血液生物标志物在慢性阻塞性肺疾病中的研究进展
Advances in Blood Biomarkers in Chronic Obstructive Pulmonary Disease
DOI: 10.12677/md.2024.144065, PDF,    科研立项经费支持
作者: 贾科良:济宁医学院临床医学院,山东 济宁;韩丽萍*:济宁市第一人民医院呼吸与危重症医学科,山东 济宁
关键词: 慢性阻塞性肺疾病血液生物标志物急性加重期Chronic Obstructive Pulmonary Disease Blood Biomarkers Acute Exacerbations
摘要: 慢性阻塞性肺疾病(Chronic Obstructive Pulmonary Disease, COPD)是一种以气流受限和呼吸困难为特征的慢性炎症性疾病。近年来,血液生物标志物在COPD的诊断、病情评估和治疗监测等方面显示出重要的潜力。血液生物标志物在COPD研究中有许多重要进展,许多研究重点关注了C反应蛋白(C-Reactive Protein, CRP)、白介素-6 (Interleukin-6, IL-6)、肿瘤坏死因子-α (Tumor Necrosis Factor-α, TNF-α)、嗜酸性粒细胞、中性粒细胞与淋巴细胞比值(Nneutrophil-to-Lymphocyte Ratio, NLR)等炎症标志物,以及其他相关标志物如纤维蛋白原、D-二聚体和胱抑素C等。通过总结现有研究成果,可以探讨这些标志物在COPD中的临床应用价值及其在疾病机制研究中的意义,进一步的研究有望揭示更多具有临床意义的生物标志物。
Abstract: Chronic obstructive pulmonary disease is a chronic inflammatory disease characterized by airflow limitation and dyspnea. In recent years, blood biomarkers have shown significant potential in the diagnosis, disease assessment and treatment monitoring of COPD. There have been many important advances in blood biomarkers in COPD research, with many studies focusing on inflammatory markers such as C-reactive protein, interleukin-6, tumor necrosis factor-α, eosinophils, and neutrophil-to-lymphocyte ratio, as well as other related markers such as fibrinogen, D-dimer and cystatin C. By summarizing the existing research results, the clinical application value of these markers in COPD and their significance in the study of disease mechanisms can be explored, and further studies are expected to reveal more biomarkers with clinical significance.
文章引用:贾科良, 韩丽萍. 血液生物标志物在慢性阻塞性肺疾病中的研究进展[J]. 医学诊断, 2024, 14(4): 448-455. https://doi.org/10.12677/md.2024.144065

参考文献

[1] 杨国林, 易何娟. 血清CRP、PCT、IL-17对慢性阻塞性肺疾病稳定期患者急性发作的预测作用[J]. 检验医学与临床, 2024, 21(7): 999-1002.
[2] Tang, L., Shi, S., Wang, B., Liu, L., Yang, Y., Sun, X., et al. (2021) Effect of Urban Air Pollution on CRP and Coagulation: A Study on Inpatients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. BMC Pulmonary Medicine, 21, Article No. 296. [Google Scholar] [CrossRef] [PubMed]
[3] Butler, C.C., Gillespie, D., White, P., Bates, J., Lowe, R., Thomas-Jones, E., et al. (2019) C-reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations. New England Journal of Medicine, 381, 111-120. [Google Scholar] [CrossRef] [PubMed]
[4] Al-Hasan, M.N. and Al-Jaghbeer, M.J. (2020) Use of Antibiotics in Chronic Obstructive Pulmonary Disease: What Is Their Current Role in Older Patients? Drugs & Aging, 37, 627-633. [Google Scholar] [CrossRef] [PubMed]
[5] Aslani, M., Amani, M., Moghadas, F. and Ghobadi, H. (2022) Adipolin and IL-6 Serum Levels in Chronic Obstructive Pulmonary Disease. Advances in Respiratory Medicine, 90, 391-398. [Google Scholar] [CrossRef] [PubMed]
[6] Huang, H., Huang, X., Zeng, K., Deng, F., Lin, C. and Huang, W. (2021) Interleukin-6 Is a Strong Predictor of the Frequency of COPD Exacerbation within 1 Year. International Journal of Chronic Obstructive Pulmonary Disease, 16, 2945-2951. [Google Scholar] [CrossRef] [PubMed]
[7] Aslani, M.R., Ghazaei, Z. and Ghobadi, H. (2020) Correlation of Serum Fatty Acid Binding Protein-4 and Interleukin-6 with Airflow Limitation and Quality of Life in Stable and Acute Exacerbation of COPD. Turkish Journal of Medical Sciences, 44, 337-345. [Google Scholar] [CrossRef] [PubMed]
[8] Bradford, E., Jacobson, S., Varasteh, J., Comellas, A.P., Woodruff, P., O’Neal, W., et al. (2017) The Value of Blood Cytokines and Chemokines in Assessing COPD. Respiratory Research, 18, Article No. 180. [Google Scholar] [CrossRef] [PubMed]
[9] Feng, Y. and Liu, E. (2022) Detection of Respiratory Viruses and Expression of Inflammatory Cytokines in Patients with Acute Exacerbation Chronic Obstructive Pulmonary Disease in Mongolia China. Brazilian Journal of Biology, 82, e231134. [Google Scholar] [CrossRef] [PubMed]
[10] 李建英, 刘远程, 潘杨. 8-异前列腺素F2α和白细胞介素-17预测慢性阻塞性肺疾病稳定期患者急性发作的作用[J]. 医学研究生学报, 2022, 35(8): 863-867.
