诱导型一氧化氮合酶在变应性真菌性鼻-鼻窦炎黏膜中的表达

目的 :通过对变应性真菌性鼻 鼻窦炎窦腔病变黏膜 (AFRS)和慢性鼻窦炎 (CRS)病变黏膜中诱导型一氧化氮合酶 (iNOS)的定位和半定量研究 ,探讨AFRS和CRS发病机制的差异 ,一氧化氮 (NO)的生成情况和意义。方法 :用免疫组化 (S P法 )的方法对 2 8例AFRS和 6例CRS标本中iNOS进行定位和半定量检测。并且用Ridit分析进行统计分析。结果 :iNOS广泛存在于上皮组织、血管内皮、平滑肌细胞、黏膜下浆液性腺体和炎症细胞中 ,以细颗粒或粗颗粒存在于细胞质中 ,细胞膜上偶见。细胞核及间质细胞内无iNOS表达。AFRS黏膜与CRS黏膜之间的表达差异有显著性意义 (P <0 .0 1)。结论 :iNOS在AFRS窦腔黏膜中呈大量表达 ,iNOS对AFRS发病起重要作用 ;AFRS与CRS可能是不同的两个疾病     

The role of interleukin-16 in eosinophilic chronic rhinosinusitis

Eosinophilic granulocytes (Eos) are found in great numbers both in the tissue and in the mucus of patients suffering from chronic rhinosinusitis with polyposis (ECRS). Interleukin-16 (IL-16) is known as a highly potent chemotactic and chemoattractant molecule (ED 10−11) for Eos. In an open, explorative, controlled study we examined the presence of IL-16 in mucosa tissue, mucus and serum in patients suffering from ECRS and its association to Eos activation. Tissue and nasal mucus specimen from 10 previously untreated, non allergic ECRS-patients undergoing paranasal sinus surgery and from 10 healthy non sinusitis subjects, undergoing nasal surgery because of anatomic nasal obstruction were investigated by real-time (RT-) PCR targeting human IL-16 mRNA. Haematoxylin-eosin (HE) staining and immunohistochemistry of formalin embedded tissue and mucus were applied for detection and determination of the proportion of activated Eos (aEos) and IL-16. Serum IL-16 was analyzed by enzyme-linked-immunosorbent assay (ELISA). IL-16 mRNA and IL-16 protein levels were elevated in nasal mucus, polyp tissue and in the serum of ECRS patients compared to healthy controls. There was a high proportion of aEos in ECRS patients compared to healthy subjects. Serum IL-16, IL-16 mRNA expression and IL-16 protein in mucus and tissue specimens were significantly associated with the presence of aEos in polyps of ECRS patients. Immunohistochemically IL-16 protein was mainly expressed in aEos, mast cells, lymphocytes and epithelial cells. In conclusion our data indicate that IL-16 may stimulate the migration and persistence of activated Eos in ECRS. IL-16 production in ECRS patients is not mediated by Immunglobuline-E (IgE). Andreas Lackner and Reinhard Raggam contributed equally to this article.     

Increased expression of pendrin in eosinophilic chronic rhinosinusitis with nasal polyps

IntroductionChronic rhinosinusitis with nasal polyps is a heterogeneous disease and appropriate diagnostic algorithms in individual cases are necessary for effective medical treatment.ObjectiveThe purpose of this study was to clarify the relationship between the pendrin expression of nasal polyps and clinical and pathological characteristic features of eosinophilic chronic rhinosinusitis.MethodsA total of 68 patients were classified into eosinophilic chronic rhinosinusitis or non-eosinophilic chronic rhinosinusitis groups according to the degree of eosinophilic infiltration into the nasal polyps. Clinical, hematological, and immunohistochemical analyses were performed and statistically compared between both groups.ResultsThirty-eight were classified into eosinophilic chronic rhinosinusitis and 30 into non-eosinophilic chronic rhinosinusitis groups. There were no significant differences in age distribution, sex ratio, prevalence of asthma, or any other complications between the groups. The mean Lund–Mackay score and the number of serum eosinophils was significantly higher in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. The pendrin expression was more frequently detected in the epithelial surface layer of nasal polyps in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. In addition, mucin 5AC was more widely expressed in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis.ConclusionIncreased expression of pendrin and mucin 5AC in the nasal polyps would be associated with development of eosinophilic chronic rhinosinusitis. This finding could allow the development of a novel therapeutic agent targeted specifically to patients with eosinophilic chronic rhinosinusitis.     

