基于ABM探讨吸烟对重度哮喘影响的机制

目的探讨吸烟影响重度哮喘的机制,为治疗由吸烟引起的重度哮喘奠定理论基础。方法本文以基本免疫仿真器（basic immune simulator,BIS）为平台,仿真出THl7对免疫系统影响的模型（agent based modeling,ABM）,与BIS已仿真出的DCs模型对比,并结合吸烟的临床数据,验证模型的正确性。结果本文提出吸烟弓I起重度哮喘可能的机制是：烟雾中的氧化物能激发成熟DCs细胞产生IL-8细胞因子,随着烟雾作用时间的延长,产生的IL-8增多,使吸烟的哮喘者加重病情。结论Dcs-IL23-THl7-IL8-嗜中性炎症可能是导致重度哮喘的路径。以THl7为靶标,减少DCs,切断IL23-THl7-IL8路径,可以控制吸烟引起重度哮喘的症状。     

支气管哮喘重度发作患者的急诊护理浅析

目的 探讨支气管哮喘重度发作患者的急诊护理方法,提高急救的成功率,降低患者的死亡率.方法 收集自2012年来就诊于我院的64例确诊为支气管重度发作的患者的临床资料,并进行回顾性分析.结果 通过采取积极有效地护理措施,64例患者除1例死亡,病情均明显好转.结论 积极有效的护理措施在提高支气管哮喘重度发作患者的抢救成功率及降低患者死亡率中具有重要作用.     

黄芪在树突状细胞水平对哮喘TH 1/TH 2平衡的调节作用

目的 探讨黄芪在树突状细胞(DC)水平对过敏性哮喘TH/TH2平衡的调节作用.方法 用rhGM-CSF和rhIL-4诱导培养外周血来源的DC并予鉴定,ELISA法检测其分泌的细胞因子IL-12、IL-10以及与自身T细胞反应后,RT-PCR检测T-bet和GATA-3 mRNA含量,流式细胞术检测T细胞分泌的胞内细胞因子IL-4和IFN-γ水平.结果 哮喘患儿外周血DC分泌IL-10高于对照组(P＜0.05);黄芪干预后DC分泌IL-10降低,与哮喘组比较差异有统计学意义(P＜0.05).哮喘患儿外周血DC分泌IL-12低于对照组(P＜0.05);黄芪干预后DC分泌IL-12增加,但与哮喘组比较差异无统计学意义.混合培养第7天哮喘组T细胞内IL-4水平显著高于正常对照组(P＜0.01);而IFN-γ水平则显著低于正常对照组(P＜0.05);哮喘组IL-4/IFN-γ比值高于正常对照组(P＜0.01).黄芪干预后T细胞内IL-4水平与哮喘组比较差异无统计学意义,而IFN-γ水平增加,与哮喘组比较差异有统计学意义(P＜0.05),IL-4/IFN-γ比值降低,与哮喘组比较差异有统计学意义(P＜0.01).哮喘组T-bet mRNA的表达强度明显低于正常对照组(P＜0.01);而哮喘组GATA-3 mRNA的表达强度则明显高于正常对照组(P＜0.05);哮喘组GATA-3/T-bet比值高于正常对照组(P＜0.05).黄芪干预后T细胞GATA-3 mRNA的表达强度与哮喘组比较差异无统计学意义,而T-bet mRNA水平增加,与哮喘组比较差异有统计学意义(P＜0.05),GATA-3/T-bet比值降低,与哮喘组比较差异有统计学意义(P＜0.01).结论 哮喘患儿DC功能缺陷,产生IL-12减少、IL-10增加导致TH2优势分化,从而使TH1/TH2平衡向TH2倾斜,合成IFN-γ减少,进而造成气道慢性炎症、气道高反应性而致哮喘发作.黄芪对DC的调节主要通过降低IL-10的分泌水平,从而降低其抑制TH0细胞向TH 1分化的功能,即间接抑制了TH0细胞向TH2的分化.     

TH2类细胞因子与哮喘关系研究进展

TH2淋巴细胞通过分泌IL-4,IL-13,IL-5和Ⅱ9等细胞因子触发气道炎症引起哮喘.编码TH2类细胞因子的基因位于染色体5q31～33区,与哮喘有连锁关系.TH2类细胞因子是治疗哮喘病人的重要目标靶.     

