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.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (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 Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids 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.

[The first year of the SARS-CoV-2 pandemic-impact on otorhinolaryngology]. / Das erste Jahr der Pandemie mit SARS-CoV-2 ­ Auswirkungen auf die Hals-Nasen-Ohren-Heilkunde.

BACKGROUND: The first year of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has already affected our public health care system to an enormous extent and will continue to do so in the future. Otorhinolaryngologists (ORLs) are suspected to be at high risk of infection, due to the high viral load in the mucosa of the upper airways. The current review evaluates the impact of the pandemic on ORLs' activities and assesses the risk infection. METHODS: A selective literature research was conducted using relevant English and German terms for ORL, SARS-CoV­2, risk, and infection at PubMed, medRxiv, and bioRxiv, as well as in the Deutsches Ärzteblatt and on the websites of the Robert Koch Institute and the Johns Hopkins University. RESULTS: Protection recommendations for ORL include general hygiene measures and wearing KN95 masks for routine professional activities. When in contact with coronavirus disease 2019 (COVID-19) patients, it is recommended to extend the personal protective equipment by eye protection, gloves, cap, and gown. International otorhinolaryngology societies have released guidelines for procedures (e.g., tracheostomy, sinus surgery), propagating personal protection for the surgical team and reduction of aerosols. Testing for SARS-CoV­2 in patients and medical staff can contribute to reducing the risk of infection. Vaccination would provide some additional protection for ORLs and other health care professionals with increased exposure to aerosols. There is increasing evidence that ORLs are at a high risk of contracting SARS-CoV­2. CONCLUSION: Consequent personal protection, frequent testing of patients and health care professionals, and the promised SARS-CoV­2 vaccinations may provide adequate protection for highly exposed persons.

Prevalence and risk factors of smell dysfunction - a comparison between five German population-based studies.

BACKGROUND: The prevalence of olfactory impairment increases with age and is known to be an early sign of different neurodegenerative diseases. Only few population-based studies examined the prevalence of olfactory impairment and comparisons across studies are scarce. Aim of this analysis was to compare the prevalence and determinants of normosmia across five population based studies in Germany. METHODOLOGY: Data from five population-based, cross-sectional studies were included. They were independently conducted and used the same test system (Sniffin' Sticks Screening 12) to measure olfactory function. This system consists of 12 odor-dispensing felt-tip pens; the task is a forced-choice selection among four alternative odors per pen. Sociodemographic information and comorbidities were assessed in face-to-face interviews. Univariate, descriptive statistics and multivariable logistic regression models stratified by study, were performed to determine risks, i.e. prevalence odds ratios, associated with olfactory function. RESULTS: The prevalence of normosmic participants varied considerably across studies. Olfactory function was lower in men, decreased with age, and increased with higher education. Several individual comorbidities and a comorbidity index were associated with olfactory dysfunction. Recognition performance for three of the 12 pens was especially low in all studies. CONCLUSION: Four factors, well known to describe population composition, contribute to explain differences in the prevalence of olfactory function between studies when the same test system is used. Our results indicate that comorbidities and educational level should always be considered when test systems based on smell recognition are used in population-based studies.

[The association between allergic rhinitis control and sleep quality]. / Assoziation zwischen Kontrolle der allergischen Rhinitis und Schlafqualität.

BACKGROUND: Allergic rhinitis (AR) is the most common form of atopic disease, comprising 50% of atopic diseases. Recently, this disease has increasingly been the focus of intensive research. Previous work has shown that AR has a significant impact on sleep quality. To date there are no published studies demonstrating a quantitative association between the extent of control of AR and the severity of compromised sleep quality. METHODS: Patients with AR were prospectively recruited into our cross-sectional study. Sleep quality was assessed using five of the sleep subdomain questions from the 22-item Sinonasal Outcome Test (SNOT-22). Control of AR was assessed using the Rhinitis Control Assessment Test (RCAT). Association was sought between the degree of allergic rhinitis control (RCAT) as independent variable and sleep quality as dependent variable using linear regression. RESULTS: A total of 104 patients (54.8% female and 45.2% male) with an average age of 41.4 years (SD: 15.9 years) were included in the study. There were statistically significant associations between the RCAT score and the score of each of the five SNOT-22 questions used to assess decreased sleep quality (p < 0.001). These associations remained significant (p < 0.001) even after controlling participants' clinical and demographic characteristics. CONCLUSION: This is the first study showing that level of control of AR correlates with the severity of subjectively perceived sleep quality detriment. These results indicate that an improvement in AR control could lead to improved subjective sleep quality but a prospective interventional study is needed to confirm these results.

