Guia prático para o uso de imunobiológicos em doenças alérgicas - ASBAI / Practical guide for the use of immunobiologic agents in allergic diseases - ASBAI

Os anticorpos monoclonais são uma nova classe de medicamentos que representa um marco na evolução da terapia de doenças alérgicas graves. Além de possibilitar uma terapia imunológica alvo específico, proporciona maior controle de sintomas, redução de exacerbações, melhoria da qualidade de vida e da segurança. A eficácia e a segurança dos anticorpos monoclonais no tratamento de doenças alérgicas estão bem documentadas nos estudos clínicos pivotais, de extensão e de vida real. No Brasil, estão licenciados atualmente pela Agência Nacional de Vigilância Sanitária (ANVISA) imunobiológicos para asma, dermatite atópica (DA), esofagite eosinofílica (EoE), granulomatose eosinofílica com poliangeíte (GEPA), rinossinusite crônica com pólipo nasal (RSCcPN), síndromes hipereosinofílicas (SHE) e urticária crônica espontânea (UCE). Com a incorporação do uso dessas novas terapias no dia a dia do médico alergologista e imunologista, naturalmente emergem aspectos práticos que exigem orientações práticas perante as evidências científicas mais atuais, a fim de se manter a boa prática médica, com uso criterioso e consciente pelo especialista capacitado. Assim, nesse guia prático, abordaremos os imunobiológicos aprovados até o momento para doenças alérgicas graves, com objetivo de auxiliar o especialista em Alergia e Imunologia na prescrição e manejo dessas medicações, incluindo indicações, contraindicações, monitoramento da eficácia e segurança, notificação de eventos adversos, bem como aspectos associados aos cuidados com vacinas, populações especiais, acesso, transporte, armazenamento e aplicação domiciliar.

Monoclonal antibodies are a new class of drugs that represent a milestone in the evolution of therapy for severe allergic diseases. In addition to allowing targeted immunologic therapy, they can improve symptom control, reduce exacerbations, and increase quality of life and safety. The efficacy and safety of monoclonal antibodies in the treatment of allergic diseases are well documented in pivotal, extension, and real-life clinical studies. In Brazil, immunobiologic agents are currently licensed by the National Health Surveillance Agency (ANVISA) for use in asthma, atopic dermatitis (AD), eosinophilic esophagitis (EoE), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyps (CRSwNP), hypereosinophilic syndrome (HES), and chronic spontaneous urticaria (CSU). With the incorporation of these new therapies into the daily practice of the allergist and immunologist, practical aspects will naturally emerge and require practical guidelines in light of the most current scientific evidence in order to maintain good medical practice, with judicious and conscious use by a qualified specialist. Therefore, in this practical guide, we will address the immunobiologic agents currently approved for severe allergic diseases, aiming to assist allergy and immunology specialists in the prescription and practical management of these medications, including indications, contraindications, efficacy and safety monitoring, adverse event reporting, as well as health care factors associated with vaccination, special populations, access, transport, storage, and home use.

Rinosinusitis crónica en fibrosis quística: una actualización / Chronic rhinosinusitis in cystic fibrosis: an update

En las últimas décadas, el tratamiento agresivo, protocolizado y realizado en centros multidisciplinarios de fibrosis quística (FQ), ha mejorado notablemente la sobrevida media de los pacientes. Como consecuencia, síntomas más bien secundarios, como los derivados del compromiso de la vía aérea superior, entre ellos la rinosinusitis crónica (RSC), con o sin pólipos nasales (PN), han empezado a impactar en la calidad de vida y en el curso de la enfermedad. Esto hace del diagnóstico y tratamiento oportuno de esta complicación un objetivo importante en el manejo de la FQ. El propósito de esta revisión es proporcionar una actualización sobre los aspectos diagnósticos y las terapias disponibles para el manejo de la RSC en pacientes con FQ.

In recent decades, aggressive, protocolized treatment conducted in multidisciplinary cystic fibrosis (CF) centers has significantly improved the median survival of patients. Consequently, secondary symptoms, such as those arising from upper airway involvement, including chronic rhinosinusitis (CRS), with or without nasal polyps (NP), have begun to impact the quality of life and the course of the disease. This makes timely diagnosis and treatment of this complication an important goal in CF management. The purpose of this review is to provide an update on diagnostic aspects and available therapies for managing CRS in patients with CF.

