Correlation of patient reported outcome measures with endoscopic findings in pediatric chronic adenoiditis and chronic rhinosinusitis.

BACKGROUND: Studies in adult chronic rhinosinusitis (CRS) showed poor correlation between patient reported outcome measures (PROMs) and objective findings. Our goal is to study the correlation between the sinus and nasal quality of life (SN-5) and the 22-items sinonasal outcome test (SNOT-22) surveys with endoscopy findings in children with chronic adenoiditis (CA) and CRS. METHODS: Cross-sectional study of all pediatric patients (age 2-18) presenting for CA or CRS was performed. Patients and caregivers were asked to fill the SN-5 and SNOT-22 questionnaires at initial and follow up visits. Demographics and comorbidities were collected. Objective findings included endoscopy Modified Lund-Kennedy (MLK) scores and adenoid tissue size. RESULTS: 124 children were included, with mean age of 9.9 years (SD = 4.8) and 46.8% female. 36.3% had allergic rhinitis, 23.4% had asthma, and 4% had obstructive sleep apnea. Moderate correlation was found between the rhinologic domain of SNOT-22 and MLK scores (r = 0.36, p = 0.001) and between SN5 scores and adenoid size in all patients (r = 0.39, p < 0.001). SNOT-22 scores showed moderate correlation with adenoid size (r = 0.42, p < 0.001) more specifically in CA patients (r = 0.54, p < 0.001). The correlation of SN5 and MLK scores were higher in children with allergic rhinitis or asthma. The correlation between SN5 and adenoid size was lower in children with allergic rhinitis or asthma. CONCLUSION: There is discrepancy between the subjective measures and the objective findings in children with CA or CRS. The physical exam findings may not reflect the effect of CRS on the quality of life of children.

Prevalence and predictors of depression and anxiety in patients with chronic rhinosinusitis: a systematic review and meta-analysis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinuses. As a result of long-term discomfort, patients may experience symptoms of common mental disorders such as anxiety and depression. This may affect the quality of life and disease progression. However, there is still uncertainty about the extent of the problem. OBJECTIVE: This meta-analysis aimed to determine the prevalence of depression and anxiety symptoms in patients with CRS. SEARCH STRATEGY: We searched PubMed, Embase, Web of Science, Cochrane Library, and CBM databases for relevant studies published before 15 July 2022 in patients with CRS with concomitant depression and anxiety symptoms. DATA COLLECTION AND ANALYSIS: Two authors independently performed screening and quality assessment using validated tools. Extraction of data using predefined standardised data collection spreadsheets. Heterogeneity and inconsistency were checked using the I² statistic. RESULTS: The meta-analysis included 32 articles involving 56 933 patients. The prevalence of depression and anxiety symptoms was estimated at 24.7% (95% CI, 21.3% to 28. 1%) and 29.7% (95% CI, 19.3% to 40.2%). Subgroup analysis revealed the following: (1) CRS without nasal polyps (CRSsNP): 26.2% (95% CI, 21.9% to 30.5%), CRS with nasal polyps(CRSwNP): 20% (95% CI, 15.9% to 24%); (2) Female patients: 36. 1% (95% CI, 25.3% to 46.9%), male patients: 24.3% (95% CI, 12. 1% to 36.6%); and (3) The average age≤50 years patients: 29.8% (95% CI, 21.3% to 38.2%), the average age>50 years patients: 22. 1% (95% CI, 17.1% to 27%). CONCLUSION: A significant proportion of people with CRS have symptoms of depression and anxiety, and early screening for depression and anxiety in people with CRS is critical. And, more attention needs to be given to females and patients with CRSsNP during screening. PROSPERO REGISTRATION NUMBER: CRD42022345959).

A Novel Model of Staphylococcus aureus-Induced Lymphoplasmacytic Rhinosinusitis in Rats.

