嗜酸性粒细胞与慢性鼻-鼻窦炎伴鼻息肉的相关性研究进展

慢性鼻窦炎（chronic rhinosinusitis,CRS）是鼻腔黏膜和鼻窦黏膜的慢性炎性疾病,根据有无鼻息肉可分为慢性鼻-鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps,CRSwNP）和慢性鼻-鼻窦炎（chronic rhinosinusitis without nasal polyps,CRSsNP）。鼻息肉组织常见有嗜酸性粒细胞(eosinophils,EOS) 浸润增多,根据嗜酸性粒细胞的浸润程度可将CRSwNP分为两个亚型：嗜酸粒细胞型慢性鼻窦炎伴鼻息肉(eosinophilic chronic rhinosinusitis with nasal polyps, ECRSwNP)和非嗜酸粒细胞型慢性鼻窦炎伴鼻息肉 (nonesinophilc chronic rhinosinusitis with nasal polyps,nonECRSwNP);将慢性鼻窦炎分为：嗜酸粒细胞型慢性鼻窦炎（eosinophilic chronic rhinosinusitis, ECRS)和非嗜酸粒细胞型慢性鼻窦炎(non eosinophilic,NECRS)。嗜酸性粒细胞在鼻息肉形成、发展机制中的作用多年来一直备受学者们关注。随着研究的不断深入,嗜酸性粒细胞在鼻窦炎鼻息肉炎症趋化、息肉形成、分型和预后中的作用得到越来越多的重视。     

表观遗传学在慢性鼻窦炎伴鼻息肉发病机制中的作用

慢性鼻窦炎伴鼻息肉其确切的发病机制尚未完全明确。表观遗传学(Epigenetics)主要指基于非基因序列改变所致基因表达水平的变化,包括DNA甲基化、组蛋白修饰和非编码RNA调控等。就相关基因的表观遗传学修饰及其引起的相应细胞因子和蛋白质等的表达改变在CRS发病机制中的作用作一综述,从全新的角度认识CRS,为明确其发病过程、探究治疗方法提供新的方向。     

慢性鼻-鼻窦炎伴鼻息肉合并哮喘患者肺功能分析

目的 分析慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)合并哮喘患者肺功能情况。 方法 选取74例经鼻内镜手术(FESS)的CRSwNP合并哮喘患者,分组进行肺功能比较:男49例(男性组),女25例(女性组);吸烟32例(吸烟组),不吸烟42例(非吸烟组);血清特异性IgE阳性者27例(IgE组),阴性者47例(非IgE组);外周血嗜酸粒细胞升高(外周血嗜酸粒细胞绝对值>0.5×10⁹/L)者27例(外周血嗜酸粒细胞升高组),未升高者47例(外周血嗜酸粒细胞非升高组);术后送检鼻息肉组织嗜酸粒细胞升高(嗜酸粒细胞平均>10个/HPF)者31例(组织嗜酸粒细胞升高组),未升高者43例(组织嗜酸粒细胞非升高组)。所有肺功能检测均在具有上岗资质变态反应科专业医师指导下完成,检测数据由德国康讯肺功能仪(PowerCubeBody)采集,肺功能指标包括第1秒用力呼气容积(FEV₁)占预计值的百分比(FEV₁% pre)、FEV₁与用力肺活量(FVC)的比值占预计值的百分比(FEV₁/FVC% pre)、最大通气量(MVV)占预计值的百分比(MVV% pre)、用力呼出50%肺活量时的瞬间呼气流(FEF_50%)、用力呼出75%肺活量时的瞬间呼气流(FEF_75%)及最大呼气中期流量(MMEF)。74例患者评估肺功能下降程度后针对性给予雾化吸入治疗,2~3次/d,沙美特罗替卡松粉吸入剂1吸,2次/d,予孟鲁司特钠 10 mg/d,氯雷他定10 mg/d口服,同时给予盐酸氮卓斯汀鼻喷剂 2次/d+布地奈德鼻喷雾剂 2次/d喷鼻治疗。自入院至术前,患者行药物治疗时间为1~14 d。所有患者术前30 min雾化吸入1次,麻醉前行沙美特罗替卡松粉吸入剂1吸。对术前药物干预后肺功能改善情况进行判定。 结果 74例患者均顺利完成手术。入院时女性组FEF_50%、FEF_75%及MMEF低于男性组(t分别为3.213、2.829、3.644,P分别为0.002 0、0.006 1、0.000 5),吸烟组较非吸烟组、外周血及鼻息肉组织中嗜酸粒细胞升高组均较非升高组FEV₁/FVC% pre下降(t分别为2.032、2.259、2.634,P分别为0.045 8、0.029 2、0.010 3),同时鼻息肉组织嗜酸粒细胞升高组较非升高组MVV% pre降低(t=2.453, P=0.0166)。经术前规范药物干预后,患者肺功能指标FEV₁%pre、FEV₁/FVC% pre、MVV% pre、FEF_50%、FEF_75%及MMEF均较入院时改善(t分别为6.640、6.071、8.166、5.554、6.137、4.256, P均为0.000 0)。 结论 CRSwNP合并哮喘患者中,女性较男性更易伴发小气道功能障碍;吸烟、外周血及鼻息肉组织嗜酸粒细胞升高亦可影响肺功能;规范的术前药物干预可有效改善CRSwNP合并哮喘患者的肺功能,减少围术期哮喘急性发作风险,有助于手术顺利实施。     

