炎症小体Nod样受体在鼻黏膜炎性疾病中的研究进展

目前炎症小体Nod样受体（nod-like receptors,NLRs）的研究主要集中在先天性免疫及心血管等领域较多,而在鼻黏膜炎性疾病中的研究相对较少。本文概述了炎症小体的结构与功能激活与调节以及NLRs在鼻黏膜炎性疾病中的作用,综述当前有关NLRP3炎症小体在鼻黏膜炎性疾病中的研究进展。     

NLRP3炎性小体在变应性鼻炎中的作用

变应性鼻炎（AR）是一种以免疫球蛋白E （IgE）介导的多种免疫细胞、细胞因子和炎症介质等参与的鼻黏膜非感染性炎性反应性疾病,鼻腔黏膜炎症反应是AR的重要病理机制之一。核苷酸结合寡聚化结构域（NOD）样受体蛋白3（NLRP3）炎性小体活化诱导半胱氨酸蛋白酶1（caspase-1）前体转化,促进炎症细胞因子白介素1β（IL-1β）和白介素18（IL-18）表达,参与AR的炎性级联反应过程,对AR的发生发展起促进作用,应用NLRP3炎性小体相关通路抑制剂可抑制下游炎性细胞因子表达,减轻AR症状。本文围绕NLRP3炎性小体在AR中的作用及调控机制,和适用于AR治疗的NLRP3炎性小体相关通路抑制剂的研究进行综述如下。     

Toll样受体激动剂在变应性鼻炎免疫治疗中的研究进展

变应性鼻炎(AR)是由多种信号通路和细胞因子共同参与的鼻腔黏膜慢性炎症性疾病。Toll样受体(TLRs)作为一种重要模式识别受体(PRRs),介导细胞内信号转导通路,参与机体天然免疫和适应性免疫应答,在AR的发生、发展过程中发挥重要作用。近年来,TLRs作为治疗靶点在AR的治疗中取得良好疗效,TLRs激动剂可作为免疫制剂或免疫佐剂,在AR的免疫治疗中有广阔的应用前景。为进一步开发TLRs激动剂在临床上的可能价值,本文总结了TLRs激动剂在AR治疗中的研究进展。     

Galectin-9及其受体Tim-3在慢性鼻窦炎中的表达及临床意义

目的研究半乳糖凝集素9(Galectin-9)及其受体T细胞免疫球蛋白及粘蛋白结构域分子3(T cell immunoglobulin and mucin domain-3, Tim-3)在慢性鼻窦炎(chronic rhinosinusitis, CRS)患者鼻黏膜中的表达与对照组的差异,探讨Galectin-9及其受体Tim-3与CRS发病的关系。方法选取2019年1～9月住院确诊为CRS的患者为实验组(A组),选同期住院的单纯鼻中隔偏曲患者作为对照组(B组),所有患者均在手术中取窦口鼻窦复合体区黏膜作为标本。经实时荧光定量PCR(qPCR)、HE染色及免疫组化检测各组鼻黏膜中Galectin-9与Tim-3的表达及分布情况。分析比较各组间的差异,阐述Galectin-9及其受体Tim-3与CRS发病的关系。结果 Galectin-9及Tim-3在实验组及对照组鼻黏膜中均有表达,且实验组Galectin-9及Tim-3的表达明显高于对照组,差异有统计学意义(P0.05)。结论 CRS患者鼻黏膜中Galectin-9与Tim-3表达量较单纯鼻中隔偏曲患者鼻黏膜中高,提示Galectin-9及其受体Tim-3与CRS的炎症反应有关,可能参与CRS的炎症调节过程。     

气道慢性炎症与慢性鼻窦炎中PPARγ和ILC2s关系的研究进展

Ⅱ型固有淋巴样细胞(ILC2s)是一种非B、非T的新型淋巴细胞,可以产生大量促炎和调节性细胞因子,以应对局部损伤、炎症、病原体感染或肿瘤。过氧化物酶体增殖物激活受体γ(PPARγ)属于细胞核激素受体超家族配体激活转录因子之一,与相应配体结合后调节细胞增殖、分化、代谢等,从而在炎症反应中发挥重要作用。PPARγ广泛分布在人类鼻黏膜及鼻息肉黏膜中,并通过作用于ILC2s上的抑制肿瘤发生受体(ST2)、程序性细胞死亡蛋白-1(PD-1)以及影响ILC2s的能量代谢等途径影响ILC2s的功能。本文就PPARγ与ILC2s的关系以及在气道慢性炎症及慢性鼻窦炎(CRS)中的表达及相互作用进行综述,从而为气道慢性炎症性疾病及CRS的发病机制及治疗提供新思路。     

与NLRP3炎性小体通路相关感音神经性聋的研究现状

核苷酸结合寡聚结构域样受体蛋白3 (N OD-like receptor protein 3 ,NLRP3)作为模式识别受体,可识别各种危险信号,帮助炎症小体组装,促使半胱氨酸天冬氨酸蛋白酸1 (caspase-1 )前体成熟并释放白介素-1β(IL-1β)、白介素-18 (IL-18 ) ,间接促进肿瘤坏死因子(tu...     

