慢性鼻-鼻窦炎与全身性糖皮质激素应用

慢性鼻-鼻窦炎（chronic rhinosinusitis,CRS）是涉及一个或几个鼻窦的黏膜炎性病变,是重要的医疗问题。CRS分为慢性鼻-鼻窦炎伴或不伴鼻息肉。中国CRS发病率约为2.2%,低于欧美国家（5%～15%）。CRS不伴鼻息肉有Th1倾向性,转化生长因子-β在其发病过程中起重要作用。CRS伴鼻息肉有Th2偏向性,嗜酸性粒细胞、Th2型淋巴样细胞等炎性细胞及各类Th2介质共同起作用。CRS伴或不伴鼻息肉患者均推荐使用鼻用糖皮质激素。CRS伴鼻息肉尤其是严重、复发性鼻息肉患者,推荐使用全身性糖皮质激素;CRS不伴鼻息肉及儿童患者不推荐使用全身性糖皮质激素。     

口服糖皮质激素治疗慢性鼻-鼻窦炎伴鼻息肉

慢性鼻-鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps,CRSwNP）是严重影响患者健康及生活质量的慢性疾病。有多项临床研究报道了口服糖皮质激素（glucocorticoids,GC）治疗CRSwNP具有一定的疗效。但临床证据质量不高,疗效难以维持以及可能产生的不良反应,目前对口服GC的治疗还存在争议。因此,本文对GC治疗CRSwNP的作用机制,短期和术前口服GC治疗CRSwNP的疗效及药物不良反应进行综述。     

局部糖皮质激素治疗慢性鼻-鼻窦炎的疗效研究

目的 观察单独应用局部糖皮质激素治疗中国人慢性鼻-鼻窦炎(chronic rhinosinusitis,CRS)的疗效.方法 随机选取2010年11月至2011年12月就诊于中山大学附属第一医院耳鼻咽喉科,未经治疗的CRS伴或不伴鼻息肉患者34例.使用鼻腔局部喷布地奈德规律治疗3个月.以视觉模拟量表(visual analogue scale,VAS)评估治疗前及治疗后第1、2、3个月鼻部症状评分;以鼻腔鼻窦结局测试-20(sino-nasal outcome test-20,SNOT-20)评估治疗前后患者的生活质量;以Lund-Mackay CT评分评估治疗前后影像学的改变.采用SPSS 16.0软件进行统计学分析.结果 34例患者中,脱落4例.患者治疗前鼻塞、鼻漏、头痛、面部压迫感、总体症状的VAS评分分别为(4.84±3.15)、(6.03±2.93)、(1.68±2.66)、(2.04±2.97)、(6.00±2.75)分,治疗后第3个月分别为(2.26±2.27)、(1.96±2.23)、(0.42±0.95)、(0.58±1.42)、(2.71±1.90)分,差异有统计学意义(t值分别为4.386、6.740、2.445、2.980、6.989,P值均＜0.05);嗅觉下降或障碍治疗前后差异无统计学意义(t=0.902、P＞0.05).治疗后第1个月鼻塞、鼻漏、总体症状的VAS评分较治疗前差异有统计学意义(P值均＜0.05);而治疗后第1、2、3个月之间各种鼻部症状的VAS评分差异无统计学意义(P值均＞0.05).治疗后SNOT-20得分较治疗前差异有统计学意义(t=3.687,P＜0.01).从CT表现上评估总体治愈率为22.2％.结论 局部糖皮质激素治疗中国人CRS有明确疗效,22.2％的患者能达到CT的痊愈,症状改善出现在第1个月.     

大环内酯类药物治疗慢性鼻-鼻窦炎的疗效观察

目的　探讨大环内酯类药物治疗慢性鼻-鼻窦炎不伴鼻息肉（chronic rhinosinusitis without nasal polyp,CRSsNP）的临床疗效。方法　对82例成人CRSsNP患者按照鼻窦CT评分严重情况随机分成治疗组和对照组两组,每组各41例。治疗组给予布地奈德喷鼻,2次/d,克拉霉素250 mg口服,1次/d,连续3个月;对照组予布地奈德喷鼻,2次/d。所有患者均每1个月进行1次肝肾功能评估,观察比较两组用药前、后主观客观指标的变化（视觉模拟量表评分,鼻内镜检查Lund-Kennedy评分,鼻窦CT扫描评分）。结果　治疗组所有患者视觉模拟量表评分、鼻内镜检查Lund-Kennedy评分及鼻窦CT扫描评分均明显下降（t =23.79、31.69、26.06,P 均<0.05）,与对照组比较（t =10.42、13.28、10.17,P 均<0.05）差异有统计学意义。结论　大环内酯类药物能有效控制CRSsNP的症状,特别对于激素治疗不敏感的患者,不适于手术的患者更是一种有效的治疗手段。     