Effects of respiratory syncytial virus infection on nasal epithelial barrier function in chronic rhinosinusitis with polyps / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore the effect of respiratory syncytial virus(RSV)infection on the expression of key factors in the epithelial barrier of the human nasal epithelial cells(hNECs)derived from patients with chronic rhinosinusitis with nasal polyps(CRSwNP)and normal control mucosa.METHODS RSV with different multiplicity of infection(MOI)(0.1 and 0.3)infected hNECs derived from patients with CRSwNP(n=21)and normal control mucosa(n=9)for 24 h and 48 h,respectively.To detect the gene expression ZO-1,ZO-2,Claudin-1,Claudin-4,Occludin,E-cadherin and N-cadherin,total RNA was extracted and reverse transcribed into cDNA for real-time fluorescence quantification PCR.RESULTS The relative expression level of ZO-1,ZO-2,Claudin-1,Claudin-4,Occludin,E-cadherin and N-cadherin were decreased in hNECs post RSV infection.However,there was a statistical difference only in hNECs derived from CRSwNP(P<0.05).There was no significant difference in hNECs infected with RSV between eosinophilic CRSwNP(ECRSwNP)and non-eosinophilic CRSwNP(nonECRSwNP).CONCLUSION RSV infection could disrupt the epithelial barrier of the nasal mucosa,and patients with CRSwNP are more severely affected by RSV infection compared to healthy controls.The impact of RSV infection on mucosa between ECRSwNP group and nonECRSwNP group was no significant difference.

Effect of nasal microflora on nasal function after endoscopic surgery in patients with chronic sinusitis and nasal polyps / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the effect of nasal microflora on nasal function after endoscopic surgery in patients with chronic sinusitis and nasal polyps.METHODS There were 88 patients with chronic sinusitis with nasal polyps who underwent elective nasal endoscopic surgery in Daxing District People's Hospital from May 2021 to May 2022.High-throughput sequencing technology was used to analyze the distribution of microflora in nasal secretions,and the patients were divided into a microbial-negative group(24 cases),a bacteria-positive group(42 cases)and a fungus-positive group(22 cases).Visual analog scale,Lund-Kennedy endoscopic score and Lund-Mackay CT were used to evaluate the nasal function of the patients before and 6 months after surgery,respectively.After surgery,nasal endoscopy was used to evaluate the degree of nasal mucosal injury and the thickness of the basement membrane of the nasal mucosal tissue was measured.RESULTS There were 64 pathogens who were detected in nasal secretions of 88 patients with chronic sinusitis and nasal polyps,accounting for 47.73%of bacteria and 25.00%of fungi.After operation,the nasal function score of the three groups was significantly lower than that before operation,and the pair-to-pair comparison between the three groups had statistical significance(P<0.05).The damage degree and basement membrane thickness of nasal mucosal epithelium in bacteria positive group and fungi positive group were higher than those in microbial negative group(P<0.05),but there was no difference between groups(P>0.05).CONCLUSION Bacteria and fungi in nasal secretions can affect the recovery of nasal function after endoscopic surgery in patients with chronic sinusitis and nasal polyps,and affect the effect of endoscopic surgery.

Retrospective study of bilateral frontal sinus stent implantation in patients with chronic rhinosinusitis with nasal polyps undergoing full functional endoscopic sinus surgery / 中国耳鼻咽喉头颈外科

OBJECTIVE To assess the efficacy of bioabsorbable steroid-releasing sinus stents for improving surgical outcomes and subjective symptoms when placed in the bilateral frontal sinus opening(FSO)following full functional endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyps(CRSwNP).METHODS CRSwNP patients who had under full functional endoscopic sinus surgery with complete data of nasal endoscopy and sinus computed tomography data were identified and included in the study.The patients were divided into a control group consisting of patients receiving only full functional endoscopic sinus surgery(n=92)and a stent group consisting of patients receiving full functional endoscopic sinus surgery combined with placement of steroid implants in both FSO(n=38).The visual analogue scale(VAS)subjective symptom scores and surgical outcomes were compared preoperatively,and on postoperative day(PD30 and PD90)between the two groups.RESULTS Compared to baseline,the overall symptom VAS scores of patients after operation decreased significantly in both groups(P<0.05),and the degree of improvement of overall symptoms in the stent group was significantly better than in the control group(P<0.05).On PD30,the proportion of patients requiring postoperative interventions for bilateral FSO was reduced by 42.3%in the stent group,and was significantly lower than in the control group(P<0.05).Compared to the control group,the proportion of patients needing postoperative intervention in both ethmoid sinus on the stent group decreased by 17.7%(P>0.05).The results at PD90 were consistent with those at PD30.CONCLUSION Full functional endoscopic sinus surgery in combination with bilateral frontal sinus stent implantation is better than full functional endoscopic sinus surgery alone.

