Keenan R J, Iacono A, Dauber J H, Zeevi A, Yousem S A, Ohori N P, Burckart G J, Kawai A, Smaldone G C, Griffith B P
Department of Surgery, University of Pittsburgh, Pa., USA.
J Thorac Cardiovasc Surg. 1997 Feb;113(2):335-40; discussion 340-1. doi: 10.1016/S0022-5223(97)70331-3.
Lung transplant recipients who have persistent acute cellular rejection are at increased risk for the development of chronic rejection, the leading cause of reduced long-term survival. This study evaluated the use of aerosolized cyclosporine as rescue therapy for unremitting acute rejection. Between June 1993 and March 1996, 18 patients with rejection that failed to resolve after therapy with pulse steroids and antilymphocyte globulin were enrolled in the study. Aerosolized cyclosporine A (300 mg) treatment was initiated for 10 consecutive days followed by a maintenance regimen of 3 days per week. Efficacy was assessed by graft histologic and pulmonary function testing. With the use of linear regression, results in these patients were compared with those in 23 control patients, matched for histologic acute rejection, who had continued to receive conventional rescue therapy. Two patients were unable to tolerate the treatments and were withdrawn from the study. Significant improvement in histologic rejection occurred in 14 of the remaining 16 patients after a mean of 37 days of aerosolized cyclosporine therapy. Measures of forced vital capacity and forced expiratory volume in 1 second (change in percent predicted/100 days plus or minus the standard error) increased over time in the treated patients whereas the condition of control patients declined despite repeated attempts at conventional rescue (forced vital capacity, aerosolized cyclosporine group, 4.6 +/- 2.9 vs control group -8.1 +/- 1.9, p = 0.001; forced expiratory volume in 1 second, aerosolized cyclosporine group, 2.1 +/- 4.4 vs control group -9.8 +/- 2.6, p = 0.043). Renal and hepatic toxicity during cyclosporine therapy was not observed. The incidence of acute histologic rejection (> or = A2) decreased from 2.49 +/- 0.68 episodes/100 days before aerosolized cyclosporine therapy to 0.72 +/- 0.3 episodes/100 days (p < 0.05). In summary, aerosolized cyclosporine is a safe and effective therapy for acute rejection that has failed to improve with conventional treatment.
持续发生急性细胞排斥反应的肺移植受者发生慢性排斥反应的风险增加，而慢性排斥反应是导致长期生存率降低的主要原因。本研究评估了雾化环孢素作为难治性急性排斥反应挽救治疗的应用。1993年6月至1996年3月期间，18例在接受脉冲类固醇和抗淋巴细胞球蛋白治疗后排斥反应仍未缓解的患者被纳入研究。开始连续10天雾化环孢素A（300毫克）治疗，随后每周3天维持治疗方案。通过移植组织学和肺功能测试评估疗效。使用线性回归分析，将这些患者的结果与23例组织学急性排斥反应相匹配的对照患者进行比较，这些对照患者继续接受传统的挽救治疗。两名患者无法耐受治疗，退出研究。在雾化环孢素治疗平均37天后，其余16例患者中有14例组织学排斥反应有显著改善。治疗患者的用力肺活量和1秒用力呼气量（预测值百分比变化/100天加减标准误）随时间增加，而对照患者尽管多次尝试传统挽救治疗但病情仍恶化（用力肺活量，雾化环孢素组4.6±2.9 vs对照组-8.1±1.9，p = 0.001；1秒用力呼气量，雾化环孢素组2.1±4.4 vs对照组-9.8±2.6，p = 0.043）。未观察到环孢素治疗期间的肾毒性和肝毒性。急性组织学排斥反应（≥A2）的发生率从雾化环孢素治疗前的2.49±0.68次/100天降至0.72±0.3次/100天（p < 0.05）。总之，雾化环孢素是一种安全有效的治疗方法，可用于传统治疗未能改善的急性排斥反应。
