Background: Managing patients with severe asthma with an eosinophilic phenotype (SEA) with comorbid respiratory conditions such as chronic rhinosinusitis with nasal polyps (CRSwNP) continues to encounter significant challenges and lack of coordinated management among treating physicians. Objective: The OverSEA study aims to provide insights into current clinical practices and formulate recommendations for managing these patients. Methods: The two-round Delphi survey, conducted March-June 2023, was developed by a multidisciplinary 11-member Scientific Committee including pulmonologists, allergists, and ear, nose and throat specialists, and involved 205 experts from these specialties across 8 European countries. Consensus was defined as ≥70% agreement. Topics covered included the initial assessment, treatment, follow-up, and multidisciplinary management of patients with SEA and CRSwNP. Results: There was a consensus that evaluating for CRSwNP (88%), allergic rhinitis (79%), chronic rhinosinusitis without nasal polyps (77%), and aspirin/nonsteroidal anti-inflammatory-exacerbated respiratory disease (71%) is crucial for diagnosing upper respiratory tract comorbidities in patients with SEA. The necessity of a multidisciplinary approach for all stages of disease management (diagnosis, 82%; treatment decision-making, 83%, follow-up, 79%), and the usefulness of biologics in simultaneously managing asthma and CRSwNP symptoms (87%) were emphasized. Conclusion: The OverSEA study is the largest European initiative providing recommendations for optimizing the management of patients with SEA and comorbid CRSwNP. It underscores the importance of evaluating patients with SEA for comorbid upper airways diseases, particularly CRSwNP, and promotes a multidisciplinary approach, encouraging pulmonologists, allergists, and otorhinolaryngologists to collaborate closely to streamline patient diagnosis, follow-up, and treatment decisions.

‘Post-COVID Syndrome’ (PCS), which encompasses the multifaceted sequelae of COVID-19, can be severity-graded by a previously defined score encompassing 12 different long-term symptom complexes. The PCS score was shown to have two main predictors, namely acute COVID-19 severity and individual resilience. The purpose of the present study was to verify these predictors and to assess their detailed relationship to the symptom complexes constituting the PCS score. The study drew upon a largely expanded dataset (n = 3,372) from COVIDOM, the cohort study underlying the original PCS score definition. Classification and Regression Tree (CART) analysis served to resolve the detailed relationship between the predictors and the constituting symptom complexes of the PCS score. Among newly recruited COVIDOM participants (n = 1,930), the PCS score was again found to be associated with both its putative predictors. Of the score-constituting symptom complexes, neurological symptoms, sleep disturbance, and fatigue were predicted by individual resilience whereas the acute disease severity predicted exercise intolerance, chemosensory deficits, joint or muscle pain, signs of infection, and fatigue. These associations inspired the definition of two novel PCS scores that included the above-mentioned subsets of symptom complexes only. Similar to the original PCS score, both novel scores were found to be inversely correlated with quality of life as measured by the EQ-5D-5L index. The two newly defined PCS scores may enable a more refined assessment of PCS severity, both in a research context and to delineate distinct PCS subdomains with possibly different therapeutic and interventional needs in clinical practise.

