Effects Of Sirolimus On Survival And Lipid Metabolism In Patients With Lymphangioleiomyomatosis (LAM)

Background:Sirolimus as an immunosuppression agent is mainly used in patients after renal transplantation. In recent reports, sirolimus has been confirmed as an effective treatment for lymphangioleimyomatosis (LAM). Sirolimus improves lung function, reduces size of angiomyolipoma (AML), and decreases chylous effusions, et al. Several studies suggested that sirolimus regulates lipid metabolism in patients after renal transplant, limited data were available on the effects of sirolimus on the lipid metabolism in patients with LAM. In this survey, we mainly discuss the effects of sirolimus on survival and lipid metabolismin patients with LAM.Chapter 1 Survival in patients with Lymphangioleiomyomatosis (LAM) treated with sirolimusObjective:To investigate the survival after sirolimus therapy in patients with LAM and prognostic factors.Methods:Patients were from LAM Clinic in Peking Union Medical College Hospital. Age at diagnosis, lung function, serum vascular endothelial growth factors D (VEGF-D) were analyzed retrospectively. Patients were followed-up via outpatient or inpatient departments, telephone, or mobile-based APP. Kaplan-Meier survival curves were used to analyze the survival. Log-rank tests were used to analyze the factors associated with survival for any significant differences. Cox proportional hazards regression models were used to analyze the multi-factors related to prognosis.Results:219 patients met the inclusion and exclusion criteria,131 patients were in sirolimus group, and 88 patients were not treated.5 years survival rate was 97.2%,10 years survival rate was 92.3%. In single factor analyses, the forced vital capacity at 1 second (FEV1), the forced vital capacity (FVC), age at diagnosis, sirolimus or not, VEGF-D had not reached significant difference in single factor analysis (P>0.05). Multi-factor analysis showed that FEV1, sirolimus therapy and VEGF-D were associated with the prognosis of LAM.Conclusion:FEV1, sirolimus and VEGF-D levels were associated with the survival in multiple analysis of the prognosis of LAM.Chapter2 Effects of sirolimus on lipids in patients with lymphangioleiomyomatosis (LAM).Objective:To investigate the lipid changes after treatment with sirolimus in LAM and the relationship between sirolimus concentration and incidence of hyperlipidemia.Methods:Patients were from LAM clinic in Peking Union Medical College Hospital. Data was collected from 2013 to 2015. Cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) were analyzed before and after sirolimus treatment in one month. Paired t test were used to analyze lipid changes between pre-treatment and post-treatment. The Chi-square test was conducted to test whether there was significant difference between the two groups (sirolimus concentration≥10ng/ml and sirolimus concentration<10ng/ml) in the incidence of hyperlipidemia.Results:70 patients met the inclusion and exclusion criteria. TC, TG, LDL-C, apolipoproteinB (ApoB) had reached significant difference in samples paired t test (P>0.05). The incidence of hyperlipidemia is 43.75% (sirolimus concentrations≥10ng/ml) and 11.90% (sirolimus concentration<10ng/ml), significant difference had reached between the two groups (P=0.045)Conclusion:Sirolimus regulates lipid metabolism, it mainly influence TC, TG, LDL, ApoB. The incidence of hyperlipidemia was associated with the sirolimus concentration.