肺移植受者吸入环孢素的随机试验。

A randomized trial of inhaled cyclosporine in lung-transplant recipients.

作者信息

Iacono Aldo T, Johnson Bruce A, Grgurich Wayne F, Youssef J Georges, Corcoran Timothy E, Seiler Deidre A, Dauber James H, Smaldone Gerald C, Zeevi Adriana, Yousem Samuel A, Fung John J, Burckart Gilbert J, McCurry Kenneth R, Griffith Bartley P

机构信息

Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, USA.

出版信息

N Engl J Med. 2006 Jan 12;354(2):141-50. doi: 10.1056/NEJMoa043204.

DOI:10.1056/NEJMoa043204

PMID:16407509

Abstract

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. (ClinicalTrials.gov number, NCT00268515.).

摘要

背景

免疫抑制药物的传统治疗方案往往无法预防肺移植后的慢性排斥反应。在传统全身免疫抑制的基础上局部应用环孢素可能有助于预防急慢性排斥反应事件。

方法

我们进行了一项单中心、随机、双盲、安慰剂对照试验，对移植后六周内开始吸入环孢素并联合全身免疫抑制治疗进行研究。共有58例患者被随机分配，在移植后的前两年每周三天吸入300毫克环孢素气雾剂（28例患者）或气雾剂安慰剂（30例患者）。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级或更高等级的急性排斥反应发生率相似：分别为每位患者每年0.44次发作（95%置信区间，0.31至0.62）和0.46次发作（95%置信区间，0.33至0.64）（泊松回归分析P = 0.87）。吸入环孢素可改善生存率，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（死亡相对风险，0.20；95%置信区间，0.06至0.70；P = 0.01）。通过肺功能分析（环孢素组10例事件，安慰剂组20例事件；慢性排斥反应相对风险，0.38；95%置信区间，0.18至0.82；P = 0.01）和组织学分析（分别为6例和19例事件；相对风险，0.27；95%置信区间，0.11至0.67；P = 0.005）确定，环孢素也改善了无慢性排斥反应的生存率。环孢素组和安慰剂组患者发生肾毒性作用和机会性感染风险相似。