Query: "H. Renz"

title: Environmental exposure to endotoxin and its relation to asthma in school age children.
abstract: In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such as animal dander or tree and grass pollen.  Parents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine production profiles of peripheral blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children.  Endotoxin levels in samples of dust from the child's mattress were inversely related to the occurrence of hay fever, atopic asthma, and atopic sensitization. Nonatopic wheeze was not significantly associated with the endotoxin level. Cytokine production by leukocytes (production of tumor necrosis factor alpha, interferon gamma, interleukin 10, and interleukin 12) was inversely related to the endotoxin level in the bedding, indicating a marked down regulation of immune responses in exposed children.  A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.

title: Risk factors for severity and mortality in adult COVID 19 inpatients in Wuhan
abstract: In December 2019, COVID 19 outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID 19 are limited.  The severity on admission, complications, treatment, and outcomes of COVID 19 patients were evaluated.  Patients with COVID 19 admitted to Tongji Hospital from January 26, 2020 to February 5, 2020 were retrospectively enrolled and followed up until March 3, 2020. Potential risk factors for severe COVID 19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients.  We identified 269 (49.1% of 548 patients as severe cases on admission. Elder age, underlying hypertension, high cytokine levels (IL 2R, IL 6, IL 10, and TNF a) and high LDH level were significantly associated with severe COVID 19 on admission. The prevalence of asthma in COVID 19 patients was 0.9% markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow up period. Survival analysis revealed that male, elder age, leukocytosis, high LDH level, cardiac injury, hyperglycemia, and high dose corticosteroid use were associated with death in patients with severe COVID 19.  Patients with elder age, hypertension, and high LDH level need careful observation and early intervention to prevent the potential development of severe COVID 19. Severe male patients with heart injury, hyperglycemia, and high dose corticosteroid use may have high risk of death.

title: SARS CoV 2 antibody testing questions to be asked
abstract: SARS CoV 2 infection and development of COVID 19 disease presents a major healthcare challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against the SARS CoV 2 virus presents a major cornerstone in handling the pandemic. Currently there is an increase in demand of antibody testing and a large number of tests are already marketed or in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross reactivity and cross protectivity; the diagnostic value of antibodies of different isotypes, the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article the recently established COVID 19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues based on the currently available datasets in this rapidly moving field.

title: Allergen induced asthmatic responses modified by a GATA3 specific DNAzyme.
abstract: The most prevalent phenotype of asthma is characterized by eosinophil dominated inflammation that is driven by a type 2 helper T cell (Th2) Therapeutic targeting of GATA3, an important transcription factor of the Th2 pathway, may be beneficial. We evaluated the safety and efficacy of SB010, a novel DNA enzyme (DNAzyme) that is able to cleave and inactivate GATA3 messenger RNA (mRNA)  We conducted a randomized, double blind, placebo controlled, multicenter clinical trial of SB010 involving patients who had allergic asthma with sputum eosinophilia and who also had biphasic early and late asthmatic responses after laboratory based allergen provocation. A total of 40 patients could be evaluated; 21 were assigned to receive 10 mg of SB010, and 19 were assigned to receive placebo, with each study drug administered by means of inhalation once daily for 28 days. An allergen challenge was performed before and after the 28 day period. The primary end point was the late asthmatic response as quantified by the change in the area under the curve (AUC) for forced expiratory volume in 1 second (FEV1) RESULTS After 28 days, SB010 attenuated the mean late asthmatic response by 34% as compared with the baseline response, according to the AUC for FEV1, whereas placebo was associated with a 1% increase in the AUC for FEV1 (P=0.02) The early asthmatic response with SB010 was attenuated by 11% as measured by the AUC for FEV1, whereas the early response with placebo was increased by 10% (P=0.03) Inhibition of the late asthmatic response by SB010 was associated with attenuation of allergen induced sputum eosinophilia and with lower levels of tryptase in sputum and lower plasma levels of interleukin 5. Allergen induced levels of fractional exhaled nitric oxide and airway hyperresponsiveness to methacholine were not affected by either SB010 or placebo.  Treatment with SB010 significantly attenuated both late and early asthmatic responses after allergen provocation in patients with allergic asthma. Biomarker analysis showed an attenuation of Th2 regulated inflammatory responses.

