Efficacy of dupilumab on chronic rhinosinusitis with nasal polyps and concomitant asthma in biologic-naive and biologic-pretreated patients.

OBJECTIVES: Dupilumab, an anti-IL-4 receptor monoclonal antibody (mAb), was recently approved for the treatment of severe chronic rhinosinusitis with nasal polyps (CRSwNP). The main objective of this study was to assess whether previous exposure to biological treatment affected the clinical outcomes in CRSwNP and asthma patients, treated with dupilumab over time. A collateral secondary objective was to analyse the effects over time of dupilumab in patients with and without aeroallergen sensitization. METHODS: Single-centre retrospective observational study on severe CRSwNP patients treated with dupilumab. Nasal polyp score (NPS), visual analogue scale (VAS) symptom score, sinonasal outcome test (SNOT-22), aeroallergen sensitization, total serum IgE levels, and blood eosinophil counts were assessed at baseline and after 4, 6 and 12 months. RESULTS: 42 patients were included, 40 (95.2%) had asthma. Twenty-one (50%) patients received dupilumab without prior biological treatment (Group A: naive) and 50% switched to dupilumab from previous biological treatment (Group B: pre-treated). NPS, VAS symptoms, SNOT-22 improved significantly after 12 months treatment in both groups of patients (p < 0.001). After 12 months, VAS overall symptom score showed a significant reduction from 6 (IQR, 4.6-8.6) and 6 (IQR, 3.8-7.1) for Group A and Group B patients respectively, to 1.2 (IQR, 0.8-2.7) and 1.2 (IQR, 0.2-2.5); NPS from 6 (IQR, 4.0-7.0) and 5 (IQR, 3.5-6.0), respectively, to 1 (IQR, 0.0-2.0) and 0 (IQR, 0.0-3.0) and SNOT-22 from 64 (IQR, 56-78) and 71 (IQR, 47.5-76.0) respectively, to 5.5 (IQR, 4-21) and 6 (IQR, 4-15). IgE reduced from 57 to 22.1 and from 46.9 to 30.2 in Group A and Group B respectively (p < 0.001). CONCLUSIONS: Dupilumab improves symptom severity, polyp size, and health-related quality of life, regardless of the presence or absence of comorbid aeroallergen sensitization and previous administration of biologic therapy.

Dupilumab proved to be effective in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP).We observed that dupilumab for CRSwNP leads to a very rapid improvement in polyps, symptoms, and quality of life, regardless of previous biologic treatment status and presence or absence of allergic rhinitis.VAS, SNOT-22 and NPS may be established as outcome markers in everyday clinical practice during dupilumab treatment.

Biologics in Chronic Rhinosinusitis: Current and Emerging.

Chronic rhinosinusitis (CRS) is categorized phenotypically into CRS with and without nasal polyps (CRSwNP, CRSsNP). Endotyping categorizes the disease based on immune cell activity and inflammatory mechanisms into Type 1, Type 2, and Type 3. The Type 2 endotype is the most researched and associated with asthma, atopic disease, and severe CRSwNP. For patients with poorly controlled CRSwNP, there are 3 approved biologic treatments: omalizumab, dupilumab, and mepolizumab. Many other biologics are being tested in Type 2, non-Type 2, and mixed endotypes in CRSwNP and CRSsNP. These studies will play a significant role in shaping the future of CRS management.

Orbital apex syndrome secondary to acute invasive fungal rhinosinusitis diagnosed by transnasal endoscopic biopsy of the optic canal:A case report.

