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Multicenter Study
. 2024 Jan-Dec:18:17534666241272928.
doi: 10.1177/17534666241272928.

Diagnostic value of serum vascular endothelial growth factor-D in Korean patients with lymphangioleiomyomatosis

Hee-Young Yoon  1 , Su-Jin Moon  2 , Song Yee Kim  3 , Jong Sun Park  4 , Sun Mi Choi  5 , Hyung Koo Kang  6 , Jin Woo Song  7
Affiliations
Multicenter Study

Diagnostic value of serum vascular endothelial growth factor-D in Korean patients with lymphangioleiomyomatosis

Hee-Young Yoon et al. Ther Adv Respir Dis. 2024 Jan-Dec.

Abstract

Background: Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder characterized by the proliferation of abnormal smooth muscle-like cells. Although serum vascular endothelial growth factor-D (VEGF-D) is currently used as a diagnostic biomarker for LAM, its diagnostic value in Korean patients is unclear.

Objectives: To evaluate the diagnostic value of serum VEGF-D for LAM in Korean patients.

Design: A multicenter prospective cohort study.

Methods: Serum samples were prospectively collected from five medical institutions, from patients with LAM (n = 40) and controls (n = 24; healthy participants = 3, other cystic lung diseases = 13, idiopathic pulmonary fibrosis = 4, idiopathic nonspecific interstitial pneumonia = 4). Serum VEGF-D levels were measured using the enzyme-linked immunosorbent assay, and the diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis.

Results: The mean age of patients with LAM was 44.5 years, and all were female (controls: 47.8 years; female: 70.8%, p < 0.001). The serum VEGF-D levels were significantly higher in patients with LAM than those in the control group (median: 708.9 pg/mL vs 325.3 pg/mL, p < 0.001). In the ROC curve analysis, serum VEGF-D levels showed good predicting performance for LAM diagnosis (area under the curve = 0.918) with an optimal cut-off value of 432.7 pg/mL (sensitivity = 85.0%, specificity = 87.5%). When 800 pg/mL was used as the cut-off value, the specificity of serum VEGF-D for LAM diagnosis increased to 100.0%.

Conclusion: Our results suggest that serum VEGF-D may be a useful biomarker for diagnosing LAM in Korean patients, similar to previous reports.

Keywords: biomarker; diagnosis; lymphangioleiomyomatosis; rare lung disease; vascular endothelial growth factor-D.

Plain language summary

Blood test for diagnosis of lymphangioleiomyomatosis in Korea: role of vascular endothelial growth factor-DIn this study, we discuss a blood test to diagnose a rare lung disease, called lymphangioleiomyomatosis (LAM). LAM primarily affects women, especially during their childbearing years, and can cause serious lung problems such as damage and cyst (air-filled sac) formation. The blood test looks for a special protein in the blood, called vascular endothelial growth factor-D (VEGF-D). If someone has a lot of this protein, it usually means that they have LAM. We have found that when VEGF-D levels are high, the test can effectively separate LAM from other lung diseases. We also found that raising this threshold to higher levels made it much more likely to correctly distinguish a group of people who do not have the disease from patients with LAM. Our study is important because it’s the first to show the usefulness of blood VEGF-D testing in Korean LAM patients, and because it suggests an easier and less inconvenient way for physicians to diagnose LAM in Koreans. Our findings are an important step in improving the management of Korean patients with LAM.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Comparison of serum VEGF-D levels between patients with LAM and controls. (a) Comparisons of serum VEGF-D levels between the LAM and control groups. The box and whisker plot shows all points in the data distribution. (b) Receiver operator characteristic curve for VEGF-D in diagnosing LAM. The dashed line is the reference. VEGF, Vascular endothelial growth factor; LAM, lymphangioleiomyomatosis.
Figure 2.
Figure 2.
Comparison of serum VEGF-D levels in relation to complications in patients with LAM. (a) Pneumothorax, (b) Lymphangioleiomyoma, (c) Angiomyolipoma, (d) Tuberous sclerosis. The box and whisker plot shows the full range of the data distribution. We assessed the presence of complications at the sampling time. AML, angiomyolipoma; LAM, lymphangioleiomyoma; LYMP, lymphangioma; ns, non-significant; PNX, pneumothorax; TSC, tuberous sclerosis complex; VEGF, Vascular endothelial growth factor.
Figure 3.
Figure 3.
Correlation between serum VEGF-D levels and clinical parameters. (a) DLCO (b) Resting SpO2 during the 6MWT (c) Lowest SpO2 during the 6MWT. The plot displays slopes (lines) obtained through simple linear regression, along with their 95% confidence intervals (dash lines), using all data points. VEGF, Vascular endothelial growth factor; LAM, lymphangioleiomyomatosis; DLCO, diffusing capacity for carbon monoxide; 6MWT, 6-minute walk test; SpO2, saturation of oxygen.
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