抗IgE单克隆抗体治疗难治性鼻窦炎伴鼻息肉三例

鼻息肉是鼻腔和鼻窦黏膜最常见的慢性变态反应相关疾病之一,难治性鼻窦炎伴鼻息肉常合并哮喘,手术和药物治疗都很难控制病情。奥马珠单克隆抗体是人源性IgE单克隆抗体,国外已有应用IgE单克隆抗体治疗鼻息肉,特别是哮喘合并鼻息肉的报道。本研究对3例哮喘合并慢性鼻窦炎伴鼻息肉（CRSwNP）的患者采用奥马珠单克隆抗体治疗,随访1...     

度普利尤单抗在慢性鼻窦炎伴鼻息肉治疗中的研究进展

慢性鼻窦炎(CRS)是一种常见的鼻窦黏膜炎症性疾病,复杂的发生机制造就了CRS的高度异质性,部分患者无法从目前标准的药物治疗和手术中得到缓解。CRS具有不同的炎症内型和临床表型,慢性鼻窦炎伴鼻息肉(CRSwNP)一直是治疗难点,其症状相对较重还常合并哮喘,易对常规药物和手术的疗效不佳并伴有较高的复发风险。近年来,度普利尤单抗(dupilumab)在成人顽固性CRSwNP中疗效显著,其通过阻断Ⅱ型炎症中关键驱动因子IL-4和IL-13的信号传导,达到治疗作用。目前度普利尤单抗对国人CRSwNP治疗研究尚无报道。本文将对度普利尤单抗治疗CRSwNP的研究进展进行综述,以期为其在CRSwNP中的进一步应用研究提供参考。     

鼻窦球囊扩张联合药物支架治疗儿童慢性鼻-鼻窦炎伴鼻息肉的疗效及并发症分析

目的 观察鼻窦球囊扩张联合药物支架在儿童慢性鼻-鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyps,CRSwNP)治疗中的疗效及并发症,为儿童CRSwNP的有效治疗提供可行性方案.方法 10例全组鼻窦炎患儿伴一侧或双侧鼻息肉,10例患儿共计13侧合并有鼻息肉,所有患儿均在全...     

慢性鼻-鼻窦炎-鼻息肉伴哮喘患者鼻内镜围手术期药物治疗

目的 探讨慢性鼻-鼻窦炎-鼻息肉(CRSwNP)伴支气管哮喘患者鼻内镜围手术期药物治疗原则及效果。方法 收集2010年6月至2013年12月山东大学齐鲁医院耳鼻咽喉科收治的109例CRSwNP伴支气管哮喘患者行鼻内镜手术(ESS)的临床资料。术前均对哮喘进行全面评估, 哮喘完全控制6个月后行ESS手术治疗, 围手术期采用雾化吸入及全身糖皮质激素等药物治疗。结果 围手术期无哮喘急性发作, 仅1例患者术后第2天因口服镇痛剂出现喘息;术后随访1~3年, 采用鼻内镜检查并行ESS临床疗效评估, 病情完全控制者5例(4.59%), 病情部分控制者94例(86.24%), 病情未控制10例(9.17%);仅1例术后13个月因股骨头坏死行手术治疗。结论 全面细致的哮喘病情评估和ESS围手术期药物治疗有利于防止围手术期哮喘发作及控制术后CRSwNP患者鼻息肉复发, 有利于提高手术疗效。     

奥玛株单抗在慢性鼻窦炎伴鼻息肉患者治疗中的应用

慢性鼻窦炎伴鼻息肉(CRSwNP)的炎症机制复杂,现有治疗方式对其病情控制欠佳。奥玛株单抗可通过与IgE受体结合降低患者的免疫级联反应,已有研究证明其对缓解CRSwNP合并哮喘患者的鼻部症状有良好的效果,但针对伴嗜酸性粒细胞增多、IgE水平高的难治性复发性CRSwNP治疗效果的探索还需要更多、更大规模的随机对照实验来证明。本文结合该背景对奥玛株单抗的作用机制以及在CRSwNP中的应用进行阐述,为CRSwNP的治疗提供参考。     