Chronic rhinosinusitis (CRS) is characterized by sinonasal mucosal inflammation. Staphylococcus aureus (S. aureus) is associated with severe CRS phenotypes. Different animal models have been proposed to study the association of CRS and S. aureus. However, current animal models are expensive due to the use of large animals, have high barriers to ethics approval, or require invasive surgical intervention, necessitating a need for a model that can overcome these limitations. This study aimed at establishing a reliable and efficient rat lymphoplasmacytic inflammatory model for rhinosinusitis. Sprague Dawley rats received a daily intranasal application of 20 µL of saline, S. aureus CI-182 exoprotein (250 µg/mL), or exoprotein CI-182 in combination with S. aureus clinical isolate (CI-908 or CI-913) 108 colony-forming unit (CFU)/mL. The rats' sinuses were harvested at 1 and 2 weeks post-intervention. The CFU and histopathologic examination of inflammation were evaluated. S. aureus clinical isolates CI-908 or CI-913 in combination with the exoprotein (CI-182) had higher CFUs and caused persistently higher inflammation at both the 1 and 2-week post-intervention compared to the exoprotein and saline group. The observed inflammatory cell type was lymphoplasmacytic. This study provided evidence that the combination of a S. aureus exoprotein with S. aureus induces inflammation that persists for a minimum of two weeks post-intervention. This model is the first known animal model to create the lymphoplasmacytic inflammation subtype seen in CRS patients. This offers a cost-effective, accessible, non-invasive, and easy-to-replicate model to study the causes and treatment of such inflammation.

SerpinB3/B4 Abates Epithelial Cell-Derived CXCL8/IL-8 Expression in Chronic Rhinosinusitis with Nasal Polyps.

Background: Serine proteinase inhibitors, clade B, member 3 (SerpinB3) and B4 are highly similar in amino acid sequences and associated with inflammation regulation. We investigated SerpinB3 and B4 expression and their roles in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: The expression of SerpinB3 and B4 in nasal mucosa tissues, brush cells, and secretions from CRSwNP patients was measured, and their regulation by inflammatory cytokines were investigated. Their functions were also analyzed using air-liquid interface (ALI)-cultured primary human nasal epithelial cells (HNECs) and transcriptomic analysis. Results: Both SerpinB3 and B4 expression was higher in nasal mucosa, brush cells, and secretions from eosinophilic (E) CRSwNP and nonECRSwNP patients than in healthy controls. Immunofluorescence staining indicated that SerpinB3 and B4 were primarily expressed in epithelial cells and their expression was higher in CRSwNP patients. SerpinB3 and B4 expression was upregulated by interleukin-4 (IL-4), IL-5, IL-6, and IL-17a. Transcriptomic analysis identified differentially expressed genes (DEGs) in response to recombinant SerpinB3 and B4 stimulation. Both the DEGs of SerpinB3 and B4 were associated with disease genes of nasal polyps and inflammation in DisGeNET database. Pathway enrichment indicated that downregulated DEGs of SerpinB3 and B4 were both enriched in cytokine-cytokine receptor interactions, with CXCL8 as the hub gene in the protein-protein interaction networks. Furthermore, CXCL8/IL-8 expression was downregulated by recombinant SerpinB3 and B4 protein in ALI-cultured HNECs, and upregulated when knockdown of SerpinB3/B4. Conclusion: SerpinB3/B4 expression is upregulated in nasal mucosa of CRSwNP patients. SerpinB3/B4 may play an anti-inflammatory role in CRSwNP by inhibiting the expression of epithelial cell-derived CXCL8/IL-8.

Surgical and medical management of chronic rhinosinusitis in pediatric cystic fibrosis patients: Impact on olfactory symptoms.