Orbital apex syndrome (OAS) is a complex condition characterized by visual loss, diplopia, and eye pain that occurs secondary to several pathological processes involving the orbital apex. We report a case of acute invasive fungal rhinosinusitis (AIFRS) associated with OAS. A 76-year-old man with left-sided visual loss, diplopia, palpebral ptosis, and headache was diagnosed with OAS secondary to Tolosa-Hunt syndrome and received systemic corticosteroid therapy from his neurologist. Owing to persistent symptoms, we opened the optic canal using a transnasal endoscopic approach for a surgical biopsy of the orbital apex lesions. Histopathological evaluation revealed numerous Aspergillus organisms in the biopsied granuloma. After surgical debridement, he received a 12-month course of voriconazole, and no recurrence of AIFRS occurred during 8-year follow-up. Patients with OAS may occasionally be prescribed corticosteroids because the clinical manifestations of AIFRS-induced OAS are similar to those observed in OAS secondary to Tolosa-Hunt syndrome, especially no nasal symptoms which is known to respond to corticosteroid therapy. Because both AIFRS-induced OAS and OAS secondary to Tolosa-Hunt syndrome induce ophthalmoplegia, proptosis, eye pain, it is sometimes difficult to differentiate these two diseases in early stage. However, corticosteroid therapy causes exacerbation of fungal infection in patients with AIFRS-induced OAS resulting in delayed accurate diagnosis and poor prognosis. AIFRS is associated with a high mortality rate ; therefore, transnasal endoscopic biopsy of orbital apex lesions before corticosteroid administration is recommended in patients with OAS. J. Med. Invest. 71 : 310-313, August, 2024.

Causal relationships between allergic and autoimmune diseases with chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a prevalent inflammatory airway disease affecting over 10% of the global population, leading to considerable socio-economic impacts, especially in developing countries. The pathogenesis of CRS is multifactorial, involving potential contributions from both genetic and environmental factors. While the influence of allergic and autoimmune diseases on CRS has been observed, the causal relationships between these diseases and CRS remain unclear. We extracted data from large-scale genome-wide association studies (GWAS) and utilized a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationships between CRS and ten autoimmune and allergic diseases, including asthma, allergic rhinitis (AR), atopic dermatitis (AD), psoriasis, type 1 diabetes (T1D), hypothyroidism, celiac disease (CeD), multiple sclerosis (MS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Additionally, we conducted colocalization analysis to determine whether the allergic/autoimmune diseases showing statistical causal relationships with CRS are driven by the same genetic variants. The MR analysis identified that AR (OR = 1.30; 95% CI = 1.21-1.40; P = 3.26E-13), asthma (OR = 1.35; 95% CI = 1.25-1.45; P = 1.35E-14), and AD (OR = 1.17; 95% CI = 1.06-1.30; P = 0.003) were significantly associated with an increased risk of developing CRS. Interestingly, psoriasis (OR = 0.05; 95% CI = 0.01-0.37; P = 0.004) appeared to have a protective effect against CRS. Associations for T1D and hypothyroidism were also suggestive as potential risk factors for CRS. No significant associations in the reverse MR analysis, suggesting a one-directional relationship. Colocalization analysis indicated that asthma (PP.H4 = 0.99) shared the same genetic variant (IL-33 rs3939286) with CRS. In conclusion, our study confirmed the causal relationships between allergic and autoimmune diseases (AR, asthma, AD, and psoriasis) and CRS. Notably, we identified a shared genetic variant, rs3939286 in the IL-33 gene, between asthma and CRS, suggesting that targeting the IL-33 pathway may provide a therapeutic strategy for both diseases.

IL-1ß-induced epithelial cell and fibroblast transdifferentiation promotes neutrophil recruitment in chronic rhinosinusitis with nasal polyps.

Neutrophilic inflammation contributes to multiple chronic inflammatory airway diseases, including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), and is associated with an unfavorable prognosis. Here, using single-cell RNA sequencing (scRNA-seq) to profile human nasal mucosa obtained from the inferior turbinates, middle turbinates, and nasal polyps of CRSwNP patients, we identify two IL-1 signaling-induced cell subsets-LY6D+ club cells and IDO1+ fibroblasts-that promote neutrophil recruitment by respectively releasing S100A8/A9 and CXCL1/2/3/5/6/8 into inflammatory regions. IL-1ß, a pro-inflammatory cytokine involved in IL-1 signaling, induces the transdifferentiation of LY6D+ club cells and IDO1+ fibroblasts from primary epithelial cells and fibroblasts, respectively. In an LPS-induced neutrophilic CRSwNP mouse model, blocking IL-1ß activity with a receptor antagonist significantly reduces the numbers of LY6D+ club cells and IDO1+ fibroblasts and mitigates nasal inflammation. This study implicates the function of two cell subsets in neutrophil recruitment and demonstrates an IL-1-based intervention for mitigating neutrophilic inflammation in CRSwNP.

The safety and efficacy of spray cryotherapy after endoscopic sinus surgery in chronic rhinosinusitis: A systematic review of randomized controlled trials.

