included 1,736 participants who had completed the 15-year follow-up from birth cohort and 84.6% (1,468/1,736) had clearly reported whether they have ever had hand eczema. All the data was based on questionnaires and blood tests (immunoglobulin E). Multivariable logistic regression analysis was used to examine endogenous and exogenous factors in relation to the lifetime prevalence of hand eczema among adolescents. RESULTS: 1,468 adolescents (715 girls, 48.7%) were included in the final analysis. The lifetime prevalence of hand eczema among adolescents at the age of 15 was 10.4% (95% confidence interval [CI]: 8.9%-12.1%), with a significantly higher lifetime prevalence among girls than boys (12.7% vs. 8.2%, P = 0.005). Multivariable logistic regression analysis indicated statistically significant associations between the lifetime prevalence of hand eczema and having ever been diagnosed with atopic dermatitis (aOR = 1.8, 95% CI: 1.1-2.8) or having ever had dry skin (aOR=1.9, 95% CI: 1.1-3.1), respectively. No statistically significant independent associations were found between asthma, hay fever, allergy-related clinical symptoms, immunoglobulin E positivity and other exogenous factors in relation to hand eczema. CONCLUSION: Our study fills a research gap on the epidemiological burden of hand eczema among adolescents. One out of ten ever suffered from hand eczema until age 15 years indicating that hand eczema constitutes a significant burden in pediatric populations. The role of atopic dermatitis in hand eczema reinforces previous findings. Exogenous risk factors warrant further investigation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34769928

RESUMO

Molar-incisor hypomineralization (MIH) is a condition with specific clinical presentation whose etiology to date still remains unknown. This study prospectively investigated the association between nutrition during the 1st year of life and the presence of MIH in the permanent dentition. Data from 1070 10-year-old children from two prospective birth cohort studies were included. Information on exclusive breastfeeding (EBF) and introduction of 48 food items into the child's diet was assessed at 4-, 6-, and 12-month time-points. Food diversity was defined according to the number of food items or food groups introduced into the child's diet and then subsequent categorization into low-, middle- and high-diversity groups was performed. MIH was scored in the permanent dentition at age of 10 years. The statistical analysis included logistic and Poisson hurdle regression models adjusted for potential confounders. EBF, food item and food group diversity at 4-, 6-, 12-month time-points were found to be non-significant in most of the categories for the development of MIH. However, significantly higher odds for the presence of MIH were found for certain categories. Despite the limitation of this study, such as arbitrary cut-offs for categorization of food items, the results of this study suggest the lack of an association between early nutrition in the first year of life and MIH in the permanent dentition.


Assuntos
Hipoplasia do Esmalte Dentário , Incisivo , Criança , Estudos de Coortes , Hipoplasia do Esmalte Dentário/epidemiologia , Hipoplasia do Esmalte Dentário/etiologia , Dentição Permanente , Humanos , Prevalência , Estudos Prospectivos
5.
Nutrients ; 13(9)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34579168

RESUMO

In any research field, data access and data integration are major challenges that even large, well-established consortia face. Although data sharing initiatives are increasing, joint data analyses on nutrition and microbiomics in health and disease are still scarce. We aimed to identify observational studies with data on nutrition and gut microbiome composition from the Intestinal Microbiomics (INTIMIC) Knowledge Platform following the findable, accessible, interoperable, and reusable (FAIR) principles. An adapted template from the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) consortium was used to collect microbiome-specific information and other related factors. In total, 23 studies (17 longitudinal and 6 cross-sectional) were identified from Italy (7), Germany (6), Netherlands (3), Spain (2), Belgium (1), and France (1) or multiple countries (3). Of these, 21 studies collected information on both dietary intake (24 h dietary recall, food frequency questionnaire (FFQ), or Food Records) and gut microbiome. All studies collected stool samples. The most often used sequencing platform was Illumina MiSeq, and the preferred hypervariable regions of the 16S rRNA gene were V3-V4 or V4. The combination of datasets will allow for sufficiently powered investigations to increase the knowledge and understanding of the relationship between food and gut microbiome in health and disease.


