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1.
Aging (Albany NY) ; 12(16): 16539-16554, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747609

RESUMO

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32645895

RESUMO

Increasing evidence suggests adults living in greener areas tend to have more favourable sleep-related outcomes, but children and adolescents are under-researched. We hypothesised that children and adolescents living in greener areas would have better quality and more sufficient levels of sleep on average, especially within the context of high traffic noise exposure. These hypotheses were tested using multilevel logistic regressions fitted on samples from the nationally representative Longitudinal Study of Australian Children (10-11 years old, n = 3469, and 14-15 years old, n = 2814) and the GINIplus and LISA cohorts (10 years old, n = 1461, and 15 years old, n = 4172) from the Munich, Wesel, and Leipzig areas of Germany. Questionnaire-based binary indicators of sleep sufficiency and sleep quality in each cohort were assessed with respect to objectively measured green space exposures adjusting for age, sex, and maternal education. Models were augmented with proxy measures of traffic noise and two-way interaction terms to test for effect modification. Cross-tabulations illustrated little convincing evidence of association between green space and insufficient sleep or poor sleep quality in either sample, except for insufficient sleep among 10 year old participants in Germany. These null findings were replicated in adjusted models. The proxy for traffic noise was associated with poor quality sleep in 15 year old participants in Germany, but no convincing evidence of modified association with green space was observed.


Assuntos
Sono/fisiologia , Adolescente , Austrália , Ambiente Construído , Criança , Estudos de Coortes , Meio Ambiente , Feminino , Alemanha , Humanos , Estudos Longitudinais , Masculino , Parques Recreativos , Qualidade de Vida , Características de Residência/estatística & dados numéricos
3.
Sleep Med ; 72: 65-74, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32554326

RESUMO

STUDY OBJECTIVES: Population-based studies on the association of objectively assessed physical activity (PA) with sleep among adolescents are rare. We examined this association by applying accelerometry and accounting for the day-by-day variability. METHODS: Accelerometers (Actigraph GT3X) were worn for one week by 1223 participants during the 15-year follow-up of the German birth cohorts (German infant study on the Influence of Nutrition Intervention plus air pollution and genetics on allergy development, GINIplus) and (Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany, LISA) to measure PA and sleep. PA was categorised into sedentary, lifestyle and moderate-to-vigorous physical activity (MVPA) referring to Sasaki and Romanzini. Sleep was analysed according to the algorithm developed by Sadeh. Sleep quality was represented by sleep efficiency (SE), sleep onset latency (SOL) and time awake per hour after sleep onset (TAPH). Sleep and activity were additionally reported by diaries. Linear and generalized mixed-effects-models with logit-link with subject specific random intercepts were used stratified by sex and adjusted for confounding variables. RESULTS: Physical activity appears to be associated only with sleep quality the following night. Among female participants, SE improved (ß = 0.12 [95% CI = (0.05; 0.18)]) per 10 minutes increase of MVPA. SOL decreased (OR = 0.83 [95% CI = (0.69; 0.99)]) among male participants with at least 60 min of MVPA per day. Engaging in leisure sport MVPA was associated with higher SE among female (ß = 0.70 [95% CI = (0.22; 1.17)]) and male participants (ß = 0.76 [95% CI = (0.18; 1.34)]). Also, TAPH among female (ß = -0.37 [95% CI = (-0.65; -0.09)]) and SOL among male subjects (OR = 0.70 [95% CI = (0.57; 0.85)]) decreased. Increasing lifestyle activity was related to longer SOL among female (OR = 1.36 [95% CI = (1.15; 1.62)]) and male subjects (OR = 1.32 [95% CI = (1.10; 1.58)]). CONCLUSIONS: In this large population-based sample of German adolescents MVPA and leisure sport improved short term sleep quality, supporting regular PA in adolescents for their health benefit.

4.
Int J Behav Nutr Phys Act ; 17(1): 38, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32183834

RESUMO

BACKGROUND: Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe. METHODS: Six databases were systematically searched to identify pan-European and national data sets on physical activity and sedentary time assessed by the same accelerometer in children (2 to 9.9 years) and adolescents (≥10 to 18 years). We harmonized individual-level data by reprocessing hip-worn raw accelerometer data files from 30 different studies conducted between 1997 and 2014, representing 47,497 individuals (2-18 years) from 18 different European countries. RESULTS: Overall, a maximum of 29% (95% CI: 25, 33) of children and 29% (95% CI: 25, 32) of adolescents were categorized as sufficiently physically active. We observed substantial country- and region-specific differences in physical activity and sedentary time, with lower physical activity levels and prevalence estimates in Southern European countries. Boys were more active and less sedentary in all age-categories. The onset of age-related lowering or leveling-off of physical activity and increase in sedentary time seems to become apparent at around 6 to 7 years of age. CONCLUSIONS: Two third of European children and adolescents are not sufficiently active. Our findings suggest substantial gender-, country- and region-specific differences in physical activity. These results should encourage policymakers, governments, and local and national stakeholders to take action to facilitate an increase in the physical activity levels of young people across Europe.


