Refine
Year of publication
Document Type
- Article (42)
- Conference Proceeding (3)
- Preprint (1)
Has Fulltext
- yes (46)
Is part of the Bibliography
- no (46) (remove)
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
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.
Strong dose response after immunotherapy with PQ grass using conjunctival provocation testing
(2019)
Background: Pollinex Quattro Grass (PQ Grass) is an effective, well-tolerated, short pre-seasonal subcutaneous immunotherapy to treat seasonal allergic rhinoconjunctivitis (SAR) due to grass pollen. In this Phase II study, 4 cumulative doses of PQ Grass and placebo were evaluated to determine its optimal cumulative dose.
Methods: Patients with grass pollen-induced SAR were randomised to either a cumulative dose of PQ Grass (5100, 14400, 27600 and 35600 SU) or placebo, administered as 6 weekly subcutaneous injections over 31–41 days (EudraCT number 2017-000333-31). Standardized conjunctival provocation tests (CPT) using grass pollen allergen extract were performed at screening, baseline and post-treatment to determine the total symptom score (TSS) assessed approximately 4 weeks after dosing. Three models were pre-defined (Emax, logistic, and linear in log-dose model) to evaluate a dose response relationship.
Results: In total, 95.5% of the 447 randomized patients received all 6 injections. A highly statistically significant (p < 0.0001), monotonic dose response was observed for all three pre-specified models. All treatment groups showed a statistically significant decrease from baseline in TSS compared to placebo, with the largest decrease observed after 27600 SU (p < 0.0001). The full course of 6 injections was completed by 95.5% of patients. Treatment-emergent adverse events were similar across PQ Grass groups, and mostly mild and transient in nature.
Conclusions: PQ Grass demonstrated a strong curvilinear dose response in TSS following CPT without compromising its safety profile.
Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)
Die Häufigkeitsrate atopischer Erkrankungen bei Kindern, wie Heuschnupfen, Asthma, Neurodermitis (atopische Dermatitis), nimmt weltweit zu. Die Gründe sind vielschichtig. Gesichert ist der Zusammenhang zwischen der erblichen Überempfindlichkeit gegenüber natürlichen Substanzen (Atopie) und vermehrter Allergen- und Passivrauch-Exposition sowie Zunahme der Ein-Kind-Familien, Veränderung der mikrobiologischen Besiedlung des Darmes und Infektexposition. Besonders gut untersucht wurden diese Zusammenhänge von Erika von Mutius in einer Studie, in der sie von 1991 bis 1992 die Häufigkeit von Asthma in München (5030 Kinder) und Leipzig/Bitterfeld (2623 Kinder) verglichen hat.
Background: Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia, growth retardation, immunodeficiency, chronic pulmonary disease and chromosomal instability. Cutaneous granulomas are a known phenomenon in A-T but extra-dermal manifestation of granulomas at bone and synovia has not been reported so far. The clinical presentation, immunological findings, the long-term course and treatment options of eight patients with severe granulomas will be reported.
Methods: From our cohort of 44 classical A-T patients, eight patients aged 2–11 years (18.2%) presented with granulomas. Immunological features of patients with and without granulomas were compared. Five patients suffered from cutaneous manifestation, in two patients we detected a bone and in one a joint involvement. Patients with significant extra-dermal involvement as well as one patient with massive skin manifestation were treated with TNF inhibitors. The patient with granulomas at his finger joint and elbow was treated with hematopoietic stem cell transplantation (HSCT).
Results: Interestingly, seven of eight patients with granulomas were total IgA deficient, but there were no differences in IgG and IgM levels. All lymphocytes subsets were equally distributed except patients with granuloma had significantly lower naïve CD8 cells. In patients without treatment, four of eight showed a slow but significant enlargement of the granuloma. Treatment success with TNF inhibitors was variable. In one patient, treatment with TNF inhibitors led to a total remission for 3 years up to now. In two patients, treatment with TNF inhibitors led to a partial regression of granulomas. Treatment interruptions caused deterioration again.
Conclusions: Granulomas in A-T progress slowly over years and can lead to significant morbidity.Treatment with TNF inhibitors was safe and in part successful in our patients. Interestingly HSCT leads to complete remission, and indicates that aberrant immune function is responsible for granulomas in A-T patients.
At a glance commentary:
Scientific knowledge on the subject: Little is known about the clinical presentation, course and treatment of granulomas in ataxia telangiectasia (A-T). In addition, this is the first report of extra-dermal manifestation of granulomas at bone and synovia in patients with A-T.
What This Study Adds to the Field: Granulomas in A-T progress slowly over years and can lead to significant morbidity. Treatment with TNF inhibitors was safe and in part successful in our patients.
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.
Background: The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX® Quattro Plus 1.0 ml Birch 100%) is an effective, well‐tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose.
Methods: The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012‐004336‐28 PQBirch203 and 2015‐000984‐15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3‐4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED50), a measure of potency.
Results: Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED50 2723 SU, just over half the current dose. Prevalence of treatment‐emergent adverse events was similar for active doses, most being short‐lived and mild. Compliance was over 85% in all groups.
Conclusion: Increasing the cumulative dose of PQBirch 5.5‐fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.
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.
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.