Analysis of the MILES cohort reveals determinants of disease progression and treatment response in lymphangioleiomyomatosis

作者：Nishant Gupta, Hye‐Seung Lee, Lisa R. Young, Charlie Strange, Joel Moss, L.G. Singer, Koh Nakata, Alan F. Barker, Jeffrey T. Chapman, Mark Brantly, James Stocks, Kevin K. Brown, Joseph P. Lynch, Hilary J. Goldberg, Gregory P. Downey, Angelo M. Taveira‐DaSilva, Jeffrey P. Krischer, Kenneth D.R. Setchell, Bruce C. Trapnell, Yoshikazu Inoue, Francis X. McCormack · 发表于：European Respiratory Journal · 年份：2019 · DOI：10.1183/13993003.02066-2018 · 被引用次数：66 · 研究领域：Tuberous Sclerosis Complex Research、PI3K/AKT/mTOR signaling in cancer、Vascular Tumors and Angiosarcomas

Introduction The Multicenter International Lymphangioleiomyomatosis (LAM) Efficacy of Sirolimus (MILES) trial revealed that sirolimus stabilised lung function in patients with moderately severe LAM. The purpose of this study was to further examine the MILES cohort for the effects of racial, demographic, clinical and physiological patient characteristics on disease progression and treatment response in LAM. Methods MILES subjects were stratified on the basis of menopausal status (pre-menopausal/post-menopausal), race (Asian/Caucasian), bronchodilator responsiveness (present/absent), initial forced expiratory volume in 1 s (FEV 1 ; 51–70% versus ≤50% predicted) and tuberous sclerosis complex (TSC) association (yes/no). A linear mixed effects model was used to compare slope differences, and nonparametric tests were used to compare medians and proportions between treatment groups in each stratum. Results In the MILES placebo group, pre-menopausal patients declined 5-fold faster than post-menopausal patients (mean± se FEV 1 slope −17±3 versus −3±3 mL·month −1 ; p=0.003). Upon treatment with sirolimus, both the pre-menopausal (−17±3 versus −1±2 mL·month −1 ; p<0.0001) and post-menopausal patients (−3±3 versus 6±3 mL·month −1 ; p=0.04) exhibited a beneficial response in mean± se FEV 1 slope compared with the placebo group. Race, LAM subtype, bronchodilator responsiveness or baseline FEV 1 did not impact the rate of disease progression in the placebo group or treatment response in...