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.     

可乐定透皮贴剂治疗儿童抽动障碍的随机双盲对照研究

抽动障碍是儿童时期最常见的运动障碍之一,表现为突然的不自主运动性抽动和发声性抽动。目前治疗抽动障碍的药物主要有氟哌啶醇、泰必利等,均有一定疗效,但仍有部分患儿得不到控制。可乐定是选择性肾上腺α2受体激动剂,其透皮贴剂是一种可连续7d向体内恒定释放可乐定的透皮治疗系统。早在上世纪80年代国外就有学者将可乐定用于儿童抽动障碍的治疗。为了解可乐定透皮贴剂治疗儿童抽动障碍的疗效,我们使用可乐定透皮贴剂和安慰剂对我院门诊抽动障碍患儿进行了随机双盲对照研究,报告如下。[第一段]     

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.     

孟鲁司特钠单用于轻度持续哮喘患儿疗效和安全性的随机双盲安慰剂对照试验

目的：研究孟鲁司特钠单用于治疗5~14岁轻度持续哮喘患儿的疗效和安全性。方法：采用安慰剂随机双盲对照试验,对首诊诊断为轻度持续哮喘患儿,采用调查问卷方式采集患儿基线数据,经过2周安慰剂洗脱期,随机分为治疗组和对照组,分别睡前咀嚼口服孟鲁司特钠或安慰剂5 mg·d-1,疗程均为12周。在入组后4、8和12周记录哮喘日记卡内容：日间和夜间哮喘症状评分、β2受体激动剂使用频率、最大呼气峰流速（PEF）、因哮喘急性发作而需急诊或住院治疗的次数等;于治疗后12周检测肺功能指标：FEV1%预计值、FEF25%~75%。结果：2009年9月至2010年9月上海交通大学附属第一人民医院儿科哮喘专科门诊的轻度持续哮喘患儿安慰剂组纳入42例,孟鲁司特钠组纳入89例,至观察终点安慰剂组35例,孟鲁司特钠组77例进入分析。与安慰剂组相比,孟鲁司特钠组的PEF明显改善（P<0.05）;每周日间和夜间哮喘症状平均评分、每月因哮喘发作而需急诊或住院就诊率和每周平均β2受体激动剂使用次数均下降,差异有显著统计学意义（P<0.01）;治疗后12周孟鲁司特钠组FEV1%、FEF25%~75%较安慰剂组显著提高（P<0.05）;研究期间两组患儿均未观察到不良反应事件。结论：孟鲁司特钠单独用于轻度持续性哮喘患儿具有良好的疗效,不良反应少,患儿依从性高。     

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。     

孟鲁司特钠治疗汉族儿童支气管哮喘疗效与ABCC1、SLCO2B1基因单核苷酸多态性的相关性研究

目的 探讨白三烯受体拮抗剂(leukotriene receptor antagonists,LTRA)与ATP结合盒亚家族C1(ATP-binding cassette sub-family C member 1,ABCC1)基因rs119774位点、溶质载体有机阴离子转运蛋白家族成员2B1 (solute carrier organic anion transporter family member 2B1,SLCO2B1)基因rs12422149位点的单核苷酸多态性(single nucleotide polymorphism,SNP)治疗汉族儿童支气管哮喘疗效的相关性。方法 选取2019年4月至2021年12月于福建中医药大学附属厦门市中医院就诊的4～13岁汉族支气管哮喘患儿100例为研究对象,采用一代测序法对患儿的ABCC1基因rs119774位点、SLCO2B1基因rs12422149位点进行检测,分析比较2个位点的SNP分布情况。入组患儿均应用LTRA进行治疗,分别于治疗前与治疗12周时进行肺通气功能及脉冲震荡功能检测,并评估临床症状控制水平,分析患儿疗效与SNP的相关性...     

PI3K、NF-κB和STAT1在支气管哮喘儿童外周血单个核细胞的表达和临床意义

目的检测PI3K、NF-κB和STAT1在支气管哮喘儿童外周血单个核细胞(PBMC)中的表达,探讨其在哮喘发病机制的临床意义。方法选取30例急性发作期的支气管哮喘患儿作为哮喘组,随机选取同期健康儿童20例作为对照组。应用RT-PCR和Western blot方法检测PBMC中PI3K、NF-κB和STAT1的m RNA和蛋白表达,肺功能仪检测两组肺功能,并分析支气管哮喘儿童PI3K、NF-κB和STAT1的m RNA水平与其肺功能的相关性。结果哮喘组的PI3K、NF-κB和STAT1的m RNA和蛋白水平均高于对照组(P0.05)。与对照组相比,哮喘组FEV1%、FEV1/FVC、PEF%等肺功能指标均下降(P0.05)。哮喘儿童的PI3K、NF-κB和STAT1的m RNA表达水平与FEV1%、FEV1/FVC、PEF%均呈负相关(P0.05)。结论哮喘患儿的PI3K、NF-κB和STAT1表达上调并与肺功能呈负相关,三者可能共同参与儿童支气管哮喘的发生、发展。     