BACKGROUND AND PURPOSE: Olfactory dysfunction (OD) commonly occurs in patients with sinonasal dysfunction, but the prevalence and severity of olfactory issues in adolescents with cystic fibrosis (AwCF) is unclear. OD may contribute to dietary deficiencies and exacerbate nutritional challenges. We sought to review literature on the effectiveness of medical and surgical management of sinonasal symptoms in AwCF and the associated impact on olfactory function. METHODS: We performed a systematic literature search of PubMed, Embase, Web of Science, and Ebsco CINAHL from 1980 to 2022 per PRISMA-ScR protocols to conduct a scoping review in an effort to compile data on study design, patient demographics, clinical characteristics and outcomes, along with risk of bias. RESULTS: Of 368 abstracts, 3 articles exclusively evaluated AwCF for a total of 34 patients. Two studies evaluated endoscopic sinus surgery (ESS) and dornase alfa. An additional 6 articles were included for mixed pediatric and adult CF populations totaling 313 patients. Interventions included ESS, elexacaftor-tezacaftor-ivacaftor (ETI), ivacaftor, saline, dornase alfa, hyaluronic acid, and hyaluronic acid-tobramycin combination. Outcome measures included subjective assessment of OD using non-validated (4/9) and validated (4/9) surveys, and psychophysical (1/9) smell testing. Studies evaluating ESS, FESS, dornase alfa, ivacaftor, and both hypertonic and isotonic saline reported statistically significant improvement in OD, whereas ETI failed to improve OD despite improvement in other quality of life measures. CONCLUSIONS: There is limited data regarding the impact of medical and surgical interventions on olfaction for AwCF. Assessment of olfaction was often limited to subjective and qualitative self-report. We suggest that tracking of olfactory outcomes with psychophysical testing is critical in this population with dietary challenges and weight management issues.

Epidemiological characterization and risk factors of rhinitis and rhinoconjunctivitis among preschool children in Shanghai, China.

BACKGROUND: Previous studies have reported an increasing prevalence of childhood allergic rhinitis in developing countries. There is still a lack of the recent epidemiology of allergic rhinitis among Chinese preschool children. Therefore, this study explored the prevalence of rhinitis symptoms and identified their associations with potential risk factors among children at the age of 3-6 in Shanghai, China. METHODS: Validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was adopted to collect information about rhinitis symptoms and potential risk factors. Univariate and multivariate logistic regression analyses were used to assess associations between risk factors and allergic rhinitis and rhinoconjunctivitis. RESULTS: A total of 6183 questionnaires were included in our study. The prevalence of rhinitis ever, current rhinitis, and physician-diagnosed rhinitis were 32.6%, 29.2%, and 14.3%, respectively, while the prevalence of current rhinoconjunctivitis was 11.3%. The higher prevalence was observed in boys than in girls in terms of rhinitis ever, current rhinitis, current rhinoconjunctivitis and doctor-diagnosed rhinitis. Autumn had the highest prevalence among four seasons. In our multivariate logistic regression analyses, history of allergic diseases and paracetamol use in the last year showed positive associations with the increased risk of both current rhinitis and rhinoconjunctivitis, and antibiotic use was an independent significant risk factor only for current rhinitis. Genetic factors, including maternal and paternal rhinitis, asthma, and eczema, were significantly associated with the prevalence of current rhinitis. Similar associations were seen between these factors and current rhinoconjunctivitis, except for paternal eczema. Among environmental factors, smoking exposure at home, heavy truck traffic in home's street, floor heating system were independent risk factors for both current rhinitis and rhinoconjunctivitis in the adjusted model, while cleaning the house less than once a week was only associated with current rhinitis. CONCLUSION: The prevalence of current rhinitis was 29.2% among children aged 3-6 in Shanghai, China. Sex differences and seasonal variations were observed in the prevalence of rhinitis symptoms. The identified risk factors would provide a basis for policy makers and medical experts to take intervention measures to prevent allergic rhinitis and rhinoconjunctivitis.

Is generative pre-trained transformer artificial intelligence (Chat-GPT) a reliable tool for guidelines synthesis? A preliminary evaluation for biologic CRSwNP therapy.

