Abstract：
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.
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.
摘要：
背景：尽管肺移植（LTx）是终末期淋巴管平滑肌瘤病（LAM）患者的最后手段，在日本，高候补死亡率是一个令人担忧的问题。由于严重不良事件的发生率，建议在LTx之前停用雷帕霉素（mTOR）抑制剂的机制靶标。因此,我们假设mTOR抑制剂可能会影响LTx等待名单上LAM患者的死亡率.
方法：我们回顾性比较了LTx候补名单上LAM患者的特征，这些患者接受和未接受mTOR抑制剂。
结果：从数据库中选择了2004年1月至2021年12月在我们中心上市的29例LAM患者，并纳入本研究。17例患者（58.6%）正在接受mTOR抑制剂，西罗莫司（治疗组）。在1277天的中位上市期内，12例（41.4%）患者住院，6名患者（20.7%）在LTx之前死于疾病，15例患者接受LTx。在死者中，4例患者(66.6%)有气胸.治疗组的等待死亡率显著低于非治疗组(p=0.03)。在治疗组停用西罗莫司的6名患者中，4例患者(66.6%)在停用西罗莫司后因呼吸系统并发症住院.在接受LTx的治疗组中没有出现mTOR抑制剂相关的并发症（n=7），包括那些减少西罗莫司剂量的人。
结论：在LTx之前给予mTOR抑制剂可能会降低候补死亡率。由于在LTx之前停用西罗莫司后危及生命的事件，减少剂量，直到LTx是允许的。
方法：我们回顾性比较了LTx候补名单上LAM患者的特征，这些患者接受和未接受mTOR抑制剂。
结果：从数据库中选择了2004年1月至2021年12月在我们中心上市的29例LAM患者，并纳入本研究。17例患者（58.6%）正在接受mTOR抑制剂，西罗莫司（治疗组）。在1277天的中位上市期内，12例（41.4%）患者住院，6名患者（20.7%）在LTx之前死于疾病，15例患者接受LTx。在死者中，4例患者(66.6%)有气胸.治疗组的等待死亡率显著低于非治疗组(p=0.03)。在治疗组停用西罗莫司的6名患者中，4例患者(66.6%)在停用西罗莫司后因呼吸系统并发症住院.在接受LTx的治疗组中没有出现mTOR抑制剂相关的并发症（n=7），包括那些减少西罗莫司剂量的人。
结论：在LTx之前给予mTOR抑制剂可能会降低候补死亡率。由于在LTx之前停用西罗莫司后危及生命的事件，减少剂量，直到LTx是允许的。
