A5039823178- Asthma and respiratory diseases
- Cystic Fibrosis Research Advances
- Pediatric health and respiratory diseases
- Neonatal Respiratory Health Research
- Allergic Rhinitis and Sensitization
- IL-33, ST2, and ILC Pathways
- Tracheal and airway disorders
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immunodeficiency and Autoimmune Disorders
- Inhalation and Respiratory Drug Delivery
- Respiratory viral infections research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Biomedical and Chemical Research
- Respiratory and Cough-Related Research
- Mast cells and histamine
- Air Quality and Health Impacts
- Psoriasis: Treatment and Pathogenesis
- Parasites and Host Interactions
- Pneumonia and Respiratory Infections
- Medical and Biological Ozone Research
- Immunotherapy and Immune Responses
- Immune responses and vaccinations
- Immune cells in cancer
Medizinische Hochschule Hannover
2015-2025
German Center for Lung Research
2017-2025
Universität Hamburg
2023
University Medical Center Hamburg-Eppendorf
2023
Hochschule Hannover
2018
Charité - Universitätsmedizin Berlin
2002-2010
Yale University
2007-2010
Helmholtz Centre for Infection Research
2009
Fraunhofer Institute for Toxicology and Experimental Medicine
2009
Humboldt State University
2009
Rationale: The CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to improve clinical outcomes and sweat chloride concentration in patients with cystic (CF) one or two F508del alleles. However, the effect of ELX/TEZ/IVA on function airways intestine has not been studied. Objectives: To assess airway intestinal epithelia CF alleles aged 12 years older. Methods: This prospective, observational, multicenter...
Rationale: We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves function in airway and intestinal epithelia to 40–50% of normal patients cystic (CF) one or two F508del alleles. In previous studies, this improvement was shown improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout abnormalities...
Background We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in morphology detected by magnetic resonance imaging (MRI) adolescent adult patients with cystic fibrosis (CF). However, real-world data on effect of ETI these sensitive outcomes structure function school-age children CF have not been reported. The aim this study was therefore to examine LCI MRI score aged 6–11 years one or two F508del alleles. Methods...
Purpose To assess the feasibility of monitoring effects elexacaftor-tezacaftor-ivacaftor (ETI) therapy on lung ventilation and perfusion in people with cystic fibrosis (CF), using phase-resolved functional (PREFUL) MRI. Materials Methods This secondary analysis a multicenter prospective study was carried out between August 2020 March 2021 included participants 12 years or older CF who underwent PREFUL MRI, spirometry, sweat chloride test, clearance index assessment before 8–16 weeks after...
Recently, we have identified the inducible co-stimulator (ICOS), an activation-dependent, T cell-specific cell surface molecule related to CD28 and CTLA-4. Detailed analysis of human ICOS presented here shows that it is a 55-60-kDa homodimer with differently N-glycosylated subunits 27 29 kDa. requires both phorbol 12-myristate 13-acetate ionomycin for full induction, sensitive Cyclosporin A. up-regulated early on all cells, including CD28– subset, continues be expressed into later phases...
Abstract Numerous epidemiological studies have shown an inverse correlation between helminth infections and the manifestation of atopic diseases, yet immunological mechanisms governing this phenomenon are indistinct. We therefore investigated effects infection with filarial parasite Litomosoides sigmodontis on allergen-induced immune reactions airway disease in a murine model asthma. Infection L. suppressed all aspects asthmatic phenotype: Ag-specific Ig production, reactivity to inhaled...
ObjectivesThe impressive improvements of CFTR function by elexacaftor/tezacaftor/ivacaftor (ETI) result in changes the detection frequencies Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). We assessed determinants response to ETI with regards SA PA as documented German CF Registry for people (pwCF) ≥12 years.MethodsWe evaluated 21 months before after initiation used different statistical tests identify changes.ResultsWe included data from 1,092 pwCF results culture-dependent...
Interleukin (IL)-17A signaling via 17 receptor A (Il17ra) contributes to the inflammatory host response by inducing recruitment of innate immune cells, but also plays a role in homeostatic neutrophilic granulocyte regulation. Monocytes, other main cell, have longer life span and can pursue multiple differentiation pathways towards tissue macrophages. Monocytes are divided into two subpopulations expression Ly6C/Gr1 surface marker mice. We here investigated Il17ra monocyte homeostasis...
Asthma and wheezing disorders in childhood adulthood are clinically heterogeneous regarding disease presentation, natural course, response to treatment. Deciphering common mechanisms distinct subgroups requires harmonized molecular (endo-) phenotyping of both children adult patients with asthma a prospective, longitudinal setting. The ALL Age Cohort (ALLIANCE) the German Center for Lung Research (DZL) is multi-center, observational cohort study seven recruiting sites across Germany. Data...
X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency is a developmental and immunologic disorder caused by mutations in nuclear factor-κB essential modulator (NEMO), which for activation. Early life, affected boys present typical appearance, hypotrichosis or atrichosis, hypohidrosis anhidrosis, hypodontia anodontia conical incisors. They are also susceptible to various microorganisms, mostly pyogenic bacteria mycobacteria. Here we report 2 unrelated boys, aged 6 11 years,...
Rationale: Lumacaftor/ivacaftor (LUM/IVA) was shown to be safe and well tolerated in children 2 through 5 years of age with cystic fibrosis (CF) homozygous for F508del-CFTR a Phase 3 open-label study. Improvements sweat chloride concentration, markers pancreatic function, lung clearance index2.5 (LCI2.5), along increases growth parameters, suggested the potential early disease modification LUM/IVA treatment. Objective: To further assess effects on CF progression using chest magnetic...
Abstract Objectives To investigate whether 3D phase-resolved functional lung (PREFUL)-MRI parameters are suitable to measure response elexacaftor/tezacaftor/ivacaftor (ETI) therapy and their association with clinical outcomes in cystic fibrosis (CF) patients. Methods Twenty-three patients CF (mean age: 21; age range: 14–46) underwent MRI examination at baseline 8–16 weeks after initiation of ETI. Morphological PREFUL scans assessed pulmonary ventilation. images were evaluated using a...
The aim of the present study was to identify and validate biological significance new genes/proteins involved in development allergic airway disease a murine asthma model. Gene microarrays were used genes with at least two-fold increase gene expression lungs two separate mouse strains high low susceptibility. Validation mRNA data obtained by western blotting immunohistochemistry, followed functional analysis one identified mice targeted disruption specific expression. Expression antioxidant...
Abstract Different models of experimental allergic asthma have shown that the TLR7/8 agonist resiquimod (R848) is a potential inhibitor type 2 helper cell–driven inflammatory responses. However, mechanisms mediating its therapeutic effects are not fully understood. Using model asthma, we show induction IL-27 by R848 critical for observed ameliorative effects. significantly inhibited all hallmarks including airway hyperreactivity, eosinophilic inflammation, mucus hypersecretion, and...
Rationale: The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes.Objectives: To identify biological targets underlying escalated clinical phenotype mediated by locus.Methods: Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 wheezing at preschool age, 104 asthmatic) within ALLIANCE (All-Age-Asthma) cohort, a median age 10.0 (range, 1.0–20.0)...
Aims Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in children aged 6–11 years with cystic fibrosis (CF) heterozygous for F508del a minimal function CFTR variant ( F /MF genotypes) 24-week, placebo-controlled trial. We conducted 96-week open-label extension study who completed the 24-week parent study. Methods In this phase 3b study, dosing based on weight age weighing <30 kg <12 receiving ELX 100 mg once daily (qd), TEZ 50 qd, IVA 75 every 12 h (q12) ≥30 or...