Effects of Metabolic Syndrome and its components on the postoperative recurrence in Chronic Rhinosinusitis with Nasal Polyps' patients

Abstract Objectives Metabolic Syndrome (MetS) has been established as a significant factor in the pathogenesis of numerous chronic inflammatory conditions. However, its role in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is unknown. This study aims to investigate the association between MetS, its components, and the risk of postoperative recurrence in Chinese patients with CRSwNP. Methods A retrospective cohort study was conducted on CRSwNP patients who underwent endoscopic sinus surgery in our hospital. Patients were divided into MetS and non-MetS groups, and the clinical characteristics and recurrence rates were compared. All CRSwNP patients were followed up for more than 2-years and further categorized into non-recurrent and recurrent groups. Binary logistic regression analyses were performed to examine the effects of MetS and its components on the risk of postoperative recurrence. Results A total of 555 CRSwNP patients were enrolled in the present study, 157 patients were included in the MetS group and 398 patients were categorized into the non-MetS group. The recurrence rate in the MetS group was significantly higher compared to the non-MetS group (p< 0.05). The rate of MetS, overweight or obesity, hyperglycemia and dyslipidemia were higher in the recurrent group in comparison with the non-recurrent group (p< 0.05). Multivariate logistic regression analysis suggested that MetS, overweight or obesity, hyperglycemia, dyslipidemia, and accompanying allergic rhinitis were associated with the risk of postoperative recurrence of CRSwNP (p< 0.05). Moreover, adjusted and unadjusted regression models showed that MetS was an independent risk factor for postoperative recurrence of CRSwNP, and the risk increased with more components of MetS included (p< 0.05). Conclusion Our findings revealed that MetS independently increased the risk of postoperative recurrence in patients with CRSwNP, with the risk escalating as the number of MetS components increased. Moreover, accompanying allergic rhinitis was also demonstrated to be a potential risk factor for CRSwNP recurrence. Level of evidence: Level 4.

Regressão da polipose nasal induzida pelo dupilumabe / Regression of dupilumab-induced nasal polyps

Relato de caso de paciente com rinossinusite crônica com polipose nasal em tratamento com dupilumabe. São descritos os aspectos clínicos e o impacto na qualidade da vida do paciente. Imagens tomográficas evidenciam a melhora do processo inflamatório e a regressão dos pólipos nasais.

We report the case of a patient with chronic rhinosinusitis with nasal polyps treated with dupilumab. The clinical features and impact on the patient's quality of life are described. Computed tomography shows improvement of the inflammatory process and regression of the nasal polyps.

Sinonasal Outcomes Using Oral Corticosteroids in Patients with Chronic Rhinosinusitis with Nasal Polyps and Positive Sinonasal Cultures

Abstract Introduction Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and positive sinonasal bacterial cultures may be recalcitrant to topical therapy alone due to the additional local inflammatory burden associated with bacterial infection/colonization. Objectives To evaluate sinonasal outcomes in CRSwNP patients with a positive perioperative bacterial culture, who were treated with postoperative intranasal corticosteroids (INCS) alone versus INCS in combination with a short-term course of oral corticosteroids (OCS). Methods This is a retrospective chart review of CRSwNP patients. A total of 59 patients met inclusion criteria, including positive perioperative bacterial culture and treatment with INCS with or without concomitant use of OCS. Two cohorts were formed based on the chosen postoperative medical treatment; 32 patients underwent postoperative INCS alone, while 27 underwent INCS plus a ≤ 2-week course of OCS. The 22-item sinonasal outcome test (SNOT-22) scores and Lund-Kennedy scores (LKS) were assessed preoperatively, and at 2-week, 4-week, and 4 to 6 months after endoscopic sinus surgery (ESS). Results There were no statistically significant differences in postoperative sinonasal symptoms or endoscopic scores between the cohorts treated with INCS plus OCS versus those prescribed INCS alone (p > 0.05). Our regression model failed to demonstrate a relationship between the use of OCS and better sinonasal outcomes at 2-week, 4-week, and 4 to 6 months after ESS (p > 0.05). Conclusions Our study suggests that in a cohort of CRSwNP patients with recent bacterial infections, the postoperative use of combined OCS and INCS did not result in a statistical improvement of endoscopic and symptomatic outcomes over INCS irrigation alone. However, both treatment groups had a clinically significant improvement based on the Minimal Clinically Important Difference.