哮喘患儿激素治疗后TH1/TH2的变化

目的观察哮喘患儿血清中白细胞介素IL12、IL13和IgE水平的变化及糖皮质激素对其的影响。方法采用ELISA法分别检测哮喘患儿急性期及口服强的松5～7天后、健康对照组血清中IL12、IL13和IgE的水平。结果哮喘组患儿IL12水平急性发作期较治疗后和健康对照组低,差异均有显著性（P〈0.01）。IL13水平急性发作期较治疗后和健康对照组高,差异均有显著性（P〈0.01）,IgE水平急性发作期较治疗后和健康对照组高,差异均有显著性（P〈0.01）。直线相关分析表明,血清中IL12与IL13负相关,与IgE呈负相关,IL13与IgE呈正相关。结论哮喘患者血清中IL13、IgE水平升高,IL12水平下降,3者的变化相关,糖皮质激素可使IL13水平下降,IL12水平升高。     

卡介苗对哮喘小鼠TH1/TH2平衡的影响

目的　探讨卡介苗 (BCG)对哮喘小鼠TH1 TH2平衡的影响。方法　C5 7BL 6小鼠以卵白蛋白 (OVA)致敏激发建立哮喘模型。于第一次抗原激发前 2周以BCG皮内注射干预 ,在最后 1次抗原激发后 4 8h收集支气管肺泡灌洗液 (BALF)和外周血 ,ELISA方法测定外周血清及BALF中IL 5与IFN γ水平 ,并采用三色光流式细胞分析法测定外周血TH1 TH2细胞比。结果　与阴性对照组相比 ,OVA致敏激发组外周血清及BALF中IL 5水平升高而IFN γ水平降低 ,BCG干预组外周血清及BALF中IL 5较OVA致敏激发组低而IFN γ较后者升高 ,与阴性对照组水平相近。此外 ,OVA致敏激发组外周血中TH2 TH1比值 (1.5 7± 0 .5 6 )较阴性对照组 (0 .37± 0 .0 5 )明显增高 (P <0 .0 1) ,BCG干预后TH2 TH1比值 (0 .5 9± 0 .11)较OVA致敏激发组下降 (P <0 .0 5 ) ,同时Tc2 Tc1比值 (0 .6 2± 0 .0 7)也较OVA致敏激发组 (1.15± 0 .18)降低 (P <0 .0 5 )。结论　哮喘小鼠中TH2型免疫应答占优势 ,BCG干预不仅在细胞因子水平 ,也在细胞数量上校正了TH1 TH2失平衡。     

支气管哮喘的免疫治疗研究进展

支气管哮喘是受遗传因素和环境因素双重影响的气道炎症性疾病,是目前危害公共健康的问题之一,在过去的几十年里其发病率呈现上升的趋势。随着对哮喘发病机制的深入研究,辅助性T淋巴细胞亚群功能失调,即Th1Th2细胞失衡,在哮喘发生中的作用已越来越为人们所认识,故针对调节Th1Th2细胞间平衡的哮喘免疫治疗已成为研究热点,抑制Th2细胞免疫或增强Th1细胞免疫的治疗方法取得了一定的进展。     

细胞因子信号抑制因子在支气管哮喘TH1/TH2细胞失衡中的作用

目的 探讨细胞因子信号抑制因子（SOCS）在支气管哮喘（简称哮喘）患儿TH细胞亚群（TH1／TH2）功能失衡中的作用，以及转录因子T-bet和GATA3与TH1／TH2反应的关系。方法 观察20例哮喘患儿及相同数量同龄对照，采用流式细胞术（FCM）检测哮喘患者外周血CD4^＋T淋巴细胞浆中白细胞介素4（IL-4）和γ干扰素（INF-γ）的表达，逆转录-聚合酶链反应（RT-PCR）和荧光定量聚合酶链反应（real time PCR）测定淋巴细胞SOCS3、SOCS5、T-bet、GATA3 mRNA表达水平。结果 急性发作期哮喘患儿TH1细胞比例显著下降，TH2细胞显著增高（P〈0．01）；哮喘患儿淋巴细胞SOCS3、GATA3 mRNA表达水平显著高于正常同龄对照（P〈0．01），SOCS5、T-bet mRNA表达显著下降（P〈0．01）。结论 SOCS3、SOCS5、T-bet和GATA3表达异常与哮喘患儿TH1／TH2失衡有关，其中SOCS3和SOCS5表达异常可能是重要的因素之一。     

