扎那米韦吸入粉雾剂治疗流行性感冒的临床研究

发布时间：2018-04-24 11:52

本文选题：流感 + 扎那米韦　；参考：《第二军医大学》2013年硕士论文

【摘要】：研究目的： 1.评价吸入性扎那米韦治疗我国流感患者的疗效及安全性。 2.研究甲、乙型流感患者血清中发生变化的细胞因子，探讨与流感患者临床症状严重程度相关的细胞因子。研究方法：第一部分吸入性扎那米韦粉雾剂治疗中国流感患者的疗效及安全性采用多中心、随机双盲、安慰剂平行对照临床试验设计方法，入选流感患者，全部患者随机分为2组，扎那米韦组应用吸入性扎那米韦10mg，安慰剂组应用安慰剂，bid，治疗5d，两组常规给予对症、支持治疗。观察指标包括体温、鼻塞、咽喉痛、咳嗽、肌肉酸痛、乏力、头痛及寒战，在开始治疗后的day6和day21天进行辅助检查、生命体征检查并记录不良事件，以评定药物的安全性。第二部分甲、乙型流感患者血清中细胞因子水平的变化及与临床症状严重性相关的细胞因子的研究 1.收集确诊流感病人治疗前和治疗后d6天血清，ELISA法检测血清中IL-6、IL-17A、IL-29、IL-32、IL-33、TNF-α、IFN-γ、IP-10表达水平。 2.运用SPSS17.0统计软件进行分析，比较甲、乙型流感患者血清中发生变化的细胞因子水平的差异，运用斯皮尔曼相关分析找出与流感患者临床症状严重程度相关的细胞因子。研究结果: 1.扎那米韦组疑似流感患者临床症状缓解时间为84h，安慰剂组临床症状缓解时间96h，两者差异有统计学意义（P0.05）。 2.扎那米韦组疑似流感患者在开始治疗后60h和72h的疾病缓解率分别为37.59%和44.68%，高于相应时间点安慰剂组患者疾病缓解率（分别为22.92%和25.00%），差异均有统计学意义（P均0.05）。 3.扎那米韦组确诊流感患者临床症状缓解时间短于安慰剂组，差异有统计学意义（P0.05）。 4.本研究中扎那米韦组和安慰剂组不良事件发生率分别为23.94%和22.22%，差异无统计学意义（P0.05）。 5.与健康人群相比较，甲、乙型流感患者血清中细胞因子IL-6、IL-33、TNF-α、IFN-γ、IP-10水平升高，差异有统计学意义（P0.05）；甲、乙型流感患者血清细胞因子水平相比，，乙型流感患者血清中细胞因子IL-17A, IL-29, IFN-γ和IP-10表达水平显著升高（P均0.05）。 6.甲、乙型流感患者血清中表达水平发生变化的细胞因子中，IFN-γ和IP-10表达水平与患者淋巴细胞计数呈负相关（r=-0.39, P=0.013; r=-0.44, P=0.005）。研究结论： 1.吸入性扎那米韦粉雾剂治疗流感患者安全、有效。 2.季节性流感患者血清中一系列促炎细胞因子表达水平发生显著变化，其中，乙型流感患者血清中适应性免疫应答相关细胞因子（IL-17A, IL-29, IFN-γ和IP-10）的表达水平在比甲型流感患者高。 3. IFN-γ和IP-10可作为流感患者病情严重程度的标志物，早期检测可帮助发现重症患者并及时采取治疗。
[Abstract]:Objectives of the study: 1. To evaluate the efficacy and safety of inhaled zanamivir in the treatment of influenza patients in China. 2. To study the cytokines in the serum of patients with influenza A and B, and to explore the cytokines related to the severity of clinical symptoms in patients with influenza. Research methods: Part I efficacy and safety of inhaled zanamivir powder in the treatment of influenza patients in China A multicenter, randomized, double-blind, placebo controlled clinical trial was used to select patients with influenza. All patients were randomly divided into two groups. Zanamivir group received inhaled zanamivir 10 mg, placebo group received placebo bid for 5 days, the two groups were routinely treated with symptomatic and supportive therapy. The parameters included body temperature, nasal obstruction, sore throat, cough, muscle soreness, fatigue, headache and chills. Adjuvant examinations were performed on day6 and day21 days after treatment, vital signs were examined and adverse events were recorded to assess the safety of the drug. The changes of serum cytokines in patients with influenza A and B and the study of cytokines related to the severity of clinical symptoms 1. The serum levels of IL-6, IL-17, IL-17, IL-29, IL-32, IL-33, TNF- 伪, IFN- 纬 and IP-10 in patients with confirmed influenza were detected by Elisa before treatment and 6 days after treatment. 2. SPSS17.0 software was used to analyze the difference of serum cytokine levels in patients with influenza A and B, and the cytokines related to the severity of clinical symptoms of influenza patients were found by Spelman correlation analysis. Results of the study: 1. The remission time of clinical symptoms of suspected influenza patients in zanamivir group was 84 hours, and that of placebo group was 96 hours, the difference was statistically significant (P 0.05). 2. The remission rates of suspected influenza patients in zanamivir group were 37.59% and 44.68% at 60 h and 72 h after treatment, respectively, which were higher than those in placebo group (22.92% and 25.00%, respectively). The difference was statistically significant (P < 0.05). 3. The duration of remission of clinical symptoms in patients with confirmed influenza in zanamivir group was significantly shorter than that in placebo group (P 0.05). 4. The incidence of adverse events in zanamivir group and placebo group was 23.94% and 22.22%, respectively. 5. Compared with the healthy population, the serum levels of IL-6, IL-3, TNF- 伪, IFN- 纬, IP-10 in patients with influenza A and B were significantly higher than those in healthy people, and the levels of serum cytokines in patients with influenza A and B were significantly higher than those in patients with influenza A and B, and the levels of cytokines in patients with influenza A and B were significantly higher than those in patients with influenza A and B. The levels of cytokines IL-17A, IL-29, IFN- 纬 and IP-10 in serum of patients with influenza B increased significantly (P < 0.05). 6. The expression levels of IFN- 纬 and IP-10 in serum of patients with influenza A and B were negatively correlated with the lymphocyte counts of patients with influenza A and B, and were negatively correlated with lymphocyte counts (P = 0.39, P = 0.013; r = -0.44, P = 0.005). The study concluded that: 1. Inhaled zanamivir powder is safe and effective in the treatment of influenza patients. 2. The expression of a series of pro-inflammatory cytokines in the serum of patients with seasonal influenza showed significant changes. The expression levels of IL-17A, IL-29, IFN- 纬 and IP-10) were higher in patients with influenza B than in patients with influenza A. 3. IFN- 纬 and IP-10 can be used as markers of severity of influenza patients.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R511.7

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