IntroductionSeveral aspects of the involvement of HPV in the pathogenesis of HPV-associated diseases remain poorly understood including mechanistic aspects of infection and the question of why the majority of HPV-positive HNSCC-patients are non-smokers, whereas HPV-negatives are smokers. Our previous research, based on 1,100 patient samples, hypothesized an explanation for this phenomenon: Smoking induces upregulation of a mucosal protective protein (SLPI), which competes with HPV for binding to Annexin A2 (AnxA2), pivotal for HPV cell entry. Here we investigate the mechanistic aspects of our hypothesis using transfection assays.MethodsHaCaT and HeLa cell lines were used to investigate the effects of shRNA transfection and nicotine exposure on HPV16-PsV-uptake. Cells were treated with Lipofectamine™ RNAiMAX for 48 or 72 hours with specific shRNA-concentrations, while nicotine was added to the cell medium at the indicated concentrations. Protein isolation, SLPI- and AnxA2-quantification, LDH cytotoxicity assessment, HPV16-PsV-uptake measurement, mRNA-isolation, cDNA-synthesis and RT-qPCR were performed.ResultsIn vitro transfection experiments with HPV16 pseudovirions (PsVs) showed that PsVs entered cells significantly better when SLPI was downregulated and significantly less when AnxA2 was downregulated. Nicotine exposure increased SLPI levels and reduced PsV uptake.ConclusionsThe overexpression of SLPI caused by tobacco-smoking can hinder HPV cell entry by binding to AnxA2 and thus prevent successful HPV infection. Conversely, non-smokers have lower SLPI-levels, associated with an excess of unbound AnxA2, favoring HPV cell-entry. These findings support our hypothesis, suggesting a paradigm shift in understanding virus-related pathogenesis, particularly in the head and neck region, and the nature of HPV infection.

Olfactory dysfunction (OD) as a symptom of COVID-19 has received significant attention in research due to its high prevalence. While it is transient in the majority of individuals, post-COVID OD persists in a notable subset of patients even months to years after the acute infection. A deeper understanding of the underlying factors driving this phenomenon is essential. There is increasing evidence for an involvement of the central nervous system in this deficit. The objective of this study was to investigate the structural connectivity and integrity of white matter pathways in brain regions associated with olfactory processing using MRI with diffusion tensor imaging (DTI) in patients with persistent post-COVID OD. The study involved 61 patients, divided into two groups: 31 participants with post-COVID OD (PC-OlfDys) and 30 post-COVID normosmic controls (PC-N). For MRI analyses, a region of interest (ROI)-based approach and voxelwise statistical comparisons between the groups with age as a covariate was used. Fractional anisotropy (FA) in the left amygdala was higher in the PC-OlfDys than in the PC-N group, and radial diffusivity (RD) in the right amygdala was higher in the PC-OlfDys group than in PC-N. The PC-OlfDys group exhibited higher depression and anxiety scores, as measured by the eight-item Patient Health Questionnaire depression scale and the Generalized Anxiety Disorder 7 questionnaire, respectively. This study shows that post-COVID OD is associated with significant changes in the myelination or axonal diameter of olfactory-related brain regions. As the amygdala, putamen and piriform cortex (all involved in olfactory function and emotional well-being) showed associations with depression and anxiety scores, we hypothesise that post-COVID OD and depression and anxiety are interrelated, although the direction of this relationship remains to be elucidated.

BACKGROUND AND OBJECTIVES:This paper presents an overview on nasal packing materials which are available in Germany. The current literature is analyzed whether there are robust criteria regarding use nasal packing after sinonasal surgery, whether there are fundamental and proven advantages or disadvantages of products, and what this means in clinical practice.MATERIALS AND METHODS:Selective literature analysis using the PubMed database (key words "nasal packing", "nasal tamponade", "nasal surgery", "sinonasal surgery", or "sinus surgery"), corresponding text books and resulting secondary literature.RESULTS AND CONCLUSIONS:Because of systematic methodological shortcomings, the literature does not help in the decision-making about which nasal packing should be used after which kind of sinonasal surgery. In fact, individual approaches for the many different clinical scenarios are recommended. In principle, nasal packing aims in hemostasis, should promote wound healing, and should not result in secondary morbidity. Nasal packing materials should be smooth (non-absorbable materials), inert (absorbable materials), and should not exert excessive pressure. Using non-absorbable packing entails the risk of potentially lethal aspiration and ingestion. For safety reasons inpatient control is recommended as long as this packing is in situ. With other, uncritical packing materials and in patients with special conditions, outpatient control could be justified.

