Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

[Based on CT imaging, surgical approach selection for frontal and ethmoid sinus osteoma].

Objective:To investigate the criteria for selecting surgical approaches for frontal and ethmoid sinus osteomas of different locations and sizes on CT imaging. Methods:Using sagittal and coronal CT images, the following lines were delineated: the F-line（a horizontal line passing nasofrontal beak）, the M-line（a vertical line passing paries medialis orbitae）, and the P-line（a vertical line passing the center of the pupil）. Classification of frontal and ethmoid sinus osteomas was based on their relationship with these lines. Appropriate surgical approaches were selected, including pure endoscopic approaches, endoscopic combined with eyebrow incision approach, and endoscopic combined with coronal incision approach. This method was applied to a single center at the Third Affiliated Hospital of Sun Yat-sen University for endoscopic resection of frontal and ethmoid sinus osteoma. Case Data: Sixteen cases of ethmoid sinus osteomas were treated from January 2020 to September 2023. Among these cases, there were 9 males and 7 females, with ages ranging from 18 to 69 years, and a median age of 48 years. Results:Thirteen cases underwent pure endoscopic resection of the osteoma, while in three cases, a combined approach was utilized. Among the combined approach cases, two exceeded both the M-line and the F-line but did not cross the P-line; therefore, they underwent endoscopic combined with eyebrow incision approach. One case exceeded all three lines and thus underwent endoscopic combined with coronal incision. In all cases, complete resection of the osteoma was achieved as per preoperative planning, and none of the patients experienced significant postoperative complications. Conclusion:For frontal and ethmoid sinus osteomas, it is advisable to perform a thorough preoperative radiological assessment. Based on the size of the osteoma and its relationship to the three lines, an appropriate surgical approach should be chosen to optimize the diagnostic and treatment plan.

Evaluating ChatGPT's Performance in Answering Questions About Allergic Rhinitis and Chronic Rhinosinusitis.

OBJECTIVE: This study aims to evaluate the accuracy of ChatGPT in answering allergic rhinitis (AR) and chronic rhinosinusitis (CRS) related questions. STUDY DESIGN: This is a cross-sectional study. SETTING: Each question was inputted as a separate, independent prompt. METHODS: Responses to AR (n = 189) and CRS (n = 242) related questions, generated by GPT-3.5 and GPT-4, were independently graded for accuracy by 2 senior rhinology professors, with disagreements adjudicated by a third reviewer. RESULTS: Overall, ChatGPT demonstrated a satisfactory performance, accurately answering over 80% of questions across all categories. Specifically, GPT-4.0's accuracy in responding to AR-related questions significantly exceeded that of GPT-3.5, but distinction not evident in CRS-related questions. Patient-originated questions had a significantly higher accuracy compared to doctor-originated questions when utilizing GPT-4.0 to respond to AR-related questions. This discrepancy was not observed with GPT-3.5 or in the context of CRS-related questions. Across different types of content, ChatGPT excelled in covering basic knowledge, prevention, and emotion for AR and CRS. However, it experienced challenges when addressing questions about recent advancements, a trend consistent across both GPT-3.5 and GPT-4.0 iterations. Importantly, the accuracy of responses remained unaffected when questions were posed in Chinese. CONCLUSION: Our findings suggest ChatGPT's capability to convey accurate information for AR and CRS patients, and offer insights into its performance across various domains, guiding its utilization and improvement.

[Characteristics and therapeutic strategies of Pott's puffy tumor].

Objective:To explore the characteristics and therapeutic strategies of Pott's puffy tumor（PPT）. Methods:The clinical data of two patients with PPT were retrospectively analyzed and combined with the literature, focusing on the comprehensive analysis of perioperative diagnosis and treatment strategies. Both patients underwent muti-disciplinary treatment, including timely administration of sufficient antibiotics capable of penetrating the blood-brain barrier. Early removal of PPT lesions was performed using a combined internal and external approach under nasal endoscopic guidance. Results:After standardized perioperative management, the symptoms of the two patients were completely relieved, with no recurrence after one=year follow=up. Postoperative complications such as frontal pain, numbness, local depression, or scar hyperplasiawere not present. Conclusion:PPT, being relatively rare and severe, requires careful attention. Key strategies for standardized perioperative management include multi-disciplinary consultation, timely and adequate antibiotic administration, and surgical intervention using a combined intranasal and extranasal endoscopic approach for lesion removal.

