他汀类药物的使用可能与肺移植受者侵袭性曲霉菌病的风险降低有关。

Statin Use May Be Associated With a Lower Risk of Invasive Aspergillosis in Lung Transplant Recipients.

机构信息

Transplant Infectious Diseases, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.

Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

出版信息

Clin Infect Dis. 2023 Feb 8;76(3):e1379-e1384. doi: 10.1093/cid/ciac551.

DOI:10.1093/cid/ciac551

PMID:35900334

Abstract

BACKGROUND

Statins are competitive inhibitors of 3-hydroxy-3methylglutaryl coenzyme A reductase (HMG-CoA reductase) that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented.

METHODS

This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of 2 weeks duration prior to IA), adjusting for other known IA risk factors.

RESULTS

We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). In total, 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (interquartile range [IQR]: 305 to 346). And 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (P = .002, SHR 0.30, 95% confidence interval [CI] 95% .14-.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs 123 (27%) in the statin group (P = .038).

CONCLUSIONS

The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.

摘要

背景

他汀类药物是 3-羟基-3-甲基戊二酰辅酶 A 还原酶（HMG-CoA 还原酶）的竞争性抑制剂，催化 HMG-CoA 转化为甲羟戊酸，这是人类合成胆固醇和真菌合成麦角固醇的过程。他汀类药物的使用对肺移植受者（LTR）侵袭性曲霉菌病（IA）发展风险的影响尚未得到充分证实。

方法

本回顾性研究纳入了 2010 年至 2017 年接受移植后随访 1 年的 LTR。根据 ISHLT 标准诊断确诊或疑似 IA。我们使用多变量 Cox 比例风险模型，对 IA 与他汀类药物使用（IA 前至少 2 周）之间的相关性进行了分析，并调整了其他已知的 IA 危险因素。

结果

我们共纳入了 785 例 LTR，其中 44%为女性，平均年龄为 53 岁，最常见的基础疾病是肺纤维化（23.8%）。共有 451 例 LTR（57%）在移植后接受了他汀类药物治疗，阿托伐他汀是最常用的他汀类药物（68%）。移植后他汀类药物的平均使用时间为 347 天（IQR：305-346）。55 例（7%）LTR 在移植后 1 年内发生了 IA。在这 55 例 LTR 中，有 9 例（16.3%）在发生 IA 前使用了他汀类药物。多变量分析显示，他汀类药物的使用与 IA 的风险降低独立相关（P=.002，SHR 0.30，95%CI 95%.14-.64）。他汀类药物的使用还与移植后曲霉菌定植的发生率降低相关，无他汀类药物组为 114 例（34%），他汀类药物组为 123 例（27%）（P=.038）。