Prospects for treatment of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for better prediction of outcome: a systematic review.
Prospects for treatment of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for better prediction of outcome: a systematic review.
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通过免疫抑制药物治疗帕拉奎特诱导的肺纤维化的前景，并且需要更好地预测结果：系统评价。
DOI：
10.1093/qjmed/hcg137
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发表时间：
2003-11
期刊：
影响因子：
--
通讯作者：
Buckley NA
中科院分区：
文献类型：
--
作者：
Eddleston M;Wilks MF;Buckley NA
急性百草枯自身中毒是亚洲、太平洋和加勒比部分地区的一个严重临床问题。摄入大量浓缩百草枯制剂会导致多器官衰竭和心源性休克而迅速死亡。摄入较小的体积通常会导致延迟性肺纤维化，这在大多数患者中是致命的。在过去的30年里，抗中性粒细胞（通常称为“免疫抑制剂”）治疗已被各种团体推荐用于预防肺纤维化，但对其疗效尚无共识。至i.审查在百草枯中毒中使用免疫抑制剂的证据;二.确定经过验证的预后系统，允许使用历史对照研究的数据，并在未来确定可能从免疫抑制中获益的患者。在系统性综述中，我们检索了PubMed、Embase和科克伦数据库（最后一次检索时间为2002年4月11日）中的“百草枯”以及“中毒”或“过量”。我们交叉检查了参考文献，联系了专家，并使用“百草枯”，“环磷酰胺”，“甲泼尼龙”和“预后”[<www.google.com>和<www.yahoo.com>]（最后一次检查是2002年11月23日）搜索互联网。我们发现了10项关于百草枯中毒免疫抑制的临床研究。一项是随机对照试验（RCT），但其方法和分析提出了问题，作者承认其结论是初步的。其他7项研究使用历史对照，而不是平行组，而两个报告了一个和四个病例。对照组和治疗组的死亡率在研究之间存在显著差异。七项非随机对照试验对照研究中有三项测量了血浆百草枯;使用最广泛使用的预后指标（使用Proudfoot或哈特曲线评价血浆百草枯浓度）进行的再分析不支持这些研究中免疫抑制增加存活率的提议。我们对16项百草枯中毒预后系统研究的分析表明，没有一项研究在大型患者队列中得到独立验证，因此对其可靠性和准确性提出了质疑。随机对照试验的作者进行了有价值的困难的研究; 2然而，目前，他们的结果必须被看作是假设形成而不是结论性的。其他7项研究使用了历史对照，这与利益膨胀和证据质量差有关。这些试验的主要限制之一是缺乏一个普遍适用的，有效的预后系统。我们认为，由于缺乏任何经证实有效的百草枯中毒治疗方法，因此必须确定抗中性粒细胞疗法是否有效。在缺乏适当验证的预后标志物以允许使用非随机研究的情况下，需要使用死亡作为主要结局的大型RCT。这项随机对照试验应用于前瞻性测试和验证可用的预后方法，以便未来的患者可以选择这种治疗和其他治疗入院。
acute paraquat self-poisoning is a significant clinical problem in parts of Asia, the Pacific and the Caribbean. Ingestion of large amounts of concentrated paraquat formulations results in rapid death from multi-organ failure and cardiogenic shock. Ingestion of smaller volumes often causes a delayed lung fibrosis that is fatal in most patients. Anti-neutrophil (often referred to as ‘immunosuppressive’) treatment has been recommended by various groups over the last 30 years to prevent lung fibrosis but there is no consensus on efficacy. to i. review the evidence for the use of immunosuppression in paraquat poisoning and ii. identify validated prognostic systems that would allow the use of data from historical control studies and the future identification of patients who might benefit from immunosuppression. systematic review we searched PubMed, Embase and Cochrane databases (last search 04/11/02) for ‘paraquat’ together with ‘poisoning’ or ‘overdose’. We cross checked references and contacted experts, and searched the internet using ‘paraquat’, ‘cyclophosphamide’, ‘methylprednisolone’ and ‘prognosis’ [<www.google.com> and <www.yahoo.com>] (last checked 23/11/02). we found ten clinical studies of immunosuppression in paraquat poisoning. One was a randomised controlled trial (RCT) but its methodology and analysis raise questions and its conclusions were acknowledged by the authors to be preliminary. Seven other studies used historical, not parallel group, controls, while two reported one and four cases each. Mortality in control and treatment groups varied markedly between studies. Three of the seven non-RCT controlled studies measured plasma paraquat; reanalysis using the most widely used prognostic indicator (evaluation of plasma paraquat concentration using Proudfoot's or Hart's curves) did not support the proposal that immunosuppression increased survival in these studies. Our analysis of sixteen studies of prognostic systems for paraquat poisoning showed that none have been independently validated in a large cohort of patients, thus raising questions regarding their reliability and accuracy. the authors of the RCT have performed valuable and difficult research; at present, however, their results must be seen as hypothesis-forming rather than conclusive. Seven of the other studies used historical controls, which are associated with inflation of benefit and poor quality of evidence. One of the main constraints in these trials is the lack of a universally applicable, validated prognostic system. we believe that the lack of any therapy of proven efficacy for paraquat poisoning makes it imperative to determine whether anti-neutrophil therapies work. In the absence of a properly validated prognostic marker to allow the use of nonrandomised studies, a large RCT using death as the primary outcome is required. This RCT should be used to prospectively test and validate the available prognostic methods so that future patients can be selected for this and other therapies on admission to hospital.
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