Bronchial asthma and the short-term quality of life: follow-up study of childhood bronchial asthma in Hungary

The aim of our study is to determine and describe the current short-term health-related quality of life of recent adult patients who had bronchial asthma in childhood. Our objective was to investigate if symptom control in bronchial asthma could be in conflict with general quality of life. We made a follow-up study of 152 patients (105 male, 47 female) over the age of 30 (31-55 yr) who were allergic asthmatics in childhood. The patients' current symptoms and short-term quality of life were evaluated by a questionnaire. The patients developed asthmatic symptoms by age 4.4 (0.5-13) years on the average. Now 60% (91 persons) have no symptoms. They became symptom-free between 3 and 41 yr of age (mean = 14.2 +/- 8.2). Amongst the currently asthmatic patients (58 patients, 38%), 34 patients (22%) belong to the Global Initiative for Asthma (GINA) I, nine patients (6%) to the GINA II, five patients (3.3%) to the GINA III, and five patients (3.3%) to the GINA IV classification. Five patients (3.3%) did not specify their own symptoms. Three persons (2%) did not answer this question. Symptomatic patients reached 5.28 on the Juniper Asthma Quality of Life Questionnaire, while their asymptomatic peers scored statistically higher with 6.8 on the scale. Amongst the symptomatic patients, the most limited areas were: 'bothered by heavy breathing', 'had to avoid a situation or environment because of dust', 'experienced difficulty breathing out as a result of asthma', 'experienced asthma symptoms as a result of the weather or air pollution outside'. They were least 'concerned about medication', 'frustrated as a result of their asthma', they were least limited in 'going outside because of the weather or air pollution'. The most problematic areas for the symptom-free patients were 'had to avoid a situation or environment because of dust', 'had to avoid a situation or environment because of cigarette smoke', 'experiencing asthma symptoms as a result of being exposed to dust and the 'need to clear throat'. It seems that having no asthma symptoms is not equal to having a good quality of life for asthmatic patients. Moreover, symptom control in bronchial asthma is in conflict with quality of life, as many prophylactic measures to prevent exposure to allergens also restrict the patient's life.     

小儿支气管哮喘与HLA的相关性研究

目的探讨小儿支气管哮喘与HLA-DRB1的相关件。方法采用序列特异性引物．聚合酶链反应方法（PCR／SSP）对78例支气管哮喘患儿和82例健康儿章进行HLA-DRB1基因分析，患儿的年龄为1～14岁，平均6．5岁。HLA-DRB。有19个等位基因，包括DR1-DRw18、DRw52和DRw53。计算各个位点的基因分布频率、危险性比值比OR值；并进行卡方检验，筛选有意义基因。结果支气管哮喘患儿HLA-DRB1^＊9的基因频率为10．8％；HLA-DRB1^＊10为11．5％；HLA-DRB1^＊1为1．92％。以上3个基因型住疾病组与正常组之间进行卡方检验，x^2值分别为4．39、4．44、6．7，与正常对照组比较差异有显著性（P均〈0．05），其余16个位点差异无显著性。观察组与对照组间进行逐个等位基凶比较，计算比值比OR结果HLA-DRB1^＊1的OR值为0．25；HLA—DRB1^＊9的OR值为2．58；HLA-DRB1^＊10的OR值为2．43。结论HLA-DRB1^＊9和HLA-DRB1^＊10可能是汉族小儿哮喘的易感基因；而HLA-DRB1^＊1可能为保护件基因。     

��轻Ƹ�������������ͯ��Ч������Ѫ��Th1 Th2���ϸ������ ������ø1ˮƽ��Ӱ��

??Objective??To observe the clinical efficacy of Huaiqihuang in the treatment of children with bronchial asthma and its effects on the level of cytokines Th1??Th2 and PON1. Methods??A total of 180 children with bronchial asthma admitted between June 2014 and June 2015 in the Fourth Hospital of Baotou were randomized into the observation group??96 cases of GINA regimen treatment combined with Huaiqihuang??and the GINA regimen treatment group??84 cases????healthy children were enrolled as control group??50 cases??. Times of respiratory tract infection occurrence, asthmatic attacks, application of emergency medicine, hospitalization due to asthmatic and the levels of IL-4??IL-12??IL-13??INF-γ and PON1 were observed before and after treatment. Results??There were significant differences about the times of upper respiratory tract infections, bronchitis and pneumonia, asthma attacks, application of emergency medicine and hospitalization due to asthmatic??P??0.05??. There were significant differences about the changes of IL-4, IL-12, IL-13, INF-γ and PON1 before and after treatment??P??0.01??. Conclusion??The treatment of bronchial asthma in children with Huaiqihuang granule can reduce the incidence of respiratory infections and the number of asthmatic attacks and improve clinical effect. The Huaiqihuang granule alleviating asthma symptoms may by decreasing the levels of Th2 cytokines??IL-4??IL-13??and also by increasing the levels of Th1 cytokines??IL-12, IFN-γ??and PON1.     

