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TNF-α 抑制剂在哮喘和 COPD 中的应用:我们不能因噎废食。

TNF-alpha inhibitors in asthma and COPD: we must not throw the baby out with the bath water.

机构信息

Second University of Naples, Department of Experimental Medicine, Unit of Pharmacology and Toxicology, Naples, Italy.

出版信息

Pulm Pharmacol Ther. 2010 Apr;23(2):121-8. doi: 10.1016/j.pupt.2009.10.007. Epub 2009 Oct 22.

Abstract

Tumor necrosis factor (TNF)-alpha, a pleiotropic cytokine that exerts a variety of effects, such as growth promotion, growth inhibition, angiogenesis, cytotoxicity, inflammation, and immunomodulation, has been implicated in several inflammatory conditions. It plays a significant role in many inflammatory diseases of lungs. Given that there is significant literature supporting the pathobiologic role of TNF-alpha in asthma, mainly in severe refractory asthma, and COPD, TNF-alpha inhibitors (infliximab, golimumab and etanercept) are now regarded as the potential new medications in asthma and COPD management. The studies reported in literature indicate that TNF-alpha inhibitors are effective in a relatively small subgroup of patients with severe asthma, possibly defined by an increased TNF axis, but they seem to be ineffective in COPD, although an observational study demonstrated that TNF-alpha inhibitors were associated with a reduction in the rate of COPD hospitalisation among patients with COPD receiving these agents to treat their rheumatoid arthritis. These findings require a smart approach because there is still good reason to target TNF-alpha, perhaps in a more carefully selected patient group. TNF-alpha treatment should, therefore, not be thrown out, or abandoned. Indeed, since severe asthma and COPD are heterogeneous diseases that have characteristics that occur with different phenotypes that remained poorly characterized and little known about the underlying pathobiology contributing to them, it is likely that definition of these phenotypes and choice of the right outcome measure will allow us to understand which kind of patients can benefit from TNF-alpha inhibitors.

摘要

肿瘤坏死因子 (TNF)-α 是一种具有多种作用的多效细胞因子,如促进生长、抑制生长、血管生成、细胞毒性、炎症和免疫调节等,与多种炎症状态有关。它在肺部的许多炎症性疾病中发挥着重要作用。鉴于有大量文献支持 TNF-α 在哮喘中的病理生物学作用,主要在严重难治性哮喘和 COPD 中,TNF-α 抑制剂(英夫利昔单抗、戈利木单抗和依那西普)现在被认为是哮喘和 COPD 管理的潜在新药。文献中的研究表明,TNF-α 抑制剂在一小部分严重哮喘患者中有效,这些患者可能具有增加的 TNF 轴,但它们在 COPD 中似乎无效,尽管一项观察性研究表明,在接受这些药物治疗类风湿关节炎的 COPD 患者中,TNF-α 抑制剂与 COPD 住院率降低相关。这些发现需要一种明智的方法,因为仍然有充分的理由靶向 TNF-α,也许在更仔细选择的患者群体中。因此,TNF-α 治疗不应被抛弃或放弃。事实上,由于严重哮喘和 COPD 是异质性疾病,具有不同表型的特征,这些表型的特征仍未得到充分描述,并且对导致它们的潜在病理生物学知之甚少,因此定义这些表型和选择正确的结局测量方法可能使我们能够了解哪些类型的患者可以从 TNF-α 抑制剂中获益。

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