Eosinophilic bacterial chronic rhinosinusitis

BACKGROUND: A subset of Chronic Rhinosinusitis (CRS) patients are those with eosinophilic CRS (ECRS). These patients remain the most refractory to medical and surgical intervention, and are thought to reflect an inflammatory process arising from a variety of causes. Recently the role of fungus in ECRS, defined as the presence of fungi in the eosinophilic mucin of CRS, has been proposed as causal in many cases. Other proposed causes of ECRS include bacterial superantigen induction of inflammation and aspirin sensitivity. DESIGN: Retrospective review. METHODS: Histopathology from patients with previously diagnosed ECRS was prospectively re-reviewed for bacterial and fungal presence and correlated with patients' demographic data. The study population was comprised of 55 specimens with ECRS from 34 patients, over a 3-year period from a single investigator at the University of Pittsburgh Medical Center. RESULTS: Histologic presence of bacteria was shown in 34 of 55 (62%) of all ECRS specimens. Specimens with fungal colonization were more often associated with bacterial presence than without bacteria (17 of 22 [77%] vs. 5 of 22 [23%], P < .02). CONCLUSION: Bacteria were present in almost two-thirds of all specimens, and most cases of fungal presence were accompanied by bacterial presence, potentially providing support for bacteria as a source of superantigen. Other possible reasons for the high rate of bacterial and fungal colonization of ECRS include increased pathogen exposure, or failure to eliminate pathogens.     

Histologic and immunologic observations of viral-induced rhinosinusitis in the mouse

Viral upper respiratory infection is one of the most common diagnoses made in primary care offices. Although symptoms resolve within 1 week for many patients, a percentage develops rhinosinusitis, and many of these patients are treated with antibiotics. We have developed a model of viral rhinosinusitis using intranasal inoculation of reovirus into mice that were then killed on postinoculation days 2, 4, 7, 10, 14, or 21 and heads were embedded in paraffin for histological and immunohistochemical analyses. Reovirus-like immunoreactivity was noted in the septa and paranasal sinus mucosa in mice as early as day 2, with peak intensity seen on day 4, and scant staining seen on day 7. Complete absence of viral staining was seen by day 10, which corresponded with increased intracellular adhesion molecule 1 immunostaining in the nose. By day 10, a large mucosal influx of B cells was observed, with a moderate influx of macrophages and smaller influx of T cells. By day 14, there was a peak in the number of B cells with a corresponding, but less pronounced peak in T cells, while macrophages began to decline at this point. By day 21, the panel of immune markers returned to near normal levels. The results of this study suggest that the immune system continues to produce a response as long as 2 weeks after clearance of viral antigens. One proposed mechanism for this phenomenon is that local factors such as cytokines are released continually after infection, even in the absence of persistent viruses or bacteria.     

难治性慢性鼻-鼻窦炎与细菌生物膜

慢性鼻-鼻窦炎（CRS）是鼻腔和鼻窦黏膜的慢性炎症,症状持续至少12周,是宿主和环境多因素相互作用的结果。CRS是耳鼻咽喉科的常见疾病,最近有报道指出美国CRS患病率大于16％,     

Th2 immunological inflammation in allergic fungal sinusitis, nonallergic eosinophilic fungal sinusitis, and chronic rhinosinusitis

BACKGROUND: Noninvasive fungal sinusitis is a heterogenous group of conditions including allergic fungal sinusitis (AFS) and nonallergic eosinophilic fungal sinusitis (NEFS). Th2-mediated cascades have been postulated to be the major inflammatory response in patients with AFS although other mechanisms also may be involved. The detailed mucosal Th2 cytological status of NEFS still has not been studied in great depth. METHODS: Using a meticulous patient selection algorithm over a 2-year period, infundibular mucosal tissue from patients with AFS, NEFS, chronic rhinosinusitis (CRS), and normal controls was studied (n = 59). Immunohistochemistry for mast cells, eosinophils, and immunoglobulin E (IgE) cells was performed and cell counts per unit area were measured. RESULTS: Mast cell, eosinophil, and IgE+ cell numbers were significantly raised in patients with AFS, NEFS, and CRS when compared with controls. There was no significant difference between cell numbers in patients with AFS and NEFS. CONCLUSION: Patients with AFS exhibit a classic Th2 inflammatory response in nasal mucosal tissue with NEFS and CRS patients showing evidence of a similar Th2 cascade, including the presence of IgE+ cells.     

