慢性阻塞性肺疾病急性加重期生物标志物的研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

贾心予 , 吴桢珍 , 吉宁飞 ,  黄茂

南京医科大学第一附属医院呼吸与危重症医学科（江苏南京 210029）;

Corresponding author：

黄茂, Email: hm6114@126.com

Keywords：

DOI：

10.7507/1671-6205.201902005

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Citation： 贾心予, 吴桢珍, 吉宁飞, 黄茂. 慢性阻塞性肺疾病急性加重期生物标志物的研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2020, 19(3): 299-303. doi: 10.7507/1671-6205.201902005 Copy

1.	GOLD Executive Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2018 updated)[EB/OL]2018-11-10. Available at: https://goldcopd.org/.
2.	Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet, 2007, 370(9589): 786-796.
3.	Alotaibi NM, Chen V, Hollander Z, et al. Phenotyping COPD exacerbations using imaging and blood-based biomarkers. Int J Chron Obstruct Pulmon Dis, 2018, 13: 217-229.
4.	Chen YR, Chen V, Hollander Z, et al. C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations. PLoS One, 2017, 12(3): e0174063.
5.	Chang C, Zhu H, Shen N, et al. Utility of the combination of serum highly-sensitive C-reactive protein level at discharge and a risk index in predicting readmission for acute exacerbation of COPD. J Bras Pneumol, 2014, 40(5): 495-503.
6.	Chalmers JD, Singanayagam A, Hill AT. C-reactive protein is an independent predictor of severity in community-acquired pneumonia. Am J Med, 2008, 121(3): 219-225.
7.	Qian W, Huang GZ. Neutrophil CD64 as a marker of bacterial infection in acute exacerbations of chronic obstructive pulmonary disease. Immunol Invest, 2016, 45(6): 490-503.
8.	Mathioudakis AG, Chatzimavridou-Grigoriadou V, Corlateanu A, et al. Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis. Eur Respir Rev, 2017, 26(143): 160073.
9.	Li Y, Xie L, Xin S, et al. Values of procalcitonin and C-reactive proteins in the diagnosis and treatment of chronic obstructive pulmonary disease having concomitant bacterial infection. Pak J Med Sci, 2017, 33(3): 566-569.
10.	Barnes PJ. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin Chest Med, 2014, 35(1): 71-86.
11.	Hoenderdos K, Condliffe A. The neutrophil in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2013, 48(5): 531-539.
12.	Polosa R, Malerba M, Cacciola RR, et al. Effect of acute exacerbations on circulating endothelial, clotting and fibrinolytic markers in COPD patients. Intern Emerg Med, 2013, 8(7): 567-574.
13.	Hu HL, Nie ZQ, Lu Y, et al. Circulating miR-125b but not miR-125a correlates with acute exacerbations of chronic obstructive pulmonary disease and the expressions of inflammatory cytokines. Medicine (Baltimore), 2017, 96(51): e9059.
14.	Gao P, Zhang J, He X, et al. Sputum inflammatory cell-based classification of patients with acute exacerbation of chronic obstructive pulmonary disease. PLoS One, 2013, 8(5): e57678.
15.	Han MK, Quibrera PM, Carretta EE, et al. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med, 2017, 5(8): 619-626.
16.	Sabit R, Thomas P, Shale DJ, et al. The effects of hypoxia on markers of coagulation and systemic inflammation in patients with COPD. Chest, 2010, 138(1): 47-51.