The analysis of independent factors affecting tissue inflammatory cells changes in recurrent nasal polyps / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore the independent factors affecting tissue inflammatory cells changes in recurrent nasal polyps.METHODS The clinical data of 31 patients with nasal polyps who underwent endoscopic surgery at the Department of Otolaryngology Head and Neck Surgery,Yantai Yuhuanding Hospital from December 2007 to December 2021 were selected and analyzed by stepwise regression logistic analysis.RESULTS The number of tissue inflammatory cells in recurrent nasal polyps changed compared with that in primary nasal polyps,and the number and percentage of neutrophils in recurrent polyps increased(P<0.05).Logistic analysis revealed that smoking was an independent risk factor for eosinophilia in recurrent nasal polyps,increasing age was an independent factor for lowering neutrophils,and the comorbid allergic rhinitis and the time interval of recurrence were independent factors for lowering and increasing lymphocytes,respectively.CONCLUSION The number of tissue-infiltrating cells is altered in recurrent polyps compared with primary polyps.Smoking is an independent risk factor for eosinophilia in recurrent polyps.

Regulation of Local Immunoglobulin Expression by MZB1 in Chronic Rhinosinusitis with Nasal Polyps / 中山大学学报(医学科学版)

ObjectiveThe heightened expression of local immunoglobulins is a significant pathological characteristic of chronic rhinosinusitis with nasal polyps （CRSwNP）， particularly in the Asian population. This study is centered on exploring the association between MZB1 and the localized aggregation of immunoglobulins in Asian individuals with CRSwNP. MethodsNasal polyp tissues obtained from 40 CRSwNP patients and inferior turbinates from 6 healthy controls underwent examination for both mRNA and protein levels. The assessments were conducted using polymerase chain reaction， luminex， and immunohistochemical staining. Statistical analyses， including one-way Anova （ANOVA）， independent samples t-test， and Pearson's correlation analysis， were employed for comprehensive data evaluation. ResultsThe mRNA expression levels of MZB1（P < 0.01） and HSP90B1 （P < 0.01） were significantly higher in type 2 CRSwNP patients compared with those in healthy controls. Immunohistochemical staining revealed a significant increase in MZB1 protein expression in type 2 CRSwNP. MZB1 demonstrated correlation with the expression of immunoglobulin E in nasal polyp tissues （P < 0.01， r = 0.52）. Additionally，MZB1correlated with the expression ofIL-5（P < 0.05， r = 0.4） and IL-13 （P < 0.05， r = 0.44） in nasal polyp tissues. Furthermore，MZB1showed correlation with the number of eosinophils in nasal polyp tissues （P < 0.05， r = 0.72）. ConclusionThe expression of MZB1 is notably elevated in Asian CRSwNP， particularly in type 2 CRSwNP， when compared with controls.MZB1expression correlates significantly with high IgE expression and disease severity in nasal polyp tissues.

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.

Development of a mobile app for the evaluation of patients with chronic rhinosinusitis

Abstract Objective To develop a mobile application with a standardized routine, to be used by general otolaryngologists for evaluating patients with chronic rhinosinusitis. Methods A systematic review was made to identify outcomes, recommendations and what tests that would be used in the routine evaluation of patients with chronic rhinosinusitis; establish an expert consensus on items to be included in this routine evaluation of patients with chronic rhinosinusitis using the Delphi method; development of an application for use on a mobile device, with the routine evaluation of patients with chronic rhinosinusitis. Results Based on the systematic review, the outcomes used in studies about chronic rhinosinusitis were identified, as well as guidelines recommendations, which showed discrepancies between them. These recommendations and outcomes were presented to specialists in chronic rhinosinusitis, until a consensus was reached. As a result of the Delphi method, the flowchart of the routine evaluation of patients with chronic rhinosinusitis was defined, and then was used for the development of the mobile application. Conclusion The creation of the mobile application for evaluating patients with chronic rhinosinusitis followed an adequate methodology of elaboration made by specialists in the field of chronic rhinosinusitis, standardizing the investigation of these patients. Level of evidence: Level 5.

