The value of serum ANGPTL-4, GDF-15 and FGF-21 levels in evaluating the condition and predicting the prognosis of patients with ARDS_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 LI Qiuxiang , WANG Chengcun , XIE Wuju , QIN Yuchun , XU Zhenlang

Department of Respiratory Medicine, Hainan West Central Hospital, Danzhou, Hainan 571799, P. R. China;

Corresponding author：

LI Qiuxiang, Email: l18876649612@163.com

Keywords：

Acute respiratory distress syndrome; angiopoietin like protein-4; growth differentiation factor-15; fibroblast growth factor-21

DOI：

10.7507/1671-6205.202203007

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Objective To investigate the value of serum angiopoietin like protein 4 (ANGPTL-4), growth differentiation factor 15 (GDF-15) and fibroblast growth factor 21 (FGF-21) in evaluating the condition and predicting the prognosis of patients with acute respiratory distress syndrome (ARDS). Methods The clinical data of 147 patients with ARDS admitted in our hospital from January 2019 to December 2021 were collected. The levels of serum ANGPTL-4, GDF-15 and FGF-21 in the ARDS patients on the day of admission were detected. According to the oxygenation index(OI), the ARDS patients were divided into a mild group with 38 cases (200 mm Hg <OI≤300 mm Hg), a moderate group with 63 cases (100 mm Hg <OI≤200 mm Hg) and a severe group with 46 cases (OI≤100 mm Hg). According to the survival within 28 days after entering the intensive care unit, the ARDS patients were divided into a survival group with 90 cases and a death group with 57 cases. Multivariate logistic regression analysis was used to analyze the risk factors of death in the patients with ARDS. Receiver operator characteristic curve were drawn to analyze the value of serum ANGPTL-4, GDF-15 and FGF-21 levels in predicting the prognosis of ARDS patients. Pearson correlation was used to analyze the correlation between serum ANGPTL-4, GDF-15 and FGF-21 levels. Results The levels of serum ANGPTL-4, GDF-15 and FGF-21 in the death group were significantly higher than those in the survival group (all P<0.001). The levels of serum ANGPTL-4, GDF-15 and FGF-21 in the severe group were significantly higher than those in the mild group and the moderate group (all P<0.001). Multivariate logistic regression analysis showed that the levels of OI (OR=2.416, 95%CI 1.615 - 5.470), APACHEⅡ score (OR=2.795, 95%CI 1.973 - 6.874), SOFA score (OR=1.692, 95%CI 1.170 - 3.105), ANGPTL-4 (OR=1.951, 95%CI 1.360 - 4.208), GDF-15 (OR=2.583, 95%CI 1.804 - 6.195) and FGF-21 (OR=3.116, 95%CI 2.513 - 9.307) were the risk factors of death in patients with ARDS (P<0.05). The area under the ROC curve of combination of ANGPTL-4, GDF-15 and FGF-21 was the highest (0.953, 95%CI 0.892 - 0.998) for prediction the death of ARDS patients, with a sensitivity of 98.0% and specificity of 87.3%. Correlation analysis showed that serum ANGPTL-4 level was positively correlated with GDF-15 and FGF-21 in the ARDS patients (P<0.001). Conclusions The elevated levels of serum ANGPTL-4, GDF-15 and FGF-21 are related to the severity and death of ARDS patients. The combined detection of serum ANGPTL-4, GDF-15 and FGF-21 is helpful to predict the prognosis of ARDS patients.

Citation： LI Qiuxiang, WANG Chengcun, XIE Wuju, QIN Yuchun, XU Zhenlang. The value of serum ANGPTL-4, GDF-15 and FGF-21 levels in evaluating the condition and predicting the prognosis of patients with ARDS. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(7): 465-470. doi: 10.7507/1671-6205.202203007 Copy

1.	Williams GW, Berg NK, Reskallah A, et al. Acute respiratory distress syndrome. Anesthesiology, 2021, 134(2): 270-282.
2.	Hung CF, Holton S, Chow YH, et al. Pericyte-like cells undergo transcriptional reprogramming and distinct functional adaptations in acute lung injury. FASEB J, 2021, 35(4): e21323.
3.	Skowrońska M, Skrzyńska M, Machowski M, et al. Plasma growth differentiation factor 15 levels for predicting serious adverse events and bleeding in acute pulmonary embolism: a prospective observational study. Pol Arch Intern Med, 2020, 130(9): 757-765.
4.	Ebrahimi F, Wolffenbuttel C, Blum CA, et al. Fibroblast growth factor 21 predicts outcome in community-acquired pneumonia: secondary analysis of two randomised controlled trials. Eur Respir J, 2019, 53(2): 1800973.
5.	Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA, 2012, 307(23): 2526-2533.
6.	Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet, 2021, 398(10300): 622-637.
7.	刘胜岗, 杨红忠. 血管生成素样蛋白4(Angptl4)在肺纤维化过程中的作用. 中国医师杂志, 2018, 20(5): 712-714,719.
8.	Wu YQ, Shen YC, Wang H, et al. Serum angiopoietin-like 4 is over-expressed in COPD patients: association with pulmonary function and inflammation. Eur Rev Med Pharmacol Sci, 2016, 20(1): 44-53.
9.	Song HY, Chen Q, Xie SP, et al. GDF-15 prevents lipopolysaccharide-mediated acute lung injury via upregulating SIRT1. Biochem Biophys Res Commun, 2020, 526(2): 439-446.
10.	Gao J, Liu QH, Li JL, et al. Fibroblast growth factor 21 dependent TLR4/MYD88/NF-κB signaling activation is involved in lipopolysaccharide-induced acute lung injury. Int Immunopharmacol, 2020, 80(3): 106219.
11.	Li L, Foo BJW, Kwok KW, et al. Antibody treatment against angiopoietin-like 4 reduces pulmonary edema and injury in secondary pneumococcal pneumonia. mBio, 2019, 10(3): e02469-18.
12.	Rosenberg BJ, Hirano M, Quinzii CM, et al. Growth differentiation factor-15 as a biomarker of strength and recovery in survivors of acute respiratory failure. Thorax, 2019, 74(11): 1099-1101.
13.	张放, 郭树彬, 姬文卿, 等. 外周血成纤维细胞生长因子-21在脓毒症及感染性休克中的表达. 中国急救医学, 2020, 40(7): 644-648.
14.	Sehgal IS, Agarwal R, Dhooria S, et al. Risk stratification of acute respiratory distress syndrome using a PaO₂: FiO₂ threshold of 150 mmHg: a retrospective analysis from an Indian intensive care unit. Lung India, 2020, 37(6): 473-478.
15.	Yoo JW, Ju SM, Lee SJ, et al. Geriatric nutritional risk index is associated with 30-day mortality in patients with acute respiratory distress syndrome. Medicine (Baltimore), 2020, 99(25): e20671.
16.	Hu J, Liu L, Zeng XH, et al. Prognostic value of angiopoietin-like 4 in patients with acute respiratory distress syndrome. Shock, 2021, 56(3): 403-411.
17.	尚明升, 高延秋, 贾宝辉, 等. 生长分化因子-15和血管外肺水指数在ARDS患者严重程度分级及预后预测中的价值. 中华危重病急救医学, 2020, 32(10): 1226-1230.
18.	Li X, Shen H, Zhou TH, et al. Does an increase in serum FGF21 level predict 28-day mortality of critical patients with sepsis and ARDS?. Respir Res, 2021, 22(1): 182.

