Einfluss von Geschlecht und Pubertätsbeginn auf Asthma, Rhinitis und respiratorische Multimorbidität im Kindes- und Jugendalter

Einführung: Rhinitis und Asthma sind chronisch-entzündliche Atemwegserkrankungen mit weltweit häufigem Auftreten bereits im Kindes- und Jugendalter. Bei der Asthma- Prävalenz scheint eine männliche Dominanz in der Kindheit zu bestehen, die von einer weiblichen Dominanz in der Jugend und im Erwachsenenalter abgelöst wird. Die Datenlage zur Prävalenz von Rhinitis und von respiratorischer Multimorbidität (d.h. dem gleichzeitigen Auftreten von Rhinitis und Asthma) ist dagegen unzureichend. Die vorliegende Dissertation untersuchte geschlechtsspezifische Prävalenzen und Inzidenzen von Rhinitis, Asthma und respiratorischer Multimorbidität vor und nach Pubertätsbeginn. Methoden: In einer systematischen Übersichtsarbeit mit Metaanalyse (Publikation I) wurden 6.540 Publikationen zu Rhinitis-Prävalenzen vom Kindes- bis Erwachsenenalter gescreent; 67 Publikationen erfüllten die Kriterien zum Einschluß in die Metaanalyse. Des Weiteren wurden zwei Metaanalysen zur Bestimmung der geschlechtsspezifischen Prävalenzen (Publikation II) und Inzidenzen (Publikation III) von Rhinitis, Asthma und respiratorischer Multimorbidität in Abhängigkeit vom Pubertätsstatus durchgeführt. Primärdaten internationaler bevölkerungsbasierter Geburtskohortenstudien mit über 18.000 rekrutierten Kindern konnten harmonisiert und analysiert werden. Spezifisches Immunoglobulin-E (IgE) gegen Aeroallergene wurde im Serum bestimmt, um für IgE- versus nicht-IgE-assoziierte Rhinitis, Asthma und respiratorische Multimorbidität zu stratifizieren. Ergebnisse: Publikation I zeigte für die Rhinitis-Prävalenz im Kindesalter eine Dominanz der Jungen und bei Jugendlichen und Erwachsenen eine Dominanz der weiblichen Teilnehmer. Die Publikationen II (Prävalenz) und III (Inzidenz) zeigten eine männliche Dominanz für Rhinitis, Asthma und respiratorischer Multimorbidität vor Pubertätsbeginn. Für IgE-assoziierte Rhinitis- Inzidenz blieb die männliche Dominanz auch nach Pubertätsbeginn bestehen (female/male Harzard Ratio (HR) 0,66; 95% Konfidenzintervall 0,54-0,80), während sich für die nicht-IgE-assoziierte Rhinitis-Inzidenz eine Tendenz zu einer weiblichen Dominanz zeigte (1,20; 0,98-1,47). Nach Pubertätsbeginn deutete sich für die Inzidenz von IgE-assoziiertem Asthma (0,77; 0,53-1,11) und IgE-assoziierter respiratorischer Multimorbidität (0,74; 0,50-1,08) eine Tendenz zu einem ausgeglicheneren Geschlechterverhältnis an. Dies war deutlicher für die Inzidenzen von nicht-IgE- assoziiertem Asthma (1,23; 0,75-2,00) und nicht-IgE-assoziierter respiratorischer Multimorbidität (0,96; 0,54-1,71). Die Ergebnisse für die Prävalenzen waren ähnlich. Diskussion: Die vorliegenden Analysen großer bevölkerungsbezogener Datensätze zeigten, dass der Pubertätsbeginn das geschlechtsspezifische Auftreten respiratorischer Erkrankungen, insbesondere der nicht-IgE-assoziierten, beeinflusste. Weibliche Teilnehmer hatten nach Pubertätsbeginn im Vergleich zu vor Pubertätsbeginn ein erhöhtes Risiko für Asthma, Rhinitis und respiratorische Multimorbidität. Diese Erkenntnisse sollten nicht nur in der Grundlagenforschung bei der Aufklärung der den Allergien zugrundeliegenden Mechanismen berücksichtigt werden, sondern auch Implikationen für die klinische Forschung und Praxis haben. Um eine mögliche Unterversorgung zu vermeiden, bedarf es einer erhöhten Aufmerksamkeit bezüglich neuauftretender Rhinitis, Asthma und respiratorischer Multimorbidität bei weiblichen Patienten ab Pubertätsbeginn, insbesondere bei negativen IgE-Status und Skin-Prick-Test.Introduction: Rhinitis and asthma are common chronic inflammatory airway diseases, which can start as early as in childhood or adolescence. For asthma the prevalence shows a male predominance during childhood whereas it switches to a female predominance starting after puberty-onset; data for rhinitis and respiratory multimorbidity (i.e. the co-occurrence of rhinitis and asthma) are scarce. The current dissertation investigated the possible sex-switch of incidences and prevalences of rhinitis, asthma and respiratory multimorbidity before and after puberty-onset in large international population-based datasets. Methods: In a systematic review and meta- analysis (publication I) 6,540 publications were screened for data of sex-specific rhinitis prevalences throughout the lifespan; 67 publications fulfilled the inclusion criteria for the meta-analyses. Additionally, two meta-analyses included population-based birth cohort studies with over 18,000 recruited children to determine sex-specific prevalences (publication II) and incidences (publication III) of rhinitis, asthma and respiratory multimorbidity before and after puberty-onset. The participants’ status of serum Immunoglobulin-E (IgE) was assessed to stratify for IgE-associated versus non-IgE- associated rhinitis, asthma and respiratory multimorbidity. Results: Publication I showed a male predominance in childhood compared to a female predominance in adolescence and adulthood for the rhinitis prevalence. Similarly, publications II (prevalence) and III (incidence) based on European birth cohorts found a male predominance in rhinitis, asthma and respiratory multimorbidity before puberty-onset. For IgE-associated incident rhinitis a male predominance remained after puberty-onset (female/male Hazard Ratio (HR) 0.66; 95%Confidence-interval 0.54-0.80); whereas, for non-IgE-associated incident rhinitis there was a tendency towards a female predominance (1.20; 0.98-1.47). IgE-associated incident asthma (0.77; 0.53-1.11) and IgE-associated incident respiratory multimorbidity (0.74; 0.50-1.08) showed a slight tendency towards a more sex-balanced distribution after puberty-onset. For non-IgE- associated incident asthma (1.23; 0.75-2.00) and respiratory multimorbidity (0.96; 0.54- 1.71) the tendency towards a sex balanced distribution seemed more pronounced. The results for the prevalences were similar. Discussion: Independent of age, puberty- onset was related to a sex-switch of prevalence and incidence distribution patterns of rhinitis, asthma and respiratory multimorbidity, especially for non-IgE-associated conditions. Females had an increased risk for asthma, rhinitis and respiratory multimorbidity after puberty-onset compared to before puberty-onset. These results should be considered in basic scientific research to investigate underlying mechanism of allergies and also lead to implications in clinical research and practice. Clinicians should be attentive to detect incident respiratory diseases in adolescent girls for a timely diagnosis and treatment, especially with a negative IgE-status and skin prick test to avoid possible insufficient medical care in this patient group

