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他汀类药物治疗和暴露对中国肺移植受者慢性移植物功能障碍风险的影响。

Impact of statin treatment and exposure on the risk of chronic allograft dysfunction in Chinese lung transplant recipients.

机构信息

Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, China.

Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, China; Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100029, China.

出版信息

Pulm Pharmacol Ther. 2023 Oct;82:102243. doi: 10.1016/j.pupt.2023.102243. Epub 2023 Jul 16.

Abstract

PURPOSE

Chronic lung allograft dysfunction (CLAD) was a common complication following lung transplantation that contributed to long-term morbidity and mortality. Statin therapy had been suggested to attenuate recipient inflammation and immune response, potentially reducing the risk and severity of CLAD. This study aimed to evaluate the impact of statin use and in vivo exposure on the incidence of CLAD in lung transplant recipients (LTRs), as well as their effects on immune cells and inflammatory factors.

METHODS

A retrospective cohort study was conducted on patients who underwent lung transplantation between January 2017 and December 2020. The incidence of CLAD, as per the 2019 ISHLT criteria, was assessed as the clinical outcome. The plasma concentrations of statin were measured using a validated UPLC-MS/MS method, while inflammation marker levels were determined using ELISA kits.

RESULTS

The statin group exhibited a significantly lower rate of CLAD (P = 0.002). Patients receiving statin therapy showed lower CD4 T-cell counts, total T-lymphocyte counts, and IL-6 levels (P = 0.017, P = 0.048, and P = 0.038, respectively). Among the CLAD groups, the atorvastatin level (2.51 ± 1.31 ng/ml) was significantly lower than that in the non-CLAD group (OR = 1.438, 95%CI (1.007-2.053), P = 0.046).

CONCLUSION

Statin therapy significantly reduced the incidence of CLAD, as well as immune cell counts and inflammatory cytokine levels in LTRs. Although the statin exposure was significantly lower in CLAD patients, it was not associated with the incidence of CLAD.

摘要

目的

慢性肺移植物功能障碍(CLAD)是肺移植后的常见并发症,导致长期发病率和死亡率增加。他汀类药物治疗被认为可以减轻受者的炎症和免疫反应,从而降低 CLAD 的风险和严重程度。本研究旨在评估他汀类药物的使用和体内暴露对肺移植受者(LTR)CLAD 发生率的影响,以及它们对免疫细胞和炎症因子的影响。

方法

对 2017 年 1 月至 2020 年 12 月期间接受肺移植的患者进行回顾性队列研究。采用 2019 年 ISHLT 标准评估 CLAD 的发生率作为临床结局。采用经验证的 UPLC-MS/MS 方法测定他汀类药物的血浆浓度,采用 ELISA 试剂盒测定炎症标志物水平。

结果

他汀组 CLAD 发生率明显较低(P=0.002)。接受他汀类药物治疗的患者 CD4 T 细胞计数、总淋巴细胞计数和 IL-6 水平均较低(P=0.017、P=0.048 和 P=0.038)。在 CLAD 组中,阿托伐他汀水平(2.51±1.31ng/ml)明显低于非 CLAD 组(OR=1.438,95%CI(1.007-2.053),P=0.046)。

结论

他汀类药物治疗可显著降低 LTR 中 CLAD 的发生率,以及免疫细胞计数和炎症细胞因子水平。尽管 CLAD 患者的他汀类药物暴露明显较低,但与 CLAD 的发生率无关。

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