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Background: Chronic or recurrent rhinosinusitis without polyps (CRSsNP) is characterized by a persistent inflammation of the sinonasal mucosa. The underlying cause is unclear but increasing interest has been directed toward changes in the sinonasal microbiome as a potential driver., Methods: Twenty-two patients diagnosed with CRSsNP were treated with antibiotics for 13 days, followed by 5 consecutive days of nasal microbiome transplants from healthy donors. Outcome measures were 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire, total nasal symptom score (TNSS), endoscopic grading, 16S ribosomal RNA (rRNA) next generation sequencing (microbiome analysis), and nasal lavage fluid analysis of inflammatory cytokines. Patients were examined at the start of the study and after antibiotic treatment as well as 10 days and 3 months after the transplant series., Results: At the end of the study, patients reported significantly reduced SNOT-22 scores and microbiome analysis showed significantly increased abundance and diversity. No significant change was observed for TNSS or endoscopic scoring., Conclusion: Nasal microbiome transplants obtained from healthy individuals and administered as nasal lavages to patients with CRSsNP are feasible. The patients reported significant and lasting reduction of symptoms and these findings were associated with a lasting increase in abundance and diversity of the local bacterial flora. The observations, which need to be confirmed by randomized controlled trials, may constitute a new treatment avenue for these difficult to treat patients where antibiotics only provide short lasting symptom control., (© 2022 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Topical steroids are first-line treatment for chronic rhinosinusitis (CRS), but fail to provide adequate symptom control for all patients. Designed for medical treatment failures, LYR-210 is an implantable matrix that locally elutes mometasone furoate to inflamed sinonasal tissue for up to 24 weeks in CRS patients. In an open-label phase 1 study, LYR-210 demonstrated clinically relevant improvement in the 22-item Sino-Nasal Outcome Test (SNOT-22). Safety and efficacy of LYR-210 in CRS were evaluated in the LANTERN Phase 2 study., Methods: Sixty-seven surgically naive adult CRS patients who were inadequately controlled by previous medical management and seeking an alternative treatment enrolled in a multicenter, blinded, controlled, dose-ranging study. Patients had moderate-to-severe disease based on SNOT-22 and composite 7-day average scores of the 4 cardinal CRS symptoms (4CS), with diagnosis confirmed by nasal endoscopy and magnetic resonance imaging. Patients were randomized (1:1:1) to saline irrigation-only control or bilateral in-office administration of LYR-210 (2500 μg) or LYR-210 (7500 μg). Safety and efficacy were evaluated over 24 weeks., Results: Both LYR-210 doses were safe and well-tolerated over the 24-week treatment period. LYR-210 demonstrated rapid and durable dose-dependent symptom improvement based on 4CS and SNOT-22, with LYR-210 (7500 μg) achieving statistical significance as early as 8 weeks and out to 24 weeks compared with control. LYR-210 (7500 μg) reduced rescue treatment use and radiographic ethmoid opacification at week 24., Conclusions: LYR-210 is the first implantable sinonasal treatment to achieve up to 24 weeks of benefit from a single administration in surgically naive CRS patients with and without nasal polyps., (© 2021 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both., Methods: LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 were two multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies assessing dupilumab added to standard of care in adults with severe CRSwNP. SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries. Eligible patients were 18 years or older with bilateral CRSwNP and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had sinonasal surgery. Patients in SINUS-24 were randomly assigned (1:1) to subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned (1:1:1) to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks. All patients were randomly assigned centrally with a permuted block randomisation schedule. Randomisation was stratified by asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery at screening, and country. Patients with or without comorbid asthma were included. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores (a coprimary endpoint in Japan), done in an intention-to-treat population. Safety was assessed in a pooled population of both dupilumab groups in SINUS-52 up to week 24 and the dupilumab group in SINUS-24 and the placebo groups in both studies until week 24. The trials are complete and registered at ClinicalTrials.gov, NCT02912468 and NCT02898454., Findings: Between Dec 5, 2016, and Aug 3, 2017, 276 patients were enrolled in SINUS-24, with 143 in the dupilumab group and 133 in the placebo group receiving at least one study drug dose. Between Nov 28, 2016, and Aug 28, 2017, 448 patients were enrolled in SINUS-52, with 150 receiving at least one dose of dupilumab every 2 weeks, 145 receiving at least one dose of dupilumab every 2 weeks for 24 weeks and every 4 weeks until week 52, and 153 receiving at least one dose of placebo. Dupilumab significantly improved the coprimary endpoints in both studies. At 24 weeks, least squares mean difference in NPS of dupilumab treatment versus placebo was -2·06 (95% CI -2·43 to -1·69; p<0·0001) in SINUS-24 and -1·80 (-2·10 to -1·51; p<0·0001) in SINUS-52; difference in nasal congestion or obstruction score was -0·89 (-1·07 to -0·71; p<0·0001) in SINUS-24 and -0·87 (-1·03 to -0·71; p<0·0001) in