嗜酸性粒细胞型慢性鼻窦炎小鼠模型构建的研究进展

慢性鼻-鼻窦炎(CRS)是上呼吸道最常见的慢性炎症性疾病之一,其中嗜酸性粒细胞型慢性鼻窦炎(ECRS)具有较高的治疗抵抗率及复发率,目前其病因及发病机制尚不明确。ECRS动物模型的成功构建是研究该疾病病理机制和治疗方案的理想手段。小鼠是常用的建模动物,但目前基础研究中仍缺乏一种公认成熟稳定的ECRS小鼠模型,成为对该病发病机制解析、药物筛选、精准治疗、诊断预后的关键瓶颈。本文回顾目前常用的ECRS小鼠模型,对其建模原理、方法步骤、评价指标及模型应用作一综述,以期为ECRS小鼠模型的成功建立及相关实验研究提供方法和理论依据。     

鼻呼出一氧化氮对慢性鼻窦炎诊断的临床应用价值

目的 探讨鼻呼出一氧化氮(nNO)在慢性鼻窦炎(CRS)临床诊断中的应用价值。 方法 回顾性分析135例CRS患者及40例非CRS患者的临床资料,包括患者nNO水平的差异,nNO水平与年龄、BMI、外周血嗜酸性粒细胞计数及百分比、CT Lund-Mackay评分及E/M比值的相关性,通过Logistic回归及ROC曲线分析nNO在CRS中的诊断应用价值。 结果 CRS组、CRSsNP组及CRSwNP组的nNO水平显著低于非CRS组(P<0.001),CRSwNP组的nNO水平显著低于CRSsNP组(P<0.001);eCRSwNP组及non-eCRSwNP组患者的nNO水平显著低于非CRS组患者(P<0.001),eCRSwNP组的nNO水平显著低于non-eCRSwNP组患者(P<0.05)。CRS组和CRSwNP组nNO水平均与E/M比值及Lund-Mackay评分呈显著负相关性(r=-0.423, P<0.001;r=-0.650, P<0.001;r=-0.434, P<0.001;r=-0.608, P<0.001)。Logistic回归分析发现nNO水平与CRS分型显著相关(P<0.01)。nNO对鉴别非CRS与CRS、CRSsNP及CRSwNP具有中度预测价值(AUC=0.849,P<0.001;AUC=0.771,P<0.001;AUC=0.894,P<0.001),对鉴别CRSsNP与CRSwNP具有中度预测价值(AUC=0.776,P<0.01)。对鉴别非CRS与non-eCRSwNP具有中度预测价值(AUC=0.861,P<0.001),eCRSwNP具有高度预测价值(AUC=0.910,P<0.001)。 结论 nNO水平对CRS、CRSsNP和CRSwNP、eCRSwNP和non-eCRSwNP的初步诊断以及鼻息肉病变范围的预测具有一定的临床应用价值。     

