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BackgroundA perennial house dust mite-associated allergic rhinitis has a major impact on the quality of life of patients and is associated with a high socioeconomic burden. The most common symptoms of allergic rhinitis include a runny nose and nasal congestion, sneezing, itching of nose, mouth and/or throat, and/or ocular symptoms. Affected patients often develop allergic bronchial asthma. Therapy options for allergic rhinitis include allergen avoidance, symptomatic treatment, and allergen immunotherapy. Allergen immunotherapy is the only disease-modifying treatment that can permanently alleviate the symptoms of allergic rhinitis. In July 2021, a new sublingual mite tablet was approved in Germany.MethodsThis review summarizes clinical studies on the 300 IR (index of reactivity) mite tablet in adolescents and adults with house dust mite-associated allergic rhinitis and presents the results.ResultsIn the phase II and phase III studies considered here, different dosages of the mite tablet were investigated. The 300 IR mite tablet showed the best benefit–risk profile and has been approved in Europe, Japan, South Korea, Australia, and New Zealand for the treatment of house dust mite-associated allergic rhinitis.ConclusionAllergen immunotherapy with the 300 IR mite tablet is an effective treatment that relieves allergic symptoms, reduces the need for symptomatic medication, and improves the quality of life in both adults and adolescents with house dust mite-associated allergic rhinitis. At the same time, treatment with the 300 IR mite tablet is well tolerated. Mild to moderate reactions at the application site subside after a few days.

House dust mites are a major source of allergens in house dust and, thus, the main trigger of perennial allergic respiratory diseases [1–5]. Scientific research on the life cycle, diet, and reproductive behavior of dust mites and on the biology of mite allergens has uncovered mechanisms leading to the development of respiratory allergies and suggests measures that can minimize exposure to dust mite allergens. Here, we discuss the evidence linking house dust mite exposure and respiratory allergies and present the efficacy of avoidance measures and their scientific evidence.

Background Storage mites are frequently found in our daily environment. Nevertheless, storage mite allergy is often neglected in allergological diagnostics and possible allergies requiring therapy are thus overlooked. Methods Recommendations for action are made based on a literature review from March 2021 to August 2021 in PubMed, Medline, and GoogleScholar. Results This review article provides an overview of the species of storage mites, sensitization rates in different countries and occupations, and co-sensitization rates to house dust mite. Recommendations for diagnosis as well as therapy are given. The importance of provocation testing as well as causal therapy by allergen immunotherapy (AIT) is presented. Conclusion The position paper gives recommendations for the diagnosis and therapy of allergic rhinitis in case of storage mite allergy. AIT is recommended in symptomatic allergy and proven storage mite allergy. Reliable detection by provocation testing is advised in this persistent allergy. The therapy should be carried out independently of the treatment of a possible house dust mite allergy.

The epithelial immune regulation is an essential and protective feature of the barrier function of the mucous membranes of the airways. Damage to the epithelial barrier can result in chronic inflammatory diseases, such as chronic rhinosinusitis (CRS) or bronchial asthma. Thymic stromal lymphopoietin (TSLP) is a central regulator in the epithelial barrier function and is associated with type 2 (T2) and non-T2 inflammation.The immunology of chronic rhinosinusitis with polyposis nasi (CRSwNP) was analyzed in a literature search, and the existing evidence was determined through searches in Medline, Pubmed as well as the national and international study and guideline registers and the Cochrane Library. Human studies or studies on human cells that were published between 2010 and 2020 and in which the immune mechanisms of TSLP in T2 and non-T2 inflammation were examined were considered.TSLP is an epithelial cytokine (alarmin) and a central regulator of the immune reaction, especially in the case of chronic airway inflammation. Induction of TSLP is implicated in the pathogenesis of many diseases like CRS and triggers a cascade of subsequent inflammatory reactions.Treatment with TSLP-blocking monoclonal antibodies could therefore open up interesting therapeutic options. The long-term safety and effectiveness of TSLP blockade has yet to be investigated.

Vitamin D (VitD) and its receptor (VDR) have been intensively investigated in many cancers. As knowledge for head and neck cancer (HNC) is limited, we investigated the (pre)clinical and therapeutic relevance of the VDR/VitD-axis. We found that VDR was differentially expressed in HNC tumors, correlating to the patients’ clinical parameters. Poorly differentiated tumors showed high VDR and Ki67 expression, whereas the VDR and Ki67 levels decreased from moderate to well-differentiated tumors. The VitD serum levels were lowest in patients with poorly differentiated cancers (4.1 ± 0.5 ng/mL), increasing from moderate (7.3 ± 4.3 ng/mL) to well-differentiated (13.2 ± 3.4 ng/mL) tumors. Notably, females showed higher VitD insufficiency compared to males, correlating with poor differentiation of the tumor. To mechanistically uncover VDR/VitD’s pathophysiological relevance, we demonstrated that VitD induced VDR nuclear-translocation (VitD < 100 nM) in HNC cells. RNA sequencing and heat map analysis showed that various nuclear receptors were differentially expressed in cisplatin-resistant versus sensitive HNC cells including VDR and the VDR interaction partner retinoic acid receptor (RXR). However, RXR expression was not significantly correlated with the clinical parameters, and cotreatment with its ligand, retinoic acid, did not enhance the killing by cisplatin. Moreover, the Chou–Talalay algorithm uncovered that VitD/cisplatin combinations synergistically killed tumor cells (VitD < 100 nM) and also inhibited the PI3K/Akt/mTOR pathway. Importantly, these findings were confirmed in 3D-tumor-spheroid models mimicking the patients’ tumor microarchitecture. Here, VitD already affected the 3D-tumor-spheroid formation, which was not seen in the 2D-cultures. We conclude that novel VDR/VitD-targeted drug combinations and nuclear receptors should also be intensely explored for HNC. Gender-specific VDR/VitD-effects may be correlated to socioeconomic differences and need to be considered during VitD (supplementation)-therapies.

Introduction: Type 2 targeting biologics have reached the market first for asthma and since 2019 also for CRSwNP. As clear guidelines and predictors for optimal biological choice are missing, patients are sometimes required to switch biologic therapy in order to find the optimal treatment result. In this paper, we evaluate reasons for switching biologics and the treatment effects after each sequential switch. Materials and methods: Ninety-four patients who switched from one biologic to another for their treatment of CRSwNP and asthma were evaluated. Results: Twenty patients experienced satisfactory control of CRSwNP, but insufficient control of severe asthma. Fifty-one patients experienced satisfactory control of severe asthma, but insufficient control of CRSwNP/EOM. Twenty-eight patients experienced insufficient control of both upper and lower airways. Thirteen patients had to switch because of side effects. Furthermore, two cases are described to clarify clinical decision-making. Discussion: For abovementioned patients, a multidisciplinary approach is mandatory to find the best suitable biologic. It seems ineffective to switch to a second anti-IL5 treatment if the first one is not successful. Most patients that failed omalizumab and/or an anti-IL-5 treatment are well controlled on dupilumab. Therefore, we suggest to use dupilumab as first choice when switching biologic agents.

Hintergrund Die chronische Rhinosinusitis (CRS) betrifft weltweit ca. 5–12 % der Allgemeinbevolkerung und wird traditionell eingeteilt in einen Phanotyp ohne (CRSsNP) und einen mit Ausbildung von Nasenpolypen (CRSwNP). Wurden Nasenpolypen bis vor kurzem eher als mechanisches Hindernis mit der Notwendigkeit einer operativen Beseitigung betrachtet, wird die CRSwNP heute als eine multifaktorielle entzundliche Erkrankung der nasalen und paranasalen Schleimhaute angesehen, der als Endotyp haufig eine T2-Inflammation zugrunde liegt. Biologika, die mit diesen Entzundungsmechanismen interferieren, stellen interessante neue Therapiemoglichkeiten dar. Methoden Das aktuelle Wissen zur Immunologie der CRSwNP und Wirkung von Biologika wurde mittels einer Literaturanalyse durch Recherchen in Medline, PubMed sowie den nationalen und internationalen Studien- und Leitlinienregistern und der Cochrane Library zusammengestellt. Ergebnisse Basierend auf der internationalen Literatur und bisherigen Erfahrungen werden von einem Expertengremium Empfehlungen fur die Anwendung von Biologika bei CRSwNP im deutschen Gesundheitssystem auf der Grundlage eines Dokumentationsbogens gegeben. Schlussfolgerung Das Verstandnis uber die immunologischen Grundlagen der CRSwNP eroffnet neue nichtoperative Therapieansatze mit Biologika fur Patienten mit schweren Verlaufsformen.

ZusammenfassungHintergrund Die chronische Rhinosinusitis mit Nasenpolypen (CRSwNP) ist eine multifaktorielle entzündliche Erkrankung, oftmals auf der Grundlage einer Typ-2-Inflammation. Für die Behandlung von Patienten mit einer schweren Ausprägung ohne ausreichendes Ansprechen auf die Standardtherapie mit topischen nasalen Steroiden und/oder Zustand nach endonasaler Operation sind als Biologika aktuell Dupilumab und Omalizumab für die Therapie zugelassen. Nachdem wir in einer früheren Publikation für Dupilumab bereits entsprechende Hinweise gegeben haben, ist das Ziel der vorliegenden Arbeit die Standardisierung von Patienteninformation und -aufklärung vor einer Therapie mit Omalizumab.Methoden Auf Grundlage des aktuellen Wissensstandes zur Immunologie der CRSwNP und zu den erwünschten und möglichen unerwünschten Wirkungen von Omalizumab werden Empfehlungen für die Patienteninformation entwickelt.Ergebnisse Basierend auf der internationalen Literatur, der aktuellen Fachinformation und Erfahrungen aus der praktischen Anwendung und den derzeitigen Pharmakovigilanz-Daten hat ein Expertengremium Empfehlungen für die Patienteninformation und -aufklärung zur Anwendung von Omalizumab bei CRSwNP entwickelt und auf dieser Grundlage einen Patienteninformations- und Aufklärungsbogen erstellt.Schlussfolgerung Die Information und Einwilligung des Patienten wird vor der Verordnung bzw. Verabreichung von allen Biologika, damit auch Omalizumab, empfohlen. Das vorliegende Positionspapier enthält wichtige Informationen zur praktischen Umsetzung und einen Vorschlag für eine Patienteninformation.

Treatment success of head and neck squamous cell carcinoma (HNSCC) is often hindered by cisplatin resistance. As inherent and acquired therapy resistance counteracts improvement in long-term survival, novel multi-targeting strategies triggering cancer cell apoptosis are urgently required. Here, we identify the vitamin D receptor (VDR) as being significantly overexpressed in tumors of HNSCC patients (n = 604; p = 0.0059), correlating with tumor differentiation (p = 0.0002), HPV status (p = 0.00026), and perineural invasion (p = 0.0087). The VDR, a member of the nuclear receptor superfamily, is activated by its ligand vitamin D (VitD) and analogs, triggering multiple cellular responses. As we found that the VDR was also upregulated in our cisplatin-resistant HNSCC models, we investigated its effect on overcoming cisplatin resistance. We discovered that VitD/cisplatin combinations synergistically killed even cisplatin-resistant cells at clinically achievable levels. Similar results were obtained for the clinically used VitD analog Maxacalcitol. Moreover, VitD/cisplatin combinations inhibited tumor cell migration by E-cadherin upregulation. Signaling pathway analyses revealed that VitD co-treatments triggered cancer cell death by increasing the expression of the pro-apoptotic BCL-2 family protein BIM. BIM’s pro-apoptotic activity in HNSCC cells was confirmed by ectopic overexpression studies. Importantly, BIM expression is positively associated with HNSCC patients’ (n = 539) prognosis, as high expression correlated with improved survival (p = 0.0111), improved therapy response (p = 0.0026), and remission (p = 0.004). Collectively, by identifying, for the first time, the VDR/BIM axis, we here provide a molecular rationale for the reported anti-cancer activity of VitD/analogs in combination therapies. Our data also suggest its exploitation as a potential strategy to overcome cisplatin resistance in HNSCC and other malignancies by inducing additional pro-apoptotic pathways.

Dynamic deacetylation of non-histone proteins by histone deacetylases (HDACs) is a key regulator of protein functions, interactions, and turnover. Among class I HDACs, human HDAC1 and HDAC2 share more than 80% global homology at the amino acid level. However, despite the high redundancy, there are examples for differential substrate specificities of HDAC1 and HDAC2. Until now it remains quite unclear how specific and overlapping functions of HDAC1/HDAC2 are regulated in different contexts. Here, we describe molecular cloning techniques for the generation of HDAC1/HDAC2 hybrid proteins, HDAC1/HDAC2 mutants lacking known interaction domains, and HDAC1/HDAC2 hybrid proteins with interchanged N-terminal domains. These proteins are tools for the analysis of specific protein interactions and functions in mammalian cells.

BackgroundChronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID-19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type-2 (T2) inflammation endotypes. MethodsThe current knowledge on COVID-19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. ResultsBased on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID-19 pandemic. ConclusionIntranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID-19 infection.

Weniger als ein Jahr nach der Entdeckung des „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV-2) wurden in zahlreichen Landern Impfstoffe fur den Routineeinsatz zugelassen und bereits in der Massenimpfung eingesetzt, darunter die mRNA-Impfstoffe BNT162b2 und mRNA-1273. Allergische Reaktionen und Anaphylaxien machen einen wesentlichen Teil der bislang beobachteten unerwunschten Reaktionen auf diese Impfstoffe aus, sind insgesamt aber selten. Die Inzidenz von Anaphylaxien im Kontext der SARS-CoV-2-Impfung mit den mRNA-Impfstoffen scheint mit ungefahr 1 auf 100.000 Impfinjektionen etwa zehnmal so hoch zu sein wie bei fruheren Impfstoffen. Ein Schwerpunkt des vorliegenden Beitrags ist die systematische Betrachtung der Inhaltsstoffe von mRNA-Impfstoffen gegen die „coronavirus disease 2019“ (COVID-19). Dabei wird auf die Unterschiede zu etablierten Impfstoffen eingegangen und das allergische Potenzial von Liposomen, Polyethylenglykol, Tromethamin/Trometamol sowie mRNA diskutiert. Ein weiterer Fokus sind die klinische Prasentation und der Verlauf allergischer Reaktionen nach Applikation der COVID-19-Impfstoffe. Im Anschluss wird auf das therapeutische Vorgehen bei anaphylaktischer Reaktion und die dafur notwendigen Medikamente und medizinischen Materialien eingegangen. Zu beachten ist, dass eine Anaphylaxie jeden Geimpften treffen kann, unabhangig davon, ob bereits allergische Erkrankungen vorbekannt sind. Daher muss jede Impfstelle und jeder Impfarzt darauf vorbereitet sein, schwere allergische Reaktionen zu erkennen und zu behandeln.

Zusammenfassung Hintergrund Die hygienische, richtliniengetreue Wiederaufbereitung von komplexen Instrumenten wie flexiblen HNO-Endoskopen mit und ohne Arbeitskanal stellt Kliniken und Praxen zunehmend vor große Herausforderungen. Ziel der vorliegenden Studie war es daher, die Kosten für ein wiederaufbereitbares Endoskopie-System mit 2 Einweg-Endoskopie-Systemen zu vergleichen und daraus mögliche strategische Überlegungen abzuleiten. Methodik Hierzu wurde eine Kostenvergleichsanalyse bzw. Kostenminimierungsanalyse des an der Hals-, Nasen-, Ohrenklinik und Poliklinik der Universitätsmedizin Mainz vorgehaltenen Endoskopie-Systems mit 2 Einweg-Endoskopie-Systemen der Firma Ambu und Karl Storz durchgeführt. Ergebnisse Die Berechnung der Gesamtkosten des wiederaufbereitbaren Endoskopie-Systems ergab einen Gesamtbetrag von 23,03 € pro Untersuchung (11,60 € Investitionskosten + 5,09 € Reparaturkosten + 6,34 € Wiederaufbereitungskosten). Das Einweg-Endoskopie-System der Firma Ambu schlug mit 120,43 € pro Untersuchung (120,00 € Anschaffungskosten + 0,43 € Lagerungskosten) zu Buche. Das Einweg-Endoskopie-System der Firma Karl Storz kostete 223,44 € pro Untersuchung (Investitionskosten für Monitor 3,01 € + 220,00 € Anschaffungskosten + 0,43 € Lagerungskosten). Diskussion Flexible HNO-Einweg-Endoskope verursachen im Vergleich zu konventionellen, wiederaufbereitbaren Systemen höhere Kosten. Aus medizinischer, aber auch ökonomischer Sicht bieten sie jedoch auch Vorteile. Schlussfolgerung Ein guter Mix aus wiederaufbereitbaren Endoskopie-Systemen und Einweg-Systemen, z. B. zur Behandlung von Patienten mit Besiedelung durch kritische Erreger, erscheint daher sinnvoll.

ZusammenfassungDerzeit existieren für Kopf- und Halskarzinome (HNSCC) keine evidenzbasierten Leitlinien für das Re-Staging oder die Tumornachsorge nach primärer Radio(chemo)therapie. In Deutschland ist die hochauflösende Sonografie mit Verwendung von Farbduplexverfahren neben der Computertomografie (CT) und der Magnetresonanztomografie (MRT) ein bewährtes Verfahren zur Therapiekontrolle (Re-Staging) im Rahmen der Tumornachsorge nach der Primärtherapie von Kopf-Hals-Karzinomen. Die PET/CT gilt seit Kurzem als Standard. Es fehlt an klaren Empfehlungen, wie sich die unterschiedlichen in der Routine angewendeten Verfahren ergänzen. Außerdem fehlt es an validen Selektionsalgorithmen für die Indikation zur PET/CT. Indikationen für und wider eine Salvage Neck Dissection werden häufig als Einzelfallentscheidung getroffen. Dieser Artikel soll die gängigen Re-Staging Modalitäten darstellen und ein aktuelles Studienkonzept kurz erläutern.

SummaryLoss of olfaction is one of the symptoms most commonly reported by patients with coronavirus disease 2019 (COVID-19). Although the spontaneous recovery rate is high, recent studies have shown that up to 7% of patients remain anosmic for more than 12 months after the onset of infection, leaving millions of people worldwide suffering from severe olfactory impairment. Olfactory training remains the first recommended treatment. With the continued lack of approved drug treatments, new therapeutic options are being explored. This article reviews the current state of science on COVID-19-related olfactory disorders, focusing on epidemiology, pathophysiology, cure rates, currently available treatment options, and research on new treatments.

Olfactory dysfunction is common in COVID-19, and sudden-onset dysosmia is an early marker for wild-type SARS-CoV-2 infection. Over 10 000 mutations of SARS-CoV-2 have been registered, with variants of concern (VOC) under particular scrutiny. We report a telemedicine-based, multicentre, prospective cohort study with quantitative olfaction testing comparing 79 patients with a confirmed VOC-Delta (n = 21) or wild-type (WT) SARS-CoV-2 infection. Acute SARS-CoV-2 infection led to significant decrease of olfactory function in both cohorts. A majority of patients suffered from hyposmia or anosmia at inclusion with only 26 individuals performing normosmic. Sniffin'Sticks total scores were significantly higher for VOC-Delta patients at onset of illness, compared to WT patients (p < 0.001). At 4 weeks follow-up, olfaction scores recovered only partially for WT patients, thus odds of recovery were stronger in VOC-Delta patients. Also, subjective self-rating of chemosensory function was lower in WT, compared to VOC-Delta patients. The need for ongoing olfaction studies and their prognosis in SARS-CoV-2 background remains urgent, also in the light of increasing numbers of olfaction-related patient presentations.

Therapy resistance is the major cause of cancer death. As patients respond heterogeneously, precision/personalized medicine needs to be considered, including the application of nanoparticles (NPs). The success of therapeutic NPs requires to first identify clinically relevant resistance mechanisms and to define key players, followed by a rational design of biocompatible NPs capable to target resistance. Consequently, we employed a tiered experimental pipeline fromiin silico/ito analytical andiin vitro/ito overcome cisplatin resistance. First, we generated cisplatin-resistant cancer cells and used next-generation sequencing together with CRISPR/Cas9 knockout technology to identify the ion channel LRRC8A as a critical component for cisplatin resistance. LRRC8A's cisplatin-specificity was verified by testing free as well as nanoformulated paclitaxel or doxorubicin. The clinical relevance of LRRC8A was demonstrated by its differential expression in a cohort of 500 head and neck cancer patients, correlating with patient survival under cisplatin therapy. To overcome LRRC8A-mediated cisplatin resistance, we constructed cisplatin-loaded, polysarcosine-based core cross-linked polymeric NPs (NPsubCis/sub, Ø ∼ 28 nm) with good colloidal stability, biocompatibility (low immunogenicity, low toxicity, prolongediin vivo/icirculation, no complement activation, no plasma protein aggregation), and low corona formation properties. 2D/3D-spheroid cell models were employed to demonstrate that, in contrast to standard of care cisplatin, NPsubCis/subsignificantly (ip/ilt; 0.001) eradicated all cisplatin-resistant cells by circumventing the LRRC8A-transport pathwayivia/ithe endocytic delivery route. We here identified LRRC8A as critical for cisplatin resistance and suggest LRRC8A-guided patient stratification for ongoing or prospective clinical studies assessing therapy resistance to nanoscale platinum drug nanoformulations versus current standard of care formulations.

Simple Summary Treatment success of head and neck cancers (HNSCC) is often hindered by chemoresistance. In this study, next-generation sequencing transcriptomics and CRISPR/Cas9 knockout strategies were used to identify cisplatin resistance mechanisms and potential (personalized) biomarkers. Moreover, employing a tiered experimental pipeline, the cisplatin uptake transporter VRAC was found to be critical for cisplatin sensitivity and specificity in 2D/3D-HNSCC cell culture models as well as for tumor relapses in the clinical setting. Our study suggests exploiting VRAC as a potential drug target as well as a personalized prognostic biomarker to improve the treatment of HNSCC patients in the future. Abstract Treatment success of head and neck cancers (HNSCC) is often hindered by tumor relapses due to therapy resistances. This study aimed at profiling cisplatin resistance mechanisms and identifying biomarkers potentially suitable as drug targets and for patient stratification. Bioinformatic analyses of suggested resistance factors in a cohort of 565 HNSCC patients identified the VRAC ion channel as a clinically relevant indicator for recurrent diseases following radiochemotherapy (p = 0.042). Other drug import/export transporters, such as CTR1, OCT1, or MRP1, were found to be less relevant. To experimentally verify VRAC’s critical role for cisplatin resistance, we used CRISPR/Cas9 knockout resulting in cisplatin-resistant HNSCC cells, which could be resensitized by VRAC expression. Next-generation sequencing further underlined VRAC’s importance and identified VRAC-regulated signaling networks, potentially also contributing to cisplatin resistance. CTR1, OCT1, or MRP1 did not contribute to increased cisplatin resistance. In addition to two-dimensional HNSCC models, three-dimensional tumor spheroid cultures confirmed VRAC’s unique role for cisplatin sensitivity. Here, resistance correlated with DNA damage and downstream apoptosis. The cisplatin specificity of the identified VRAC pathway was verified by testing paclitaxel and doxorubicin. Our results were independently confirmed in naturally occurring, cisplatin-resistant HNSCC cancer cell models. Collectively, we here demonstrate VRAC’s role for cisplatin resistance in HNSCC and its relevance as a potential drug target and/or prognostic biomarker for chemotherapy resistance.

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for “social distancing” and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2. Materials and methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 – April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic. Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future. Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.

Background Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases. Among these patients the prevalence of immune defects is higher than in the healthy general population. Methods A selective review of the literature was carried out in PubMed and Medline covering the period between 2008 and 2019. Additionally, recent German publications in journals not listed in the abovementioned databases were analyzed. Results The diagnostic workflow with respect to the immunodeficiency consists of a detailed anamnesis and physical examination, laboratory tests and the antibody reaction to polysaccharide vaccines and antigens. Beside antibiotic treatment, vaccinations and immunoglobulin replacement are available. Notwithstanding the above, functional endoscopic surgery of the paranasal sinuses should be performed according to guideline recommendations. Conclusion Patients with CRS who do not sufficiently respond to conservative and surgical treatment should be checked for underlying immunodeficiencies.

Background Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). Conclusions This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.

