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.     

先天免疫分子Toll-Like-Receptor-9在慢性鼻窦炎鼻息肉发病机制中的作用探讨

目的:检测先天免疫分子Toll-Like-Receptor-9(TLR-9)蛋白在鼻息肉黏膜上皮细胞中的存在及表达,以期探讨其在鼻息肉发病中的作用及功能.方法:取鼻窦内镜下摘除的鼻息肉标本10例(鼻息肉组),鼻中隔偏曲和鼻外伤等手术切除的下鼻甲标本10例作对照组,消化法行原代细胞培养,流式细胞仪双抗纯化上皮细胞和检测上皮细胞中TLR-9蛋白含量.结果:①消化法培养人鼻黏膜原代细胞中上皮占98%;②鼻息肉组和对照组上皮细胞均有TLR-9表达,但鼻息肉组的TLR-9表达(11%～15%)显著低于对照组(49%～60%).结论:TLR-9存在于正常和鼻息肉的黏膜上皮中,但鼻息肉组水平下降,推测先天免疫分子TLR-9可以在鼻息肉发病机制中起作用.     

Indoleamine 2,3-dioxygenase expression is associated with chronic rhinosinusitis with nasal polyps and antrochoanal polyps

Chronic rhinosinusitis without and with nasal polyps (CRSwNP and CRSsNP), and antrochoanal polyps are different phenotypes with different pathomechanisms. Indoleamine 2,3-dioxygenase (IDO) is an enzyme expressed in many cells involved in the catabolism of the essential amino acid tryptophan to kynurenine. IDO might have a role in allergic airway inflammation. The aim was to evaluate if IDO expression is associated with CRSsNP, CRSwNP, or ACP. One hundred fifty specimens from the nasal cavity and sinus mucosa were immunohistochemically stained with mAb anti-IDO. The expression of epithelial and leukocyte IDO was associated with CRSwNP and ACP. The presence of ASA intolerance, asthma, atopy, smoking and use of medication did not significantly change the results. The different expression of IDO could putatively indicate the differences in the pathomechanisms of CRSsNP, CRSwNP and ACP. Further studies on the role of IDO in upper airways pathologies are required.     

变应性因素在慢性鼻窦炎鼻息肉发病中的作用

目的探讨变应性因素与慢性鼻窦炎鼻息肉的临床表现和病理生理改变的关系。方法回顾性分析81例慢性鼻窦炎鼻息肉患者,根据是否存在变应性因素,将其分为为菲变应性因素组和变应性因素组,比较两组症状VAS评分、鼻息肉主观评分、鼻窦CT Lund-MacKay评分、嗅觉功能、鼻阻力等指标问的差异。结果81例患者中,非变应性因素组45例,变应性因素组36例。两组问症状VAS评分和鼻息肉主观评分无显著性差异（t=0．87,P=0．40：t=0．58,P=0.64）。鼻窦CT的Lund—MacKay评分,变应性因素组的前组筛窦病变程度较非变应性因素组严重,存在显著性差异（f=2．11,P=0．03）,而其余各鼻窦及OMC区均无显著性差异。两组间嗅觉功能以及双侧鼻腔总阻力亦无显著性差异（t=0．15,P=0.88：t=0．57,P=0．61）。结论变应性因素在慢性鼻窦炎鼻息肉的发病中不起主导作用,对临床症状、鼻息肉大小、嗅觉功能和鼻阻力等方面没有显著影响,但可能与前组筛窦的病变程度存在一定相关性。     

半乳糖凝集素10与慢性鼻窦炎伴鼻息肉

半乳糖凝集素10(Galectin-10)被发现已有很长的历史,但是探索其病理作用的研究很少。近几年,半乳糖凝集素10受到越来越多的关注,特别是其在气道嗜酸性粒细胞疾病中研究越来越多。综述了Galectin-10历史回顾及其在慢性鼻窦炎中的相关研究,Galectin-10/CLC蛋白不仅仅可作为以2型免疫反应为特征的CRSwNP的生物标志物,而且可能在其发病机制中发挥一定作用,并且很有希望作为以2型免疫反应为特征的CRSwNP的药物靶点。     

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.     

