Refine
Year of publication
Document Type
- Article (41)
- Conference Proceeding (3)
- Preprint (1)
Has Fulltext
- yes (45)
Is part of the Bibliography
- no (45)
Keywords
- ataxia telangiectasia (5)
- Ataxia telangiectasia (4)
- ATM (3)
- Ataxia-telangiectasia (3)
- asthma (3)
- lung function (3)
- primary immunodeficiency (3)
- Allergic asthma (2)
- Cytokines (2)
- Neurodegeneration (2)
- body plethysmography (2)
- cystic fibrosis (2)
- malignancy (2)
- Albumin ratio (1)
- Allergen immunotherapy (1)
- Allergic rhinitis (1)
- Allergoid (1)
- Aspergillus fumigatus (1)
- Ataxia score (1)
- Atm (1)
- Biomarker (1)
- Bronchial inflammation (1)
- CD23 (1)
- CD45RA naïve lymphocytes (1)
- CRP (1)
- CVID (1)
- Cell distribution (1)
- Cerebrospinal fluid (1)
- Cumulative dose (1)
- Curvilinear dose response (1)
- D-dimer (1)
- Disease progression (1)
- Double-blind placebo-controlled trial (1)
- Epidemiologie (1)
- Erregernachweis (1)
- European Society for Immunodeficiencies (ESID) (1)
- Exercise challenge (1)
- Exercise challenge at an ambient temperature (1)
- Exercise challenge in a cold chamber (1)
- Exercise-induced asthma (1)
- Exercise-induced bronchoconstriction (1)
- Exhaled nitric oxide (1)
- F508del homozygous (1)
- Fever (1)
- Forced expiratory volume in 1 s (1)
- German PID-NET registry (1)
- Grass pollen (1)
- GvHD (1)
- HSCT (1)
- HbA1c (1)
- Healthcare worker (1)
- Hexavalent vaccine (1)
- House dust mite allergy (1)
- IgA deficiency (1)
- IgE (1)
- IgG substitution therapy (1)
- Immunodeficiency (1)
- Immunoglobulins (1)
- Induced sputum (1)
- LABAs (1)
- Labordiagnostik (1)
- Local IgE (1)
- Local allergic rhinitis (1)
- Longchain polyunsaturated fatty acids (1)
- Lymphopenia Mortality (1)
- Methacholine challenge test (1)
- Mortality (1)
- Neurofilament light chain (1)
- NfL (1)
- Non-allergic-rhinitis (1)
- OGTT (1)
- PID prevalence (1)
- Paracetamol (1)
- Pertussis (1)
- Pneumococcal conjugate vaccine (1)
- Prophylaxis (1)
- Respimat® Soft Mist™ Inhaler (1)
- Respiratorische Infekte (1)
- SARS-CoV-2 (1)
- Smart nebulizer (1)
- T-lymphocytes (1)
- TNF inhibitors (1)
- Ultrasonic nebulizer (1)
- Vaccine uptake rate (1)
- Viruspneumonien (1)
- acute lung injury (1)
- allergen immunotherapy (1)
- allergic rhinitis (1)
- asthma phenotypes (1)
- ataxia score (1)
- autovaccine (1)
- basic mechanisms (1)
- bio imaging (1)
- biologics (1)
- bioluminescence (1)
- birch pollen allergoid (1)
- bronchial allergen challenge (1)
- bronchial allergen provocation (1)
- bronchiolitis obliterans syndrome (1)
- cancer surveillance (1)
- chronic inflammation (1)
- clinical immunology (1)
- combined immunodeficiency (1)
- cumulative dose (1)
- demonstration of the infectious agent (1)
- desensitization (1)
- device handling (1)
- diabetes (1)
- diabetes therapy (1)
- dose response curve (1)
- epidemiology (1)
- gap junction protein alpha 4-genotype (1)
- granulomas (1)
- granulomatous inflammation (1)
- haploidentical (1)
- healthcare worker (1)
- hepatic steatosis (1)
- hospitalization (1)
- house dust mite allergy (1)
- immune deficiency (1)
- immunologic (1)
- inflammation (1)
- inflammatory markers (1)
- inhalation flow profiles (1)
- inhaled steroids (1)
- laboratory diagnostic (1)
- ligelizumab (1)
- liver disease (1)
- long-acting β2-agonists (1)
- lung disease (1)
- lung disease phenotype (1)
- mesenchymal stromal/stem cells (1)
- miRNA (1)
- neurodegeneration (1)
- omalizumab (1)
- pertussis (1)
- phenotype/genotype relation (1)
- pollen allergy (1)
- postinfectious bronchiolitis obliterans (1)
- pre-emptive allogeneic hematopoietic stem cell transplantation (1)
- pre-school asthma (1)
- precision medicine (1)
- preschool asthma (1)
- preschool children (1)
- primary immunodeficiency (PID) (1)
- qRT-PCR (1)
- radio sensitivity (1)
- readmission rates (1)
- real-world evidence (1)
- registry for primary immunodeficiency (1)
- respiratory disease (1)
- respiratory failure (1)
- respiratory infections (1)