慢性鼻-鼻窦炎细菌生物膜形态观察

目的 观察慢性鼻-鼻窦炎患者,鼻内镜所取钩突、筛泡或上颌窦黏膜样本是否存在细菌牛物膜及其形态特征.方法 本实验共取鼻内镜术中黏膜样本12份,实验组为慢性鼻.鼻窦炎鼻内镜手术患者6例,对照组为阻塞性睡眠呼吸暂停综合征鼻内镜手术患者6例.样本用标准的扫描电镜方法 处理.实验组详细记录患者的年龄、性别、症状、鼻窦CT、鼻内镜检查和变应原皮肤点刺试验结果 .结果 扫描电镜下见慢性鼻一鼻窦炎患者鼻腔鼻窦黏膜纤毛缺失、倒伏、排列紊乱,实验组中5例可见不同形成阶段、各种形态的细菌生物膜,1例可见丝状真菌样结构.实验组细菌生物膜出现率为83.3%.对照组6例均未观察到细菌生物膜.结论 慢性鼻-鼻窦炎鼻腔鼻窦黏膜纤毛有不同程度的损伤,黏膜表面存在处于生命周期不同阶段的细菌牛物膜.     

变应性因素对慢性鼻-鼻窦炎影响的研究

目的:探讨变应性因素与慢性鼻-鼻窦炎(CRS)疾病严重程度之间的相关性以及其对CRS的病情发展和转归的影响.方法:101例CRS患者进行变应性因素血清相关指标检测:血清总IgE浓度、血清特异性变应原IgE半定量检测、血清嗜酸粒细胞阳离子蛋白(ECP)浓度及病史询问、Lund-Mackay CT系统评分.结果:CRS组血清总IgE浓度及血清ECP浓度均高于正常对照组(P＜0.01);CRS组血清总IgE浓度增高发生率及血清ECP浓度增高发生率随着临床分型的加重而显著增加,并且在有既往相关手术史的患者中较无相关手术史患者中亦有显著增高(P＜0.05);血清总IgE浓度及血清ECP浓度增高患者的平均Lund-Mackay CT评分较浓度正常患者CT评分有显著性增高.CRS组血清特异性变应原IgE半定量检测阳性率为67.32%,强阳性率27.72%;各分型之间特异性变应原强阳性率差异有统计学意义(P＜0.05);有既往相关手术史的患者变应原强阳性率较无手术史患者的强阳性率显著性增高(P＜0.05);变应原强阳性患者CT评分较阴性患者CT评分有显著性增高(P＜0.05).结论:变应性因素对CRS的病变程度有一定负面作用,是影响疾病严重度及手术预后的不良因素.     

Demonstration of biofilm in human bacterial chronic rhinosinusitis

BACKGROUND: Bacterial biofilms may explain why some patients with bacterial chronic rhinosinusitis (CRS) improve while on antibiotics but relapse after completion of the antibiotic. In the human host, biofilms exist as a community of bacteria surrounded by a glycocalyx that is adherent to a foreign body or a mucosal surface with impaired host defense. Biofilms generate planktonic, nonadherent bacterial forms that may metastasize infection and generate systemic illness. These planktonic bacteria are susceptible to antibiotics, unlike the adherent biofilm. METHODS: We reviewed four cases of CRS using transmission electron microscopy (TEM) to assay for typical colony architecture of biofilms. Bacterial communities surrounded by a glycocalyx of inert cellular membrane materials consistent with a biofilm were shown in two patients. RESULTS: In the two patients without biofilm, a nonbacterial etiology was discovered (allergic fungal sinusitis) in one and in the other there was scant anaerobic growth on culture and the Gram stain was negative. Culture of the material from the biofilm grew Pseudomonas aeruginosa in both patients. Pseudomonas from the biofilm showed a glycocalyx, not present in Pseudomonas cultured for 72 hours on culture media. Both patients' symptoms with bacterial biofilms were refractory to culture-directed antibiotics, topical steroids, and nasal lavages. Surgery resulted in cure or significant improvement. CONCLUSION: Biofilms are refractory to antibiotics and often only cured by mechanical debridement. We believe this is the first TEM documentation of bacterial biofilms in CRS in humans.     

