Diagnostic significance of serum periostin in eosinophilic chronic sinusitis with nasal polyps

Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease. Eosinophilic CRSwNP (ENP) exhibits a strong tendency for recurrence after surgery. Given that the treatment strategy of ENP differs from that of non-eosinophilic CRSwNP (nENP), clinical diagnostic criteria that distinguish ENP from nENP are needed.

Methods: In total, 94 CRSwNP patients were enrolled in the cohort. Factors associated with ENP were determined with regression analysis, and optimal cutoff points of the predictors were determined by a receiver operating characteristic curve.

Results: Serum periostin levels, blood eosinophils and basophils counts significantly differed between ENP and nENP. A combination of the cut-off values for the three predictors, including absolute blood eosinophil and basophil counts, yielded a sensitivity of 79.2% and 70.8%, and a specificity of 84.8% and 73.9%, respectively. Serum periostin levels yielded a sensitivity of 72.9% and a specificity of 60.9% for the diagnosis of ENP. The predicted probability of periostin in combination with blood eosinophils and basophils counts (AUC, 0.872) exhibited moderate accuracy. In addition, patients with ENP displayed an increased prevalence of smoking.

Conclusions: Periostin in combination with blood eosinophils and basophils counts has the potential to better refine current CRSwNP phenotypes.     

嗜酸性粒细胞与慢性鼻-鼻窦炎伴鼻息肉的相关性研究进展

慢性鼻窦炎（chronic rhinosinusitis,CRS）是鼻腔黏膜和鼻窦黏膜的慢性炎性疾病,根据有无鼻息肉可分为慢性鼻-鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps,CRSwNP）和慢性鼻-鼻窦炎（chronic rhinosinusitis without nasal polyps,CRSsNP）。鼻息肉组织常见有嗜酸性粒细胞(eosinophils,EOS) 浸润增多,根据嗜酸性粒细胞的浸润程度可将CRSwNP分为两个亚型：嗜酸粒细胞型慢性鼻窦炎伴鼻息肉(eosinophilic chronic rhinosinusitis with nasal polyps, ECRSwNP)和非嗜酸粒细胞型慢性鼻窦炎伴鼻息肉 (nonesinophilc chronic rhinosinusitis with nasal polyps,nonECRSwNP);将慢性鼻窦炎分为：嗜酸粒细胞型慢性鼻窦炎（eosinophilic chronic rhinosinusitis, ECRS)和非嗜酸粒细胞型慢性鼻窦炎(non eosinophilic,NECRS)。嗜酸性粒细胞在鼻息肉形成、发展机制中的作用多年来一直备受学者们关注。随着研究的不断深入,嗜酸性粒细胞在鼻窦炎鼻息肉炎症趋化、息肉形成、分型和预后中的作用得到越来越多的重视。     

Expression and distribution of glucocorticoid receptor isoforms in eosinophilic chronic rhinosinusitis

Objective

Patients with eosinophilic chronic rhinosinusitis (ECRS) show a high percentage of eosinophilic infiltration in the paranasal sinus mucosa. It is well documented that topical steroids have a beneficial effect in ECRS with nasal polyposis. We investigated mucosal distribution and cellular localization of glucocorticoid receptor (GR) isoform expression in human paranasal sinuses in relation to the clinical characteristics of eosinophilic chronic rhinosinusitis (ECRS) patients.

Methods

Mucosal specimens were obtained from 20 sinusitis patients by endoscopic sinus surgery (ESS). Quantitative fluorescence immunohistochemical analysis was employed to examine the degree of glucocorticoid receptor (GR) isoform expression in sinus mucosa specimens. An RT-PCR procedure was performed to determine the relative quantities of mRNA for the human GRα and GRβ genes.

Results

Patients in the ECRS group showed significant increases in peripheral blood eosinophils as compared to the non-ECRS group (16.98% vs. 2.31%). Positive immunoreactivity of GRβ expression was predominantly found to be positive in inflammatory cells. The absolute number of GRβ-positive cells in the ECRS group was increased in comparison with that in the non-ECRS group. The difference was statistically significant both in the maxillary (179.7 cells/mm² vs. 82.5 cells/mm²) and ethmoid sinus (302.0 cells/mm² vs. 61.5 cells/mm²) mucosa. The GRβ/GRα cell ratio in the ECRS group was elevated when compared with that in the non-ECRS group both in the maxillary and the ethmoid sinus mucosa, with the latter difference being significant.

Conclusions

The presence of high peripheral eosinophilia indicates a high likelihood of ECRS disease. Our results support the association of GRβ expression with ECRS. The expression of GRβ immunoreactivity, an endogenous inhibitor of steroid action previously associated with steroid insensitivity, may be one of major contributing factors in ECRS.     

Heme oxygenase-1 expression in chronic rhinosinusitis with eosinophilic infiltration

Objectives

Chronic rhinosinusitis (CRS) with eosinophilic infiltration is a type of intractable rhinosinusitis often associated with asthma. The oxidants are well known to induce aggravate asthma. Heme oxygenase-1 (HO-1), a cytoprotective enzyme against oxidant, has been extensively studied in airway diseases. However, no study that observed HO-1 in both epithelial and subepithelial tissues of CRS has been reported.

Methods

Part of each specimen derived from the nasal polyps of CRS with and without eosinophilic infiltration was promptly fixed for hematoxylin–eosin staining and immunohistochemical analysis for HO-1 and macrophages.