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.

The development of nasal polyps involves early middle meatus mucous remodeling via TGF-β1 mediated PAI-1 reduction

Abstract Objective Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Methods Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. Results The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Conclusion Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-β1-mediated PAI-1 reduction. Level of evidence 3b.

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.

Comparative analysis of curative endoscopic surgery and functional endoscopic surgery in the treatment of EosCRSwNP / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore the clinical effect of radical endoscopic sinus surgery(RESS)in the treatment of eosinophilic chronic sinusitis with nasal polyps(EosCRSwNP).METHODS There were 84 EosCRSwNP patients admitted to the Department of Otolaryngology in Tianjin Beichen Hospital from January,2020 to January,2022.They were divided into an observation group(42 cases)and a control group(42 cases)according to the random number table method.The control group and the observation group received functional endoscopic sinus surgery(FESS)and RESS respectively.The nasal visual analogue score(VAS)and Lund-Kennedy score were compared before surgery and in 1,3,and 12 months after surgery,and the olfactory threshold in 6 months before and after surgery,Ciliary clearance rate,ciliary clearance rate,and serum interleukin-1β(IL-1β),IL-35 and squamous cell carcinoma antigen(SCCA)levels were compared between the two groups.The recurrence rates in 12 months between the two groups after surgery.RESULTS The VAS and Lund-Kennedy scores of the observation group were lower than those of the control group in 12 months after surgery(P＜0.01);The olfactory threshold and serum IL-1β in 6 months after surgery,the level of SCCA of the observation group was lower than those of the control group(P＜0.01),and the Cilia clearance speed,the clearance rate and serum IL-35 level were higher than those of the control group(P＜0.01).The recurrence rate in 12 months of the observation group was lower than that of the control group(P＜0.05).CONCLUSION RESS is beneficial for reducing nasal VAS and Lund-Kennedy scores,alleviating nasal inflammation,restoring olfactory and nasal mucosal function,and reducing postoperative recurrence rate.It can be used as the optimal surgical plan for EosCRSwNP.

Analysis of potential diagnostic genes for eosinophilic chronic rhinosinusitis with nasal polyps based on GEO datasets / 中国耳鼻咽喉头颈外科

OBJECTIVE To utilize RNA sequencing(RNA-seq)data from the GEO database to identify genes with potential diagnostic value for eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP).METHODS Three datasets were obtained,and samples were divided into ECRSwNP and nonECRSwNP groups based on the expression levels of CST1 and CLC.A diagnostic model for ECRSwNP was established using R software and algorithms,and its accuracy was assessed.RESULTS The samples were grouped as follows:GSE136825(ECRSwNP 7,nonECRSwNP 19),GSE72713(ECRSwNP 3,nonECRSwNP 3),and GSE179265(ECRSwNP 11,nonECRSwNP 2).The diagnostic performance of the upregulated gene model(ADH1C,CCL26,HRH1,NOS2)and the downregulated gene model(LCN2,MUC5B,PLAT,TMEM45A,XDH)constructed based on the support vector machine(SVM)algorithm for ECRSwNP was excellent.CONCLUSION The diagnostic genes identified by the SVM model may serve as biological markers for the non-invasive diagnosis of ECRSwNP and potentially play a crucial role in the pathogenesis of ECRSwNP.

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.