Background: Chronic rhinosinusitis (CRS) is a condition that affects 5-12% of the general population. Endoscopic sinus surgery (ESS) is the preferred treatment because of its few adverse effects and highest success rates. The most common post-operative consequences include synechia, nasal blockage, and disease recurrence. Spray cryotherapy is a novel therapeutic approach with promising outcomes for the treatment of upper airway disorders.This review aimed to investigate the effects of spray cryotherapy (SCT) following ESS in patients with chronic rhinosinusitis. Methods: Six electronic databases were searched for randomized clinical trials (RCTs). The selected trials were evaluated for methodological quality, and data were extracted by two independent reviewers. The Cochrane risk-of-bias tool was used to assess the quality of evidence. Results: Three RCTs with 85 patients were included in the final analysis. SCT was related to -16 and -77 reductions in Lund-McKay and SNOT-22 scores after 36 weeks of follow-up, in contrast to a placebo, which showed -10.4, -65. Regarding the side effects of SCT, no adverse effects were reported, and visual assessments showed no pain, visual field loss, or any other ocular complications. Conclusions: SCT is a new treatment modality after endoscopic sinus surgery that shows an effective post-operative management strategy with better post-operative scales (Lund-McKay, SNOT-22, POSE, and Lund-Kennedy) and less edema, obstruction, crusting, and inflammation with minimal or no side effects. However, further research with longer follow-ups, a larger sample size, and subjective assessment is needed to assess any possible long-term side effects.

When the Nose Meets the Lab: Histopathological Analysis in Chronic Rhinosinusitis with Nasal Polyps for Routine Clinical Practice.

PURPOSE OF REVIEW: We aimed to review the latest evidence regarding the value of tissue histopathological analysis in chronic rhinosinusitis with nasal polyps (CRSwNP) and to facilitate tissue analysis by proposing a pragmatic checklist for clinical settings. RECENT FINDINGS: CRSwNP is a chronic inflammatory disease that severely impairs the patient's quality of life. The severity of the disease can be correlated with nasal polyps enriched in eosinophils/IL-5 and, although ≥ 10 eosinophils per high power field are considered enough to determine an eosinophilic CRS, this cut-off value, the biopsy method, and the sampling location are still a matter of debate. Besides, tissue eosinophil values might also have some added value when combined with other cellular counts (e.g., eosinophil-to-lymphocyte ratio, Charcot-Leyden crystals). Structured histopathology analysis of sinonasal tissue-including, for instance, tissue remodelling biomarkers, fibrosis, and eosinophilic aggregates-has proven to be a valuable tool for healthcare professionals to identify different pheno-endotypes of CRSwNP and to improve the prioritisation of candidates to targeted therapies. Patients with CRSwNP are treated according to their severity with corticosteroids (intranasal and systemic), endoscopic sinus surgery, and/or biological therapy. A panel of expert ear, nose, and throat specialists and pathologists proposed a pragmatic checklist to improve the clinical practice around tissue analysis in CRSwNP, to facilitate communication between hospital-based healthcare professionals, and to standardize the evaluation of inflammatory biomarkers.

Assessing the Use of Patient-Reported Outcome Measures in the Routine Clinical Care of Chronic Rhinosinusitis Patients: A Canadian Perspective.