Investigations on allergic fungal genesis of chronic rhinosinusitis

BACKGROUND: The incidence of allergic fungal sinusitis (AFS) is estimated differently. The importance of hyphal findings in nasal mucus for initiation of chronic hyperplastic sinusitis is not proven. METHODS: 124 patients with clinical signs and CT-scan findings of a chronic-hyperplastic rhinosinusitis were treated by functional endoscopic sinus surgery. During the operation a thick mucus was found in each patient. The mucus was isolated and investigated by histopathological analysis with special Grocott-stain and a culture for fungal growth was initiated. Furthermore the diagnostic for allergic reactions against fungus was done by prick- and RAST-tests. RESULTS: 21 patients had positive histopathological findings of fungus. In 10 cases fungal hyphae were found embedded in typical eosinophilic mucus. A positive allergic reaction against fungus was seen in 7 of these 10 patients. The culture results showed different pictures according to the isolated species, in 3 cases of the 10 AFS cases the culture was negative. The other 11 cases of 21 positive histological findings of fungus were cases of a fungus ball. The other 103 patients were without any sign for fungus in the HE- or Grocott-stain. CONCLUSIONS: A high incidence of AFS is not evident in group of chronic hyperplastic rhinosinusitis. The presence of eosinophilic "allergic" mucus is not the evidence for AFS. The inflammatory cascade leading to the clinical picture is a multifactorial event. The role of detectable fungus hyphae have to be estimated by further investigations.     

浅谈伴有变应性鼻炎的慢性鼻窦炎的治疗

慢性鼻窦炎和变应性鼻炎是两种常见的慢性上呼吸道疾病,存在着某些内在联系以及类似炎症机制。有必要完善慢性鼻窦炎、鼻息肉患者的术前变态反应检查以及治疗:包括避免过敏原(环境和食物)、免疫治疗、鼻腔冲洗、鼻用糖皮质激素、针对鼻窦病原体的抗菌药物、抗变态反应(抗组胺药、白三烯受体拮抗剂等)和抗胃食管反流。此外,维生素D诱导细胞分化、参加免疫调节和调节内分泌系统也在慢性鼻窦炎和变应性鼻炎的炎症过程中发挥重要作用。     

Developing a mouse model of acute bacterial rhinosinusitis

The objective of this study is to establish a mouse model of acute bacterial rhinosinusitis. 179 healthy male BALB/c mice were divided into four groups in this randomized and controlled study. Sponge slivers impregnated with methicillin-resistant Staphylococcus aureus (MRSA COL) suspension were inserted into the right nasal cavities for group A; sponge slivers impregnated with sterile saline were inserted into the right nasal cavities for group B; group C mice were inoculated with MRSA COL suspension in right nasal cavities; group D was control group without any treatment. Mice were killed on days 1, 4, 7 and 14, respectively. Nasal lavage fluid was prepared for microbiological culture. Histological examinations of nasal specimens were performed to observe the severity of inflammatory reaction. Acute bacterial rhinosinusitis was induced in all group A mice. Less severe inflammation was seen in partial group B mice compared with that in group A mice (P ≤ 0.05). No inflammatory reaction was found in group C and D mice. In conclusion, a mouse model of acute bacterial rhinosinusitis has been developed successfully using an easier, less invasive and potentially more reversible technique than those used in previous studies.     