1. Williams GW, Berg NK, Reskallah A, et al. Acute respiratory distress syndrome. Anesthesiology, 2021, 134(2): 270-282.
2. Hung CF, Holton S, Chow YH, et al. Pericyte-like cells undergo transcriptional reprogramming and distinct functional adaptations in acute lung injury. FASEB J, 2021, 35(4): e21323.
3. Skowrońska M, Skrzyńska M, Machowski M, et al. Plasma growth differentiation factor 15 levels for predicting serious adverse events and bleeding in acute pulmonary embolism: a prospective observational study. Pol Arch Intern Med, 2020, 130(9): 757-765.
4. Ebrahimi F, Wolffenbuttel C, Blum CA, et al. Fibroblast growth factor 21 predicts outcome in community-acquired pneumonia: secondary analysis of two randomised controlled trials. Eur Respir J, 2019, 53(2): 1800973.
5. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA, 2012, 307(23): 2526-2533.
6. Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet, 2021, 398(10300): 622-637.
7. 刘胜岗, 杨红忠. 血管生成素样蛋白4(Angptl4)在肺纤维化过程中的作用. 中国医师杂志, 2018, 20(5): 712-714,719.
8. Wu YQ, Shen YC, Wang H, et al. Serum angiopoietin-like 4 is over-expressed in COPD patients: association with pulmonary function and inflammation. Eur Rev Med Pharmacol Sci, 2016, 20(1): 44-53.
9. Song HY, Chen Q, Xie SP, et al. GDF-15 prevents lipopolysaccharide-mediated acute lung injury via upregulating SIRT1. Biochem Biophys Res Commun, 2020, 526(2): 439-446.
10. Gao J, Liu QH, Li JL, et al. Fibroblast growth factor 21 dependent TLR4/MYD88/NF-κB signaling activation is involved in lipopolysaccharide-induced acute lung injury. Int Immunopharmacol, 2020, 80(3): 106219.
11. Li L, Foo BJW, Kwok KW, et al. Antibody treatment against angiopoietin-like 4 reduces pulmonary edema and injury in secondary pneumococcal pneumonia. mBio, 2019, 10(3): e02469-18.
12. Rosenberg BJ, Hirano M, Quinzii CM, et al. Growth differentiation factor-15 as a biomarker of strength and recovery in survivors of acute respiratory failure. Thorax, 2019, 74(11): 1099-1101.
13. 张放, 郭树彬, 姬文卿, 等. 外周血成纤维细胞生长因子-21在脓毒症及感染性休克中的表达. 中国急救医学, 2020, 40(7): 644-648.
14. Sehgal IS, Agarwal R, Dhooria S, et al. Risk stratification of acute respiratory distress syndrome using a PaO₂: FiO₂ threshold of 150 mmHg: a retrospective analysis from an Indian intensive care unit. Lung India, 2020, 37(6): 473-478.
15. Yoo JW, Ju SM, Lee SJ, et al. Geriatric nutritional risk index is associated with 30-day mortality in patients with acute respiratory distress syndrome. Medicine (Baltimore), 2020, 99(25): e20671.
16. Hu J, Liu L, Zeng XH, et al. Prognostic value of angiopoietin-like 4 in patients with acute respiratory distress syndrome. Shock, 2021, 56(3): 403-411.
17. 尚明升, 高延秋, 贾宝辉, 等. 生长分化因子-15和血管外肺水指数在ARDS患者严重程度分级及预后预测中的价值. 中华危重病急救医学, 2020, 32(10): 1226-1230.
18. Li X, Shen H, Zhou TH, et al. Does an increase in serum FGF21 level predict 28-day mortality of critical patients with sepsis and ARDS?. Respir Res, 2021, 22(1): 182.

Chinese Journal of Respiratory and Critical Care Medicine

The value of serum ANGPTL-4, GDF-15 and FGF-21 levels in evaluating the condition and predicting the prognosis of patients with ARDS

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