白细胞介素13在嗜酸粒细胞性慢性鼻-鼻窦炎合并鼻息肉组织中的表达及其与黏蛋白高分泌的相关性研究

目的 明确白细胞介素13(IL-13)在嗜酸粒细胞性慢性鼻-鼻窦炎(eosinophilic chronic rhinosinusitis with nasal polyps,EOS-CRSwNP)中的表达,探讨在EOS-CRSwNP中IL-13和黏蛋白5AC(mucin 5AC,MUC5AC)的相关性.方法 利用免疫组化和ELISA方法观察和测量MUC5AC在对照组鼻黏膜组织和EOS-CRSwNP组织的表达,ELISA法检测IL-13在对照组鼻黏膜组织和EOS-CRSwNP组织的表达;双变量相关性分析研究EOS-CRSwNP中IL-13和MUC5AC的相关性.IL-13与原代培养鼻黏膜上皮细胞共孵育,ELISA检测细胞上清中MUC5AC的表达.结果 免疫组化染色见MUC5AC主要表达在鼻黏膜上皮,通过ELISA检测,EOS-CRSwNP中MUC5AC和IL-13均较对照组显著升高.双变量相关性分析表明在EOS-CRSwNP中MUC5AC与IL-13存在高度相关,进一步通过IL-13与气液界面原代培养人鼻黏膜上皮细胞共孵育,MUC5AC分泌显著增加.结论 MUC5AC和IL-13在EOS-CRSwNP中表达升高,MUC5AC的高分泌与IL-13高表达密切相关.     

慢性鼻窦炎伴鼻息肉患者组织嗜酸性粒细胞与血清特异性IgE的相关性

目的 分析慢性鼻窦炎伴鼻息肉(CRSwNP)患者组织嗜酸性粒细胞与血清特异性免疫球蛋白E(sIgE)的关系及其临床特征。方法 选取2019年6月—2021年6月行功能性鼻窦内镜手术的192例CRSwNP患者,根据血清sIgE检测结果分为sIgE阳性组和sIgE阴性组,比较两组患者组织嗜酸性粒细胞计数、术前VAS评分、Lund-Mackay评分及Lund-Kennedy评分。结果 两组在性别、年龄比较无统计学意义(P>0.05);sIgE阳性与否和嗜酸性粒细胞是否浸润在例数上比较差异无统计学意义(P>0.05);在临床学特征方面,sIgE阳性嗜酸性粒细胞浸润组和其他3组比较在术前VAS评分(P<0.05),Lund-Mackay评分及Lund-Kennedy评分差异具有统计学意义(P<0.05)。结论 CRSwNP患者组织嗜酸性粒细胞浸润程度与过敏反应关系并不确定。患者嗜酸性粒细胞浸润同时合并sIgE阳性主客观症状加重。     

慢性鼻窦炎鼻息肉伴发嗅觉障碍病人iNOS在嗅粘膜中的表达

目的 探讨诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)在慢性鼻窦炎鼻息肉嗅觉障碍发病过程中的作用。方法 30例慢性鼻窦炎嗅觉障碍病人经临床分型分期,行嗅觉功能检查后,取嗅粘膜标本,行iNOS的免疫组化染色,光镜观察。结果 慢性鼻窦炎鼻息肉2型2,3期和3型的嗅粘膜中iNOS的表达显著高于1型和2型1期(P<0.05)。并与嗅觉障碍的严重程度呈正相关。结论 iNOS可能参与了慢性鼻窦炎所致嗅觉障碍的嗅觉损害过程,损害程度与慢性耳窦炎鼻息肉的临床分型分期有关。     

鼻息肉中一氧化氮合酶表达及其意义

目的 :了解鼻息肉 (NP)中一氧化氮合酶 (NOS)的分布特点和活性及其在NP发病中的作用。方法 :用免疫组织化学法检测 30例NP(NP组 )及 2 0例正常鼻黏膜 (正常鼻黏膜组 )中NOS的表达 ,并用分光光度计法检测其活性。结果 :NP组NOS活性为 (4.0 79± 0 .6 5 5 )U/mg蛋白 ,正常鼻黏膜组为 (1.5 2 6± 0 .310 )U/mg蛋白 ,二者间差异有统计学意义 (P <0 .0 1) ;NP组iNOS有大量细胞表达 ,分布在黏膜上皮、腺体和血管内皮细胞以及炎症细胞中 ,与正常鼻黏膜组比较 ,差异有统计学意义 (P <0 .0 1) ;而eNOS也有表达 ,但与正常鼻黏膜组比较 ,差异无统计学意义 ;NP组i NOS表达明显高于eNOS表达 ,其差异有统计学意义 (P <0 .0 1)。结论 :NP主要表达iNOS ,分布在黏膜上皮、腺体和血管内皮细胞以及炎症细胞中 ,其产生的大量一氧化氮在NP的发病过程中可能起着重要的作用     

