金黄色葡萄球菌超抗原与慢性鼻窦炎伴鼻息肉发病的荟萃分析

目的：慢性鼻窦炎伴鼻息肉是全球健康问题,因其易复发且症状较重,而严重影响患者生存质量。细菌超抗原学说有可能解释其发病机制。本荟萃分析旨在研究金葡菌超抗原与慢性鼻窦炎伴鼻息肉发病的关系。方法计算机检索Pubmed、MEDLINE、EMBASE、中国知网、万方数据库、CBM和VIP中关于金葡菌超抗原与慢性鼻窦炎伴鼻息肉的病例对照研究,时限为从建库到2013年1月。对纳入研究的质量进行严格评价与提取资料,对符合标准的文献进行荟萃分析。统计学分析应用RevMan 5.0软件和和GRADEprofiler 3.2.2软件。结果共纳入12篇病例对照研究。荟萃分析结果显示：病例组与对照组的鼻腔金葡菌培养阳性率[OR=5.16,95%CI（2.44,10.90）,P〈0.0001]、金葡菌超抗原阳性率[OR=11.79,95%CI（3.69,37.63）,P〈0.0001]、特异性IgE阳性率[OR=12.67,95%CI （5.08,31.61）,P〈0.00001]的差异均有统计学意义。病例组中金葡菌超抗原或抗体阳性组与阴性组嗜酸性粒细胞计数相比较,其差异没有统计学意义[WMD=36.75,95%CI（-8.09,81.60）,P=0.11]。结论金葡菌超抗原与慢性鼻窦炎伴鼻息肉具有相关性,金葡菌超抗原可能是慢性鼻窦炎伴鼻息肉发病的危险因素。     

鼻息肉组织中抗金黄色葡萄球菌肠毒素IgE的检测及超抗原学说分析

目的寻找鼻息肉组织中金黄色葡萄球菌(简称金葡菌)肠毒素发挥超抗原作用的证据,为鼻息肉发病的超抗原假说提供佐证。方法在42例主要由不伴哮喘的鼻息肉、慢性鼻-鼻窦炎患者和对照组构成的人群中,运用UniCAP系统检测鼻黏膜组织中抗金葡菌肠毒素(staphylococcusaureusenterotoxins,SE)A和B的特异性IgE(SIgE)、总IgE、嗜酸粒细胞阳离子蛋白(eosinophiliccationicprotein,ECP);以及外周血中总IgE和抗SEA和SEB的SIgE(仅在8例中)。同时对中鼻道分泌物进行需氧菌培养。结果在所有组织样本中(42例)和部分(8例)患者的血清样本中,没有明确证据支持抗SEA和SEB的SIgE存在。组织中的总IgE(以每2mg组织蛋白中的含量表示)范围为4·59~70·21kIU,平均(x-±s,17·85±14·31)kIU;血清中总IgE为7·44~344·00kIU/L,平均(88·65±80·03)kIU/L。金葡菌培养阳性3例(鼻息肉1例,单纯鼻-鼻窦炎2例)。在鼻息肉组、慢性鼻-鼻窦炎组和对照组之间,SIgE的荧光值、总IgE、ECP值差异均无统计学意义(P值均>0·05)。结论在不伴持续性哮喘的鼻息肉患者中,没有发现金葡菌超抗原作用的证据,提示对超抗原假说仍需要大量的临床调查和研究来论证。     

鼻窦炎口服液对鼻黏膜中嗜酸粒细胞作用的超微结构研究

目的：探讨鼻窦炎口服液对鼻息肉组织中及鼻腔术后黏膜下嗜酸粒细胞超微结构的影响。方法：12例鼻息肉患者术后分成3组,分别用生理盐水、地塞米松和鼻窦炎口服液冲洗鼻腔,每日2次,连续冲洗4周。鼻息肉组织在鼻窦炎口服液和地塞米松培养液中进行体外细胞培养,7d后取出制备成电镜切片。结果：应用鼻窦炎口服液和地塞米松者,电镜均发现嗜酸粒细胞的超微结构发生退行性变。结论：鼻窦炎口服液对鼻腔黏膜下嗜酸粒细胞有抑制作用。     

