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.     

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.     

Isolation of fungi by standard laboratory methods in patients with chronic rhinosinusitis

OBJECTIVES/HYPOTHESIS: Allergic fungal sinusitis and the role of fungi in the pathogenesis of chronic rhinosinusitis are topics of interest and controversy in rhinology. The classification of chronic rhinosinusitis as either a bacterial infection or an allergic (eosinophilic) reaction to fungi has significant implications for treatment of this disease process. We designed a study to determine whether standard isolation techniques, as employed in a university hospital mycology laboratory, could isolate and identify fungi in the intraoperative specimens from patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis. STUDY DESIGN: Forty-five random patients with a diagnosis of chronic rhinosinusitis by clinical and computed tomography criteria underwent endoscopic sinus surgery during 2001, performed by two senior surgeons (J.B.J., R.A.L.). Specimens of mucin, sinus secretions, and/or tissue were obtained intraoperatively and sent to the New York University Medical Center (New York, NY) mycology laboratory for isolation and identification of fungi. METHODS: Specimens were treated with Sputolysin and chloramphenicol; plated on Sabouraud, ChromAgar/Candida, Mycosel, and Niger seed agar plates; and incubated at 30 degrees C (or 37 degrees C) for up to 1 month. RESULTS: We were able to demonstrate the presence of fungi in 56% of intraoperative specimens obtained from patients undergoing surgery for chronic rhinosinusitis. CONCLUSIONS: Using a standard hospital mycology laboratory protocol, which is relatively inexpensive and readily available, fungus can be isolated from a majority of patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis. Educational statement: Discuss the possible role of fungus in chronic rhinosinusitis and evaluate the efficacy of documenting the presence of fungus in a routine fashion to encourage clinically relevant directed treatments.)     

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.     

Biotherapy and treatment of adult primary chronic rhinosinusitis with nasal polyps: Cellular and molecular bases

The present article reviews the molecular and cellular mechanisms involved in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwCRSwNP) and underlying the action mechanisms of biotherapies. Biotherapy uses substances naturally produced by the organism or their specific antagonists targeting a proinflammatory mechanism. CRSwCRSwNP is a form of chronic rhinosinusitis (CRS), which is classically subdivided in to 2 types according to the presence of polyps. In recent years, the concept of endotypes emerged, with a more exhaustive definition of the types of CRS according to inflammatory mechanism, with a view to developing personalized treatments. CRSwNP pathophysiology is poorly understood. Polyps arise from a primary epithelial lesion in a context of chronic local inflammation, mainly type 2 in Europe, implicating eosinophils, IgE, Th2 cytokines (IL-4/IL-13, IL-5) and T and B cells. Biotherapy seems promising in CRSwNP. The present review details the various pathophysiological pathways underlying the action mechanisms of biotherapies, and the various published studies, assessing efficacy and mode of action in the treatment of CRSwNP.     

Influence of age on the surgical outcome after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis

OBJECTIVES: To determine whether patient age is associated with the surgical outcome after endoscopic sinus surgery (ESS) with polypectomy. STUDY DESIGN: A prospective, controlled case series. MATERIALS AND METHODS: This study consisted of 60 patients who were diagnosed as having chronic rhinosinusitis (CRS) with nasal polyposis (NP) that was refractory to medical treatment. Three groups were classified according to patient age: pediatric (5-18 yr), adult (19-65 yr), and geriatric (over 65 yr). We collected 20 patients in each age group after applying the exclusion criteria. The extent of the polyps and the Lund-Mackay score were calculated for each patient, and they underwent ESS with polypectomy. We compared the objective endoscopic findings and subjective improvements in symptoms among the groups 6 months after the procedure. RESULTS: There were no statistical differences in polyp extent or Lund-Mackay score between the three age groups. The objective surgical outcome based on the endoscopic findings was worst in the pediatric group (45%), whereas the geriatric group showed the best results (90%). The differences in objective outcome among the three groups were significant, and patient age was a predictive variable for surgical result based on multiple logistic regression analysis. No major complications occurred, and the overall improvement in subjective symptoms was statistically significant in all three age groups at 6 months postoperatively. The subjective surgical outcome did not differ statistically between the groups, with the exception of olfactory disturbance. CONCLUSIONS: The results of the present study suggest that patient age influences the objective postoperative outcome in the endoscopic treatment of CRS with NP, and that ESS is an effective and reliable method for improving the subjective symptoms in patients of all age groups despite the statistically different objective surgical outcomes between the groups.     

Role of blood inflammatory cells in chronic rhinosinusitis with nasal polyps

Background/Objective: The pathophysiological and prognostic role of blood inflammatory cells in chronic rhinosinusitis with nasal polyps (CRSwNP) emerging from recent studies was investigated.

Material and Methods: The main available evidence and largely-recent publications were critically analyzed.

Results: Several authors reported a direct association between blood eosinophilia and CRSwNP recurrence rates. In some large series, a direct association between recurrent CRSwNP and blood basophil values emerged too. CRSwNP patients’ blood eosinophil and basophil values were strongly related. It was also found that preoperative neutrophil-to-lymphocyte, eosinophil-to-lymphocyte, and basophil-to-lymphocyte ratios were significantly higher in patients who experienced a disease relapse than in those who did not. In histologically-confirmed eosinophilic-type CRSwNP treated with endoscopic sinus surgery, mean blood eosinophil values dropped significantly from before to after the surgical procedure.