Significance of leukocyte-specific transcript 1 levels in nasal mucosal tissue to predict recurrence of nasal polyps

Abstract Objective: Chronic Rhinosinusitis with Polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aims to explore the clinical significance of tissue Leukocyte-Specific Transcript 1 (LST1) in predicting CRSwNP recurrence. Methods: We enrolled 62 CRSwNP patients including 30 primary CRSwNP and 32 recurrent CRSwNP patients, and 40 Healthy Controls (HC). Tissue samples were collected. Tissue LST1 expression was assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blotting (WB) and Immunofluorescence (IF) staining. The predictive values of LST1 expression for CRSwNP postoperative recurrence were assessed through the Receiver Operating Characteristic (ROC) curves. Results: The tissue levels of LST1 were significantly increased in the CRSwNP group than the HC group, especially in the recurrent group, and the elevated LST1 mRNA levels were positively correlated with the peripheral eosinophil percentages, tissue eosinophil counts and percentages. IF staining results showed that the LST1 protein levels were higher in CRSwNP patients, especially in the recurrent patients than in the HC group. ROC curves highlighted that tissue LST1 levels were associated with recurrent CRSwNP and exhibited a higher predictive ability for postoperative CRSwNP recurrence. Conclusion: This was the first report suggesting that LST1 expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Tissue LST1 could be a promising biomarker for predicting postoperative recurrence in CRwNP patients.

The expression and significance of Piezo1 in chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To explore the expression and importance of Piezo1, E-cadherin, and Vimentin in nasal polyps patients. Methods:Thirty-five patients undergoing endoscopic sinus surgery under general anesthesia were streamed into 20 cases of nasal polyps（NP group） and 15 cases of simple septoplasty without any sinus disease（Control group）. Immunofluorescence staining and Western Blot were applied to detect the protein level of Piezo1, E-cadherin, and Vimentin in NP tissues and nasal polyp-derived primary human nasal epithelial cells（pHNECs）. Also, BEAS-2B cell lines were treated with human TGF-β1 protein to establish epithelial mesenchymal transition（EMT） model in vitro and quantitative real-time polymerase chain reaction were used to calculate Piezo1 and above biomarkers in the model. Results:Compared with control group, Piezo1 and Vimentin showed higher level while E-cadherin was lower in NP tissues and pHNECs.In EMT model in vitro, Piezo1 and Vimentin were demonstrated higher expression with decreased level of E-cadherin. Conclusion:The tendency of Piezo1 is consistent with the mesenchymal-related biomarker Vimentin, going against with epithelial-related biomarker E-cadherin, implying its involvement with EMT process in nasal polyps.

Altered expression of 15-hydroxyprostaglandin dehydrogenase in chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the expression level and regulatory mechanism of 15-hydroxyprostaglandin dehydrogenase（HPGD） in chronic rhinosinusitis with nasal polyps（CRSwNP）. Methods:The expression pattern and level of HPGD in CRSwNP and control was observed using immunofluorescence, and western blot was used for analysis of HPGD expression in nasal polyp tissues. The effect of recombinant human high mobility group box-1（HMGB1） on HPGD expression in primary human nasal epithelial cells was observed, and the potential blocking effect of RAGE neutralizing antibody on HMGB1-induced HPGD expression was investigated. Results:The expression of HPGD was elevated in CRSwNP patients compared to the control, while the protein mainly localized at CD68-positive cells and epithelial cells. Recombinant human HMGB1 stimulated an increase in HPGD expression in primary human nasal mucosal epithelial cells at a time-dependent manner. Additionally, increased phosphorylation levels of MEK and elevated RAGE expression were also observed at 12 hours, but decreased at 24 hours after the incubation of HMGB1. The increase in the expression of HPGD induced by HMGB1 in primary human nasal epithelial cells was partly inhibited with RAGE neutralizing antibody. Conclusion:Elevated HPGD expression is observed in CRSwNP, predominantly in macrophages and epithelial cells. HMGB1 regulates HPGD expression through the RAGE-MEK signaling pathway, potentially providing a new target for future regulation of PGE2levels in CRSwNP.