健康成人口鼻呼出气一氧化氮含量测定及其影响因素分析

目的 呼出气中一氧化氮(nitric oxide,NO)含量是反映上下气道炎性反应程度的指标,为此测定健康成人经口和经鼻呼出气中NO含量,得到相应的参考值并分析其影响因素.方法 健康成人80名(男20名,女60名),年龄18～44岁,中位数年龄25岁.采用耐尔斯(NIOX)呼出气NO测定系统,分别测定口呼出气和鼻呼出气中NO含量,进而采用多元线性回归分析法,研究性别、年龄、身高、体质量指数(body mass index,BMI)、测量时间和环境NO含量对检测结果的影响.结果 ①健康成人121呼出气NO含量为(17±8)×10-9[95%可信区间:(0.3～33)×10-9];鼻呼出气NO含量为(819±211)×10-9[95%可信区间:(400～1238)×10-9].②口呼出气NO含量与受试者身高呈正相关,回归方程:Y(口呼出气NO含量)=-58.524+0.457X(身高,cm),t=-2.985,P<0.01.受试者的年龄、性别、BMI、测量时间和环境NO含量对口呼出气NO含量无显著影响.③健康成人鼻呼出气NO含量与年龄呈正相关,与性别呈负相关,回归方程:Y(鼻呼出气NO含量)=760.245+9.417X,(年龄)-111.222X2(性别),t=5.188,P<0.01.患者鼻腔左右侧别、身高和BMI、测量时间和环境NO含量对鼻呼出气NO含量无显著影响.结论 口、鼻呼出气中NO含量测定操作简便、灵敏度较高,是一种非侵袭性的临床检测手段,正常参考值可受到受试者性别、身高和年龄等因素的影响.     

New clinical diagnostic criteria for eosinophilic chronic rhinosinusitis

Objective

Chronic rhinosinusitis is a heterogeneous disease. Most cases of chronic rhinosinusitis with nasal polyp(s) (CRSwNP) in Western countries show a strong tendency for recurrence after surgery and pronounced eosinophil infiltration in the nasal polyps. The prevalence of CRSwNP with pronounced eosinophilic inflammation is steadily increasing and is classified as eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, less than 50% of CRSwNP patients in Japan and East Asia show such features. Since the treatment strategy of ECRS differs from that of non-ECRS, clinical diagnostic criteria that distinguish ECRS from non-ECRS are needed.

Methods

A total of 124 patients with CRSwNP patients who underwent endonasal sinus surgery were classified as ECRS or non-ECRS according to their clinical characteristics and the clinical features of the two groups were compared. Computed tomography (CT) images of the sinuses were graded according to the Lund-Mackay system. We also graded CT images of the olfactory cleft. Blood examination findings, sinus CT images and asthma complications were analyzed by multivariate logistic regression. Clinical findings that were significantly different between ECRS and non-ECRS were analyzed by receiver operating characteristic curves to determine optimal predictors of ECRS.

Results

Blood eosinophilia, asthma complications and CT image scores were significantly different between ECRS and non-ECRS. In particular, increased blood eosinophil percentage and CT image scores for the posterior ethmoid and the olfactory cleft showed good accuracy as predictors of ECRS. A combination of the cut-off values for three predictors (increased blood eosinophil percentage above the normal range, olfactory cleft score ≥1 and posterior ethmoid score ≥1) indicated high accurate diagnostic ability (sensitivity, 84.6%; specificity, 92.3%).

Conclusion

A set of three clinical findings can differentiate ECRS from non-ECRS with high accuracy, even when these findings are assessed in regular outpatient clinics.     

