Clinical Characteristics of Lymphangioleiomyomatosis and Application of a Novel Automated Cyst Burden Score

LAM is a rare cystic lung disease;estimated prevalence is 3-8/million women.Serum VEGF-D can predict progression but is normal in approximately 1/3 of cases.With effective therapy available,accurate biomarkers are important. Method: Age, menopausal status, presence of tuberous sclerosis complex, VEGF-D levels, pneumothorax and chylous effusion history,renal angiomyolipomas (AMLs) and PFTs for patients with LAM were collated.Fully automated CT-derived clustered volumetric analyses was performed on HRCT images using Siemens SyngoVia software.Clustering of low attenuation cysts by volume was quantified to determined percentage of total lung involvement and distribution of cyst size.Cyst scores were calculated for a range of Hounsfield units (HU) from -900HU to -950HU.Cyst scores were correlated with DLCO, FEV1 and VEGF-D. Results: 27 patients had a mean age 50.78.Seven had previous pneumothorax, 3 had chylothorax and 8 had AML.Mean VEGF-D level was 660.83pg/mL (SD+/-623.22).Six had a history of mTOR inhibitor use.Mean DLCO was 69.89% predicted (SD+/-20.7%).There was a negative correlation between VEGF-D and DLCO (n=13; R2 0.458; p=0.0111) and VEGF-D and FEV1 (n=14; R2=0.2741, p=0.0547).Cyst scores calculated at -940HU and at - 900HU positively correlated with VEGF-D levels (n=6; R2=0.8847; p=0.0052 and n=6, R2=0.7957; p=0.0169, respectively).There was an inverse correlation between DLCO and cyst burden scores at -940HU (R2 0.8239; p=0.0124) and -900HU (R2 0.749; p=0.0259). Conclusion: Identifying 27 patients,we suggest the prevalence of LAM in Ireland to be at least 11.25 per million women.We propose and aim to further explore prospectively an automated cyst score as a useful biomarker.