内镜鼻窦手术治疗慢性鼻-鼻窦炎临床结局的主客观评估

目的评估内镜鼻窦手术治疗慢性鼻．鼻窦炎的主客观临床结局并构建临床实用性的主客观结局评估体系。方法通过前瞻性队列研究，对120例慢性鼻-鼻窦炎患者术前和术后12个月的临床结局进行视觉模拟量表（visual analog scale，VAS）、医学结局研究简表36项（medical outcome study short-form 36-items，SF-36）和鼻腔鼻窦结局测试20条（sino-nasal outcome test-20，SNOT-20）等症状与生存质量的主观评估，以及内镜下黏膜形态、纤毛功能与组织病理学等客观评估。数据统计采用t检验、Х^2检验和Spearman相关分析处理手术前后主客观结局的变化及其相互关系。结果①术后12个月，VAS、SF-36和SNOT-20整体评分较术前明显改善（P〈0．01），其中85．96％、77．19％和83．33％的个体三项主观指标评分分别较术前改善，同时改善的比例为72．28％；手术前后各个时期，三种主观指标评分均具相关性（P值均〈0．01），其中SNOT-20兼性作用最大。②术后12个月，内镜下黏膜形态、纤毛功能和组织病理学整体评分较术前明显改善（P值均〈0．05），其中86．84％、86．81％和75．57％的个体三种客观指标评分分别较术前改善，同时改善的比例为71．85％；手术前后各个时期，三种客观指标评分均具相关性（P值均〈0．05），其中内镜下黏膜形态兼性作用最大。③SNOT-20与内镜下黏膜形态同时评估显示：术后12个月74．56％的患者主客观评分升降结局一致，而25．44％的患者主客观结局不一致，其中伴发鼻息肉患者更容易出现这种差异性（P〈0．05）。④手术前后不同时期，SNOT-20与内镜下黏膜形态评分均无相关性（P〉0．05），但前10位条目总分与内镜下黏膜形态评分具有相关性（0．18≤r≤0．42，P〈0．05），而后10位条目总分与之不相关（P〉0．05）。结论①内镜鼻窦手术可有效改善慢性鼻-鼻窦炎患者术后的症状、生存质量、内镜下黏膜形态、纤毛功能及组织状态等临床结局；②构建以SNOT-20和内镜下黏膜形态评估为主体的主客观结局评估体系，简约可靠，合理有效，具有临床实用性。     

长期小剂量克拉霉素联合鼻用激素治疗慢性鼻-鼻窦炎的初步观察

目的:观察长期小剂量大环内酯类药物联合鼻用糖皮质激素治疗慢性鼻-鼻窦炎(CRS)的疗效.方法:克拉霉素片0.25 g口服,2次/d,2周后改为1次/d;曲安奈德喷雾剂喷鼻,1次/d.不伴鼻息肉的CRS患者26例给药时间12~28周,平均16.62周.伴鼻息肉的CRS患者30例,先在内镜下切除鼻息肉(手术前后用抗生素、激素5~7 d),然后开始药物疗法.给药时间12~33周,平均20.03周.治疗前后采用Lund-Mackey鼻窦CT评分,主观症状自评治疗效果.结果:伴息肉组治疗后鼻窦CT平均得分2.83±1.86,显著低于治疗前(7.20±2.06,t=11.41,P<0.01);不伴息肉组治疗后鼻窦CT平均得分2.43±1.91,显著低于治疗前(6.23±1.88,t=12.86,P<0.01).伴息肉组和不伴息肉组鼻窦CT评分疗效治愈率分别达到43.3%和50.0%.两组的自评疗效与鼻窦CT评分疗效比较无明显差异.结论:长期使用小剂量的克拉霉素联合鼻用糖皮质激素治疗CRS有效.鼻息肉多发和手术处理次数多的患者疗效相对较差.鼻息肉切除和围手术期集中使用大剂量抗生素、糖皮质激素有利于提高伴息肉的CRS患者药物疗法的疗效.     