The predicting role of postoperative changes in self-reported symptoms in patients with recurrence eosinophilic chronic sinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate whether changes in postoperative symptoms and signs in patients can predict the recurrence of ECRS after nasal endoscopic sinus surgery. Methods:A total of 70 adult patients with ECRS were enrolled for ESS surgery from June 2020 to March 2022 in a single center. There were 50 males and 20 females, with an average age of （46.9±14.5） years. Follow-up after ESS was at least 52 weeks. Patients undergo peripheral blood tests, CT of the sinuses, olfactory T&T test, visual analogue scale of symptoms（VAS）, and endoscopic scoring. Results:VAS scores and endoscopic scores were analyzed at preoperative and 6th week, 12th week, 24th week and 52th week postoperative. After 12th week postoperatively, there was a clear correlation between symptom scores and endoscopic scores. Moreover, olfactory disorder and nasal discharge were the two most obvious symptoms. There were differences in the expression of multiple preoperative clinical inflammatory indicators between the symptom-controled group and the symptom-uncontrolled group（previous surgical history, concomitant asthma, nasal smear eosinophil, serum EOS%, total IgE, CT score, olfactory score, and symptom score, all with P<0.05）, while there was no difference in baseline endoscopic score（P>0.05）. At 12th week postoperative, the two groups of patients showed significant differences in both symptom scores and endoscopic scores. The symptoms and endoscopic score at the 12th week point of follow-up were used as predictive indicators for recurrence, with sensitivity and specificity of 62.5% and 83.3%, respectively. Conclusion:The changes in postoperative symptom score and endoscopic score in ECRSwNP patients indicated that the recurred ECRS. In the symptom-uncontrolled group, symptomatic and endoscopic scores showed consistent increased scores; In the symptom-controlled group, conflicting results between increased endoscopic scores and stable symptoms suggest that the presence of asymptomatic recurrence must be considered. The changes in symptoms and signs at the 12th week point of follow-up can serve as clinical indicators for preventing disease recurrence.

The perspectives of biologics in the treatment of chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Chronic rhinosinusitis with nasal polyps （CRSwNP） remains the most difficult-to-treat subtype in the world. Biologics have shown positive results, especially in reducing nasal polyp size and improving patient-reported outcomes. The development of biologics has the potential to fulfill the unmet medical needs of treatment.

Three-dimensional cell culture for the study of nasal polyps

Abstract Objectives: Three-dimensional (3D) cell cultures have many applications such as stem cell biology research, new drug discovery, cancer, and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). This disease is characterized by a significant impact on quality of life and productivity. The diversity of factors that act in the progression of CRSwNP point to the creation of a cell culture model that allows the integration of different cell types with extracellular matrix. This work aimed to create a cell culture model in 3 dimensions (spheroids) for the study of Nasal Polyposis. Methods: Nasal polyp tissue from patients diagnosed with CRSwNP was mechanically dissociated using tweezers and a scalpel and the solution containing cells and small aggregates of nasal polyps was transferred to a Petri dish containing 5 mL of culture medium at the concentration of 106 cells/mL. Results: The spheroids were cultivated for 20 days, fixed and analyzed using confocal microscopy. In a 3D culture environment, the spheroids were formed both by clustering cells and from small tissue fragments. In the cultures analyzed, the ciliary beat was present from the dissociation of the cells up to 20 days in culture. Conclusion: Our findings also point to these characteristics showing the environment generated in our study, the cells remained differentiated for a longer time and with ciliary beating. Thus, this work shows that nasal polyp-derived cells can be maintained in a 3D environment, enabling better strategies for understanding CRSwNP in situations similar to those found in vivo. Level of evidence: Laboratory studies.

Modified Jiegeng Yuansentang Combined with Conventional Therapy Improves Postoperative Mucosal Edema of Chronic Rhinosinusitis Patients with Nasal Polyps and Its Mechanism of Action / 中国实验方剂学杂志