慢性鼻窦炎鼻息肉合并哮喘患者外周血和鼻息肉组织中炎症细胞的对比分析

探讨哮喘对慢性鼻窦炎鼻息肉（CRSwNP）患者外周血、鼻息肉组织炎症细胞数目和比例的影响。方法选取2016年1月—2018年2月就诊于中国医科大学附属第一医院耳鼻咽喉科并接受鼻内镜手术的CRSwNP的住院患者,根据患者症状以及术前肺功能及支气管舒张试验的结果纳入明确诊断哮喘的患者21例,同期随机纳入CRSwNP不合并哮喘的患者56例作为对照比较。所有患者均为双侧鼻息肉,术前CT评估患者息肉严重程度大致相同。术前空腹采血分类计数炎症细胞、检测吸入物变应原。术前1周对患者进行盐水冲洗鼻腔、抗生素治疗、鼻喷激素及黏液促排剂规范化治疗,术中取同部位鼻息肉标本进行切片HE染色,高倍镜下分类计数以嗜酸粒细胞（EOS）为主的各炎症细胞。并统计所有患者2次及多次鼻内镜手术情况。利用SPSS 17.0软件对数据进行统计学分析。结果CRSwNP合并哮喘组比CRSwNP不合并哮喘组有着更高的外周血EOS百分比（P＜0.05）,两组外周血淋巴细胞与中性粒细胞(NEU)百分比无明显差异。而CRSwNP合并哮喘组与CRSwNP不合并哮喘组相比组织EOS、浆细胞、淋巴细胞、NEU及炎症细胞总数的绝对值及百分比均无统计学差异。哮喘组患者患变应性鼻炎比例及二次手术率较非哮喘组高（P＜0.05）。结论炎症细胞数目和比例与CRSwNP合并哮喘有一定相关性,合并哮喘患者提示有更高可能外周血EOS升高。哮喘可能影响鼻息肉组织中炎症细胞分布,但局部炎症细胞的数目和比例可能受多种因素影响。     

慢性鼻窦炎鼻息肉患者血清金黄色葡萄球菌肠毒素IgE抗体检测

目的检测慢性鼻窦炎伴和不伴鼻息肉患者金黄色葡萄球菌肠毒素(Staphylococcus aureus enterotoxins,SEs)A、B、C型的血清特异性IgE抗体,探讨SEs在慢性鼻窦炎、鼻息肉发病中的作用。方法研究对象包括慢性鼻窦炎不伴鼻息肉(CRSsNP)患者30例、慢性鼻窦炎伴鼻息肉(CRSwNP)患者40例和健康对照组30例,应用ImmunoCAP100E系统检测血清SEA、SEB和SEC特异性IgE水平,并采用统计学软件SPSS11.0进行分析。结果 CRSsNP和CRSwNP患者的血清SEB特异性IgE水平较之对照组均明显增高,差异有统计学意义(P0.05),而血清SEA和SEC特异性IgE水平未见明显升高(P0.05)。结论金黄色葡萄球菌感染产生的肠毒素B(SEB)在慢性鼻窦炎、鼻息肉的发病过程中发挥一定作用。     

自噬相关基因Atg3、Ambra1与慢性单纯性鼻窦炎、鼻息肉及鼻息肉伴发哮喘的相关性研究

目的 自噬是机体的一种重要的保护和防御机制.研究拟通过对自噬相关基因Atg3、Ambra1表达的观察,探讨自噬与慢性鼻窦炎(CRS)及哮喘之间的关联性及可能的作用机制.方法收集24例鼻中隔偏曲患者的下鼻甲黏膜作为正常对照组,选取21例慢性单纯性鼻窦炎患者(CRSsNP组)、22例慢性鼻窦炎鼻息肉患者(CRSwNP组)及18例慢性鼻窦炎鼻息肉伴发哮喘患者(CRSwNP伴哮喘组)的鼻腔黏膜组织为实验组.采用免疫组织化学染色技术检测Atg3、Ambra1在各组中的表达强度及分布,分析自噬相关基因在各组间表达的差异,并分析各组中两基因之间的相关性.结果 ①自噬相关基因Atg3在对照组、CRSsNP组、CRSwNP组、CRSwNP伴哮喘组中表达逐渐增强,在各组间表达差异有统计学意义(x2=31.080,P＜0.001);进一步两两比较,在对照组与CRSsNP组之间(P=0.002)、对照组与CRSwNP组之间(P＜0.001)、对照组与CRSwNP伴哮喘组之间(P＜0.001)、CRSsNP组与CRSwNP伴哮喘组之间(P =0.002)、CRSwNP组与CRSwNP伴哮喘组之间(P =0.024)表达差异均有统计学意义,在CRSsNP组与CRSwNP组之间(P=0.304)表达差异无统计学意义.②自噬相关基因Ambra1在对照组、CRSsNP组、CRSwNP组、CRSwNP伴哮喘组中表达逐渐增强,在各组间表达差异有统计学意义(x2=33.000,P＜0.001);进一步两两比较,在对照组与CRSsNP组之间(P=0.009)、对照组与CRSwNP组之间(P＜0.001)、对照组与CRSwNP伴哮喘组之间(P ＜0.001)、CRSsNP组与CRSwNP伴哮喘组之间(P ＜0.001)、CRSwNP组与CRSwNP伴哮喘组之间(P=0.009)表达差异均有统计学意义,在CRSsNP组与CRSwNP组之间(P =0.205)表达差异无统计学意义.③8.Atg3与Ambra1在CRSsNP组(r=0.619,P=0.003)、CRSwNP组(r=0.392,P=0.022)和CRSwNP伴哮喘组(r =0.552,P=0.033)中表达呈正相关性,在对照组中无相关性(r=0.316,P=0.133).结论 细胞自噬与CRS疾病的发生发展密切相关,可能参与了CRSwNP伴哮喘的发生,且自噬相关基因Atg3与Ambra1在CRS的发生发展过程中可能存在协同作用,自噬可成为CRS诊疗新的研究方向.     