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 efficacy and safety of glucocorticoid stent implantation compared with oral glucocorticoid during perioperative period in chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To compare the perioperative efficacy and safety of postoperative oral glucocorticoid and glucocorticoid stent implantation in patients with chronic rhinosinusitis with nasal polyps（CRSwNP） undergoing functional endoscopic sinus surgery（FESS）. Methods:Sixty patients with bilateral CRSwNP with similar degree of lesions were selected and divided into three groups: conventional surgical treatment group（20 cases）, glucocorticoid stent group（20 cases）, and oral glucocorticoid group（20 cases）. All three groups underwent routine FESS, patients in the sinus glucocorticoid stent group receiving sinus glucocorticoid stent placed in the ethmoid sinuses（one on each side） during surgery, and patients in the oral glucocorticoid group received postoperative oral methylprednisolone at a dose of 0.4 mg/kg per day for 7 days, followed by a tapering of 8 mg per week to 8 mg followed by maintenance therapy for 1 week, for a total of 3-4 weeks. Visual analog scale（VAS） scores were used to evaluate nasal congestion, rhinorrhea, olfaction, and facial pressure symptoms before surgery, as well as at 2, 4, 8, and 12 weeks after surgery. Nasal endoscopic Lund-Kennedy scores were recorded, and adverse reactions such as stent detachment, stent-related allergic reactions, sleep disorders, edema, gastrointestinal symptoms, rash/acne, behavioral/cognitive changes, weight gain, limb pain, and infection risk were documented. Results:The nasal congestion symptom scores at 2, 4, 8, and 12 weeks after surgery were significantly lower than those before operationin all three groups, and the differences were statistically significant（P<0.05）. The sinus glucocorticoid stent group exhibited significantly lower nasal congestion symptom scores at 4 and 8 weeks after surgery compared to the conventional surgical treatment group. The rhinorrhea symptom scores at 2, 8, and 12 weeks after surgery were significantly lower than preoperative scores in all three groups. Additionally, the sinus glucocorticoid stent group had significantly lower rhinorrhea scores than the conventional surgical treatment group at 2 weeks postoperatively. Concerning olfaction, the sinus glucocorticoid stent group showed a significant reduction in scores at 12 weeks postoperatively, while the oral glucocorticoid group exhibited significant improvement starting from 8 weeks after surgery. There were no statistically significant differences in nasal congestion, rhinorrhea, facial pressure, and olfaction scores between the sinus glucocorticoid stent and oral glucocorticoid groups at 2, 4, 8, and 12 weeks postoperatively. Nasal endoscopy scores revealed lower polyp scores and edema at 2, 4, 8, and 12 weeks postoperatively for all three groups compared to preoperative scores. The conventional surgical treatment group exhibited a significant reduction in nasal secretion scores starting from 8 weeks after surgery, while both the sinus glucocorticoid stent and oral glucocorticoid groups showed significant reductions starting from 2 weeks postoperatively, with scores significantly lower than those of the conventional surgical treatment group at 2 weeks. Scab/scar scores in the conventional surgical treatment group significantly decreased from 8 weeks after surgery, while both the sinus glucocorticoid stent and oral glucocorticoid groups exhibited significant reductions starting from 4 weeks. No statistically significant differences were observed in endoscopy scores（including polyps, edema, nasal secretion, scars, and scabs） between the sinus glucocorticoid stent and oral glucocorticoid groups at 2, 4, 8, and 12 weeks postoperatively. Regarding adverse reactions, no postoperative complications related to sinus glucocorticoid stent were observed in the sinus glucocorticoid stent group. In the oral glucocorticoid group,1 patient experienced irritability, and 1 patient experienced weight gain. Conclusion:The glucocorticoid stent implantation has comparable effects to oral glucocorticoid in improving postoperative nasal symptoms, reducing nasal mucosal edema, scar formation, and nasal secretion in patients with CRSwNP undergoing FESS, with a better safety profile.

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.

Differential expression of NEDD8 in different pathological types of chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the differential expression of neural precursor cell-expressed developmentally downregulated 8（NEDD8） protein in nasal polyp tissues of patients with different pathological types of chronic rhinorhinosinusitis with nasal polyps（CRSwNP）. Methods:All specimens were obtained from the specimen library of Beijing Tongren Hospital, and were all patients who underwent nasal endoscopic surgery for chronic rhinosinusitis in Beijing Tongren Hospital. Hematoxylin-eosin staining（HE） was used to detect the number of eosinophils in nasal polyps, and CRSwNP patients were grouped according to the number of eosinophils in nasal polyps, immunohistochemistry was used to detect and analyze the expression level of NEDD8 protein in nasal polyps. Results:The expression level of NEDD8 protein in nasal polyps of patients with eosinophilic chronic rhinorhinosinusitis with nasal polyps was significantly higher than that of patients with non-eosinophilic chronic rhinosinusitis and nasal polyps（P<0.05）. In addition, there was a significant positive correlation between the expression level of NEDD8 protein and the number of eosinophils in nasal polyp tissue（r=0.79, P=0.02）. Conclusion:There are differences in the expression of NEDD8 protein in patients with chronic rhinosinusitis and nasal polyps of different pathological types.