糖皮质激素短疗程雾化吸入对嗜酸粒细胞性鼻窦炎伴鼻息肉患者鼻部症状及肾上腺皮质功能的影响

目的 探讨糖皮质激素短疗程雾化吸入对嗜酸粒细胞性鼻窦炎伴鼻息肉患者鼻部症状及肾上腺皮质功能的影响。 方法 将嗜酸粒细胞性慢性鼻窦炎伴鼻息肉患者40例,以随机数字表法分为对照组(20例)和观察组(20例),分别给予糖皮质激素短疗程喷鼻和雾化吸入方案治疗。比较两组患者近期疗效,治疗前后鼻部症状VAS评分,内镜Lund-Kennedy评分,嗜酸性粒细胞绝对值(EOS)计数水平、血清皮质醇水平及随访复发率等。 结果 观察组患者治疗显效率和总有效率均高于对照组(P<0.05);观察组患者治疗后鼻部症状VAS评分和内镜Lund-Kennedy评分均低于对照组及本组治疗前(P<0.05);观察组患者随访3个月和6个月复发率均低于对照组(P<0.05);观察组患者治疗后EOS计数水平均低于对照组及本组治疗前(P<0.05);同时两组患者治疗前后血清皮质醇水平比较差异无统计学意义(P>0.05)。 结论 相较于喷鼻方案,糖皮质激素短疗程雾化吸入方案治疗嗜酸粒细胞性鼻窦炎伴鼻息肉可有效缓解鼻部症状体征,抑制嗜酸性粒细胞聚集,降低远期复发风险,且未对肾上腺皮质功能产生明显影响。     

变应性鼻炎患者鼻分泌物中嗜酸粒细胞计数与鼻用糖皮质激素治疗反应的关系

目的 观察常年性持续性变应性鼻炎(allergic rhinitis,AR)患者不同炎症类型(嗜酸粒细胞炎症型与非嗜酸粒细胞炎症型)对鼻用糖皮质激素治疗的反应性.方法 选择近3个月内未接受糖皮质激素治疗的常年性持续性AR患者42例,根据鼻分泌物嗜酸粒细胞计数将患者分为嗜酸粒细胞组(A组,嗜酸粒细胞数≥0.03,23例)与非嗜酸粒细胞组(B组,嗜酸粒细胞数<0.03,19例)进行AR症状、体征评分和鼻分泌物细胞分类计数.采用酶联免疫荧光法测定鼻分泌物嗜酸粒细胞阳离子蛋白浓度.糖皮质激素治疗2、4、6个月时进行随访,并进行疗效评价.结果 A组鼻分泌物中嗜酸粒细胞数[中位数M(25分位数;75分位数),下同]、嗜酸粒细胞阳离子蛋白水平(x±s,下同)基线值分别为0.086[0.065;0.176]、(326±145)μg/L,B组分别为0.016[0.005;0.022]、(154±58)μg/L,两组比较差异有统计学意义(t值分别为4.40、3.33,P值均<0.01).鼻用糖皮质激素治疗2、6个月后,A组嗜酸粒细胞数,嗜酸粒细胞阳离子蛋白水平分别为0.038[0.006;0.070]、0.019[0.010;0.060]、(175±122)μg/L、(175±153)μg/L,与基线值比较差异均有统计学意义(F值分别为6.73、7.38,P值均<0.05);B组分别为0.014[0.004;0.032]、0.015[0.000;0.026]、(118±60)μg/L、(112±60)μg/L,与基线值比较,嗜酸粒细胞数差异无统计学意义(F=0.82,P>0.05),而嗜酸粒细胞阳离子蛋白水平差异有统计学意义(F=3.78,P<0.05).A组平均症状、体征评分与B组在基线及2,4、6个月时不同时间点比较差异均无统计学意义.鼻用糖皮质激素用量,两组各时间点比较差异均无统计学意义(P值均>0.05).结论 对于鼻分泌物嗜酸粒细胞数增高的AR患者,鼻用糖皮质激素能够抑制嗜酸粒细胞性炎症,改善AR患者的症状和体征.非嗜酸粒细胞数增高的AR患者对糖皮质激素治疗反应性差.     

