Remission in Type 2 Inflammatory Diseases: Current Evidence, Unmet Needs, and Suggestions for Defining Remission in Chronic Rhinosinusitis with Nasal Polyps.

PURPOSE OF REVIEW: The development of biological therapies for type 2 inflammatory diseases raises the possibility of addressing remission in those dis-immune conditions. No consensus exists for a definition of remission in chronic rhinosinusitis with nasal polyps (CRSwNP). This review aims to critically evaluate the published data to provide the basis for defining remission in CRSwNP. RECENT FINDINGS: The published evidence has yet to provide an unequivocal definition on remission in type 2 inflammatory diseases, in part reflecting differences in approaches to diagnosis and follow-up. A multidimensional evaluation is necessary when considering complete remission, including clinical, inflammatory, and histologic criteria, but how to combine or tailor the three perspectives according to disease severity at baseline or timing of assessment of treatment category is yet to reach consensus. We suggest defining remission starting from the approach taken in asthma and eosinophilic esophagitis, that is, including the resolution of symptoms and improvements in objective parameters of disease severity and/or inflammatory activity. Future studies and consensuses should provide validated criteria with cutoffs for the day-to-day definition of remission. The definition of remission in CRSwNP should include the following criteria, to be verified and maintained for a period of ≥ 12 months: absence of symptoms (nasal obstruction, loss of smell, rhinorrhea as the main ones); no impact of symptoms on quality of life; no need of surgery; no chronic or rescue medications (systemic corticosteroids or antibiotics); and recovery of smell function, possibly evaluated by objective test. Assessment of underlying inflammation should also be considered once accurate and feasible biomarkers are available in clinical practice.

Patient-reported outcome measures for acute rhinosinusitis in adults and children: a systematic review of the quality of existing instruments.

BACKGROUND: Acute rhinosinusitis (ARS) is a self-limiting inflammation of the nose and sinuses caused by viral or bacterial infections that requires primarily symptomatic treatment. Patient-reported outcome measures (PROMs) are suitable tools for the assessment of the effectiveness of remedies for ARS from the patient's perspective in clinical trials and real-world studies. Data regarding the quality of existing PROMs for ARS are limited. PURPOSE: To conduct a systematic review of the quality of existing disease-specific PROMs for use in adults and children with ARS according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology, and to derive recommendations for use of the identified instruments in future clinical studies. METHODS: We systematically searched PubMed, Web of Science and Embase for studies reporting on the development and/or validation of PROMs for ARS. We assessed the methodological quality of each included study, evaluated the quality of measurement properties per PROM and study, and graded the evidence. Based on the overall evidence, we derived recommendations for use of the instruments. RESULTS: We identified four studies on three PROMs measuring symptoms of ARS and quality of life in adults (Sinonasal Outcome Test-16, SNOT-16; Measurement of Acute Rhinosinusitis, MARS; Rhinosinusitis Quality-of-Life Assessment, RhinoQoL). For ARS in children, we identified two studies on two PROMs measuring symptoms of ARS (Pediatric Rhinosinusitis Symptom Scale, PRSS; Sinus Symptom Questionnaire, S5). Our assessment of measurement properties indicates that all instruments require further validation before they can be unrestrictedly recommended for use in future research (COSMIN category B). In particular, there were no content validity studies for any of the identified instruments, but also data on other important measurement properties, e.g., structural validity, are lacking. CONCLUSION: Currently, no PROM for ARS in adults and children can be unrestrictedly recommended based on the evaluation of their quality. Further validation is required for all identified PROMs. Content validation involving patients and experts should be given priority. SYSTEMATIC REVIEW REGISTRATION: OSF ( https://doi.org/10.17605/OSF.IO/VAP8U ).

Effect of Different Therapeutic Strategies on Olfactory Outcomes in Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review.

