布地奈德/福莫特罗干粉吸入剂和喘可治联合治疗儿童支气管哮喘的临床研究

目的 评估布地奈德/福莫特罗干粉吸入剂和喘可治注射液联合治疗儿童支气管哮喘(轻度持续-中度持续)的临床疗效、依从性和安全性.方法 采用随机、开放、平行对照研究方法,将64例患儿分为A组(布地奈德/福莫特罗干粉吸入剂组)37例和B组(布地奈德/福莫特罗干粉吸入剂+喘可治联合治疗组)27例,观察临床症状评分、视觉近似评价量尺(VAS量尺)、儿童哮喘控制测试(ACTCH)、最大呼气峰流速(PEF占预计值%)、肺功能(FEV1占预计值%)和不良事件发生情况.结果 A、B两组药物治疗都可改善患儿的临床症状,但B组改善更明显(P<0.05);PEF占预计值%和FEV1占预计值%方面,两组都有改善,B组在治疗后4周改善PEF占预计值%快于A组(P<0.05),在治疗后4周、8周、12周改善FEV1占预计值%也优于A组(P<0.05),两组无明显不良事件发生.结论 布地奈德/福莫特罗干粉吸入治疗和布地奈德/福莫特罗干粉吸入剂+喘可治联合治疗儿童支气管哮喘(轻度持续-中度持续)都具有良好的疗效和安全性,依从性好,但布地奈德/福莫特罗干粉吸入剂+喘可治联合治疗改善病情更快,疗效更好.     

布地奈德雾化吸入对支气管哮喘儿童肺功能的影响

目的观察布地奈德混悬液雾化吸入对支气管哮喘患儿肺功能的影响。方法100例支气管哮喘患儿随机分为治疗组和对照组,每组各50例。对照组常规治疗,治疗组在常规治疗基础上加用布地奈德雾化吸入治疗3~7 d。观察两组疗效及肺功能指标第1秒最大呼气量(FEV1)、FEV1%、最大呼气流速峰值(FVC)、FVC%、峰流速(PEF)、PEF%的变化。结果治疗组显效42例,有效8例,显效率84%;对照组显效28例,有效22例,显效率58%。治疗组治疗后FEV1、FEV1%、FVC、FVC%、PEF、PEF%均较治疗前及对照组明显升高。结论布地奈德混悬液雾化吸入对支气管哮喘患儿的肺功能指标有明显改善作用。     

特异性免疫治疗对哮喘患儿的免疫干预作用及肺功能的影响

目的探讨特异性免疫治疗(SIT)对哮喘患儿Th1/Th2及肺功能的影响。方法哮喘发作期患儿43例随机分为A组28例(加用SIT治疗),B组15例(对照组)。在SIT前和SIT后6个月对患儿进行过敏原皮试并检测血IL4和IFNγ、IgE、肺功能,进行临床疗效评价。结果A组SIT后血浆总IgE、尘螨特异性IgE、血清IL4下降,而IFNγ及IFNγ/IL4比值升高;两组肺通气功能均明显改善。A组总有效率92.86%,B组80.00%,两组比较无差异(F=1.56P>0.05)。结论SIT可促进Th2向Th0转化,恢复Th1/Th2平衡,SIT可明显改善肺通气功能。     

巨细胞病毒肝炎婴儿外周血IL-33、sST2表达及意义

目的探讨白细胞介素-33(IL-33)、可溶性致癌抑制因子2(sST2)在婴儿巨细胞病毒(HCMV)肝炎中的表达及意义。方法选取HCMV感染婴儿40例,其中肝炎组20例,其他疾病组20例;另选择同期健康婴儿20例作为对照组。采用ELISA法检测三组婴儿血浆IL-33、sST2、IFN-γ、IL-4浓度,采用流式细胞术检测外周血Th1、Th2细胞比例。结果HCMV阳性肝炎组和HCMV阳性其他疾病组患儿的血浆IL-33、sST 2、IFN-γ、IL-4浓度及Th 1、Th 2细胞比例均高于对照组,肝炎组高于其他疾病组。肝炎组和其他疾病组患儿IFN-γ/IL-4及Th1/Th2均低于对照组,肝炎组低于其他疾病组,差异均有统计学意义(P0.05)。HCMV肝炎组血浆IL-33浓度与sST2、IL-4浓度及Th2细胞比例呈显著正相关(P0.05),与IFN-γ/IL-4、Th1/Th2呈显著负相关(P0.05)。结论 HCMV肝炎婴儿存在Th1/Th2失衡,IL-33可能参与HCMV感染所致Th2优势应答和Th1/Th2失衡。     