[11] Shen, S. and Xiao, Y. (2023) Association between C-Reactive Protein and Albumin Ratios and Risk of Mortality in Patients with Chronic Obstructive Pulmonary Disease. International Journal of Chronic Obstructive Pulmonary Disease, 18, 2289-2303. [Google Scholar] [CrossRef
[12] Yao, Y., Zhou, J., Diao, X. and Wang, S. (2019) Association between Tumor Necrosis Factor-Α and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis. Therapeutic Advances in Respiratory Disease, 13, 1-17. [Google Scholar] [CrossRef] [PubMed]
[13] Chiang, C., Chuang, C. and Liu, S. (2013) Transforming Growth Factor-Β1 and Tumor Necrosis Factor-Α Are Associated with Clinical Severity and Airflow Limitation of COPD in an Additive Manner. Lung, 192, 95-102. [Google Scholar] [CrossRef] [PubMed]
[14] Mohan, A., Arora, S., Uniyal, A., Poulose, R., Luthra, K., Pandey, R., et al. (2017) Evaluation of Plasma Leptin, Tumor Necrosis Factor-Α, and Prealbumin as Prognostic Biomarkers during Clinical Recovery from Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Lung India, 34, 3-8. [Google Scholar] [CrossRef] [PubMed]
[15] Celli, B.R., Anderson, J.A., Brook, R., Calverley, P., Cowans, N.J., Crim, C., et al. (2019) Serum Biomarkers and Outcomes in Patients with Moderate COPD: A Substudy of the Randomised SUMMIT Trial. BMJ Open Respiratory Research, 6, e000431. [Google Scholar] [CrossRef] [PubMed]
[16] Duvoix, A., Dickens, J., Haq, I., Mannino, D., Miller, B., Tal-Singer, R., et al. (2012) Blood Fibrinogen as a Biomarker of Chronic Obstructive Pulmonary Disease: Table 1. Thorax, 68, 670-676. [Google Scholar] [CrossRef] [PubMed]
[17] Sun, W., Cao, Z., Ma, Y., Wang, J., Zhang, L. and Luo, Z. (2022) Fibrinogen, a Promising Marker to Evaluate Severity and Prognosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Retrospective Observational Study. International Journal of Chronic Obstructive Pulmonary Disease, 17, 1299-1310. [Google Scholar] [CrossRef
[18] Mohan, M., Parthasarathi, A., S K, C., Biligere Siddaiah, J. and Mahesh, P.A. (2021) Fibrinogen: A Feasible Biomarker in Identifying the Severity and Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Cureus, 13, e16864. [Google Scholar] [CrossRef] [PubMed]
[19] Zhou, B., Liu, S., He, D., Wang, K., Wang, Y., Yang, T., et al. (2020) Fibrinogen Is a Promising Biomarker for Chronic Obstructive Pulmonary Disease: Evidence from a Meta-Analysis. Bioscience Reports, 40, BSR20193542. [Google Scholar] [CrossRef] [PubMed]
[20] Chen, L., Xu, W., Chen, J., Zhang, H., Huang, X., Ma, L., et al. (2023) Evaluating the Clinical Role of Fibrinogen, D-Dimer, Mean Platelet Volume in Patients with Acute Exacerbation of COPD. Heart & Lung, 57, 54-58. [Google Scholar] [CrossRef] [PubMed]
[21] Lazovic, B. (2012) Correlation of CRP and Serum Level of Fibrinogen with Severity of Disease in Chronic Obstructive Pulmonary Disease Patients. Medical Archives, 66, 159-160. [Google Scholar] [CrossRef] [PubMed]
[22] Fruchter, O., Yigla, M. and Kramer, M.R. (2015) D-Dimer as a Prognostic Biomarker for Mortality in Chronic Obstructive Pulmonary Disease Exacerbation. The American Journal of the Medical Sciences, 349, 29-35. [Google Scholar] [CrossRef] [PubMed]
[23] Liu, B.H., Sun, M.X., Zhou, N., et al. (2016) Detection and Study of Plasma D-Dimer Change in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Journal of Biological Regulators and Homeostatic Agents, 30, 839-845.