Assuntos
Acelerometria , Exercício Físico/fisiologia , Comportamento Sedentário , Adolescente , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino
5.
Caries Res ; 54(1): 87-95, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31786571

RESUMO

This epidemiological study aimed to compare the caries and molar incisor hypomineralisation (MIH) experience in asthmatic and non-asthmatic adolescents assessed at 10 and 15 years of age. 730 adolescents from ongoing birth cohort studies (GINIplus/LISA) from Munich, Germany, were examined for carious lesions at the age of 10 and 15 years to determine caries experience under inclusion of non-cavitated carious lesions D1-2T and the tooth-related decay-missing-filled index. Furthermore, MIH was scored on all permanent teeth according to the criteria of the European Academy of Paediatric Dentistry. The association between caries and MIH prevalence at the 10-year and 15-year follow-up as well as caries incidence with ever having an asthma diagnosis was analysed using hurdle regression models adjusted for potential confounders. Of the 730 adolescents, 52 and 78 were identified as asthmatics at the 10- and 15-year follow-up, respectively. There were no significant differences in caries prevalence or experience between asthma-free participants and any of the asthma groups (taking metered-dose inhaler (MDI) medication vs. taking no MDI medication). However, a significant positive association was found for asthmatic adolescents who did not take MDI medication with higher MIH/T values (OR = 2.56, 95% CI = 1.03-6.37, p = 0.043) compared to non-asthmatics. In conclusion, asthma did not influence the caries status of adolescents in the present study. Interestingly, a significant association was found between adolescents with asthma who did not take MDI medication and the number of MIH-affected teeth. The association between asthma, medication, and MIH needs further confirmation.


Assuntos
Asma , Cárie Dentária , Hipoplasia do Esmalte Dentário , Adolescente , Asma/complicações , Asma/epidemiologia , Criança , Cárie Dentária/epidemiologia , Hipoplasia do Esmalte Dentário/epidemiologia , Hipoplasia do Esmalte Dentário/etiologia , Dentição Permanente , Alemanha/epidemiologia , Humanos , Prevalência
6.
Sci Adv ; 5(9): eaaw3095, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31840077

RESUMO

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.


Assuntos
Índice de Massa Corporal , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Característica Quantitativa Herdável , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Criança , Feminino , Predisposição Genética para Doença , Genômica , Gráficos de Crescimento , Humanos , Lactente , Estudos Longitudinais , Masculino , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Receptores para Leptina/genética
7.
Eur Respir J ; 54(1)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31073081

RESUMO

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute ß-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.


Assuntos
Metilação de DNA , Epigênese Genética , Estudo de Associação Genômica Ampla , Fumar/genética , Adulto , Idoso , Ilhas de CpG , Feminino , Volume Expiratório Forçado , Humanos , Modelos Lineares , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Valores de Referência , Fumar/fisiopatologia , Espirometria
8.
Metabolites ; 9(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939782

RESUMO

Determination of metabolomic signatures of pulmonary function and chronic obstructive pulmonary disease (COPD) in the general population could aid in identification and understanding of early disease processes. Metabolome measurements were performed on serum from 4742 individuals (2354 African-Americans and 1529 European-Americans from the Atherosclerosis Risk in Communities study and 859 Europeans from the Cooperative Health Research in the Region of Augsburg study). We examined 368 metabolites in relation to cross-sectional measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio (FEV1/FVC) and COPD using multivariable regression followed by meta-analysis. At a false discovery rate of 0.05, 95 metabolites were associated with FEV1 and 100 with FVC (73 overlapping), including inverse associations with branched-chain amino acids and positive associations with glutamine. Ten metabolites were associated with FEV1/FVC and seventeen with COPD (393 cases). Enriched pathways of amino acid metabolism were identified. Associations with FEV1 and FVC were not driven by individuals with COPD. We identified novel metabolic signatures of pulmonary function and COPD in African and European ancestry populations. These may allow development of biomarkers in the general population of early disease pathogenesis, before pulmonary function has decreased to levels diagnostic for COPD.

9.
Respir Res ; 20(1): 33, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764884

RESUMO

BACKGROUND: Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. METHODS: We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. RESULTS: Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (ß: - 49 ml; 95%-CI: -132, 35 for FEV1 and ß: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. CONCLUSION: Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes.


