儿童哮喘与成人慢性阻塞性肺疾病相关性研究进展

儿童哮喘与慢性阻塞性肺疾病(COPD)是儿童期与成人期常见的存在气流受限的慢性气道疾病。研究发现,儿童哮喘会增加成年期罹患COPD的风险,而肺功能变化是预测COPD患病风险的重要指标。针对哮喘患儿建立长期肺功能监测管理,对于评估其成年后存在不可逆气道阻塞的风险有重要意义。文章综述儿童哮喘与COPD相关的研究进展。     

哮喘相关基因与治疗药物的生物信息学分析

目的:通过生物信息学技术比较哮喘患者与健康人的基因芯片数据,初步鉴定与哮喘相关的基因以及治疗哮喘的潜在药物。方法:从基因表达数据库下载GSE74986基因芯片,使用GEO2R分析得出差异表达基因,采用Morpheus制作差异表达基因的热图;通过DAVID 6.8对差异表达基因进行基因本体及京都基因与基因组百科全书分析,使用String 10.5构建蛋白质-蛋白质相互作用网络,筛选核心基因。进一步使用Cytoscape 3.6.1的插件MCODE对差异表达基因进行模块分析。通过医学本体信息检索平台筛选治疗哮喘的小分子药物。结果:筛选出510个差异表达基因,包括29个上调基因和481个下调基因。差异表达基因生物过程与通路主要富集在染色质沉默、核糖核酸聚合酶Ⅱ启动子的转录调节、蛋白质转运、信使核糖核酸加工、核糖核酸剪接以及泛素介导的蛋白水解、内质网中的蛋白质加工、核糖核酸转运、髓样分化因子依赖性Toll样受体信号通路、血小板激活、核苷酸结合寡聚化结构域样受体信号通路等。共得出9个核心基因,包括T-复合蛋白1θ亚基(CCT8),T复合物蛋白1α亚单位(TCP1),26S蛋白酶调节亚单位S10B(PSMC6),热休克蛋白90α(HSP90A) A1,细胞周期蛋白C(CCNC),HSP90AB1,26S蛋白酶体非ATP酶调节亚基6(PSMD6),泛素特异性蛋白酶14(USP14),真核细胞翻译起始因子4E(EIF4E)。得出2个重要模块,模块里的基因主要涉及剪接体和泛素介导的蛋白水解、蛋白修饰以及核糖核酸修饰等生物过程。治疗哮喘的潜在小分子药物有茴香霉素和金雀异黄素等。结论:差异表达基因和核心基因促进了对哮喘发病分子机制的理解,为哮喘的诊治提供了潜在的基因靶标与治疗药物。     

温肺平喘法治疗支气管哮喘发作期冷哮证临床研究

目的观察温肺平喘法治疗支气管哮喘发作期冷哮证的临床疗效。方法患者150例随机分为两组各75例,中药组采用温肺平喘法治疗,西药组给予多索茶碱片治疗,必要时用沙丁胺醇气雾剂,疗程均为7 d。观察比较两组临床效果、治疗前后单项中医证候积分以及肺功能(FEV1%、FVC%、FEV1/FVC)指标。结果中药组总有效率为92.00%,显著高于西药组的80.00%(P<0.05)。两组喘息、咳嗽、胸闷气短、咯痰、喉中哮鸣音症状的单项积分均较治疗前改善(P<0.05),中药组改善更为显著(P<0.05)。治疗后两组的肺功能指标FEV1%、FVC%、FEV1/FVC均有所提高(P<0.05);中药组改善更为显著(P<0.05)。结论温肺平喘法治疗支气管哮喘发作期冷哮证疗效显著,能够改善支气管哮喘发作期冷哮证的临床症状,降低再次复发率,无明显不良反应。     

An evaluation of nebulised amphotericin B deoxycholate (Fungizone®) for treatment of pulmonary aspergillosis in the UK National Aspergillosis Centre

Antifungal treatment options for allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) are largely limited to itraconazole based on the outcome of randomised controlled trials. It is unclear if nebulised amphotericin B deoxycholate (Fungizone^®) is a viable therapeutic option. We evaluated the safety and efficacy of nebulised Fungizone^® in the long‐term treatment of various forms of pulmonary aspergillosis. We assessed the records of 177 patients with various forms of pulmonary aspergillosis attending the National Aspergillosis Centre in Manchester who had received Fungizone^®. Patients first received a challenge test with nebulised Fungizone^® in hospital with spirometry pre/post‐Fungizone^® and nebulised salbutamol given pre‐Fungizone^®. Tolerability and changes in Aspergillus IgE, Aspergillus IgG and total IgE were evaluated. Sixty‐six per cent (117/177) were able to tolerate the test dose of Fungizone^® and in all cases, the reason for discontinuation of the first test dose was worsening breathlessness. Twenty six (21%) stopped therapy within 4‐6 weeks, and the commonest reason cited for discontinuation of therapy was increased breathlessness, hoarseness and cough. Eighteen (10.2%) patients continued the Fungizone^® for >3 months of which 5 (27.8%) recorded an improvement in total IgE, Aspergillus‐specific IgE and Aspergillus IgG. Eleven had ABPA, four had SAFS, two had Aspergillus bronchitis and one had Aspergillus sensitisation with cavitating nodules. Among these 18 patients, sputum fungal culture results went from positive to negative in five patients, became positive in one patient, remained positive in three patients, and remained negative in seven patients. Nebulised Fungizone^® appears to be a poorly tolerated treatment for pulmonary Aspergillosis with high dropout rates. There appears to be both clinical and serological benefits following sustained treatment with nebulised Fungizone^® in some patients.