Anaphylaxis in Elderly Patients-Data From the European Anaphylaxis Registry

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more. Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18–64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed. Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness (33%, p < 0.001) and preexisting cardiovascular comorbidity (59%, p < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p < 0.001) and hospitalization was more often required (60 vs. 50%, p < 0.001). Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome

Peanut‐induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

A comprehensive model for transient moisture transport in wood below the fiber saturation point: physical background, implementation and experimental validation

During the last three decades the macroscopic formulation of moisture transport in wood below the fiber saturation point has motivated many research efforts. From experiments the difference in steady-state and transient transport processes is well known, but it could not be explained in a fully physically motivated manner. In this article, we aim at enhancing the current understanding and improving the mathematical description of the moisture transport process in wood. For this purpose, we first present the microstructure of wood and then describe the physical background of steady-state and transient transport processes in wood, based on which we finally derive a suitable mathematical model. For a correct macroscopic description of transient transport processes, three coupled differential equations have to be solved in parallel, which is done using the finite element method. A comparison of model predictions for the sorption behavior of wood specimens with corresponding experimentally derived values yields very promising results and confirms the suitability of the assumptions underlying the model

Multiscale prediction of viscoelastic properties of softwood under constant climatic conditions

This paper covers the development and validation of a multiscale homogenization model for linear viscoelastic properties of wood. Starting point is the intrinsic structural hierarchy of wood, which is accounted for by several homogenization steps. Using the correspondence principle, an existing homogenization model for the prediction of elastic properties of wood is adapted herein for upscaling of viscoelastic characteristics. Accordingly, self-consistent, Mori–Tanaka, and unit-cell-based techniques are employed, leading to pointwise defined tensorial creep and relaxation functions in the Laplace-Carson domain. Subsequently, these functions are back-transformed into the time domain by means of the Gaver-Stehfest algorithm. With this procedure the orthotropic macroscopic creep behavior of wood can be derived from the isotropic shear behavior of the lignin-hemicellulose phase. A comparison of model predictions for viscoelastic properties of softwood with corresponding experimentally derived values yields very promising results and confirms the suitability of the model

Prediction of transport properties of wood below the fiber saturation point – a multiscale homogenization approach and its experimental validation: Part I: thermal conductivity

This two-part paper covers the development and validation of a multiscale homogenization model for macroscopic transport properties of wood. The starting point is the intrinsic structural hierarchy of wood, which is accounted for by several homogenization steps. Starting on a length scale of a few nanometers the model ends up with macroscopic properties by including the morphology of the intermediate hierarchical levels. In this first part this is done for thermal conductivity, based on a six-level homogenization scheme. The used homogenization technique is continuum micromechanics in terms of self-consistent and Mori-Tanaka schemes. Model validation rests on statistically and physically independent experiments: the macroscopic thermal conductivity values predicted by the multiscale homogenization model on the basis of tissue-independent (universal) phase conductivity properties of hemicellulose, cellulose, lignin, and water (input data set I) for tissue-specific data (input data set II) are compared to corresponding experimentally determined tissue-specific conductivity values (experimental data set)

Multiscale homogenization of wood transport properties: diffusion coefficients for steady-state moisture transport

This paper describes a multiscale homogenization model for macroscopic diffusion properties of wood. After a short introduction the physical background of steady-state diffusion processes in wood will be highlighted, resulting in a physically motivated macroscopic description of diffusion processes with only one diffusion equation and thus one diffusion tensor. This macroscopic diffusion tensor is derived by revisiting the morphological structure of wood in the framework of continuum micromechanics. The starting point is the cellular structure of wood; further homogenization steps include wood rays and the succession of annual rings. The quality of the model is assessed by a comparison of model predictions and measured values at different temperatures and moisture contents