慢性鼻窦炎特异性生物治疗研究进展

慢性鼻窦炎(CRS)是一种常见的鼻窦鼻腔黏膜炎症所引起的一组临床综合征, 具有高异质性。在临床常用的治疗方法中并没有基于CRS内在型不同的病理生理学发病机制的针对性治疗, 且常规治疗存在各种不良反应及潜在并发症, 这使得生物治疗CRS进入大众视野, 被认为是CRS治疗后效果维持和改变CRS自然过程的潜在性治疗选择。本研究就CRS的内在分型, 特异性生物治疗的作用机制, 常用靶向药物及最新研究进展做一综述。     

慢性鼻窦炎生物靶向药物治疗的研究进展

慢性鼻窦炎(CRS)是一种鼻腔鼻窦的慢性炎症性疾病,根据其发病机制可分为1型、2型和3型炎症内在型。目前CRS的药物治疗及手术治疗方法均存在发生各种不良反应和并发症的风险,其中部分难治性鼻窦炎虽经适当的药物和手术治疗仍不能取得满意效果并极易复发,严重影响患者的生活质量。生物靶向药物的应用和发展为CRS的治疗提供了一种有效和安全的替代方案。本文着重介绍针对CRS三种炎症内在型的相关细胞因子(包括TNF-α、IL-4、IL-5、IL-13、IgE和IL-17等)的生物靶向药物治疗的研究进展。     

慢性鼻窦炎发病中离子通道作用研究进展

慢性鼻窦炎(CRS)是鼻科目前常见的慢性炎症性疾病,其病因及发病机制尚未完全明确。离子通道参与稳定细胞膜电位、维持细胞液体平衡和调节细胞间信号转导等多种生理活动。目前研究发现钙离子通道、钾离子通道、钠离子通道、氯离子通道及氢离子相关离子通道等与CRS发病密切相关。大量研究发现在CRS的鼻黏膜组织中离子通道表达异常,提示离子通道调控紊乱可能参与CRS的炎症免疫反应过程并导致CRS进一步加重。本文就离子通道在CRS发病中作用的研究进展进行综述,以期为下一步深入探索CRS发病机制及治疗方案提供新的思路。     

中性粒细胞和嗜酸性粒细胞在慢性鼻窦炎中的相互影响及临床治疗思考

慢性鼻窦炎(CRS)按其病理特征分为嗜酸性粒细胞(EOS)型和非嗜酸性粒细胞(nEOS)型,其中nEOS型中最常见的是中性粒细胞(neutrophil, NEU)浸润。EOS主导Th2型炎症,NEU浸润更多见于Th1和Th17型炎症。长期以来,认为NEU和EOS在CRS发病机制中可能处于相互排斥的对立关系。但近年研究发现,在临床症状最重的难治性CRS鼻黏膜或鼻息肉组织中,NEU和EOS浸润均明显增多,并且相互影响。通过文献复习,对CRS中NEU和EOS混合性炎症及两者之间相互影响的研究进展进行综述,并就临床治疗对策进行讨论。     

南京市儿童鼻-鼻窦炎性疾病与支气管哮喘相关性流行病学调查

目的:了解儿童鼻-鼻窦炎性疾病与支气管哮喘相关性流行病学特征。方法:2004年3~9月,用“南京市儿童呼吸道疾病问卷调查表”,对随机选择的南京市7所小学3年级学生(9~10岁)进行问卷调查。根据诊断标准对问卷中有相关症状者,由专科医师进行集中检查,结果进行统计学处理。结果:共发放问卷调查表1087份,回收989份,应答率91%,有效答卷942份。9~10岁儿童慢性鼻-鼻窦炎(慢性鼻-鼻窦炎组)发病率为8.8%,其中男9.1%,女8.5%;变应性鼻炎(变应性鼻炎组)发病率为5.1%,其中男5.6%,女4.6%,两者发病率与性别差异无统计学意义(P>0.05)。支气管哮喘总发病率为5.3%,其中男6.8%,女3.7%,男、女发病率差异有统计学意义(χ2=4.518,P<0.05)。慢性鼻-鼻窦炎并发支气管哮喘发病率为19.3%,变应性鼻炎并发支气管哮喘发病率为39.6%,均较无鼻疾病者(无鼻病组)的发病率(1.8%)高,支气管哮喘在慢性鼻-鼻窦炎和变应性鼻炎组中发病率明显升高,均差异有统计学意义(均P<0.01)。结论:支气管哮喘在鼻-鼻窦炎性疾病儿童中的发病率明显升高。     