[Artificial intelligence-assisted prediction of olfactory disorders in patients with chronic rhinosinusitis].

Objective:To analyze the influencing factors and perform the prediction of olfactory disorders in patients with chronic rhinosinusitis（CRS） based on artificial intelligence. Methods:The data of 75 patients with CRS who underwent nasal endoscopic surgery from October 2021 to February 2023 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively. There were 53 males and 22 females enrolled in the study, with a median age of 42.0 years old. The CRS intelligent microscope interpretation system was used to calculate the proportion of area glands and blood vessels occupy in the pathological sections of each patient, and the absolute value and proportion of eosinophils, lymphocytes, plasma cells and neutrophils. The patients were grouped according to the results of the Sniffin' Sticks smell test, and the clinical baseline data, differences in nasal mucosal histopathological characteristics, laboratory test indicators and sinus CT were compared between the groups. Determine the independent influencing factors of olfactory disorders and receiver operating characteristic curves（ROC） were used to evaluate the performance of the prediction model. Statistical analysis was performed using SPSS 25.0 software. Results:Among the 75 CRS patients, 25 cases（33.3%） had normal olfaction and 50 cases（66.7%） had olfactory disorders. Multivariate Logistic regression analysis showed that tissue eosinophils percentage（OR=1.032, 95%CI 1.002-1.064, P=0.036）, Questionnaire of olfactory disorders-Negative statement（QOD-NS）（OR=1.079, 95%CI 1.004-1.160, P=0.040） and Anterior olfactory cleft score（AOCS）（OR=2.672, 95%CI 1.480-4.827, P=0.001） were independent risk factors for olfactory disorders in CRS patients. Further research found that the area under the ROC curve（AUC） of the combined prediction model established by the tissue eosinophil percentage, QOD-NS and AOCS was 0.836（95%CI 0.748-0.924, P<0.001）, which is better than the above single factor prediction model in predicting olfactory disorders in CRS. Conclusion:Based on pathological artificial intelligence, tissue eosinophil percentage, QOD-NS and AOCS are independent risk factors for olfactory disorders in CRS patients, and the combination of the three factors has a good predictive effect on CRS olfactory disorders.

Risk Factors for Abnormal Small Airway Function Indicators in Nasal Polyp Patients with and without Asthma.

INTRODUCTION: Small airway dysfunction (SAD) is associated with type 2 inflammation in patients who have non-asthmatic chronic rhinosinusitis with nasal polyps (CRSwNPs); however, the risk factors for abnormal small airway function indicators in CRSwNP patients with and without asthma remain unclear. METHODS: We retrospectively analyzed 41 asthmatic and 109 non-asthmatic CRSwNP patients. Clinical characteristics were compared between groups, correlations between small airway function and clinical parameters were calculated, and independent risk factors for every small airway indicator were identified in each group. RESULTS: Asthmatic CRSwNP patients had significantly reduced small airway function, and the proportion of patients with SAD was higher in asthmatic CRSwNP patients (65.85%) than in patients without asthma (9.17%). With regard to specific airway function indicators, age and a patient's blood eosinophil (%) were identified as independent risk factors for lower FEF50% %pred and FEF25-75% pred, with age being an independent risk factor for FEF75% %pred in asthmatic CRSwNP patients. In non-asthmatic CRSwNP patients, allergic rhinitis comorbidity was found to be an independent risk factor for FEF50% %pred, FEF75% %pred, and FEF25-75% %pred. CONCLUSION: Physicians should pay greater attention to risk factors for abnormal small airway function indicators in patients with CRSwNPs to prevent the occurrence of SAD.

Advances in Image-Based Artificial Intelligence in Otorhinolaryngology-Head and Neck Surgery: A Systematic Review.