INTRODUCTION: Biologic therapies for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) have emerged as an auspicious treatment alternative. However, the ideal patient population, dosage, and treatment duration are yet to be well-defined. Moreover, biologic therapy has disadvantages, such as high costs and limited access. The proposal of a novel Artificial Intelligence (AI) algorithm offers an intriguing solution for optimizing decision-making protocols. METHODS: The AI algorithm was initially programmed to conduct a systematic literature review searching for the current primary guidelines on biologics' clinical efficacy and safety in treating CRSwNP. The review included a total of 12 studies: 6 systematic reviews, 4 expert consensus guidelines, and 2 surveys. Simultaneously, two independent human researchers conducted a literature search to compare the results. Subsequently, the AI was tasked to critically analyze the identified papers, highlighting strengths and weaknesses, thereby creating a decision-making algorithm and pyramid flow chart. RESULTS: The studies evaluated various biologics, including monoclonal antibodies targeting Interleukin-5 (IL-5), IL-4, IL-13, and Immunoglobulin E (IgE), assessing their effectiveness in different patient populations, such as those with comorbid asthma or refractory CRSwNP. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, demonstrated significant improvement in nasal symptoms and quality of life in patients with CRSwNP in several randomized controlled trials and systematic reviews. Similarly, mepolizumab and reslizumab, which target IL-5, have also shown efficacy in reducing nasal polyp burden and improving symptoms in patients with CRSwNP, particularly those with comorbid asthma. However, additional studies are required to confirm the long-term efficacy and safety of these biologics in treating CRSwNP. CONCLUSIONS: Biologic therapies have surfaced as a promising treatment option for patients with severe or refractory CRSwNP; however, the optimal patient population, dosage, and treatment duration are yet to be defined. The application of AI in decision-making protocols and the creation of therapeutic algorithms for biologic drug selection, could offer fascinating future prospects in the management of CRSwNP.

Association between peripheral eosinophilia, JESREC score, and olfactory dysfunction in patients with chronic rhinosinusitis.

Objective: The purpose was to evaluate the relationship between peripheral eosinophilia, Japan Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, and olfactory dysfunction in chronic rhinosinusitis (CRS) patients and to explore the accuracy and specific cut points of the JESREC score in predicting olfactory dysfunction. Methods: In this cross-sectional, retrospective study, olfactory function was assessed by the Sniffin' Sticks 12-item test and multivariate logistic regression analyses were carried out. Receiver operating characteristic curves were plotted to derive accuracy and cutoff values for the JESREC scores of the olfactory dysfunction criterion. Results: A total of 354 patients [mean (SD) age, 50.0 (14.9) years; 41.8% women] were included in the final analysis. The prevalence of olfactory dysfunction was 46.3%. Individuals who had olfactory dysfunction were more likely to be male (64.6% vs. 52.6%), have eosinophilic chronic rhinosinusitis (ECRS) (39.0% vs. 7.9%), have a longer course of CRS (2.3 years vs. 1.5 years), have higher JESREC scores (8.5 vs. 4.5), and have higher proportions of nasal polyps (78.7% vs. 18.9%) and peripheral eosinophilia (3.3% vs. 1.4%). In logistic analysis, the percentage of eosinophils (1.25, 1.13-1.37), JESREC score (1.31, 1.22-1.40), bilateral lesion (2.06, 1.25-3.41), nasal polyps (15.83, 9.23-27.16), CT shadow (2.73, 1.69-4.43), and ECRS (6.86, 3.68-12.80) were associated with olfactory dysfunction in CRS patients after controlling for covariates, while peripheral neutrophils were not significant. In addition, the area under the curve was 0.778 and the cutoff value for JESREC score for olfactory dysfunction was defined as 5.5. Conclusions: Peripheral eosinophilia and high JESREC scores were significantly associated with the risk of olfactory dysfunction in CRS patients, and special attention should be paid to patients with a JESREC score ≥6.

Patterns of Olfactory Impairment Among Patients with Uncontrolled Chronic Rhinosinusitis.