糖皮质激素受体在慢性鼻-鼻窦炎伴鼻息肉激素敏感性中的研究进展

慢性鼻-鼻窦炎是一种临床常见,具有高度异质性,发病机制复杂的鼻黏膜持续反应性炎性疾病。作为临床中治疗鼻-鼻窦炎的一线药物,糖皮质激素的生物学效应主要由糖皮质激素受体介导。该受体的表达具有明显的异质性,受转录水平、翻译水平以及翻译后修饰等多层面调控。慢性鼻-鼻窦炎疾病本身和激素治疗以及所处微环境变化会影响糖皮质激素受体的表达及功能,最终影响糖皮质激素的敏感性。本文总结了糖皮质激素受体在慢性鼻-鼻窦炎伴鼻息肉激素敏感性中的研究进展。     

大环内酯类药物治疗慢性鼻-鼻窦炎的Meta分析

目的：系统评价大环内酯类药物治疗慢性鼻-鼻窦炎（CRS）的临床疗效及安全性。方法计算机检索PubMed、OVID、EMBASE、中国学术期刊全文数据库、万方数据库中关于大环内酯类药物治疗CRS的随机对照试验（Randomized controlled trials,RCT）,同时追索纳入文献的参考文献。检索年限均从建库检索至2016年1月。由2名评价员独立筛查文献,对纳入的文献进行质量评价,并提取资料,对符合质量标准的RCTs进行Meta分析,比较大环内酯类药物组与安慰剂组鼻腔鼻窦结局评分（sinonasal outcome test,SNOT）、患者反应量表评分和安全性评估。统计学分析采用RevMan 5.3软件。结果共纳入3篇RCTs,Meta分析结果显示,长期低剂量应用大环内酯类药物第24周时患者SNOT评分（WMD=-0.43,P=0.03）降低,第12周时SNOT变化（WMD=-0.23,P=0.25）和患者反应量表评分变化（WMD=-0.40,P=0.28）无统计学意义。大环内酯类药物的不良反应发生率与安慰剂组相似。结论长期低剂量应用大环内酯类药物不能明显改善CRS患者的临床症状,其不良反应发生率与对照组相近。     

糖皮质激素抵抗性慢性鼻-鼻窦炎研究进展

糖皮质激素（glucocorticoid,GC）抵抗性慢性鼻-鼻窦炎（CRS）是指CRS患者经过规范化鼻内GC治疗,随访3个月以上,病情未控制,表现为患者鼻塞、流脓涕、面部不适、头痛症状无改善或无明显改善,各项评分与治疗前无显著差异,鼻内镜检查表现为鼻黏膜充血水肿,息肉组织仍存在,窦口狭窄或闭锁,有黏性或黏脓性分泌物。因其致病因素复杂及CRS中GC抵抗机制未明,目前尚无统一的治疗方案,因此在深入研究其致病因素及GC抵抗机制的基础上,以手术治疗为基础,实施系统化、个体化的综合治疗是必要的。     

Long-term outcomes of endoscopic sinus surgery for chronic rhinosinusitis with and without nasal polyps

Chronic rhinosinusitis (CRS) significantly affects patient quality of life. Medical and surgical treatments aim to clinically manage the condition.ObjectiveTo assess the long-term quality of life and clinical management of CRS in patients submitted to endoscopic sinus surgery.MethodThis prospective cross-sectional cohort study enrolled 38 patients and looked into the follow-up data of subjects diagnosed with CRS before surgery, three months after surgery, and at least two years after surgery. The Sinonasal Outcome Test 22 (SNOT-22) was used to assess response to treatment and long-term clinical management of the disease.ResultsSignificant improvements in the SNOT-22 scores were seen between the preoperative (61.3) and postoperative assessments with three (16.9) and 24 (32.3) months. No statistically significant differences were seen when patients with polyps were compared to polyp-free subjects. Few patients were controlled in both groups, and 7.89% of the subjects had revision surgery during the study.ConclusionEndoscopic sinus surgery significantly improved the quality of life of patients with chronic rhinosinusitis. Clinical control of the condition was acceptable, with few patients requiring re-operation within two years of the first surgery.     

Bacterial biofilms in chronic rhinosinusitis; distribution and prevalence

Conclusion: Biofilms were more prevalent in patients with CRSwNP compared to both CRSsNP and controls, and also on the ethmoid bulla compared to the middle turbinate, supporting a biofilm-related pathogenesis of CRSwNP.

Objective: To investigate the prevalence of biofilms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) compared to patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. To examine the prevalence of biofilms in different anatomical localizations.