INTRODUCTION: Olfactory impairment is one of the cardinal symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of currently available therapeutic options on the recovery of the sense of smell is not well defined. The aim of this systematic review was to compile evidence on the impact of medical, surgical, and biological treatment on olfactory outcomes in patients with CRSwNP. METHODS: This review was conducted by 2 reviewers according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence of all the studies included in the qualitative synthesis was evaluated using the Critical Appraisal Skills Programme (CASP). RESULTS: Forty-four studies were included in the qualitative synthesis. These assessed sinonasal surgery (n=23), biologics (n=15), and conventional medical treatment (n=6). The methodological quality was moderate-to-high in most. Overall, significant improvements in the sense of smell were detected with all the interventions analyzed and measured using an objective tool, a subjective tool, or both. However, most studies used different outcome measures, thus hindering comparisons between interventions, and data on clinically relevant changes were missing. CONCLUSION: Oral corticosteroids, biologics, and sinonasal surgery improve the olfactory impairment associated with CRSwNP. However, the heterogeneous nature of existing studies does not allow accurate comparisons.

Invasive fungal sinusitis: A comparison of pediatric versus adult cases.

BACKGROUND: Invasive fungal sinusitis (IFS) is a rare infection with high mortality, mainly impacting immunocompromised patients. Given its significant mortality, timely recognition and treatment is crucial. This study aims to highlight the differences in presentation of IFS between pediatric and adult patients to aid in prompt diagnosis and treatment of this condition. METHODS: A comprehensive literature search of PubMed, EMBASE, Web of Science, Global Index Medicus, Global Health (EBSCO) and Cochrane Database of Systematic Reviews was conducted to identify articles relating to IFS. Patient demographics, comorbidities, presentation, disease characteristics, treatments and outcomes were extracted from the studies, and statistical analyses were conducted to compare these variables between pediatric and adult patients. RESULTS: 111 studies identified 22 pediatric and 132 adult patients worldwide. Children were more likely to have hematologic malignancies compared to adults (59.1 % vs. 15.2 %, p < 0.001). Facial symptoms such as pain, edema, and numbness were the most common symptoms for both age groups. In the pediatric population, fever and nasal or oral mucosal lesions were more common presenting symptoms (both p < 0.001). Pediatric patients were more likely to present without disease extension beyond the sinuses (p < 0.001). There was no significant difference in either medication treatment or mortality between the two cohorts. CONCLUSION: IFS often presents with non-specific symptoms and a unique presentation in pediatric and adult populations. Clinical awareness of the varying presentations in both populations is important to treat in a timely manner given the rapid progression and high mortality rates of IFS.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 2: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (eGPA) are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of GPA and eGPA were collected and reported in this review. RESULTS: 467 references were discovered during literature review process. In total, 42 references for GPA and 35 references for eGPA were included in this review. CONCLUSION: GPA and eGPA are vasculitis syndromes which commonly present in the context of multisystem disease. For GPA, pulmonary and renal disease are common; for eGPA a history of asthma is nearly ubiquitous. Sinonasal disease is a very common feature for both disease processes and may precede the development of systemic symptoms in many patients. Clinical work up and diagnosis is complex and generally requires multidisciplinary care. Treatment primarily consists of immunosuppressive agents, and a number of steroids, steroid sparing agents, and biologics have been shown to be effective. The role of sinus surgery includes tissue biopsy for diagnosis, functional surgery for symptom management in select cases, and reconstruction of cosmetic and functional defects.

The percentage of controlled chronic rhinosinusitis after treatment: a systematic review and meta-analysis.

PURPOSE: Chronic rhinosinusitis (CRS) is a chronic disease with a high recurrence rate, and the aim of treating CRS is to maintain disease control. Recently, a series of CRS control instruments have been developed to assess the control levels. We pooled existing studies to evaluate the percentage of controlled CRS after treatment in patients with CRS. METHODS: A systematic literature review and meta-analysis using PubMed, Google Scholar, Scopus, and Cochrane databases was conducted to identify studies assessing CRS control. Both comprehensive assessments and self-report of CRS control were included. RESULTS: 9 studies with 1931 patients after treatment and 295 patients before treatment were included. CRS control assessments of the 2012 European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2012), EPOS 2020, and Sinus Control Test (SCT) were comprehensive assessments utilized in the clinic practice. The self-report assessment included patient-reported global level of CRS control. These existing disease control instruments categorized patients into three (uncontrolled, partly controlled, and controlled) or five (not at all, a little, somewhat, very, and completely) control categories. Only 8% (95% CI 0.05-0.11) of patients with CRS stayed well controlled before treatment assessed by comprehensive assessments. About 35% (95% CI 0.22-0.49) of patients achieved well controlled after treatment when assessed by the comprehensive measures. Meanwhile, 40% (95% CI 0.28-0.52) of patients reported well controlled after treatment when using self-report. CONCLUSION: About 35-40% of patients with CRS showed well controlled after treatment, which stressed the importance of identifying these undertreated patients with CRS.

