Metalloproteinase function in chronic rhinosinusitis with nasal polyposis

OBJECTIVES: Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma share characteristic inflammatory features and histopathologic findings of airway remodeling. Remodeling, which is controlled by matrix metalloproteinases (MMP), is a key event in the pathogenesis of asthma. The MMP functions have rarely been evaluated in CRSwNP. STUDY DESIGN: Prospective and in vivo. METHODS: MMP-7, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations were analyzed by enzyme-linked immunosorbent assay and their molecular forms by Western immunoblotting and gelatin zymography in 24 patients operated on for CRSwNP and in nasal lavages from 19 healthy controls. MMP function, protective or destructive, was evaluated by comparing MMP/TIMP-1 levels with the disease activity, estimated by tissue eosinophilia and a need for re-operations. RESULTS: Significantly increased levels of MMP-8/TIMP-1 and MMP-9/TIMP-1 were found in patients without tissue eosinophilia relative to eosinophil-positive CRSwNP patients and controls, as well as in patients who did not require re-operation in comparison with re-operated patients. In eosinophil-positive and re-operated patients, these parameters were within the same range than in controls. CONCLUSIONS: Proteolytic spectrum is different in eosinophilic and noneosinophilic CRSwNP, suggesting a new mechanism for eosinophil accumulation in the disease pathogenesis. Enhanced MMP-8 and MMP-9 expression was associated with a better prognosis/clinical outcome, and thus these results may represent a synergic, protective role of MMP-8 and MMP-9 in host response in CRSwNP. Because synthetic MMP inhibitors, capable of equilibrating the unfavorable MMP/TIMP-ratio, may be of potential therapeutic value in chronic respiratory tract diseases, the MMP functions in inflammatory conditions need to be carefully established.     

The importance of follow-up examinations in chronic rhinosinusitis with nasal polyposis

PurposeClinical examinations following functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) are critical for physicians to assess results of the intervention and to early identify recurrences. However, no clear consensus on the frequency and timing of clinical examinations following surgery exists. The aim of this study was to analyze CRSwNP recurrences after FESS with a specific focus on the adherence to follow-up examinations.Materials and methodsSixty patients who underwent FESS for CRSwNP were enrolled. Clinical parameters were recorded. Adherence to follow-up examinations with nasal fiber optic endoscopy and regular administration of nasal steroids were analyzed.ResultsAdherence to periodic clinical examinations and regular treatment with nasal steroids was 25 %. CRSwNP recurrence was observed in 56.7 % of cases at the last follow-up examination. No statistically significant difference concerning nasal symptoms was observed between patients with and without current recurrence (p > 0.05). Subjects who underwent regular examinations and prompt treatment of small recurrences had a lower probability of relapse at their last examination (7.7 % versus 38.2 %, respectively; p < 0.001). Polyp grade > 2 in patients with or without adherence were seen in 15.4 % and 42.9 % of cases, respectively (p < 0.05).ConclusionsAdherence to follow-up examinations with nasal optic fiber endoscopy is crucial to early identify recurrence after surgery and promptly treat it with medical therapy.     

Current concepts in therapy of chronic rhinosinusitis and nasal polyposis

The exact pathophysiological mechanisms leading to chronic rhinosinusitis (CRS) still to a large extent remain obscure. However, recently there has been some progress in elucidating the etiology of nasal polyposis, especially regarding tissue eosinophilia as well as the role of aspirin intolerance and eicosanoid mediators. Endonasal sinus surgery has evolved to be the treatment of choice in CRS and nasal polyposis in all cases where conservative treatment has failed or resulted in only a partial or temporary relief. Today, state of the art in surgical technique includes the ability to combine microscopic and endoscopic procedures. Regardless of technical advances like powered instrumentation or computer-aided surgery, in a modern protocol, surgical therapy can offer only one option within a complex and individually tailored therapeutical concept. This review discusses current concepts and new developments in the diagnosis and treatment of CRS and nasal polyposis.     

IL-17C expression in nasal epithelial cells of chronic rhinosinusitis with nasal polyposis

Interleukin 17C (IL-17C) is a functionally distinct member of the IL-17 family that is selectively induced in epithelia by bacterial challenge and inflammatory stimuli. The goal of this study was to explore the expression of IL-17C in nasal epithelial cells and their role in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNPs). IL-17C expression was detected using immunohistochemistry (IHC) of the epithelial cell layers and using the western blot assay on whole tissue homogenates from control subjects (n = 10) and CRSwNP patients [10 non-eosinophilic polyps and 10 eosinophilic polyps (EPs)]. Expression of IL-17C and P47-phox were evaluated in the human nasal epithelial cells (RPMI-2650 cells) after treatment with staphylococcal enterotoxin B (SEB) and pretreatment with reactive oxygen species (ROS) scavenger, N-acetyl l-cysteine (NAC). Finally, IL-17C expression was demonstrated in eosinophilic rhinosinusitis murine model using IHC. Epithelial expression of IL-17C was higher in nasal polyps (especially in EPs) compared to control mucosa. SEB increased the expression of IL-17C and P47-phox in RPMI-2650 cells. SEB-induced expressions of both IL-17C and P47-phox were significantly decreased in NAC-pretreated cells. Epithelial expression of IL-17C was significantly higher in experimental mice compared to control mice. SEB-induced IL-17C expression in nasal epithelial cells is mediated by ROS production. This pathway may be associated with the pathogenesis of CRSwNP, especially eosinophilic nasal polyps.     