IMPORTANCE: Chronic rhinosinusitis (CRS) is a common inflammatory disease of the paranasal sinuses with significant quality of life impairments. There is a need to implement outcome-based metrics to evaluate the outcomes of CRS treatment with endoscopic sinus surgery or biologics. OBJECTIVE: We aimed to understand Canadian otolaryngologists' opinions on patient-related outcome measures (PROM) for CRS and identify potential barriers to implementation. DESIGN: Qualitative research. SETTING AND PARTICIPANTS: A cross-sectional survey was distributed via the Canadian Society of Otolaryngology-Head and Neck Surgery and direct emailing. MEASURES: Participants' demographics, practice information, and opinions on PROM were collected. RESULTS: Of 346 (23%) Canadian otolaryngologists, 78 responded to the survey (26 rhinology fellowship-trained, 51 non-fellowship-trained, and 1 missing data). Thirty-eight responded that they collect PROM (69% with fellowship-trained, 39% non-fellowship-trained, P = .029). Regarding opinions on PROM, 74% of respondents agreed that it helps patients report their symptoms, 42% agreed that it improves the efficiency of the patient encounter, 54% agreed that it is easy for patients to understand, 62% agreed that it improves management and monitoring of clinical outcomes, and 71% disagreed that PROM is not helpful. Fellowship-trained otolaryngologists were 4 times more likely to agree that PROM improves management and monitoring of clinical outcomes (P = .014), and no other differences in opinions were significant. The most-frequently-identified barriers to PROM usage were lack of time for 67% of respondents, difficulty integrating into clinical workflow for 64%, and lack of integration into the electronic medical record for 47%. If these barriers were addressed, 86% of respondents said they would use PROM in their practice. CONCLUSIONS AND RELEVANCE: Despite the low uptake of PROM among otolaryngologists without rhinology fellowship, opinions were generally favorable. We identified barriers that, if addressed, may increase their use in clinical practice. As resource-limited therapies such as biologics become more prevalent in CRS management, PROM may find more applications in shared clinical decision making.

Improvement in health-related quality of life questionnaires with biologic treatment in severe asthma and comorbid chronic rhinosinusitis with or without nasal polyposis: a real-life experience.

BACKGROUND: Patients with severe asthma frequently have comorbid chronic rhinosinusitis (CRS) with or without nasal polyps, that can increase the symptom burden and complicate treatment. Real-life clinical data on the impact of biologic treatments on CRS-specific quality-of-life questionnaires are still lacking. MATERIALS AND METHODS: In this retrospective real-life study, we collected data from patients with severe asthma with comorbid CRS with/without nasal polyposis at baseline, and after 3, 6 and 12 months of treatment with omalizumab, mepolizumab, benralizumab or dupilumab. In particular, we evaluated improvements in HRQoL as measured by SinoNasal Outcome Test-22 (SNOT-22, 0 - 110), Visual Analog Scale symptom scores (VAS, 0-10), and Asthma Control Test (ACT, 5-25) and the proportion of patients meeting the minimal clinically important difference (MCID). RESULTS: Disease-specific HRQoL, as measured by SNOT 22 and VAS score improved in all patients at 3, 6, and 12 months of treatment compared with baseline (SNOT-22: 14, IQR: 0-52 vs 10, IQR:0-30 vs 0, IQR:0-15 vs 0, IQR:0-12, p < 0.001, VAS score: 1, IQR: 0-5 vs 0, IQR:0-3 vs 0, IQR:0-2 vs 0, IQR 0-1, p < 0.001). After 3 months of treatment >80% of patients reached the MCID for ACT, while only patients on dupilumab showed to reach a MCID in 100% of cases. The effect size depended upon the symptom burden at baseline. CONCLUSIONS: The study confirms the efficacy of omalizumab, mepolizumab, benralizumab, and dupilumab in a real-life setting, with a rapid improvement in CRS-specific HRQoL and general health status. These data highlight the importance of targeting type 2 inflammation in asthmatic patients with co-existing upper and lower airways disease.The Authors disclose that preliminary data and analysis of the present study have been presented in abstract form during the "X International Workshop on Lung Health - Respiratory Disease and Immune Response", held in Nice on 19-21 January 2023.

Most Common Pathogens Causing Rhinosinusitis in Patients Who Underwent Endoscopic Sinus Surgery Before, During, and After the COVID-19 Pandemic.