Pediatric chronic rhinosinusitis.

PURPOSE: An up-to-date overview of diagnosis, differential diagnosis, comorbidities, and current medical and surgical management of pediatric chronic rhinosinusitis (PCRS). METHODS: Review of current evidence-based literature on PCRS. RESULTS: Diagnosis of PCRS seems to be improving based on recent evidence using nasal endoscopy as well as computed tomography scanning. Recent literature supports the fact that chronic adenoiditis can be an independent etiology of symptoms of chronic sinusitis, that are very similar to chronic adenoiditis. Allergic rhinitis and immune deficiency play important roles in the management of PCRS. Surgery for PCRS has evolved significantly in the last 15-20 years to include adenoidectomy as well as endoscopic sinus surgery. CONCLUSIONS: PCRS is very common in children causing poor QOL for these children. Medical management remains the main stay of treatment with attention to management of co-morbidities that may contribute to the disease severity. Making the correct diagnosis will help with the choice of surgical intervention if medical management fails.

Management of patients with chronic rhinosinusitis with nasal polyps in Spain: learnings from a nationwide survey of otorhinolaryngologists.

PURPOSE: To describe the self-reported practices on the diagnosis, treatment, and follow-up of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by ear, nose, and throat (ENT) specialists in Spain to identify potential areas for management optimization. METHODS: A cross-sectional online survey with 16 questions was carried out. Recruitment was performed by emailing registered ENT specialists in the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC). RESULTS: In total, 127 ENT specialists completed the survey. Fifty-one percent of respondents combined clinical criteria and objective evidence of mucosal inflammation to diagnose CRSwNP. Patient interview and, to a lower degree, a visual analogue scale were the most employed diagnostic tools to quantify symptom severity. Less than half (45%) routinely used the 22-item sino-nasal outcomes test (SNOT-22) to assess the impact of CRSwNP disease in quality of life. The use of patient-reported outcomes and other clinical evaluation tools showed a larger uptake among ENT specialists that worked at an ENT department with an available rhinology unit. Almost all the specialists surveyed (95%) recommended biological treatment, particularly in patients with uncontrolled CRSwNP with respiratory comorbidities (76%), as well as in candidates for revision surgery (66%). CONCLUSION: Spanish otorhinolaryngologists showed a trend toward incorporating CRSwNP guideline recommendations in their clinical practice. The observed low uptake of patient-reported outcomes and objective clinical evaluation tools in routine clinical practise have been identified as areas for optimizing the management of patients with CRSwNP.

EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

Eosinophils are the dominant type2 marker for the current indication of biological treatment in severe uncontrolled chronic rhinosinusitis with nasal polyps.

The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) defines markers for type2 inflammation in the context of indicating biological therapy in severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as either a total serum immunoglobulin E (total-IgE) <100 kU/L, a blood eosinophil count (BEC, expressed as -109 cells / L) >=0.25, or a tissue eosinophil count >=10 per high power field (HPF) (1). Recently, an EPOS/EUFOREA expert panel advised to lower the threshold for BEC from >=0.25 (EPOS2020) to >=0.15 (EUFOREA2023) to align with thresholds used for biological indication in asthma patients (2). As far as we know, there is no literature supporting the cut-off value for total-IgE.

Cavernous Sinus Syndrome Caused by Noninvasive Fungal Maxillary Sinusitis.

It is rare that cavernous sinus complications are caused by maxillary sinus lesions because the locations of these lesions are some distant from each other. The authors describe an unusual presentation that the primary lesion was located in the maxillary sinus and triggered cavernous sinus syndrome and optic nerve symptoms. The most likely possibility was that the infection traveled retrograde along the vascular plexus. Removal of maxillary sinus lesions and establishment ventilation may achieve source control.

Outcome measures for chronic rhinosinusitis with nasal polyps.

BACKGROUND: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus. METHODS: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses. RESULTS: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each. CONCLUSIONS: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Genetics and epigenetics of chronic rhinosinusitis.