肺炎支原体肺炎及支气管哮喘HLA-DRB1基因位点频率研究

为探讨肺炎支原体（MP）肺炎的免疫致病机理及其与支气管哮喘9简称哮喘）之间的关系。应用颗粒凝集法检测29例MP肺炎患儿，40例哮喘患儿及92例正常对照组的血清MP特异性IgM抗体，PCR-SSOP法标记HLA-DRB1等痊基因位点。结果显示MP肺炎组，哮喘组的DRB1*08基因频率明显低于正常对照组（P=0.035)。但MP肺炎组与哮喘组之间差异无显著性，哮喘组中除DRB*08外，DRB1*02基因出现频率亦较正常人显著降低（P=0.041)；各组间HLA-DRB1*04，07，09，10，11，12基因频率虽有所变化，但均无统计学差异。提示MP肺炎与哮喘有着极为相似的遗传易感性。     

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.     

Role of atopy in the natural history of wheeze and bronchial hyper-responsiveness in childhood

The role of atopy in the development of asthma has become increasingly recognised. We have been prospectively following a birth cohort of children of atopic parents to document the development of atopic disease. Our aim in this study was to document the natural history of BHR and wheeze at 10 years of age and to relate this to atopy. We reviewed 47 of our original cohort of 79 infants at 10 years of age and documented their clinical history of atopic disease and performed allergen skin prick tests and BHR to histamine. Thirty-three (70%) children wheezed at some time during their 10 years of life, with 13 commencing in infancy. Twenty-two children (47%) had current wheeze at 10 years of age. Wheeze in infancy was a poor predictor (RR 1.23, Cl₉₅ 0.66–2.23) of current wheeze while wheeze commencing after infancy was a good predictor (RR 2.89, Cl₉₅ 1.45–5.2). In contrast both atopy in infancy (RR 2.94, Cl₉₅ 1.92–4.53) and current atopy (RR 3.58, Cl₉₅ 1.43–9.03) were strong predictors of current wheeze. Analysis of BHR confirmed the importance of atopy in predicting its occurrence and severity. Sensitisation to D. pteronyssinus appeared to be the strongest predictor of both current wheeze and BHR. These observations confirm the importance of atopy in predicting outcome in children with asthma and suggest that wheezing in infancy and wheezing in later childhood may have different pathogenetic mechanisms.     

Evaluation of efficacy of traditional Chinese medicines in the treatment of childhood bronchial asthma: clinical trial, immunological tests and animal study

Traditional Chinese medicines (TCM) have been used to treat bronchial asthma for several centuries and a certain degree of clinical benefit has been observed; however, scientific substantiation is lacking. A multicenter, double-blind and placebo-controlled study was therefore conducted to evaluate the clinical efficacy in terms of symptom score, medication score, morning and evening PEFRs, and changes of immunoregulatory function, such as distribution of lymphocyte subsets and in vivo and in vitro production of lymphokines (IFN-γ and IL-4) and inflammatory mediators (histamine, PGE2 and LTC4). Furthermore, the protective effect of TCM on the late asthmatic reaction (LAR) was evaluated by using asthmatic guinea pigs. Three hundred and three asthmatic children were classified by Chinese doctors, according to a standardized questionnaire designed on the basis of basic logic of Chinese medicine, into three groups of specific constitution (group A, B and C). Group A consisted of 32 herb A-treated patients and 34 placebo-treated; group B, 74 herb B-treated and 64 placebo-treated; and group C, 55 herb C-treated and 44 placebo-treated. The study period was six months. The results were: 1) Both treatment group and placebo group showed an improvement in all clinical parameters, thus demonstrating a placebo effect. However, the improvement was usually greater in the former than the latter, although only the difference in PEFR was significant; 2) Herb A could increase total T cell and decrease B cell; 3) Herb A and B enhanced production of PGE2 but not LTC4, IFN-γ and IL-4; 4) There was a general tendency for in vivo and in vitro production of histamine to decrease at the end of study in both treatment group and placebo group; however, the decrease was significantly greater in the former than the latter; 5) In asthmatic guinea pigs, 10-day's pretreatment with Chinese herbs could reverse the decrease of sGaw, suppress eosinophilia in bronchoalveolar lavage fluid (BALF), prevent the eosinophil infiltration of airways, increase PGE2 production and decrease LTC4 production in serum and BALF. Thus, traditional Chinese medicines did show a certain degree of clinical efficacy. The decreased production of histamine and LTC4, increased production of PGE2 that were found in both asthmatic children and asthmatic guinea pigs, and prevention of occurrence of LAR by suppressing eosinophil infiltration of airways and preserving airway conductance that were observed in asthmatic guinea pigs after allergen challenge might be used to account partly for the effectiveness.