Effect of mTOR inhibitors on the mortality and safety of patients with lymphangioleiomyomatosis on the lung transplantation waitlist: A retrospective cohort study

Teiko Sakurai; Takashi Kanou; Soichiro Funaki; Eriko Fukui; Toru Kimura; Naoko Ose; Yoshikazu Inoue; Yasushi Shintani

doi:10.1016/j.resinv.2024.05.008

Effect of mTOR inhibitors on the mortality and safety of patients with lymphangioleiomyomatosis on the lung transplantation waitlist: A retrospective cohort study

Respir Investig. 2024 May 17;62(4):657-662. doi: 10.1016/j.resinv.2024.05.008. Online ahead of print.

Authors

Teiko Sakurai¹, Takashi Kanou², Soichiro Funaki¹, Eriko Fukui¹, Toru Kimura¹, Naoko Ose¹, Yoshikazu Inoue³, Yasushi Shintani¹

Affiliations

¹ Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Yamadagaoka 2-2(L5), Suita, Osaka, 565-0871, Japan.
² Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Yamadagaoka 2-2(L5), Suita, Osaka, 565-0871, Japan. Electronic address: kanoutakashi0999@yahoo.co.jp.
³ Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai, Osaka, 591-8555, Japan; Department of Internal Medicine, Osaka Anti-tuberculosis Association Osaka Fukujuji Hospital, 3-10 Uchiagetakatsuka, Neyagawa, Osaka, 572-0859, Japan.

PMID: 38761480
DOI: 10.1016/j.resinv.2024.05.008

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.

Keywords: Lung transplantation; Lymphangioleiomyomatosis; Pneumothorax; Sirolimus.