A randomized trial of inhaled cyclosporine in lung-transplant recipients
A randomized trial of inhaled cyclosporine in lung-transplant recipients
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DOI：
10.1056/nejmoa043204
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发表时间：
2006-01-12
影响因子：
158.5
通讯作者：
Griffith, BP
中科院分区：
文献类型：
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作者：
Iacono, AT;Johnson, BA;Griffith, BP
背景：传统的免疫抑制剂方案通常不能预防肺移植后的慢性排斥反应。局部递送环孢素除了常规的全身免疫抑制剂可能有助于防止急性和慢性排斥events.METHODS：我们进行了一项单中心，随机，双盲，安慰剂对照试验吸入环孢素移植后6周内开始，并给予除了全身免疫抑制剂。共有58名患者被随机分配到吸入300毫克的气雾剂环孢素（28名患者）或气雾剂安慰剂（30名患者），每周三天，在移植后的头两年。主要终点是组织学急性排斥反应的发生率。结果：环孢素组和安慰剂组2级或更高的急性排斥反应的发生率相似：每例患者每年分别为0.44次（95%置信区间，0.31 - 0.62）和0.46次（95%置信区间，0.33 - 0.64）（Poisson回归P = 0.87）。接受雾化环孢素治疗的患者生存率提高，接受环孢素治疗的患者中有3例死亡，接受安慰剂治疗的患者中有14例死亡（死亡的相对风险为0.20; 95%置信区间为0.06至0.70; P = 0.01）。根据肺量测定分析，环孢菌素也可以改善慢性无排斥生存率（环孢素组10例，安慰剂组20例;慢性排斥反应的相对风险为0.38; 95%可信区间为0.18 - 0.82; P = 0.01）和组织学分析（分别为6对19起事件;相对风险为0.27; 95%置信区间为0.11至0.67; P = 0.005）。肾毒性作用和机会性感染的风险是相似的患者在环孢素组和安慰剂group.CONCLUSIONS：吸入环孢素并没有提高急性排斥反应的发生率，但它确实提高了生存期和延长慢性排斥反应的生存期。
BACKGROUND:Conventional regimens of immunosuppressive drugs often do not prevent chronic rejection after lung transplantation. Topical delivery of cyclosporine in addition to conventional systemic immunosuppression might help prevent acute and chronic rejection events.METHODS:We conducted a single-center, randomized, double-blind, placebo-controlled trial of inhaled cyclosporine initiated within six weeks after transplantation and given in addition to systemic immunosuppression. A total of 58 patients were randomly assigned to inhale either 300 mg of aerosol cyclosporine (28 patients) or aerosol placebo (30 patients) three days a week for the first two years after transplantation. The primary end point was the rate of histologic acute rejection.RESULTS:The rates of acute rejection of grade 2 or higher were similar in the cyclosporine and placebo groups: 0.44 episode (95 percent confidence interval, 0.31 to 0.62) vs. 0.46 episode (95 percent confidence interval, 0.33 to 0.64) per patient per year, respectively (P=0.87 by Poisson regression). Survival was improved with aerosolized cyclosporine, with 3 deaths among patients receiving cyclosporine and 14 deaths among patients receiving placebo (relative risk of death, 0.20; 95 percent confidence interval, 0.06 to 0.70; P=0.01). Chronic rejection-free survival also improved with cyclosporine, as determined by spirometric analysis (10 events in the cyclosporine group and 20 events in the placebo group; relative risk of chronic rejection, 0.38; 95 percent confidence interval, 0.18 to 0.82; P=0.01) and histologic analysis (6 vs. 19 events, respectively; relative risk, 0.27; 95 percent confidence interval, 0.11 to 0.67; P=0.005). The risks of nephrotoxic effects and opportunistic infection were similar for patients in the cyclosporine group and the placebo group.CONCLUSIONS:Inhaled cyclosporine did not improve the rate of acute rejection, but it did improve survival and extend periods of chronic rejection-free survival.