患者术前临床特征对嗜酸性粒细胞型慢性鼻窦炎伴鼻息肉的预测价值

目的 探讨患者的术前临床特征对嗜酸性粒细胞型慢性鼻窦炎伴鼻息肉(ECRSwNP)的预测价值,并构建用于临床实践的诺模图。方法 选取2019年9月—2020年9月就诊于新乡医学院第一附属医院并行功能性鼻内镜手术治疗的慢性鼻窦炎伴鼻息肉(CRSwNP)患者97例,根据术后病理结果嗜酸性粒细胞(EOS)浸润程度将其分为ECRSwNP组和非嗜酸性粒细胞型慢性鼻窦炎伴鼻息肉(nonECRSwNP)组,收集并比较两组患者的临床特征资料,采用单因素及多因素二元Logistic回归分析筛选对ECRSwNP有预测价值的术前特征资料,并构建用于临床实践的诺模图。采用SPSS 26.0和R语言软件4.1.2对数据进行分析。结果 两组患者在是否合并哮喘史、外周血嗜酸性粒细胞(EOS)计数、外周血嗜碱性粒细胞(Baso)计数、日本难治性嗜酸性慢性鼻窦炎流行病学调查(JESREC)评分、上颌窦评分、前后组筛窦评分、CT总分、E/M(筛窦与上颌窦的Lund-Mackay评分比值)上差异具有统计学意义(P<0.05)。单因素及多因素二元Logistic回归分析并构建的诺模图显示,基于哮喘史、外周血EOS、外周血...     

诱生型一氧化氮合酶在慢性上颌窦炎黏膜的表达

目的 观察诱生型一氧化氮合酶(inducible nitric oxide synthase，iNOS)在慢性鼻窦炎病人鼻窦粘膜中的表达。方法 将实验分为两组：对照组为正常成人，无鼻窦病变。实验组为确诊为慢性上颌窦炎的病人。在局麻鼻内镜下行鼻窦黏膜活检，石蜡包埋、切片，用免疫组织化学的方法观察iNOS在两组上颌窦黏膜中的表达。结果 iNOS在正常上颌窦炎黏膜呈阴性表达，在慢性上颌窦炎黏膜呈阳性表达，阳性区域主要在黏膜上皮细胞。结论 iNOS在慢性上颌窦炎黏膜呈阳性表达，提示一氧化氮在慢性上颌窦炎的发病机制中起重要作用。     

瘦素在肥胖成人慢性鼻-鼻窦炎伴鼻息肉发病中的作用

1007 1520.202003008·论著· 目的初步探讨瘦素（Leptin）在肥胖成人慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）发病中的作用及机制。方法按照体重指数（BMI）随机选取肥胖CRSwNP患者40例,体重正常CRSwNP患者30例,选取同期肥胖鼻中隔偏曲患者30例为对照组。通过酶联免疫吸附法（ELISA）测定3组患者血清中Leptin及其受体水平、EOS相关因子IL 4、IL 13的水平;RT PCR及免疫组织化学方法检测3组患者局部鼻黏膜中Leptin及其受体水平表达;苏木精-伊红染色法观察3组患者组织中EOS细胞浸润程度。另Pearson相关性分析Leptin水平与EOS相关指标及浸润程度的关系。结果与对照组比较,两组CRSwNP患者的血清与局部Leptin及其受体水平表达均升高,血清中EOS相关因子IL 4、IL 13的水平表达均显著升高,差异具有统计学意义（P<0.05）;两组CRSwNP患者中肥胖患者的各项检测指标均显著高于体重正常患者（P<0.05）,且Leptin及其受体水平与EOS相关指标、EOS浸润程度均呈正相关（P<0.05）。结论Leptin在CRSwNP患者中水平显著升高,且肥胖患者组更高,并与EOS浸润及其促进因子显著相关,提示Leptin可能通过促进EOS增殖浸润参与肥胖成人CRSwNP发病。     

Heme oxygenase-1 expression in chronic rhinosinusitis with eosinophilic infiltration

Objectives

Chronic rhinosinusitis (CRS) with eosinophilic infiltration is a type of intractable rhinosinusitis often associated with asthma. The oxidants are well known to induce aggravate asthma. Heme oxygenase-1 (HO-1), a cytoprotective enzyme against oxidant, has been extensively studied in airway diseases. However, no study that observed HO-1 in both epithelial and subepithelial tissues of CRS has been reported.