Assuntos
Microbioma Gastrointestinal , Inquéritos Nutricionais , Ciências da Nutrição , Estudos Observacionais como Assunto , Inquéritos sobre Dietas/métodos , Ingestão de Alimentos , Europa (Continente) , Humanos , Disseminação de Informação , Metadados , Inquéritos Nutricionais/métodos , Ciências da Nutrição/métodos
6.
J Clin Med ; 10(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34575235

RESUMO

BACKGROUND: COVID-19-associated restrictions impact societies. We investigated the impact in a large cohort of inflammatory bowel disease (IBD) patients. METHODS: Pediatric (pIBD) and adult patients and pIBD parents completed validated questionnaires for self-perceived stress (Perceived Stress Questionnaire, PSQ) and quality of life from July to October 2020 (1st survey) and March to April 2021 (2nd survey). Analyses were stratified by age groups (6-20, >20-40, >40-60, >60 years). Perceived risk of infection and harm from COVID-19 were rated on a 1-7 scale. An index for severe outcome (SIRSCO) was calculated. Multivariable logistic regression analysis was performed. RESULTS: Of 820 invited patients, 504 (62%, 6-85 years) patients and 86 pIBD parents completed the 1st, thereof 403 (80.4%) the 2nd survey. COVID-19 restrictions resulted in cancelled doctoral appointments (26.7%), decreased physical activity, increased food intake, unintended weight gain and sleep disturbance. PSQ increased with disease activity. Elderly males rated lower compared to females or younger adults. PSQ in pIBD mothers were comparable to moderate/severe IBD adults. Infection risk and harm were perceived high in 36% and 75.4%. Multivariable logistic models revealed associations of higher perceived risk with >3 household members, job conditions and female gender, and of perceived harm with higher SIRSCO, unintended weight change, but not with gender or age. Cancelled clinic-visits were associated with both. SARS-CoV-2 antibodies prior 2nd infection wave were positive in 2/472 (0.4%). CONCLUSIONS: IBD patients report a high degree of stress and self-perceived risk of complications from COVID-19 with major differences related to gender and age. Low seroprevalence may indicate altered immune response.

7.
Clin Nutr ; 40(10): 5339-5345, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34543890

RESUMO

BACKGROUND: Variability in the FADS2 gene, which codifies the Delta-6 Desaturases and modulates the conversion of essential n-3 and n-6 fatty acids into long-chain polyunsaturated fatty acids, might modify the impact of prenatal supplementation with n-3 docosahexaenoic acid (DHA) on neurodevelopment. OBJECTIVE: To assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years. DESIGN: We conducted a post-hoc interaction analysis of the POSGRAD randomized controlled trial (NCT00646360) of prenatal supplementation with algal-DHA where 1094 pregnant women originally randomized to 400 mg/day of preformed algal DHA or a placebo from gestation week 18-22 through delivery. In this analysis, we included offspring with information on maternal genotype and neurodevelopment at 5 years (DHA = 316; Control = 306) and used generalized linear models to assess interactions between FADS2 SNPs rs174602 or rs174575 and prenatal DHA on neurodevelopment at 5 years measured with McCarthy Scales of Children's Abilities (MSCA). RESULTS: Maternal and offspring characteristics were similar between groups. At baseline, mean (±standard deviation) maternal age was 26 ± 5 years and schooling was 12 ± 4 years. Forty-six percent (46%) of the children were female. Maternal minor allele frequencies were 0.37 and 0.33 for SNPs rs174602 and rs174575, respectively. There were significant variations by SNP rs174602 and intervention group (p for interactions <0.05) where children in the intervention group had higher MSCA scores on the quantitative (DHA: mean ± SEM = 22.6 ± 0.9 vs. Control = 19.1 ± 0.9, mean difference (Δ) = 3.45; p = 0.01) and memory (DHA = 27.9 ± 1.1 vs. Control = 23.7 ± 1.1, Δ = 4.26; p = 0.02) scales only among offspring of TT (minor allele homozygotes). CONCLUSIONS: Maternal FADS2 SNP rs174602 modified the effect of prenatal DHA on cognitive development at 5 years. Variations in the genetic make-up of target populations could be an important factor to consider for prenatal DHA supplementation interventions.