OBJECTIVES: Self-reported olfactory dysfunction is an assessment component criterion for chronic rhinosinusitis (CRS) disease control of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). No studies have objectively explored olfactory function across different psychophysical olfactory domains among patients with uncontrolled CRS. We aimed to investigate the patterns of olfactory impairment in patients with uncontrolled CRS with Sniffin' Sticks test. METHODS: A total of 79 patients with CRS were prospectively recruited and assessed for disease control based on the EPOS criteria. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, olfactory cleft endoscopy scale (OCES), questionnaire of olfactory disorders-negative statements (QOD-NS), and sinonasal outcome test-22 (SNOT-22) were obtained. Multiple logistic regression was applied to explore risk factors of uncontrolled CRS. RESULTS: Twenty-six percent of patients with CRS presented with uncontrolled status. The odor threshold (OT) (p = 0.005), odor identification (OI) (p = 0.041), and thresholds-discrimination-identification (TDI) (p = 0.029) scores were significantly lower in patients with uncontrolled CRS when compared with patients with controlled CRS. Furthermore, patients with uncontrolled CRS presented with a significantly increased percentage of anosmia (p = 0.014), olfactory cleft CT score (p = 0.038), OCES (p = 0.016), QOD-NS(p = 0.008), and SNOT-22 (p < 0.001) scores than patients with controlled CRS. After adjusting for patient demographics, as for the subdomain of olfaction, only the OT score was an independent risk factor for uncontrolled CRS (odds ratio = 0.604; p = 0.030). The OT scores less than 5.950 were the best predictor of uncontrolled CRS. CONCLUSION: Patients with uncontrolled CRS demonstrated distinct patterns of olfactory impairment, and a reduced olfactory threshold was highly associated with uncontrolled CRS. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2341-2348, 2024.

[Decision-making in the treatment of chronic rhinosinusitis with nasal polyps in the era of biologics]. / Entscheidungsfindung bei der Behandlung der chronischen Rhinosinusitis mit Nasenpolypen in der Ära der Biologika.

Chronic rhinosinusitis is one of the most common chronic diseases in the population. Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults is predominantly characterized by a type 2 inflammatory endotype. If sufficient control cannot be achieved through primary drug therapy, surgical intervention is usually recommended as the next stage of treatment. Nowadays, various biologics are available that have been or will be approved for use in these patients. This review summarizes the presentations from the 29th Congress of the European Rhinologic Society in Sofia 2023 and the latest findings on decision-making in the treatment of CRSwNP. Standard therapy with medication and sinus surgery fails in some patients with CRSwNP. Biologics that act on the type 2 inflammatory pathway led to a reduction in the nasal polyp score (NPS), an improvement in nasal obstruction, and an improvement in quality of life without significant side effects. Biomarkers such as total IgE, serum eosinophils, and Osteoprotegerin (OPG) can provide indications of the success of the treatment. In summary, it can be said that for many patients with recurrent CRSwNP, a combination of paranasal sinus surgery and treatment with a biologic that is precisely tailored to the patient's endotype is the best option. However, the question of which surgical approach and which biologic at which time and for which patient is still ongoing and requires further studies.

Adherence to guidelines prior to endoscopic sinus surgery in patients with chronic rhinosinusitis and asthma.

INTRODUCTION: Optimal care for patients with simultaneous chronic rhinosinusitis (CRS) and asthma is often complicated due to interaction between these conditions. This study depicts the lack of attention to asthma within the otorhinolaryngological field, and the relationship between CRS and asthma, including the risk of revision surgery in such patients. METHODS: A retrospective cohort study was conducted on patients undergoing functional endoscopic sinus surgery (FESS) because of CRS with nasal polyps (CRSwNP) and without nasal polyps in a five-year period. Patients were examined for adherence to guidelines, asthma, revision FESS, allergies and septo-/turbinoplasty. Results were compared to international reports. RESULTS: A total of 589 patients had FESS because of CRS of whom 203 (34.5%) had co-existing asthma. A higher risk of asthma (relative risk (RR) = 1.82 (95% confidence interval (CI): 1.29-2.56), p less-than 0.001) and revision FESS (RR = 2.20 (95% CI: 1.33-3.65), p less-than 0.001) was found in patients with CRSwNP. Attention to asthma was poor in patients with no asthma diagnosis before referral. CONCLUSIONS: Asthma was lower in the study population than in the literature. Danish national guidelines on CRS management are insufficient regarding attention to asthma. Results call attention to the need for more multidisciplinary team management. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Association of allergic rhinitis with persistent obstructive sleep apnea: A secondary analysis of the childhood adenotonsillectomy trial.

