COVID-19 and chronic rhinosinusitis: management and comorbidity - what have we learned?

INTRODUCTION: Approximately 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 COVERED: A 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 OPINION: Intranasal 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.

[Neuroimmunology of allergic rhinitis part 2 : Interactions of neurons and immune cells and neuroimmunological units]. / Neuroimmunologie der allergischen Rhinitis Teil 2 : Interaktionen von Neuronen und Immunzellen und neuroimmunologische Einheiten.

Allergic rhinitis is an IgE-mediated, type­2 inflammatory disease. neuropeptides are released by neurons and interact with immune cells. Via colocalization, neuroimmune cell units such as nerve-mast cell units, nerve-type 2 innate lymphoid cell (ILC2) units, nerve-eosinophil units, and nerve-basophil units are formed. Markedly elevated tryptase levels were found in nasal lavage fluid and were strongly associated with neuropeptide levels. A close anatomical connection allows bidirectional communication between immune and neuronal cells. Transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin repeat 1 (TRPA1) are critically involved in immunological reactions in the setting of allergic rhinitis. Neuroimmunological communication plays an important role in the inflammatory process, so that allergic rhinitis can no longer be considered a purely immunological disease, but rather a combined neuroimmunological disease.

[Neuroimmunology of allergic rhinitis : Part 1: Cellular and humoral basic principles]. / Neuroimmunologie der allergischen Rhinitis : Teil 1: Zelluläre und humorale Grundlagen.

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.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

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.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem.

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.

[Allergic reactions to COVID-19 vaccines: evidence and practice-oriented approach]. / Allergische Reaktionen auf COVID-19-Impfstoffe ­ Evidenz und praxisorientiertes Vorgehen.

Less than a year after the first detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccines have been approved for routine use in numerous countries and have already been used in mass vaccination programs. Vaccines include the mRNA BNT162b2 and mRNA 1273. Allergic reactions and anaphylaxis account for a substantial proportion of the adverse reactions to these vaccines observed to date, but overall they are rare. The incidence of anaphylaxis in the context of SARS-CoV­2 vaccination with the mRNA vaccines appears to be approximately 10-fold higher than with previous vaccines, at approximately 1 per 100,000 vaccine injections. One focus of the present article is a systematic review of the components of mRNA vaccines against " coronavirus disease 2019 " (COVID-19). Differences from established vaccines are addressed and the allergic potential of liposomes, polyethylene glycol, tromethamine/trometamol, and mRNA are discussed. Another focus is on the clinical presentation and course of allergic reactions to the COVID-19 vaccines. This is followed by a discussion of the therapeutic approach to anaphylactic reactions, as well as the drugs and medical supplies required to treat them. It is important to note that any vaccinee may be affected by anaphylaxis, regardless of whether or not allergic diseases are already known. Therefore, every vaccination site and every vaccinator must be prepared to recognize and treat severe allergic reactions.

[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.

[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.