生物制剂治疗支气管哮喘的研究进展

支气管哮喘是呼吸系统常见的气道慢性炎症性疾病，吸入皮质激素是其主要治疗策略。随着哮喘发病机制的深入研究，发现气道炎症类型不同，吸入激素治疗的反应不同。针对气道炎症反应过程中的炎性介质，已经开发了多种生物制剂。临床随机对照研究中，严重嗜酸粒细胞性哮喘患者从中获益，部分临床疗效存在争议。儿童用药的疗效和安全性及药物对疾病产生的长期影响还需进一步研究证实。     

变应性鼻炎和哮喘的相关性分析

目的 了解变应性鼻炎与哮喘的相关性。方法 对1526例变应性鼻炎患者与哮喘的相关性进行了临床调查。采用阿罗格点刺试验对患者进行变应原检查。结果 发现43．8％的变应性鼻炎患者并发哮喘。其中,先有鼻炎后有哮喘者占52．3％,先有哮喘后有鼻炎者占36．5％,二者在统计学上有明显差异。42．4％的变应性鼻炎患者有明显的过敏性疾病家族遗传史,而合并哮喘的患者过敏性疾病家族遗传史高达61．7％。调查中还发现有30．7％的变应性鼻炎患者合并过敏性皮肤病。结论 特应性个体产生呼吸道炎症后,不管哮喘发生在先,还是鼻炎发生在先,都容易诱发全呼吸道炎症;变应性鼻炎不仅和支气管哮喘相关,也和其他过敏性疾病相关;变应原点刺试验结果以屋尘螨的阳性率最高。     

气道慢性炎症与慢性鼻窦炎中PPARγ和ILC2s关系的研究进展

Ⅱ型固有淋巴样细胞(ILC2s)是一种非B、非T的新型淋巴细胞,可以产生大量促炎和调节性细胞因子,以应对局部损伤、炎症、病原体感染或肿瘤。过氧化物酶体增殖物激活受体γ(PPARγ)属于细胞核激素受体超家族配体激活转录因子之一,与相应配体结合后调节细胞增殖、分化、代谢等,从而在炎症反应中发挥重要作用。PPARγ广泛分布在人类鼻黏膜及鼻息肉黏膜中,并通过作用于ILC2s上的抑制肿瘤发生受体(ST2)、程序性细胞死亡蛋白-1(PD-1)以及影响ILC2s的能量代谢等途径影响ILC2s的功能。本文就PPARγ与ILC2s的关系以及在气道慢性炎症及慢性鼻窦炎(CRS)中的表达及相互作用进行综述,从而为气道慢性炎症性疾病及CRS的发病机制及治疗提供新思路。     

变应性鼻炎和哮喘患者变应原类型及免疫治疗疗效的比较

目的 比较单纯性变应性鼻炎患者和哮喘患者变应原阳性率及变应原免疫治疗情况,分析机体对变应原反应程度与疾病的发生、发展及免疫治疗的关系.方法 对100例单纯性变应性鼻炎和100例哮喘患者行皮肤点刺试验,根据变应原类型从中挑选各30名符合混合螨免疫治疗条件者进行变应原免疫治疗.标准化皮肤点刺液和脱敏制剂均由阿罗格公司提供.结果 单纯变应性鼻炎组的主要吸入性变应原和摄入性变应原阳性率均显著低于哮喘组,且主要吸入性变应原屋尘螨和粉尘螨的强阳性率亦明显低于哮喘组.变应原免疫治疗则无显著差异.结论 机体对变应原的反应程度与疾病的发生、发展可能存在一定的关系.对变应性鼻炎的早期干预是必要的.     

前列腺源性ETS因子在哮喘及鼻黏膜炎性疾病中的研究进展

含SAM尖端结构域的E26转化特异性因子(SPDEF)是ETS转录因子家族的最新成员之一, SPDEF又称为前列腺源性ETS因子(PDEF),首次发现其在前列腺癌中高度表达,参与肿瘤细胞的增殖分化、迁移凋亡和血管形成。近年来研究发现SPDEF与杯状细胞增生和分化密切相关,是调控呼吸道黏液高分泌的核心因子。对SPDEF调控黏液高分泌的机制及其在呼吸道慢性炎性疾病中的研究进展做一综述,以期为呼吸道黏液高分泌疾病的发病机制和诊治提供新思路。     

Waardenburg综合征Ⅰ型PAX3基因突变筛查及遗传咨询

目的Waardenburg综合征Ⅰ型患者及父母临床和基因诊断及再生育聋儿风险评估。方法采集1个Waardenburg综合征I型中国家系详细的临床资料,签署知情同意书获取血样。聚合酶链反应扩增PAX3基因编码区的全部外显子,在ABI自动测序仪上进行正反向测序,利用GeneTool软件及分子生物学网站的信息分析数据。结果患者PAX3基因第2外显子第142位G〉A杂合突变,导致甘氨酸到丝氨酸的突变。父母均未检测到突变。结论发现PAX3基因新的致病突变。患者临床和遗传诊断符合Waardenburg综合征Ⅰ型诊断,可对患者遗传咨询提供依据,为父母提供再生育聋儿风险评估及产前诊断。     

Upper airway cough syndrome in children and two inflammatory factors: TRPV1 and TGF-β2

Objectives

The aim of the study was to investigate upper airway cough syndrome (UACS) in children and to determine alternative methods to explore the relationships among TRPV1, TGF-β2, and UACS.