17.	Haapaniemi E, Tatlisumak T. Is D-dimer helpful in evaluating stroke patients? A systematic review. Acta Neurol Scand, 2009, 119(3): 141-150.
18.	Zhang M, Zhang J, Zhang QH, et al. D-dimer as a potential biomarker for the progression of COPD. Clin Chim Acta, 2016, 455: 55-59.
19.	Fruchter O, Yigla M, Kramer MR. D-dimer as a prognostic biomarker for mortality in chronic obstructive pulmonary disease exacerbation. Am J Med Sci, 2015, 349(1): 29-35.
20.	王芳, 程兆忠, 王镜銮, 等. 慢性阻塞性肺疾病急性加重期肺栓塞发生率的荟萃分析. 中华医学杂志, 2013, 93(24): 1868-1871.
21.	Gumus A, Altintas N, Cinarka H, et al. Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD. Int J Chron Obstruct Pulmon Dis, 2015, 10(1): 357-365.
22.	Zhou AY, Zhou ZJ, Zhao YY, et al. The recent advances of phenotypes in acute exacerbations of COPD. Int J Chron Obstruct Pulmon Dis, 2017, 12: 1009-1018.
23.	Shaw JG, Vaughan A, Dent AG, et al. Biomarkers of progression of chronic obstructive pulmonary disease (COPD). J Thorac Dis, 2014, 6(11): 1532-1547.
24.	Crisafulli E, Torres A, Huerta A, et al. C-Reactive Protein at Discharge, Diabetes Mellitus and ≥ 1 Hospitalization During Previous Year Predict Early Readmission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Copd, 2015, 12(3): 306-314.
25.	Winther JA, Brynildsen J, Hoiseth AD, et al. Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 study. Respir Res, 2017, 18(1): 184.
26.	Adrish M, Nannaka VB, Cano EJ, et al. Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction. Int J Chron Obstruct Pulmon Dis, 2017, 12: 1183-1189.
27.	Mandal J, Roth M, Costa L, et al. Vasoactive intestinal peptide for diagnosing exacerbation in chronic obstructive pulmonary disease. Respiration, 2015, 90(5): 357-368.
28.	Ruzsics I, Nagy L, Keki S, et al. L-Arginine Pathway in COPD Patients with Acute Exacerbation: A New Potential Biomarker. Copd, 2016, 13(2): 139-145.
29.	Vogeli A, Ottiger M, Meier MA, et al. Asymmetric Dimethylarginine Predicts Long-Term Outcome in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Lung, 2017, 195(6): 717-727.
30.	Demling N, Ehrhardt C, Kasper M, et al. Promotion of cell adherence and spreading: a novel function of RAGE, the highly selective differentiation marker of human alveolar epithelial type I cells. Cell Tissue Res, 2006, 323(3): 475-488.
31.	Zhang Y, Li S, Wang G, et al. Changes of HMGB1 and sRAGE during the recovery of COPD exacerbation. J Thorac Dis, 2014, 6(6): 734-741.
32.	Fujita M, Shannon JM, Ouchi H, et al. Serum surfactant protein D is increased in acute and chronic inflammation in mice. Cytokine, 2005, 31(1): 25-33.
33.	Ozyurek BA, Ulasli SS, Bozbas SS, et al. Value of serum and induced sputum surfactant protein-D in chronic obstructive pulmonary disease. Multidiscip Respir Med, 2013, 8(1): 36.
34.	Rahimirad S, Ghaffary MR, Rahimirad MH, et al. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease. Tuberk Toraks, 2017, 65(1): 25-31.
