奥马珠单抗治疗慢性鼻-鼻窦炎伴鼻息肉的研究进展[综述]

慢性鼻-鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps,CRSwNP）是临床常见疾病,复发率较高。对于部分应用传统鼻内镜手术和常规药物疗效并不理想的患者,奥马珠单抗可能成为他们的治疗选择之一。奥马珠单抗是一种重组人源化单克隆抗体,近年来国外应用其治疗CRSwNP的文献多显示出良好的应用前景。本文对目前奥马珠单抗治疗CRSwNP的临床研究进展做一综述。     

慢性鼻窦炎伴鼻息肉与哮喘的相关性机制及治疗策略研究进展

慢性鼻窦炎伴鼻息肉(CRSwNP)和哮喘作为上下呼吸道最具代表性的慢性炎症性疾病，二者在发病过程中常相互并存，临床诊治棘手。目前对CRSwNP和哮喘的相互作用机制尚未阐明。欧洲鼻窦炎鼻息肉诊疗指南(EPOS 2012)对治疗CRSwNP伴或不伴哮喘已给出具体的指导意见，其常规治疗包括鼻用糖皮质激素、生理盐水洗鼻等，并进一步根据CRSwNP的特点、症状严重程度等进行后续的联合治疗。据报道，鼻窦手术和药物治疗CRSwNP对合并支气管哮喘的转归有益。但CRSwNP合并哮喘患者经药物与手术治疗后的疗效判定尚缺乏足够的随机对照试验证据。     

编辑导读

本期无重点号。论著《阿司匹林激发试验在诊断非甾体抗炎药加重呼吸道疾病中的价值》以50例慢性鼻窦炎伴鼻息肉(CRSwNP)伴/不伴哮喘的患者为研究对象, 实施非甾体抗炎药加重呼吸道疾病(NERD)的规范化诊断流程, 发现仅通过病史诊断会造成漏诊, 鼻腔阿司匹林激发试验用于诊断NERD的准确性高、安全性良好, 若鼻腔激发试验阴性, 则需进一步进行口服阿司匹林激发试验。《小剂量奥马珠单抗在嗜酸粒细胞增多的难治性鼻窦炎患者扩大鼻窦开放术后的应用初探》探讨了小剂量(150 mg/月)奥马珠单抗在24例嗜酸粒细胞增多的难治性鼻窦炎患者鼻窦扩大开放术后的近期应用疗效, 证实小剂量奥马珠单抗可有效控制术腔黏膜炎性反应, 促进黏膜上皮化进程, 在疾病早期转归关键阶段发挥重要作用。《三叶因子家族3对嗜酸粒细胞性慢性鼻窦炎鼻黏膜上皮中紧密连接的作用》收集11例对照患者鼻黏膜组织和37例慢性鼻窦炎伴鼻息肉患者鼻息肉组织, 观察三叶因子家族(trefoil factor family, TFF)3对嗜酸粒细胞性慢性鼻窦炎(eCRS)鼻黏膜上皮中紧密连接蛋白的影响, 发现TFF3可通过PI3K/Akt上调occl...     

