{"title":"mTOR抑制剂对肺移植候选名单中淋巴管瘤病患者死亡率和安全性的影响:回顾性队列研究","authors":"Teiko Sakurai , Takashi Kanou , Soichiro Funaki , Eriko Fukui , Toru Kimura , Naoko Ose , Yoshikazu Inoue , Yasushi Shintani","doi":"10.1016/j.resinv.2024.05.008","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Although lung transplantation (LTx) is the last resort for patients with end-stage lymphangioleiomyomatosis (LAM), the high waitlist mortality is a source of concern in Japan. Discontinuation of mechanistic target of rapamycin (mTOR) inhibitors prior to LTx is recommended due to the incidence of severe adverse events. Therefore, we hypothesized that mTOR inhibitors may affect the mortality of patients with LAM on the LTx waitlist.</p></div><div><h3>Methods</h3><p>We retrospectively compared the characteristics of consecutive patients with LAM on the LTx waitlist who were and were not receiving mTOR inhibitors.</p></div><div><h3>Results</h3><p>Twenty-nine consecutive patients with LAM who listed our center between January 2004 and December 2021 were selected from the database and enrolled in the present study. Seventeen patients (58.6%) were receiving a mTOR inhibitor, sirolimus (treatment group). During a median listing period of 1277 days, 12 patients (41.4%) were hospitalized, six patients (20.7%) died from disease before LTx, and 15 patients underwent LTx. Among the deceased patients, four patients (66.6%) had pneumothoraces. The waitlist mortality in the treatment group was significantly lower than that in the non-treatment group (p = 0.03). Among the six patients who discontinued sirolimus in the treatment group, four patients (66.6%) were hospitalized with respiratory complications after the discontinuation of sirolimus. No mTOR inhibitor-related complications arose in the treatment group undergoing LTx (n = 7), including those on a reduced sirolimus dose.</p></div><div><h3>Conclusions</h3><p>Administration of an mTOR inhibitor until LTx may decrease waitlist mortality. Due to life-threatening events after discontinuing sirolimus pre-LTx, a reduced dose until LTx is permissible.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of mTOR inhibitors on the mortality and safety of patients with lymphangioleiomyomatosis on the lung transplantation waitlist: A retrospective cohort study\",\"authors\":\"Teiko Sakurai , Takashi Kanou , Soichiro Funaki , Eriko Fukui , Toru Kimura , Naoko Ose , Yoshikazu Inoue , Yasushi Shintani\",\"doi\":\"10.1016/j.resinv.2024.05.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Although lung transplantation (LTx) is the last resort for patients with end-stage lymphangioleiomyomatosis (LAM), the high waitlist mortality is a source of concern in Japan. Discontinuation of mechanistic target of rapamycin (mTOR) inhibitors prior to LTx is recommended due to the incidence of severe adverse events. Therefore, we hypothesized that mTOR inhibitors may affect the mortality of patients with LAM on the LTx waitlist.</p></div><div><h3>Methods</h3><p>We retrospectively compared the characteristics of consecutive patients with LAM on the LTx waitlist who were and were not receiving mTOR inhibitors.</p></div><div><h3>Results</h3><p>Twenty-nine consecutive patients with LAM who listed our center between January 2004 and December 2021 were selected from the database and enrolled in the present study. Seventeen patients (58.6%) were receiving a mTOR inhibitor, sirolimus (treatment group). During a median listing period of 1277 days, 12 patients (41.4%) were hospitalized, six patients (20.7%) died from disease before LTx, and 15 patients underwent LTx. Among the deceased patients, four patients (66.6%) had pneumothoraces. The waitlist mortality in the treatment group was significantly lower than that in the non-treatment group (p = 0.03). Among the six patients who discontinued sirolimus in the treatment group, four patients (66.6%) were hospitalized with respiratory complications after the discontinuation of sirolimus. No mTOR inhibitor-related complications arose in the treatment group undergoing LTx (n = 7), including those on a reduced sirolimus dose.</p></div><div><h3>Conclusions</h3><p>Administration of an mTOR inhibitor until LTx may decrease waitlist mortality. Due to life-threatening events after discontinuing sirolimus pre-LTx, a reduced dose until LTx is permissible.</p></div>\",\"PeriodicalId\":20934,\"journal\":{\"name\":\"Respiratory investigation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-05-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Respiratory investigation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2212534524000832\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory investigation","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212534524000832","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Effect of mTOR inhibitors on the mortality and safety of patients with lymphangioleiomyomatosis on the lung transplantation waitlist: A retrospective cohort study
Background
Although lung transplantation (LTx) is the last resort for patients with end-stage lymphangioleiomyomatosis (LAM), the high waitlist mortality is a source of concern in Japan. Discontinuation of mechanistic target of rapamycin (mTOR) inhibitors prior to LTx is recommended due to the incidence of severe adverse events. Therefore, we hypothesized that mTOR inhibitors may affect the mortality of patients with LAM on the LTx waitlist.
Methods
We retrospectively compared the characteristics of consecutive patients with LAM on the LTx waitlist who were and were not receiving mTOR inhibitors.
Results
Twenty-nine consecutive patients with LAM who listed our center between January 2004 and December 2021 were selected from the database and enrolled in the present study. Seventeen patients (58.6%) were receiving a mTOR inhibitor, sirolimus (treatment group). During a median listing period of 1277 days, 12 patients (41.4%) were hospitalized, six patients (20.7%) died from disease before LTx, and 15 patients underwent LTx. Among the deceased patients, four patients (66.6%) had pneumothoraces. The waitlist mortality in the treatment group was significantly lower than that in the non-treatment group (p = 0.03). Among the six patients who discontinued sirolimus in the treatment group, four patients (66.6%) were hospitalized with respiratory complications after the discontinuation of sirolimus. No mTOR inhibitor-related complications arose in the treatment group undergoing LTx (n = 7), including those on a reduced sirolimus dose.
Conclusions
Administration of an mTOR inhibitor until LTx may decrease waitlist mortality. Due to life-threatening events after discontinuing sirolimus pre-LTx, a reduced dose until LTx is permissible.