Gemert Johanna P van, Fleurke Ger Jan, Akkerman Onno W, Gan C Tji, Steenhuis Willie N, Kerstjens Huib A M, Verschuuren Erik A M, Postma Douwe F
Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Transpl Infect Dis. 2025 Jul-Aug;27(4):e70020. doi: 10.1111/tid.70020. Epub 2025 Mar 18.
Invasive pulmonary aspergillosis (IA) poses significant challenges for lung transplant (LTx) patients, with unclear risk factors and preventive strategies. The effectiveness of nebulized amphotericin B (AmB) or statins for IA prevention and the effect of IA on chronic lung allograft dysfunction (CLAD) and mortality remain questionable.
Data were collected from all LTx patients transplanted between December 1, 2013 and January 1, 2022 at the University Medical Center Groningen. IA, was defined according to published criteria. Prespecified risk factors were compared between patients with and without IA post-LTx and were entered in a logistic regression model. Two additional logistic regression models were built with factors that might be associated with statin or AmB prophylaxis and IA. A matched case-control study was conducted for the association between statins and IA, with matching based on follow-up time.
Aspergillus was cultured in 110 /274 (40%) patients post-LTx and 89/110 (81%) were classified as probable IA. MMF use, airway stenosis, Aspergillus cultured pre-LTx, CLAD, and acute rejection (AR), were significantly associated with IA. Statin use was associated with a lower incidence of IA, while AmB prophylaxis showed no significant effect. A significant statin effect could not be confirmed by the case control analysis. There was no significant difference in all-cause mortality between patients with and without IA (34% vs. 29%).
The high incidence of IA post-LTx necessitates more effective strategies. Key targets for intervention include prior positive cultures, airway stenosis, AR, and the use of MMF. The role of statins remains unclear and requires further research.
侵袭性肺曲霉病(IA)给肺移植(LTx)患者带来了重大挑战,其危险因素和预防策略尚不明确。雾化两性霉素B(AmB)或他汀类药物预防IA的有效性以及IA对慢性肺移植功能障碍(CLAD)和死亡率的影响仍存在疑问。
收集了2013年12月1日至2022年1月1日在格罗宁根大学医学中心接受移植的所有LTx患者的数据。IA根据已发表的标准进行定义。对LTx后发生IA和未发生IA的患者的预设危险因素进行比较,并纳入逻辑回归模型。另外建立了两个逻辑回归模型,纳入可能与他汀类药物或AmB预防及IA相关的因素。针对他汀类药物与IA之间的关联进行了匹配病例对照研究,根据随访时间进行匹配。
110/274(40%)例LTx后患者培养出曲霉菌,其中89/110(81%)被分类为可能的IA。使用霉酚酸酯(MMF)、气道狭窄、LTx前培养出曲霉菌、CLAD和急性排斥反应(AR)与IA显著相关。使用他汀类药物与IA发病率较低相关,而AmB预防未显示出显著效果。病例对照分析未证实他汀类药物有显著效果。发生IA和未发生IA的患者全因死亡率无显著差异(34%对29%)。
LTx后IA的高发病率需要更有效的策略。干预的关键目标包括先前的阳性培养、气道狭窄、AR和MMF的使用。他汀类药物的作用仍不明确,需要进一步研究。