Assuntos
Nível de Saúde , Sistema Respiratório/fisiopatologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Asma/epidemiologia , Asma/etiologia , Bronquite Crônica/epidemiologia , Bronquite Crônica/etiologia , Dispneia/epidemiologia , Dispneia/etiologia , Europa (Continente)/epidemiologia , União Europeia , Seguimentos , Inquéritos Epidemiológicos , Humanos , Incidência , Prevalência , Testes de Função Respiratória , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/etiologia , Fatores Socioeconômicos , Poluição por Fumaça de Tabaco/estatística & dados numéricos
10.
Addiction ; 114(2): 216-225, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30209858

RESUMO

AIMS: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E. DESIGN: Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions. SETTING: Europe. PARTICIPANTS: We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015. MEASUREMENTS: The rs1229984 (ADH1B) was genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum samples. FINDINGS: Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for asthma, an OR = 0.971 (95% CI =  0.804, 1.174; P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE. CONCLUSIONS: In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Asma/etiologia , Hipersensibilidade/etiologia , Adolescente , Idoso de 80 Anos ou mais , Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/epidemiologia , Asma/epidemiologia , Dinamarca/epidemiologia , Feminino , Genótipo , Humanos , Hipersensibilidade/epidemiologia , Imunoglobulina E/metabolismo , Masculino , Análise da Randomização Mendeliana , Testes de Função Respiratória , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/etiologia , Adulto Jovem
11.
Respir Res ; 18(1): 138, 2017 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-28701166

RESUMO

BACKGROUND: Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. METHODS: Best subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF25-75)) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. RESULTS: A higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF25-75. Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (≤23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were consistently negatively associated with airway function. CONCLUSIONS: Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents.


Assuntos
Desenvolvimento do Adolescente , Meio Ambiente , Hipersensibilidade/fisiopatologia , Estilo de Vida , Pulmão/crescimento & desenvolvimento , Adolescente , Fatores Etários , Asma/epidemiologia , Asma/fisiopatologia , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Feminino , Volume Expiratório Forçado , Alemanha/epidemiologia , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , Lactente , Recém-Nascido , Modelos Lineares , Estudos Longitudinais , Masculino , Fluxo Máximo Médio Expiratório , Prevalência , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/fisiopatologia , Fatores de Risco , Espirometria , Inquéritos e Questionários , Poluição por Fumaça de Tabaco/efeitos adversos , Capacidade Vital , Vitamina D/sangue
12.
Sci Rep ; 7(1): 2224, 2017 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28533558

RESUMO

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.


Assuntos
Asma/epidemiologia , Asma/etiologia , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/etiologia , Adolescente , Adulto , Alelos , Suscetibilidade a Doenças , Predisposição Genética para Doença , Genótipo , Humanos , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Razão de Chances , Fumar/efeitos adversos , Adulto Jovem
13.
Eur Respir J ; 49(4)2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28446555

RESUMO

Vitamin D plays a role in the development of the immune system and the lung, as well as in airway remodelling. Therefore, this study investigated the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and spirometric lung function parameters at age 15 years.In the German birth cohorts GINIplus and LISAplus, lung function testing by spirometry and 25(OH)D measurements were performed during the 15-year follow-up examinations. Valid lung function measurements pre- and/or post-bronchodilation and serum 25(OH)D concentrations, which were adjusted for the date of blood sampling to account for seasonal variability, were available for 2607 adolescents. Associations between 25(OH)D concentrations and spirometric parameters were analysed using generalised additive models adjusted for confounding factors.Serum 25(OH)D concentrations were significantly associated with forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC measured before bronchodilation after adjustment for potential confounders: FEV1 increased by 10 mL (95% CI 2-17), FVC by 20 mL (95% CI 12-28) and FEV1/FVC decreased by 0.177% (95% CI -0.286 to -0.067) per 10 nmol·L-1 increase in 25(OH)D concentrations. Flow rates (forced expiratory flow rates at 25, 50 and 75% of exhaled FVC (FEF25, FEF50, FEF75) and mean flow rate between 25 and 75% of FVC (FEF25-75)) were not associated with vitamin D. Similar associations were observed for lung function parameters measured after bronchodilation.Vitamin D concentrations are positively associated with volume-related lung function parameters pre- and post-bronchodilation, suggesting structural changes in peripheral airways.


