Ding Chuan Tang, a Chinese herb decoction, could improve airway hyper-responsiveness in stabilized asthmatic children: a randomized, double-blind clinical trial.

Traditional Chinese medicine has a long history of application in the treatment of bronchial asthma. Solid scientific evidence, however, is not available despite its widespread use among patients worldwide and in Taiwan. To assess the effect of Ding Chuan Tang (DCT) in airway hyper-responsiveness (AHR) on asthmatic children via randomized, double blind, placebo-controlled clinical trial. This study enrolled children who were aged 8-15 and diagnosed as mild to moderate persistent asthma patients. They were randomly allocated to receive 6.0 g DCT or placebo daily for 12 wk. Self-recorded daily symptom scores, medication scores, and morning and evening peak expiratory flow rates were returned at the monthly clinic. Pulmonary function test, methacholine challenge test, and serum inflammatory mediators were measured before and at the end of the trial. Fifty-two asthmatic children completed the clinical study. Twenty-eight patients were assigned to the treatment group and 24 to the placebo group. At the end of the treatment period, AHR determined by log PC(20) was significantly improved in the DCT group (0.51 +/- 1.05 mg/ml vs. 0.26 +/- 0.84 mg/ml, p = 0.034). The total clinical and medication reduced parameters showed improvement in the DCT group (p = 0.004). The AHR, symptom and medication scores in children with persistent asthma were significantly improved with DCT treat for 12 wk. The results suggested more stable airways achieved with such an add-on complementary therapy.     

哮喘儿童 PBMC培养上清中 IL-13变化及其与嗜酸细胞计数、IgE关系探讨

目的 探讨白介素13（IL-13）在儿童支气管哮喘发病中的作用及其与嗜酸细胞（EOS）、IgE之间的关系。方法 测定32例哮喘儿童急性发作期外周血单个核细胞（PBMC）培养上清中IL-13水平,其中20例测定了恢复期PBMC培养上清中IL-13水平,20例正常儿童PBMC培养上清IL-13作对照,同时检测外周血EOS及血清IgE。结果 哮喘儿童在急性期和恢复期PBMC培养上清中IL-13均高于正常对照组,差异有统计学意义（P均〈0．05）,IL-13水平变化与EOS、IgE呈显著正相关（r=0.7498,0．9218,P均〈0.001）。结论 IL-13参与了儿童支气管哮喘的发病,在嗜酸细胞激活、活化及炎性介质的释放以及IgE分泌、合成方面可能具有一定的作用;减少IL-13生成的治疗对控制儿童支气管哮喘发作可能有重要意义。     

不同年龄哮喘患儿尘螨过敏及其临床意义

目的探讨尘螨过敏与哮喘之间的关系.方法测定不同年龄哮喘患儿和正常儿童的血清IgE水平以及尘螨皮试反应.结果①婴幼儿哮喘屋尘螨皮试阳性率较低(34%),在儿童哮喘则明显上升达70%(P＜0.001);②各年龄组皮试阳性的哮喘患儿血清IgE水平均明显高于皮试阴性哮喘患儿(P＜0.001);③婴幼儿期血清IgE迅速升高,尤其婴幼儿哮喘上升幅度更加明显;进入儿童期后上升幅度明显放慢.结论屋尘螨过敏是婴幼儿哮喘发展成儿童哮喘的重要因素之一;血清IgE升高与屋尘螨皮试表达有一定的关系,但它的表现明显早于屋尘螨皮试的表达;为此动态测定婴幼儿哮喘血清IgE水平有助于判断婴幼儿哮喘的预后.     