STUDY OBJECTIVES: Allergic rhinitis (AR) is frequently reported in children suffering from obstructive sleep apnea (OSA). This study aimed to assess whether children with AR are more likely to experience persistent OSA after AT. METHODS: This study is a secondary analysis of a multi-center randomized clinical trial, the Childhood Adenotonsillectomy Trial. Children were categorized into the AR group or Non-AR group according to AR response. A subgroup analysis was conducted using a logistic regression model. RESULTS: A total of 372 children (177 boys [47.6%]; median [IQR] age, 6.0 [5.0-8.0] years) were analyzed. Approximately 25% (93/372) of children presented with AR. Baseline data indicated higher PSQ scores and OSA-18 scores in the AR group. Children with AR demonstrated lower OSA resolution rates after AT (aOR, 0.43; 95% CI, 0.19 to 0.96). However, there was no significant difference in OSA resolution between the AR and Non-AR groups who underwent watchful waiting (aOR, 0.98; 95% CI, 0.50 to 1.93). Also, the AR group was more likely to maintain a PSQ score greater than 0.33 after AT (OR, 2.16; 95% CI, 1.01 to 4.61). There was no significant association between AR and higher follow-up OSA-18 scores after AT and watchful waiting. CONCLUSIONS: In this secondary analysis, children with AR were more likely to experience persistent OSA, highlighting the importance of effective AR management even post-adenotonsillectomy. A purposefully designed, prospective randomized trial is needed to verify the association between AR and persistent OSA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00560859.

Postinfectious conditions challenge disease-specificity of SNOT-22.

PURPOSE: The Sino-Nasal-Outcome-Test 22 (SNOT-22) questionnaire assesses treatment outcome and health-related quality of life (HRQOL) in patients with chronic rhinosinusitis (CRS). However, given the overlap between CRS and olfaction in terms of nasal function and the definition of CRS, a fundamental question arises: can patients with olfactory dysfunction (OD) stemming from other causes attain SNOT-22 scores similar to those seen in CRS, even in the absence of CRS? Our study aimed to explore whether OD arising from various postinfectious mechanisms challenges the disease-specificity of SNOT-22 for CRS. If so, could focus on scores within specific symptom domains of SNOT-22 prove valuable in distinguishing between different etiologies. METHODS: The study adopted an observational, retrospective cohort design based on prospectively registered patients and related variables using the REDCap platform. 460 patients experiencing OD due to either (1) simple or (2) complex post-COVID-19, (3) postinfectious non-COVID-19, and (4) CRS, were included in the analysis. RESULTS: The study revealed that the total SNOT-22 score lacks disease-specificity for CRS. This is evident, because complex postinfectious mechanisms resulting from COVID-19 can produce similar symptoms in patients. Notably, elevated total scores were primarily driven by high subdomain scores within the "sleep and cognition" domain. CONCLUSIONS: The application of SNOT-22 as a screening tool needs to be approached with caution, as the total score alone does not provide disease-specific insights. A more thorough exploration of the four symptom domains and the identification of distinctive scoring patterns within the clinical context may prove pivotal in effectively differentiating between various underlying causes.