35.	GOLD Executive Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2019 updated)[EB/OL]2019-01-10. Available at: https://goldcopd.org/.
36.	Tanriverdi H, Ornek T, Erboy F, et al. Comparison of diagnostic values of procalcitonin, C-reactive protein and blood neutrophil/lymphocyte ratio levels in predicting bacterial infection in hospitalized patients with acute exacerbations of COPD. Wien Klin Wochenschr, 2015, 127(19-20): 756-763.
37.	Antus B, Drozdovszky O, Barta I. Assessment of exhaled carbon monoxide in exacerbations of chronic obstructive pulmonary disease. Physiol Int, 2016, 103(2): 211-219.
38.	Drozdovszky O, Barta I, Antus B. Sputum eicosanoid profiling in exacerbations of chronic obstructive pulmonary disease. Respiration, 2014, 87(5): 408-415.
39.	Saito J, Mackay AJ, Rossios C, et al. Sputum-to-serum hydrogen sulfide ratio in COPD. Thorax, 2014, 69(10): 903-909.
40.	Mohan S, Ho T, Kjarsgaard M, et al. Hemosiderin in sputum macrophages may predict infective exacerbations of chronic obstructive pulmonary disease: a retrospective observational study. BMC Pulm Med, 2017, 17(1): 60.
41.	Pizzini A, Filipiak W, Wille J, et al. Analysis of volatile organic compounds in the breath of patients with stable or acute exacerbation of chronic obstructive pulmonary disease. J Breath Res, 2018, 12(3): 036002.
42.	董肖琦, 沈茜, 姚一楠, 等. 慢性阻塞性肺疾病急性加重患者呼出气冷凝液中白细胞介素-6 与白三烯 B4 的检测及其临床意义. 中华结核和呼吸杂志, 2017, 40(2): 114-117.
43.	Kunisaki KM, Rice KL, Janoff EN, et al. Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: a prospective study. Ther Adv Respir Dis, 2008, 2(2): 55-64.
44.	Lu Z, Huang W, Wang L, et al. Exhaled nitric oxide in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis, 2018, 13: 2695-2705.
45.	Patel N, Belcher J, Thorpe G, et al. Measurement of C-reactive protein, procalcitonin and neutrophil elastase in saliva of COPD patients and healthy controls: correlation to self-reported wellbeing parameters. Respir Res, 2015, 16(1): 62.
46.	Sriram KB, Singh M. Lung ultrasound B-lines in exacerbations of chronic obstructive pulmonary disease. Intern Med J, 2017, 47(3): 324-327.
47.	Golpon HA, Coldren CD, Zamora MR, et al. Emphysema lung tissue gene expression profiling. Am J Respir Cell Mol Biol, 2004, 31(6): 595-600.
48.	Melguizo C, Prados J, Luque R, et al. Modulation of multidrug resistance gene expression in peripheral blood mononuclear cells of lung cancer patients and evaluation of their clinical significance. Cancer Chemother Pharmacol, 2013, 71(2): 537-541.
49.	Wu XD, Sun XR, Chen CS, et al. Dynamic gene expressions of peripheral blood mononuclear cells in patients with acute exacerbation of chronic obstructive pulmonary disease: a preliminary study. Crit Care, 2014, 18(6): 508.
50.	Shi L, Zhu B, Xu M, et al. Selection of AECOPD-specific immunomodulatory biomarkers by integrating genomics and proteomics with clinical informatics. Cell Biol Toxicol, 2017, 34(5454): 1-15.
51.	Gulcev M, Reilly C, Griffin TJ, et al. Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis, 2016, 11(1): 2435-2446.