OBJECTIVE: To update the literature and provide a systematic review of image-based artificial intelligence (AI) applications in otolaryngology, highlight its advances, and propose future challenges. DATA SOURCES: Web of Science, Embase, PubMed, and Cochrane Library. REVIEW METHODS: Studies written in English, published between January 2020 and December 2022. Two independent authors screened the search results, extracted data, and assessed studies. RESULTS: Overall, 686 studies were identified. After screening titles and abstracts, 325 full-text studies were assessed for eligibility, and 78 studies were included in this systematic review. The studies originated from 16 countries. Among these countries, the top 3 were China (n = 29), Korea (n = 8), the United States, and Japan (n = 7 each). The most common area was otology (n = 35), followed by rhinology (n = 20), pharyngology (n = 18), and head and neck surgery (n = 5). Most applications of AI in otology, rhinology, pharyngology, and head and neck surgery mainly included chronic otitis media (n = 9), nasal polyps (n = 4), laryngeal cancer (n = 12), and head and neck squamous cell carcinoma (n = 3), respectively. The overall performance of AI in accuracy, the area under the curve, sensitivity, and specificity were 88.39 ± 9.78%, 91.91 ± 6.70%, 86.93 ± 11.59%, and 88.62 ± 14.03%, respectively. CONCLUSION: This state-of-the-art review aimed to highlight the increasing applications of image-based AI in otorhinolaryngology head and neck surgery. The following steps will entail multicentre collaboration to ensure data reliability, ongoing optimization of AI algorithms, and integration into real-world clinical practice. Future studies should consider 3-dimensional (3D)-based AI, such as 3D surgical AI.

Individual exposure of ambient particulate matters and eosinophilic chronic rhinosinusitis with nasal Polyps: Dose-Response, mediation effects and recurrence prediction.

PURPOSE: We evaluated the association between ambient particulate matter (PM) exposure and eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), and predicted the CRSwNP recurrence risk using machine learning algorithms. METHODS: In total, 1,086 patients with CRSwNP were recruited from nine hospitals in China during 2014-2019. The average annual concentrations of ambient PMs before surgery were assessed using satellite-based daily concentrations of PM2.5 and PM10 for a 1 × 1-km2 area. Linear regression and logistic regression models were used to evaluate the associations of PM exposure with eosinophilia and risks of eosinophilic CRSwNPs. In addition, mediation effect analysis was used to validate the interrelationships of the aforementioned factors. Finally, machine learning algorithms were used to predict the recurrence risks of CRSwNPs. RESULTS: There was a significantly increased risk of eosinophilic CRSwNPs with each 10 µg/m3 increase in PMs, with odds ratios (ORs) of 1.039 (95% confidence interval [CI] = 1.007-1.073) for PM10 and 1.058 (95% CI = 1.007- 1.112) for PM2.5. Eosinophils had a significant mediation effect, which accounted for 52% and 35% of the relationships of CRSwNP recurrence with PM10 and PM2.5, respectively. Finally, we developed a naïve Bayesian model to predict the risk of CRSwNP recurrence based on PM exposure, inflammatory data, and patients' demographic factors. CONCLUSIONS: Increased PM exposure is associated with an increased risk of eosinophilic CRSwNP in China. Therefore, patients with eosinophilic CRSwNP should reduce PM exposure to mitigate its harmful impacts.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Deep learning-based prediction of treatment prognosis from nasal polyp histology slides.

BACKGROUND: Histopathology of nasal polyps contains rich prognostic information, which is difficult to extract objectively. In the present study, we aimed to develop a prognostic indicator of patient outcomes by analyzing scanned conventional hematoxylin and eosin (H&E)-stained slides alone using deep learning. METHODS: An interpretable supervised deep learning model was developed using 185 H&E-stained whole-slide images (WSIs) of nasal polyps, each from a patient randomly selected from the pool of 232 patients who underwent endoscopic sinus surgery at the First Affiliated Hospital of Sun Yat-Sen University (internal cohort). We internally validated the model on a holdout dataset from the internal cohort (47 H&E-stained WSIs) and externally validated the model on 122 H&E-stained WSIs from the Seventh Affiliated Hospital of Sun Yat-Sen University and the University of Hong Kong-Shenzhen Hospital (external cohort). A poor prognosis score (PPS) was established to evaluate patient outcomes, and then risk activation mapping was applied to visualize the histopathological features underlying PPS. RESULTS: The model yielded a patient-level sensitivity of 79.5%, and specificity of 92.3%, with areas under the receiver operating characteristic curve of 0.943, on the multicenter external cohort. The predictive ability of PPS was superior to that of conventional tissue eosinophil number. Notably, eosinophil infiltration, goblet cell hyperplasia, glandular hyperplasia, squamous metaplasia, and fibrin deposition were identified as the main underlying features of PPS. CONCLUSIONS: Our deep learning model is an effective method for decoding pathological images of nasal polyps, providing a valuable solution for disease prognosis prediction and precise patient treatment.