Single-cell RNA sequencing reveals the epithelial cell, fibroblast, and key gene alterations in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the nasal mucosa, and epithelial-mesenchymal transition (EMT) is thought to be an essential process in the pathogenesis of CRSwNP. However, the mechanisms of epithelial and fibroblastic changes at the single-cell level are unclear. In this study, we investigated the epithelial cell, fibroblast, and key gene alterations in the development of CRSwNP. We revealed major cell types involved in CRSwNP and nasal mucosal inflammation formation, then mapped epithelial and fibroblast subpopulations. We showed that the apical and glandular epithelial cells and the ADGRB3+ and POSTN+ fibroblasts were the key cell subtypes in the progression of CRSwNP. Pseudotime and cell cycle analysis identified dynamic changes between epithelial cells and fibroblasts during its development. WFDC2 and CCL26 were identified as the key marker genes involved in the development of CRSwNP and were validated by IHC staining, which may provide a potential novel target for future CRSwNP therapy. ScRNA-seq data provided insights into the cellular landscape and the relationship between epithelial cells and fibroblasts in the progression of CRSwNP. WFDC2 and CCL26 were identified as the key genes involved in the development of CRSwNP and may be the potential markers for gene therapy.

Sustained efficacy of mepolizumab in patients with severe chronic rhinosinusitis with nasal polyps: SYNAPSE 24-week treatment-free follow-up.

BACKGROUND: In the 52-week Phase III SYNAPSE study, mepolizumab given every 4 weeks (100 mg subcutaneously) reduced nasal polyp (NP) size, improved symptoms and quality of life (QoL), and reduced corticosteroid use and number of sinus surgeries in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), versus placebo. Because the durability of mepolizumab's efficacy after discontinuation is poorly understood in CRSwNP, the efficacy of mepolizumab after discontinuation was analyzed in severe CRSwNP, over a 24-week follow-up. METHODS: Changes from SYNAPSE baseline to end of treatment (week 52) and end of follow-up (week 76) were assessed for total endoscopic NP score, nasal obstruction and overall symptoms visual analog scale scores, and 22-item Sino-Nasal Outcome Test score. Time to first sinus surgery, time to first corticosteroid use, and geometric mean blood eosinophil counts (BECs) were also assessed. RESULTS: Among 134 follow-up patients, clinical improvements observed with mepolizumab versus placebo were partially evident 24 weeks after discontinuation despite BEC returning to baseline. The mean (95% confidence interval [CI]) change from baseline in NP score (week 52: -1.3 [1.8 to -0.9] vs. -0.3 [-0.6 to 0.1]; week 76: -1.2 [-1.6 to -0.7] vs. -0.1 [-0.5 to 0.3]) and the proportion of patients having sinus surgery (week 52: 4% vs. 25%; week 76: 9% vs. 31%) remained substantially improved with mepolizumab versus placebo. Mepolizumab-associated improvements in overall symptoms, quality of life, and corticosteroid use versus placebo were partially sustained at week 76. CONCLUSION: Fifty-two weeks of mepolizumab treatment is associated with sustained clinical benefits up to 24 weeks after discontinuation in patients with severe CRSwNP, which should be considered by physicians when making treatment decisions.

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022.

KEYPOINTS: Between 2007 and 2022, the FDA received 119 US-based reports mentioning budesonide nasal irrigation. Most reports were submitted by patients and alerted FDA to off-label usage of budesonide. Notable adverse events reported to the FDA included headache, dyspnea, and blurred vision.

Chronic rhinosinusitis with nasal polyps (CRSwNP) treated with omalizumab, dupilumab, or mepolizumab: A systematic review of the current knowledge towards an attempt to compare agents' efficacy.

BACKGROUND: The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the selection of the proper biologic in treatment of chronic rhinosinusitis (CRS) with nasal polyps. The aim of this study is to summarize the current knowledge regarding the efficacy of omalizumab, dupilumab, and mepolizumab in CRS treatment. We also attempt to proceed to an indirect comparison of the agents and try to answer the tricky question: which agent to select and why? METHODS: An extensive search in English literature was conducted in PubMed/Medline, Embase, Google Scholar, and Cochrane Database/Library. Eligibility criteria included papers with full text published in English, adult population studies, clearly described intervention protocol, and documented primary and secondary outcomes. RESULTS: The studies included numbered 37. All agents provided significant improvement in polyp size, sinuses opacification, severity of symptoms, need for surgery and systemic corticosteroids use. Analysis of available systematic reviews, meta-analyses and indirect treatment comparison studies showed that dupilumab appeared to be the most beneficial agent, in terms of primary and secondary outcomes. However, these results are of relatively low level of evidence due to several methodological limitations. CONCLUSIONS: Although the present analysis showed a moderate supremacy of dupilumab, there is still no evidence-based answer to the question "which biologic agent is the most effective in CRS treatment?" Improved statistical methodology, head-to-head trials, and real-life studies could lead to more robust conclusions, establishing the real role of the specific biologic agents.

