Should mammalian target of rapamycin inhibitors be stopped in women with lymphangioleiomyomatosis awaiting lung transplantation?

Abstract

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease characterized by proliferation of smooth muscle like cells (LAM cells) that have mutations in the tuberous sclerosis gene (TSC2), leading to the activation of the mammalian target of rapamycin (mTOR). Rapamycin, an inhibitor of the mTOR pathway, has been shown in a landmark clinical trial to halt the decline in lung function, as long as it is used continuously. Women with severe pulmonary LAM still progress to require lung transplantation. The use of inhibitors of the mTOR pathway immediately after transplant has been linked to bronchial anastomotic dehiscence, a potentially fatal complication of lung transplantation. Currently, it is recommended that women with LAM stop taking rapamycin once listed for lung transplant, which could potentially lead to faster lung function decline while awaiting organ transplantation. Here we review the existing evidence and discuss potential recommendations for the management of the inhibitors of the mTOR pathway while awaiting lung transplantation.

Keywords::

• bronchial dehiscence
• everolimus
• lung transplant
• lymphangioleiomyomatosis
• mTOR inhibitors
• sirolimus
• TSC

Financial & competing interests disclosure

Research in the El-Chemaly laboratory is supported by funds from the NIH/NHLBI and the Department of Defense Congressionally Directed Medical Research Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.