Abstract
Allergologie select, Vol. 6/2022 (148-166)
Epithelial immune regulation of inflammatory airway diseases: Chronic rhinosinusitis with nasal polyps (CRSwNP)
Ludger Klimek1,2, Jan Hagemann2, Hans-Jürgen Welkoborsky3, Mandy Cuevas4, Ingrid Casper1, Ulrike Förster-Ruhrmann5, Felix Klimek1, Constantin A. Hintschich6, Tilman Huppertz2, Christoph Bergmann7, Peter-Valentin Tomazic8, and Sven Becker9
1Center for Rhinology and Allergology, Wiesbaden, 2Clinic and Polyclinic for Otolaryngology, University Medical Center Mainz, Mainz, 3Clinic for Ear, Nose and Throat Medicine, Head and Neck Surgery, Nordstadt Clinic of the KRH, Hannover, 4Clinic and Polyclinic for Otolaryngology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, 5HNO-University Clinic Charité, Berlin, 6Clinic and Polyclinic for Ear, Nose and Throat Medicine, University Hospital Regensburg, Regensburg, 7HNO RKM740 Interdisciplinary Specialist Clinic, Düsseldorf, Germany, 8HNO-University Clinic Graz, Medical University Graz, Austria, and 9HNO-University Clinic Tübingen, Germany
Background: 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. Materials and methods: 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. Results: 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.Correspondence to:
Prof. Dr. med. L. Klimek, Zentrum für Rhinologie und Allergologie Wiesbaden, An den Quellen 10, 65183 Wiesbaden, Germany
Email: [email protected]
Abstract
Allergologie select, Vol. 8/2024 (26-39)
Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?
Ludger Klimek1, Ulrike Förster-Ruhrmann2, Heidi Olze2, Achim G. Beule3,4, Adam M. Chaker5,6, Jan Hagemann7, Tilman Huppertz7, Thomas K. Hoffmann8, Stefan Dazert9, Thomas Deitmer10, Sebastian Strieth11, Holger Wrede12, Wolfgang W. Schlenter13, Hans-Jürgen Welkoborsky14, Barbara Wollenberg5, Sven Becker15, Fredericke Bärhold15, Felix Klimek1, Ingrid Casper1, Jaron Zuberbier2, Claudia Rudack3, Mandy Cuevas16, Constantin A. Hintschich17, Orlando Guntinas-Lichius18, Timo Stöver19, Christoph Bergmann20, Pascal Werminghaus21, Oliver Pfaar22, Jan Gosepath23, Moritz Gröger24, Caroline Beutner25, Martin Laudien26, Rainer K. Weber27, Tanja Hildenbrand28, Anna S. Hoffmann29, and Claus Bachert30
1Center for Rhinology and Allergology, Wiesbaden, 2HNO-University Clinic Charité, Berlin, 3Clinic for Otorhinolaryngology, Münster University Hospital, 4Clinic for Otorhinolaryngology, Head and Neck Surgery at Greifswald University Medical Center, 5Department of Otolaryngology - Head and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, 6Center of Allergy and Environment (ZAUM) of the Technical University of Munich, 7Clinic and Polyclinic for Otolaryngology, University Medical Center Mainz, Mainz, 8Department of Otorhinolaryngology, Head and Neck Surgery, University of Ulm, Ulm, 9Clinic for Otorhinolaryngology, Head and Neck Surgery, Ruhr University Bochum, St. Elisabeth Hospital, 10German Society for Otorhinolaryngology, Head and Neck Surgery, Bonn, 11Clinic and Polyclinic for Otorhinolaryngology, University Hospital Bonn, 12Ear, nose and throat specialist, Herford, 13Medical Association of German Allergists, Wiesbaden, 14Clinic for Ear, Nose and Throat Medicine, Head and Neck Surgery, Nordstadt Clinic of the KRH, Hannover, 15HNO-University Clinic Tübingen, 16K Clinic and Polyclinic for Otolaryngology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, 17Clinic and Polyclinic for Ear, Nose and Throat Medicine, University Hospital Regensburg, Regensburg, 18Clinic for Otorhinolaryngology, Jena University Hospital, 19Otorhinolaryngology University Clinic Frankfurt am Main, 20HNO RKM740 Interdisciplinary Specialist Clinic, Düsseldorf, Germany, 21Praxis für Hals-, Nasen-, Ohrenheilkunde und Allergologie, Düsseldorf, 22Kl Clinic for Ear, Nose and Throat Medicine, University Hospital Giessen and Marburg GmbH, Marburg site, Philipps University Marburg, Marburg, 23Clinic for Otorhinolaryngology, HSK Wiesbaden, 24Clinic and Polyclinic for Otorhinolaryngology, University Hospital LMU Munich, 25K Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Germany Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen, 26Department of Otorhinolaryngology, Head and Neck Surgery, Kiel University, University Medical Centre Schleswig-Holstein, Kiel, 27Clinic for Otorhinolaryngology, Karlsruhe Municipal Hospital, 28Department of Ear, Nose and Throat Medicine, Freiburg University Medical Center, 29Clinic for Ear, Nose and Throat Medicine, University Medical Center Hamburg-Eppendorf, 30Kli Upper Airways Research Laboratory and Department of Oto-Rhino-Laryngology, Ghent University and Ghent, University Hospital, Ghent, Belgien
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-IL-5 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 should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. Materials and 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 discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. Conclusion: 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.Correspondence to:
Professor Dr. med. L. Klimek, Zentrum für Rhinologie und Allergologie Wiesbaden, An den Quellen 10, 65183 Wiesbaden, Germany
Email: [email protected]
Abstract
Allergologie select, Vol. 8/2024 (40-50)
Eosinophil granulocytes in chronic inflammatory respiratory diseases and CRSwNP: Function, immunological basis, and clinical significance
Felix Klimek1, Christoph Bergmann2, Jan Hagemann3, Mandy Cuevas4, Sven Becker5, Oliver Pfaar6, Ingrid Casper1, and Ludger Klimek1
1Center for Rhinology and Allergology, Wiesbaden, 2Practice for Ear, Nose and Throat disease, Clinic RKM 740, Düsseldorf, 3Department for Otolaryngology, University Medical Center Mainz, Mainz, 4Department for Otolaryngology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, 5Department for Otolaryngology, University Hospital Tübingen, Tübingen, and 6Section of Rhinology and Allergy, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
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. Materials and methods: A literature search was conducted to determine the immunologic basis, mode of action, clinical significance, and available evidence for therapeutic approaches using eosinophil-targeted monoclonal antibodies by searching Medline, Pubmed, and the national and international trial database (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.Correspondence to:
Professor Dr. med. L. Klimek, Center for Rhinology and Allergology, An den Quellen 10, 65183 Wiesbaden, Germany
Email: [email protected]