Study design: Cross-sectional.

Methods: This study comprised 27 patients with CRSsNP, 34 patients with CRSwNP, and 25 controls. Biopsies from the middle turbinate, the uncinate process, and the ethmoid bulla were harvested pre-operatively, snap frozen in isopentane, cooled, and stored at??80°C. Prepared with Invitrogens’ Baclight LiveDead kit and investigated with confocal scanning laser microscopy.

Results: Biofilms were studied in 33/34 (97%) CRSwNP, 22/27 (82%) CRSsNP, and 14/25 (56%) controls. The difference in point prevalence between patients with CRSwNP vs CRSsNP (p?=?0.042, χ²?=?4.12), CRSwNP vs Controls (p?χ²?=?15.0), and CRSsNP vs controls (p?=?0.047, χ²?=?3.96) were all significant. Biofilms were found in 43/54 (80%) ethmoid bulla, 39/55 (71%) uncinate process, and 31/50 (62%) middle turbinate. The difference between the ethmoid bulla and the middle turbinate locations (p?=?0.047, χ²?=?3.93) was significant.     

Real-world characterisation of patients with chronic rhinosinusitis with nasal polyps with and without surgery in England

Objectives

To characterise the real-world burden of chronic rhinosinusitis with nasal polyps (CRSwNP) in the UK, stratified by number of surgeries.

Design

Retrospective cohort study.

Setting

UK Clinical Practice Research Datalink Aurum database with Hospital Episodes Statistics linkage (2007–2019).

Participants

Adults ≥18 years of age with a first NP diagnosis (index) and 365 days of baseline and ≥180 days of follow-up data. Follow-up continued until disenrollment, death or end of data collection.

Main Outcome Measures

Primary: primary care physician prescribed CRSwNP-related treatments, and all-cause healthcare resource utilisation (HCRU) in 90 days post-index, stratified by surgeries during follow-up. Secondary: rate of surgery and CRSwNP point prevalence. Baseline patient demographics, clinical characteristics and comorbidities were also assessed.

Results

Of the 33 107 patients included, 23.5% and 2.2% had ≥1 and ≥2 surgeries during follow-up, respectively (mean follow-up: 5.3 years). Patients with more surgeries (≥2/≥1/0) during follow-up were more likely to be male (67.3%/69.0%/58.0%), have asthma (37.8%/28.2%/20.2%) and have baseline blood eosinophil counts ≥300 cells/μL (68.5%/66.0%/51.5%). During the first 90-days post-index as surgery number increased, the proportion of patients using oral corticosteroids (25.8%/20.7%/14.2%) and mean (SD) number of all-cause healthcare visits (5.9 [4.2]/5.4 [4.0]/4.9 [4.2]) increased. Time between surgeries was shorter among patients with more surgeries. CRSwNP prevalence on 31 December 2018 was 476 cases per 100 000 persons.

Conclusion

A small proportion of patients in the UK required multiple surgeries for CRSwNP and this was associated with increasing comorbidity burden, baseline blood eosinophil counts, CRSwNP-related treatment and HCRU use.     

慢性鼻-鼻窦炎患者药物治疗的生存质量及相关研究

目的 使用鼻窦炎症状视觉模拟量表(VAS)及鼻窦炎专用量表-鼻腔鼻窦结局测试20(SNOT-20)中文版评价慢性鼻-鼻窦炎患者药物治疗前与治疗后不同时间的生存质量(QOL),探讨药物治疗对患者QOL的影响。 方法 收集慢性鼻-鼻窦炎患者100例作为实验组,给予药物联合治疗12周,每4周进行一次VAS评分及SNOT-20评分。另收集100例健康体检者作为对照组,进行一次相同的评分。分析实验组治疗前后及停药后患者VAS评分、SNOT-20评分的变化及与对照组的差异。 结果 实验组治疗前后及停药后VAS评分差异具有统计学意义(F=38.39,P<0.01)。实验组治疗12周后与对照组VAS评分比较差异具有统计学意义(t=7.93,P<0.01)。实验组VAS、CT评分于治疗后5个症状占比分别有所下降,每种症状的VAS、CT评分也有所下降。实验组治疗前后及停药后SNOT-20评分经单因素方差分析显示差异具有统计学意义(F=27.93,P<0.01)。实验组治疗12周后与对照组SNOT-20评分比较差异具有统计学意义(t=19.93,P<0.01)。实验组于治疗后各症状占比人数分别有所下降,每种症状的SNOT-20评分也有所下降。 结论 药物治疗作为慢性鼻-鼻窦炎的首选治疗方式,可有效改善患者的QOL,但长期小剂量使用的远期疗效尚有待进一步证实。     