1. GOLD Executive Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2018 updated)[EB/OL]2018-11-10. Available at: https://goldcopd.org/.
2. Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet, 2007, 370(9589): 786-796.
3. Alotaibi NM, Chen V, Hollander Z, et al. Phenotyping COPD exacerbations using imaging and blood-based biomarkers. Int J Chron Obstruct Pulmon Dis, 2018, 13: 217-229.
4. Chen YR, Chen V, Hollander Z, et al. C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations. PLoS One, 2017, 12(3): e0174063.
5. Chang C, Zhu H, Shen N, et al. Utility of the combination of serum highly-sensitive C-reactive protein level at discharge and a risk index in predicting readmission for acute exacerbation of COPD. J Bras Pneumol, 2014, 40(5): 495-503.
6. Chalmers JD, Singanayagam A, Hill AT. C-reactive protein is an independent predictor of severity in community-acquired pneumonia. Am J Med, 2008, 121(3): 219-225.
7. Qian W, Huang GZ. Neutrophil CD64 as a marker of bacterial infection in acute exacerbations of chronic obstructive pulmonary disease. Immunol Invest, 2016, 45(6): 490-503.
8. Mathioudakis AG, Chatzimavridou-Grigoriadou V, Corlateanu A, et al. Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis. Eur Respir Rev, 2017, 26(143): 160073.
9. Li Y, Xie L, Xin S, et al. Values of procalcitonin and C-reactive proteins in the diagnosis and treatment of chronic obstructive pulmonary disease having concomitant bacterial infection. Pak J Med Sci, 2017, 33(3): 566-569.
10. Barnes PJ. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin Chest Med, 2014, 35(1): 71-86.
11. Hoenderdos K, Condliffe A. The neutrophil in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2013, 48(5): 531-539.
12. Polosa R, Malerba M, Cacciola RR, et al. Effect of acute exacerbations on circulating endothelial, clotting and fibrinolytic markers in COPD patients. Intern Emerg Med, 2013, 8(7): 567-574.
13. Hu HL, Nie ZQ, Lu Y, et al. Circulating miR-125b but not miR-125a correlates with acute exacerbations of chronic obstructive pulmonary disease and the expressions of inflammatory cytokines. Medicine (Baltimore), 2017, 96(51): e9059.
14. Gao P, Zhang J, He X, et al. Sputum inflammatory cell-based classification of patients with acute exacerbation of chronic obstructive pulmonary disease. PLoS One, 2013, 8(5): e57678.
15. Han MK, Quibrera PM, Carretta EE, et al. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med, 2017, 5(8): 619-626.
16. Sabit R, Thomas P, Shale DJ, et al. The effects of hypoxia on markers of coagulation and systemic inflammation in patients with COPD. Chest, 2010, 138(1): 47-51.
17. Haapaniemi E, Tatlisumak T. Is D-dimer helpful in evaluating stroke patients? A systematic review. Acta Neurol Scand, 2009, 119(3): 141-150.
18. Zhang M, Zhang J, Zhang QH, et al. D-dimer as a potential biomarker for the progression of COPD. Clin Chim Acta, 2016, 455: 55-59.
19. Fruchter O, Yigla M, Kramer MR. D-dimer as a prognostic biomarker for mortality in chronic obstructive pulmonary disease exacerbation. Am J Med Sci, 2015, 349(1): 29-35.
20. 王芳, 程兆忠, 王镜銮, 等. 慢性阻塞性肺疾病急性加重期肺栓塞发生率的荟萃分析. 中华医学杂志, 2013, 93(24): 1868-1871.
21. Gumus A, Altintas N, Cinarka H, et al. Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD. Int J Chron Obstruct Pulmon Dis, 2015, 10(1): 357-365.
22. Zhou AY, Zhou ZJ, Zhao YY, et al. The recent advances of phenotypes in acute exacerbations of COPD. Int J Chron Obstruct Pulmon Dis, 2017, 12: 1009-1018.
23. Shaw JG, Vaughan A, Dent AG, et al. Biomarkers of progression of chronic obstructive pulmonary disease (COPD). J Thorac Dis, 2014, 6(11): 1532-1547.
24. Crisafulli E, Torres A, Huerta A, et al. C-Reactive Protein at Discharge, Diabetes Mellitus and ≥ 1 Hospitalization During Previous Year Predict Early Readmission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Copd, 2015, 12(3): 306-314.
25. Winther JA, Brynildsen J, Hoiseth AD, et al. Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 study. Respir Res, 2017, 18(1): 184.
26. Adrish M, Nannaka VB, Cano EJ, et al. Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction. Int J Chron Obstruct Pulmon Dis, 2017, 12: 1183-1189.
27. Mandal J, Roth M, Costa L, et al. Vasoactive intestinal peptide for diagnosing exacerbation in chronic obstructive pulmonary disease. Respiration, 2015, 90(5): 357-368.