Results

We found that the expression of HO-1 in the epithelial layers of CRS without eosinophilic infiltration was significantly enhanced as compared with that of CRS with eosinophilic infiltration. On the other hand, the number of macrophages with HO-1 positive reactions was significantly greater in CRS with eosinophilic infiltration compared with CRS without eosinophilic infiltration.

Conclusions

Our study suggests that both a reduction of HO-1 expression in epithelial cells and an increase of infiltration of macrophages positive for HO-1 are related to the epithelial damage of CRS with eosinophilic infiltration.     

患者术前临床特征对嗜酸性粒细胞型慢性鼻窦炎伴鼻息肉的预测价值

目的 探讨患者的术前临床特征对嗜酸性粒细胞型慢性鼻窦炎伴鼻息肉(ECRSwNP)的预测价值,并构建用于临床实践的诺模图。方法 选取2019年9月—2020年9月就诊于新乡医学院第一附属医院并行功能性鼻内镜手术治疗的慢性鼻窦炎伴鼻息肉(CRSwNP)患者97例,根据术后病理结果嗜酸性粒细胞(EOS)浸润程度将其分为ECRSwNP组和非嗜酸性粒细胞型慢性鼻窦炎伴鼻息肉(nonECRSwNP)组,收集并比较两组患者的临床特征资料,采用单因素及多因素二元Logistic回归分析筛选对ECRSwNP有预测价值的术前特征资料,并构建用于临床实践的诺模图。采用SPSS 26.0和R语言软件4.1.2对数据进行分析。结果 两组患者在是否合并哮喘史、外周血嗜酸性粒细胞(EOS)计数、外周血嗜碱性粒细胞(Baso)计数、日本难治性嗜酸性慢性鼻窦炎流行病学调查(JESREC)评分、上颌窦评分、前后组筛窦评分、CT总分、E/M(筛窦与上颌窦的Lund-Mackay评分比值)上差异具有统计学意义(P<0.05)。单因素及多因素二元Logistic回归分析并构建的诺模图显示,基于哮喘史、外周血EOS、外周血...     

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.     

Clinical effects of submucosal middle turbinectomy for eosinophilic chronic rhinosinusitis

Objective

The preservation or resection of the middle turbinate (MT) during endoscopic sinus surgery (ESS) currently remains a matter of debate. The present study aimed to investigate the effects of submucosal middle turbinectomy (SMT) in ESS for eosinophilic chronic rhinosinusitis (ECRS).

基于随机森林与人工神经网络慢性鼻窦炎伴鼻息肉诊断模型的构建与分析

目的 慢性鼻窦炎伴鼻息肉(CRSwNP)是一个全球性的健康问题,现有的诊断技术存在一定局限性,因此有必要开发新的诊断模型来补充现有的诊断方法。方法 利用CRSwNP患者(GSE23552、GSE36830)的公开基因表达数据来识别潜在的差异基因,应用随机森林算法和人工神经网络进一步筛选特异性基因,建立CRSwNP的早期诊断模型。结果 共发现78个上调基因和25个下调基因,随机森林算法筛选了4个特异性基因(HPGDS、IL1RL1、FMO3、DOK3),人工神经网络构建出基于上述基因的预测模型,该模型具有良好的预测效果(AUC=0.986),独立数据集GSE194282进一步验证了其准确性(AUC=0.888)。结论 采用机器学习方法建立了一个基于基因表达水平的预测模型,该模型可以预测早期CRSwNP,有助于早期诊断和改善临床决策。     

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.     

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。     

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...     

Delayed type of allergic skin reaction to Candida albicans in eosinophilic rhinosinusitis cases

Objective

Eosinophilic chronic rhinosinusitis (ECRS) is frequently complicated by asthma, and recognized as refractory and persistent rhinosinusitis. However, the detailed pathophysiology of ECRS has not been elucidated yet. In this study, we investigated the association between recurrent ECRS and intradermal testing to multi-antigens including Candida albicans.

Proteomics blood testing to distinguish chronic rhinosinusitis subtypes

Objectives: To evaluate the potential of surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF‐MS) proteomic profiling of serum samples to distinguish chronic rhinosinusitis subtypes. Study Design: Translational study of serum samples from prospectively enrolled patients undergoing sinus surgery. Methods: Patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis were prospectively enrolled in an ongoing, institutional review board approved proteomics study. SELDI‐TOF‐MS was performed on 42 serum samples in patients with chronic rhinosinusitis with nasal polyposis (15 patients diagnosed with allergic fungal rhinosinusitis, 10 patients with Samter's triad, and 17 with chronic rhinosinusitis with nasal polyposis). Classification tree analysis on protein spectra developed from peaks detected in the 0 to 100 kD range was performed to identify disease subtypes. Results: SELDI‐TOF‐MS correctly identified patients with allergic fungal rhinosinusitis from serum samples with 84% sensitivity and 90% specificity, and correctly identified patients with Samter's triad with 88% sensitivity and 88% specificity in two subtype comparison groups. SELDI‐TOF‐MS correctly identified patients with allergic fungal rhinosinusitis with 76% sensitivity and 82% specificity, and correctly identified patients with Samter's triad with 80% sensitivity and 90% specificity in three subtype comparison groups. Conclusion: The study provides molecular evidence that allergic fungal rhinosinusitis is a discrete subtype of chronic rhinosinusitis. SELDI‐TOF‐MS is a promising technology that could lead to the development of a rapid blood test, to identify severe chronic rhinosinusitis subtypes. Further investigation into the utility of this technology is warranted.