大环内酯类药物用于治疗慢性鼻窦炎及鼻息肉的抗炎机制

近年来关于应用长期低剂量大环内酯药物治疗慢性鼻窦炎及鼻息肉的文献报道较多，其作用机制目前普遍认为与其抗炎作用有关，本文着重介绍其用于治疗慢性鼻窦炎及鼻息肉的相关机制。     

度普利尤单抗治疗慢性鼻窦炎伴鼻息肉的疗效分析

目的 分析临床中IL-4Rα单克隆抗体(度普利尤单抗)治疗慢性鼻窦炎伴鼻息肉(CRSwNP)的疗效。方法 回顾性分析2020年8月—2021年4月使用度普利尤单抗治疗4例CRSwNP患者前后的临床疗效、实验室数据、主观及客观评分以及不良事件等情况,初步评价度普利尤单抗治疗CRSwNP的效果。结果 对4例CRSwNP患者随访4个月。在接受度普利尤单抗治疗前,4例患者慢性鼻-鼻窦炎急性加重次数平均为(3.25±1.50)次/年,在随访期间4例患者均未出现慢性鼻-鼻窦炎急性加重,其中3例患者的鼻窦炎症状得到完全控制。度普利尤单抗治疗前4例患者平均鼻腔鼻窦结局测试-22 (SNOT-22)、宾夕法尼亚大学的嗅觉测试(UPSIT)及副鼻窦CT扫描Lund-Mackay评分分别为52.00±9.42、7.25±1.26、14.50±5.45;治疗4个月后上述评分分别为8.25±5.74、29.25±6.34,7.00±6.38,治疗前后对比差异均具有统计学意义(P<0.05)。使用单抗治疗后4例患者平均口服糖皮质激素(OCS)量为(5.00±7.07)mg/d,对比治疗前(18.75±4.79) mg/d,差异具有统计学意义(P<0.05)。结论 通过特异性抑制白介素-4(IL-4)和白介素-13(IL-13)通路,度普利尤单抗可以显著改善CRSwNP患者鼻窦炎症状以及嗅觉水平,减少患者慢性鼻-鼻窦炎急性加重次数、鼻窦炎病变范围和全身糖皮质激素用量。     

哮喘伴慢性鼻窦炎治疗

目的探讨支气管哮喘伴有慢性鼻窦炎及鼻息肉患者行鼻内镜手术(endoscopicsinussurgery,ESS)的治疗效果。方法1998年8月～2002年10月,对25例支气管哮喘伴有慢性鼻窦炎及鼻息肉经药物治疗无效的患者,采用鼻内镜手术,按Messerklinger’s术式,切除钩突、摘除息肉、开放筛窦及上颌窦,清理窦口鼻道复合体病变组织;围手术期应用抗生素和类固醇皮质激素等。结果随访18个月～3年,支气管哮喘症状疗效为:有效10例,好转10例,无效5例;鼻窦炎及鼻息肉疗效为:治愈10例,好转12例,无效3例。结论ESS对支气管哮喘伴有慢性鼻窦炎及鼻息肉患者的治疗,可降低哮喘的发作频率和对类固醇皮质激素的依赖。     

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-鼻窦炎鼻息肉伴支气管哮喘的围手术期治疗

目的探讨慢性鼻-鼻窦炎(CRS)、鼻息肉伴有支气管哮喘患者的围手术期治疗。方法对72例伴有支气管哮喘的CRS、鼻息肉患者行鼻内镜下鼻窦功能性手术(FESS),观察不同麻醉下术中及术后哮喘发作情况并给予相应的治疗。结果局麻下30例手术患者中5例术中出现一过性焦虑、呼吸不畅,但无哮喘发作;3例术后轻度哮喘发作;全麻下42例手术患者术中均平稳,4例术后哮喘发作,其中1例哮喘持续状态,经治疗后好转。结论伴有哮喘的鼻-鼻窦炎、鼻息肉患者行FESS手术是必要、安全的。     

基于随机森林与人工神经网络慢性鼻窦炎伴鼻息肉诊断模型的构建与分析

目的 慢性鼻窦炎伴鼻息肉(CRSwNP)是一个全球性的健康问题,现有的诊断技术存在一定局限性,因此有必要开发新的诊断模型来补充现有的诊断方法。方法 利用CRSwNP患者(GSE23552、GSE36830)的公开基因表达数据来识别潜在的差异基因,应用随机森林算法和人工神经网络进一步筛选特异性基因,建立CRSwNP的早期诊断模型。结果 共发现78个上调基因和25个下调基因,随机森林算法筛选了4个特异性基因(HPGDS、IL1RL1、FMO3、DOK3),人工神经网络构建出基于上述基因的预测模型,该模型具有良好的预测效果(AUC=0.986),独立数据集GSE194282进一步验证了其准确性(AUC=0.888)。结论 采用机器学习方法建立了一个基于基因表达水平的预测模型,该模型可以预测早期CRSwNP,有助于早期诊断和改善临床决策。     