8.
Artigo em Alemão | MEDLINE | ID: mdl-34213569

RESUMO

After caries, molar incisor hypomineralisation (MIH)-also known as chalky teeth-is one the most common dental diseases in children and adolescents. In addition to aesthetic limitations, especially on the anterior teeth, hypersensitivities and enamel breakdowns on permanent molars are of functional importance. While the MIH prevalence rates range from ~ 10% to ~ 30% and is well described, the situation regarding aetiology is unsatisfactory. Although efforts have been made in the past to clarify the aetiology, no plausible reason is available so far. Aetiology research has to be judged as methodologically challenging, since it should ideally be embedded in prospectively planned birth cohort studies. The aim of this article is to summarize typical clinical characteristics of MIH, epidemiological findings and potential causes with special reference to the earlier published results from the two Munich birth cohort studies GINIplus and LISA.


Assuntos
Hipoplasia do Esmalte Dentário , Incisivo , Adolescente , Criança , Hipoplasia do Esmalte Dentário/diagnóstico , Hipoplasia do Esmalte Dentário/epidemiologia , Hipoplasia do Esmalte Dentário/etiologia , Alemanha/epidemiologia , Humanos , Dente Molar , Prevalência
9.
Artigo em Inglês | MEDLINE | ID: mdl-34063674

RESUMO

The aim of this study was to determine the proportion of adolescents with severe caries to analyze the prevalence of caries and to visualize the unequal distribution. Data from three epidemiological studies (10- and 15-year-olds: GINIplus and LISA cohorts in Munich, Bavaria; 12-year-olds: LAGZ survey in Bavaria, Germany) with 2875 adolescents were available for analysis. All individuals were examined according to the WHO standard. Statistics included the calculation of mean dmft/DMFT values (standard deviation), Significant Caries Index (SiC) values, Specific Affected Caries Index (SaC) values, and Lorenz curves. Overall caries-free status was 58.6% in primary and 83.9% in secondary teeth (10-year-olds), 61.5% (12-year-olds), and 64.6% (15-year-olds). The proportion of 12- and 15-year-olds with at least four DMFTs was 9.4% and 8.3%, respectively. In addition, eight 15-year-olds with DMFT values ≥8 (0.6%) were registered. The SaC/SiC values amounted to 1.8/0.9 DMFT (10-year-olds), 2.6/2.8 DMFT (12-year-olds), and 2.5/2.5 DMFT (15-year-olds). The mean DMFT values in the upper 1% of subjects were 4.2 DMFT (10-year-olds), 8.5 DMFT (12-year-olds), and 8.5 DMFT (15-year-olds). Thus, caries is not equally distributed throughout adolescence, but individuals with severe caries are rare. Nevertheless, further interdisciplinary research seems to be needed to clarify potential risk factors.


Assuntos
Suscetibilidade à Cárie Dentária , Cárie Dentária , Adolescente , Criança , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Alemanha/epidemiologia , Humanos , Prevalência , Fatores de Risco
10.
J Nutr ; 151(8): 2317-2329, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-33847346

RESUMO

BACKGROUND: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined. OBJECTIVE: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data. METHODS: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI. RESULTS: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91 mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age. CONCLUSIONS: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.

11.
Sci Rep ; 11(1): 5341, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674692

RESUMO

Living with dogs appears to protect against allergic diseases and airway infections, an effect possibly linked with immunomodulation by microbial exposures associated with dogs. The aim of this study was to characterize the influence of dog ownership on house dust microbiota composition. The bacterial and fungal microbiota was characterized with Illumina MiSeq sequencing from floor dust samples collected from homes in a Finnish rural-suburban (LUKAS2, N = 182) birth cohort, and the results were replicated in a German urban (LISA, N = 284) birth cohort. Human associated bacteria variable was created by summing up the relative abundances of five bacterial taxa. Bacterial richness, Shannon index and the relative abundances of seven bacterial genera, mostly within the phyla Proteobacteria and Firmicutes, were significantly higher in the dog than in the non-dog homes, whereas the relative abundance of human associated bacteria was lower. The results were largely replicated in LISA. Fungal microbiota richness and abundance of Leucosporidiella genus were higher in dog homes in LUKAS2 and the latter association replicated in LISA. Our study confirms that dog ownership is reproducibly associated with increased bacterial richness and diversity in house dust and identifies specific dog ownership-associated genera. Dogs appeared to have more limited influence on the fungal than bacterial indoor microbiota.