[Epidemiology of chronic rhinosinusitis, selected risk factors, comorbidities and economic burden]. / Epidemiologie der chronischen Rhinosinusitis, ausgewählter Risikofaktoren und Komorbiditäten, und ihre ökonomischen Folgen.

Chronic rhinosinusitis (CRS) is a relevant and prevalent medical condition in Germany, Europe and the world. If analysed in detail, the prevalence of CRS shows regional and temporary variety. In this review, currently available data regarding the prevalence of CRS is therefore sorted by country and/or region, time point of data collection and the CRS-definition employed. Risk factors like smoking and gastro-oesophageal reflux are discussed regarding their influence on CRS prevalence. Moreover, co-morbidities of CRS, like asthma, conditions of the cardiovascular system and depression are listed and their influence on CRS is discussed. Furthermore, data on CRS prevalence in special cohorts, like immunocompromised patients, are presented. To estimate the economic burden of CRS, current data e.g. from Germany and the USA are included in this review.

[Non-allergic Rhinitis: Epidemiology, Diagnostic and Therapy]. / Nicht-allergische Rhinitis: Epidemiologie, Diagnostik und Therapie.

Non-allergic rhinitis is a heterogenous group of medical diseases without an IgE-mediated pathophysiology. In this review, typical subgroups are presented with data regarding their frequency, clinical symptoms and recommendations for an effective and efficient diagnostic and therapeutic approach are indicated. The most common subtype is the non-allergic rhinopathy, also known as idiopathic or vasomotoric rhinitis. Because medication induced rhinitis is still a frequent clinical problem, a step wise approach to wean the patient is presented.

Physiologic and pathologic septal deviations: subjective and objective functional rhinologic findings.

OBJECTIVE: A high incidence of septal deviation with significant inter-rater variability has been reported. An explanation could be the presence of physiological septal deviation besides pathological ones. We differentiated an unselected cohort by their nasal resistance into groups with physiological normal and pathologically increased resistance to detect differences and analogies in comparison to healthy subjects and a pathological cohort. STUDY DESIGN: Prospective cohort study. SETTING: A total of 356 patients were assessed using rhinoresistometry, acoustic rhinometry, endoscopy and visual analogue scales. After definition of a benchmark between physiological and pathological nasal resistance, group differences were calculated and correlations analysed. RESULTS: The normal one-sided inspiratory nasal resistance was defined as less or equal to 0.35 sPa/cm^3 at a flow-velocity of 250 cm^3/s (R250). Using this benchmark, the unselected group of non-rhinological patients was differentiated into 114 subjects with physiological nasal resistance and 44 with pathological septal deviation. Nasal resistance after decongestion was significantly lower for normal or patients with a physiological septal deviation in comparison to the rhinological one on both nasal sides. Healthy subjects and patients with physiological septal deviation showed similarities in objective rhinological parameters as well as rhinological patients and patients with pathological septal deviation derived from the unselected group of non-rhinological patients. Furthermore, this benchmark of nasal resistance shows significant correlations with subjective assessment of nasal breathing. CONCLUSION: Inspiratory nasal resistance obtained at a flow-velocity of 250 cm^3/s using rhinoresistometry may be useful to distinguish patients with physiological and pathological septal deviation. Correlation with subjective assessment and endoscopic findings is improved.

Comparative investigations of anatomy and physiology in mammalian noses (Homo sapiens--Artiodactyla).