Methods

In 2012, 104 children with adenoid hypertrophy aged 2–13 years who were admitted to the otolaryngology department, Capital Institute of Pediatrics-affiliated children's hospital, were included in this study. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) studies for TRPV1 and TGF-β2 were performed to understand the relationship between the two inflammatory factors, and the correlations among the indices and UACS. The research was divided into three stages. In stage 1, 72 children (24 UACS and 48 controls) were enrolled in the study, and ELISAs for TRPV1 and TGF-β2 were performed. In stage 2, 32 children (16 UACS and 16 controls) were enrolled in the study and both ELISA and IHC for TRPV1 and TGF-β2 were performed. In stage 3, 41 children were enrolled in this research who had thick mucus secretions in the posterior nasal apertures in stage 1 and 2 (23 cases with chief complaint (or history) of chronic cough and 18 cases without). The difference between the TRPV1 and TGF-β2 serum values and the clinical factors was determined.

Results

The levels of TRPV1 and TGF-β2 were significantly increased in the UACS cases. OSAHS and thick mucus secretions correlated with a diagnosis of UACS. A history of asthma and thick mucus secretions correlated with elevation of the two inflammatory factors. There was no statistical correlation between ELISA and IHC testing. Among the children with thick mucus secretions, some had a higher possibility of chronic coughing including those who had higher levels of the two indices, larger tonsils and a history of chronic tonsillitis.

Conclusion

The detections of TRPV1 and TGF-β2 from serum and adenoid body specimens are valuable for UACS auxiliary diagnosis. Tonsil hypertrophy and chronic tonsillitis history are independent risk factors of UACS.     

Objective characterization of airway dimensions using image processing

ObjectivesWith the evolution of medical and surgical management for pediatric airway disorders, the development of easily translated techniques of measuring airway dimensions can improve the quantification of outcomes of these interventions. We have developed a technique that improves the ability to characterize endoscopic airway dimensions using common bronchoscopic equipment and an open-source image-processing platform.MethodsWe validated our technique of Endoscopic Airway Measurement (EAM) using optical instruments in simulation tracheas. We then evaluated EAM in a large animal model (Ovis aries, n = 5), comparing tracheal dimensions obtained with EAM to measurements obtained via 3-D fluoroscopic reconstruction. The animal then underwent resection of the measured segment, and direct measurement of this segment was performed and compared to radiographic measurements and those obtained using EAM.ResultsThe simulation tracheas had a direct measurement of 13.6, 18.5, and 24.2 mm in diameter. The mean difference of diameter in simulation tracheas between direct measurements and measurements obtained using EAM was 0.70 ± 0.57 mm. The excised ovine tracheas had an average diameter of 18.54 ± 0.68 mm. The percent difference in diameter obtained from EAM and from 3-D fluoroscopic reconstruction when compared to measurement of the excised tracheal segment was 4.98 ± 2.43% and 10.74 ± 4.07% respectively. Comparison of these three measurements (EAM, measurement of resected trachea, 3-D fluoroscopic reconstruction) with repeated measures ANOVA demonstrated no statistical significance.ConclusionsEndoscopic airway measurement (EAM) provides equivalent measurements of the airway with the improved versatility of measuring non-circular and multi-level dimensions. Using optical bronchoscopic instruments and open-source image-processing software, our data supports preclinical and clinical translation of an accessible technique to provide objective quantification of airway diameter.     

变应原气道激发在变应性鼻炎和哮喘研究中的作用研究进展

随着城市化进程，环境及生活方式的改变，我国变应性疾病发病率逐年升高。目前认为变应性鼻炎和哮喘的发病主要是在遗传基因、环境因素共同作用下导致，但具体发病机制复杂，尚未完全清楚。慢性气道炎症和气道高反应性是变应性鼻炎和哮喘的典型的病理生理特征。环境中变应原的暴露可诱发疾病症状发作，引起气道及全身炎症反应增加，并导致气道敏感性/反应性升高。人为给予变应性鼻炎或哮喘患者呼吸道变应原吸入刺激，可以模拟其变应原自然暴露所致疾病症状发作，研究其病理生理变化，尚可通过药物干预评估其对症状及炎症抑制程度评估药物治疗效果。同时变应性鼻炎和哮喘作为上下气道疾病，相互影响，通过一端变应原刺激研究气道另一端症状及炎症反应，探讨上下气道之间的联系。屋尘螨为我国,特别是南方地区最主要、最常见的变应原，与疾病关系密切。主要从屋尘螨变应原鼻激发和支气管激发方法学及其在鼻炎和哮喘的研究中的应用作一综述。