12.
Environ Int ; 152: 106476, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33714142

RESUMO

BACKGROUND: Air pollution is hypothesized to affect pubertal development. However, the few studies on this topic yielded overall mixed results. These studies did not consider important pollutants like ozone, and none of them involved pubertal development assessed by estradiol and testosterone measurements. We aimed to analyze associations between long-term exposure to four pollutants and pubertal development based on sex hormone concentrations among 10-year-old children. METHODS: These cross-sectional analyses were based on the 10-year follow-up medical examinations of 1945 children from the Munich and Wesel centers of the GINIplus and LISA German birth cohorts. Female and male pubertal development was assessed by dichotomizing the concentration of hormones in serum at 18.4 pmol/L and 0.087 nmol/L using the lower limits of quantification for estradiol and testosterone, respectively. Land-use regression models derived annual average concentrations of particulate matter with an aerodynamic diameter < 2.5 and 10 µm (PM2.5 and PM10), as well as spatial models assessed yearly average concentrations of nitrogen dioxide (NO2) and ozone, were calculated at the 10-year residential addresses. To evaluate associations, we utilized logistic regressions adjusted for potential covariates. The analyses were stratified by area and sex. RESULTS: Around 73% of the 943 females and 25% of the 1002 males had a high level of hormones and had already started puberty at the age of 10. Overall, we found no statistically significant associations between exposure to particles (PM2.5 or PM10) and pubertal development. Results on NO2 and ozone were not significant as well; for instance, per 10 µg/m3 increase in ozone concentration, odds ratios and 95% confidence intervals were 0.900 (0.605, 1.339) and 0.830 (0.573, 1.203) for females and males, respectively. Stratified by area, the aforementioned results did not reveal any associations either. CONCLUSIONS: Our study did not observe the associations between ambient air pollutants and pubertal development determined by estradiol and testosterone levels in children. However, due to the current limited number of studies on this topic, our results should be cautiously interpreted. Future longitudinal studies are needed to assess the association.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Estudos Transversais , Exposição Ambiental/análise , Feminino , Hormônios , Humanos , Masculino , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade
13.
Chest ; 160(1): 249-258, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33581096

RESUMO

BACKGROUND: Abnormal weights, eg, obesity, has shown a strong modifying effect on the association between air pollution exposure and lung function impairment in adults. RESEARCH QUESTION: How might weight status modify the effects of long-term air pollution exposure on adolescents' lung function, particularly in areas with pollution levels much lower than the current European Union (EU) air quality standards? STUDY DESIGN AND METHODS: In this observational study, we investigated 2,224 adolescents from the German Infant Study on the Influence of Nutrition Intervention Plus Environmental and Genetic Influences on Allergy Development and the Influence of Life Style Factors on the Development of the Immune System and Allergies in East and West Germany birth cohorts. Lung function was measured at age 15 years. Underweight, normal weight, and overweight or obese were defined using percentiles of BMI. Average concentrations of air pollution were modelled at residential addresses at four exposure windows between 0 and 15 years. Multivariate linear regression models were fitted by weight group on lung function with exposure at each window or cumulative exposure since birth. RESULTS: The median air pollution concentrations were half to two-thirds of the EU standards. Significant associations were observed only for individuals who were underweight and overweight or obese. For example, per interquartile range increase in nitrogen dioxide at the 15-year exposure window, FEV1 declined by -2.9% (95% CI, -5.2% to -0.5%) for the underweight group and -3.4% (95% CI, -5.4% to -1.2%) for the overweight or obese group. Similarly, longer exposure to moderate-level air pollution since birth was associated significantly with lung function impairment for groups with abnormal weight. INTERPRETATION: Exposure to low to moderate levels of air pollution was associated with lung function impairment for adolescents with abnormal weight. Longer exposure aggravated the adverse effect. Whether a critical exposure window since birth exists warrants further exploration.


