Lymphangioleiomyomatosis and mTOR inhibitors in real world—a narrative review

Abstract

Background and Objective Lymphangioleiomyomatosis (LAM) is a rare disease developing mostly on lung and leading to various pulmonary and extra-pulmonary manifestations. Management of this intractable illness has been mostly symptomatic and supplementary until the advent and application of a novel drug, i.e., the mechanistic target of rapamycin (mTOR) inhibitor, and successful disease control using mTOR inhibitors is improving LAM patients. Although mTOR inhibitors are showing remarkable results there are still many rooms for further progress, and partly solved issues on problems seen in LAM still remain. We searched multiple reports and investigational studies regarding LAM, especially the therapeutic achievement won by mTOR inhibitors. This article summarized several characteristics of LAM including pathogenesis, clinical manifestation, laboratory findings, and management. We also attempted to review the latest knowledge and efficacy of mTOR inhibitors and some new drugs. Methods Online searching of literature was performed. The National Center for Biotechnology Information (NCBI), PubMed, Cochrane Library, Google Scholar, and EMBASE were searched. Key Content and Findings LAM is a genetic disease with a high predilection toward female subjects. Not only lung but also other organs are involved, hence extrapulmonary symptoms and signs are also noted. Representative objective finding is a progressive deterioration of lung function, sometimes leading to respiratory failure. Supportive and symptomatic care has been the mainstay of therapy with suboptimal result, until a novel drug, the mTOR inhibitor, was developed. Successful deterrence of disease progression was achieved on management with mTOR inhibitors. Several unsolved problems using mTOR inhibitors are a pending issue, such as duration of treatment. Conclusions LAM has been a rare, stubborn disease to ameliorate in health due to its complex pathogenesis and accompanied by other manifestations. Adopting various tools for relief has been usually suboptimal, but mTOR inhibitors proved to achieve significant improvement in various aspects. Further investigation is needed including refinement of currently available therapeutic applications, development of novel remedies, and so on.