Thromboxane A2 receptor gene polymorphism is associated with the serum concentration of cat-specific immunoglobulin E as well as the development and severity of asthma in Chinese children

Thromboxane A2 and its receptor (TBXA2R) are involved in the constriction of vascular and respiratory smooth muscles. The T924C polymorphism in the TBXA2R gene was recently found to be associated with asthma in Japanese adults but not in children. Its relationship with atopy or asthma severity in children has not been defined. To investigate this further, we first assessed the severity of asthma in Chinese children using a standardized questionnaire modified from the Disease Severity Score and spirometric evaluation. Then, peripheral blood was analyzed for serum total and aeroallergen‐specific immunoglobulin E (IgE) levels, and TBXA2R T924C genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. One‐hundred and fifty three asthmatic patients and 57 control children were recruited, of respective mean ages 9.9 and 11.0 years (p = 0.07). The mean logarithmic serum total IgE concentration was 2.57 and 2.09, respectively, for the asthmatic group and control group (p < 0.0001). Atopy was detected in 132 (86%) asthmatics and 33 (58%) controls. A significant association was observed between T924C and the diagnosis of atopic asthma (p = 0.044; odds ratio: 1.84). In addition, those asthmatics homozygous for the mutant allele in T924C had a lower forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) (p = 0.032 and 0.002, respectively). Among our asthmatic patients, the TBXA2R T924C polymorphism correlated with the concentration of cat‐specific IgE in serum (p = 0.046). Nonetheless, this gene marker did not show an association with the serum total IgE concentration or any clinical indicator of asthma severity. In conclusion, our results suggest that the T924C marker in the TBXA2R gene is associated, in Chinese children, with an increased susceptibility of developing atopic asthma. This marker is also associated with the extent of allergic sensitization to cat, as well as with reduced FEV₁ and FVC values.     

Comparison of Der p1-specific antibody levels in children with allergic airway disease and healthy controls

Although children, with allergic airway disease, who are sensitized to house-dust mite (HDM) are known to have increased levels of allergen-specific IgE and IgG, the association between the quantity of those immunoglobulins and the clinical features of disease is not yet well established. The purpose of this study was (i) to evaluate Der p1-specific IgA, IgG1, IgG4, and IgE levels of children with HDM-allergic asthma and allergic rhinitis and to compare it with that of healthy controls (ii) to assess the association with disease duration. A total of 73 patients were included. Of those, 58 had asthma (M/F: 27/31, mean age 7.9 +/- 2.7 yr) and 15 were diagnosed as allergic rhinitis (M/F: 8/7, mean age 10.1 +/- 4.0 yr) without asthma. Twenty-five (M/F: 13/12, mean age 9.5 +/- 4.2 yr) non-allergic children were included as healthy controls. Data on age at onset and duration of disease were recorded. Then, Der p1-specific IgA, IgG1, IgG4, IgE levels were measured in all of the 98 subjects by ELISA. Comparison of Der p1-specific antibody levels of patients and controls revealed that Der p1-specific IgG1, IgG4 and IgE levels of patients with asthma (p = 0.012, p = 0.021, p = 0.004, respectively) were significantly higher than healthy controls. Also, the ratio of Der p1-specific IgA/IgE was significantly lower in asthmatic children when compared with children with allergic rhinitis and controls (p = 0.029, p < 0.001, respectively). Der p1-specific IgG1, IgG4, IgE and IgA levels of asthmatic children with duration of disease of >or=4 yr were significantly higher than those with disease duration of <4 yr. IgA/IgE ratio was not significantly different in those two groups of asthmatics. We concluded that although all of the specific antibody levels increased with longer duration of asthma, IgA/IgE ratio remains to be low in asthmatic children allergic to HDM.     

