Concentration of Serum Vascular Endothelial Growth Factor (VEGF-D) and Its Correlation with Functional and Clinical Parameters in Patients with Lymphangioleiomyomatosis from a Brazilian Reference Center
Beiträge zur Klinik der Tuberkulose und spezifischen Tuberkulose-Forschung - Tập 197 - Trang 139-146 - 2019
Tóm tắt
Serum vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that is considered a valuable tool in the diagnosis of lymphangioleiomyomatosis (LAM). Previous studies have reported a wide variability in VEGF-D serum levels in LAM patients and it seems to be associated with pulmonary impairment and lymphatic involvement. We conducted a cross-sectional study from 2009 to 2017 that evaluated VEGF-D serum levels in a cohort of LAM patients who were never treated with mTOR inhibitors and compared them to healthy age-matched volunteers. Clinical and functional parameters were assessed and correlated with their respective serum VEGF-D levels. One hundred and four patients were included in the analysis. Serum VEGF-D levels were higher in LAM patients compared to healthy controls: 796 (404–1588) versus 162 (117–232) pg/mL, respectively (p < 0.001). Patients with tuberous sclerosis complex–LAM, TSC–LAM (20%), had higher levels of VEGF-D when compared to patients with sporadic LAM (80%) [1005 (641–2732) vs. 772 (370–1383), p = 0.05]. Serum VEGF-D levels were weakly correlated with DLCO (r = − 0.26, p = 0.001) and lymphatic involvement was more frequent in those with serum VEGF-D levels equal or above 800 pg/mL (35% vs. 13%, p = 0.02). In LAM, serum VEGF-D is weakly associated with lung function impairment and strongly associated with lymphatic involvement. VEGF-D is validated for use in Brazilian patients with LAM whose characteristics must be accounted for when evaluating their serum VEGF-D levels.
Tài liệu tham khảo
McCormack FX, Gupta N, Finlay GR, Young LR, Taveira-DaSilva AM, Glasgow CG et al (2016) Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir Crit Care Med 194(6):748–761
Glassberg MK (2004) Lymphangioleiomyomatosis. Clin Chest Med 25(3):573–582, vii
Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT et al (2006) The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med 173(1):105–111
Freitas CSG, Baldi BG, Jardim C, Araujo MS, Sobral JB, Heiden GI et al (2017) Pulmonary hypertension in lymphangioleiomyomatosis: prevalence, severity and the role of carbon monoxide diffusion capacity as a screening method. Orphanet J Rare Dis 12(1):74
Baldi BG, Salim C, Freitas G, Araujo MS, Dias OM, Pereira DAS et al (2014) Clinical course and characterisation of lymphangioleiomyomatosis in a Brazilian reference centre. Sarcoidosis Vasc Diffus Lung Dis 31(2):129–135
Carsillo T, Astrinidis A, Henske EP (2000) Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci USA 97(11):6085–6090
Sengupta S, Peterson TR, Sabatini DM (2010) Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 40(2):310–322
Kumasaka T, Seyama K, Mitani K, Sato T, Souma S, Kondo T et al (2004) Lymphangiogenesis in lymphangioleiomyomatosis: its implication in the progression of lymphangioleiomyomatosis. Am J Surg Pathol 28(8):1007–1016
Nascimento ECT, Baldi BG, Mariani AW, Annoni R, Kairalla RA, Pimenta S et al (2018) Immunohistological features related to functional impairment in lymphangioleiomyomatosis. Respir Res 19:83
Radzikowska E, Jagus P, Skoczylas A, Sobiecka M, Chorostowska-Wynimko J, Wiatr E et al (2013) Role of serum vascular endothelial growth factor D in discrimination of patients with polycystic lung diseases. Pol Arch Med Wewn 123(10):533–538
Young LR, Vandyke R, Gulleman PM, Inoue Y, Brown KK, Schmidt LS et al (2010) Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases. Chest 138(3):674–681
Young LR, Inoue Y, McCormack FX (2008) Diagnostic potential of serum VEGF-D for lymphangioleiomyomatosis. N Engl J Med 358(2):199–200
Xu KF, Zhang P, Tian X, Ma A, Li X, Zhou J et al (2013) The role of vascular endothelial growth factor-D in diagnosis of lymphangioleiomyomatosis (LAM). Respir Med 107(2):263–268
Chang WYC, Cane JL, Blakey JD, Kumaran M, Pointon KS, Johnson SR (2012) Clinical utility of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis. Respir Res 13:13–34
Glasgow CG, Avila NA, Lin JP, Stylianou MP, Moss J (2009) Serum vascular endothelial growth factor-D levels in patients with lymphangioleiomyomatosis reflect lymphatic involvement. Chest 135(5):1293–1300
Young L, Lee HS, Inoue Y, Moss J, Singer LG, Strange C et al (2013) Serum VEGF-D a concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial. Lancet Respir Med 1(6):445–452
Radzikowska E, Jagus P, Sobiecka M, Chorostowska-Wynimko J, Wiatr E, Kus J et al (2015) Correlation of serum vascular endothelial growth factor-D concentration with clinical presentation and course of lymphangioleiomyomatosis. Respir Med 109(11):1469–1475
Seyama K, Kumasaka T, Souma S, Sato T, Kurihara M, Mitani K et al (2006) Vascular endothelial growth factor-D is increased in serum of patients with lymphangioleiomyomatosis. Lymphat Res Biol 4(3):143–152
Baldi BG, Araujo MS, Freitas CSG, da Silva Teles GB, Kairalla RA, Dias OM et al (2014) Evaluation of the extent of pulmonary cysts and their association with functional variables and serum markers in lymphangioleiomyomatosis (LAM). Lung 192(6):967–974
Taveira-DaSilva AM, Jones AM, Julien-Williams P, Stylianou M, Moss J (2018) Long-term effect of sirolimus on serum vascular endothelial growth factor D levels in patients with lymphangioleiomyomatosis. Chest 153(1):124–132
Johnson SR, Cordier JF, Lazor R, Cottin V, Costabel U, Harari S et al (2010) European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J 35(1):14–26
Macintyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CP, Brusasco V et al (2005) Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 26(4):720–735
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A et al (2005) Standardisation of spirometry. Eur Respir J 26(2):319–338
Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F et al (2005) Standardisation of the measurement of lung volumes. Eur Respir J 26(3):511–522
Neder J, Andreoni S, Peres C, Nery LE (1999) Reference values for lung function tests. III. Carbon monoxide diffusing capacity (transfer factor). Braz J Med Biol Res 32(6):729–737
Pereira CA, Sato T, Rodrigues SC (2007) New reference values for forced spirometry in white adults in Brazil. J Bras Pneumol publicaça̋o Of da Soc Bras Pneumol e Tisilogia 33(4):397–406
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002) ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 166(1):111–117
Gupta N, Finlay GA, Kotloff RM, Strange C, Wilson KC, Young LR et al (2017) Lymphangioleiomyomatosis Diagnosis and Management: High-Resolution Chest Computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline. Am J Respir Crit Care Med 196(10):1337–1348