青岛地区儿童过敏性鼻炎的致敏原检测、舌下免疫治疗的临床疗效及机制研究

发布时间：2018-03-05 15:39

  本文选题：过敏性鼻炎　切入点：儿童　出处：《青岛大学》2015年博士论文　论文类型：学位论文

【摘要】：目的过敏性鼻炎是一种常见的气道疾病,在不同的地区有不同的发病率和致敏特征。本研究旨在了解青岛地区过敏性鼻炎儿童常见过敏原及其特点,为儿童过敏性鼻炎的诊断、治疗及预防提供科学依据;同时评价儿童过敏性鼻炎患者进行舌下免疫治疗(sublingual immunotherapy SLIT)过程中的短期临床疗效,并检测部分显效患者微小RNA(micro RNA,mi RNA)-146a的表达变化;观察粉尘螨滴剂舌下免疫治疗过敏性鼻炎患儿的临床疗效。方法回顾性分析2003年1月至2014年12月间2841例过敏性鼻炎(伴或不伴哮喘)儿童过敏原点刺实验检查结果,其中3-5岁者1500例,6-12岁者1341例,分析其中尘螨及其他过敏原组成,研究其相关性。为评估SLIT的短期疗效及机制,纳入42例年龄6~11岁过敏性鼻炎患者,采用商品化粉尘螨滴剂(畅迪)舌下含服治疗半年,比较治疗前后鼻炎症状评分的改变。同时选取13例临床疗效显著的患者,采用反转录聚合酶链反应(RT-PCR)检测外周血单个核细胞mi R-146a和Foxp3基因表达的改变,采用酶联免疫吸附试验(ELISA)检测血清IL-5和IL-10蛋白水平的改变。为评估舌下免疫治疗的临床疗效,选择到我院就诊的尘螨过敏的过敏性鼻炎患儿110例,按患儿监护人意愿分为舌下免疫治疗组(60例)和药物对照组(50例),舌下免疫治疗组使用粉尘螨滴剂联合对症药物治疗,药物组仅使用单纯对症药物治疗;治疗2年结束后评估舌下免疫治疗组和药物对照组的鼻部症状总评分(total nasal symptom scores,TNSS)和药物总评分(Total medication scores,TMS)。结果2841例过敏性鼻炎患儿皮肤点刺试验结果显示:(1)吸入性过敏原中前三位分别是屋尘螨(69.3%)、粉尘螨(66.2%)、点青霉(38.9%),食物性过敏原中前三位分别为蚌类(39.2%)、鲤鱼(36.5%)、海虾(36.3%)。(2)3-5岁儿童中,吸入性过敏原中前三位分别是屋尘螨(67.53%)、粉尘螨(62.47%)、点青霉(36.40%);6-12岁儿童中,吸入性过敏原中前三位分别是屋尘螨(71.96%)、粉尘螨(70.84%)、点青霉(41.98%)。例数最多的前10种过敏原两组间比较,粉尘螨、屋尘螨、点青霉、烟曲霉、夏秋花、豚草、禾本科等过敏原差异有统计学意义(P0.05)。(3)3-5岁儿童中,食物性过敏原中前三位分别为蚌类(39.60%)、鲤鱼(34.33%)、海虾(34.13%);6-12岁儿童中,食物性过敏原中前三位分别为鲤鱼(39.00%)、蚌类(38.70%)、海虾(38.63%)。例数最多的前10种过敏原两组间比较,其中海虾、鲤鱼、鳗鱼、海蟹4种过敏原差异有统计学意义(P0.05)。(4)不同性别比较,吸入性过敏原中的点青霉、豚草和食入性过敏原中的牛奶,差异有统计学意义(P0.05)。(5)粉尘螨及屋尘螨同时出现过敏的阳性率为60.0%,其中伴随出现其他一种或多种过敏原阳性者占56.7%。屋尘螨阳性强度高于粉尘螨,差异有统计学意义(P0.05)。(6)6-12岁儿童尘螨感染率高于3-5岁儿童,差异有统计学意义(P0.05)。男童尘螨感染率高于女童,其差异有统计学意义(P0.05)。SLIT治疗半年后AR患者临床症状评分较治疗前出现显著改善,差异有统计学意义(P0.01)。检测13例显效患者治疗前后外周血单个核细胞mi R-146a、Foxp3基因表达和血清IL-10蛋白表达,与基线值比较均出现显著的增高,而血清IL-5蛋白水平显著下降,差异均有有统计学意义(P0.05)。mi R-146a表达水平与Foxp3 m RNA表达水平之间存在显著的关联性,有统计学意义(P0.01)。SLIT治疗2年结束时,与药物对照组相比,TMS、TNSS评分显著低于药物组且差异具有统计学意义(P0.01)。SLIT组治疗2年结束时和治疗前基线相比,TMS、TNSS评分均有显著降低且差异具有统计学意义(P0.01)。药物治疗2年和治疗前相比,用药评分显著升高且差异具有统计学意义(P0.01),TNSS没有显著变化(P0.05)。治疗2年结束后,SLIT组60例患者中有41例(68.33%)停止使用对症药物,药物对照组50例患者中有8例(16.0%)停止使用对症药物,两者相比差异有显著统计学意义(P0.01)。结论在青岛地区,屋尘螨和粉尘螨是儿童过敏性鼻炎最常见的过敏原,临床中多见二者同时出现,常伴随其他一种或多种过敏原阳性。随着年龄增长,过敏性鼻炎儿童对尘螨敏感性更高,尤其是男性患儿。因此,明确尘螨主要过敏原后可以采取相应的措施避免接触尘螨或进行特异性免疫治疗以减轻机体过敏反应,从而大大降低患儿的痛苦。畅迪SLIT治疗过敏性鼻炎的临床疗效可能与诱导mi R-146a介导的调节性T细胞上调有关。经过2年左右的对比研究证实,SLIT联合药物治疗过敏性鼻炎临床效果优于单纯对症药物治疗。