Cytokine production, activation marker, and skin homing receptor in children with atopic dermatitis and bronchial asthma

T cells are known to develop a critical role in the pathogenesis of atopic dermatitis (AD) and bronchial asthma. T cells involved in AD express the skin homing receptor CLA, but no lung homing receptor has been identified in bronchial asthma. We compared different cell markers and the cytokine production in T cells from children with AD or bronchial asthma. We studied the involvement of CLA+ and CLA- T-cell subpopulations in these diseases. We studied 20 children with acute AD lesions, 15 with mild persistent asthma, and 15 non-atopic controls. All patients were sensitized to house dust mite (DP) and evaluated during the acute phase. Total and specific IgE were measured by immunoassay and the expression of different cell markers and the cytokine production was analyzed by flow cytometry in peripheral blood mononuclear cells. Total IgE was significantly higher in AD children and IgE to DP in the asthmatic children. There was a significant increase in CD25+ CD4+ cells in asthmatic children and in HLA-DR+ CD4+ and HLA-DR+ CD8+ cells in AD. In the CD4+ subsets, there was an increase in IL-13, IL-5 and TNF-alpha in AD compared to controls, a decrease in IFN-gamma in asthmatic children compared to controls, and an increase in IL-13, IL5, IL2, TNF-alpha, and IFN-gamma in the AD compared to asthmatic children. Changes in cytokine production were mainly detected in CLA+ cells in AD and in CLA- cells in asthma. Differences exist in total and specific IgE, activation markers, and cytokine patterns between AD children and children with asthma, with the former expressing a Th2 pattern whereas in asthmatic children we only detected a decrease in IFN-gamma. Moreover, the subpopulations (CLA+ vs. CLA-) expressing these changes were different, indicating that the underlying mechanisms in the two diseases are not exactly the same.     

鼻炎与支气管哮喘发病的关系

目的探讨小儿鼻炎与支气管哮喘发病的关系。方法鼻炎患者130例分成2组,单纯鼻炎组60例,鼻炎并哮喘组70例,分析两组年龄、性别、既往湿疹史、毛细支气管炎史、吸烟家族史、哮喘家族史、变应原检测、外周血总IgE及嗜酸性粒细胞(EOS)计数等方面的差别。并用Logistic回归分析进一步确定鼻炎患者发生哮喘的危险因素。结果将两组比较,发现既往毛细支气管炎史、哮喘家族史、母亲哮喘及变应原屋尘、粉尘螨阳性在鼻炎并哮喘组中更多见。此外,外周血总IgE和EOS计数在鼻炎并哮喘组高于单纯鼻炎组。Logistic回归分析发现,外周血总IgE和EOS计数增高是鼻炎并哮喘的重要的危险因素。结论若鼻炎患者存在既往毛细支气管炎史、哮喘家族史、变应原检测阳性,尤其是外周血总IgE和EOS计数增高者,应视为哮喘的前驱表现,需及早防治。     

An asthmatic adolescent with a rash and eosinophilia

Children frequently visit emergency departments with asthma exacerbations. Many of these asthmatic children may have fever and/or pneumonia, but when associated with eosinophilia or evidence of vasculitis, other diagnoses should be considered. Churg-Strauss syndrome is a rare form of systemic vasculitis, which usually occurs in patients with asthma in association with eosinophilia. The diagnosis of Churg-Strauss syndrome can be difficult because this syndrome may arise at first as a common association between asthma and allergic rhinitis. A delay in diagnosis and treatment may increase the morbidity from the complications of vasculitis. We report a young asthmatic adolescent who presented with vasculitis, eosinophilia, and peripheral neuropathy.     

哮喘缓解期儿童血清白细胞介素-13与免疫球蛋白E水平变化

目的探讨哮喘患儿IL-13及总IgE变化的意义。方法采用酶联免疫吸附试验(ELISA)方法和Pharmacia UniCAP检测系统检测88例6~14岁的哮喘缓解期和40例正常对照儿童血清IL-13与总IgE水平。结果哮喘缓解期儿童临床症状和肺功能改善;血清IL-13水平高于正常儿童对照组(U=3.93 P<0.01);血清总IgE水平仍明显高于正常儿童对照组(U=10.52 P<0.01)。血清IL-13水平与总IgE水平呈显著正相关(r=0.2685 P>0.05)。结论哮喘缓解期变态反应性炎症持续存在,血清高质量浓度的IL-13和IgE与哮喘的免疫病理相关。     

Bronchial challenge with purified protein derivative of Mycobacterium tuberculosis in asthma.