Effectiveness of balloon sinuplasty in patients with chronic rhinosinusitis without polyposis

IntroductionBalloon sinuplasty is a minimally invasive endoscopic procedure, developed with the aim of restoring patency of the paranasal sinuses ostia with minimal damage to the mucosa.ObjectiveTo evaluate the effectiveness of balloon sinuplasty in patients with chronic rhinosinusitis.MethodsThis was a prospective cohort study comprising 18 patients with chronic rhinosinusitis without polyposis who underwent balloon sinuplasty. Patients were evaluated for clinical criteria, quality of life (Sino-Nasal Outcome Questionnaire Test-20 [SNOT-20]), and computed tomography of the sinuses (Lund–Mackay staging) preoperatively and three to six months after the procedure.ResultsOut of 18 patients assessed, 13 were included, with a mean age of 39.9 ± 15.6 years. Ostia sinuplasty was performed in 24 ostia (four sphenoid, ten frontal, and ten maxillary sinus). At the follow-up, 22 (92%) ostia were patent and there was no major complication. There was symptomatic improvement (SNOT-20), with Cronbach coefficients for consistency of the questionnaire items of 0.86 (95% CI: 0.73–0.94) preoperatively and of 0.88 (95% CI: 0.77–0.95) postoperatively, the difference being statistically significant (p < 0.001). In addition, there was marked reduction of the computed tomography signs, an average of 4.2 point score (p < 0.001).ConclusionSinuplasty is effective in reducing symptoms and improving quality of life as a treatment option for chronic rhinosinusitis in selected patients.     

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.     

Optical coherence tomography for biofilm detection in chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease that seems to be associated with the presence of microbial biofilms and corresponding subepithelial inflammatory reactions. Optical coherence tomography (OCT) might be applied to detect bacterial and fungal biofilms in patients with CRSwNP. A total of 27 patients with CRSwNP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of six patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa specimens applied as negative controls were processed to OCT analysis and H.E. and Gram staining. Biofilm was detected in 22 of 27 patients (81.5 %) with CRSwNP and in none of six negative controls. In our series, OCT scan showed an obvious association with the findings of H.E. and Gram staining and was allocated to be a good predictor of biofilm existence. On OCT images, biofilms were displayed as distinct superficial layers with high optical density. It was found that microscopic architecture of biofilms was strongly associated with the integrity of nasal mucosa and to the cellular pattern of subepithelial inflammatory reaction. This study confirmed the presence of microbial biofilms in patients with CRSwNP according to OCT scans and histological analysis. Since biofilms may affect the severity and recurrence rate of CRS treated by ESS they should be detected preoperatively. In conclusion, single application of OCT analysis or combination with conventional histological protocols provides a robust and reliable method for the detection of bacterial and fungal biofilms in CRSwNP. Level of evidence 3b, individual case–control study.     

Evidence-based recommendations for antimicrobial nasal washes in chronic rhinosinusitis

BACKGROUND: Chronic rhinosinusitis (CRS) refractory to medical and surgical therapy is a difficult problem for patients and physicians. Topical antimicrobial nasal irrigations are commonly used for treatment with great variation in methodology and without clear scientific support for current treatment formulations. The purpose of this study was to develop a scientific rationale for creating standardized recommendations for clinical practice in the use of topical antimicrobial washes for CRS. METHODS: An extensive review of basic science and clinical literature on the treatment of CRS with topical antimicrobial washes was completed. Pharmacokinetics of and organism susceptibility to appropriate topically applied antimicrobial agents were reviewed. RESULTS: The most common organisms associated with CRS were identified. The relevant pharmacokinetics of drugs targeted at these organisms are presented. Susceptibility breakpoints set by the National Committee for Clinical Laboratory Standards are identified to help establish the most effective concentration of the identified drugs. Recommendations for agent selection, agent concentration, length of treatment, dosing schedule, and methods of irrigation are presented. CONCLUSION: Antimicrobial nasal washes provide a potentially effective treatment for the growing population of patients who remain symptomatic after appropriate medical and surgical intervention. This study establishes the basic principles supporting this treatment option and offers rational, evidence-based treatment guidelines. The study has identified additional areas that need to be investigated before prospective clinical trials can be effectively undertaken.     

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.     

Downregulation of caveolin-1 in chronic rhinosinusitis with and without nasal polyps

European Archives of Oto-Rhino-Laryngology - The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that caveolin-1 (Cav-1) is a 22&nbsp;kDa...