title: Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78
abstract: The pre and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9 knockout mice. The asthma preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78 treated TLR2/3/4/7/9 homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78 exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.

title: A WAO ARIA GA2LEN consensus document on molecular based allergy diagnosis (PAMD@ Update 2020
abstract: Precision allergy molecular diagnostic applications (PAMD@ is increasingly entering routine care. Currently, more than 130 allergenic molecules from more than 50 allergy sources are commercially available for in vitro specific immunoglobulin E (sIgE) testing. Since the last publication of this consensus document, a great deal of new information has become available regarding this topic, with over 100 publications in the last year alone. It thus seems quite reasonable to publish an update. It is imperative that clinicians and immunologists specifically trained in allergology keep abreast of the new and rapidly evolving evidence available for PAMD@ PAMD@ may initially appear complex to interpret; however, with increasing experience, the information gained provides relevant information for the allergist. This is especially true for food allergy, Hymenoptera allergy, and for the selection of allergen immunotherapy. Nevertheless, all sIgE tests, including PAMD@ should be evaluated within the framework of a patient's clinical history, because allergen sensitization does not necessarily imply clinical relevant allergies.

title: Laboratory characteristics of patients infected with the novel SARS CoV 2 virus
abstract: A subgroup of COVID 19 patients develop very severe disease with requirement for ICU treatment, ventilation, and ECMO therapy. Laboratory tests indicate that the immune and clotting system show marked alterations with hyper activation, hyper inflammation, cytokine storm development. Furthermore, organ specific biomarkers demonstrate the involvement of cardiac muscle, kidney, and liver dysfunction in many patients. In this article the use of laboratory biomarkers is discussed with regard to their use for diagnosis, disease progression, and risk assessment.

title: Molecular diagnosis for allergen immunotherapy.
abstract: The extensive use of allergen molecules in birth cohort studies revealed that atopic sensitization is a sequential IgE response to distinct non cross reacting molecules from the same allergenic source (ie, molecular spreading) starting with an initiator molecule. This phenomenon reaches different degrees of progression (monomolecular, oligomolecular, and polymolecular) according to the individual atopic propensity and allergen exposure, thus producing an extreme heterogeneity of IgE sensitization profiles in patient populations. In patients with allergic rhinitis, the broader the IgE molecular sensitization profile, the greater is the risk of asthma and other allergic comorbidities, such as oral allergy syndrome. Hence it has been proposed to anticipate immunologic intervention at disease onset (early allergen immunotherapy) or even earlier during the preclinical sensitization stage (allergen immunoprophylaxis) Diagnostic algorithms based on singleplex or multiplex molecular IgE tests allow the discrimination of genuine from cross reacting sensitization and the selection of the right extracts for allergen immunotherapy composition. Patients with extreme molecular poly sensitization and greater risk of asthma or other IgE mediated comorbidities, can be easily identified by means of allergen microarray or macroarray procedures and might benefit from anti IgE treatment. IgE molecular tests have opened the era of precision allergology, and their routine use should aim at cost effectiveness, according to the principles of the Choosing Wisely initiative.

title: The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.
abstract: Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD) obesity, and associated noncommunicable diseases (NCDs) There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention.

title: Epigenetics and allergy: from basic mechanisms to clinical applications.
abstract: Allergic diseases are on the rise in the Western world and well known allergy protecting and driving factors such as microbial and dietary exposure, pollution and smoking mediate their influence through alterations of the epigenetic landscape. Here, we review key facts on the involvement of epigenetic modifications in allergic diseases and summarize and critically evaluate the lessons learned from epigenome wide association studies. We show the potential of epigenetic changes for various clinical applications: as diagnostic tools, to assess tolerance following immunotherapy or possibly predict the success of therapy at an early time point. Furthermore, new technological advances such as epigenome editing and DNAzymes will allow targeted alterations of the epigenome in the future and provide novel therapeutic tools.