慢性鼻窦炎患者血清IgG4测定的临床意义

目的探讨慢性鼻窦炎患者血清中IgG4含量的临床意义.方法采用双抗体夹心ELISA法检测79例慢性鼻窦炎患者、40例健康成人血清免疫球蛋白G4(IgG4)水平,同时对患者组和对照组作鼻分泌物嗜酸性粒细胞瑞氏染色计数和吸入物变应原皮肤试验.结果慢性鼻窦炎患者血清IgG4水平为对照组的2.09倍,差异经统计学处理有显著性意义(P＜0.01,t=5.745).患者组鼻分泌物嗜酸性粒细胞阳性率为44.3%,吸入物变应原皮肤试验阳性率为494%,明显高于对照组.结论慢性鼻窦炎反复发作往往有变应性因素参与.慢性鼻窦炎的发病是在一般炎症的基础上引起变态反应,而变态反应的发生又加重了炎症.     

EOS与COX-2在阿司匹林三联征患者鼻息肉组织中的表达及意义

目的:探讨嗜酸粒细胞(EOS)的聚集和COX-2在阿司匹林三联征(ST)发病过程中的调控作用。方法:取94例鼻内镜手术患者鼻息肉组织,其中ST患者34例(ST组),慢性鼻窦炎鼻息肉伴哮喘患者30例(ATA组),慢性鼻窦炎鼻息肉患者30例(对照组),应用苏木精-伊红染色及免疫组织化学SP法检测EOS的分布及COX-2的表达,并经统计学分析EOS、COX-2的表达和分布与临床病理和发病机制的关联。结果:EOS在3组患者鼻息肉组织中均大量浸润,EOS计数均数分别为80.02±6.11、76.62±5.22、65.97±4.78,ST组、ATA组分别与对照组比较差异均有统计学意义(均P<0.05),而ST组与ATA组比较差异无统计学意义(P>0.05)。COX-2在鼻息肉组织中主要表达于黏膜下腺体、腺上皮细胞、上皮细胞、血管内皮细胞及间质中的EOS,阳性细胞计数分别为88.13±6.26、89.46±5.97、91.22±4.11,ST组与对照组表达差异有统计学意义(P<0.05);ATA组表达与对照组比较差异无统计学意义(P>0.05);ST组与ATA组比较差异无统计学意义(P>0.05)。结论:EOS浸润程度不同可能是ST患者接触非甾体抗炎药后发生特有临床表现的炎症基础,COX-2在ST患者息肉组织中表达的差异可能与花生四烯酸代谢途径的转换及鼻息肉的形成有关。     

黏附分子-1对鼻息肉中嗜酸性粒细胞聚集及临床预后的意义

目的 :探讨黏附分子 1(ICAM 1)在鼻息肉中的表达及对嗜酸性粒细胞聚集和临床预后的意义。方法 :采用荧光免疫组织化学法检测 35例慢性鼻窦炎、鼻息肉患者 (鼻息肉组 )的鼻息肉组织及 15例慢性鼻炎患者 (对照组 )的下鼻甲黏膜中ICAM 1的表达并进行定量分析。结果 :鼻息肉组和对照组嗜酸性粒细胞平均计数分别为 (2 8.4± 10 .7)个 /mm2 和 (9.9± 8.6 )个 /mm2 ,ICAM 1相对荧光强度为 115 .9± 82 .4和 2 8.2± 17.1,随鼻息肉严重程度的加重 ,ICAM 1的表达强度逐渐增高。结论 :ICAM 1对鼻息肉中嗜酸性粒细胞的聚集及鼻息肉的预后具有重要的意义 ,抗感染和抗变态反应在鼻息肉的治疗上具有同等的地位     

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。     

The role of superantigens in chronic rhinosinusitis with nasal polyps

Recent reports suggest that staphylococcal exotoxins, acting as superantigens, activate T cells with subsequent massive proliferation, thereby contributing to the etiology of chronic rhinosinusitis with nasal polyps (CRSwNP). The objectives of this study are (1) to demonstrate directly the presence of staphylococcal exotoxins in nasal mucosa and sinonasal polyp tissue, and (2) provide indirect evidence of the effect of superantigens on the T cells expressing the target of superantigen, i.e., the beta variable chain receptor (TCRBV) in polyp tissue and peripheral blood of patients with CRSwNP. Sinonasal polyp tissue and peripheral blood specimens were obtained from 37 patients with chronic rhinosinusitis (22 patients with bilateral nasal polyps, 15 without nasal polyps) and 12 normal subjects for comparative negative controls. Tissue specimens were assayed by enzyme-linked immunosorbent assay (ELISA) for the most common staphylococcal exotoxins (A-D) and toxic shock syndrome toxin type 1. Fresh tissue and blood samples were analyzed by flow cytometry to determine the expression of TCRBV. In the CRSwNP subjects 12 of 22 samples (54.54%) demonstrated reactivity for at least 1 staphylococcal exotoxin, while 2 of the 12 were positive for 2 toxins. There were no positive results in the CRS without nasal polyps or control groups. There was a clear trend of increased TCRBV expression in the ELISA-positive group both for tissue and blood specimens. Staphylococcal superantigens were present in the nasal cavity of patients with CRSwNP with a high percentage of TCRBV, which suggests the possibility of superantigens as etiological agents of CRSwNP.     

