Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis

Background Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide. Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied. Objectives To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis. Search strategy To identify randomised controlled trials on this topic, we searched the Cochrane Injuries Group's Specialised Register (searched 15 Sept 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid SP) (1950 September Week 1 2009), EMBASE (Ovid SP) (1980 to 2009 Week 37), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to Sept 2009), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (1990 to Sept 2009), Chinese bio-medical literature & retrieval system (CBM) (1978 to Sept 2009), Chinese medical current contents (CMCC) (1995 to Sept 2009), and Chinese medical academic conference (CMAC) (1994-Sept 2009). The searches were completed in September 2009. Selection criteria Randomised controlled trials (RCTs) were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone, or any other therapy in addition to standard care. Data collection and analysis The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effects model. Main results This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72 (95% CI 0.59 to 0.89)). Authors' conclusions Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.