慢性鼻-鼻窦炎鼻息肉患者细菌生物膜的观察

目的 观察慢性鼻-鼻窦炎鼻息肉患者手术黏膜组织中细菌生物膜的形态特征,并分析其与临床因素、术后疗效的关系.方法 试验组获取72例慢性鼻-鼻窦炎鼻息肉患者手术中筛窦黏膜组织,对照组获取15例鼻中隔偏曲患者、10例鼻骨骨折患者钩突黏膜组织(患者均知情同意),所有组织标本均行扫描电镜检查.对两组患者进行术后随访,分别应用Lund-Kennedy鼻内镜检查、慢性鼻窦炎疗效评定标准(1997年,海口)评估患者病情改善程度.采用t检验分析细菌生物膜对术后Lund-Kennedy评分的影响;采用卡方检验分析细菌生物膜与内镜手术疗效的相关性,以P＜0.05为差异有统计学意义.结果 试验组72例慢性鼻-鼻窦炎鼻息肉患者中有3例患者失访,失访率为4.2%.69例慢性鼻-鼻窦炎鼻息肉患者的细菌生物膜阳性率71.0%(49/69),并且可以观察到黏膜组织纤毛不同程度的损伤.对照组未发现细菌生物膜,可以观察到黏膜纤毛较浓密,排列整齐.卡方检验结果显示,性别、慢性鼻-鼻窦炎鼻息肉类型、病程等因素在试验组细菌生物膜阴性组与阳性组间差异无统计学意义(P值均＞0.05).细菌生物膜阳性组患者术后6个月和12个月的Lund-Kennedy 评分(4.78 ±1.67;4.55 ±1.61)分别高于细菌生物膜阴性组患者(3.65 ±1.39;3.65 ±1.18),差异均有统计学意义(t=-2.654,P＜0.01;t=-2.264,P＜0.05);细菌生物膜阴性组术后6个月和12个月的疗效明显优于细菌生物膜阳性组,差异有统计学意义(x2值分别为18.014、22.063,P值均＜0.001).结论 慢性鼻.鼻窦炎鼻息肉患者手术黏膜组织中存在细菌生物膜的生命周期不同形态,细菌生物膜的存在与否,与慢性鼻-鼻窦炎鼻息肉的类型、性别、病程无明显相关.细菌生物膜可能对患者术后疗效产生不良的影响.

Abstract：

Objective To explore the presence of bacterial biofilms(BF) in patients with CRS and the effect of BF on clinical symptoms and postoperative outcomes.Methods Seventy-two patients with chronic sinusitis were enrolled in this study.The control group included 15 patients with deviation of the nasal septum and 10 patients had a fracture of the nasal bone.Mucosa of the uncinate process or ethmoid near the ostium of the maxillary sinus was obtained during endoscopic sinus surgery.The specimens were subjected to scanning electron microscopy.Patients were followed for 1 year and observed by the LundKennedy endoscopy,and the Haikou standard classification (ESS-1997).Statistical analysis was performed by t-test or chi-square test Results Three patients were lost to follow-up.The scanning electron microscopy analysis showed bacterial biofilms in 49 of the 69 patients with chronic sinusitis.A marked destruction of the epithelium and cilia was observed in samples positive for bacterial biofilms.No bacterial biofilms were detected in the control group,and scanning electron microscopy showed normal epithelium and cilia in those specimens.There was no significant difference in gender,classification or duration of disease between the BF(-) and BF( + ) groups.At six months and one year postoperative,the Lund-Kennedy endoscopy scores for CRS patients with BF(4.78 ± 1.67 ;4.55 ± 1.61) were significantly higher than those without BF(3.65 ±1.39;3.65 ±1.18) (t =-2.654,P＜0.01;l =-2.264,P＜0.05).Based on the Haikou standard classification,there was a significantly difference between patients with BF and those without BF( x2 = 18.014,22.063 ,P ＜ 0.001,respectively).Conclusions Different life stages of bacterial biofilms were demonstrated to be present in CRS.Gender,classification or duration of disease did not affect the presence of bacterial biofilms in patients with CRS.There is a correlation between bacterial biofilms and an unfavorable outcome in patients with CRS after ESS.     