Response to bronchial challenge (BC) with purified protein derivative of Mycobacterium tuberculosis (PPD), was studied in children with bronchial asthma and correlated with Mantoux test and serum immunoglobulin E (IgE) against PPD (PPD-Sp IgE). Nearly 59% patients with bronchial asthma and 12.2% patients with pulmonary tuberculosis gave positive BC. Children with extra-pulmonary tuberculosis and normal children did not show positive BC. In asthma, 25% gave early (EAR), 50% gave late (LAR) and 25% gave both early and late (DAR) asthmatic response. Forced expiratory flow volumes in 1 sec (FEV.1) of 13 age and sex matched asthmatic and normal children showed similar volumes before BC, however, the values were significantly lower in asthma at 20 min (p less than 0.005) and 24 h (p less than 0.005) after BC. There was no relationship between response to BC and the severity or chronicity of asthma. PPD-Sp IgE was estimated by the radioimmunoassay method (Pharmacia Diagnostics). It was detected in 75% with positive BC and none of the controls. The titre was of Phadebas RAST Class III in 66.7%, Class II in 22.2% and Class I in 11.1%. The presence of early Mantoux reactions, positive BC with PPD and serum PPD-Sp IgE suggest the existence of Type I or Arthus type of reactions to PPD, which could cause hyperreactive airways in some cases of asthma.     

支气管哮喘儿童血清25-（OH）D3和总免疫球蛋白E的变化

目的：研究支气管哮喘儿童血清25-羟维生素D3［25-（OH）D3］和总免疫球蛋白E（TIgE）的变化及临床意义。方法采用放射免疫分析法,检测30例支气管哮喘、40例喘息性支气管炎患儿及40例正常对照儿童血清25-（OH）D3及TIgE含量,比较3组间其血清含量的差异。结果支气管哮喘组血清25-（OH）D3含量（18±3 ng/mL）明显低于喘息性支气管炎组（43±3 ng/mL）和正常对照组（43±3 ng/mL）,且TIgE含量（192±16 IU/mL）明显高于喘息性支气管炎组（123±14 IU/mL）和正常对照组（118±15 IU/mL）,差异均有统计学意义（P＜0.01）。支气管哮喘组血清25-（OH）D3与TIgE呈负相关（r=-0.783,P＜0.01＝,喘息性支气管炎组、正常对照组血清25-（OH）D3与TIgE均无相关性。结论血清25-（OH）D3缺乏可能是导致儿童支气管哮喘发作的原因。血清25-（OH）D3水平增高可以抑制IgE的过度表达,这可能成为预防和治疗支气管哮喘等过敏性疾病的一种新的有效途径。     

PPD反应与发作期哮喘患儿ECP IgE及细胞因子表达的关系

目的：探讨PPD反应与发作期哮喘患儿ECP,IgE及细胞因子表达的关系。方法：实验分健康对照组和哮喘发作组,均进行结核菌素纯蛋白衍化物(PPD)试验。观察PPD反应与哮喘临床症状、肺通气功能测定。血清ECP、IgE等的关系以及PPD试验后哮喘患儿外周血IFN-γ,IL-4,IL-12P40 mRNA的表达。结果：哮喘患儿PPD阴性者(24/32例)明显多于阳性者(8/32例),且PPD反应阴性患儿哮喘中/重度发作(16/24例)较PPD阳性患儿(2/8例)多,P<0.05。PPD阴性的哮喘患儿血嗜酸性细胞阳离子蛋白(ECP)及IgE较PPD阳性的哮喘患儿明显增高(P<0.05)。哮喘患儿PPD试验后IL-12 P40 mRNA,IFN-γ mRNA无明显变化,而IL-4 mRNA升高较对照组明显(P<0.05),致IFN-γ/IL-4 mRNA比值下降。结论：PPD反应阴性的哮喘患儿可能存在着细胞免疫功能低下。PPD正向免疫刺激作用在哮喘患儿中受到抑制。[中国当代儿科杂志,2003,5(1):20-22]     

