Long-Term Effect of Sirolimus on Serum Vascular Endothelial Growth Factor D Levels in Patients With Lymphangioleiomyomatosis.

Abstract

BACKGROUND:

Sirolimus reduces serum levels of vascular endothelial growth factor D (VEGF-D); the size of chylous effusions, lymphangioleiomyomas, and angiomyolipomas; and stabilizes lung function in patients with lymphangioleiomyomatosis (LAM).

METHODS:

To determine whether reductions in VEGF-D levels are sustained over time, as well as parallel changes in lung function and lymphatic disease, we evaluated 25 patients with LAM and measured VEGF-D levels, lung function, and extent of lymphatic disease before and during sirolimus therapy.

RESULTS:

Treatment with sirolimus stabilized FEV1 and diffusion capacity for carbon monoxide (Dlco) over a period of 4.5 ± 1.6 years, caused resolution of lymphatic disease, and reduced the size of angiomyolipomas and VEGF-D levels (3,720 ± 3,020 pg/mL to 945 ± 591 pg/mL; P < .0001). Yearly changes in FEV1 % predicted and Dlco % predicted were reduced from -7.4% ± 1.4% to -0.3% ± 0.5% (P < .001) and -6.4% ± 0.9% to -0.4% ± 0.5% (P < .001), respectively. Lower VEGF-D levels correlated with sirolimus therapy (P < .001), but no significant relationship was observed between reduction in VEGF-D levels and FEV1 and Dlco during sirolimus therapy. The magnitude of VEGF-D decline was not related to the effect on lung function. Patients with lymphatic disease had higher serum VEGF-D levels, a greater reduction in VEGF-D levels, and better long-term sustained improvement in lung function during sirolimus therapy than did those without lymphatic disease.

CONCLUSIONS:

Sirolimus therapy stabilizes lung function over many years of therapy while producing a sustained reduction in VEGF-D levels in patients with elevated levels preceding therapy. An association was not demonstrated between the magnitude of VEGF-D decline and the beneficial effect of sirolimus on lung function. Persistent improvement in lung function was observed in patients with lymphatic disease.

• Authors: Angelo M Taveira-DaSilva, Amanda M Jones, Patricia Julien-Williams, Mario Stylianou, Joel Moss
• Journal: Chest (Chest) Vol. 153 Issue 1 Pg. 124-132 (01 2018) ISSN: 1931-3543 [Electronic] United States
• PMID: 28533049 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Immunosuppressive Agents
• VEGFD protein, human
• Vascular Endothelial Growth Factor D
• Carbon Monoxide
• Sirolimus

Topics

• Adult
• Age of Onset
• Carbon Monoxide (blood)
• Female
• Forced Expiratory Volume (drug effects)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Long-Term Care
• Lymphangioleiomyomatosis (blood, drug therapy, physiopathology)
• Menopause (physiology)
• Middle Aged
• Premenopause (physiology)
• Sirolimus (therapeutic use)
• Vascular Endothelial Growth Factor D (metabolism)
• Young Adult