Objective To systematically evaluate the effectiveness and safety of omalizumab in treating allergic bronchial asthma. Methods The randomized controlled trials (RCTs) about omalizumab in treating allergic bronchial asthma were searched in databases such as MEDILINE, EMbase, The Cochrane Library, CBM, CNKI, VIP and WanFang Data from inception to April 2013. The references of included studies and relevant conference proceedings were also retrieved manually. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the quality, and then RevMan 5.1 software was used for meta-analysis. Results A total of 13 RCTs involving 4 195 patients were included. The results of meta-analysis showed that: a) Compared with the control group, the trial group revealed lower acute exacerbation of asthma during treatment (RR=0.71, 95%CI 0.65 to 0.77, Plt;0.000 01), and higher rate of patients achieved best/better results in Global Evaluation of Treatment Effectiveness (GETE) (RR=1.61, 95%CI 1.32 to 1.97, Plt;0.000 01). More patients could reduce the inhaled cortisteroid (ICS) by 50% during both treatment (RR=1.40, 95%CI 1.29 to 1.52) and 24-week follow-up period (RR=1.69, 95%CI 1.41 to 2.03). And it also increased the ratio of patients whose Asthma Quality Of Life Questionnaire (AQLQ) score got improved by 0.5 and 1.5 socres. b) There were no significant differences in the incidence of overall adverse events (RR=1.01, 95%CI 0.98 to 1.04) and severe adverse events (RR=0.94, 95CI 0.68 to 1.28). c) There might be the effects of omalzumab in improving lung function and reducing rescue medication use, but they were not obviously observed in the studies. Conclusion In the treatment of asthma, omalizumab can decrease the acute exacerbation of asthma and ICS use, and it is safer to improve the therapeutic effects and quality of life.
Objective To investigate the expression of aquaporin-1( AQP-1) in pulmonary tissues of asthma mice and the effects of acetazolamide( AZ) on AQP-1 expression. Methods Forty C57BL/6 mice were randomly divided into five groups. Group A was treated with phosphate buffer as a non-asthmatic group.The mice in group B, C, D, and E were sensitized with ovalbumin( OVA) and challenged with aerosol OVA to establish asthma model. The mice in group B, C, and D were interperitoneally injected with AZ at doses of 300, 200, 100 mg/kg, respectively during the challenge period. Results ①Wet/dry weight ratio of lung tissues in group E was significantly higher than that in group A( P lt;0. 05) , while it was lower in B, C and D groups than group E. ②The total number of cells, the number of eosinophils, and interleukin-5( IL-5) inBALF of group E were higher than those in group A( P lt;0. 05) , and interferon-γ( IFN-γ) level was lower in group E than in group A ( P lt; 0. 05) . After AZ treatment, the total number of cells, the number of eosinophils, neutrophils and lymphocytes were significantly decreased( P lt; 0. 05) , which were positively correlated with the dose of AZ. ③AQP-1 were expressed in tracheal epithelium, microvascular endothelial cell and bronchial peripheral vascular bed, and the expression in group E was significantly higher than that in group A( P lt;0. 01) . AQP-1 expression was significantly decreased after the intervention of AZ ( P lt;0. 05) .The decrease was positively correlated with the dose of AZ. The expression of AQP-1 mRNA showed no significant difference among these groups( P gt;0. 05) . Conclusions AQP-1 was over-expressed in the lung tissue of mice with asthma. AZ can inhibit the expression of AQP-1 and relieve lung inflammatory cells infiltrationin a dose-dependent manner. It is the protein expression of AQP-1 not the AQP-1 mRNA which were significantly different in different groups, suggesting that AZ affected AQP-1 in the post-transcriptional stage.