Assuntos
Poluição do Ar/efeitos adversos , Anticoncepção/métodos , Exposição Ambiental/efeitos adversos , Pneumopatias/epidemiologia , Pulmão/fisiopatologia , Sobrepeso/complicações , Adolescente , Europa (Continente)/epidemiologia , União Europeia , Feminino , Seguimentos , Humanos , Incidência , Pneumopatias/etiologia , Masculino , Material Particulado/efeitos adversos , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Tempo
14.
Environ Res ; 196: 110835, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33582132

RESUMO

BACKGROUND: Microbial exposures in early childhood direct the development of the immune system and their diversity may influence the risk of allergy development. We aimed to determine whether the indoor microbial diversity at early-life is associated with the development of allergic rhinitis and inhalant atopy. METHODS: The study population included children within two birth cohorts: Finnish rural-suburban LUKAS (N = 312), and German urban LISA from Munich and Leipzig study centers (N = 248). The indoor microbiota diversity (Chao1 richness and Shannon entropy) was characterized from floor dust samples collected at the child age of 2-3 months by Illumina MiSeq sequencing of bacterial and fungal DNA amplicons. Allergic rhinitis and inhalant atopy were determined at the age of 10 years and analyzed using logistic regression models. RESULTS: High bacterial richness (aOR 0.19, 95%CI 0.09-0.42 for middle and aOR 0.12, 95%CI 0.05-0.29 for highest vs. lowest tertile) and Shannon entropy were associated with lower risk of allergic rhinitis in LISA, and similar trend was seen in LUKAS. We observed some significant associations between bacterial and fungal diversity measured and the risk of inhalant atopy, but the associations were inconsistent between the two cohorts. High bacterial diversity tended to be associated with increased risk of inhalant atopy in rural areas, but lower risk in more urban areas. Fungal diversity tended to be associated with increased risk of inhalant atopy only in LISA. CONCLUSIONS: Our study suggests that a higher bacterial diversity may reduce the risk of allergic rhinitis later in childhood. The environment-dependent heterogeneity in the associations with inhalant atopy - visible here as inconsistent results between two differing cohorts - suggests that specific constituents of the diversity may be relevant.


Assuntos
Hipersensibilidade Imediata , Microbiota , Rinite Alérgica , Alérgenos , Criança , Pré-Escolar , Poeira/análise , Fungos , Humanos , Lactente , Rinite Alérgica/epidemiologia
15.
Hum Mol Genet ; 30(5): 393-409, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33517400

RESUMO

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.


Assuntos
Estudo de Associação Genômica Ampla , Cadeias HLA-DRB1/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1/genética , Interleucina-6/genética , Receptores de Interleucina-6/genética , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Regulação da Expressão Gênica , Loci Gênicos , Predisposição Genética para Doença , Humanos , Interleucina-6/sangue , Polimorfismo de Nucleotídeo Único
16.
Environ Int ; 146: 106195, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33099064

RESUMO

BACKGROUND: Limited evidence exists on how air pollution exposure during infancy, i.e. the first year of life, may affect lung function development into adolescence. OBJECTIVES: To investigate the association between exposure to air pollution during the first-year of life and lung function development up to the age of 15 in Germany. METHODS: We investigated 915 children from the GINIplus and LISA birth cohorts from Munich (n = 181) and Wesel (n = 734), who had at least two spirometric measurements at ages 6, 10 and 15. Z-scores of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were calculated. Annual average concentrations of nitrogen dioxide, particulate matter with diameters <2.5, <10 and 2.5-10 µm (PM2.5/10/coarse), and PM2.5 absorbance at home addresses during the first-year of life, were estimated by land-use regression models. Associations between infancy exposure and lung function changes were fitted using multivariable linear mixed models with adjustment for potential confounders. RESULTS: For per interquartile range increase in air pollutants during the first-year life, FEV1 z-scores declined annually by -0.012 (95% confidence interval (CI): -0.014, -0.009) for PM2.5 to -0.023 (95%CI: -0.028, -0.018) for PMcoarse. The declines in FVC were lower than FEV1 [-0.006 (95%CI: -0.008, -0.003) to -0.011 (95%CI: -0.019, -0.003)]. In Munich, the attenuations were only significant for FEV1. Effect estimates of infancy exposure for certain air pollutants were higher for groups with asthma, older maternal age, and breastfeeding <12 weeks than their counterparts. DISCUSSION: Infancy exposure to higher air pollution may reduce lung function development up to adolescence, with airway size more affected than lung volume restriction. The potential modifying effects of maternal age, asthmatic status of children and breastfeeding warrant further exploration.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adolescente , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Exposição Ambiental/análise , Volume Expiratório Forçado , Alemanha , Humanos , Lactente , Pulmão , Material Particulado/análise
17.
J Allergy Clin Immunol ; 147(2): 713-722, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32926877

RESUMO

BACKGROUND: Whether long-term exposure air to pollution has effects on allergic sensitization is controversial. OBJECTIVE: Our 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. METHODS: A 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). RESULTS: Air 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). CONCLUSION: Air 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.