喘息性疾病患儿非细菌性病原体感染分析

目的：探讨呼吸道非细菌性病原体与婴幼儿喘息性疾病的相关性,以及血清总IgE水平和外周血中嗜酸性粒细胞计数在其感染中的临床意义。方法：对2010年9月至2011年9月住院治疗的490例喘息性疾病患儿,采用间接免疫荧光法检测血清中9种呼吸道感染非细菌性病原体IgM抗体并进行病原学分析,并同时检测血清中总IgE水平和外周血中嗜酸性粒细胞计数。结果：490例喘息性疾病患儿中, 检测出非细菌性病原体IgM抗体阳性233例,阳性率为47.6%,其中肺炎支原体（MP）的阳性率最高(25.3%),其次为腺病毒（ADV） （8.9%）和乙型流感病毒（FluB）（8.8%）。 36例患儿同时检测出两种以上非细菌性病原体,且主要为MP与其他病原体的混合感染（94%）。各年龄组（0 d~、1个月～、6个月～、1岁～、3~8.9岁）IgM抗体的总检出率分别为50.0%、67.3%、33.1%、57.3%、61.7%,各组间差异有统计学意义（P<0.05）。支气管哮喘的呼吸道感染病原体IgM抗体检出率最高,其次为喘息性支气管炎,最低为毛细支气管炎。病原体检出阳性的患儿,血中嗜酸性粒细胞的数目明显减少,而血清总IgE水平显著升高。结论：喘息性疾病患儿的非细菌性病原体主要是MP、ADV和FluB;MP和其他非细菌性病原体的混合感染比较普遍;1～6个月婴幼儿感染率较高;监测总IgE水平及嗜酸性粒细胞计数的变化对于婴幼儿喘息性疾病临床诊断和治疗有重大意义。     

哮喘患儿血清IL 12 TGFβ1 与IgE 水平变化的研究

目的：检测哮喘患儿不同病期的白细胞介素12 ( IL-12) 、转化生长因子β1 ( TGFβ1 ) 与免疫球蛋白E( IgE) 水平变化的规律,并探讨不同病期IL-12,TGFβ1水平与IgE水平的相关性,据此阐述它们在哮喘中的临床意义。方法：采用ELISA 方法检测85例哮喘患儿及30例正常儿童的血清IL-12,TGFβ1与总IgE 水平。结果：哮喘组血清IL-12,TGFβ1水平明显低于对照组,而IgE 水平则哮喘组明显高于对照组,且发作期IL-12,TGFβ1 水平（28.42±10.73 ng/L,40.25±11.73 pg/mL）明显低于缓解期（40.42±15.26 ng/L,65.41±22.38 pg/mL）,差异有显著性 (P< 0. 01),缓解期血清IL-12,TGFβ1 水平明显低于对照组（67.42±20.58 ng/L,178.54±90.56 pg/mL）,差异有显著性(P<0.01),发作期血清IgE 水平（280.35±80.54 IU/mL）明显高于缓解期（145.67±51.25 IU/mL）, 差异有显著性(P< 0.01), 缓解期血清IgE 水平明显高于对照组（53.61±13.32 IU/mL）, 差异有显著性(P<0.01),哮喘患儿血清IL-12,TGFβ1水平与IgE呈负相关(P< 0.01)。结论：哮喘患儿存在IL-12,TGFβ1及IgE 水平失衡,提示IL-12,TGFβ1 在哮喘的发病中起着重要作用,检测它们的水平可为哮喘的诊断及判断病情提供依据。     