慢性咳嗽儿童140例肺功能的特点

目的分析慢性咳嗽儿童肺功能,探讨慢性咳嗽病因与咳嗽变异性哮喘(CVA)的相关性。方法慢性咳嗽患儿140例,根据第1s用力呼气容积(FEV1)或最大呼气流量(PEF)分成二组:运动试验组93例,舒张试验组47例。二组分别予运动和舒张试验。检测二组患儿肺功能,包括用力肺活量(FVC)、FEV1、PEF、用力呼吸50%及75%肺活量时瞬间流量(FEF50及FEF75)。结果运动试验组阳性30例,其FEV1及PEF变异率分别为(18.30±10.50)%及(18.78±9.44)%;舒张试验组阳性35例,FEV1及PEF变异率分别为(30.36±27.27)%及(36.13±26.83)%。结论FEV1、PEF可用于评价CVA儿童的呼吸道阻塞程度。肺功能可客观评价慢性咳嗽呼吸道反应性及炎性反应程度。     

卡介苗多糖核酸治疗哮喘儿前后PPD反应与Th1／Th2的相关性

目的 观察卡介苗多糖核酸（斯奇康）治疗前后PPD反应,了解哮喘儿与Th1/Th2的相关性和疗效观察。方法 对52例哮喘儿检测PPD反应,分成阳性组22例和阴性组30例,对比两组白细胞介素4（IL-4）、IFN-γ和血清IgE水平,用斯奇康注射液进行治疗。结果 PPD反应阳性组病情轻于阴性组。且IL-4、IFN-γ、IgE与阴性组比较有统计学差异。且斯奇康效果两组疗效均可,但是阳性组更好。结论 检测哮喘儿PPD反应可了解Th1-Th2亚群功能有无失衡,建议对哮喘儿抗炎平喘同时加用免疫调节剂。     

不同浓度地塞米松和甲泼尼龙对支气管哮喘患儿外周血单个核细胞免疫功能的影响

目的 观察不同浓度地塞米松(DEX)和甲泼尼龙(MP)对支气管哮喘患儿外周血单个核细胞(PBMC)中CD4+T淋巴细胞中2个功能性亚群(Th1/Th2)功能状态的影响.方法 选择2001年6月-2002年6月在重庆医科大学附属儿童医院就诊的15例哮喘患儿和14例健康体检儿童为研究对象.分为哮喘对照组、10-7mol·L-1DEX干预组、10-8mol·L-1DEX干预组、10-9mol·L-1DEX干预组、10-7mol·L-1MP干预组、10-8mol·L-1MP干预组、10-9mol·L-1MP干预组.清晨取其空腹静脉血5 mL,肝素抗凝,采用密度梯度离心法分离PBMC,加植物血凝素进行刺激培养,分别用10-7mol·L-1、10-8mol·L-1及10-9mol·L-1DEX或MP体外干预培养48 h.同期采集健康儿童空腹静脉血,同法分离培养.用ELISA法测定培养上清中γ干扰素(IFN-γ)、IL-4、IL-10及IL-12水平,并计算不同浓度DEX或MP对PBMC分泌细胞因子的抑制率.结果 1.哮喘对照组PBMC分泌IL-4水平显著高于健康对照组(P<0.05),IFN-γ/IL-4比值较健康对照组显著降低(P<0.05),2组间IFN-γ、IL-10及IL-12水平比较差异均无统计学意义(Pa>0.05).2.DEX和MP均可明显抑制哮喘患儿PBMC分泌IFN-γ、IL-4及IL-12,但对IL-10抑制作用差;与健康对照组比较,哮喘组DEX和MP抑制PBMC分泌IL-10的作用弱,差异有统计学意义(Pa<0.05).3.DEX和MP均以浓度依赖方式抑制哮喘患儿PBMC分泌IL-4,DEX在10-9mol·L-1时有促进IL-4分泌的效应,MP在10-9mol·L-1时可抑制IL-4的分泌,二组比较差异有统计学意义(P<0.05). 若以IFN-γ/IL-4表示Th1/Th2间的平衡,则MP可恢复Th1/Th2平衡(P<0.05).结论 DEX和MP均可抑制Th1/Th2类细胞因子分泌,但MP有助于恢复Th1/Th2平衡,提示临床选择MP治疗支气管哮喘更有利.     