SINUS-52; and difference in Lund-Mackay CT scores was -7·44 (-8·35 to -6·53; p<0·0001) in SINUS-24 and -5·13 (-5·80 to -4·46; p<0·0001) in SINUS-52. The most common adverse events (nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema) were more frequent with placebo., Interpretation: In adult patients with severe CRSwNP, dupilumab reduced polyp size, sinus opacification, and severity of symptoms and was well tolerated. These results support the benefits of adding dupilumab to daily standard of care for patients with severe CRSwNP who otherwise have few therapeutic options., Funding: Sanofi and Regeneron Pharmaceuticals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007.The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disabling airway disease that significantly impacts patients' lives through the severity of symptoms, the need for long-term medical treatment and the high risk of recurrence post-surgery. Biological agents targeting type 2 immune responses underlying the pathogenesis of CRSwNP have shown effectiveness in reducing polyp size and eosinophilic infiltrate, and in decreasing the need for additional sinus surgeries. However, despite recent progress in understanding and treating the disease, type 2 inflammation-driven severe CRSwNP continues to pose challenges to clinical management due to several factors such as persistent inflammation, polyp recurrence, heterogeneity of disease, and comorbidities. This article presents the findings of a scientific discussion involving a panel of ear, nose and throat (ENT) specialists and pulmonologists across Sweden and Finland. The discussion aimed to explore current management practices for type 2 inflammation-driven severe CRSwNP in the Nordic region. The main topics examined encompassed screening and referral, measurements of disease control, treatment goals, and future perspectives. The experts emphasized the importance of a collaborative approach in the management of this challenging patient population. The discussion also revealed a need to broaden treatment options for patients with type 2 inflammation-driven CRSwNP and comorbid conditions with shared type 2 pathophysiology. In light of the supporting evidence, a shift in the disease model from the presence of polyps to that of type 2 inflammation may be warranted. Overall, this discussion provides valuable insights for the scientific community and can potentially guide the future management of CRSwNP. [ABSTRACT FROM AUTHOR]

Objective A locally disturbed commensal microbiome might be an etiological factor in chronic rhinosinusitis (CRS) in general and in CRS without nasal polyps (CRSsNP) in particular. Lactic acid bacteria (LAB) have been suggested to restore commensal microbiomes. A honeybee LAB microbiome consisting of various lactobacilli and bifidobacteria have been found potent against CRS pathogens in vitro. Recently, we examined effects of single nasal administrations of this microbiome in healthy subjects and found it inert. In this study, we examined effects of repeated such administrations in patients with CRSsNP. Study Design The study was of a randomized, double-blinded, crossover, and sham-controlled design. Methods Twenty patients received 2 weeks' treatment administered using a nasal spray-device. The subjects were monitored with regard to symptoms (SNOT-22 questionnaire, i.e., the primary efficacy variable), changes to their microbiome, and inflammatory products (IL-6, IL-8, TNF-, IL-8,a, and MPO) in nasal lavage fluids. Results Neither symptom scores, microbiological explorations, nor levels of inflammatory products in nasal lavage fluids were affected by LAB (c.f. sham). Conclusion Two weeks' nasal administration of a honeybee LAB microbiome to patients with CRSsNP is well tolerated but affects neither symptom severity nor the microbiological flora/local inflammatory activity. Level of Evidence 1b [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) patients who fail medical management have few treatment options other than endoscopic sinus surgery (ESS). A novel biodegradable mometasone furoate drug delivery system (LYR‐210) providing continuous topical steroid therapy to sinonasal mucosa over 24 weeks was developed to treat unoperated CRS patients who have failed medical management prior to ESS. LYR‐210 was designed to slowly expand in the middle meatus, ensuring efficient drug delivery as mucosal swelling reduces. Methods: A prospective, multicenter, open‐label study was conducted in 20 CRS subjects who were determined to be candidates for ESS. Under endoscopic guidance and topical anesthesia, LYR‐210 was placed in both middle meatuses. The primary endpoint was product‐related serious adverse events (SAEs) at 4 weeks. Additional assessments included plasma drug concentration, morning serum cortisol levels, intraocular pressures (IOPs), and Sino‐Nasal Outcome Test (SNOT‐22) scores. Results: LYR‐210 was successfully placed bilaterally in 20 subjects (12 without nasal polyps and 8 with polyps) in an office setting. There were no product‐related SAEs through 24 weeks, at which point 86% of LYR‐210 depots were still retained in the middle meatus. Serum cortisol, IOP, and plasma drug concentrations supported systemic safety at all time points tested. Subjects experienced significant reductions in their SNOT‐22 scores as early as week 1, and this reduction persisted through week 24 (p < 0.01). Significant symptom improvement was achieved in the SNOT‐22 rhinologic, extranasal rhinologic, ear‐facial, psychological, and sleep dysfunction subdomains at 24 weeks (p < 0.05). Conclusion: LYR‐210 is safe and well‐tolerated in ESS‐naive CRS patients and leads to sustained symptom improvement in patients. [ABSTRACT FROM AUTHOR]