Superantigens and chronic rhinosinusitis: detection of staphylococcal exotoxins in nasal polyps

OBJECTIVE/HYPOTHESIS: The role of infectious agents in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unclear. Recent studies have provided indirect evidence of exposure to staphylococcal exotoxins in the blood and polyp tissue of patients with CRSwNP. These exotoxins have the capacity to act as superantigens, bypassing normal antigen processing and directly stimulating a massive inflammatory response. The objective of the study was to analyze mucus and polyp tissue samples from patients with CRSwNP for the presence of staphylococcal exotoxins. STUDY DESIGN: Prospective study. METHODS: Tissue and mucus samples were obtained from 42 patients undergoing endoscopic sinus surgery for chronic rhinosinusitis and 11 normal control patients. Twenty-nine of 42 patients had chronic rhinosinusitis with bilateral nasal polyposis, 2 had antrochoanal polyps, and 11 had chronic rhinosinusitis without nasal polyps. Eleven patients without chronic rhinosinusitis or polyps served as normal control patients. Specimens were analyzed for the presence of five staphylococcal exotoxins (SEA, SEB, SEC, SED, and toxic shock syndrome toxin type 1 [TSST-1]) using enzyme-linked immunosorbent assay (ELISA). Histological analysis of specimens and mean eosinophil counts were correlated with the presence of toxin. RESULTS: At least one toxin was detected in 14 of 29 patients with bilateral nasal polyposis. Nine of the 14 patients also had positive findings for additional toxins. The dominant histological pattern in the CRSwNP patient group was polypoid mucosa with edema, which was found in both ELISA-positive and ELISA-negative patients. Mean eosinophil counts tended to be higher in ELISA-positive patients with polyps compared with patients without toxin detection. No toxin was detected in the 11 specimens taken from normal control patients. Only 1 of the 13 patients with CRS without polyps had positive ELISA results for toxin. CONCLUSION: The current study demonstrates the presence of superantigen toxins in 14 of 29 patients with CRSwNP, with SEB and TSST-1 being the most common. Further studies are necessary to correlate the presence of toxin with the pathological changes present in polyp tissue.     

糖皮质激素受体α和β在慢性鼻-鼻窦炎鼻息肉中的表达

目的 探讨糖皮质激素受体(glucocorticoid receptor,GR)α和β在鼻-鼻窦炎鼻息肉发生发展中的表达情况.方法 采用免疫组化SP法和计算机图像分析系统,观察17例复发性鼻息肉和术后随访无鼻息肉复发的18例Ⅱ型、12例Ⅰ型慢性鼻-鼻窦炎患者鼻息肉或鼻窦黏膜组织中GRα和GR β的表达情况.结果 GRα阳性细胞数(-x±s)在复发组(20.2±6.9)、鼻息肉组(20.7±7.2)、鼻窦炎组(16.9±7.2)和对照组(16.1±5.3)中差异无统计学意义(P值均＞0.05).GR β在复发组(34.2±7.4)和鼻息肉组(31.5±5.9)中高表达,与鼻窦炎组(19.8±7.8)和对照组(10.1±6.7)比较差异有统计学意义(P值均＜O.05);复发组GR β阳性细胞数较鼻息肉组有增高趋势,但差异无统计学意义(P=0.558).GR β/GR α比值(-x±s)复发组(1.80±0.47)和鼻息肉组(1.65±0.49)与对照组(0.77±0.66)间差异有统计学意义(P值均＜0.05),与鼻窦炎组(1.23±0.27)差异无统计学意义(P值均＞0.05).结论 GR β在鼻息肉组织中高表达,可能是促进鼻息肉发生发展的一个重要因素.     