Toll样受体及其传导通路在慢性鼻窦炎鼻息肉中的表达

目的：探讨Toll样受体（TLRs）及其传导通路在慢性鼻窦炎鼻息肉组织中的表达及意义。方法：慢性鼻窦炎鼻息肉及正常对照组各10例分别抽提RNA,逆转录成eDNA后扩增cRNA并标记,采用SuperArray第2代功能分类芯片技术检测TLRs及其传导通路表达,化学发光的芯片图像通过X胶片和台式扫描仪获得。使用GEArray表达分析配套软件进行完整的芯片数据分析。结果：与正常对照组织相比,鼻息肉组织中表达上调2倍的基因有4条,表达下调2倍的基因有15条。结论：TLRs及其传导通路在慢性鼻窦炎鼻息肉组织与正常鼻黏膜中的表达差异提示天然免疫在慢性鼻窦炎发病中发挥一定的作用。TLR9及其激动剂在慢性鼻窦炎发病及治疗中的作用需进一步研究。     

The role of ADAM-like decysin 1 in non-eosinophilic chronic rhinosinusitis with nasal polyps

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is classified into two subtypes: eosinophilic (ECRSwNP) and non-eosinophilic (NECRSwNP). Although the inflammatory patterns of ECRSwNP have been elucidated, NECRSwNP is poorly understood.

Aims/objectives: The metalloproteinase ADAM-like decysin 1 (ADAMDEC1) has been reported to play a role in the early stages of the inflammatory response. We investigated the role of ADAMDEC1 in the pathogenesis of CRSwNP.

Material and methods: We compared ADAMDEC1 expression in nasal polyp tissue from CRS patients using immunohistochemistry and RT-qPCR. Macrophages were cultured and ADAMDEC1 expression was determined at baseline and after exposure to lipopolysaccharide (LPS).

Results: ADAMDEC1 was virtually undetectable in tissues from control patients but was highly expressed in the NECRSwNP group compared with the ECRSwNP group. In nasal polyp tissues, ADAMDEC1 was expressed by CD68-positive cells, with a positive correlation between ADAMDEC1-positive and CD68-positive cells, and also between ADAMDEC1 and CD68 mRNA levels. Furthermore, stimulation of monocyte-derived macrophages with LPS induced ADAMDEC1 expression.

Conclusions and significance: This study demonstrates that ADAMDEC1 is involved in the pathogenesis of NECRSwNP, and also bacterial endotoxin signalling in macrophages; however, the underlying mechanism remains to be elucidated.     

伴和不伴鼻息肉的慢性鼻-鼻窦炎患者筛窦的细菌学研究

目的:比较伴和不伴鼻息肉的慢性鼻-鼻窦炎患者及正常对照患者前筛黏膜标本的细菌学特征.方法:在鼻内镜手术中获取前筛黏膜标本,进行需氧和厌氧培养.结果:送检前筛黏膜标本119例,经需氧和厌氧组织匀浆半定量细菌培养,104例标本细菌培养为阳性(细菌培养总阳性率为87.4%);其中慢性鼻-鼻窦炎不伴鼻息肉组(CRSNP-组)、慢性鼻-鼻窦炎伴鼻息肉组(CRSNP+组)、正常对照组需氧或兼性厌氧细菌培养阳性率分别为86.5%、85.7%、90.0%,3组比较差异无统计学意义(P>0.05).3组患者的黏膜标本以需氧菌和厌氧菌混合感染为主,混合感染率分别为CRSNP-组78.4%、CRSNP+组81.0%、对照组85.0%,差异无统计学意义(P>0.05).3组最常见需氧菌株为凝固酶阴性葡萄球菌、棒状杆菌属细菌,比较差异均无统计学意义(均P>0.05).厌氧菌培养阳性率3组分别为78.4%、76.2%、77.5%,差异无统计学意义(P>0.05);最常见厌氧菌株为丙酸杆菌属细菌、消化链球菌属细菌,差异均无统计学意义(均P>0.05).结论:CRSNP-组和CRSNP+组及对照组患者前筛黏膜标本的细菌学特征无明显差异,细菌感染并非是慢性鼻-鼻窦炎发生鼻息肉这一机制中的惟一因素.     

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.