变应性因素对鼻内镜手术疗效的影响

目的：探讨变应性因素对慢性鼻窦炎伴鼻息肉患者行鼻窦内窥镜手术疗效的影响。方法对我院2011～2012年入院手术的II型慢性鼻窦炎伴鼻息肉患者,术前根据其是否伴有变应性鼻炎症状和体征、是否伴有过敏性疾病史及支气管哮喘病史、术前鼻腔分泌物涂片嗜酸粒细胞检查、变应原皮肤试验、血清特异性IgE检查、过敏性鼻炎,筛选出伴有变应性因素的慢性鼻窦炎伴鼻息肉患者为试验组。选择同期无变应性因素的单纯慢性鼻窦炎伴鼻息肉患者作为对照组。比较两组患者手术后疗效,并同时比较各种变应性因素对手术疗效的影响。结果伴有变应性因素的慢性鼻窦炎伴鼻息肉患者,手术疗效为80.95%（136/168）,同期单纯慢性鼻窦炎伴鼻息肉患者,手术疗效为91.75%（189/206）,两组间差异有显著性（P〈0.01）。在各种变应性因素中,伴有变应性鼻炎症状和体征、嗜酸粒细胞阳性、变应原皮肤试验阳性、血清特异性IgE、过敏性鼻炎的慢性鼻窦炎伴鼻息肉患者,与无变应性因素的慢性鼻窦炎伴鼻息肉患者比较,差异均有显著性（P〈0.05）,伴有过敏性疾病史及伴支气管哮喘病史患者与无变应性因素的慢性鼻窦炎伴鼻息肉患者比较,差异无显著性（P〉0.05）。结论变应性因素与鼻窦内窥镜手术疗效密切相关,是术后复发的重要因素。对慢性鼻窦炎伴鼻息肉患者行鼻窦内窥镜手术时,必须加强围手术期抗变应性治疗。     

联合应用奥马珠单抗在儿童中重度变应性哮喘合并慢性鼻窦炎中的疗效观察

目的 探讨奥马珠单抗在儿童中重度变应性哮喘合并慢性鼻窦炎治疗中的疗效。方法 分析2020年9月至2022年4月间使用奥马珠单抗治疗的儿童中重度变应性哮喘合并慢性鼻窦炎的临床资料,比较治疗前后儿童哮喘控制评分(childhood asthma control test, C-ACT)、呼出气一氧化氮(fractional concentration of exhaled nitric oxide, FeNO)浓度、第1秒用力呼气量占预计值百分比(first second percentage to predicted value, FEV₁%pred)和小气道功能指标等肺功能检查的变化以及患儿慢性鼻窦炎症状改善情况。结果 完成治疗随访的患儿共26例。奥马珠单抗治疗16周后患儿哮喘症状及肺功能均改善,C-ACT从(15.57±3.25)分升至(24.98±5.21)分(F=15.711 2,P<0.001);FeNO从(31.55±15.57) ppb降至(19.86±9.80)ppb(F=4.426 5,P=0.002 2);肺功能提示FEV₁     

慢性鼻-鼻窦炎伴鼻息肉的临床特征分析

目的　分析慢性鼻-鼻窦炎伴鼻息肉患者的临床和病理资料，总结其临床特征。方法　纳入2017年10月～2018年12月于中山大学附属第三医院确诊为慢性鼻-鼻窦炎伴鼻息肉并接受手术治疗的患者170例，比较嗜酸性粒细胞型慢性鼻-鼻窦炎伴鼻息肉（eosinophilic chronic rhinosinusitis with nasal polyps，ECRSwNP）和非嗜酸性粒细胞型慢性鼻-鼻窦炎伴鼻息肉（non-eosinophilic chronic rhinosinusitis with nasal polyps，non-ECRSwNP）之间各项临床特征的差异。结果　ECRSwNP占38.2%，non-CRSwNP占61.2%，前者更容易合并变应性鼻炎、哮喘，其外周血IgE水平、嗜酸性粒细胞绝对值及百分比、嗜碱粒细胞绝对值及百分比更高，且CT评分筛窦/上颌窦比值也更高，差异具有统计学意义。结论　ECRSwNP与non-ECRSwNP具有不同的临床特征。     

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。     

慢性鼻窦炎鼻息肉的特异性免疫治疗进展

慢性鼻-鼻窦炎是鼻科常见慢性疾病,根据2007年“欧洲鼻-鼻窦炎和鼻息肉诊疗意见书”(EPOS 2007)[1],依其是否伴发鼻息肉分为慢性鼻-鼻窦炎不伴鼻息肉(CRSw/oNP)、慢性鼻-鼻窦炎伴鼻息肉(CRSwNP).另外依据遗传缺陷和针对真菌的特异性IgE介导的免疫反应,把囊性纤维化(cystic fibrosis,CF)[1]和变应性真菌性鼻窦炎(allergic fungal rhinosinusitis,AFRS)[2]的鼻息肉区分为特定的类型.     