Epithelial genes in chronic rhinosinusitis with and without nasal polyps

BACKGROUND: Genetic studies on chronic inflammatory diseases have resulted in an emphasis on the epithelial interface with the environment and the genes that influence this interaction. This study examines the expression of key epithelial genes implicated in the pathogenesis of other inflammatory disorders for their role in chronic rhinosinusitis (CRS). METHODS: Epithelial cells were collected from the inferior turbinate, middle turbinate, and/or uncinate from 62 subjects undergoing sinonasal surgery. Patient groups included 21 CRS patients with nasal polyposis, 23 CRS patients without nasal polyposis, and 18 controls. Samples were analyzed for S100A7, S100A8, S100A9, SLC9A3R1, G-protein-coupled receptor for asthma, and serine protease inhibitor kazal type 5 (SPINK5) by quantitative real-time polymerase chain reaction. Immunohistochemistry (IHC) was performed to analyze expression of SPINK5 lympho epithelial kazal-type inhibitor (LEKTI) in sinonasal samples. RESULTS: Expression of S100A7 and S100A8 was significantly decreased in CRS with and without nasal polyps when compared with controls. S100A9 expression was significantly decreased in CRS without nasal polyps, and SPINK5 expression was significantly decreased in CRS with nasal polyps. SPINK5 (LEKTI) protein was detected in sinonasal tissue and was significantly decreased in polyp samples using IHC. CONCLUSION: This study shows marked reductions in the level of expression of several genes involved in epithelial barrier maintenance and repair in the inflammatory state of CRS.     

Decreased PLUNC expression in nasal polyps is associated with multibacterial colonization in chronic rhinosinusitis patients

PLUNC (palate, lung, and nasal epithelium clone) is an epithelium-secreted protein that plays a crucial role in the host’s defense against bacterial infection. The function of PLUNC in the sinus remains poorly understood. To examine whether the expression levels of PLUNC could serve as a predictive outcome biomarker for patients with CRSwNP and bacterial colonization, we investigated the association of PLUNC expression levels with bacterial colonization in the sinuses. A total of 174 patients who underwent sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled in this study. The tissue samples obtained from patients were examined using preoperative sinus computed tomography (CT) scans, postoperative bacterial cultures, and nasal polyp examinations. PLUNC mRNA and protein expression were quantified using RT-PCR and immunohistochemistry. We identified that decreased PLUNC expression is associated with multibacterial colonization (P = 0.0001), specifically those mediated by Staphyloccocus aureus (P = 0.037) and Pseudomonas aeruginosa (P = 0.002). The patients who required repeated sinus surgeries for recurrent or persistent sinusitis also presented much lower PLUNC expression than those who did not require repeated sinus surgery (P = 0.001). However, gender, age, and CT scores were not associated with PLUNC expression. These results suggest that reduced PLUNC expression is associated with bacterial colonization as well as treatment outcome in CRSwNP patients. Investigation of the association between PLUNC expressions and chronic rhinosinusitis may lead to the development of a novel biomarker for treatment outcome in CRSwNP patients.     

The expression of cancerous inhibitor protein phosphatase 2A in chronic rhinosinusitis with nasal polyps

Conclusion: The study suggests that cancerous inhibitor of protein phosphatase 2A (CIP2A) expression and eosinophilia associate with chronic rhinosinusitis with nasal polyps with aspirin exacerbated respiratory disease (CRSwNP?+?AERD). Further studies with a larger sample size are needed to evaluate further the role of CIP2A and related pathways in CRSwNP?+?AERD.

Objectives: Low prostaglandin E2 levels putatively associate with CRSwNP?+?AERD and decreased c-Myc levels. The aim of this study was to evaluate the expression and revision-predictive role of oncoprotein CIP2A, another c-Myc modulator, in CRSwNP with/without AERD, and in antrochoanal polyps.

Method: Ninety retrospective archival objective glasses of nasal polyp tissue from CRSwNP or ACP patients were used for assessing mucosal eosinophilia. Of this population, 90 archival nasal polyp specimens were available for immunohistochemical staining with a polyclonal anti-CIP2A antibody, together with 19 control nasal mucosa specimens. CIP2A staining intensity and tissue eosinophilia were assessed by two blinded observers with a light microscope. Subject characteristics from 90 patients and 19 controls were obtained from patient records and additionally by a questionnaire from controls. The follow-up data was available from patient records of 84 patients and 16 controls.