BACKGROUND: Knowledge of airflow in animal noses is sparse. Such knowledge could be important for selection of animal models used in environmental studies. From the phylogenetic and ontogenetic point of view, a comparison between the animal and human nose is interesting. METHOD: Nose models of 5 even-toed ungulate species (he-goat, sheep, cow, roebuck, wild boar) and two humans (new born infant and adult) were examined. Anatomical and physiological features of the nasal cavities of all species were compared. All models were rinsed with water and the flow was visualized for observation. Geometric and rhinoresistometric measurements were then performed. RESULTS AND CONCLUSIONS: Even-toed ungulates have two turbinates directly in the main part of the nasal airflow (respiratory turbinates) and a different number of turbinates in a so-called dead space of the nasal airflow above the nasopharyngeal duct (ethmoidal turbinates). The latter correspond with the upper and middle turbinate in analogy to the human nose. Respiratory turbinates of even-toed ungulates insert immediately behind the external nasal ostium. Thus, the whole nasal cavity acts as a functional area with the exception of a small area acting as dead space only detectable in ruminants, possibly indicating a small evolutionary progress from suinae to bovidae. The shape of the animal nasal cavity is stretched and flat. The airflow runs nearly completely turbulent through the nose. The nasal cavity in the adult human is relatively short and high. The area between the external nasal ostium and the head of the inferior turbinate is called inflow area. It distributes the airflow over the whole nasal cross section and generates a turbulent flow. So the airflow is prepared to contact the mucosa in the functional area (turbinate area). The morphology of the inflow area is approximately formed by the shape of the external nose. The nasal cavity of a newborn child is also stretched and flat and more similar to the nasal shape of the investigated animals. The inflow area in the newborn nose is not yet developed and corresponds with the growing external newborn nose. One can hypothesize that the inflow area in human noses is a morphological adaptation in the changed length-height-ratio of the nasal cavity.

[Perioperative pain and anxiety in endoscopic sinus surgery]. / Perioperative Schmerzen und Ängste bei endoskopischen Nasennebenhöhleneingriffen mit konventioneller Nasentamponade.

BACKGROUND: Aim of this study was to evaluate the perioperative level of pain and anxiety for endoscopic sinus surgery, and to compare 3 different types of nasal packing. MATERIAL AND METHODS: Prospective, controlled, randomized study comparing different types of nasal packing in regard to perioperative anxiety and pain. Patients suffered from chronic rhinosinusitis with nasal polyps involving all paranasal sinuses. Patients daily evaluated by standardized questionnaires (FPI-R, KASA, STAI) and also visual analog scale for pain on 5 consecutive days before and after endoscopic sinus surgery of all paranasal sinuses. Nasal packings were removed on 2(nd) postoperative day. RESULTS: A total of 73 patients (polyvinyl acetate packing N = 14, glove packing N = 37, glove packing with breathing tubes N = 22) completed the study. Female gender, bad preoperative mood and absence of pain were associated with increased preoperative state anxiety based on regression analysis. Also, preoperative gathering of additional information from relatives and friends was correlated with increased preoperative anxiety. Patients had significantly minor preoperative anxiety if they could expect use of nasal packings with breathing tubes. CONCLUSION: Female patients, who gathered information about the operation from friends or relatives or patient in worse preoperative mood are at risk for increased state anxiety and should be identified prior to rhinosurgical procedures. Use of nasal packing with at least partially preserved nasal breathing is recommended in clinically anxious patients.

Response analysis of stimulating efficacy of polihexanide in an in vitro wound model with respiratory ciliary epithelial cells.

In animal wound models, accelerated wound closure has been shown by use of polihexanide applied in antimicrobially effective concentrations. Additionally, an increased ATP production of keratinocytes in vitro induced by polihexanide was demonstrated and interpreted as a stimulatory effect on cell proliferation. Based on these results and the clinical reports on improved wound healing after introduction of polihexanide for preoperative antisepsis in the nasal cavity, polihexanide was tested in a wound model on respiratory ciliary epithelial cells allowing measurement of the healing process after artificial injury. 0.5 µg/ml polihexanide accelerated wound healing in terms of proliferation and migration significantly after an exposure time of 1 and 96 h. At a concentration of 1 µg/ml polihexanide, the stimulation of wound healing was significantly increased only after an exposure time of 96 h. This is the first study to demonstrate acceleration of wound healing in a standardized in vitro model using an epithelial cell line. Considering the present results and previous reports on the impact of polihexanide on wound healing, the conclusion is drawn that the positive effect of polihexanide on wound healing is a separate, dose-dependent effect independent of its antiseptic properties.

[Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses]. / Funktionen und Funktionsstörungen der respiratorischen Schleimhaut der Nase und der Nasennebenhöhlen.

In this review, anatomy and physiology of the respiratory mucosa of nose and paranasal sinuses are summarized under the aspect of its clinical significance. Basics of endonasal cleaning including mucociliary clearance and nasal reflexes, as well as defence mechanisms are explained. Physiological wound healing, aspects of endonasal topical medical therapy and typical diagnostic procedures to evaluate the respiratory functions are presented. Finally, the pathophysiologies of different subtypes of non-allergic rhinitis are outlined together with treatment recommendations.