[T-cell immune responses in chronic inflammatory diseases of the nasal mucosa]. / T-Zell-Immunreaktionen bei chronisch entzündlichen Erkrankungen der nasalen Schleimhäute.

Acute rhinosinusitis and chronic rhinosinusitis are inflammatory diseases of the mucosal membranes due to mislead immunological reactions to aeroallergens. T­cells are divided into different groups based on their cytokine secretion: T­helper type 1 (Th1) and type 2 (Th2) cells. The allergic immune response is caused by activation of specific Th2 cells. With specific immunotherapy, the mislead hyperactivated "allergic" immune response is reduced to a reaction within the normal range. The inflammatory forms of chronic rhinosinusitis are called endotypes, and, in the future, could enable a targeted, pathomechanistic therapy. These endotype-based treatment approaches target specific signaling pathways that have already shown good effects for chronic rhinosinusitis with nasal polyps using monoclonal antibodies. However, so far, only selected patients with non-rhinologic indications, off-label treatments, or in clinical trials have benefited from these treatments.

[Immunodeficiency in chronic rhinosinusitis : An important and often underestimated cause]. / Immundefekte bei chronischer Rhinosinusitis : Eine bedeutende und oft unterschätzte Ursache.

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.

[Histamine receptors in chronic inflammatory diseases of the nose and paranasal sinuses]. / Histaminrezeptoren bei chronisch-entzündlichen Erkrankungen der Nase und Nasennebenhöhlen.

BACKGROUND: Release of histamine from mast cells and basophils in inflammatory diseases of the nose and paranasal sinuses has been demonstrated in allergic and non-allergic processes. METHODS: A selective literature search was conducted in PubMed and Medline, and publications in German-language journals were additionally analyzed. RESULTS: The histamine receptors H1-H4 play a role in otorhinolaryngologic inflammatory diseases. To date, the histamine receptor subtype 4 (H4R), which is functionally expressed by immune cells in chronic inflammatory diseases, has received little attention. Stimulation of H4R influences the release of cytokines and chemokines as well as the migration behavior of immune cells. In animal models blockade of H4R reduced inflammation symptoms and pruritus. CONCLUSIONS: H4R plays a key role in the pathogenesis of chronic inflammatory diseases and may represent an interesting future therapeutic target.

[Reasons for the development of allergies in children]. / Gründe für die Entstehung von Allergien bei Kindern.

Allergies are one of the most common chronic diseases in childhood, contributing to a tremendous medical and economical burden in health care systems of most industrialized countries. The development of allergies is dependent on a complex interaction of-among others-environmental factors, nutrition, genetic and epigenetic mechanisms as well as the microbiome. These diverse factors can influence early life immune regulation including innate and adaptive immune mechanisms in a complex fashion. In case of any Childhood allergies have increased significantly in past decades. In addition to environmental factors and nutrition, genetic and epigenetic mechanisms as well as the microbiome of children play an important role. Of relevance is the way in which these diverse factors influence early immune development of the innate and adaptive immune systems of children. Their complex regulation is decisive for whether or not a child develops an allergy that manifests in most cases as atopic dermatitis, bronchial asthma, or allergic rhino conjunctivitis, or whether a child develops an immune tolerance. These influences can begin prenatally, already setting the course for later immune system development and occurrence of disease.

[Immunology of chronic rhinosinusitis with nasal polyps as a basis for treatment with biologicals]. / Immunologie der Polyposis nasi als Grundlage für eine Therapie mit Biologicals.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial inflammation of the nasal and paranasal mucosa. Until now, no internationally standardized classification could be developed. In most cases, CRS is phenotypically classified according to chronic rhinosinusitis with (CRScNP) and without nasal polyps (CRSsNP). However, recent studies could show that there are numerous endotypes within these phenotypes based on different inflammatory mechanisms. This review describes the important immunological mechanisms of CRScNP and highlights modern treatment options with biologicals directly addressing particular immunological processes. METHODS: Current knowledge on immunological and molecular processes of CRS, particularly CRScNP, was extracted from Medline, PubMed, national and international study- and guideline-registers, and the Cochrane library by a systematic review of the literature. RESULTS: Based on current literature, various immunological mechanisms for CRS and CRScNP could be identified. Relevant studies for the treatment of eosinophilic conditions such as asthma or CRScNP are presented and, if available, results of these studies are discussed. CONCLUSION: The growing insight into the underlying immunological mechanisms of CRScNP could pave the way for new personalized treatment options such as biologicals in the future.

[Regulatory dysfunctions in nasal polyposis]. / Regulatorische Dysfunktionen bei der Polyposis nasi.

Chronic rhinosinusitis is a heterogeneous group of inflammatory diseases with significant annual costs for the health care system. To date, there is no distinct signaling pathway known that explains the entire process from the beginning to tissue transformation. Due to the diversity of chronic rhinosinusitis, no uniform treatment has yet been developed. With a focus on chronic rhinosinusitis with nasal polyps (CRSwNP), molecular biologic gene expression studies have been performed to identify specific characteristics of nasal polyps that might allow the development of new therapeutic procedures. Microarray analysis revealed alterations in cell adhesion and differentiation as well as blood vessels. Further examinations identified two mechanisms that could play an important role in the pathogenesis of nasal polyps. In the context of the underlying disease, i.e., Th2-mediated chronic inflammation with predominantly eosinophilic cell infiltration, these findings might explain the pathogenesis of nasal polyps and allow development of new therapeutic strategies.

A possible role of stem cells in nasal polyposis.

Since its discovery, the understanding of stem/progenitor cells raised dramatically in the last decade. Their regenerative potential is important to develop new therapeutic applications, but the identification advanced much faster than our understanding of stem/progenitor cells. In nasal polyposis, little is known about stem cells/progenitor cells and their ability. However, the further characterization of stem cells/progenitor cells may provide new treatment options for combating nasal polyposis. This review highlights the knowledge of the current literature about stem cells/progenitor cells in nasal polyposis and how this may be exploited in the development of novel treatment strategies.

EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis.

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.