How effective is the early support program Babylotse-Plus for psychosocially burdened mothers and their infants? A comparative intervention study

Objectives: Our aim was to examine the effects of an early perinatal prevention program offered to mothers and families suffering from significant psychosocial burden. Methods: All mothers giving birth in a Berlin university hospital during Jan-Aug 2013 were screened with a standardized 27-item questionnaire by trained staff. Mothers with a screening-score ≥ 3, who were not enrolled in other public support programs, were defined as psychosocially burdened. They received a detailed needs assessment and were followed up with counseling. When necessary, affected mothers were voluntarily guided through to specialized 'early support' institutions during the 12-month-intervention period. The historical control group (care-as-usual) consisted of children born at the same hospital the year before.At 12 months postnatally, we interviewed mothers in both groups to assess their stress burden and coping skills by Parenting Stress Index and assessed the current childcare condition. Differences between the groups were compared by multivariable logistic regression analyses adjusting for potential confounders. Results: The intervention group and the control group included 225 and 157 families, respectively. After 12-months, mothers in the 'early support' intervention group had significantly less often depression (adjusted odds ratio 0.25, 95%-confidence interval 0.07-0.94), less often a disturbed relationship with the parenting partner (0.34, 0.10-1.14) and reported reduced stress due to the child's demands (0.40, 0.15-1.10) compared to the control group. Childcare indicators did not differ between the 2 groups. Conclusions: In mothers at high psychosocial risk, the 'early support' intervention program Babylotse-Plus seemed to reduce the occurrence of depression and several stress indicators in the first postnatal year