- safety (1)
- severe uncontrolled asthma (1)
- spirometry (1)
- stem cell transplantation (1)
- subcutaneous immunotherapy (1)
- sublingual immunotherapy (1)
- tailored treatment schedule (1)
- tiotropium (1)
- tolerability (1)
- tolerance (1)
- tracking (1)
- vaccine uptake rate (1)
- virus pneumonia (1)
Institute
Die Einteilung der Pneumonien richtet sich neben klinischen und pathologischen vor allem nach ätiologischen Gesichtspunkten. Es werden diesbezüglich die respirato- bzw. pneumotropen Viren vorgestellt, daneben differentialdiagnostisch wichtige andere Infektionserreger der "Viruspneumonie" (M. pneumoniae, Chlamydia psittaci, Coxiella burnetii) beschrieben und ihre klinischen Aspekte, labordiagnostischen Möglichkeiten sowie die Aussagekraft der verschiedenen Nachweisverfahren diskutiert. Die Letalität der primär virusbedingten Pneumonien ist zwar niedrig, der respiratotrope Virusbefall kann aber Schrittmacher für schwerebakterielle Superinfektionen sein.
Ataxia telangiectasia (A-T) is a progressive and life-limiting disease associated with cerebellar ataxia due to progressive cerebellar degeneration. In addition to ataxia, which is described in detail, the presence of chorea, dystonia, oculomotor apraxia, athetosis, parkinsonism, and myoclonia are typical manifestations of the disease. The study aimed to evaluate the specificity and sensitivity of neurofilament light chain (NfL) as a biomarker of neurodegeneration in relation to SARA score. In this prospective trial, one visit of 42 A-T patients aged 1.3–25.6 years (mean 11.6 ± 7.3 years) was performed, in which NfL was determined from serum by ELISA. Additionally, a neurological examination of the patients was performed. Blood was collected from 19 healthy volunteers ≥ 12 years of age. We found significantly increased levels of NfL in patients with A-T compared to healthy controls (21.5 ± 3.6 pg/mL vs. 9.3 ± 0.49 pg/mL, p ≤ 0.01). There was a significant correlation of NfL with age, AFP, and SARA. NfL is a new potential progression biomarker in blood for neurodegeneration in A-T which increases with age.
ecently, pertussis has become a problem also in the adult population, with incidences even higher than in children. Pediatric health care workers (HCWs) are an important source of transmission, exposing very young and immunocompromised patients to an increased risk of potentially severe pertussis infections. Encouraging HCWs to get vaccinated can play a vital role in stopping the transmission of pertussis, thereby reducing institutional outbreaks.
In Germany, HCWs come up with all sorts of reasons for not getting pertussis vaccination. This study was meant to provide information in order to better understand the backgrounds of these attitudes.
A survey was conducted at the children's university hospital in Frankfurt, using an anonymous questionnaire. Survey results were used to design an intervention to increase the immunization rate of staff. Disappointingly, our efforts to increase the acceptance of the immunization program by providing information in advance were not yet satisfying.
Misconception about pertussis vaccination was prevalent especially among nursing staff. The main reasons for non-compliance included: unawareness of an own risk of infection, the belief that pertussis is not a serious illness, fear of side effects, the belief that the pertussis vaccine might trigger the pertussis disease itself, and skepticism about the efficacy of the pertussis vaccination.
Recently, pertussis has become a problem also in the adult population, with incidences even higher than in children. Pediatric health care workers (HCWs) are an important source of transmission, exposing very young and immunocompromised patients to an increased risk of potentially severe pertussis infections. Encouraging HCWs to get vaccinated can play a vital role in stopping the transmission of pertussis, thereby reducing institutional outbreaks.