Objective:To explore the curative effect and mechanism of modified Jiegeng Yuansentang combined with conventional therapy for postoperative mucosal edema in patients with cchronic rhinosinusitis with nasal polyps due to pulmonary Qi stagnation， and to explore its mechanism of action. Method:The 90 patients were randomly divided into control group and observation group， 45 cases in each group.All patients were given conventional therapy after nasal endoscopy.Patients in control group were also given mometasone furoate combined with clarithromycin， and patients in observation group were given modified Jiegeng Yuansentang for internal administration and local irrigation.The course of the treatment was 6 weeks.The sino nasal outcome test-20 （SNOT-20）， nasal situation Lund-Kennedy， rhinoconjunctivitis quality of life questionnaire （RQLQ）， traditional Chinese medicine （TCM） syndrome， serum and nasal secretions inflammatory cytokines ［tumor necrosis factor-alpha （TNF-<italic>α</italic>）， interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， interleukin-5 （IL-5），interleukin-17 （IL-17）］， serum protein ［aquaporin-1 （AQP-1）， aquaporin-3 （AQP-3）， aquaporin-5 （AQP-5）， fibronectin （Fn）］ were observed before and after treatment in two groups.The clinical symptoms， safety and recurrence after a follow-up of 12 months were compared between two groups. Result:The total effective rate was 97.73% （43/44） in observation group， which was higher than 80.95% （34/42） in control group （<italic>χ</italic>²=4.726， <italic>P</italic><0.05）.The patients were followed up for at least 12 months， and the recurrence rate was 4.65% （2/43） in observation group， which was lower than 32.35% （11/34） in control group （<italic>χ</italic>²=4.129， <italic>P</italic><0.05）.Compared with control group after treatment， the SNOT-20， Lund-Kennedy， RQLQ， TCM syndrome， TNF-<italic>α</italic>， IL-1<italic>β</italic>， IL-5， IL-17， AQP-5 were significantly decreased in observation group （<italic>P</italic><0.05）， while AQP-1， AQP-3， Fn were significantly increased in observation group （<italic>P</italic><0.05）.The incidence of adverse reactions was 2.27% （1/44） in observation group， lower than 57.14% （24/42） in control group （<italic>χ</italic>²=5.243， <italic>P</italic><0.05）. Conclusion:Modified Jiegeng Yuansentang can significantly improve postoperative mucosal edema in patients with chronic rhinosinusitis with nasal polyps due to pulmonary Qi stagnation， and the mechanism may be related to the regulation of inflammatory factors in serum and nasal secretions.

Local Immunoglobulin E in the Nasal Mucosa: Clinical Implications

Immunoglobulin E (IgE) can be highly elevated in the airway mucosa independently of IgE serum levels and atopic status. Mostly, systemic markers are assessed to investigate inflammation in airway disease for research or clinical practice. A more accurate but more cumbersome approach to determine inflammation at the target organ would be to evaluate markers locally. We review evidence for local production of IgE in allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Diagnostic and therapeutic consequences in clinical practice are discussed. We describe that the airway mucosa has the intrinsic capability to produce IgE. Moreover, not only do IgE-positive B cells reside within the mucosa, but all tools are present locally for affinity maturation by somatic hypermutation (SHM), clonal expansion, and class switch recombination to IgE. Recognizing local IgE in the absence of systemic IgE has diagnostic and therapeutic consequences. Therefore, we emphasize the importance of local IgE in patients with a history of AR or CRSwNP.

TMEM16A-Mediated Mucin Secretion in IL-13-Induced Nasal Epithelial Cells From Chronic Rhinosinusitis Patients

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP), a mainly Th2 cytokine-mediated disease, often involves mucus secretion. Recent evidence suggests that transmembrane protein 16A (TMEM16A), a calcium-activated Cl- channel (CaCC), can regulate mucus secretion from airway epithelium by transepithelial electrolyte transport and hydration. However, the role of TMEM16A in mucin production/secretion in the airway epithelium is not clear. This study was conducted to determine the role of TMEM16A in mediating mucin secretion in human nasal polyp epithelial cells (HNPECs) induced by IL-13. METHODS: Human sinonasal mucosa tissue and dissociated sinonasal epithelium from control subjects and patients with CRSwNP were assessed for the expression of TMEM16A and the secretion of human mucin 5AC (MUC5AC) by immunohistochemistry, Western blot analysis, and enzyme-linked immuno-sorbent assay (ELISA). A model of the Th2 inflammatory environment was created by exposure of primary air-liquid interface (ALI)-cultured HNPECs to interleukin-13 (IL-13) for 14 days, with subsequent assessment of TMEM16A expression in cell lysates by Western blotting and MUC5AC secretion in apical washings of cells by ELISA. RESULTS: The expressions of TMEM16A and MUC5AC were increased in human nasal polyp tissue and dissociated nasal polyp epithelium. TMEM16A was detected in IL-13-treated HNPECs, specifically in MUC5AC-positive cells but not in ciliated cells. IL-13 treatment increased percentages of TMEM16A-positive cells, MUC5AC-positive cells, and cells coexpressing TMEM16A/MUC5AC, the expression of TMEM16A protein, and the secretion of MUC5AC. T16Ainh-A01, a TMEM16A inhibitor, attenuated these IL-13-induced effects. CONCLUSIONS: The expression of TMEM16A and MUC5AC are increased in CRSwNP, which might be a direct effect of Th2 cytokines present in the sinonasal mucosa in CRSwNP. Down-regulation of TMEM16A expression and MUC5AC secretion in HNPECs by T16Ainh-A01 indicates that TMEM16A might play an important role in mucin secretion in upper airway inflammatory diseases.