Research article

Diagnostic value of Endothelin 1 as a marker for diagnosis of pulmonary parenchyma involvement in patients with systemic sclerosis

  • Received: 07 September 2020 Accepted: 07 September 2020 Published: 25 September 2020
  • Background Systemic sclerosis (SSc) is a connective tissue disease and one of the manifestations associated with this disease is pulmonary involvement. Studies showed that endothelin 1 (ET-1) plays a role in pulmonary dysfunction due to SSc. The aim of this study was to determine the level of ET-1 in SSc patients and to evaluate its association with the early stages of pulmonary fibrosis.
    Methods In this cross-sectional study, 48 patients with SSc were enrolled in the study. The stiffness of the skin was evaluated based on the modified Rodnan skin score. CT records, lung function tests and echocardiography were done. The samples were divided into two groups of patients with and without pulmonary parenchymal involvement. Blood sample was taken to measure the serum levels of ET-1 by ELISA method. ANOVA and Tukey HSD tests were used for statistical analysis.
    Results According to pulmonary CT scan, 68.2% of patients had pulmonary involvement. There was no significant difference in the presence of honeycomb lesions and fibrosis in lung CT scan of the patients in case of gender (P = 0.819 and P = 0.356, respectively). There was no statistical difference between the results of spirometry in patients with anti-Scl-70 and anti-centromere test. The mean serum level of ET-1 in the studied population was 0.55 ± 0.232 pg/mL, in the men was 0.47 ± 0.14 pg/mL and in the women was 0.55 ± 0.24 pg/mL. There was no significant difference between the two groups in the case of gender and type of the disease (P = 0.475 and P = 0.150, respectively). The ROC diagram of serum level of ET1 in patients based on the type of the disease shows that the serum level of ET-1 of 55% has 50% sensitivity and 52.2% specificity.
    Conclusion Serum level of ET-1 could not be used for screening of pulmonary involvement in SSc because its sensitivity and specificity is related to pulmonary fibrosis, honeycomb lesions and disease form. Anti Scl-70 with low levels, DLCO, FVC, FEV1, TLC can be used to assess the possibility of pulmonary involvement and response to treatment.

    Citation: Masoud Nazemiyeh, Mehrzad Hajalilou, Mohsen Rajabnia, Akbar Sharifi, Sabah Hasani. Diagnostic value of Endothelin 1 as a marker for diagnosis of pulmonary parenchyma involvement in patients with systemic sclerosis[J]. AIMS Medical Science, 2020, 7(3): 234-242. doi: 10.3934/medsci.2020014

    Related Papers:

  • Background Systemic sclerosis (SSc) is a connective tissue disease and one of the manifestations associated with this disease is pulmonary involvement. Studies showed that endothelin 1 (ET-1) plays a role in pulmonary dysfunction due to SSc. The aim of this study was to determine the level of ET-1 in SSc patients and to evaluate its association with the early stages of pulmonary fibrosis.
    Methods In this cross-sectional study, 48 patients with SSc were enrolled in the study. The stiffness of the skin was evaluated based on the modified Rodnan skin score. CT records, lung function tests and echocardiography were done. The samples were divided into two groups of patients with and without pulmonary parenchymal involvement. Blood sample was taken to measure the serum levels of ET-1 by ELISA method. ANOVA and Tukey HSD tests were used for statistical analysis.
    Results According to pulmonary CT scan, 68.2% of patients had pulmonary involvement. There was no significant difference in the presence of honeycomb lesions and fibrosis in lung CT scan of the patients in case of gender (P = 0.819 and P = 0.356, respectively). There was no statistical difference between the results of spirometry in patients with anti-Scl-70 and anti-centromere test. The mean serum level of ET-1 in the studied population was 0.55 ± 0.232 pg/mL, in the men was 0.47 ± 0.14 pg/mL and in the women was 0.55 ± 0.24 pg/mL. There was no significant difference between the two groups in the case of gender and type of the disease (P = 0.475 and P = 0.150, respectively). The ROC diagram of serum level of ET1 in patients based on the type of the disease shows that the serum level of ET-1 of 55% has 50% sensitivity and 52.2% specificity.
    Conclusion Serum level of ET-1 could not be used for screening of pulmonary involvement in SSc because its sensitivity and specificity is related to pulmonary fibrosis, honeycomb lesions and disease form. Anti Scl-70 with low levels, DLCO, FVC, FEV1, TLC can be used to assess the possibility of pulmonary involvement and response to treatment.