[24] Zhang, M., Zhang, J., Zhang, Q., Yang, X., Shan, H., Ming, Z., et al. (2016) D-Dimer as a Potential Biomarker for the Progression of COPD. Clinica Chimica Acta, 455, 55-59. [Google Scholar] [CrossRef] [PubMed]
[25] Hu, G., Wu, Y., Zhou, Y., Wu, Z., Wei, L., Li, Y., et al. (2016) Prognostic Role of D-Dimer for In-Hospital and 1-Year Mortality in Exacerbations of COPD. International Journal of Chronic Obstructive Pulmonary Disease, 11, 2729-2736. [Google Scholar] [CrossRef
[26] Zhang, Q., Liu, J., Bai, J., Wang, J., Fu, A., Liu, R., et al. (2023) D-Dimer and Procalcitonin Improve the Sensitivity of BAP-65 Score in Predicting AECOPD Patients Admission to ICU. Clinical Laboratory, 69, 238-245. [Google Scholar] [CrossRef] [PubMed]
[27] Husebø, G.R., Gabazza, E.C., D’Alessandro Gabazza, C., Yasuma, T., Toda, M., Aanerud, M., et al. (2020) Coagulation Markers as Predictors for Clinical Events in COPD. Respirology, 26, 342-351. [Google Scholar] [CrossRef] [PubMed]
[28] Zhang, M., Li, Y., Yang, X., Shan, H., Zhang, Q., Ming, Z., et al. (2015) Serum Cystatin C as an Inflammatory Marker in Exacerbated and Convalescent COPD Patients. Inflammation, 39, 625-631. [Google Scholar] [CrossRef] [PubMed]
[29] Zhang, Y., Zhu, Y., Wu, Y., et al. (2014) Serum Cystatin C as a Potential Biomarker for the Evaluation COPD. International Journal of Clinical and Experimental Medicine, 7, 5484-5490.
[30] Chai, L., Feng, W., Zhai, C., Shi, W., Wang, J., Yan, X., et al. (2020) The Association between Cystatin C and COPD: A Meta-Analysis and Systematic Review. BMC Pulmonary Medicine, 20, Article No. 182. [Google Scholar] [CrossRef] [PubMed]
[31] Telo, S., Kuluöztürk, M., Deveci, F., Kırkıl, G., Öner, Ö. and Kaman, D. (2018) Serum Cystatin C Levels in COPD: Potential Diagnostic Value and Relation between Respiratory Functions. Journal of Medical Biochemistry, 37, 434-440. [Google Scholar] [CrossRef] [PubMed]
[32] Hu, G., Wu, Y., Zhou, Y., Yu, Y., Liang, W. and Ran, P. (2016) Cystatin C as a Predictor of In-Hospital Mortality after Exacerbation of COPD. Respiratory Care, 61, 950-957. [Google Scholar] [CrossRef] [PubMed]
[33] Papaporfyriou, A., Bakakos, P., Hillas, G., Papaioannou, A.I. and Loukides, S. (2021) Blood Eosinophils in COPD: Friend or Foe? Expert Review of Respiratory Medicine, 16, 35-41. [Google Scholar] [CrossRef] [PubMed]
[34] Zeiger, R.S., Tran, T.N., Butler, R.K., Schatz, M., Li, Q., Khatry, D.B., et al. (2018) Relationship of Blood Eosinophil Count to Exacerbations in Chronic Obstructive Pulmonary Disease. The Journal of Allergy and Clinical Immunology: In Practice, 6, 944-954.e5. [Google Scholar] [CrossRef] [PubMed]
[35] Tashkin, D.P. and Wechsler, M.E. (2018) Role of Eosinophils in Airway Inflammation of Chronic Obstructive Pulmonary Disease. International Journal of Chronic Obstructive Pulmonary Disease, 13, 335-349. [Google Scholar] [CrossRef
[36] Kang, H.S., Kim, S.K., Kim, Y.H., Kim, J.W., Lee, S.H., Yoon, H.K., et al. (2021) The Association between Eosinophilic Exacerbation and Eosinophilic Levels in Stable COPD. BMC Pulmonary Medicine, 21, Article No. 74. [Google Scholar] [CrossRef] [PubMed]
[37] MacDonald, M.I., Osadnik, C.R., Bulfin, L., Hamza, K., Leong, P., Wong, A., et al. (2019) Low and High Blood Eosinophil Counts as Biomarkers in Hospitalized Acute Exacerbations of COPD. Chest, 156, 92-100. [Google Scholar] [CrossRef] [PubMed]