鼻细菌微生物组与慢性鼻窦炎伴鼻息肉相关性的研究进展

慢性鼻窦炎伴鼻息肉(CRSwNP)是慢性鼻窦炎的难治性亚型,其病理生理机制尚不明确,细菌在其发病机制中发挥着重要作用,但具体作用机制尚不清楚。微生物组是包括呼吸道疾病在内的人类健康研究的新视角之一。随着新一代测序技术的发展,CRSwNP鼻部细菌微生物群落的复杂性得到了进一步的认识。鼻腔细菌丰富度和多样性的改变可能与CRSwNP的炎症类型、伴随疾病和预后有关。鼻部细菌在CRSwNP的诊断和治疗等多方面都有较好的前景和潜在意义。本文就鼻腔鼻窦细菌微生物组与慢性鼻窦炎伴鼻息肉相关性的研究进展加以综述。     

无创性临床指标在慢性鼻窦炎伴鼻息肉合并哮喘诊断中的应用价值

目的　比较无创性临床指标在预测慢性鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps,CRSwNP）合并哮喘诊断中的价值。方法　纳入30例CRSwNP不合并哮喘和40例CRSwNP合并哮喘患者。用Logistic回归分析CRSwNP伴哮喘的因素。用受试者工作特征（receiver operating characteristic,ROC）曲线评价各指标在CRSwNP合并哮喘诊断中的预测效能。结果　Logistic回归分析显 示,年龄、第1秒用力呼气容积（forced expiratory volume in one second,FEV1）/用力肺活量（forced vital capacity,FVC）和呼出气一氧化氮（fractional exhaled nitric oxide,FeNO）与CRSwNP合并哮喘相关（P 均<0.05）。ROC曲线显示FEV1/FVC和FeNO对CRSwNP合并哮喘有中等程度的准确性（AUC分别为0.816和0.768）,年龄有较低的准确性（AUC=0.658）,而联合模型可进一步提高诊断准确性（AUC=0.921）。结论　无创性临床指标FEV1/FVC、FeNO和年龄联合模型对于CRSwNP合并哮喘具有更高的诊断价值。     

老年慢性鼻-鼻窦炎伴鼻息肉患者鼻内镜术后复发的影响因素分析

目的 探讨老年慢性鼻-鼻窦炎伴鼻息肉(chronic rhinosinusitis with or without nasal polyps,CRSwNP)患者鼻内镜术后复发的影响因素.方法 行鼻内镜治疗的老年CRSwNP患者126例,根据是否复发分为复发组(52例)和未复发组(74例),对可能影响其术后复发的相关因素...     