慢性鼻窦炎伴或不伴鼻息肉患者血清嗜酸粒细胞阳离子蛋白水平的比较

目的 比较慢性鼻窦炎伴有鼻息肉（CRSwNP）和不伴鼻息肉（CRSsNP）患者中血清嗜酸粒细胞阳离子蛋白（ECP）水平的差异。方法 采用ImmunoCAP100E系统,检测99例CRSwNP患者和59例CRSsNP患者的血清ECP水平,并与健康对照组84例比较。结果 三组间血清ECP水平的差异有统计学意义（P＜0.05）,其中CRSwNP组明显高于健康对照组（P＜0.01）,尤其是中-重度患者与健康对照组比较血清ECP水平显著升高（P＜0.01）。但CRSwNP组与CRSsNP组比较,差异无统计学意义（P＞0.05）;两组轻度与中-重度患者之间分别进行比较,差异均无统计学意义（P＞0.05）。结论 嗜酸粒细胞性炎症反应在慢性鼻窦炎伴或不伴鼻息肉的发病中可能均发挥了作用,但疾病的严重程度与炎性指标ECP的血清浓度之间未见明显相关性,有待进一步探讨。     

不伴有下气道疾病的慢性鼻-鼻窦炎患者肺功能及相关因素分析

目的 探讨不伴有下气道疾病的慢性鼻-鼻窦炎伴息肉患者的肺功能及其影响因素。 方法 选取161例慢性鼻-鼻窦炎伴鼻息肉患者(CRSwNP组),26例慢性鼻-鼻窦炎不伴鼻息肉患者(CRSsNP组)和34例正常人(对照组)进行肺功能检测,比较三组肺功能的各项指标,并分析CRSwNP组肺功能和临床各参数之间的关系,这些参数包括外周血嗜酸粒细胞数、血清特异性IgE、Lund-Mackay评分、呼出一氧化氮水平和视觉模拟量表评分(VAS)。 结果 CRSwNP组患者的肺功能指标FEV₁%pre低于正常组,差异有统计学意义(P=0.045);血清特异性IgE(sIgE)与VC%、FEV₁%pre、FEV₁/FVC呈负相关(P<0.05)。 结论 不伴下气道疾病的CRSwNP患者存在潜在的阻塞性肺功能改变;sIgE与CRSwNP的肺功能异常有关。     

Causes of higher symptomatic airway load in patients with chronic rhinosinusitis

Background

Chronic rhinosinusitis display a variety of different phenotypes. The symptoms of disease are characterised by various signs and symptoms such as nasal congestion, nasal discharge, pressure sensation in the face and reduced or complete loss of smell.In a patient population undergoing functional endoscopic sinonasal surgery (FESS) for chronic rhinosinusitis, we wanted to investigate the clinical features and explore if the presence of biofilm, nasal polyps or other disease characteristic could serve as predictor for the symptomatic load. A patient group undergoing septoplasty without disease of the sinuses was included as control.

Methods

The Sinonasal outcome test (SNOT-20), EPOS visual analogue scale (VAS) and the Lund-Mackey CT score (LM CT score) were used to examine 23 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), 30 patient with nasal polyps (CRSwNP) and 22 patients with septal deviation. Tissue samples were collected prospectively during surgery. The cohort has previously been examined for the presence of biofilm.

Results

Patients with CRSsNP and CRSwNP had significantly higher degree of symptoms compared to the septoplasty group (SNOT-20 scores of 39.8, 43.6 and 29.9, respectively, p?=?0.034). There were no significant differences in the total SNOT-20 or VAS symptoms scores between the CRSsNP and CRSwNP subgroups. However patients with nasal polyps showed significantly higher scores of symptoms related to sinonasal discomfort such as cough, runny nose and need to blow nose (p?=?0.011, p?=?0.046, p?=?0.001 respectively). Patients with nasal polyps showed a significantly higher LM CT score compared to patients without polyps (12.06 versus 8.00, p?=?0.001). The presence of biofilm did not impact the degree of symptoms.

Conclusion

The presence of nasal polyp formations in CRS patients was associated with a higher symptomatic airway load as compared to patients without polyps. These findings suggest that nasal polyps could be an indicator of more substantial sinonasal disease. The presence of biofilm did not impact the degree of symptoms, however, as biofilm seem to be a common feature of chronic rhinosinusitis (89% in this cohort), it is more likely to be involved in the development of the CRS, rather than being a surrogate marker for increased symptomatic load.