慢性鼻-鼻窦炎变应原特征初步探讨

目的　探讨变应原在慢性鼻-鼻窦炎（CRS）伴或不伴鼻息肉患者中的分布特点及临床意义。方法　回顾性分析CRS患者136例,比较伴鼻息肉组及不伴息肉组患者的变应原特征。以变应性鼻炎（AR）患者36例为对照组,分析CRS与AR变应原的差异。结果　CRS患者变应原总阳性率为48.5%,其两种亚型在变应原阳性率、吸入性和食物变应原分布比例、各类变应原分布比例、单一和多种变应原分布比例均无显著性差异（P >0.05）。CRS致敏原主要为单纯吸入性变应原（84.8%）,食物变应原致敏者较少（9.1%）,少数为吸入物和食物混合型变应原（6.1%）。与AR相比,CRS的吸入性和食物变应原分布比例（χ2=14.801,P =0.001）、变应原亚类（χ2=12.951,P =0.005）以及单一或多种变应原（χ2=9.067,P =0.003）方面均有显著性差异。结论　CRS患者变应原阳性率远高于过敏性疾病的普通人群患病率,提示变应性因素可能与CRS的发病有着密切的相关性。CRS伴有或不伴有息肉,其变应原的临床特征相似,但与AR的变应原特征有显著性差异。变应原的检测可能对CRS的预防和治疗有一定的指导意义。     

YKL-40与慢性鼻-鼻窦炎组织重构的相关性探讨

YKL-40是哺乳类动物类几丁质酶蛋白家族的一员。近年来的多项研究则进一步表明YKL-40在哮喘、关节炎等多种炎性疾病中表达升高,并在疾病的组织重塑中发挥了重要作用。慢性鼻-鼻窦炎(CRS)是鼻-鼻窦黏膜的持续性炎症,主要表现为鼻塞、黏性分泌物、鼻黏膜充血和后鼻滴漏,次要表现为面部压迫感和头痛。CRS的发病机制十分复杂,目前已知炎性反应和组织重构在病理进程中发挥重要作用。在CRS临床分型、诊断和治疗等诸多方面尚存在争议,目前临床上主要依靠鼻内镜检查及CT扫描进行分型诊断,缺乏能在病理生理机制及分子细胞水平深入反映疾病特征的标志物。结合文献探讨YKL-40与慢性鼻窦炎组织重构和炎性反应的相关性以及作为血清标志物的可能性。     

Micro-RNA在变应性鼻炎中的作用及其研究进展

变应性鼻炎(AR)是发生在鼻黏膜的变态反应性疾病，其特征是与血清IgE水平升高相关的辅助型T细胞2(Th2)主导的免疫反应。它不同程度影响个人社会生活、睡眠和工作，并可增加家庭和社会经济负担。目前AR的治疗在免疫疗法、鼻内类固醇、抗组胺药和肥大细胞稳定剂等方面取得了有效进展，但20%的AR患者并未表现出足够的主观和客观改善。因此，深入研究AR的发病机制，并开发用于治疗AR的新型制剂已是当务之急。Micro-RNA(miRNA)是一种基因表达调控小分子RNA,被认为与许多炎症性疾病有关，已经逐渐成为国内外学者研究的重点。本文系统综述了与AR密切相关的miRNA,并对研究现状做了简要评析，指出了当前亟待深入研究的问题，希望能对该领域的发展提供一定的参考。     

Tim-3在变应性鼻炎中的作用及机制研究进展

变应性鼻炎(AR)是一种慢性非特异性鼻黏膜炎性病变,属于Ⅰ型变态反应,是一个全球性健康问题,可导致许多疾病和劳动力丧失,给社会带来的负担也越来越重。其发病过程中所包括的免疫细胞受到了不同的基因组的调控作用。现已有研究论证T细胞免疫球蛋白黏蛋白结构域分子-3(Tim-3)参与到免疫细胞的表达中,对很多免疫反应都有调节作用,与免疫系统疾病密切相关。目前针对变应性鼻炎的药物及治疗方法存在一定的局限性,因此找到更多有效的治疗方法刻不容缓。关于Tim-3在变应性鼻炎中的作用机制的相关研究很多,但其综述却是匮乏的,希望该文章,希望能丰富AR的免疫调控机制研究,并且为其治疗方法提供新的思路。     

Acoustic rhinometry in persons recruited from the general population and diagnosed with chronic rhinosinusitis according to EPOS