[Abstract]:The purpose of allergic rhinitis is a common airway disease in different regions have different incidence and sensitization characteristics. This study aims to understand children with allergic rhinitis in Qingdao area and the characteristics of common allergens in children with allergic rhinitis, diagnosis, treatment and prevention to provide the scientific basis for the evaluation of patients with allergic children; rhinitis of sublingual immunotherapy (sublingual immunotherapy SLIT) short-term clinical effect in the process of detection and effective part of patients with small RNA (micro RNA, MI RNA) the expression of -146a; to observe the clinical effect of Dermatophagoides Farinae Drops sublingual immunotherapy in children with allergic rhinitis. Methods Retrospective analysis of January 2003 to December 2014 of 2841 cases of allergic rhinitis (with or without asthma) children prick test results, including 1500 cases of 1341 patients 3-5 years of age, 6-12 years of age, the analysis of dust mites and other allergens, Study on the relationship between the curative effect and mechanism. For the assessment of SLIT, included 42 cases of aged 6~11 patients with allergic rhinitis, the commercialization of Dermatophagoides Farinae Drops (Chang DI) sublingual treatment for half a year, before and after the treatment of rhinitis symptoms score changes. At the same time selected 13 cases of clinical curative effect significantly in patients by reverse transcription polymerase chain reaction of (RT-PCR) MI in mononuclear cells of R-146a and Foxp3 gene expression in peripheral blood detected changes by enzyme-linked immunosorbent assay (ELISA) detection of serum IL-5 and IL-10 protein levels. The change of clinical curative effect evaluation of sublingual immunotherapy, 110 cases of children with allergic rhinitis in our hospital from dust mite allergy according to the children, guardian will be divided into sublingual immunotherapy group (60 cases) and control group (50 cases), sublingual immunotherapy using Dermatophagoides Farinae Drops combined symptomatic drug treatment, the drug group using only simple medicine 娌荤枟;娌荤枟2骞寸粨鏉熷悗璇勪及鑸屼笅鍏嶇柅娌荤枟缁勫拰鑽�鐗╁�圭収缁勭殑榧婚儴鐥囩姸鎬昏瘎鍒，

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