Methods

Part of each specimen derived from the nasal polyps of CRS with and without eosinophilic infiltration was promptly fixed for hematoxylin–eosin staining and immunohistochemical analysis for HO-1 and macrophages.

Results

We found that the expression of HO-1 in the epithelial layers of CRS without eosinophilic infiltration was significantly enhanced as compared with that of CRS with eosinophilic infiltration. On the other hand, the number of macrophages with HO-1 positive reactions was significantly greater in CRS with eosinophilic infiltration compared with CRS without eosinophilic infiltration.

Conclusions

Our study suggests that both a reduction of HO-1 expression in epithelial cells and an increase of infiltration of macrophages positive for HO-1 are related to the epithelial damage of CRS with eosinophilic infiltration.     

Bacteriology of postradiotherapy chronic rhinosinusitis in nasopharyngeal carcinoma patients and chronic rhinosinusitis

The purpose of this study was to investigate and compare the bacteriology of postradiotherapy chronic rhinosinusitis (postRT-CRS) and chronic rhinosinusitis (CRS) by evaluating the aspiration materials of the maxillary sinus of patients with postRT-CRS and patients with CRS. We collected the secretions of the maxillary sinus from 30 nasopharyngeal carcinoma patients with postRT-CRS and 30 patients with CRS for aerobe/facultative anaerobe bacteria culture. The most common isolates in the postRT-CRS group were Streptocuccus viridans, Staphylococcus aureus and Haemophilus influenzae, while those in the CRS group were Haemophilus influenzae, Pseudomonas aeruginosa and Staphylococcus aureus. Isolated Gram-positive coccus rate in postRT-CRS patients was significantly higher than in CRS patients (62.50% compared with 30.00%, respectively; P < 0.05), and isolated Gram-negative bacilli rate in postRT-CRS patients was significantly lower than in CRS patients (31.25% compared with 70.00%, respectively; P < 0.05). However, the incidence of positive cultures was not significantly different between the postRT-CRS group and the CRS group (P > 0.05). This study found that there were some differences in bacteriology between postRT-CRS and CRS. Gram-positive coccus was the predominant aerobic/facultative anaerobe pathogenic bacterium in patients with postRT-CRS, and Gram-negative bacilli was predominant in CRS patients.     

慢性鼻窦炎伴鼻息肉复发手术时的组织病理学及外周血特征变化

目的:探讨慢性鼻窦炎伴鼻息肉（CRSwNP）患者复发手术时的组织病理学及外周血特征变化趋势。方法:回顾性分析1999年2月至2019年4月于北京协和医院连续2次接受内镜鼻窦手术的41例CRSwNP患者的临床资料,其中男性25例,女性16例,年龄前次手术时为（40.7±13.6）岁（ xˉ±s,下同）,复发手...     

NOS在分泌性中耳炎所致感音神经性聋中的作用

目的:探讨NOS及NO在分泌性中耳炎(SOM)所致感音神经性聋(SNHL)中的作用。方法:治疗前分别抽取16例伴有SNHL的SOM患者(A组)及16例不伴有SNHL的SOM患者(B组)的中耳积液,检测两组中耳积液内NOS活性和NO含量。结果:A组中耳积液内NO含量(181.19±44.31)μmol/L明显高于B组(137.00±40.67)μmol/L(P<0.01),A组中耳积液内NOS活性(97.69±29.62)U也明显高于B组(75.50±26.99)U(P<0.05)。结论:NO可能通过直接损伤和与其他炎症递质共同作用增强局部炎症反应,在SOM所致的SNHL过程中发挥重要作用。