Assuntos
Pulmão/fisiologia , Vitamina D/análogos & derivados , Adolescente , Estudos Transversais , Feminino , Seguimentos , Fluxo Expiratório Forçado , Volume Expiratório Forçado , Alemanha , Humanos , Masculino , Análise de Regressão , Espirometria , Volume de Ventilação Pulmonar , Vitamina D/sangue
14.
Sleep ; 39(10): 1859-1869, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27568811

RESUMO

STUDY OBJECTIVES: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits. METHODS: We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Consortium. 10,554 children of European ancestry were included in the discovery, and 1,250 children in the replication phase. RESULTS: We found evidence of significant but modest SNP heritability of sleep duration in children (SNP h2 0.14, 95% CI [0.05, 0.23]) using the LD score regression method. A novel region at chromosome 11q13.4 (top SNP: rs74506765, P = 2.27e-08) was associated with sleep duration in children, but this was not replicated in independent studies. Nominally significant genetic overlap was only found (rG = 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism. CONCLUSIONS: The significant SNP heritability of sleep duration in children and the suggestive genetic overlap with type 2 diabetes support the search for genetic mechanisms linking sleep duration in children to multiple outcomes in health and disease.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Característica Quantitativa Herdável , Sono/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores de Tempo
15.
PLoS One ; 11(7): e0159678, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27438002

RESUMO

A hallmark of the newly published GLI (Global Lungs Initiative) spirometric reference values is their "all-age" (3-95yr) predictive power, accomplished by incorporating non-linear age dependencies into modelling parameters. This modelling strategy is especially promising for the age range of puberty; however, the performance of GLI-values for adolescents is currently unknown. We calculated GLI-based z-scores for children/adolescents without apparent respiratory diseases from two different German studies, LUNOKID (N = 1943, 4-19 years) and GINIplus (N = 1042, 15 years) and determined the goodness of fit for specific age groups. We defined fit sufficient if the absolute mean of z-scores was <0.5. For children (<10yr) the mean GLI-based z-scores for FEV1 and FVC reached a good fit with mean z-scores for FEV1 between -0.11 and 0.01 and mean z-scores for FVC between 0.01 and 0.16, but larger deviations were observed in adolescents, especially boys (mean z-score -0.58 for FEV1 and -0.57 for FVC in GINIplus). The fit for FEV1/FVC was sufficient. GLI reference values provided reasonable estimates for the individuals enrolled in our studies, which span the age range of lung growth and development. However, we found that GLI-predictions overestimated lung volumes, especially those for German adolescent boys, which may, left unrecognised, lead to erroneous diagnosis of lung disease. Caution should be taken when applying these reference values to epidemiologic studies.


Assuntos
Volume Expiratório Forçado/fisiologia , Pneumopatias/fisiopatologia , Pulmão/fisiopatologia , Espirometria/métodos , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Grupo com Ancestrais do Continente Europeu , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Pneumopatias/epidemiologia , Masculino , Puberdade/fisiologia , Valores de Referência , Adulto Jovem
16.
Hum Mol Genet ; 25(2): 389-403, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26604143

RESUMO

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.


Assuntos
Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Criança , Pré-Escolar , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Loci Gênicos , Humanos , Masculino , Risco , Adulto Jovem
17.
J Allergy Clin Immunol ; 137(4): 1026-1035, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26548843

RESUMO

BACKGROUND: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE: We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.


Assuntos
Asma/etiologia , Desenvolvimento Infantil/fisiologia , Doenças do Prematuro/etiologia , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Pulmão/fisiopatologia , Adolescente , Asma/fisiopatologia , Criança , Pré-Escolar , Volume Expiratório Forçado , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Doenças do Prematuro/fisiopatologia , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Modelos Estatísticos , Fatores de Risco , Capacidade Vital , Ganho de Peso/fisiologia
18.
Nat Commun ; 6: 8658, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26635082

RESUMO

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.


Assuntos
Estudo de Associação Genômica Ampla , Pneumopatias/genética , Pulmão/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Volume Expiratório Forçado , Humanos , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
19.
BMC Public Health ; 15: 841, 2015 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-26329931