Post-operative steroid treatment for eosinophilic-type sinonasal polyposis

Conclusions: The preliminary finding of significantly lower eosinophilic-type CRSwNP recurrence rates in patients with associated asthma or ASA intolerance treated post-operatively with local nasal and oral steroids warrants further investigation in larger, prospective series. Objective: A high recurrence rate after functional endoscopic sinus surgery (FESS) has been widely reported in patients with eosinophilic-type chronic rhinosinusitis with nasal polyps (CRSwNP). This study compared the influence of two post-operative medical treatments – local nasal steroids alone vs local nasal and oral steroids – on the recurrence of eosinophilic-type CRSwNP. Method: Between January 2009–December 2010, 32 patients with eosinophilic-type CRSwNP received local steroid nasal therapy after FESS (Group A); from January 2011 onwards, another 28 patients were treated post-operatively with the same nasal treatment plus two cycles a year of oral steroids (Group B). All patients in both groups had a follow-up of at least 36 months. Results: Groups A and B did not differ significantly in recurrence rate (31.25% vs 32.14%, p = 1) or disease-free interval (p = 0.91), but Group B patients who were asthmatic or ASA-intolerant had a significantly lower recurrence rate than Group A patients with asthma or ASA intolerance (p = 0.04 and p = 0.004, respectively).     

Evaluation of aspirin hypersensitivity in patients with chronic rhinosinusitis

Conclusion The recurrence rates of chronic rhinosinusitis (CRS) were higher in the aspirin nasal provocation test (ANPT)-positive group, regardless of the presence of nasal polyps. Thus, a careful endoscopic examination is required during follow-up in ANPT-positive patients with CRS. Objectives The aim of this study was to evaluate the clinical features and prognosis after surgical treatment in patients with CRS and aspirin hypersensitivity. Methods In a prospective study, 100 patients were analyzed with CRS who underwent endoscopic sinus surgery at the hospital from October 2012 to March 2013. This study measured changes in nasal volume and symptoms before and after the ANPT and examined patient’s asthma history, allergy, Lund–Mackay score (LMS), total immunoglobulin E, percentage of peripheral eosinophils, and objectively measured relapse at 6 months. Results Patients wwith CRS and nasal polyps (CRSwNP) were more likely to have a positive ANPT test result compared to those without nasal polyps (CRSsNP) (21.4% vs 5.5%). The ANPT-positive group had a higher LMS and required more revision endoscopic sinus surgery than those in the ANPT-negative group. The results were that similar results were observed in CRSwNP and CRSsNP.     

The effect of endoscopic sinus surgery on asthma: management of patients with chronic rhinosinusitis, nasal polyposis, and asthma.

We attempted to determine the efficacy of endoscopic sinus surgery in adult patients with asthma and chronic rhinosinusitis or nasal polyposis. Fifty asthmatic patients from 17 to 74 years of age with a history of either chronic rhinosinusitis or nasal polyposis were examined. Sinonasal disease was confirmed endoscopically and with computerized tomography, and all had failed aggressive medical management of their sinonasal disease before undergoing endoscopic sinus surgery performed by the same surgeon in all cases. The following were compared for 12 months: preoperative and postoperative overall asthma control, peak flow measurements, asthma medication requirements, including the use of oral steroids, and hospitalizations for asthma. Twenty patients felt that their asthma control had improved postoperatively. Twenty per cent used less steroid inhaler, and 28% less bronchodilator inhaler. Of those 23 patients measuring peak flows, seven achieved higher levels and seven noted fewer dips and swings. Significant reductions in oral steroid requirements (p < 0.001) and hospitalization for asthma (p < 0.025) were also recorded postoperatively. Irrespective of whether the patient had chronic rhinosinusitis or nasal polyposis, both groups improved postoperatively. The commonest symptoms experienced by the group as whole and by the nasal polyposis patients were hyposmia and nasal obstruction. Postnasal discharge and headache were more important in the chronic rhinosinusitis group. Mean visual analog scores improved for all symptoms; in particular for nasal obstruction and sense of smell. Aggressive management of sinonasal pathology can improve asthma status. No major differences were recorded for outcomes when comparing patients with chronic rhinosinusitis or nasal polyposis; in particular there was no evidence for a worsening of asthma after nasal polypectomy.     

Increased expression of acidic mammalian chitinase in chronic rhinosinusitis with nasal polyps