孟鲁司特治疗儿童中重度哮喘疗效观察

目的　观察孟鲁司特治疗儿童中重度哮喘的疗效和安全性。方法　将 88例 4～ 14岁哮喘患儿随机分为治疗组和对照组。治疗组在吸入激素的基础上加用孟鲁司特 (商品名 :顺尔宁 ) (4～ 6岁 4mg ,1次 /d ;6～ 14岁 5mg ,1次 /d) ,疗程 6周 ,治疗期间监测最大呼气流量 (PEF)、第 1秒末用力呼气量 (FEV1) ,记录患儿日间哮喘症状评分 ,夜间憋醒次数 ,咳嗽分数 ,吸入 β2 受体激动剂的使用喷数 ,无症状天数及药物副作用。疗程结束时对两组进行临床疗效判定。结果　治疗组肺功能有明显改善 (χ2 =2 5 .14　P <0 .0 1)。日夜间PEF均值治疗 1周后即显著上升 ;治疗后 6周日夜间PEF改善率为 12 .1%和 11.2 % ,对照组为 4 .7%和 5 .9% ,两组比较 ,差异均有显著性 (P <0 .0 5 )。治疗组 β2 爱体激动剂用量减少 5 7.2 % ,无症状天数增加 3d/周。结论　孟鲁司特治疗中重度哮喘起效迅速 ,临床控制率高 ,肺功能改善明显 ,无严重不良反应 ,患儿依从性好     

呼吸道合胞病毒感染大鼠转录因子T-bet表达及与Th1/Th2的关系

目的 探讨呼吸道合胞病毒(RSV)感染时肺T-bet(T-box expressed in T cells)表达对Th1/Th2类细胞因子分泌的调控作用.方法 随机将20只SD大鼠分为对照组、RSV感染组,每组10只.在第6周时测定气道反应性;取肺组织苏木素伊红(HE)染色观察病理改变;通过蛋白质印迹法检测T-bet在肺组织中的表达;酶联免疫吸附法检测肺组织匀浆白细胞介素4(IL-4)和干扰素Ⅱ型(IFN-γ)水平.结果 RSV感染组大鼠肺部病理学切片呈现典型的间质性肺炎表现,而且RSV感染组大鼠气道阻力程度明显高于对照组.肺组织中T-bet表达RSV感染组相对灰度值0.61 ± 0.23较对照组0.81 ± 0.35显著减低(t ＝ 16.345,P ＜ 0.01).RSV感染组的IL-4蛋白水平较对照组明显增高(P ＜ 0.01),而IFN-γ蛋白水平明显减低(P ＜ 0.01).肺T-bet蛋白水平与IFN-γ蛋白水平呈正相关(r ＝ 0.725,P ＜ 0.01),与IL-4 蛋白水平及IL-4/IFN-γ比值均呈负相关(r ＝ -0.837、-0.864,P均＜ 0.01).结论 RSV感染可以下调T-bet在肺组织中表达,并与Th1/Th2免疫失衡相关.     

哮喘缓解期患儿Th1/Th2相关上游转录因子及细胞因子的表达

目的从基因和蛋白质水平了解哮喘缓解期患儿T辅助淋巴细胞(Th)免疫平衡状况。方法选取24例哮喘缓解期和12例健康儿童作为对照,采用酶联免疫吸附法(ELISA)和实时荧光定量PCR(real time PCR)法分别测定外周血细胞因子干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)水平及外周血单个核细胞(PBMC)中特异性转录因子T-bet、GATA-3表达情况。结果病例组血浆IL-4水平(37.14±12.77)ng/L显著高于对照组(27.08±6.12)ng/L,t=2.467 P<0.05;病例组PBMC中GATA-3的表达强度(5.45±1.11)较对照组(4.70±0.86)显著增高(t=2.049 P<0.05);病例组与对照组比较IFN-γ/IL-4及T-bet/GATA-3比率均显著降低(t=-2.208,-4.212 P<0.05,P<0.01)。结论哮喘缓解期患儿体内存在基因和蛋白质水平Th1/Th2平衡的紊乱,以Th2亚群亢进为主。     

Relation between stressful life events,neuropeptides and cytokines: results from the LISA birth cohort study

Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-γ (IFN-γ) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-γ concentrations in children’s blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation.     

