Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation, and limited therapeutic options are available to slow the progressive decline in lung function. Most interventions are only temporarily effective in stabilizing the loss of or modestly improving lung function, with disease progression resuming over time in the majority of patients. Therefore, identification of effective treatments that prevent the onset or halt progression of CLAD is urgently needed. As a key effector cell in its pathophysiology, lymphocytes have been considered a therapeutic target in CLAD. The aim of this review is to evaluate the use and efficacy of lymphocyte depleting and immunomodulating therapies in progressive CLAD beyond usual maintenance immunosuppressive strategies. Modalities used include anti-thymocyte globulin, alemtuzumab, methotrexate, cyclophosphamide, total lymphoid irradiation, and extracorporeal photopheresis, and to explore possible future strategies. When considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin and total lymphoid irradiation appear to offer the best treatment options currently available for progressive CLAD patients.

中文翻译：

---

慢性同种异体肺移植功能障碍的淋巴细胞消耗和调节疗法

慢性肺排斥，也称为慢性肺同种异体移植功能障碍（CLAD），仍然是限制肺移植后长期生存的主要障碍，并且可用于减缓肺功能进行性下降的治疗选择有限。大多数干预措施只能暂时有效稳定肺功能的丧失或适度改善肺功能，随着时间的推移，大多数患者的疾病进展会恢复。因此，迫切需要找到有效的治疗方法来预防 CLAD 的发生或阻止其进展。作为其病理生理学中的关键效应细胞，淋巴细胞被认为是 CLAD 的治疗靶点。本综述的目的是评估淋巴细胞清除和免疫调节疗法在进行性 CLAD 中的使用和疗效，超越通常的维持性免疫抑制策略。使用的方法包括抗胸腺细胞球蛋白、阿仑单抗、甲氨蝶呤、环磷酰胺、全淋巴照射和体外光采术，并探索未来可能的策略。当考虑疗效和副作用风险时，体外光分离术、抗胸腺细胞球蛋白和全淋巴照射似乎为进展性 CLAD 患者提供了目前可用的最佳治疗选择。