可溶性TNF-α受体融合蛋白(Etanercept)对激素抵抗的难治性哮喘的作用：一项双盲、随机、安
2008/06/06
肿瘤坏死因子α (TNF-α) 是哮喘发病过程中的重要细胞因子，具有广泛的生物学活性。拮抗TNF-α活性可能有助于慢性炎症性疾病如哮喘等的治疗。Morjaria JB等以39例激素抵抗的难治性哮喘患者为研究对象，探讨了可溶性TNF-α受体融合蛋白Etanercept的平喘疗效。研究中采用哮喘生命质量问卷(AQLQ)、哮喘控制问卷(ACQ)、肺功能、气道高反应性(BHR)等作为评价指标；以痰和血清中炎症细胞和细胞因子量，血清白蛋白、C-反应蛋白(CRP)作为炎症的评价指标。该研究发现Etanercept治疗12周后，哮喘及全身炎症反应均得到显著改善。
（毛辉 四川大学华西医院呼吸科 610041 摘译）
(Thorax. 2008 Feb 1 [Epub ahead of print] Links)
The Role Of A Soluble Tnf-A Receptor Fusion Protein (Etanercept) In Corticosteroid-Refractory Asthma: A Double Blind, Randomised Placebo-Controlled Trial.
Morjaria JB, Chauhan AJ, Babu KS, Polosa R, Davies DE, Holgate ST.
University of Southampton, United Kingdom.
Rationale: TNF-alpha is a cytokine recognized as a therapeutic target in chronic inflammatory diseases.
Objectives and METHODS: We report a randomised double-blind placebo-controlled parallel group trial of etanercept (an IgG1-TNF p75 receptor fusion protein), administered once weekly for 12 weeks in 39 patients with symptomatic corticosteroid refractory asthma. Efficacy was measured by change from the pre-treatment baseline in Asthma Related Quality of Life (AQLQ) and Asthma Control (ACQ) Questionnaires scores (the primary end-points), lung function, PEF and bronchial hyperresponsiveness (BHR). We also assessed sputum and serum inflammatory cells and cytokines, serum albumin and C-reactive protein as biomarkers of inflammation.
MAIN RESULTS: There was a small but significant difference in reduction of ACQ scores between treatment and placebo (-1.11 (95%CI -1.56, -0.75) and -0.52 (95%CI -0.97, -0.07) respectively, p=0.030). There was no significant difference in improvements in AQLQ scores between groups (p=0.084), though sub group analyses restricted to 29 patients not taking antidepressants revealed significant improvements in both AQLQ and ACQ. There were no differences in lung function, PEF, BHR or exacerbation rates between groups. Minor adverse events including injection site pain and skin rashes were more frequent with etanercept. There was a significant reduction in sputum macrophages and CRP, and increases in serum TNF-alpha and albumin following treatment, but not in other laboratory parameters.
CONCLUSION: ETanercept therapy over 12 weeks demonstrated only a small but significant improvement in asthma control and systemic inflammation as measured by serum albumin and CRP. Larger randomised placebo-controlled trials are required to clarify the role of TNF-alpha antagonism in subjects with severe refractory asthma.
Thorax. 2008 Feb 1 [Epub ahead of print] Links
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3～18岁儿童变应性哮喘患者的舌下免疫治疗疗效荟萃分析
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ADRB多态性与长效β2受体激动剂的疗效:对两个随机对照试验进行的药物基因学分析