    加载中


    Conflict of interest



    The authors declare no conflict of interest.

    [1] Abraham DJ, Varga J (2005) Scleroderma: From cell and molecular mechanisms to disease models. Trends Immunol 26: 587-595. doi: 10.1016/j.it.2005.09.004
    [2] Mason RC, Murray JF, Nadel JA, et al. (2015)  Murray & Nadel's Textbook of Respiratory Medicine E-Book Elsevier Health Sciences.
    [3] Feghali-Bostwick C, Medsger TA, Wright TM (2003) Analysis of systemic sclerosis in twins reveals low concordance for disease and high concordance for the presence of antinuclear antibodies. Arthritis Rheum 48: 1956-1963. doi: 10.1002/art.11173
    [4] Mayes MD, Lacey JV, Beebe-Dimmer J, et al. (2003) Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum 48: 2246-2255. doi: 10.1002/art.11073
    [5] Pietra GG, Capron F, Stewart S, et al. (2004) Pathologic assessment of vasculopathies in pulmonary hypertension. J Am Coll Cardiol 43: 25S-32S. doi: 10.1016/j.jacc.2004.02.033
    [6] Tashkin DP, Elashoff R, Clements PJ, et al. (2006) Cyclophosphamide versus placebo in scleroderma lung disease. New Engl J Med 354: 2655-2666. doi: 10.1056/NEJMoa055120
    [7] Clements PJ, Furst DE (2002)  Systemic Sclerosis Philadelphia: Lippincott Williams & Wilkins.
    [8] Strimbu K, Tavel JA (2010) What are biomarkers? Curr Opin HIV AIDS 5: 463. doi: 10.1097/COH.0b013e32833ed177
    [9] Wagner J, Atkinson A (2015) Measuring biomarker progress. Clin Pharmacol Ther 98: 2-5. doi: 10.1002/cpt.133
    [10] Humbert M, Barst R, Robbins I, et al. (2004) Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 24: 353-359. doi: 10.1183/09031936.04.00028404
    [11] Williams MH, Das C, Handler CE, et al. (2006) Systemic sclerosis associated pulmonary hypertension: improved survival in the current era. Heart 92: 926-932. doi: 10.1136/hrt.2005.069484
    [12] Leask A (2008) Targeting the TGFβ, endothelin-1 and CCN2 axis to combat fibrosis in scleroderma. Cell Signal 20: 1409-1414. doi: 10.1016/j.cellsig.2008.01.006
    [13] Yamane K, Kashiwagi H, Suzuki N, et al. (1991) Elevated plasma levels of endothelin-1 in systemic sclerosis. Arthritis Rheum 34: 243-244. doi: 10.1002/art.1780340220
    [14] Vancheeswaran R, Azam A, Black C, et al. (1994) Localization of endothelin-1 and its binding sites in scleroderma skin. J Rheumatol 21: 1268-1276.
    [15] Kowal-Bielecka O, Landewé R, Avouac J, et al. (2009) EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 68: 620-628. doi: 10.1136/ard.2008.096677
    [16] Galie N, Rubin L, Hoeper M, et al. (2008) Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): A double-blind, randomised controlled trial. Lancet 371: 2093-2100. doi: 10.1016/S0140-6736(08)60919-8
    [17] Clements P, Lachenbruch P, Seibold J, et al. (1993) Skin thickness score in systemic sclerosis: An assessment of interobserver variability in 3 independent studies. J Rheumatol 20: 1892-1896.
    [18] Codullo V, Cavazzana I, Bonino C, et al. (2009) Serologic profile and mortality rates of scleroderma renal crisis in Italy. J Rheumatol 36: 1464-1469. doi: 10.3899/jrheum.080806