IMPORTANCE: Chronic rhinosinusitis (CRS) significantly impacts patients' quality of life and incurs substantial healthcare costs. Understanding pathogen trends before, during, and after the COVID-19 pandemic can inform better management and treatment strategies. OBJECTIVE: To identify the common pathogens associated with CRS and compare them across pre-pandemic, during-pandemic, and post-pandemic periods. DESIGN: Retrospective chart review. SETTING: McGill University Health Centre, Montreal, Canada. PARTICIPANTS: Around 147 patients were 18 years and older, diagnosed with CRS, underwent endoscopic sinus surgery within the specified timeframe (January 2017 to September 2023), and whose charts contained relevant microbiology information. Patients were categorized into 3 groups based on surgery dates: pre- (January 2018 to November 2019), during- (January 2020 to December 2021), and post-pandemic (February 2022 to September 2023). MAIN OUTCOME MEASURES: Distribution and prevalence of pathogens associated with CRS across the 3 time periods. Microbiology results from nasal cultures were analyzed to identify predominant pathogens. RESULTS: Among the 147 patients, 46 distinct organisms were identified. Staphylococcus aureus was the most prevalent pathogen, increasing during the COVID-19 period (24.7%) compared to pre-pandemic (17.9%) and post-pandemic (21.5%) periods. Significant increases during the COVID-19 period were noted for Aspergillus fumigatus (6.8%, P < .001), Enterobacter cloacae (6.8%, P = .01), and Cutibacterium acnes (6.8%, P = .03). Post-pandemic, significant rises were observed in Serratia marcescens (P < .001) and Achromobacter denitrificans (P = .03). CONCLUSIONS AND RELEVANCE: Significant shifts in CRS-associated pathogens occurred during the COVID-19 pandemic. Notable changes in the prevalence of S. aureus, A. fumigatus, E. cloacae, and C. acnes were observed during the pandemic, with increases in S. marcescens and A. denitrificans post-pandemic. These findings suggest that the pandemic's impact on healthcare practices and environmental factors influenced the microbial etiologies of CRS. Future research may explore the mechanisms driving these changes and their long-term implications for CRS management.

Evaluation and treatment of rhinosinusitis with primary antibody deficiency in children: Evidence-based review with recommendations.

BACKGROUND: There is clear evidence that prevalence of primary antibody deficiency (PAD) is higher in children with chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in children with PAD. METHODS: The PubMed, Embase, and Cochrane databases were systematically reviewed from inception through December 2023. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated. RESULTS: A total of 50 studies were included in this evidence-based review. These studies were evaluated on the incidence of PAD in rhinosinusitis patients, the incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence varied across the reviewed domains. CONCLUSION: Based on the currently available evidence, the incidence of PAD in children with recalcitrant CRS can be significantly elevated. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher level studies that compare different treatments in children with PAD and rhinosinusitis.

Analysis of olfactory function in patients with chronic rhinosinusitis and Staphylococcus aureus enterotoxin positivity.

To investigate disparities in sensitisation to Staphylococcus aureus enterotoxin A/B (SEA/SEB) and olfactory function in patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), those with CRS without nasal polyps (CRSsNP), and healthy controls who underwent septoplasty only. We retrospectively reviewed the medical records of 388 subjects aged ≥ 8 years, collected between January 2021 and June 2023. We analysed patient demographics, medical history, serum IgE levels against staphylococcal enterotoxins (SEs), and serum total IgE levels against inhalant allergens. We performed olfactory and taste function tests in the participants to evaluate the relationship between olfactory function and SEs. Of 388 patients enrolled, 145 were healthy controls, 111 had CRSsNP, and 133 had CRSwNP. The prevalence of SEA/SEB positivity was significantly higher among the patients with CRSwNP than among those in the CRSsNP and healthy controls. The olfactory test results showed significant differences among the groups; anosmia was observed in 9.7% of healthy controls, 22.7% of patients with CRSsNP, and 45.1% of patients with CRSwNP. Olfactory threshold deterioration was evident in patients with CRS. Distinction and identification were more impaired in patients with CRSwNP than in those of the other groups. Finally, the olfactory function scores decreased as the serum levels of SEs increased. Sinusitis patients seem to suffer from perceiving odours, and patients with CRSwNP have difficulty distinguishing odours. Olfactory function test scores decreased in patients with a history of asthma, and as serum levels of staphylococcus enterotoxin and blood eosinophil percentage increase. Furthermore, our result suggests a potential role for SE sensitisation and eosinophil percentage in deteriorating olfaction, especially in patients with CRSwNP.

The Efficacy of Omalizumab in Patients with Chronic Rhinosinusitis with Nasal Polyps and Comorbid Severe Allergic Asthma.