慢性鼻窦炎的免疫病理研究：对异位和非异位由IgE激活的肥大细胞过敏性炎症的设想

早在1980年该作者就发现儿童的腺样组织中存在IgE免疫荧光阳性的肥大细胞和浆细胞,其中一些表现IgE阳性的儿童临床并无过敏症状,这种阳性表达是否为病毒或细菌感染而引起的假阳性反应,尚需进一步研究。本文实验对象为54例在1994～1996年间行鼻窦外科内镜检查的住院病人,包括22例慢性鼻窦炎患者,16例慢性鼻窦炎伴哮喘者和16例慢性鼻窦炎伴鼻息肉患者。其中14例(6例男性和8例女性)对     

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。     

以耳部症状首发、合并鼻咽占位的肉芽肿性多血管炎1例并文献复习

目的 探讨1例临床少见的以耳部症状首发、合并鼻咽部占位的肉芽肿性多血管炎(GPA)的临床特征、实验室检查、病理表现及诊疗过程。方法 回顾性分析患者的病例资料,总结病例特点并回顾国内外GPA相关文献。结果 患者以中耳炎、迷路炎症状为首发表现,合并鼻咽部占位,病程中逐渐出现面瘫,三叉神经刺激症状加重。多次留取耳及鼻咽部活检示急慢性炎症细胞浸润。升级抗生素,同时为避免中耳炎侵犯岩骨及颅内行乳突开放术。中耳局部炎症改善后其耳痛、面瘫等仍不缓解,但激素治疗有效,遂进一步完善自免病相关检查并再次行鼻咽部活检,最终确诊为GPA,予激素及免疫抑制剂治疗得以控制症状。术后3个月暂无显著肺部及肾脏受累表现。结论 临床上发现不典型的中耳炎或常规治疗反复不愈,且逐渐进展出现内耳、颅神经侵犯表现如眩晕发作、面神经麻痹等,同时激素治疗有效,且合并鼻咽部占位、鼻窦炎影像学表现,或累及其他器官如肺、肾脏时,均应考虑到GPA的可能。当反复留取病理活检未能取得特异性确诊依据时,动态监测抗中性粒细胞胞浆抗体、红细胞沉降率、尿潜血、胸部CT、血肌酐等也具有重要的提示意义。     

Decreased miRNA-320e correlates with allergy in children with otitis media with effusion

ObjectiveOtitis media with effusion (OME) is a common childhood disease and the main cause of conductive hearing loss in this age group. Many factors predispose to OME but allergy is still widely disputed. The answer may lay in the molecular mechanisms of ear exudate formation and the recent studies showed miRNAs might take part in it. MiRNAs are also potent regulators of allergic response. As miRNAs are present in the middle ear, we hypothesized their expression differs between allergic and non-allergic patients and reflects the difference in pathomechanism of effusion formation between these two groups.Materials and methodsThis study aimed to establish the expression of 5 different miRNAs (miR-223-3p, miR-451a, miR-16-5p, miR-320e, miR-25-3p) in ear exudates in children diagnosed with OME. The allergy group consisted of 18 patients whereas the non-allergic group had 36 patients. MicroRNA was isolated from the middle ear fluid collected during myringotomy and transcribed into cDNA. MiRNA expression was measured with TaqMan™ MicroRNA Assays and analyzed with DataAssist software. The comparative CT method was used for calculating the relative quantification of gene expression based on the endogenous control gene expression (U6 snRNA-001973).ResultsMiR-320e expression was significantly decreased in allergic children with OME. Other studied miRNAs also showed reduced expression in allergic children, but the decrease was not significant.ConclusionsMiRNA expression differs between children with and without allergy in the course of OME, but further studies are needed to explain the exact role of miR-320e and its target genes in OME pathology in allergic patients.     