    [19] Szamosi S, Szekanecz Z, Szűcs G (2006) Gastrointestinal manifestations in Hungarian scleroderma patients. Rheumatol Int 26: 1120-1124. doi: 10.1007/s00296-006-0146-z
    [20] Mayes MD (1996) Scleroderma epidemiology. Rheum Dis Clin North Am 22: 751-764. doi: 10.1016/S0889-857X(05)70299-4
    [21] Valentini G, Black C (2002) Systemic sclerosis. Best Pract Res Clin Rheumatol 16: 807-816. doi: 10.1053/berh.2002.0258
    [22] Mottaghi P, Karimifar M, Salesi M, et al. (2010) Parenchymal lung involvement in patients with systemic sclerosis admitted to Isfahan's Noor and Al-Zahra Hospitals. Razi J Med Sci 17: 67-72.
    [23] Wells A, Hansell D, Rubens M, et al. (1997) Fibrosing alveolitis in systemic sclerosis. Indices of lung function in relation to extent of disease on computed tomography. Arthritis Rheum 40: 1229-1236.
    [24] Steen VD, Owens GR, Fino GJ, et al. (1985) Pulmonary involvement in systemic sclerosis (scleroderma). Arthritis Rheum 28: 759-767. doi: 10.1002/art.1780280706
    [25] Guillen-Del Castillo A, Simeón-Aznar CP, Fonollosa-Pla V, et al. (2014) Good outcome of interstitial lung disease in patients with scleroderma associated to anti-PM/Scl antibody. Semin Arthritis Rheum 44: 331-337. doi: 10.1016/j.semarthrit.2014.07.002
    [26] Peters-Golden M, Wise RA, Schneider P, et al. (1984) Clinical and demographic predictors of loss of pulmonary function in systemic sclerosis. Medicine 63: 221-231. doi: 10.1097/00005792-198407000-00004
    [27] Whalley D, Mckenna SP, De Jong Z, et al. (1997) Quality of life in rheumatoid arthritis. Br J Rheumatol 36: 884-888. doi: 10.1093/rheumatology/36.8.884
    [28] Aghaei M, Gharibdost F, Zayeni H, et al. (2011) The Correlation between endothelin-1 antibody plasma concentrations in patients with scleroderma and different manifestations of the disease. Tehran Univ Med J 68.
    [29] Walker U, Tyndall A, Czirjak L, et al. (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: A report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis 66: 754-763. doi: 10.1136/ard.2006.062901
    [30] Yamane K, Miyauchi T, Suzuki N, et al. (1992) Significance of plasma endothelin-1 levels in patients with systemic sclerosis. J Rheumatol 19: 1566-1571.
    [31] Vancheeswaran R, Magoulas T, Efrat G, et al. (1994) Circulating endothelin-1 levels in systemic sclerosis subsets--a marker of fibrosis or vascular dysfunction? J Rheumatol 21: 1838-1844.
    [32] Horowitz JC, Ajayi IO, Kulasekaran P, et al. (2012) Survivin expression induced by endothelin-1 promotes myofibroblast resistance to apoptosis. Int J Biochem Cell Biol 44: 158-169. doi: 10.1016/j.biocel.2011.10.011
    [33] Cozzani E, Javor S, Laborai E, et al. (2013) Endothelin-1 levels in scleroderma patients: A pilot study. ISRN Dermatol 2013: 125632. doi: 10.1155/2013/125632
  • Reader Comments
  • © 2020 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(2847) PDF downloads(106) Cited by(0)

Article outline

Figures and Tables

Figures(1)  /  Tables(3)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog