Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) was formerly known as Churg-Strauss syndrome. The condition is characterized by disseminated necrotizing vasculitis with extravascular granulomas associated with hypereosinophilia. The vasculitides affect small vessels and are associated with antineutrophil cytoplasmic antibodies (ANCAs) detectable in the blood. Distinguishing between type 2-mediated chronic airway inflammation such as chronic rhinosinusitis with nasal polyps (CRSwNP) without vasculitis can be clinically challenging and should be considered. Methods: Immunological background, diagnosis, and therapy of EGPA were identified through literature searches in Medline, PubMed, as well as national and international studies (ClinicalTrials.gov), and the Cochrane Library. Human studies published up to and including 10/2023 on the topic were considered. Results: In cases of deteriorating general health with previously known eosinophilic inflammation of the upper and lower airways, EGPA and its interdisciplinary investigation should be considered. Various types of eosinophilic inflammation and syndromes must be considered differentially. Conclusion: Characterization of mucosal airway inflammation through biomarker determination is meaningful and occasionally makes the difference for targeted therapy

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. Methods: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. Results: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. Conclusions: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Introduction: Eosinophils play an important regulatory and immunomodulatory role in airway mucosa and have antiparasitic and antiviral properties as well as pro-inflammatory effects that may also cause persistence of inflammation with tissue remodeling. The number of eosinophils and the detection of specific mediators in biological samples from, e.g., blood, nasal secretions, and bronchial fluid can serve as biomarkers that reflect the underlying pathophysiology of certain diseases, predict treatment success, and detect therapy effects. Methods: A literature search was conducted to determine the immunologic basis, mode of action, clinical significance, and available evidence for therapeutic approaches of eosinophil-addressing monoclonal antibodies by searching Medline, Pubmed, and the national and international trial and (ClinicalTrials.gov) and guideline registries as well as the Cochrane Library. Human studies published on the topic in the period up to and including 10/2023 were considered. Results: Based on the international literature and previous experience, the results are summarized, and recommendations are given. Conclusion: The important role of eosinophils in immunological processes in the airway mucosa is comprehensively analyzed and can serve as a basis for current and future treatment approaches.

Allergic rhinitis (AR) is a very common disease with a high prevalence worldwide. It is an IgE-mediated type 2 inflammatory disease following exposure to inhalant allergens. A multitude of different neuropeptides including substance P, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), and neuromedin U (NMU) can be released via peripheral axon or central reflexes, interact with immune cells, and thus contribute to neurogenic inflammation which causes the nasal hyperreactivity (NHR) characteristic of AR. Independent production of neuroendocrine hormones and neuropeptides by immune cells has also been demonstrated. Neuro-immune cell units arise when immune and neuronal cells colocalize, for which typical anatomic regions are, e.g., the mast cell-nerve functional unit. The focus of this review is the elucidation of neuroimmune communication mechanisms in AR.

IntroductionApproximately 5%-12% of the population worldwide suffer from chronic rhinosinusitis (CRS). CRS is defined as a chronic respiratory disease and is considered to be a risk factor for COVID-19 patients.Areas coveredA non-systematic literature research was conducted on COVID-19 and treatment options for CRSwNP. The latest international publications in medical databases, international guidelines, and the internet were reviewed. Since there were no publications on all aspects of this topic during the pandemic, we included our own experience in this report. Based on the conducted literature research in addition to our previously reported experience, we discuss the treatment of CRSwNP during the COVID-19 pandemic and what can be taken for future pandemics.Expert opinionIntranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Indications for surgical treatment of CRS should be critically evaluated and reserved for patients with complications and those with no other treatment options. For this purpose, COVID-19 status should be known if possible and, in case of unclear status (emergency), using appropriate personal protective equipment. Systemic corticosteroids should be avoided were possible. Biological treatment should be continued under careful monitoring in uninfected patients and should be temporarily interrupted during COVID-19 infection.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary.Methods A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered.Results Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet.Conclusions Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Die allergische Rhinitis (AR) ist eine sehr häufige Erkrankung mit weltweit hoher Prävalenz. Sie ist eine IgE-vermittelte und entzündungsbedingte Typ-2-Erkrankung nach Exposition gegenüber inhalativen Allergenen. Eine Vielzahl von Neuropeptiden wie Substanz P (SP), vasoaktives intestinales Peptid (VIP), „calcitonin gene-related peptide“ (CGRP), Nervenwachstumsfaktor (NGF) und Neuromedin U (NMU) können über periphere Axonreflexe oder zentrale Reflexe freigesetzt werden, mit Immunzellen interagieren und sind so an einer neurogenen Entzündung beteiligt, die zur nasalen Hyperreaktivität (NHR) der AR führt. Die eigenständige Produktion von neuroendokrinen Hormonen und Neuropeptiden durch Immunzellen wurde ebenfalls nachgewiesen. Neuroimmunzellverbände entstehen, wenn Immun- und neuronale Zellen kolokalisieren. Typische anatomische Regionen dafür sind beispielsweise die Nerv-Mastzellen-Einheit. In dieser Übersicht liegt der Fokus auf der Ausarbeitung neuroimmunologischer Kommunikationsmechanismen der AR.

Zusammenfassung Hintergrund Die chronische Rhinosinusitis mit Nasenpolypen (CRSwNP) ist eine multifaktorielle entzündliche Erkrankung der Schleimhäute von Nase und Nasennebenhöhlen. Eine eosinophile Entzündung wird als häufiger Endotyp beschrieben. Der Anti-IL-5-Antikörper Mepolizumab ist seit November 2021 als Zusatztherapie zu intranasalen Glukokortikosteroiden für die Behandlung Erwachsener mit schwerer chronischer Rhinosinusitis mit Nasenpolypen zugelassen, wenn systemische Glukokortikosteroide oder eine Operation keine ausreichende Krankheitskontrolle bewirken. Während nationale und internationale Empfehlungen für den Einsatz von Mepolizumab bei CRSwNP existieren, ist bislang nicht hinreichend festgelegt worden, wie diese Therapie überwacht wird, welche Folgedokumentation notwendig ist und wann sie ggf. beendet werden sollte. Methoden In einer Literatursuche wurden die bisherigen Daten zur Behandlung der CRSwNP mit Mepolizumab analysiert und die vorhandene Evidenz durch Recherchen in MEDLINE, PubMed sowie den nationalen und internationalen Studien- und Leitlinienregistern und der Cochrane Library ermittelt. Es wurden Humanstudien berücksichtigt, die im Zeitraum bis einschließlich 10/2022 publiziert wurden. Ergebnis Basierend auf der internationalen Literatur und bisherigen Erfahrungen werden von einem Expertengremium Empfehlungen für die Verlaufskontrolle, das Einhalten von Therapieintervallen und eventuelle Therapiepausen sowie eine Beendigung der Therapie bei Anwendung von Mepolizumab für die Indikation CRSwNP im deutschen Gesundheitssystem auf der Grundlage eines Dokumentationsbogens gegeben. Schlussfolgerungen Das Verständnis über die immunologischen Grundlagen der CRSwNP eröffnet neue, nichtoperative Therapieansätze mit Biologika für Patient*innen mit schweren, unkontrollierten Verlaufsformen. Hier geben wir Empfehlungen für die Verlaufskontrolle, das Einhalten von Therapieintervallen, eventuelle Therapiepausen oder eine Beendigung der Therapie bei einer Mepolizumab-Behandlung als Zusatztherapie mit intranasalen Glukokortikosteroiden zur Behandlung von erwachsenen Patient*innen mit schwerer CRSwNP, die mit systemischen Glukokortikosteroiden und/oder chirurgischem Eingriff nicht ausreichend kontrolliert werden kann.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. Methods A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. Results Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. Conclusions Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

