[COVID-19 in children and adolescents with chronic lung diseases]. / COVID-19 bei Kindern und Jugendlichen mit chronischen Lungenerkrankungen: Klinische Erfahrungen und Perspektiven.

Background: At the beginning of the SARS-CoV­2 pandemic the focus of attention was on children and adolescents with chronic lung diseases. Due to a lack of epidemiological data and clinical experience, it was feared that children with respiratory diseases were a risk group for particularly severe courses of COVID-19, as has been reported for adults. Objective: The currently available (epidemiological) data on this patient group are presented as well as a description of our own experiences based on three selected cases. Material and methods: A review of the literature was carried out and three selected case reports and a discussion of current recommendations are presented. Results: The incidence of COVID-19 is significantly lower in children than in adults. Furthermore, the known risk factors in adults cannot be simply transferred to pediatric patients. In the majority of cases, children and adolescents with chronic lung diseases show a milder course of SARS-CoV­2 infections. Conclusion: Although the hitherto available data show that children and adolescents have a lower risk for COVID-19 courses than adults, it should not be ignored that fatal outcomes have also been reported in pediatric patients. Moreover, late effects, such as the pediatric inflammatory multisystem syndrome (PIMS) can sometimes lead to a fatal outcome. Nevertheless, care must be taken that this vulnerable patient group does not suffer from avoidable negative side effects of restriction and isolation measures. As an example, the no-show behavior in outpatient departments during the lockdown might have led to a relevant undertreatment of underlying chronic health conditions.

A rare-earth free magnesium alloy with improved intrinsic ductility.

Metals are the backbone of manufacturing owing to their strength and formability. Compared to polymers they have high mass density. There is, however, one exception: magnesium. It has a density of only 1.7 g/cm3, making it the lightest structural material, 4.5 times lighter than steels, 1.7 times lighter than aluminum, and even slightly lighter than carbon fibers. Yet, the widespread use of magnesium is hampered by its intrinsic brittleness. While other metallic alloys have multiple dislocation slip systems, enabling their well-known ductility, the hexagonal lattice of magnesium offers insufficient modes of deformation, rendering it intrinsically brittle. We have developed a quantum-mechanically derived treasure map which screens solid solution combinations with electronic bonding, structure and volume descriptors for similarity to the ductile magnesium-rare earth alloys. Using this insight we synthesized a surprisingly simple, compositionally lean, low-cost and industry-compatible new alloy which is over 4 times more ductile and 40% stronger than pure magnesium. The alloy contains 1 wt.% aluminum and 0.1 wt.% calcium, two inexpensive elements which are compatible with downstream recycling constraints.

Softening non-metallic crystals by inhomogeneous elasticity.

High temperature structural materials must be resistant to cracking and oxidation. However, most oxidation resistant materials are brittle and a significant reduction in their yield stress is required if they are to be resistant to cracking. It is shown, using density functional theory, that if a crystal's unit cell elastically deforms in an inhomogeneous manner, the yield stress is greatly reduced, consistent with observations in layered compounds, such as Ti3SiC2, Nb2Co7, W2B5, Ta2C and Ta4C3. The mechanism by which elastic inhomogeneity reduces the yield stress is explained and the effect demonstrated in a complex metallic alloy, even though the electronegativity differences within the unit cell are less than in the layered compounds. Substantial changes appear possible, suggesting this is a first step in developing a simple way of controlling plastic flow in non-metallic crystals, enabling materials with a greater oxidation resistance and hence a higher temperature capability to be used.

[Normal and Adventitious Breath Sounds]. / Atemgeräusche und Atem-Nebengeräusche.

Auscultation of the lung is an inexpensive, noninvasive and easy-to-perform tool. It is an important part of the physical examination and is help ful to distinguish physiological respiratory sounds from pathophysiological events. Computerized lung sound analysis is a powerful tool for optimizing and quantifying electronic auscultation based on the specific lung sound spectral characteristics. The automatic analysis of respiratory sounds assumes that physiological and pathological sounds are reliably analyzed based on special algorithms. The development of automated long-term lungsound monitors enables objective assessment of different respiratory symptoms.

[What is Important for Diagnosis and Therapy Follow-up in Chronic Cough?]. / Was ist für die Diagnostik und Therapieverlaufskontrolle von chronischem Husten wichtig?

Within the last years there has been significant progress in the field of chronic cough. So far, the analysis and evaluation of chronic cough was done mainly on the basis of subjective methods such as manual counts of cough events, questionnaires and diaries. Testing cough hypersensitivity and monitoring 24 h cough represent objective criteria. Validated questionnaires on cough frequency and quality of life represent the impact of chronic cough. Cough frequency monitoring, the preferred tool to objectively assess cough, should be used as primary end-point in clinical trials. It will also be possible to discriminate between productive and non-productive cough. The relationship with subjective measures of cough is weak. In the future, cough and its therapy should therefore be assessed with a combination of subjective and objective tools.