In Germany, HCWs come up with all sorts of reasons for not getting pertussis vaccination. This study was meant to provide information in order to better understand the backgrounds of these attitudes.
A survey was conducted at the children's university hospital in Frankfurt, using an anonymous questionnaire. Survey results were used to design an intervention to increase the immunization rate of staff. Disappointingly, our efforts to increase the acceptance of the immunization program by providing information in advance were not yet satisfying.
Misconception about pertussis vaccination was prevalent especially among nursing staff. The main reasons for non-compliance included: unawareness of an own risk of infection, the belief that pertussis is not a serious illness, fear of side effects, the belief that the pertussis vaccine might trigger the pertussis disease itself, and skepticism about the efficacy of the pertussis vaccination.
Objective: Ligelizumab is a humanised IgG1 anti-IgE antibody that binds IgE with higher affinity than omalizumab. Ligelizumab had greater efficacy than omalizumab on inhaled and skin allergen provocation responses in mild allergic asthma. This multi-centre, randomised, double-blind study was designed to test ligelizumab in severe asthma patients not adequately controlled with high-dose inhaled corticoids plus long-acting β2-agonist.
Methods: Patients received 16 weeks ligelizumab (240 mg q2w), omalizumab or placebo subcutaneously, and ACQ-7 was measured as primary outcome at Week 16. In addition, the study generated dose-ranging data of ligelizumab and safety data.
Results: A total of 471 patients, age 47.4 ± 13.36 years, were included in the study. Treatment with ligelizumab did not significantly improve asthma control (ACQ-7) and exacerbation rates compared to omalizumab and placebo. Therefore, primary and secondary objectives of the study were not met. The compound was well tolerated, and the safety profile showed no new safety findings. Pharmacokinetic data demonstrated faster clearance and lower serum concentrations of ligelizumab than historical omalizumab data, and exploratory in vitro data showed differential IgE blocking properties relative to FcεRI and FcεRII/CD23 between the two compounds.
Conclusion: Ligelizumab failed to demonstrate superiority over placebo or omalizumab. Although ligelizumab is more potent than omalizumab at inhibiting IgE binding to the high-affinity FcεRI, there is differential IgE blocking properties relative to FcεRI and FcεRII/CD23 between the two compounds. Therefore, the data suggest that different anti-IgE antibodies might be selectively efficacious for different IgE-mediated diseases.
Tiotropium as an add-on treatment option for severe uncontrolled asthma in preschool patients
(2021)
Background: Toddlers with asthma suffer disproportionally more than school-aged children from exacerbations with emergency visits and hospital admissions despite inhaled corticosteroid (ICS) treatment. A recent trial for children ≤ 5 years showed tolerability of tiotropium and potential to reduce asthma-related events.
Methods: We conducted a retrospective analysis of electronic outpatient records (2017‒2019) of children < 6 years treated with ICS plus long-acting β2-agonists (LABAs) plus tiotropium as an add-on for uncontrolled severe asthma. The primary endpoint was a comparison of systemic corticosteroid (SCS) prescriptions 6 months before and after ICS/LABA/tiotropium start. Secondary endpoints included physician visits, hospitalisations and antibiotic prescriptions. We compared outcomes with children without asthma matched for age, sex, season and screening date.
Results: Compared with a mean 2.42 (95% CI: 1.75, 3.36) SCS courses per patient within 6 months prior to ICS/LABA/tiotropium, 0.74 (95% CI: 0.25, 1.08) SCS courses per patient were prescribed within 6 months after starting ICS/LABA/tiotropium (P< 0.001). Physician visits dropped from 9.23 (95% CI: 7.15, 12.72) to 5.76 (95% CI: 3.10, 7.70) per patient (P< 0.01). Nineteen hospitalisations were recorded 6 months before ICS/LABA/tiotropium compared with one hospitalisation after (P< 0.01). A mean 1.79 antibiotic courses (95% CI: 1.22, 2.23) per patient were prescribed before ICS/LABA/tiotropium compared with 0.74 (95% CI: 0.22, 1.00) after ICS/LABA/tiotropium (P< 0.001). Hospitalisation rates for patients at observation end were not statistically different from healthy controls before/after matching.
