ORCID Profile
0000-0003-1652-8873
Current Organisations
Ludwig-Maximilians-Universität München
,
University of South Australia School of Commerce
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Publisher: Wiley
Date: 14-09-2021
DOI: 10.1111/PAI.13657
Abstract: While childhood asthma prevalence is rising in Westernized countries, farm children are protected. The mitogen‐activated protein kinase (MAPK) pathway with its negative regulator dual‐specificity phosphatase‐1 (DUSP1) is presumably associated with asthma development. We aimed to investigate the role of MAPK signaling in childhood asthma and its environment‐mediated protection, including a representative selection of 232 out of 1062 children from two cross‐sectional cohorts and one birth cohort study. Peripheral blood mononuclear cells (PBMC) from asthmatic and healthy children were cultured upon stimulation with farm‐dust extracts or lipopolysaccharide. In subgroups, gene expression was analyzed by qPCR (PBMCs, cord blood) and NanoString technology (dendritic cells). Protein expression of phosphorylated MAPKs was measured by mass cytometry. Histone acetylation was investigated by chromatin immunoprecipitation. Asthmatic children expressed significantly less DUSP1 ( p = .006) with reduced acetylation at histone H4 ( p = .012) compared with healthy controls. Farm‐dust stimulation upregulated DUSP1 expression reaching healthy levels and downregulated inflammatory MAPKs on gene and protein levels (PBMCs p ≤ .01). Single‐cell protein analysis revealed downregulated pMAPKs upon farm‐dust stimulation in B cells, NK cells, monocytes, and T‐cell subpopulations. Lower DUSP1 baseline levels in asthmatic children and anti‐inflammatory regulation of MAPK in several immune cell types by farm‐dust stimulation indicate a regulatory function for DUSP1 for future therapy contributing to anti‐inflammatory characteristics of farming environments.
Publisher: Wiley
Date: 07-07-2023
DOI: 10.1002/SMI.3287
Abstract: Using a rich in idual level dataset from six countries, we examine the relationship between job loss and mental disorders during the first phase of the COVID‐19 pandemic. We consider four indicators of mental disorders based on their severity, viz. anxiety, insomnia, boredom, and loneliness. We draw our conclusions based on two groups of countries that differ by the timing of their peak infections count. Using a logit and a two‐stage least squares (TSLS) regression methods, we find that the people who lost their jobs due to the pandemic are more likely to suffer from mental disorders, especially insomnia and loneliness. Additionally, people with financial liabilities, such as housing mortgages, are among those vulnerable to anxiety. Women, urban residents, youth, low‐income groups, and tobacco users are more prone to mental disorders. The findings from this research have significant policy implications on infectious disease control measures and mental health conditions due to lockdowns and social distancing.
Publisher: European Respiratory Society (ERS)
Date: 29-07-2021
DOI: 10.1183/13993003.03969-2020
Abstract: Asthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3). To delineate the degradation of COL4A3 in allergic airway inflammation and evaluate the resultant product as a biomarker for anti-IgE therapy response. The serological COL4A3 degradation marker C4Ma3 (Nordic Bioscience, Denmark) and serum cytokines were measured in the ALLIANCE cohort (paediatric cases/controls: n=134/n=35 adult cases/controls: n=149/n=31). Exacerbation of allergic airway disease in mice was induced by sensitising to ovalbumin (OVA), challenge with OVA aerosol and instillation of poly(cytidylic-inosinic). Fulacimstat (chymase inhibitor Bayer) was used to determine the role of mast cell chymase in COL4A3 degradation. Patients with cystic fibrosis (n=14) and cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA n=9) as well as patients with severe allergic uncontrolled asthma (n=19) were tested for COL4A3 degradation. Omalizumab (anti-IgE) treatment was assessed using the Asthma Control Test. Serum levels of C4Ma3 were increased in asthma in adults and children alike and linked to a more severe, exacerbating allergic asthma phenotype. In an experimental asthma mouse model, C4Ma3 was dependent on mast cell chymase. Serum C4Ma3 was significantly elevated in cystic fibrosis plus ABPA and at baseline predicted the success of the anti-IgE therapy in allergic, uncontrolled asthmatics (diagnostic OR 31.5). C4Ma3 levels depend on lung mast cell chymase and are increased in a severe, exacerbating allergic asthma phenotype. C4Ma3 may serve as a novel biomarker to predict anti-IgE therapy response.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Public Library of Science (PLoS)
Date: 22-07-2022
DOI: 10.1371/JOURNAL.PONE.0271586
Abstract: This paper investigates the determinants of COVID-19 infection in the first 100 days of government actions. Using a debiased LASSO estimator, we explore how different measures of government nonpharmaceutical interventions affect new infections of COVID-19 for 37 lower and middle-income countries (LMCs). We find that closing schools, stay-at-home restrictions, and contact tracing reduce the growth of new infections, as do economic support to households and the number of health care workers. Notably, we find no significant effects of business closures. Finally, infections become higher in countries with greater income inequality, higher tourist inflows, poorly educated adults, and weak governance quality. We conclude that several policy interventions reduce infection rates for poorer countries. Further, economic and institutional factors are important thereby justifying the use, and ultimately success, of economic support to households during the initial infection period.
Publisher: Elsevier BV
Date: 04-2006
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JACI.2019.07.029
Abstract: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-α-induced protein 3 (TNFAIP3 A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, mediates environmentally induced asthma protection. We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective" farms or LPS. NF-κB signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P < .05), reflecting their increased inflammatory status. Ex vivo farm dust or LPS stimulation restored TNFAIP3 expression to healthy levels in asthmatic patients and shifted NF-κB signaling-associated gene expression toward an anti-inflammatory state (P < .001). Farm/rural children had lower expression, indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school age had reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma. Our data indicate TNFAIP3 as a key regulator during childhood asthma development and its environmentally mediated protection. Because environmental dust exposure conferred the anti-inflammatory effects, it might represent a promising future agent for asthma prevention and treatment.
Publisher: Informa UK Limited
Date: 15-12-2022
No related grants have been discovered for Bianca Prof. Dr. med. Schaub.