Chronic rhinosinusitis whit nasal polyps (CRSwNP) is the most common comorbid disease accompanying asthma. Omalizumab is a recombinant anti-immunoglobulin (Ig) E antibody, and studies suggest that omalizumab may also affect CRSwNP regardless of asthma. We aimed to assess the effect of omalizumab treatment on CRSwNP accompanying severe allergic asthma (SAA) patients. Clinical data including spirometry measurements, serum/nasal secretion biomarker levels were collected. NP scores and CRS scores (Lund-Mancay [LM] scores) were also recorded before omalizumab treatment, as well as at the 4th and 12th months of omalizumab treatment. Twenty-one patients with both CRSwNP and SAA who underwent omalizumab therapy were assessed. There was a significant difference among forced expiratory volume (FEV1), ACT scores, NP scores, LM scores, serum IgE, and blood eosinophil levels of the patients before omalizumab therapy at the 4th and 12th months of omalizumab treatment. A significant negative correlation was observed between ∆FEV1 and ∆NP scores (r=-0.485), between ∆ACT and ∆NP scores (r=-0.469), and ∆ACT and ∆LM scores (r=-0.436). When we grouped the patients who benefited from 1 year of omalizumab therapy and those who did not in terms of NP, there was no difference between the two groups related to local eosinophil and local IgE levels in the nasal polyp biopsy. Omalizumab treatment is effective for asthma and CRSwNP in patients with CRSwNP accompanied by SAA. Improvement in asthma is associated with improvement in CRSwNP. The efficacy of omalizumab on NP in patients with CRSwNP accompanied by SAA is independent of local IgE and eosinophil counts.

Invasive Fungal Rhinosinusitis: The First Histopathological Study in Vietnam.

BACKGROUND: Invasive fungal rhinosinusitis (IRFS) is a rare but highly fatal disease. The two primary groups of pathogens, Mucorales and Aspergillus, require different treatments and have distinct prognoses. PURPOSE: This study aimed to analyze the histopathological features of IFRS. METHODS: We conducted a retrospective study involving 57 IFRS cases. Demographic and comorbid characteristics were obtained from clinical records. Two pathologists independently examined the histopathological features using H&E, PAS, and GMS-stained slides. Fungal groups were identified with PCR under the guidance of histopathology. RESULTS: The mean age of IFRS was 58.9 ± 13.4. The male-to-female ratio was 1.4:1. 100% of cases had diabetes comorbidity. Mucorales, Aspergillus, and other fungi were found in 61.4%, 33.3%, and 5.3% of cases, respectively. No Aspergillus and Mucorales co-infections were detected. Histopathology and PCR results were strongly concordant in classifying pathogens (Cohen's kappa = 84.2%, 95% CI 60.1% - 100%, p < 0.001). Mucormycosis exhibited higher rates of extensive necrosis and vascular invasion, and lower rates of pigment and spore presence than the non-Mucormycosis group (p < 0.001, p = 0.01, p = 0.02, p = 0.03, respectively). Extensive necrosis and vascular invasion were statistically significantly correlative (OR = 13.03, 95% CI 2.62-64.75, p = 0.002). CONCLUSIONS: IFRS predominantly affects older adults and males. Histopathology is a reliable method for differentiating between Mucorales and Aspergillus. When extensive necrosis is detected, it is critical to investigate for vascular invasion carefully. The vascular invasion, degree of necrosis, pigments, and spores are valuable factors for distinguishing fungal agents of IFRS.

Extent of Endoscopic Sinus Surgery in Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: There is an incomplete understanding regarding the extent of endoscopic sinus surgery (ESS) in managing chronic rhinosinusitis (CRS) and its effect on outcomes. This study aimed to assess and compare limited sinus surgery, full-house, extended and radical ESS for optimizing CRS outcomes. RECENT FINDINGS: An online search in adherence with PRISMA guidelines was performed. Data were pooled for meta-analysis. Forty-six articles met inclusion criteria. Full-house ESS yielded greater improvements in SNOT-22 and endoscopy scores over limited ESS. Radical ESS improved nasal symptoms and reduced disease recurrence more than full house ESS, while extended ESS decreased revision ESS rates when compared to full-house ESS. Total ethmoidectomy reduced SNOT-22 scores more than limited ethmoidectomy. There was no difference in perioperative complications for all extents of ESS. When compared to limited ESS, full-house ESS yielded better patient symptom outcomes. Radical ESS demonstrated even greater reductions in nasal symptoms, while extended ESS additionally decreased revision surgery rates. Thus, in general, greater extent of ESS leads to better outcomes, while all extents of ESS are relatively safe.

Canadian Real-World Study Long-Term Clinical Results Using Dupilumab for Chronic Rhinosinusitis With Polyps.

