Vascular endothelial growth factor (VEGF) is a predictable marker for FEV1 progression in patients with Lymphangiolyomyomatosis (LAM)

Abstract

Introduction: LAM is a rare multisystem disease in young women. FEV1 decrease is a main complication. Several studies have shown that serum levels of VEGF levels are elevated in up to 2/3 of women with LAM. The key treatment for parenchymal lung disease is sirolimus. We here report FEV1 development in 23 LAM patients according to VEGF levels and how sirolimus affects FEV1 course dependent on VEGF levels in these patients. Methods: Data from 48 LAM patients were followed up on at pneumology of MHH regarding VEGF levels and FEV1 development over 2,7 (1,0-8,2) years. 18 Patients were transplanted and therefore excluded. For 23 non-transplanted Patients VEGF levels were available. For each Patient linear regression was conducted to specify patients FEV1-course in ml/year decrease. Linear regression was conducted to show relation of FEV1 and VEGF, further stratified by sirolimus therapy. Results: Median age of patients was 51,5 (47-62) years, whereas the mean age of time of diagnosis was 38 (37-47) years. VEGF median was 1,2 (0,62-2,23 )pg/ml; IQR of all patients, 0,96 (0,42-2,24) pg/ml; IQR of patients naive to sirolimus and 1,4 (0,71-1,97) pg/ml; IQR of patients treated with sirolimus. FEV1- decrease of all patients was 30,5 (-19,3-97,3) ml/ year; IQR. Patients without treatment showed a mean decrease of app. 24 (23,63) ml/ year in FEV1. Patients treated with sirolimus showed an increase of FEV1 of app. 96 (96,3) ml/ year. Conclusion: Elevated levels of VEGF in patients with LAM are associated with higher loss of FEV1. Treatment with sirolimus however stops FEV1-decrease and leads to improvement of FEV1 in LAM patients.