血清嗜酸粒细胞阳离子蛋白水平与变应性鼻炎及慢性鼻-鼻窦炎关系的探讨

目的 探讨变应性鼻炎(allergic rhinitis,AR)和慢性鼻-鼻窦炎伴鼻息肉(chronic rhinosinusitis with polyps,CRSWP)患者血清中嗜酸粒细胞阳离子蛋白(eosinophil cationic protein,ECP)的水平及其与患者鼻部过敏症状的关系.方法 用UniCAP100系统进行吸入物变应原过筛试验Phadiatop和检测血清ECP水平.取87例吸人性AR患者、49例CRSWP患者和20例健康人静脉血,采用荧光酶免疫分析法,检测血清ECP水平.对87例吸入性AR患者进行症状评分.结果 ①吸入性AR组和CRSWP过筛阳性组Phadiatop[中位数(M)和四分位间距[25%,75%]表示,以下同]分别为5185.0[983.0,14469.0]Fu和317.5[125.0,526.8]Fu,健康对照组和CRSWP过筛阴性组分别为43.5[29.0,105.0]Fu和30.0[28.0,43.0]Fu;②吸入性AR组血清ECP为24.8[14.6,49.1]μg/L,CRSWP过筛阳性组和阴性组分别为7.7[3.3,25.6]μg/L和12.5[6.7,16.7]μg/L,健康对照组为8.8[5.4,20.2]μg/L.吸入性AR组ECP明显高于CRSWP过筛阳性组、阴性组和健康对照组,行秩和检验示(z值分别为-2.821,-4.449和-4.028,P值均＜0.05),差异有统计学意义.CRSWP过筛阳性组和阴性组血清ECP较正常对照组无明显升高;③吸入性AR组患者鼻部症状评分(x-±s)为(9.139±1.892),与Phadiatop值呈明显正相关(r=0.854,P＜0.05);与血清ECP水平有一定相关性(r=0.434,P＜0.05).血清ECP和Phadiatop值有一定相关性(r=0.392,P＜0.05).结论 吸入性AR患者症状发作期血清ECP明显升高,且和疾病严重程度有相关性.血清ECP是一种较好且方便的吸入性AR辅助筛查工具,同时还可作为判断患者病情严重程度和预后的客观指标之一.而CRSWP患者血清ECP无明显升高.     

细菌生物膜在慢性鼻-鼻窦炎发病机制中的作用

慢性鼻-鼻窦炎（chronic rhinosinusitis，CRS）是耳鼻喉科最常见的疾病，也是全身常见的慢性疾病之一。在美国有2920万成人发病，占总人口14．2％。据统计，每年的药物、手术费用和因病造成的工作收入减少总计达60亿美元。CRS的病因和病理生理机制仍不清楚，因此目前尚缺乏有效的治疗方法。尽管CRS的药物和手术治疗取得很大进展，但仍存在一些难治性病例。因此，人们认为CRS的持续存在可能涉及其他一些未知因素。本文综述了有关细菌生物膜及其在CRS发病机制研究的最新进展。     

慢性鼻-鼻窦炎的微生态Meta分析

明确慢性鼻-鼻窦炎患者鼻腔的菌群分布情况,为指导慢性鼻-鼻窦炎的诊疗提供依据。     

Rate of allergic fungal etiology of chronic rhinosinusitis in Turkish population

The aim of this study is to investigate intranasal fungal incidence in Turkish patients with chronic rhinosinusitis (CRS). One hundred patients with CRS and 40 healthy subjects as a control group were included in the prospective study. Nasal lavage samples were investigated for the presence of fungus, using new culture techniques and histopathologic examination. Epidermal and intradermal hypersensitivity tests were used to find out fungal atopy. Levels of serum eosinophils, total IgE and presence of fungus-specific IgE were investigated in the blood samples. Quantitative parameters were analyzed using Pearson χ² test. Allergic fungal sinusitis (AFS) was diagnosed in 13(13%) patients. There was no fungal growth in the control group. Eosinophilic mucin was detected in 94% of patients. Clinical and laboratory parameters of CRS were not significantly different in patient groups with or without intranasal fungi. As a result, fungal incidence was not as high as expected in Turkish patients with CRS. Furthermore, no significant correlation could be found between presence of intranasal fungus and type-1 hypersensitivity in patients with CRS.