Discerning the genetics and epigenetics of chronic rhinosinusitis (CRS) may optimize outcomes through early diagnostics, personalized and novel therapeutics, and early prognostication. CRS associated with cystic fibrosis and primary ciliary dyskinesia has well-characterized genetic mutations. Most CRS subjects, however, do not exhibit identifiable monogenic alterations. Clustering in related individuals is seen in CRS with nasal polyps. Spouses of subjects with CRS without nasal polyps also may be at increased risk of the same disease. These observations generate questions on genetic and environmental influences in CRS. Genome-wide association studies have identified variations and polymorphisms between CRS and control subjects in genes related to innate and adaptive immunity. Candidate gene and transcriptomics studies have investigated and identified genetic variations related to immunity, inflammation, epithelial barrier function, stress-response, antigen processing, T-cell regulation, and cytokines in CRS. Epigenetic studies have identified mechanisms through which environmental factors may affect these gene functions. However, causality is not determined for most variations. Inferences drawn from these data must be measured because most investigations report unreplicated results from small study populations. Large, replicated studies in tight cohorts across diverse populations remain a pressing need in studying CRS genetics.

Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors.

BACKGROUND: Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated. OBJECTIVE: We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors. METHODS: Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining. RESULTS: Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5. CONCLUSION: Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions.

Functions and Clinical Applications of Extracellular Vesicles in TH2 Cell-Mediated Airway Inflammatory Diseases: A Review.

Type 2 airway inflammation (T2AI), driven by type 2 innate lymphoid and CD4+ T helper 2 cells, leads to various diseases and conditions, such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma. Emerging evidence suggests the involvement of extracellular vesicles (EVs) in these diseases. In this review, we describe the immunological T2AI pathogenic mechanisms, outline EV characteristics, and highlight their applications in the diagnosis and treatment of T2AI. An extensive literature search was conducted using appropriate strategies to identify relevant articles from various online databases. EVs in various biological samples showed disease-specific characteristics for chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma, with some demonstrating therapeutic effects against these conditions. However, most studies have been limited to in vitro and animal models, highlighting the need for further clinical research on the diagnostic and therapeutic applications of EVs.

[Pediatric chronic rhinosinusitis]. / Pädiatrische chronische Rhinosinusitis.

Pediatric chronic rhinosinusitis (PCRS) differs from adult chronic rhinosinusitis (CRS) in several aspects. The confrontation with the environment takes place in the growing sinus system, and the immune system is also developing. The inflammatory mechanisms differ to some extent from those of adult CRS patients. The adenoid vegetations play an important role, particularly during the first 6 years of life. Other pathogenetic aspects are important (e.g., asthma, gastroesophageal reflux disease, immunodeficiency). Genetically determined systemic diseases such as cystic fibrosis cause specific challenges in diagnostics and treatment already in childhood. Consistent conservative therapy is often successful, but surgical procedures that have been proven to be effective and associated with few complications are also increasingly used.

[Particulars of sinogenic orbital complications in children]. / Besonderheiten der sinugenen orbitalen Komplikationen bei Kindern.

BACKGROUND: Sinogenic orbital complications in children are relatively rare but critical conditions that require accurate diagnosis and timely appropriate treatment to prevent severe sequelae. OBJECTIVE: This article concentrates on clinical, diagnostic, and therapeutic specifics of sinogenic orbital complications in children. MATERIALS AND METHODS: The work is based on a literature review (PubMed, Google Scholar) and own experience as well as data from the authors' own pediatric population. RESULTS: In children, sinogenic orbital complications are usually secondary due to acute bacterial sinusitis. Correct distinction between pre- and postseptal cellulitis is of utmost importance for correct diagnostic and therapeutic management in order to prevent long-term sequelae. Preseptal cellulitis can be treated conservatively. If there are signs of postseptal involvement, prompt cross sectional imaging will be required. Depending on the severity of the postseptal involvement, surgical treatment may be necessary. CONCLUSION: Recent literature debates three main issues: 1) developing models for different combinations of symptoms that reliably distinguish between pre- and postseptal cellulitis; 2) selection of appropriate cross-sectional imaging (MRI vs. CT); and 3) indications for surgery. All three issues will be discussed in detail in this article.