Background: The epithelial immune regulation is an essential and protective feature of the barrier function in the area of the mucous membranes of the airways. Damage to the epithelial barrier can result in chronic inflammatory diseases, such as chronic rhino sinusitis (CRS) or bronchial asthma. The thymic stromal lymphopoietin (TSLP) is a central regulator in the epithelial barrier function and is associated with type 2 and non-type 2 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 type 2 and non-type 2 inflammation were examined were considered. Result: 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. Conclusion: 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.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease, often based on type 2 inflammation. Dupilumab and omalizumab are the currently approved biologics for the treatment of patients with severe CRSwNP without sufficient response to standard therapy with topical nasal steroids and/or post-endonasal surgery. After we have already given appropriate advice for dupilumab in a previous publication, the aim of the present paper is to standardise patient information and education prior to the therapy with omalizumab.Methods Based on the current state of knowledge on the immunology of CRSwNP and on the desired and possible adverse effects of omalizumab, recommendations for patient information are developed.Results Based on the international literature, current expert information and experience from practical use and current pharmacovigilance data, an expert panel developed recommendations for patient information and education on the use of omalizumab in CRSwNP and based on this, a patient information and education form was developed.Conclusion Patient information and consent are recommended prior to the prescription or administration of all biologics, thus including omalizumab. This position paper contains important information on practical implementation and a proposal for a patient information sheet.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial inflammatory disease of the nasal and paranasal mucosa. To date, no internationally standardized uniform classification has been developed for this disease. Usually, a phenotype classification according to CRS with (CRSwNP) and without (CRSsNP) polyposis is performed. However, through a variety of studies, it has been shown that even within these phenotypes, different endotypes of CRS exist, each with a different underlying inflammatory pathophysiology. In this mini-review, we aim to outline the essential immunological processes in CRSwNP and to highlight the modern therapeutic options with biologics derived from this disease. Methods: Current knowledge on the immunological and molecular processes of CRS, especially CRSwNP, was compiled by means of a structured literature review. Medline, PubMed, national/international trial and guideline registries as well as the Cochrane Library were all searched. Results: Based on the current literature, the different immunological processes involved in CRS and nasal polyps were elaborated. Current studies on the therapy of eosinophilic diseases such as asthma and polyposis are presented and their results discussed. Conclusion: Understanding the immunological basis of CRSwNP may help to develop new personalized therapeutic approaches using biologics. Currently, 2 biologics (dupilumab, omalizumab) have been approved for the therapy of CRSwNP (polyposis nasi) in Europe.

Weniger als ein Jahr nach der Entdeckung des „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV-2) wurden in zahlreichen Ländern Impfstoffe für 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 unerwünschten 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 ungefähr 1 auf 100.000 Impfinjektionen etwa zehnmal so hoch zu sein wie bei früheren 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 Präsentation und der Verlauf allergischer Reaktionen nach Applikation der COVID-19-Impfstoffe. Im Anschluss wird auf das therapeutische Vorgehen bei anaphylaktischer Reaktion und die dafür notwendigen Medikamente und medizinischen Materialien eingegangen. Zu beachten ist, dass eine Anaphylaxie jeden Geimpften treffen kann, unabhängig 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.

ZusammenfassungHintergrund Die chronische Rhinosinusitis mit Nasenpolypen (CRSwNP) ist eine multifaktorielle entzündliche Erkrankung der nasalen und paranasalen Schleimhaut, der oftmals eine Typ-2-Inflammation zugrunde liegt. Durch die Entwicklung von Biologika, die in diese Entzündungsmechanismen eingreifen können, steht eine neuartige Therapiemöglichkeit zur Verfügung.Methoden Auf Grundlage des aktuellen Wissensstandes zur Immunologie der CRSwNP und der Wirkung von Biologika sowie deren mögliche unerwünschte Wirkungen werden Empfehlungen für die Patienteninformation entwickelt.Ergebnisse Basierend auf der internationalen Literatur und bisherigen Erfahrungen hat ein Expertengremium Empfehlungen für die Patienteninformation und -aufklärung zur Anwendung von Biologika bei CRSwNP entwickelt und auf dieser Grundlage einen Aufklärungsbogen erstellt.Schlussfolgerung Die Information und Einwilligung des Patienten ist vor der Verordnung bzw. Verabreichung von Biologika erforderlich. Das vorliegende Positionspapier enthält wichtige Informationen hierzu und einen Vorschlag für eine Patienteninformation.