Chronic rhinosinusitis (CRS) is a disease related to the nose and the paranasal sinus as defined by the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria. The criteria include subjective symptoms, such as nasal obstruction, and objective findings by endoscopy. Acoustic rhinometry (AR) is an objective method to determine nasal cavity geometry. The technique is based on a sound pulse reflection analysis in the nasal cavity and determines cross-sectional areas as a function of distance as well as volume. AR measurements in persons recruited from the general population, with and without CRS based on the clinical EPOS criteria, were investigated. As part of a trans-European study, 362 persons, comprising 91 persons with CRS and 271 persons without CRS, were examined by an otolaryngologist including rhinoscopy. Minimum cross-sectional area, distance to minimum cross-sectional area, and volume in the nasal cavity were measured by acoustic rhinometry and all participants underwent Peak Nasal Inspiratory Flow (PNIF) and allergy test. A difference in AR was found before and after decongestion, but no difference was seen between CRS patients and controls. Positive correlation between AR and PNIF was found and AR was capable of identifying mucosal oedema and septum deviation visualised by rhinoscopy. In conclusion, AR, as a single instrument, was not capable of discriminating persons with CRS from persons without CRS in the general population. However, AR correlates well with PNIF and was capable of identifying septum deviation and mucosal oedema.     

Zellzahl und Entzündungsparameter im peripheren Blut bei chronischer Rhinosinusitis

Objective

The aim of this study was to verify whether the following peripheral blood cell count and inflammation-based markers differ between various types of chronic rhinosinusitis (CRS): neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR), as well as erythrocyte sedimentation rate (ESR) and C?reactive protein (CRP) levels.

Materials and methods

In all, 386 patients had complete peripheral blood count, ESR, CRP and nasal cytology. The severity of CRS symptoms was assessed using three-stage Lund–Mackay computed tomography (CT) scores. The participants were stratified based on the results of nasal cytology and by the presence of nasal polyps (NP). The inflammation-based markers were calculated by dividing the cell numbers of the different cell types by numbers of the other cell types.

Results and conclusions

Blood leukocyte and neutrophil counts were higher in neutrophilic CRS. Differences between patients with CRS with nasal polyps (NP) and CRS without NP were significant for blood leukocytes, neutrophils, monocytes, eosinophils, CRP, NLR and MLR values. In CRS with NP, peripheral blood leukocyte, neutrophil, monocyte and eosinophil counts, as well as CRP, NLR and MLR values were higher than in CRS without NP. Our results show that all individuals with CRS could benefit from the analysis of blood counts and inflammation-based markers at the beginning of their evaluation. High levels of inflammation-based markers might guide the clinician towards planning more radical CRS therapy and use of systemic anti-inflammatory medication.

     

质金属蛋白酶及抑制剂影响细胞外基质代谢参与慢性鼻-鼻窦炎组织重塑的机制研究

目的组织重塑是慢性鼻 鼻窦炎（CRS）发病机制的主要因素,细胞外基质(ECM)生成与降解紊乱是组织重塑的重要特征。在两种不同表型CRS伴息肉（CRSwNP）和不伴息肉（CRSsNP）中,组织重塑所涉及的病理生理机制并不相同。基质金属蛋白酶（MMPs）可降解ECM大部分成分,其与内源性组织金属蛋白酶抑制剂（TIMPs）的平衡是ECM代谢的主要决定因素,二者的比例失衡将通过影响ECM代谢参与CRS组织重塑过程,促进CRS疾病进展,为CRS预后评估及药物治疗靶点提供理论基础。     

Prevalence of and associations with allergic rhinitis in children with chronic rhinosinusitis

Objectives

Chronic rhinosinusitis (CRS) in children has been associated with a variety of disorders including atopic disease, cystic fibrosis, immunologic disorders and ciliary dyskinesia. Although a strong association, or even cause and effect relationship, between allergic rhinitis (AR) and CRS is commonly assumed, the epidemiologic relationship between these disorders has not yet been defined in children.

Methods

A retrospective review of all children diagnosed with CRS on otolaryngology or allergy office evaluation at a large tertiary-care pediatric hospital over a ten-year period was performed. Demographic data and concomitant diagnoses of AR, cystic fibrosis, immunologic disorders and primary ciliary dyskinesia were analyzed for relationships with CRS.

Results

A total of 4044 children with an average age of 8.9 years and a slight male predominance (53.8%) with CRS were identified. Of these children, 0.2% had primary ciliary dyskinesia, 4.1% had cystic fibrosis, 12.3% had an immunologic disorder, and 26.9% had AR. A concomitant asthma diagnosis was positively associated with a diagnosis of AR (OR = 6.24, 95% CI: 5.27–7.39, P < 0.001), whereas a concomitant cystic fibrosis diagnosis was negatively associated (OR = 0.12, 95% CI: 0.06–0.26, P < 0.001).

Conclusions

AR is more prevalent than the other comorbidities combined in children with CRS, and is independently associated with the presence of asthma. Formal allergy testing, guided by clinical history and regional allergen sensitivity prevalence, should be strongly considered in all children with CRS, in particular those with reactive airway disease.