Conclusions/Significance: CRSwNP endotypes have different inflammatory profiles reflected in the relative proportions of different types of blood cells. The available data support the theory that blood eosinophil and basophil levels should be included in the routine preoperative work-up of CRSwNP patients in order to give patients accurate prognostic information, adopt rational follow-up protocols after surgery, and provide dedicated postoperative medical treatments.     

慢性鼻-鼻窦炎伴鼻息肉合并哮喘患者肺功能分析

目的 分析慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)合并哮喘患者肺功能情况。 方法 选取74例经鼻内镜手术(FESS)的CRSwNP合并哮喘患者,分组进行肺功能比较:男49例(男性组),女25例(女性组);吸烟32例(吸烟组),不吸烟42例(非吸烟组);血清特异性IgE阳性者27例(IgE组),阴性者47例(非IgE组);外周血嗜酸粒细胞升高(外周血嗜酸粒细胞绝对值>0.5×10⁹/L)者27例(外周血嗜酸粒细胞升高组),未升高者47例(外周血嗜酸粒细胞非升高组);术后送检鼻息肉组织嗜酸粒细胞升高(嗜酸粒细胞平均>10个/HPF)者31例(组织嗜酸粒细胞升高组),未升高者43例(组织嗜酸粒细胞非升高组)。所有肺功能检测均在具有上岗资质变态反应科专业医师指导下完成,检测数据由德国康讯肺功能仪(PowerCubeBody)采集,肺功能指标包括第1秒用力呼气容积(FEV₁)占预计值的百分比(FEV₁% pre)、FEV₁与用力肺活量(FVC)的比值占预计值的百分比(FEV₁/FVC% pre)、最大通气量(MVV)占预计值的百分比(MVV% pre)、用力呼出50%肺活量时的瞬间呼气流(FEF_50%)、用力呼出75%肺活量时的瞬间呼气流(FEF_75%)及最大呼气中期流量(MMEF)。74例患者评估肺功能下降程度后针对性给予雾化吸入治疗,2~3次/d,沙美特罗替卡松粉吸入剂1吸,2次/d,予孟鲁司特钠 10 mg/d,氯雷他定10 mg/d口服,同时给予盐酸氮卓斯汀鼻喷剂 2次/d+布地奈德鼻喷雾剂 2次/d喷鼻治疗。自入院至术前,患者行药物治疗时间为1~14 d。所有患者术前30 min雾化吸入1次,麻醉前行沙美特罗替卡松粉吸入剂1吸。对术前药物干预后肺功能改善情况进行判定。 结果 74例患者均顺利完成手术。入院时女性组FEF_50%、FEF_75%及MMEF低于男性组(t分别为3.213、2.829、3.644,P分别为0.002 0、0.006 1、0.000 5),吸烟组较非吸烟组、外周血及鼻息肉组织中嗜酸粒细胞升高组均较非升高组FEV₁/FVC% pre下降(t分别为2.032、2.259、2.634,P分别为0.045 8、0.029 2、0.010 3),同时鼻息肉组织嗜酸粒细胞升高组较非升高组MVV% pre降低(t=2.453, P=0.0166)。经术前规范药物干预后,患者肺功能指标FEV₁%pre、FEV₁/FVC% pre、MVV% pre、FEF_50%、FEF_75%及MMEF均较入院时改善(t分别为6.640、6.071、8.166、5.554、6.137、4.256, P均为0.000 0)。 结论 CRSwNP合并哮喘患者中,女性较男性更易伴发小气道功能障碍;吸烟、外周血及鼻息肉组织嗜酸粒细胞升高亦可影响肺功能;规范的术前药物干预可有效改善CRSwNP合并哮喘患者的肺功能,减少围术期哮喘急性发作风险,有助于手术顺利实施。     

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...     

加速康复外科理念在慢性鼻-鼻窦炎伴鼻息肉手术治疗中的应用

目的 探讨加速康复外科(ERAS)在慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)手术患者围手术期的应用效果。 方法 选取CRSwNP患者136例,随机分为ERAS组70例,对照组66例,两组均接受鼻内镜下鼻息肉切除加鼻窦开放手术,ERAS组患者行术前宣教、围手术期气道评估干预、缩短禁食时间、术中控制性低血压、按时镇痛等一系列优化措施;对照组行传统的围术期处理。比较两组术前肺功能异常可耐受手术率、术后疼痛评分、术后24 h鼻腔出血量、术后住院时间、总住院时间。 结果 ERAS组、对照组术前肺功能异常患者可耐受手术率分别为93.3%、75.0%,两组比较差异无统计学意义(χ2=1.924, P=0.165); ERAS组患者术后鼻部疼痛、鼻塞、头痛、眼部胀痛、流泪、耳闷和睡眠困难的VAS评分均低于对照组(P均<0.001); ERAS组术后24 h内出血量为5.7(3.0,10.3)mL,对照组为7.2(5.0,13.2)mL,两组比较差异无统计学意义(U=-0.913, P=0.361)。平均住院日ERAS组、对照组分别为(4.6±0.8)、(7.5±1.1)d,两组比较差异有统计学意义(t=17.79, P<0.001);术后住院日ERAS组与对照组分别为(2.1±0.5)、(3.8±0.3)d,两组比较差异有统计学意义(t=23.94, P<0.001)。 结论 将ERAS理念贯穿于CRSwNP患者围手术期将有效减轻患者心理和生理的创伤应激反应,缩短住院时间。