Eosinophil Peroxidase: A Biomarker for Eosinophilic Chronic Rhinosinusitis Agnostic of Polyp Status.

OBJECTIVE: To evaluate eosinophil peroxidase (EPX) as a biomarker for tissue levels of eosinophilia, cytokines, and chemokines within chronic rhinosinusitis (CRS). METHODS: Twenty-eight subjects undergoing sinonasal surgery were prospectively enrolled. Ethmoid tissue was analyzed with an in-house EPX immunoassay and a 48-plex cytokine-chemokine array. Clinical severity was assessed using SNOT-22 and Lund-Mackay scores. Subjects were grouped as follows: controls, polyp status (CRS with [CRSwNP] and without nasal polyps [CRSsNP]), tissue eosinophilia (eosinophilic CRS [eCRS], non-eosinophilic CRS [neCRS]), or combinations thereof (eCRSwNP, eCRSsNP, neCRSsNP). eCRS was defined as >10 eosinophils per high power field (HPF). Subjects without CRS or asthma were enrolled as controls. RESULTS: EPX was elevated in CRSwNP compared to control (p = 0.007), in eCRS compared to neCRS (p = 0.002), and in eCRSwNP along with eCRSsNP compared to neCRSsNP (p = 0.023, p = 0.015, respectively). eCRS displayed elevated IL-5 compared to neCRS (p = 0.005). No significant differences in EPX or IL-5 were observed between eCRSwNP and eCRSsNP. IL-5 was elevated in eCRSwNP (p = 0.019) compared neCRSsNP. Area under the receiver operator characteristic curve was 0.938 (95% CI, 0.835-1.00) for EPX and tissue eosinophilia, with an optimal cut-point of 470 ng/mL being 100% specific and 81.25% sensitive for tissue eosinophilia. Linear regression revealed a strong correlation between EPX and IL-5 (R2 = 0.64, p < 0.001). Comparing EPX and IL-5, only EPX displayed significant correlation with SNOT-22 (p = 0.04) and Lund-Mackay score (p = 0.004). CONCLUSION: EPX is associated with tissue eosinophilia in CRS patients regardless of polyp status. EPX correlates with IL-5 and could be potentially considered a biomarker for anti-IL-5 therapies. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:69-78, 2024.

The influence of inhibitors of apoptosis proteins (IAPs) on chronic rhinosinusitis with nasal polyps.

BACKGROUND: Inhibitors of apoptosis proteins (IAPs) modulate the inflammatory process, and may facilitate the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to observe if IAPs were differently expressed between patients with CRSwNP and controls, and to correlate the expression of IAPs with some inflammatory markers, as with the response to nasal corticosteroids in patients with CRSwNP. METHODOLOGY: We obtained nasal biopsies from patients with CRSwNP (n=27) and controls (n=16). qRT-PCR measured the expression of IAPs and caspases, while Luminex assay measured the concentration of cytokines. Unpaired parametric tests and Principal Component Analysis (PCA) were used for statistical analysis. RESULTS: We observed lower expression of IAP genes (XIAP, BIRC2/IAP1, and BIRC3/IAP2) in CRSwNP patients compared to controls, and we identified that patients with bad response to corticosteroids presented lower levels of BIRC2/IAP1, XIAP, BCL2, CASP9, and IL-17, and higher levels of CASP7 and TGF-B. CONCLUSIONS: IAPs expression was downregulated in CRSwNP, and was associated with poorer response to nasal corticosteroids. The present findings suggest the importance of IAPs as a link between environment and the host inflammatory responses, and this pathway could be explored as a potential new target therapy for patients with CRSwNP.