Experience with vertical partial laryngectomy with special reference to laryngeal reconstruction with cervical fascia

In this paper we report our experience of vertical partial laryngectomy using the superficial cervical fascia; we describe the technique and present the functional and oncological results of this method of treatment. A total of 42 patients with squamous cell carcinoma of the true vocal folds, in stage T(1) (n = 28) or T(2) (n = 14), were treated in our department using vertical partial laryngectomy during the decade 1987-1997. Nine patients had post-operative radiotherapy. The shortest follow-up time was three years. There were six recurrences in all, four in the larynx and two in the neck. All four of the laryngeal recurrences were treated with total laryngectomy and are doing well. Both the patients with neck metastases, who were treated with neck dissection, died. Permanent tracheotomy was necessary in one patient. There were no problems with aspiration. The recurrence rate was 14 per cent, the three-year survival index was 95.2 per cent and the three-year larynx preservation index was 90 per cent. According to our experience, vertical partial laryngectomy, using the method we describe, has a good functional and oncological result for stage T(1) and T(2) tumours.     

Cytokines in children with otitis media with effusion

We assayed 38 middle ear effusions from 23 children aged 4–13 years (mean 7) undergoing tympanostomy tube placements. All fluid was assayed for tumor necrosis factor (TNF) α, interleukin (IL) 1β, IL-8, and IL-10. Cytokine concentrations were measured by means of an enzyme-linked immunosorbent assay. Detectable levels of IL-1β, IL-8, and IL-10 were found in all of the effusions. TNF-α was detected in 18 of the middle ear effusions (47.4%). The mean concentration of TNF-α, IL-1β, IL-8, and IL-10 was, respectively, 0.423 ± 1.39, 30.58 ± 68.7, 7001.9 ± 6743, and 56 ± 58.7 pg/ml. There was a strong, statistically significant correlation between the concentrations of TNF-α and IL-1β (r = 0.87, P = 0.001) and between IL-1β and IL-8 (r = 0.53, P = 0.001). There was no correlation between the concentrations of IL-10 and other cytokines examined or between tympanic membrane pathology and the concentrations of TNF-α, IL-1β, IL-8, or IL-10. The presence of IL-10 in middle ear effusions may be one of the causes of a lack of clinical features of acute inflammation and may lead to a chronic inflammatory state. Received: 25 August 1999 / Accepted: 5 January 2000     

Polymyositis with dysphagia treated with endoscopic balloon dilatation

Polymyositis is characterized by non-specific inflammatory disease associated with an autoimmune disorder involving muscles of the limbs and neck. We report a case of an 80-year-old man who was referred to our clinic with a chief complaint of dysphagia and muscle weakness in all four limbs. The patient was diagnosed with polymyositis based on pathological findings, muscle weakness, electromyogram findings, and an elevated creatine phosphokinase level. The patient was also positive for HLA-DR3. Intravenous predonine administration was initiated, but dysphagia was not improved. We considered a cricopharyngeal myotomy, but this could not be performed because of heart failure. Endoscopic balloon dilation was performed and dysphagia improved on the same day. Therefore, we suggest that this method is a safe and effective approach for polymyositis with dysphagia.     

Hearing acuity of children with otitis media with effusion

Hearing levels are reported for a cohort of 222 infants (aged 7 to 24 months) and 540 older children (aged 2 to 12 years) with otitis media with effusion (OME). The infants had an average speech awareness threshold of 24.6 dB hearing level (HL). The older group had mean bone conduction thresholds less than 10 dB HL, and air conduction thresholds averaged 27 dB HL; however, acuity was 7 dB less impaired at 2,000 Hz. The mean three-frequency pure tone average and speech reception threshold were 24.5 and 22.7 dB, respectively. Hearing acuity was not significantly related to age or previous duration of OME. The otoscopic observation of an air-fluid level or bubbles was associated with less hearing impairment; however, a predictive relationship between hearing levels and tympanogram characteristics could not be demonstrated.