[Chronic rhinosinusitis with nasal polyposis : A retrospective analysis of therapeutic approaches in 463 patients]. / Chronische Rhinosinusitis mit Polyposis nasi : Retrospektive Analyse des therapeutischen Vorgehens bei 463 Patienten.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease, the treatment of which has undergone significant changes in recent years. In addition to surgical approaches, topical and systemic steroids, and adaptive acetylsalicylic acid (ASA) desensitization, three specific antibodies have complemented the therapeutic portfolio since 2019. METHODS: A retrospective evaluation of all patients who presented as outpatients for the first time due to CRSwNP in 2007 and 2008 (collective A) and 2017 and 2018 (collective B) was performed, up to and including June 2023. RESULTS: The clinical courses of 463 patients (mean age 49.1 years, range 5-82 years; 65.9% male) were included in the analysis. Conservative treatment with nasal corticosteroids started before initial presentation was more frequent in collective B (collective A 43.9% vs. collective B 72.2%). In 278 of the 463 patients (60%; A: 62%, B: 58%), at least one operation on the nasal sinuses had been performed after initial presentation; in 101 of these patients (36.3%) recurrent polyposis (within mean follow-up of 2.4 years) required further treatment. The indication for ASA provocation/desensitization was applied less frequently in collective B, also due to a high discontinuation rate (at least 38%) of the maintenance therapy. Of the total cohort, 16 patients (3.5%; A: n = 8, B: n = 8) were meanwhile switched to antibody therapy at recurrence. CONCLUSION: A step-by-step guideline-orientated approach is recommended in the treatment of CRSwNP. Systemic antibodies as an add-on to nasal corticosteroids are a relatively new therapeutic option for treatment-refractory CRSwNP, which reduces the indication for ASA desensitization, which is associated with a relatively high incidence of side effects and poor compliance.

[Chronic rhinosinusitis in people with cystic fibrosis-an up-to-date review from the perspective of otorhinolaryngology]. / Chronische Rhinosinusitis bei Menschen mit zystischer Fibrose ­ eine aktuelle Übersicht aus der Perspektive der Hals­, Nasen­, Ohrenheilkunde.

BACKGROUND: Cystic fibrosis (CF) is a complex systemic disease involving numerous organ systems. With improved treatment options and increasing life expectancy of persons with CF (PwCF), extrapulmonary manifestations are coming increasingly into the focus. From birth, almost all PwCF have radiologically detectable pathologies in the upper airways attributable to CF-associated chronic rhinosinusitis (CF-CRS). OBJECTIVE: The aim of this work is to provide an up-to-date overview of CF-CRS from the otorhinolaryngology perspective and to provide the reader with background knowledge and current developments. PATHOPHYSIOLOGY: The cystic fibrosis transmembrane conductance regulator (CFTR) gene defect leads to increased viscosity of sinonasal secretions and reduced mucociliary clearance, causing chronic infection and inflammation in the upper airway segment and, consequently, to CF-CRS. CLINICAL PICTURE AND DIAGNOSTICS: The clinical picture of CF-CRS comprises a wide spectrum from asymptomatic to symptomatic courses. CF-CRS is diagnosed clinically and radiologically. THERAPY: Sinonasal saline irrigation is recommended as a conservative treatment measure. Topical corticosteroids are also commonly used. Surgical therapy is reserved for highly symptomatic treatment-refractory patients without a sufficient response to conservative treatment including CFTR modulator (CFTRm) therapies. Depending on the CFTR mutation, CFTRm therapies are the treatment of choice. They not only improve the pulmonary and gastrointestinal manifestations in PwCF, but also have positive effects on CF-CRS. CONCLUSION: The ENT specialist is part of the interdisciplinary team caring for PwCF. Depending on symptom burden and treatment responsiveness, CF-CRS should be treated conservatively and/or surgically. Modern CFTRm have a positive effect on the clinical course of CF-CRS.

[Biologic therapy in patients with severe NSAID-exacerbated respiratory disease and previous aspirin desensitization : Results of a multicentric study]. / Biologikatherapie bei schwer erkrankten Patienten mit "NSAID-exacerbated respiratory disease" und stattgehabter ASS­Desaktivierung : Ergebnisse einer multizentrischen Studie.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type­2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B­SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.