CTLA-4启动子-318C/T基因多态性与哮喘患儿血清总IgE水平的关系

目的探讨细胞毒T淋巴细胞相关抗原4(CTLA-4)启动子-318(C/T)基因多态性和吉林长春地区哮喘患儿血清总IgE水平的关系,以便为哮喘的诊治提供新线索。方法随机选取90例哮喘患儿及100例健康体检儿童作对照组,哮喘组和对照组的性别和年龄差异无统计学意义。采用聚合酶链式反应—限制性片段长度多态性(PCR-RFLP)技术对哮喘组和对照组CTLA-4启动子-318(C/T)基因多态性进行检测分析;同时采用酶联免疫吸附试验(ELISA)检测不同基因型哮喘患儿血清总IgE水平。结果CTLA-4启动子-318位点存在基因多态性。血清总IgE水平哮喘组(M=308.92 IU/ml,Q=254.75)高于正常对照组(M=36.66 IU/ml,Q=33.57),P<0.01;哮喘组中基因型为野生型(CC型,M=375.86 IU/ml,Q=139.95),高于突变型(TT型 CT型,M=141.25 IU/ml,Q=47.73),P<0.01。结论CTLA-4启动子-318(C/T)存在基因多态性,该位点的基因多态性可能引起血清总IgE水平下调。     

Relationship between Vitamin D and Childhood Asthma: A Case–Control Study

Objective:

Studies determining the relationship between serum vitamin D status and childhood asthma have yielded controversial results. Findings indicated that vitamin D deficiency is associated with asthma and airway hyper responsiveness. The aim of this study was to assess the relationship between serum vitamin D status and childhood asthma.

Methods:

Data were obtained from 200 asthmatic children (age 3–12 years) and 200 healthy controls. Serum levels of 25(OH) vitamin D, total IgE, calcium, phosphorus, parathormone (PTH) and eosinophil count were measured in both asthmatic children and healthy controls. Also, the mean values of 25(OH) vitamin D were compared with asthma symptom severities.

Findings:

There was a significant decrease in the concentration of serum 25(OH) vitamin D in the asthmatic patients as compared with the controls (20.34±2.8 vs 25.39±4.1 ng/mL, 95%CI: 1.46–3.86, P=0.01). Out of total asthmatic subjects, 40 (20%) were vitamin D sufficient, 48 (24%) were insufficient, and 112 (56%) were deficient. Total IgE concentration was also significantly higher in asthmatic patients having vitamin D deficiency (132.4±20.1 IU/ml, 95%CI: 1.38–3.75, P=0.03). Comparing asthmatic patients with healthy controls, odds of having vitamin D level less than 20ng/mL was 2.47.

Conclusion:

Our findings suggest that vitamin D deficiency or insufficiency may be positively related to the prevalence of asthma in children.     

Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children

Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.     

Non-atopic asthma in children is related to maternal bronchial hyperreactivity

Data on the pathogenic mechanisms underlying the development of non-atopic asthma in children are scarce. Our aim was to evaluate the association and compare the atopic status, pulmonary functions, bronchial hyperresponsiveness and serum total immunoglobulin E (IgE) levels of parents of atopic and non-atopic asthmatic children by using objective methods. Fifty-one asthmatic children aged 4–16 yr and their parents were included into the study. Initially the American Thoracic Society's Respiratory Disease questionnaire inquiring data on symptoms of asthma, rhinitis and past medical history was filled in. Afterwards, skin prick test with aeroallergens, pulmonary function and methacholine bronchial provocation tests and serum sampling for total IgE level determinations were carried out. Bronchial hyperresponsiveness to methacholine was significantly more common in the mothers of non-atopic children compared to those of atopic ones, although no significant difference was observed in the skin prick test reactivity, pulmonary function test parameters and serum IgE levels. Questionnaire data revealed that the presence of asthmatic symptoms such as wheezing and phlegm and doctor-diagnosed asthma were more common in the mothers of non-atopic children. Meanwhile, asthmatic symptoms were also found to be significantly more common in fathers of non-atopic children. Logistic regression analyses revealed that maternal PC₂₀ was the only predictive factor for the risk of displaying non-allergic asthma in children. The results demonstrate that among the risk factors studied, maternal bronchial hyperreactivity was associated with the development of asthma in non-atopic children.     

