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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 the sirolimus group. Menopausal status and race had differential effects on the adverse event profile of sirolimus. Baseline serum vascular endothelial growth factor (VEGF)-D >600 pg·mL -1 identified subgroups of patients who were more likely to decline on placebo and respond to treatment with sirolimus., Conclusions: In LAM patients, treatment with sirolimus is beneficial regardless of menopausal status, race, bronchodilator responsiveness, baseline FEV 1 or TSC association. Serum VEGF-D and menopausal status can help inform therapeutic decisions., Competing Interests: Conflict of interest: N. Gupta has nothing to disclose. Conflict of interest: H-S. Lee has nothing to disclose. Conflict of interest: L.R. Young reports advisory board work for Boehringer Ingelheim and royalties for authorship from UpToDate, outside the submitted work; and has a patent Serum VEGF-D, no royalties issued. Conflict of interest: C. Strange reports grants for studies of LAM from Novartis, outside the submitted work. Conflict of interest: J. Moss has nothing to disclose. Conflict of interest: L.G. Singer has nothing to disclose. Conflict of interest: K. Nakata has nothing to disclose. Conflict of interest: A.F. Barker has nothing to disclose. Conflict of interest: J.T. Chapman has nothing to disclose. Conflict of interest: M.L. Brantly has nothing to disclose. Conflict of interest: J.M. Stocks has nothing to disclose. Conflict of interest: K.K. Brown reports grants from NHLBI, personal fees from AstraZeneca, Biogen, Galecto, MedImmune, Novartis, ProMetic, Patara, Third Pole, Galapagos, Boehringer Ingelheim, Theravance and Three Lakes Partners, conversation under CDA only from Genoa, other (submitted grant) from Roche/Genentech, outside the submitted work. Conflict of interest: J.P. Lynch has nothing to disclose. Conflict of interest: H.J. Goldberg has nothing to disclose. Conflict of interest: G.P. Downey has nothing to disclose. Conflict of interest: A.M. Taveira-DaSilva has nothing to disclose. Conflict of interest: J.P. Krischer has nothing to disclose. Conflict of interest: K. Setchell has nothing to disclose. Conflict of interest: B.C. Trapnell has nothing to disclose. Conflict of interest: Y. Inoue reports grants from Japanese Ministry of Health, Labor, and Welfare, during the conduct of the study. Conflict of interest: F.X. McCormack has a patent on serum VEGF-D testing. All royalties are waived to the parent institution, the University of Cincinnati., (The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2019.)