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。     

Biotherapy and treatment of adult primary chronic rhinosinusitis with nasal polyps: Cellular and molecular bases

The present article reviews the molecular and cellular mechanisms involved in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwCRSwNP) and underlying the action mechanisms of biotherapies. Biotherapy uses substances naturally produced by the organism or their specific antagonists targeting a proinflammatory mechanism. CRSwCRSwNP is a form of chronic rhinosinusitis (CRS), which is classically subdivided in to 2 types according to the presence of polyps. In recent years, the concept of endotypes emerged, with a more exhaustive definition of the types of CRS according to inflammatory mechanism, with a view to developing personalized treatments. CRSwNP pathophysiology is poorly understood. Polyps arise from a primary epithelial lesion in a context of chronic local inflammation, mainly type 2 in Europe, implicating eosinophils, IgE, Th2 cytokines (IL-4/IL-13, IL-5) and T and B cells. Biotherapy seems promising in CRSwNP. The present review details the various pathophysiological pathways underlying the action mechanisms of biotherapies, and the various published studies, assessing efficacy and mode of action in the treatment of CRSwNP.     

Efficacy of combined treatment with S-carboxymethylcysteine (carbocisteine) and clarithromycin in chronic rhinosinusitis patients without nasal polyp or with small nasal polyp

Objective

In Japan, fourteen-membered ring macrolides, antibacterial agents, and S-carboxymethylcysteine (SCMC; carbocisteine), a mucolytic, are commonly used to treat chronic rhinosinusitis (CRS), and they are also used in combination. However, no large-scale randomized study has examined the effects of these pharmacotherapies. The aim of this study is to evaluate the effect of combined administration of clarithromycin (CAM), a fourteen-membered ring macrolide, and SCMC, compared with CAM single therapy.

Methods

Patients with CRS were centrally registered and randomly assigned to treatment with CAM (200 mg/day) alone (monotherapy group) or CAM (200 mg/day) in combination with SCMC (1500 mg/day; combination group) for 12 weeks. We assessed the clinical efficacy of the treatments using measures of subjective symptoms and objective findings, health-related quality of life (HRQOL) determined by the 20-Item Sino-Nasal Outcome Test (SNOT-20) score and computed tomography (CT) score.

Results

Four hundred twenty-five subjects were enrolled (combination group, 213; monotherapy group, 212). At week 12 of treatment, the rate of effectiveness was significantly higher in the combination group (64.2%) compared with the monotherapy group (45.6%; P = 0.001). In addition, objective findings, including characteristics of nasal discharge (P = 0.008) and post-nasal discharge (P = 0.002) were significantly improved in the combination group. In both groups, SNOT-20 and CT scores were significantly improved from week 0 (P < 0.001), and were not significantly different between groups.

Conclusion

The results indicated that long-term combination therapy with SCMC at a dose of 1500 mg/day and CAM at a dose of 200 mg/day is effective for improving subjective symptoms and objective findings in adult patients with CRS.     

Relationship between positive bacterial culture in maxillary sinus and surgical outcomes in chronic rhinosinusitis with nasal polyps

Objectives

There are many studies on clinical prognosis following endoscopic sinus surgery (ESS) for the treatment of chronic rhinosinusitis with nasal polyp (CRSwNP). However, there are no independent reports on bacterial infection as a factor that influences surgical outcomes. We investigated the association between bacterial infection and surgical outcomes following ESS.

Methods

This retrospective review of medical records was performed on 71 patients with CRSwNP that was refractory to medical treatment and who were diagnosed between July 2007 and June 2012. The extent of the polyps and the Lund–Mackay CT score (L–M score) were preoperatively evaluated in all the patients. For this analysis, patients were classified into three groups (normal flora, culture-positive, and culture-negative) according to their intraoperative bacterial culture results. We compared the objective endoscopic findings between these groups at 6-months postsurgery.

Results

Bacteria were cultured in 55 of the 71 patients (77%). Of these, 43 patients (61%) demonstrated endoscopic improvement at the 6-month follow-up examination. The preoperative L–M score and polyp grade demonstrated no significant statistical differences in terms of surgical outcome, but the cure rate was statistically higher in culture-negative patients in comparison with normal flora and culture-positive patients (87.5% vs. 46.2% vs. 54.8, respectively).

Conclusion

Intraoperative culture results can be a prognostic factor for the clinical outcomes of ESS in CRSwNP patients. Hence, the intraoperative culturing of pathologic secretions and the postoperative administration of susceptible antibiotics could improve surgical results.