Reprocessing of complex instruments like flexible ENT-endoscopes with and without working channel are challanging for clinics and private practices. Aim of the study was to analyse the costs of an examination with a reusable endoscope-system and to compare it with two single-use endoscope-systems.A cost minimization analysis was performed at the Department of Otorhinolaryngology, Head and Neck Surgery of the University Medical Center in Mainz, Germany. The local reusable endoscopy-system was compared with two single-use endoscopy-systems of Ambu and Karl Storz.Overall costs per examination with a reusable-scope were 23.03 € (11.60 € investment costs + 5.09 € repair costs + 6.34 € reprocessing costs). The single-use Endoscopy-system of Ambu resulted in 120.43 € per examination (120.00 € acquisition costs + 0.43 € storage costs). Overall costs for the single-use endoscopy-system of Karl Storz were 223.44 € per examination (investment costs for monitors 3.01 € + 220.00 € acquisition costs + 0.43 € storage costs).Flexible single-use ENT-endoscopy-systems generate higher costs in comparison to conventional reusable ones. But there are also advantages from the medical and economical side.A smart mix of reusable and single-use endoscopy systems seems therefore usefull.Die hygienische, richtliniengetreue Wiederaufbereitung von komplexen Instrumenten wie flexiblen HNO-Endoskopen mit und ohne Arbeitskanal stellt Kliniken und Praxen zunehmend vor große Herausforderungen. Ziel der vorliegenden Studie war es daher, die Kosten für ein wiederaufbereitbares Endoskopie-System mit 2 Einweg-Endoskopie-Systemen zu vergleichen und daraus mögliche strategische Überlegungen abzuleiten.Hierzu wurde eine Kostenvergleichsanalyse bzw. Kostenminimierungsanalyse des an der Hals-, Nasen-, Ohrenklinik und Poliklinik der Universitätsmedizin Mainz vorgehaltenen Endoskopie-Systems mit 2 Einweg-Endoskopie-Systemen der Firma Ambu und Karl Storz durchgeführt.Die Berechnung der Gesamtkosten des wiederaufbereitbaren Endoskopie-Systems ergab einen Gesamtbetrag von 23,03 € pro Untersuchung (11,60 € Investitionskosten + 5,09 € Reparaturkosten + 6,34 € Wiederaufbereitungskosten). Das Einweg-Endoskopie-System der Firma Ambu schlug mit 120,43 € pro Untersuchung (120,00 € Anschaffungskosten + 0,43 € Lagerungskosten) zu Buche. Das Einweg-Endoskopie-System der Firma Karl Storz kostete 223,44 € pro Untersuchung (Investitionskosten für Monitor 3,01 € + 220,00 € Anschaffungskosten + 0,43 € Lagerungskosten).Flexible HNO-Einweg-Endoskope verursachen im Vergleich zu konventionellen, wiederaufbereitbaren Systemen höhere Kosten. Aus medizinischer, aber auch ökonomischer Sicht bieten sie jedoch auch Vorteile.Ein guter Mix aus wiederaufbereitbaren Endoskopie-Systemen und Einweg-Systemen, z. B. zur Behandlung von Patienten mit Besiedelung durch kritische Erreger, erscheint daher sinnvoll.

Filtering facepiece particle (FFP) masks are important items of personal protective equipment in fighting COVID-19 pandemic. They shall protect the wearer of the mask from particles, droplets, and aerosols, but they also can prevent the spread of aerosol-transmitted viruses if the wearer becomes infected. Most often, FFP respirators consist of multiple layers of non-woven fabric made from polypropylene. Worldwide, FFP respirators are subject to various regulatory standards that specify physical properties and performance characteristics. During the SARS-CoV-2 pandemic, health authorities have temporarily repealed standards for respirators. We report on 46 patients that presented with rhinitis-like symptoms strongly associated to the use of FFP masks. Some of them were obliged to use FFP masks in their work environment. Nasal endoscopy showed edemata of the nasal mucosa that significantly decreased after a period of non-use of FFP masks. Subjectively reported symptom levels decreased after cessation of FFP use for 3 or more days. The presence of polypropylene fibres isolated from nasal rinsing solution was significantly associated with the use of FFP masks in our patients. Material safety and performance deregulation of FFP masks can pose a health risk. Thus, especially health care professionals and other individuals with occupational need for FFP masks should be aware of possible hazards that come with COVID-19 pandemic protection measures.