Interpretation: Our retrospective study showed that adding tiotropium to ICS/LABA is a new treatment option for patients with severe preschool asthma; however, larger confirmatory studies are needed.
Autosomal recessive Ataxia Telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the Ataxia-Telangiectasia-Mutated (ATM) gene, a serine-threonine protein kinase involved in DNA-damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood.
Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia and immunodeficiency. The neurological decline may be caused by multiple factors of which ongoing inflammation and oxidative stress may play a dominant role. The objective of the present investigation was to determine cerebrospinal fluid (CSF) proteins and possible low-grade inflammation and its relation to age and neurological deterioration. In the present study, we investigated 15 patients with A-T from 2 to 16 years. Our investigation included blood and CSF tests, clinical neurological examination, A-T score, and MRI findings. The albumin ratio (AR) was analyzed to determine the blood–brain-barrier function. In addition, inflammatory cytokines (IL-1α, IL-6, IL-8, IL-12 p40, IL-17A, IFN-γ, TNF-α) were measured by the multiplex cytometric bead array. We compared the results with those from an age-matched control group. Three of the A-T patients were analyzed separately (one after resection of a cerebral meningioma, one after radiation and chemotherapy due to leukemia, one after stem cell transplantation). Patient had significantly more moderate and severe side effects due to CSF puncture (vomiting, headache, need for anti-emetic drugs) compared with healthy controls. Total protein, albumin, and the AR increased with age indicating a disturbed blood barrier function in older children. There were no differences for cytokines in serum and CSF with the exception of IL-2, which was significantly higher in controls in serum. The AR is significantly altered in A-T patients, but low-grade inflammation is not detectable in serum and CSF.
Rationale: Postinfectious bronchiolitis obliterans (PIBO) is a rare, chronic respiratory condition, which follows an acute insult due to a severe infection of the lower airways. Objectives: The objective of this study was to investigate the long-term course of bronchial inflammation and pulmonary function testing in children with PIBO. Methods: Medical charts of 21 children with PIBO were analyzed retrospectively at the Children's University Hospital Frankfurt/Main Germany. Pulmonary function tests (PFTs) with an interval of at least 1 month were studied between 2002 and 2019. A total of 382 PFTs were analyzed retrospectively and per year, the two best PFTs, in total 217, were evaluated. Additionally, 56 sputum analysis were assessed and the sputum neutrophils were evaluated. Results: The evaluation of the 217 PFTs showed a decrease in FEV1 with a loss of 1.07% and a loss in z score of −0.075 per year. FEV1/FVC decreased by 1.44 per year. FVC remained stable, showing a nonsignificant increase by 0.006 in z score per year. However, FEV1 and FVC in L increased significantly with FEV1 0.032 L per cm and FVC 0.048 L/cm in height. Sputum neutrophils showed a significant increase of 2.12% per year. Conclusion: Our results demonstrated that in patients with PIBO pulmonary function decreased significantly showing persistent obstruction over an average follow-up period of 8 years. However, persistent lung growth was revealed. In addition, pulmonary inflammation persisted clearly showing an increasing amount of neutrophils in induced sputum. Patients did not present with a general susceptibility to respiratory infections.
Ataxia-telangiectasia (A-T) is a hereditary immune system disorder with neurodegeneration. Its first neurologic symptoms include ataxic gait in early childhood, with slowly progressive cerebellar ataxia, oculomotor apraxia, oculocutaneous telangiectasia, and progressive muscle weakness. Neonatal screening for severe T-cell deficiency was recently found to diagnose A-T patients with a significantly reduced naïve T-cell pool. Our study includes 69 A-T patients between 8 January 2002 and 1 December 2019. Nineteen cases of cancer were diagnosed in 17 patients (25%), with a median overall survival [OS; 95% cumulative indcidence (CI)] of 26·9 years for the entire cohort. The 15-year OS of 82·5% (72–95%) was significantly decreased among A-T patients with malignancies, who had a median OS of 2·11 years, with a two-year-estimated OS of 50·7% (31–82%). Haematological malignancies were the major causes of death within the initial years of life with a 15 times increased risk for death [HR (95% CI): 6·9 (3·1–15.2), P < 0·001] upon malignancy diagnosis. Male patients with A-T are at a higher cancer risk than their female counterparts. This manuscript highlights the need for cancer surveillance and prevention, as well as optimal treatment in this cohort.