过敏性哮喘的免疫治疗研究进展

过敏性哮喘是一种顽固性疾患,多数在婴幼儿时期发病,若得不到有效治疗将会伴随终身。大部分哮喘患者都存在过敏现象或者有过敏性鼻炎,有过敏性鼻炎的哮喘患者发病前兆会有打喷嚏、流鼻涕、鼻痒、眼痒、流泪等症状。由于症状与呼吸道感染或炎症相似,大人缺乏相关知识,往往在早期忽视治疗,也极有可能被误诊[1]。     

重症哮喘靶向治疗的研究进展

支气管哮喘(简称哮喘)是一种慢性气道炎症性疾病,具有明显的异质性和复杂的病理生理表现.我国成人的哮喘患病率为1.24%,其中重症哮喘占5.99%.重症哮喘表现为控制水平差,是哮喘致残、致死的主要原因,临床治疗棘手.近年来,针对辅助T细胞(helper T cell,Th)2和Th17表型的生物靶向治疗药物成为哮喘新药开发的热点之一.生物靶向治疗药物为重症哮喘患者带来了新的希望.现就重症哮喘靶向治疗的研究现状进行综述,以期为临床医师治疗重症哮喘提供参考.     

Methylprednisolone pulse therapy in severe acute asthma

In a group comparative double blind pilot study six asthmatic patients with an acute exacerbation of their disease were randomly treated with either methylprednisolone pulse therapy (MPPT) (1000 mg daily for 3 days) (n = 2) followed by placebo tablets, or standard doses of methylprednisolone (MP) (50 mg daily gradually decreased to zero over 3 weeks) (n = 4). The results showed that the effect of MPPT did not differ from that of standard doses of MP. MPPT has, however, the potential of being preferable to standard treatment with MP, because of easy administration and optimal patient compliance.     

EAACI position statement on asthma exacerbations and severe asthma

Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult‐to‐treat asthma and severe treatment‐resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment‐resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult‐to‐control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult‐to‐control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.     

Omalizumab therapy for children and adolescents with severe allergic asthma

Omalizumab, a therapeutic humanized monoclonal antibody specific for human IgE, was introduced in clinical practice more than a decade ago as an add-on therapy for moderate-to-severe allergic asthma in patients aged ≥12 years. Omalizumab has been demonstrated to be effective in adults with uncontrolled persistent asthma, with an excellent safety profile. In simple terms, omalizumab works by inhibiting the allergic cascade, that is, by neutralization of the circulating free IgE. This leads to reduction in the quantity of cell-bound IgE, downregulation of high-affinity IgE receptors, and, eventually, prevention of mediator release from effector cells. Evidence is far less abundant on the role of omalizumab in pediatric asthma. Although efficacy and safety of omalizumab in children and adolescents with uncontrolled, persistent allergic asthma has been recognized as well, further studies are needed to clarify a number of open questions in this specific patient population.     

Therapeutic options for severe asthma

As the overall prevalence of asthma has escalated in the past decades, so has the population of patients with severe asthma. This condition is often difficult to manage due to the relative limitation of effective therapeutic options for the physician and the social and economic burden of the disease on the patient. Management should include an evaluation and elimination of modifiable risk factors such as smoking, allergen exposure, obesity and non-adherence, as well as therapy for co-morbidities like gastro-esophageal reflux disease and obstructive sleep apnea. Current treatment options include conventional agents such as inhalational corticosteroids, long acting β₂ agonists, leukotriene antagonists, and oral corticosteroids. Less conventional treatment options include immunotherapy with methotrexate, cyclosporine and tacrolimus, biological drugs like monoclonal antibodies, tumor necrosis factor-α blockers and oligonucleotides, phosphodiesterase inhibitors, antimicrobials and bronchial thermoplasty.     

Methylprednisolone pulse therapy in acute severe asthma

Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.