Results: The expression of epithelial CIP2A was detected both in control inferior turbinate mucosa and nasal polyps. The expression was significantly lower in the CRSwNP?+?AERD group compared to controls and CRSwNP without AERD (p?p?p?>?0.05), whereas previous surgery, allergic rhinitis, and use of corticosteroids did predict the need for revision surgery (p?相似文献   

Prospective evaluation of clarithromycin in recurrent chronic rhinosinusitis with nasal polyps

IntroductionThe antiinflammatory effects of macrolides, especially clarithromycin, have been described in patients with chronic rhinosinusitis without polyps and also other chronic inflammatory airway diseases. There is no consensus in the literature regarding the effectiveness of clarithromycin in patients with chronic rhinosinusitis with sinonasal polyposis and the national literature does not report any prospective studies on the efficacy of clarithromycin in chronic rhinosinusitis in our population.ObjectiveTo evaluate the effect of clarithromycin in the adjunctive treatment of recurrent chronic rhinosinusitis with sinonasal polyposis refractory to clinical and surgical treatment.MethodsOpen prospective study with 52 patients with chronic rhinosinusitis and recurrent sinonasal polyposis. All subjects received nasal lavage with 20 mL 0.9% SS and fluticasone nasal spray, 200 mcg / day, 12/12 h for 12 weeks; and clarithromycin 250 mg 8/8 h for 2 weeks and, thereafter, 12/12 h for 10 weeks. The patients were assessed by SNOT 20, NOSE and Lund-Kennedy scales before, immediately after treatment and 12 weeks after treatment. The patients were also evaluated before treatment with paranasal cavity computed tomography (Lund-Mackay) and serum IgG, IgM, IgA, IgE and eosinophil levels. The outcomes evaluated were: SNOT-20, NOSE and Lund-Kennedy.ResultsMost patients were women, aged 47 (15) years (median / interquartile range), and 61.5% (32/52) had asthma. All patients completed the follow-up after 12 weeks and 42.3% (22/52) after 24 weeks. Treatment resulted in a quantitative decrease in the SNOT-20 [2.3 (1.6) vs. 1.4 (1.6); Δ = ?0.9 (1.1); p < 0.01]; NOSE [65 (64) vs. 20 (63); Δ = ?28 (38), p < 0.01] and Lund-Kennedy [11 (05) vs. 07 (05); Δ = ?2 (05); p < 0.01] scores. SNOT-20 showed a qualitative improvement (>0.8) in 54% (28/52, p < 0.04) of patients, a group that showed lower IgE level [108 (147) vs. 289 (355), p < 0.01]. The group of patients who completed follow-up 12 weeks after the end of treatment (n = 22) showed no worsening of outcomes.ConclusionLong-term adjuvant use of low-dose clarithromycin for chronic rhinosinusitis patients with recurrent sinonasal polyposis refractory to clinical and surgical treatment has resulted in improved quality of life and nasal endoscopy findings, especially in patients with normal IgE levels. This improvement persisted in the patient group evaluated 12 weeks after the end of the treatment.     

Predictive markers of long-term recurrence in chronic rhinosinusitis with nasal polyps

BackgroundIn last years, many attempts were made to recognize chronic rhinosinusitis with nasal polyps (CRSwNP) phenotypes focusing on identifying relevant key pathogenic molecules. Polyps recurrence rate ranges from 4% to 60%, so it's clear that not all clinical and immunologic factors associated with recurrence are known.ObjectiveWe investigate the inflammatory profile in patients with long term recurrent and non-recurrent CRSwNPs and if a specific profile is associated with recurrence, comparing eosinophilic, neutrophilic and lymphocytic infiltration, as well as IL-5 and IL-8 expression to long term recurrence rate.MethodsThis prospective study included 44 adult patients with CRSwNP treated with endoscopic sinus surgery between 2008 and 2010. Long term follow-up data (8–10 years) indicated that among 44 patients, 18 (40.1%) experienced long term recurrence of nasal polyposis needing maximal medical treatment or revision surgery. We realized two groups: one with patients who didn't present long term recurrence (26 patients) and another with patients who presented long term recurrence (18 patients) and in both groups eosinophilic, neutrophilic and lymphocytic infiltration and IL-5 and IL-8 expression were measured.ResultsThe parameters that reached statistical significance (p < 0.05) comparing the two groups were eosinophilic infiltration and IL-5 expression, whereas neutrophilic and lymphocytic infiltration, as IL-8 expression didn't show any significant difference.Asthma and aspirin intolerance seemed significantly more frequent in patients with recurrence, while allergy presented not statistically significant difference between two groups.ConclusionsWe can conclude that high eosinophilic infiltration and high IL-5 expression in CRSwNP correlate with higher rate of long term recurrence, while neutrophilic and lymphocytic infiltration, and IL-8 expression don't correlate with it. These findings provide the opportunity to improve our ability to predict the prognosis of surgical intervention, although it is still needed to explore the optimal predictor of outcome in CRSwNP.