European birth cohorts for environmental health research

Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning

Comorbidity of eczema, rhinitis, and asthma in IgE-sensitised and non-IgE-sensitised children in MeDALL: a population-based cohort study

n/

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Joint Data Analyses of European Birth Cohorts: Two Different Approaches Joint Data Analyses of European Birth Cohorts: Two Different Approaches

Abstract Background: Combined data analyses of birth cohorts can overcome the fragmentation of individual and inconclusive results obtained by analyses based upon single cohorts only. The European project Environmental Health Risks in European Birth Cohorts (ENRIECO) undertook four combined studies to evaluate the concept of added scientific value through harmonisation and exchange of birth cohort data for common analyses on environmental health risks

N-Glycoproteome of E14.Tg2a Mouse Embryonic Stem Cells

E14.Tg2a mouse embryonic stem (mES) cells are a widely used host in gene trap and gene targeting techniques. Molecular characterization of host cells will provide background information for a better understanding of functions of the knockout genes. Using a highly selective glycopeptide-capture approach but ordinary liquid chromatography coupled mass spectrometry (LC-MS), we characterized the N-glycoproteins of E14.Tg2a cells and analyzed the close relationship between the obtained N-glycoproteome and cell-surface proteomes. Our results provide a global view of cell surface protein molecular properties, in which receptors seem to be much more diverse but lower in abundance than transporters on average. In addition, our results provide a systematic view of the E14.Tg2a N-glycosylation, from which we discovered some striking patterns, including an evolutionarily preserved and maybe functionally selected complementarity between N-glycosylation and the transmembrane structure in protein sequences. We also observed an environmentally influenced N-glycosylation pattern among glycoenzymes and extracellular matrix proteins. We hope that the acquired information enhances our molecular understanding of mES E14.Tg2a as well as the biological roles played by N-glycosylation in cell biology in general

Sex-Related Allergic Rhinitis Prevalence Switch from Childhood to Adulthood:A Systematic Review and Meta-Analysis

Background: A sex-related switch in the prevalence of asthma from childhood (male predominance) to adulthood (female predominance) has been described, but for allergic rhinitis this remains unclear. We aimed to examine sex- and age-group-specific differences in allergic rhinitis prevalence by systematically evaluating studies from across the globe. Methods: A systematic search of MEDLINE and Embase for population-based cross-sectional studies was performed regardless of the language of publication. The search was restricted to the present millennium (2000 to June 2014). Study quality was defined by the sampling method, response rate, sample size, and data collection method. To assess sex differences in the prevalence of self-or parent-reported symptoms of rhinitis, calculated pooled estimates of the male-female ratio (MFR) were obtained using random-effects model meta-analyses due to heterogeneity. A meta-regression analysis was also performed. Results: Out of 6,539 publications identified, 67 cross-sectional population-based studies (291,726 males and 301,781 females) were included in our meta-analysis. In children (<11 years of age) significantly more boys than girls had rhinitis symptoms (MFR 1.21, 95% CI 1.17-1.25), whereas in adolescents (11 to <18 years of age) males were significantly less often affected than females (MFR 0.90, 95% CI 0.85-0.95). No sex-specific prevalence difference was observed in adults (MFR 0.96, 95% CI 0.83-1.17). These findings were consistent in all continents except in Asia, where the male predominance remained beyond childhood. Conclusions: The male predominance of rhinitis prevalence in child-hood changed towards a female predominance in adolescence across the globe, except in Asia. Longitudinal studies are needed to confirm these cross-sectional data and examine possible determinants and underlying mechanisms. (C) 2017 S. Karger AG, Base