基于过敏性疾病和健康儿童的淋巴细胞精细分型病例对照研究

背景：过敏性疾病的诊断缺乏明确的检测标准,主要依赖于病史,在无过敏原刺激情况下则无临床症状,诊断更加困难,寻找辅助诊断过敏标志物显得非常重要。 目的：检测过敏儿童淋巴细胞精细分型特征,期望对过敏性疾病的诊断提供新的标志物。 设计：病例对照研究。 方法：选择食物和呼吸道过敏儿童作为过敏性疾病组,选择与过敏性疾病组同时期在医院健康体检正常、性别和年龄匹配的儿童为健康对照组。采用流式细胞术分析对其淋巴细胞精细分型进行检测。 主要结局指标：淋巴细胞精细分型。 结果：过敏性疾病组30例,平均年龄3.6（0.7~10.6）岁;健康对照组27名,平均年龄4.1 (0.8~11) 岁。两组年龄、性别差异无统计学意义（P分别为0.616和0.574）。T淋巴细胞精细分型：Th2细胞占效应辅助性T细胞比例和Th2/Th1比值过敏性疾病组高于健康对照组［（31.34±2.52）% vs (20.02±2.05)%,（6.86±1.51） vs (2.73±0.35)］,差异均有统计学意义。B淋巴细胞精细分型：成熟B细胞比例及绝对计数、浆母细胞绝对计数、IgE+浆母细胞比例、IgE+记忆B细胞比例,过敏性疾病组均高于健康对照组［(11.53±1.22) % vs (6.02±0.52）%,(1 068±107.3)个/μL vs (578.74±58.49）个/μL ,(40.71±6.44) 个/μL vs ( 17.08±2.93)个/μL ,(8.21±1.33) % vs (1.64±0.53）%,(4.48±0.81) % vs (0.47±0.18）%。 结论：过敏儿童Th2细胞、IgE+浆母细胞和记忆B细胞比例增高,有潜力作为辅助诊断过敏性疾病的标志物。     

Association between neopterin in cord blood, urinary neopterin in early childhood and the development of atopic dermatitis, asthma and hay fever.

It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of neopterin. Thus, the determination of neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary neopterin concentrations at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.     

Early intervention with suplatast tosilate for prophylaxis of pediatric atopic asthma: A pilot study

The onset of asthma may be related to Th2 cytokine dominance at the time when food allergies occur several months after birth. This study investigated the effectiveness of early intervention with a Th2 cytokine inhibitor (suplatast tosilate) for prevention of asthma in infants with food allergies and atopic dermatitis. Suplatast tosilate dry syrup (6 mg/kg daily) or a histamine H₁-blocker (ketotifen fumarate dry syrup: 0.06 mg/kg daily) was administered randomly to 53 infants with atopic dermatitis caused by food allergies. The primary endpoints were the incidence of asthma and the time to the onset of wheezing. The peripheral blood Th1/Th2 ratio, total IgE level, and eosinophil count were measured before and after treatment. After 24 months of treatment, the prevalence of asthma was significantly lower in the suplatast group (20.8%) than in the ketotifen group (65.6%, p < 0.01). Additionally, the time from the start of treatment to the initial episode of wheezing for infants who developed asthma was significantly longer in the suplatast group than the ketotifen group (p < 0.01). Furthermore, the eosinophil count was significantly decreased by suplatast treatment (p < 0.05), and there was a significant difference between the suplatast and ketotifen groups with respect to both the eosinophil count (p < 0.01) and the Th1/Th2 ratio (p < 0.05). The results of the present pilot study suggest that suplatast tosilate is useful for the primary prevention of wheezing and asthma in children.     

mRNA expression of T-helper 1, T-helper 2 cytokines in autoimmune hepatitis in childhood

Background: In the pathology of autoimmune hepatitis the immunity mechanism of T-helper 1 (Th1) and Th2 cells was recently evaluated. The purpose of the present study was to measure the mRNA levels in peripheral mononuclear cells and serum cytokines obtained from children with autoimmune hepatitis for a better understanding of the mechanism.
Methods: Twenty-five patients with autoimmune hepatitis and seven controls were enrolled. mRNA levels in peripheral mononuclear cells and serum cytokines were measured using real-time polymerase chain reaction and immunoassay.
Results: Serum interferon-γ (IFN-γ) and interleukin-4 (IL-4) were rarely detected. In contrast the IFN-γ/β-actin mRNA levels were high.
Conclusion: Autoimmune hepatitis is a Th1-predominant state, therefore immune modulation therapies that target the control of Th1 cytokines should be used.     

