Evaluation of the Extent of Pulmonary Cysts and Their Association with Functional Variables and Serum Markers in Lymphangioleiomyomatosis (LAM)

Purpose Although computed tomography (CT) has been used previously to assess disease severity in lymphangioleiomyomatosis (LAM), the associations between the extent of pulmonary cysts on CT and six-minute walk test (6MWT), matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF-D) are not well established. We performed a cross-sectional study to quantify the extent of pulmonary cysts in CT and to establish their correlations with pulmonary function tests (PFTs), 6MWT results, including a composite index (desaturation–distance ratio, DDR), and levels of VEGF-D and MMPs in LAM. Methods Twenty-three LAM patients underwent CT scanning to automatically quantify the extent of pulmonary cysts and performed PFTs and 6MWT. Serum levels of MMP-2, MMP-9, and VEGF-D were also measured. Results The severity of pulmonary cystic involvement was mild (the extent of cysts was 6.8 %) and correlated best with FEV 1 /FVC ( r = −0.84), residual volume ( r = 0.66), DL CO ( r = −0.82), the DDR index ( r = 0.77), and desaturation during the 6MWT ( r = −0.81). There was a weak correlation with VEGF-D ( r = 0.45), but no association was found with MMP-2 and MMP-9. Conclusions The severity of pulmonary cystic involvement was mild in this sample of LAM patients and correlated best with airway obstruction, air trapping, reduced DL CO , the DDR index, and desaturation during the 6MWT. Serum VEGF-D cannot be completely defined as a valuable marker of disease severity and there may be a mechanism independent of MMPs to explain the formation of pulmonary cysts.