BACKGROUND: Dupilumab, an anti-IL4 receptor-α monoclonal antibody, was the first biologic to be approved in Canada for the treatment of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). In phase III clinical trials, it has demonstrated to be effective in reducing nasal polyp size and the severity of symptoms, improve disease-specific quality of life, and to have an acceptable safety profile. This study aims to present long-term follow-up data on disease-specific sinonasal outcomes of patients with CRSwNP who have been treated with dupilumab for up to 3 years in a real-world setting. METHODS: Retrospective review of electronic medical records of a single Canadian rhinology center evaluating disease-specific sinonasal outcomes that are routinely collected for clinical care. This study included all patients who received dupilumab for the treatment of CRSwNP and who had completed at least one follow-up visit. The Sino-Nasal Outcome Test (SNOT)-22 was used to evaluate treatment symptom improvement. RESULTS: Ninety-nine patients started dupilumab therapy during the study period. The mean SNOT-22 at the start of therapy was 61.1 (±22.91) At the time of the review, 65 patients had completed 1 year of therapy, 40 had completed 2 years of therapy, and 18 had completed 3 years of therapy. The mean SNOT-22 score at these timepoints was 16.75 (±13.86), 15.02 (±14.40), and 10.22 (±11.56), respectively. CONCLUSION: This real-world study shows that in patients with CRSwNP treated with dupilumab, improvement in disease-specific quality of life seen after 1 year continues and can be maintained at 3 years of treatment.

TIM-3-driven macrophage polarisation is associated to recalcitrant chronic rhinosinusitis with nasal polyps.

Objective: This study evaluated the expression of TIM-3 and its influence on macrophage polarisation in recalcitrant chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: We detected TIM-3 expression in serum and tissue samples of healthy controls (HC), primary CRSwNP, and patients with recurrent CRSwNP. Macrophage markers were detected among three groups, and their correlations with TIM-3 levels were examined. Macrophages from circulating blood were collected and used to examine the impact of TIM-3 on polarisation in vitro. Results: TIM-3 levels were enhanced in the CRSwNP group compared to the HC group. Tissue immunofluorescence revealed elevated TIM-3 expression in patients with CRSwNP, and patients with multiple recurrences exhibited higher TIM-3 levels compared to their first recurrence and baseline levels. Tissue CD163 and CD206 levels were higher in recurrent CRSwNP in comparison with primary cases and HCs, and had a positive correlation with TIM-3 levels. TIM-3 overexpression promoted M2 polarisation and enhanced TGF-ß1 and IL-10 secretion. Conclusions: TIM-3 expression was enhanced in patients with CRSwNP, especially in those undergoing revision surgeries. TIM-3 may be a novel biomarker for recalcitrant CRSwNP. TIM-3-driven M2 polarisation might be involved in the mechanisms of recurrent CRSwNP.

Relationship between chronic rhinosinusitis and risk of obstructive sleep apnea.

The relationship between obstructive sleep apnea (OSA) and chronic rhinosinusitis (CRS) has not yet been fully elucidated. Therefore, the objective of this study was to evaluate the connection between OSA risk and CRS by investigating associations between the STOP-Bang questionnaire and presence of CRS in a nationwide, population-based study. This is a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNHANES). We evaluated 10,081 subjects who completed both the STOP-Bang and CRS-related questionnaires. Among the total subjects, 390 (3.9%) were CRS patients. The median STOP-Bang score was 3.0 [2.0; 4.0] in CRS patients, compared to 2.0 [1.0; 3.0] in subjects without CRS. In a low-risk group according to the STOP-Bang questionnaire, 3.1% of subjects were CRS patients. However, a gradual increase was observed among different risk groups. In the higher risk group, CRS patients accounted for 5.3% (P < 0.001). Among the four main symptoms of CRS (nasal obstruction, nasal discharge, facial pain/pressure, and decreased sense of smell), nasal obstruction (4.1 to 7.3%) and a decreased sense of smell (1.9 to 3.3%) increased with higher STOP-Bang scores. This study found that the proportion of patients with CRS was significantly higher in the group at a higher STOP-Bang score in the general population. Among symptoms of CRS, nasal obstruction and anosmia were found to be associated with an increased STOP-Bang score.