【摘要翻译】 一 氧化氮合酶( NOS) -2( NOS-2) 的诱导和一氧化氮产物增加是过敏性气道疾病的共同特征。严重哮喘与气道S-亚硝基硫醇减少相关。S-亚硝基硫醇是NO的生化产物, 可通过促炎症转录因子NF-κB 的S-亚硝基化抑制炎症反应。因此, 重建气道S-亚硝基硫醇对治疗可能有益。我们对此假设在以卵清蛋白诱导的过敏性炎症大鼠模型中进行验证。未使用或使用卵清蛋白致敏的动物均在卵清蛋白激发前于气管内灌注S-亚硝基谷胱甘肽( GSNO;50 μl, 10 mM) , 并在48 h 以后进行分析。GSNO 给药增加了肺组织S-亚硝基硫醇水平。与对照组比, GSNO 降低了卵清蛋白致敏动物NF-κB 的活性, 但对支气管肺泡灌洗细胞总数、分类计数及杯状细胞化生标记物均无显著影响。GSNO给药也改变了HIF-1 的活性, 导致未致敏大鼠HIF-1 活化,但抑制卵清蛋白致敏大鼠的HIF-1 活性。我们使用NOS-2基因敲除小鼠来评价内源性一氧化氮合成酶-2 在调节NF-κB和( 或) HIF-1 活性及气道过敏性炎症的作用。尽管在NOS-2 基因敲除小鼠中卵清蛋白诱导的NF-κB 活力轻度增高, 这与支气管肺泡灌洗中性粒细胞轻度增加有关, 其他的过敏性炎症指标和HIF-1 活性在NOS-2 基因敲除及野生型小鼠之间却无明显相差。总体来说, 我们的研究表明GSNO灌注能抑制气道过敏性炎症中NF-κB 活性, 但是并不能显著地影响大部分炎症及杯状细胞化生指标, 这样可能因为对其他信号通道( 比如HIF-1) 的影响而限制了它的治疗价值。【述评】 GSNO 是近年哮喘治疗研究的热点。既往的研究发现GSNO 在哮喘治疗中有一定前景。本研究却发现GSNO 气管内滴注虽能抑制过敏性气道炎症中NF-κB 活性,但并不能显著抑制气道炎症反应及杯状细胞化生这两个哮喘关键病理改变, 可能与GSNO 同时影响了HIF-1 等其他信号通路有关。该研究表明GSNO 对哮喘气道炎症治疗效果有限, 同时表明哮喘气道炎症调控机制较为复杂, 治疗药物的设计需考虑多种信号通路对哮喘气道炎症的影响。
Objective To investigate the clinical significance of the level of serum amylase and serum IgA and total IgE in henoch-schonlein purpura patients with gastrointestinal involvement (also known as "Henoch purpura "). Methods Levels of serum amylase and serum IgA and total IgE in henoch-schonlein purpura patients with or without abdominal pain or patients with acute abdominal pain were compared. Results The average level (180.3 ± 15.8 IU) of serum amylase of Henoch purpura patients was significantly higher than HSP patients without abdominal pain and acute abdominal pain patients (F=32.214, P=0.009); Ratio of cases of increased level of serum IgA in henoch purpura abdomen patients was 44.2%, and there was no significant difference with HSP patients without abdominal pain. But ratio of two groups was respectively higher than the acute abdominal pain patients group (χ2=13.73, P=0.001); Ratio of cases of increased level of serum IgE in Henoch purpura abdomen patients accounted for 40.4%, but there was no significant difference among the three group (χ2=1.80，P=0.41). Conclusion Levels of serum amylase increase and serum IgA increase conduce to diagnose HSP patients with the onset of abdominal pain, and serum total IgE has little significance.
Objective This review compared clinical effectiveness, cardiac safety and economics of astemizole, loratadine, cetirizine and terfenadine to provide evidence for adjustment of Essential Drug List in China. Search strategy We searched Medline, Cochrane Library, Embase and Chinese Biomedical Database. Fourteen databases for drug safety and pharmaceutical economics were additionally searched. Selection Criteria Randomized controlled trials and systematic reviews, published in English and Chinese and comparing two or more of these four antihistamines for allergic rhinitis and urticaria were included for study of effectiveness. Non-randomized clinical trials were additionally included for economic evaluation. Cardiac safety studies of antihistamines for allergic diseases of any type were included. Quality Appraisal Jadad scale was primarily applied to randomized controlled trials. Allocation concealment and intention-to-treat analysis were also appraised. The QUOROM statement was applied to systematic reviews and meta-analysis. Data extraction and analyses For the study of effectiveness, composite data were primarily extracted and analyzed by fixed effect model. Sensitivity analysis was done to explore the heterogeneity. For the study of cardiac safety, cases of adverse drug reactions and death were summarized. Difference of occurrence rate in sex and age were analyzed if possible.Electrocardiography and clinical symptoms were summarized. Results No studies on economic evaluation were identified. 27 and 6 randomized controlled trials, including 3 227 participants, for allergic rhinitis and urticaria were identified. Cetirizine was superior to loratadine (n=709) in symptom score and onset of action, superior to terfenadine (n=645) in Quality of Life and superior to astemizole (n=498) in patient satisfaction and onset of action. 73 h-ADR cases were identified in astemizole, 27 cases in terfenadine, 1 case in loratadine and none in cetirizine. No deaths were identified. Combination of terfenadine plus grapefruit juice (n=l8), itraconazole (n=6), nefazodone (n=67), and loratadine administration concomitant with cemitidine (n=30) significantly prolonged QTc interval. Conclusions Cetirizine was superior to other three antihistamines in terms of clinical effectiveness and drug safety. Astemizole and terfenadine could cause significantly more cardiac-related adverse reactions than cetirizine and loratadine.