This article summarizes the essential aspects of current knowledge about eosinophils, classifies eosinophilia in terms of the dimensions healthy or harmful reaction, takes a specific look at eosinophils in the field of otorhinolaryngology, and gives recommendations for diagnostic workup and therapeutic intervention in case of proven eosinophilia, particularly as an adverse drug reaction. The thoughts are inspired by communications at the 29th Congress of the European Rhinologic Society in Sofia, Bulgaria, 2023.

Zusammenfassung Hintergrund Die Ambulantisierung rhinochirurgischer Eingriffe wird derzeit intensiv diskutiert und insbesondere von politischer Seite stark propagiert. Viele Fragen zur Stratifizierung in ambulante oder stationäre Durchführung sind unklar. Insbesondere ist das Vorgehen bei Anwendung von Nasentamponaden bisher nicht ausreichend diskutiert. Material und Methoden Deutschlandweite Umfrage unter niedergelassenen und in Kliniken tätigen Hals-, Nasen-, Ohrenärzten zur Verwendung von Nasentamponaden in der Rhinochirurgie und zum Auftreten von Komplikationen in Zusammenhang mit einer Tamponade. Ergebnisse 85,6% der Antwortenden verwenden eine Nasentamponade zumindest manchmal bei der Chirurgie von Septum und Nasenmuscheln/lateraler Nasenwand, 44,2% grundsätzlich. Bei der Nasennebenhöhlenchirurgie sind dies 94,1% bzw. 49% der Antwortenden. Überwiegend wurde die Anwendung von sich nicht auflösenden Tamponaden angegeben. Die am häufigsten beobachteten Komplikationen waren eine Blutung unter liegender Nasentamponade (>50% der Antwortenden) und eine Dislokation nach dorsal (24% der Antwortenden), die ein notfallmäßiges Eingreifen erforderte. Eine Todesfolge wurde bei 5 Patienten beschrieben. Ein Patient erlitt eine dauerhafte Hirnschädigung nach Hypoxie. Schlussfolgerungen Die Anwendung einer sich nicht auflösenden Nasentamponade mit Okklusion der Nasenhaupthöhle kann zu einer relevanten Gefährdung der Patienten führen, die ein notfallmäßiges Eingreifen erforderlich macht und deshalb die stationäre Überwachung erfordert.

Post-COVID syndrome (PCS) currently affects approximately 3-17% of people following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has the potential to become a significant global health burden. PCS presents with various symptoms, and methods for improved PCS assessment are presently developed to guide therapy. Nevertheless, there are few mechanistic insights and treatment options. Here, we performed single-cell RNA transcriptomics on nasal biopsies from 33 patients suffering from PCS with mild, moderate, or severe symptoms. We identified 17 different cell clusters representing 12 unique cell populations, including all major epithelial cell types of the conducting airways and basal, secretory, and ciliated cells. Severe PCS was associated with decreased numbers of ciliated cells and the presence of immune cells. Ensuing inflammatory signaling upregulated TGFβ and induced an epithelial-mesenchymal transition, which led to the high abundance of basal cells and a mis-stratified epithelium. We confirmed the results in vitro using an air-liquid interface culture and validated TNFα as the causal inflammatory cytokine. In summary, our results show that one mechanism for sustained PCS is not through continued viral load, but through the presence of immune cells in nasal tissue leading to impaired mucosal barrier function and repeated infections. These findings could be further explored as a therapeutic option akin to other chronic inflammatory diseases by inhibiting the TNFα-TGFβ axis, restoring the nasal epithelium, and reducing respiratory tract-related infections.### Competing Interest StatementThe authors have declared no competing interest.