小儿外科脓毒症患儿Th1/Th2细胞免疫应答状况

目的 探讨外科治疗中严重腹腔感染脓毒症患儿Th1/Th2细胞免疫应答的变化规律.方法 选择本院收治的30例严重腹腔感染患儿为脓毒症组.同期门诊查体的30例健康儿童为健康对照组.脓毒症组(于术前和术后第1、5天)及健康对照组抽取空腹静脉血2 mL,采用双抗体夹心酶联免疫吸附法(ELISA)测定各组儿童血清IFN-γ和IL-4水平,计算IFN-γ/IL-4比值.采用SPSS 10.0软件进行统计学分析.结果 脓毒症组血清IFN-γ水平术前与健康对照组、术后第5天与术前、术后第5天与健康对照组比较,均无显著性差异(Pa>0.05);术后第1天与术前比较下降(t=6.083 P<0.01).脓毒症组血清IL-4水平术前与健康对照组、术后第1天比较均升高(t=11.65,1.996 Pa<0.01),与术后第5天比较下降(t=8.275 P<0.01),术后第5天与健康对照组比较仍高,未恢复至正常水平(t=3.453 P<0.01).脓毒症组IFN-γ/IL-4比值术前与健康对照组、术后第1天比较均明显降低(t=10.98,3.072 Pa<0.05),术后第5天与术前比较明显升高(t=6.417 P<0.01),但与健康对照组比较末恢复至正常水平(t=3.482 P<0.01).结论 严重腹腔感染脓毒症患儿Th1细胞应答减弱,Th2细胞应答增强,存在免疫抑制状态,手术打击加重Th1细胞向Th2细胞偏移,经手术干预、合理治疗,免疫功能可逐渐恢复.     

连续性血液净化对多器官功能障碍幼猪T辅助细胞免疫功能影响的机制研究

目的 研究连续性血液净化(CBP)对多器官功能障碍(MODS)幼猪在疾病不同时期外周血Th1、Th2细胞数量及其细胞培养上清液中细胞因子(IFN-γ、TNF-α、IL-12,IL-10、IL-4)水平的影响.方法 24只幼猪随机分为对照组和CBP干预组,每组12只.内毒素诱导多器官功能障碍.CBP主要采用连续性静脉静脉血液透析滤过(continuous venovenous hemodiafiltration,CVVHDF).造模完成后为0 h,MODS对照组在造模后0、2、4、6 h进行检测;血液净化干预组造模后即开始CVVHDF,分别在0 h及CVVHDF干预2 h、4 h、6 h进行检测.在各时点采用免疫磁珠分离两组幼猪外周血T辅助细胞,采用流式细胞仪检测Th1、Th2细胞数目,ELISA检测各时点T细胞培养上清液中IFN-γ、TNF-α、IL-12、IL-10、IL-4的表达水平.结果 幼猪诱导MODS模型后,辅助性T细胞分泌炎症因子TNF-α明显上升,而促进Th1细胞分化的因子IL-12和Th1细胞因子IFN-γ和调节因子IL-10呈下降趋势,Th2细胞因子IL-4则没有明显的变化,Th1/Th2比值下降;经过CVVHDF治疗,TNF-α和IL-4减少,IL-12、IFN-γ和IL-10在CVVHDF6 h后明显上升,Th1/Th2比值上升.结论 MODS幼猪模型经过CVVHDF治疗,有助于炎症因子的清除,增加机体的细胞免疫功能,恢复Th1/Th2的平衡.     

Th17和自身免疫性疾病相关性研究进展

Th17是一种新近发现的CD4+T细胞亚群,它是Th1、Th2家族的新成员.近年来研究发现,Th17能够产生IL-17A、IL-17F、IL-21和IL-22等因子,而这些因子在类风湿关节炎、系统性红斑狼疮、系统性硬化病、炎性肠病、自身免疫性心肌炎等自身免疫性疾病的发生发展中起重要作用.因此,加深对Th17在免疫性疾病进展中的认识将为今后的诊断提供新的依据,Th17及其因子也将成为人类治疗自身免疫性疾病的新靶点.     

蛋白质部分水解配方奶粉对改善婴儿湿疹的作用观察

目的 探讨蛋白质部分水解配方(HA)奶粉对湿疹患儿的临床症状及免疫功能的影响.方法 将2006年4月-2008年8月就诊的符合人选条件的90例湿疹婴儿随机分为蛋白质部分水解配方奶粉组(HA组,n=60)和普通婴儿配方奶粉组(CMF组,n=30),两组均观察12周.除观察临床症状外,其中52例(HA组36例,CMF组16例)分别于观察日和第12周采集外周静脉血,检测相关实验室指标.结果 与CMF组相比,HA奶粉可改善湿疹的临床症状,明显升高Th1/Th2比值,应用HA奶粉前后差异有统计学意义(P<0.05).结论 HA奶粉可治疗婴儿湿疹,其作用机制可能与调节体内Th1/Th2的平衡有关.