28. Ruzsics I, Nagy L, Keki S, et al. L-Arginine Pathway in COPD Patients with Acute Exacerbation: A New Potential Biomarker. Copd, 2016, 13(2): 139-145.
29. Vogeli A, Ottiger M, Meier MA, et al. Asymmetric Dimethylarginine Predicts Long-Term Outcome in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Lung, 2017, 195(6): 717-727.
30. Demling N, Ehrhardt C, Kasper M, et al. Promotion of cell adherence and spreading: a novel function of RAGE, the highly selective differentiation marker of human alveolar epithelial type I cells. Cell Tissue Res, 2006, 323(3): 475-488.
31. Zhang Y, Li S, Wang G, et al. Changes of HMGB1 and sRAGE during the recovery of COPD exacerbation. J Thorac Dis, 2014, 6(6): 734-741.
32. Fujita M, Shannon JM, Ouchi H, et al. Serum surfactant protein D is increased in acute and chronic inflammation in mice. Cytokine, 2005, 31(1): 25-33.
33. Ozyurek BA, Ulasli SS, Bozbas SS, et al. Value of serum and induced sputum surfactant protein-D in chronic obstructive pulmonary disease. Multidiscip Respir Med, 2013, 8(1): 36.
34. Rahimirad S, Ghaffary MR, Rahimirad MH, et al. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease. Tuberk Toraks, 2017, 65(1): 25-31.
35. GOLD Executive Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2019 updated)[EB/OL]2019-01-10. Available at: https://goldcopd.org/.
36. Tanriverdi H, Ornek T, Erboy F, et al. Comparison of diagnostic values of procalcitonin, C-reactive protein and blood neutrophil/lymphocyte ratio levels in predicting bacterial infection in hospitalized patients with acute exacerbations of COPD. Wien Klin Wochenschr, 2015, 127(19-20): 756-763.
37. Antus B, Drozdovszky O, Barta I. Assessment of exhaled carbon monoxide in exacerbations of chronic obstructive pulmonary disease. Physiol Int, 2016, 103(2): 211-219.
38. Drozdovszky O, Barta I, Antus B. Sputum eicosanoid profiling in exacerbations of chronic obstructive pulmonary disease. Respiration, 2014, 87(5): 408-415.
39. Saito J, Mackay AJ, Rossios C, et al. Sputum-to-serum hydrogen sulfide ratio in COPD. Thorax, 2014, 69(10): 903-909.
40. Mohan S, Ho T, Kjarsgaard M, et al. Hemosiderin in sputum macrophages may predict infective exacerbations of chronic obstructive pulmonary disease: a retrospective observational study. BMC Pulm Med, 2017, 17(1): 60.
41. Pizzini A, Filipiak W, Wille J, et al. Analysis of volatile organic compounds in the breath of patients with stable or acute exacerbation of chronic obstructive pulmonary disease. J Breath Res, 2018, 12(3): 036002.
42. 董肖琦, 沈茜, 姚一楠, 等. 慢性阻塞性肺疾病急性加重患者呼出气冷凝液中白细胞介素-6 与白三烯 B4 的检测及其临床意义. 中华结核和呼吸杂志, 2017, 40(2): 114-117.
43. Kunisaki KM, Rice KL, Janoff EN, et al. Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: a prospective study. Ther Adv Respir Dis, 2008, 2(2): 55-64.
44. Lu Z, Huang W, Wang L, et al. Exhaled nitric oxide in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis, 2018, 13: 2695-2705.
45. Patel N, Belcher J, Thorpe G, et al. Measurement of C-reactive protein, procalcitonin and neutrophil elastase in saliva of COPD patients and healthy controls: correlation to self-reported wellbeing parameters. Respir Res, 2015, 16(1): 62.
46. Sriram KB, Singh M. Lung ultrasound B-lines in exacerbations of chronic obstructive pulmonary disease. Intern Med J, 2017, 47(3): 324-327.
47. Golpon HA, Coldren CD, Zamora MR, et al. Emphysema lung tissue gene expression profiling. Am J Respir Cell Mol Biol, 2004, 31(6): 595-600.
48. Melguizo C, Prados J, Luque R, et al. Modulation of multidrug resistance gene expression in peripheral blood mononuclear cells of lung cancer patients and evaluation of their clinical significance. Cancer Chemother Pharmacol, 2013, 71(2): 537-541.
49. Wu XD, Sun XR, Chen CS, et al. Dynamic gene expressions of peripheral blood mononuclear cells in patients with acute exacerbation of chronic obstructive pulmonary disease: a preliminary study. Crit Care, 2014, 18(6): 508.
50. Shi L, Zhu B, Xu M, et al. Selection of AECOPD-specific immunomodulatory biomarkers by integrating genomics and proteomics with clinical informatics. Cell Biol Toxicol, 2017, 34(5454): 1-15.
51. Gulcev M, Reilly C, Griffin TJ, et al. Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis, 2016, 11(1): 2435-2446.

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慢性阻塞性肺疾病急性加重期生物标志物的研究进展

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