Zusammenfassung Hintergrund Die Ambulantisierung rhinochirurgischer Eingriffe wird derzeit intensiv diskutiert und insbesondere von politischer Seite stark propagiert. Viele Fragen zur Stratifizierung in ambulante oder stationäre Durchführung sind unklar. Insbesondere das Vorgehen bei Anwendung von Nasentamponaden ist bisher nicht ausreichend diskutiert. Material und Methoden Entwicklung einer Checkliste zur ambulanten Durchführung rhinochirurgischer Operationen unter Berücksichtigung der aktuellen Literatur. Ergebnisse und Schlussfolgerungen Nach umfassender Auswertung der Literatur und Analyse von Risikofaktoren wird eine Liste von stationär durchzuführenden rhinochirurgischen Operationen definiert. Es wird eine Checkliste für die ambulante oder stationäre Durchführung rhinochirurgischer Operationen vorgelegt, die soziale, allgemeine medizinische und spezifische operationsbedingte Gründe berücksichtigt und hierbei die Anwendung von Nasentamponaden einschließt. Sie wird ergänzt durch eine Checkliste, anhand derer Kriterien die Entlassungsfähigkeit von Patienten nach einer ambulant geplanten rhinochirurgischen Operation bewertet wird.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and paranasal sinuses. Eosinophilic inflammation is described as a common endotype. The anti-interleukin-5 (IL-5) antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe CRSwNP when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, therapy monitoring and follow-up documentation are required, and therapy discontinuation has not been adequately established yet. In this paper, recommendations for monitoring the course and efficacy of therapy as well as for reviewing the duration and possible termination of therapy are provided. For this purpose, 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, and the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including October 2022 were considered. Based on the international literature and previous experience, 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 by an expert panel on the basis of a documentation sheet.

Objective Currently, there is an intensive discussion on advancing and expanding outpatient rhinosurgical procedures. Many questions about how to stratify into out- and inpatient procedures are still not sufficiently clarified. Particularly, the use of nasal packing materials is not adequately discussed. Material and Methods Development of a checklist to stratify sinunasal procedures into in- or outpatient procedures with consideration of current scientific literature and risk factors. Results and conclusions After comprehensive assessment of the literature and analysis of specific risk factors, a list of sinunasal procedures is presented, which should be performed as inpatient procedures. We present a checklist for in- and outpatient sinunasal procedures, which considers social, medical and surgical factors as well as the use of nasal packing materials. Furthermore, a checklist is added to assess, whether patients are ready for discharge after a planned outpatient procedure.

Der vorliegende Artikel fasst die wesentlichen Aspekte des aktuellen Wissens um eosinophile Granulozyten zusammen, ordnet die Eosinophilie in die Dimensionen gesunde oder schädigende Reaktion ein, wirft einen besonderen Blick auf das Gebiet HNO-Heilkunde in Bezug auf Eosinophile und gibt Handlungsempfehlungen zur Diagnostik und therapeutischen Intervention bei einer nachgewiesenen Eosinophilie auch und insbesondere als unerwünschte Arzneimittelwirkung (UAW) unter medikamentöser Therapie. Die Gedanken sind angeregt durch Mitteilungen auf dem 29. Kongress der European Rhinologic Society in Sofia, Bulgarien, 2023.

Objective Currently, there is an intensive discussion about enhancing and expanding outpatient rhinosurgical procedures. Many questions about how to stratify into out- and inpatient procedures are still not sufficiently clarified. Particularly, the use of nasal packing materials is not adequately discussed. Material and Methods We performed a Germany-wide survey among otorhinolaryngologists regarding the use of nasal packing materials in sinonasal surgery. Additionally, we asked for any complication in relation to nasal packing. Results In 85,6% nasal packing was used for septal and turbinate surgery at least occasionally, in 44,2% always. In sinus surgery these numbers are 94,1% and 49%, respectively. Non-resorbable nasal packing materials were predominantly used. Most frequent complications were bleeding with nasal packing in situ (> 50% of respondents) and posterior dislocation (24% of respondents), requiring emergency treatment. Death was listed in 5 patients. One patient suffered from permanent brain damage due to hypoxia. Conclusions Application of non-resorbable nasal packing materials with occlusion of the nasal cavity carry a substantial risk of complications, which necessitate emergency treatment, thus requiring inpatient care.

