Iacono A T, Keenan R J, Duncan S R, Smaldone G C, Dauber J H, Paradis I L, Ohori N P, Grgurich W F, Burckart G J, Zeevi A, Delgado E, O'Riordan T G, Zendarsky M M, Yousem S A, Griffith B P
Department of Medicine, University of Pittsburgh, Pennsylvania, USA.
Am J Respir Crit Care Med. 1996 Apr;153(4 Pt 1):1451-5. doi: 10.1164/ajrccm.153.4.8616581.
This study evaluated aerosolized cyclosporine as rescue therapy for lung transplant recipients with unremitting chronic rejection. Nine patients with histologic active obliterative bronchiolitis and progressively worsening airway obstruction refractory to conventional immune suppression received aerosolized cyclosporine. Improvement in rejection histology was seen in seven of nine patients. We compared the changes in the FVC and FEV1 over time using linear regression analysis in these seven histologic responders and nine historical control patients. During the pretreatment period for both the experimental and control groups, the FVC and FEV1 declined at comparable rates. After aerosolized cyclosporine there was stabilization of pulmonary function, whereas in the controls there was continued decline. Cyclosporine blood levels were less than 50 ng/ml 24 h after an aerosolized dose of 300 mg in five patients receiving oral tacrolimus. Nephrotoxicity, hepatotoxicity, and a greater than expected rate of infection was not observed. This study suggests that aerosolized cyclosporine is safe and may be effective therapy for refractory chronic rejection in lung transplant recipients.
本研究评估了雾化环孢素作为肺移植受者顽固性慢性排斥反应挽救治疗的效果。9例组织学表现为活动性闭塞性细支气管炎且传统免疫抑制治疗难以控制的进行性气道阻塞患者接受了雾化环孢素治疗。9例患者中有7例排斥反应组织学表现得到改善。我们使用线性回归分析比较了这7例组织学反应者和9例历史对照患者的用力肺活量（FVC）和1秒用力呼气容积（FEV1）随时间的变化。在实验组和对照组的预处理期间，FVC和FEV1以相似的速率下降。雾化环孢素治疗后肺功能稳定，而对照组肺功能持续下降。5例接受口服他克莫司的患者在雾化300mg环孢素24小时后，环孢素血药浓度低于50ng/ml。未观察到肾毒性、肝毒性以及高于预期的感染率。本研究提示，雾化环孢素对肺移植受者难治性慢性排斥反应可能是一种安全且有效的治疗方法。