Predictive significance of Charcot-Leyden crystal structures for nasal polyp recurrence.

BACKGROUND: Charcot-Leyden crystals (CLCs) are recognized to be classic hallmarks of eosinophilic inflammation. Both protein and mRNA levels of CLC in nasal secretions and nasal brushing samples have been associated with nasal polyp recurrence. However, whether the crystalline CLC structures in nasal tissue could serve as an effective biomarker to predict polyp recurrence remains unclear. METHODS: A total of 110 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) completing the postoperative follow-up over a period of 24 months were recruited. Hematoxylin and eosin staining was employed for CLCs identification. The predictive factors for polyp recurrence were determined by binary logistic regression analysis. RESULTS: Thirty three (30.00%) patients developed recurrence during a 24-month postoperative follow-up, in which 84.85% (28/33) patients had crystalline CLC structures. Logistic regression analysis showed that crystalline CLC structure in nasal tissues is predictive of polyp recurrence. Youden index demonstrated crystalline CLC structure higher than 1 per high power field can predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity. CONCLUSIONS: The crystalline CLC structures in nasal tissues may serve as an easy-counting and promising biomarker to predict CRSwNP recurrence.

Aerobic Exercise Improves Methamphetamine-Induced Olfactory Dysfunction Through α-Synuclein Intervention in Male Mice.

Methamphetamine (Meth) is a predominantly abused neurostimulant, and its abuse is often associated with multiple neurological symptoms. Olfaction, the sense of smell, is a highly neurotransmission-dependent physiological process; however, the effect of Meth on olfactory function and its underlying mechanisms remain largely unknown. This study aimed to explore the impact of Meth abuse on the olfactory system and the potential mechanisms. Chronic Meth abuse was induced by daily administration of Meth in male mice for 4 weeks, and we then systematically examined olfactory performance. Behavioral tests found that Meth-treated animals showed increased olfactory threshold, decreased olfactory sensitivity, reduced olfactory-dependent discrimination, and difficulty in seeking buried food. Notably, the increased deposition of α-synuclein (α-syn) in the olfactory bulb was detected. Adeno-associated virus (AAV)-mediated α-syn intervention therapy in the olfactory bulb significantly alleviated Meth-induced olfactory function impairment, and 8 weeks of aerobic exercise showed similar effects through the same principle of α-syn intervention. Notably, exercise-mediated reduction of α-syn inhibited abnormal firing activity and restored the inhibitory synaptic regulation of mitral cells in the olfactory bulb. These findings suggest the involvement of α-syn in the pathogenic mechanisms of Meth-induced olfactory dysfunction and shed light on the possible therapeutic applications of aerobic exercise in Meth-induced olfactory dysfunction.

Chinese Central Compartment Atopic Disease: The Clinical Characteristics and Cellular Endotypes Based on Whole-Slide Imaging.

Purpose: Histopathologic characterizations of central compartment atopic disease (CCAD) by whole-slide imaging remains lacking. We aim to study clinical presentations and cellular endotyping diagnosis of Chinese CCAD using artificial intelligence (AI). Methods: A total of 72 patients diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled. CCAD was defined by positive result of serology specific IgE, endoscopic and radiological findings. The aeroallergen sensitization status, endoscopic results, radiological findings, and symptoms were evaluated and compared between patients with CCAD (n=14), eosinophilic CRSwNP (ENP, n=32) and non-eosinophilic CRSwNP (NENP, n=26). The cellular endotypes including eosinophils, neutrophils, lymphocytes, and plasma cells were analyzed by the AI chronic rhinosinusitis evaluation platform 2.0. Results: CCAD was most common in male (71.43%). The positive rate of aeroallergen in patients with CCAD is 100%, which is much higher than those in patients with ENP (40.63%) and NENP (23.08%). Allergic rhinitis incidence was found to be 57.14% in Chinese CCAD subjects, which is obviously higher when compared with those in patients with ENP (21.88%) or NENP (0.00%). The presence of asthma was not significantly different between groups. Chinese CCAD population demonstrated mild symptoms and lower endoscopic and radiological scores than those in patients with ENP and NENP. For cellular endotypes in CCAD subjects, the median of eosinophils, neutrophils, lymphocytes, and plasma cells was 26.55%, 0.49%, 60.85%, and 7.33%, respectively. The proportion of eosinophils in nasal tissue and peripheral blood mononuclear cells from the CCAD group is between the proportions in those patients with ENP and NENP. Conclusion: Chinese CCAD was associated with aeroallergen sensitivity, and displayed an eosinophil-dominant inflammatory pattern. Thus, proper management with allergy control and topical steroids could be recommended for CCAD treatment.