RESUMO

BACKGROUND: Understanding changes in dietary intake during puberty could aid the mapping of dietary interventions for primary prevention. The present study describes dietary changes from childhood to adolescence, and their associations with parental education, family income, child education, body mass index (BMI), pubertal onset and screen-time sedentary behaviour. METHODS: Dietary data (n = 1232) were obtained from food frequency questionnaires at the 10- and 15-year follow-ups of the GINIplus birth cohort study. Intakes of 17 food groups, macronutrients and antioxidant vitamins, were described by a) paired Wilcoxon rank sum tests, comparing average intakes at each time-point, and b) Cohen's kappa "tracking" coefficients, measuring stability of intakes (maintenance of relative tertile positions across time). Further, associations of changes (tertile position increase or decrease vs. tracking) with parental education, family income, child education, pubertal onset, BMI, and screen-time, were assessed by logistic regression and multinomial logistic regression models stratified by baseline intake tertile. RESULTS: Both sexes increased average intakes of water and decreased starchy vegetables, margarine and dairy. Females decreased meat and retinol intakes and increased vegetables, grains, oils and tea. Males decreased fruit and carbohydrates and increased average intakes of meat, caloric drinks, water, protein, fat, polyunsaturated fatty acids (PUFAs), vitamin C and alpha-tocopherol. Both sexes presented mainly "fair" tracking levels [κw = 0.21-0.40]. Females with high (vs. low) parental education were more likely to increase their nut intake [OR = 3.8; 95 % CI = (1.7;8.8)], and less likely to decrease vitamin C intakes [0.2 (0.1;0.5)], while males were less likely to increase egg consumption [0.2 (0.1;0.5)] and n3 PUFAs [0.2 (0.1;0.5)]. Females with a higher (vs. low) family income were more likely to maintain medium wholegrain intakes [0.2 (0.1;0.7) for decrease vs. tracking, and 0.1 (0.0;0.5) for increase vs. tracking], and were less likely to decrease vitamin C intakes [0.2 (0.1;0.6)]. Males with high education were less likely to increase sugar-sweetened foods [0.1 (0.1;0.4)]. Finally, BMI in females was negatively associated with decreasing protein intakes [0.7 (0.6;0.9)]. In males BMI was positively associated with increasing margarine [1.4 (1.1;1.6)] and vitamin C intakes [1.4 (1.1;1.6)], and negatively associated with increasing n3 PUFA. CONCLUSIONS: Average dietary intakes changed significantly, despite fair tracking levels, suggesting the presence of trends in dietary behaviour during puberty. Family income and parental education predominantly influenced intake changes. Our results support the rationale for dietary interventions targeting children, and suggest that sex-specific subpopulations, e.g. low socio-economic status, should be considered for added impact.


Assuntos
Dieta/estatística & dados numéricos , Comportamento Alimentar , Preferências Alimentares , Puberdade , Adolescente , Criança , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Estado Nutricional , Obesidade Pediátrica/epidemiologia , Maturidade Sexual
20.
Ann Allergy Asthma Immunol ; 115(3): 183-90, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26195441

RESUMO

BACKGROUND: The prevalence of allergen sensitization reaches up to 46.6% in 14- to 17-year-old German adolescents. Polysensitization is strongly associated with a higher risk of allergic rhinitis or asthma. Whether or how sensitization also is related to lung function remains uncertain. OBJECTIVE: To assess whether sensitization to common inhalant allergens is associated with lung function in adolescents after stratification by allergic respiratory disease. METHODS: In total, 1,719 15-year-old participants of the German Infant Study on the Influence of Nutrition Intervention plus Air Pollution and Genetics on Allergy Development (GINIplus) birth cohort provided valid spirometric indices, including forced expiratory volume in 1 second, forced vital capacity (FVC), forced expiratory flow rate at 25% to 75% of the FVC, and specific immunoglobulin E (IgE) screening test to 8 inhalant allergens (ImmunoCAP). Complete information on allergic rhinitis and asthma status was available for 1,128 subjects. Associations between lung function parameters and sensitization, classified into 4 groups (no sensitization to polysensitization) were analyzed using adjusted linear regression models. RESULTS: Among participants, 21.1% (n = 347) had allergic rhinitis, 10.1% (n = 119) had asthma, and 46.4% (n = 798) had a positive screening test to inhalant allergens. Prevalences were consistently higher in boys. The percentage of subjects with rhinitis or asthma increased from 5.8% in non-sensitized subjects (n = 620) to 69.4% in polysensitized subjects (n = 144). Sensitization was not associated with any spirometric parameter considered in subjects with allergic rhinitis, asthma, or neither disease. CONCLUSION: Although allergen-specific IgE concentrations can contribute to the identification of subjects at higher risk for allergic rhinitis and asthma, sensitization to inhalant allergens is not related to impaired spirometric lung parameters within the different allergic respiratory disease subgroups.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Imunoglobulina E/sangue , Pulmão/fisiologia , Rinite Alérgica/imunologia , Adolescente , Asma/epidemiologia , Estudos de Coortes , Feminino , Volume Expiratório Forçado/fisiologia , Alemanha/epidemiologia , Humanos , Imunoglobulina E/imunologia , Exposição por Inalação , Masculino , Fluxo Máximo Médio Expiratório/fisiologia , Rinite Alérgica/epidemiologia , Capacidade Vital/fisiologia
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