Respiratory syncytial virus infection reversed anti-asthma effect of neonatal Bacillus Calmette-Guerin vaccination in BALB/c mice

Bacillus Calmette-Guerin (BCG) vaccination can protect animals from asthma, but the effect of BCG on childhood asthma prevention is controversial in humans. To verify the hypothesis that the BCG anti-asthma effect in childhood might be reversed by a respiratory virus infection, newborn BALB/c mice were divided into five groups. Control and ovalbumin (OVA) groups were mock vaccinated and mock infected. The BCG/OVA group was BCG vaccinated and mock infected. The respiratory syncytial virus (RSV)/OVA group was mock vaccinated and RSV infected. The BCG/RSV/OVA group was BCG vaccinated and RSV infected. Except for the control group, all groups underwent OVA sensitization and challenge. Airway hyperresponsiveness (AHR) was measured after challenge and cells in bronchoalveolar lavage fluid (BALF) were counted. Cytokines in BALF and serum OVA-specific IgE were detected by ELISA and inflammatory characteristics of lung sections were scored. Mice with neonatal BCG vaccination (BCG/OVA group) were significantly protected from BALF eosinophilia, AHR to methacholine, peribronchiolitis, alveolitis, and peribronchial eosinophilia in comparison with the OVA, RSV/OVA, and BCG/RSV/OVA groups. AHR in the OVA group was greater than in the BCG/OVA group but lower than in the RSV/OVA and BCG/RSV/OVA groups. No significant differences in BALF eosinophilia, AHR, and lung inflammation were found between the RSV/OVA and BCG/RSV/OVA groups. The impact of BCG vaccination on anti-asthma in mice was not dependent on interferon-gamma, IL-4, and IL-10 levels. The results suggested that RSV infection can reverse the anti-asthma effect of neonatal BCG vaccination in BALB/c mice.     

The effects of NOS1 gene on asthma and total IgE levels in Taiwanese children,and the interactions with environmental factors

Wang T‐N, Tseng H‐I, Kao C‐C, Chu Y‐T, Chen W‐Y, Wu P‐F, Lee C‐H, Ko Y‐C. The effects of NOS1 gene on asthma and total IgE levels in Taiwanese children, and the interactions with environmental factors.
Pediatr Allergy Immunol 2010: 21: 1064–1071.
© 2010 John Wiley & Sons A/S Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The aim of this study was to investigate the three microsatellite polymorphisms of GT repeats in intron 2, AAT repeats in intron 20, and CA repeats in exon 29 of the NOS1 gene in 155 asthmatic children and 301 control children, and the interaction with environmental factors in southern Taiwan. Total serum IgE, phadiatop test and genetic polymorphisms were measured. The genotype frequency of 14/14‐AAT repeats of the NOS1 gene was significantly higher in the asthmatic group (p = 0.01). Total IgE concentrations were higher in asthmatic children (p = 0.015) carrying the NOS1 14/14‐AAT genotype than in subjects with other polymorphisms. The gene and environmental interaction effects were 3.83‐fold, 6.86‐fold, and 8.04‐fold (all corrected p‐values <0.001) between subjects carrying at least one NOS1 14‐AAT allele and exposure to cockroaches, high levels of total IgE, and positive response against the phadiatop test in asthmatic children. The findings of this study provide strong evidence that NOS1 gene with 14‐AAT tandem repeats has a significant effect in asthmatic children. Environmental factors and atopic status will enhance the asthmatic risk for children who carry NOS1 susceptible allele.