Assuntos
Poluição do Ar/efeitos adversos , Hipersensibilidade/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Recém-Nascido , Masculino
18.
Sci Total Environ ; 763: 143006, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33131877

RESUMO

BACKGROUND: Pollen exposure has both acute and chronic detrimental effects on allergic asthma, but little is known about its wider effects on respiratory health. This is increasingly important knowledge as ambient pollen levels are changing with the changing global climate. OBJECTIVE: To assess associations of pollen exposure with lung function and fractional exhaled nitric oxide (FeNO) at age 15 in two prospective German birth cohorts, GINIplus and LISA. METHODS: Background city-specific pollen exposure was measured in infancy (during the first three months of life), and contemporary (on the day of and 7 days prior to lung function measurement). Greenness levels within circular buffers (100-3000 m) around the birth and 15-year home addresses were calculated using the satellite-derived Normalized Difference Vegetation Index. Regression models were used to assess the associations of grass and birch pollen with lung function and FeNO, and the modifying effects of residential greenness were explored. RESULTS: Cumulative early life exposure to grass pollen was associated with reduced lung function in adolescence (FEV1: -4.9 mL 95%CI: -9.2, -0.6 and FVC: -5.2 mL 95%CI: -9.8, -0.5 per doubling of pollen count). Acute grass pollen exposure was associated with increased airway inflammation in all children, with higher FeNO increases in children living in green areas. In contrast acute birch pollen exposure was associated with reduced lung function only in children sensitised to birch allergens. CONCLUSION: This study provides suggestive evidence that early pollen exposure has a negative effect on later lung function, which is in turn influenced by acute pollen exposures.


Assuntos
Expiração , Óxido Nítrico , Adolescente , Criança , Humanos , Pulmão , Pólen , Estudos Prospectivos
19.
Allergy ; 76(4): 1158-1172, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32794228

RESUMO

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin disease in children, with 30% of all those diagnosed developing chronic or relapsing disease by adolescence. Such disease persistence cannot yet be predicted. The aim of the present study was to predict the natural course of AD using clinical parameters and serum proteins. METHODS: Sera of 144 children with AD (age 0-3 years) were analyzed for IgE and 33 cytokines, chemokines, and growth factors. Patient disease course until the age of 7 years was assessed retrospectively. Unsupervised k-means clustering was performed to define disease endotypes. Identified factors associated with AD persistence at the age of 7 years were validated in children with AD in an independent cohort (LISA Munich; n = 168). Logistic regression and XGBoosting methods followed by cross-validation were applied to predict individual disease outcomes. RESULTS: Three distinct endotypes were found in infancy, characterized by a unique inflammatory signature. Factors associated with disease persistence were disease score (SCORAD), involvement of the limbs, flexural lesion distribution at the age of 3 years, allergic comorbidities, and disease exacerbation by the trigger factors stress, pollen exposure, and change in weather. Persistence was predicted with a sensitivity of 81.8% and a specificity of 82.4%. Factors with a high impact on the prediction of persistence were SCORAD at the age of 3 years, trigger factors, and low VEGF serum levels. CONCLUSION: Atopic dermatitis in infancy comprises three immunological endotypes. Disease persistence can be predicted using serum cytokines and clinical variables.


Assuntos
Dermatite Atópica , Eczema , Adolescente , Proteínas Sanguíneas , Criança , Pré-Escolar , Citocinas , Dermatite Atópica/diagnóstico , Dermatite Atópica/epidemiologia , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Índice de Gravidade de Doença
20.
Environ Int ; 146: 106248, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33212358

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adolescente , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Metilação de DNA , Exposição Ambiental/análise , Epigenômica , Humanos , Material Particulado/análise , Material Particulado/toxicidade
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