BACKGROUND: Chitin is an abundant polysaccharide found in fungi, insects, and parasitic nematodes. Innate immune host defense against chitin-containing pathogens include production of chitinases. In human lower airways, acidic mammalian chitinase (AMCase) is produced in epithelial cells via a Th2-specific, IL-13-dependent pathway, and may act as an inflammatory mediator in asthma. The role of AMCase in chronic rhinosinusitis (CRS) has not been studied previously. METHODS: Eleven controls and 22 subjects with medically recalcitrant CRS were prospectively enrolled before undergoing endoscopic sinus surgery. RNA was extracted from surgically obtained ethmoid mucosa, and real-time PCR was used to determine expression of AMCase, eotaxin, and IL-13. Subjects were followed for at least 6 months postoperatively to assess for polyp recurrence. Based on the presence or absence of polyps, the subjects were classified as either recalcitrant or responsive to therapy. RESULTS: AMCase mRNA was detected in the sinus mucosa of 72% of control subjects and in 72% of patients with eosinophilic CRS with nasal polyps (CRSwNP). The expression of AMCase was significantly greater in recalcitrant CRSwNP than it was in treatment-responsive CRSwNP. There was no significant difference in IL-13 expression between these two groups. CONCLUSION: AMCase may be an important mediator in the pathogenesis of Th2 inflammatory diseases of the respiratory tract. Failure of medical and surgical therapy in CRSwNP is associated with significantly increased expression of AMCase, but not the Th2 cytokines IL-13 and eotaxin. Additional studies are needed to determine the potential of AMCase as a therapeutic target in CRSwNP.     

Decreased PLUNC expression in nasal polyps is associated with multibacterial colonization in chronic rhinosinusitis patients

PLUNC (palate, lung, and nasal epithelium clone) is an epithelium-secreted protein that plays a crucial role in the host’s defense against bacterial infection. The function of PLUNC in the sinus remains poorly understood. To examine whether the expression levels of PLUNC could serve as a predictive outcome biomarker for patients with CRSwNP and bacterial colonization, we investigated the association of PLUNC expression levels with bacterial colonization in the sinuses. A total of 174 patients who underwent sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled in this study. The tissue samples obtained from patients were examined using preoperative sinus computed tomography (CT) scans, postoperative bacterial cultures, and nasal polyp examinations. PLUNC mRNA and protein expression were quantified using RT-PCR and immunohistochemistry. We identified that decreased PLUNC expression is associated with multibacterial colonization (P = 0.0001), specifically those mediated by Staphyloccocus aureus (P = 0.037) and Pseudomonas aeruginosa (P = 0.002). The patients who required repeated sinus surgeries for recurrent or persistent sinusitis also presented much lower PLUNC expression than those who did not require repeated sinus surgery (P = 0.001). However, gender, age, and CT scores were not associated with PLUNC expression. These results suggest that reduced PLUNC expression is associated with bacterial colonization as well as treatment outcome in CRSwNP patients. Investigation of the association between PLUNC expressions and chronic rhinosinusitis may lead to the development of a novel biomarker for treatment outcome in CRSwNP patients.     

Appropriate extent of surgery for aspirin-exacerbated respiratory disease

The current literature lacks strong guidelines regarding surgical management of patients with aspirin-exacerbated respiratory disease (AERD), who present with the clinical triad of chronic rhinosinusitis with nasal polyposis (CRSwNP), bronchial asthma, and aspirin/nonsteroidal anti-inflammatory drug intolerance. To further define the effectiveness of sinus surgery in treating AERD patients, this review article discusses current evidence regarding outcomes associated with more extensive surgery, the benefits of frontal sinus surgery on polyposis, and the role of Draf III intervention. Numerous studies suggest that Draf III frontal sinusotomy may be an efficacious early intervention due to increased neo-ostial patency and subsequent distribution of topical therapies. Future studies that further investigate the efficacy and safety of extensive surgery in AERD patients are warranted.     

再次鼻内镜手术患者生活质量调查

目的:探讨修正性鼻内镜手术(RESS)对慢性鼻-鼻窦炎鼻息肉患者(CRSwNP)健康相关生活质量(QOL)的影响。方法:采用国内现有的中文版SF-36量表(MOS SF-36)和汉化英文版SNOT-20量表(SNOT-20),分别对60例施行修正性鼻内镜手术组(RESS)的CRSwNP患者和120名健康体检者进行QOL的调查与评估,并将2组的结果进行对比。结果:通过SF-36量表评估显示:RESS组术前CRSwNP患者SF-36的维度计分均低于对照组,差异有统计学意义(P<0.05)。通过汉化SNOT-20评估显示:RESS组术前CRSwNP患者SNOT-20各条目计分和条目总分均高于对照组,差异有统计学意义(P<0.05)。RESS组CRSwNP患者术后6个月SF-36和SNOT-20量表评估得分与对照组差异无统计学意义(P>0.05)。结论:RESS可明显改善CRSw-NP患者的QOL;SF-36和汉化SNOT-20量表能有效调查评估CRSwNP患者的QOL。