Which Is the Best Biologic for Nasal Polyps: Dupilumab, Omalizumab, or Mepolizumab? A Network Meta-Analysis.

INTRODUCTION: Compared with the placebo, biologics are beneficial in reducing nasal polyp mass and safe in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, there lacks a head-to-head randomized trial comparing biologics. We aimed to determine the best biologic for CRSwNP. METHODS: We performed a systematic review and network meta-analysis (NMA), which was registered with PROSPERO (No. CRD42021226766). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on December 29, 2020. Only randomized controlled trials (RCTs) assessing biologics in adult patients for CRSwNP were included. RESULTS: Nine RCTs with 1,190 patients comparing 3 different biologics (dupilumab, omalizumab, and mepolizumab) and the placebo were included. Dupilumab had the best efficacy in terms of nasal polyp score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test (UPSIT) score, and nasal congestion score (NCS) for surface under the cumulative ranking curve (SUCRA) values of 0.900, 0.916, 1.000, and 0.807, respectively. Omalizumab ranked second in efficacy in terms of SNOT-22, UPSIT, and NCS for SUCRA values of 0.606, 0.500, and 0.693, respectively. Mepolizumab ranked second in efficacy in terms of NPS for SUCRA values of 0.563 and had the highest risk of adverse events (AEs) for SUCRA values of 0.746. CONCLUSION: This is the first NMA that compared different biologics in patients with CRSwNP. Based on the efficacy (NPS) and safety (AEs), dupilumab is the best choice and omalizumab is the second best option for CRSwNP. Although mepolizumab ranked second in efficacy, it had the highest risk of AEs.

Efficacy and safety of omalizumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP. DATA EXTRACTION AND SYNTHESIS: Two independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ2 test and the I2 statistic. RESULTS: A total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=-1.20; 95% CI -1.48 to -0.92), Nasal Congestion Score (MD=-0.67; 95% CI -0.86 to -0.48), Sino-Nasal Outcome Test-22 (MD=-15.62; 95% CI -19.79 to -11.45), Total Nasal Symptom Score (MD=-1.84; 95% CI -2.43 to -1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61). CONCLUSIONS: This was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated. PROSPERO REGISTRATION NUMBER: CRD42020207639.

YAP Promotes Cell Proliferation and Epithelium-Derived Cytokine Expression via NF-κB Pathway in Nasal Polyps.

BACKGROUND: Hippo-Yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and inflammation development in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the underlying mechanisms remain unclear. OBJECTIVE: This study intends to investigate the role of YAP and the nuclear factor kappa-B (NF-κB) pathway in cell proliferation and the expression of epithelium-derived cytokines in nasal polyps (NP). METHODS: The expression levels of YAP, TEA domain family member 1 (TEAD1), Ki-67, and NF-κB as well as interleukin (IL-) 33, IL-25 and thymic stromal lymphopoietin (TSLP) in sinonasal mucosa, primary nasal epithelial cells (NPECs), and human nasal epithelial RPMI 2650 cells were detected. NPECs were cultured and treated with verteporfin (VP), YAP shRNA or BAY 11-7082. RESULTS: The hippo pathway effector YAP, Ki-67, p65 NF-κB, and cyclin D1 were significantly increased in NP compared with control mucosa, which was accompanied by overexpression of IL-33, IL-25, and TSLP. Pharmaceutical inhibition of YAP by VP suppressed cell proliferation of RPMI 2650 cells by blocking cell cycle progression at G0/G1 without inducing obvious cell apoptosis. Furthermore, lentiviral transfection-mediated knockdown of hippo pathway activity reduced the expression of IL-33, IL-25, TSLP as well as p65 NF-κB in RPMI 2650 cells. Downregulation of NF-κB pathway with BAY 11-7082 in NPECs could decrease the mRNA level of TSLP, IL-33 and IL-25 accordingly. CONCLUSION: Inhibition of hippo pathway suppressed nasal epithelial cell proliferation and declined the expression of epithelium-derived cytokines via the NF-κB pathway in NPECs.