Plasmapheresis prior to omalizumab administration in a 15-year-old boy with severe asthma and very high IgE levels: sustained effect over 2 years.

BACKGROUND: Anti-IgE therapy with omalizumab is an innovative therapy option in patients with severe allergic asthma. However, many patients are excluded from this treatment due to very high serum IgE levels which lie above the weight-dependent cut-off for a reasonable omalizumab administration (700 kU/l). OBJECTIVE: We sought to evaluate whether a preceding plasma exchange is suitable to establish the starting basis for a subsequent anti-IgE therapy in a 15 year-old boy with steroid-resistant unstable allergic asthma whose pretreatment serum IgE levels ranged between 3 000 and 8 000 kU/l. METHODS: Our aim was to create a period with relatively low IgE serum concentrations, which could be overridden by a high dose of omalizumab. 3 sessions of plasmapheresis were performed and 3×3 000 ml plasma were exchanged against albumin solution. RESULTS: We removed an absolute amount of 8 650 kU total IgE. During plasmapheresis, serum IgE levels markedly declined and fell below 500 kU/l. Immediately after the third plasma exchange, we started omalizumab therapy. As expected, total IgE levels began to rise again upon cessation of plasmapheresis, and after 2 months the pre-treatment values were reached. In contrast, serum concentrations of free IgE remained stable on a level of about 80 kU/l during the whole observation period. During this period, the boy displayed a considerable improvement of asthma control and an increase in quality of life. In addition, his previously poor lung function normalized. CONCLUSIONS: Plasmapheresis prior to omalizumab administration is suitable to temporarily reduce grossly elevated serum IgE levels and might facilitate anti-IgE therapy in selected patients previously considered not suitable for this therapy.

Composition of the immunoglobulin classic antigen-binding site regulates allergic airway inflammation in a murine model of experimental asthma.

BACKGROUND: When bound to mast cell FcepsilonRI, IgE serves as antigen receptor for allergic reactions, permitting specific identification of the allergen. Although the core of the classic antigen-binding site is heavy chain complementarity determining region 3 (CDR-H3), recent studies suggest that allergens might also bind IgE in a superantigen-like fashion outside the classic antigen-binding site. OBJECTIVE: We sought to evaluate the contribution of the classic CDR-H3-centric antigen-binding site to the development of an allergic phenotype. METHODS: Using a murine model of experimental asthma, we characterized a gene-targeted mouse strain expressing an altered range of CDR-H3s (DeltaD-iD mice) in response to the hydrophobic allergen ovalbumin (OVA). Mutant and wild-type (wt) mice were sensitized intraperitoneally with OVA; non-sensitized mice served as controls. RESULTS: We found the composition of the classic CDR-H3-centric antigen-binding site to be critical for the development of characteristic aspects of allergic asthma. (i) Compared with wt animals, DeltaD-iD mice showed a significantly less pronounced OVA-induced rise in allergen-specific IgE levels and hence in total serum IgE levels. (ii) In addition, DeltaD-iD mice demonstrated a significant reduction in eosinophilic airway inflammation, as well as in interleukin-4 (IL-4), IL-5 and IL-13 levels in BAL fluids. CONCLUSION: Allergic sensitization and airway inflammation depend on the composition of the predominant CDR-H3 repertoire, suggesting that the classic CDR-H3-centric antigen-binding site plays a crucial role in creating the immunological interface between allergen and IgE. Our results further emphasize a central role of IgE, not only in mediating but also in regulating the allergic immune response.

Hyperferritinemia as the diagnostic clue in life-threatening hemophagocytic lymphohistiocytosis.

We report on a seventeen year old girl with persistent fever of unknown origin. An initial episode of abdominal pain led to laparotomy and appendectomy, which did not reveal any pathological findings. In the course of the next 3 weeks, the girl's general condition progressively deteriorated. Despite extensive diagnostics, no explanation was found. In summary, the girl was cared for by five different departments in two hospitals before she was admitted to our Children's Hospital. We too were initially misguided by the clinical picture of an infectious disease and treated the girl unsuccessfully with antibiotics. The clue in this case was the finding of a markedly elevated level of serum ferritin. While a normal upper value of less than 400 microg/l is reported, our patient displayed levels above 60,000 microg/l. Such extreme elevations of serum ferritin have been almost exclusively reported for hemophagocytic syndromes, as hemophagocytic lymphohistiocytosis (HLH). In HLH, impaired cytolytic function of T cells and natural killer cells leads to a state of hyperinflammation. We treated our patient with immunoglobulins and corticosteroids. Simultaneously, we started immunomodulatory therapy with oral cyclosporine A. The clinical response to this treatment was remarkable. The child's general condition stabilized quickly and the fever vanished. Additionally, the recovery was accompanied by a normalization of laboratory findings. In conclusion, HLH is a potentially life-threatening disease, which has to be considered in cases with fever of unknown origin. In our case, the diagnostic clue was an extreme elevation of ferritin.