Wir berichten über einen 32-jährigen Patienten, der sich erstmalig in 2021 mit rezidivierenden Sekretionen aus einer Stirnfistel sowie mit einseitiger Otorrhoe vorstellte. Seit 2011 bestand diese Symptomatik, die alio loco 2015 laborchemisch, klinisch und in einer Pansinus-Operation mit Beck"scher Bohrung zu der Diagnose einer Granulomatose mit Polyangiitis (GPA) führte. Aufgrund von Granulomen mit Dissektion der ACI resultierte ein Schlaganfall mit Hemiparese. Weiterhin bestand langjährig der Verdacht auf eine chronisch-entzündliche Darmerkrankung. Im Rahmen beider Autoimmunerkrankungen wurden diverse Therapien, u.a. mit Azathioprin, Rituximab und Prednisolon, mit denen der Patient bis zu Vorstellung eingestellt war, durchgeführt. Bildmorphologisch und laborchemisch ergab sich kein Verdacht auf Aktivität der GPA. Die genannten Infektionen führten zu operativen Sanierungen, bei denen auch histologisch keine Aktivität der GPA nachgewiesen wurde. Endoskopisch wurde Aktivität der Verdachtsdiagnose des M.Crohn ausgeschlossen. Bei B-Zell- und Antikörpermangel kam es zu rezidivierenden Infektionen (Sekretionen Stirn und Ohr; Norovirus, Covid, Nokardien sowie Haut- und Pilzinfektionen). Eine intravenöse Antikörpersubstitution führte zu einer anaphylaktischen Reaktion, sodass eine subkutane Substitution eingeleitet wurde. Eine Exonsequenzierung ergab den Nachweis einer Mutation im Gen Tumor necrosis factor receptor-associated factor 3. Derzeit ist die Symptomatik als Therapieschaden ohne erkennbare Aktivität einer autoimmunen Erkrankung zu verstehen. Unter enger klinischer Kontrolle ist jegliche immunsuppressive Therapie abgesetzt und der Patient stabil. Bei verminderter T-Zellfunktion werden mittels immunologischer in-vitro-Diagnostik weitere Therapieoptionen evaluiert.

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

Chemosensory especially olfactory dysfunction (OD) is common after COVID-19.The exact mechanism of this impairment is connected with molecular changes, which can be examined using single-cell RNA sequencing (SCS).The objective of this study was to evaluate cell populations,receptor expressions and analyze differential gene expressions leading to the identification of signaling pathways,in post-COVID patients (PCPs).

Introduction Subglottic stenoses (SGS) are constrictions in the region below the vocal folds, that can pose a life-threatening problem for those affected. The aim of this research project was to identify the patient group for which the treatment of SGS by balloon dilatation can lead to long-term success. Methods 14 patients with SGS were examined (before and up to12 months after intervention) using pulmonary function tests, laryngoscopies and two questionnaires (Clinical Chronic Obstructive Pulmonary Disease Questionnaire), (modified Medical Research Council Dyspnoea Scale) regarding the respiratory situation. Additionally, the number of necessary interventions, the degree of stenosis (according to Myer Cotton and measured in millimeters) were documented. Results Four patients who required only one intervention with the balloon showed better pre-interventional respiratory function and a higher subjective stress level. Lung function tests and evaluation of the questionnaires showed an improvement in the respiratory situation and state of health of all 14 patients after the initial intervention. The degree of stenosis measured in millimeters shows that patients with a stenosis diameter of less than 4 mm only required one intervention. All patients who received an intervention using a 12-mm-balloon had to be treated several times. Conclusions Patients with a high degree of stenosis and a tendency towards greater subjective stress and less objective restriction of the respiratory function appear to have a higher probability of long-term successful treatment with the balloon. Furthermore, the choice of balloon size seems to be an additional decisive factor for the success of an intervention.

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.