[38] Citgez, E., van der Palen, J., van der Valk, P., Kerstjens, H.A.M. and Brusse-Keizer, M. (2021) Stability in Eosinophil Categorisation during Subsequent Severe Exacerbations of COPD. BMJ Open Respiratory Research, 8, e000960. [Google Scholar] [CrossRef] [PubMed]
[39] Gueçamburu, M. and Zysman, M. (2022) BPCO et éosinophiles. Revue des Maladies Respiratoires, 39, 685-697. [Google Scholar] [CrossRef] [PubMed]
[40] Han, Z., Hu, H., Yang, P., Li, B., Liu, G., Pang, J., et al. (2022) White Blood Cell Count and Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study. Computers in Biology and Medicine, 151, Article ID: 106187. [Google Scholar] [CrossRef] [PubMed]
[41] Zinellu, A., Zinellu, E., Pau, M.C., Carru, C., Pirina, P., Fois, A.G., et al. (2022) A Comprehensive Systematic Review and Meta-Analysis of the Association between the Neutrophil-to-Lymphocyte Ratio and Adverse Outcomes in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Journal of Clinical Medicine, 11, Article No. 3365. [Google Scholar] [CrossRef] [PubMed]
[42] Lan, C., Su, W., Yang, M., Chen, S. and Wu, Y. (2023) Predictive Role of Neutrophil‐Percentage‐to‐Albumin, Neutrophil‐to‐Lymphocyte and Eosinophil‐to‐Lymphocyte Ratios for Mortality in Patients with COPD: Evidence from NHANES 2011-2018. Respirology, 28, 1136-1146. [Google Scholar] [CrossRef] [PubMed]
[43] Emami Ardestani, M. and Alavi‐Naeini, N. (2020) Evaluation of the Relationship of Neutrophil‐to-Lymphocyte Ratio and Platelet‐to‐Lymphocyte Ratio with In‐Hospital Mortality in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. The Clinical Respiratory Journal, 15, 382-388. [Google Scholar] [CrossRef] [PubMed]
[44] Singh, B., Dutta, V., Singh, S. and Pundit, P. (2024) Diagnostic Insights from Chemometric Analysis of Hemogram Inflammatory Indexes in Male Smokers with and without Asthma or Chronic Obstructive Pulmonary Disease. International Journal of Laboratory Hematology, 46, 627-636. [Google Scholar] [CrossRef] [PubMed]
[45] Gutta, L., M, S. and Ahmed, T. (2022) NLR and PLR Ratios—Accessible and Affordable Predictors of Disease Severity in COPD. Journal of the Association of Physicians of India, 70, 11-12.
[46] Sakurai, K., Chubachi, S., Irie, H., Tsutsumi, A., Kameyama, N., Kamatani, T., et al. (2018) Clinical Utility of Blood Neutrophil-Lymphocyte Ratio in Japanese COPD Patients. BMC Pulmonary Medicine, 18, Article No. 65. [Google Scholar] [CrossRef] [PubMed]
[47] Ellingsen, J., Janson, C., Bröms, K., Lisspers, K., Ställberg, B., Högman, M., et al. (2021) Neutrophil-to-Lymphocyte Ratio, Blood Eosinophils and COPD Exacerbations: A Cohort Study. ERJ Open Research, 7, Article ID: 00471-2021. [Google Scholar] [CrossRef] [PubMed]
[48] El-Gazzar, A.G., Kamel, M.H., Elbahnasy, O.K.M. and El-Naggar, M.E. (2019) Prognostic Value of Platelet and Neutrophil to Lymphocyte Ratio in COPD Patients. Expert Review of Respiratory Medicine, 14, 111-116. [Google Scholar] [CrossRef] [PubMed]
[49] Shao, S., Zhang, Z., Feng, L., Liang, L. and Tong, Z. (2023) Association of Blood Inflammatory Biomarkers with Clinical Outcomes in Patients with AECOPD: An 8-Year Retrospective Study in Beijing. International Journal of Chronic Obstructive Pulmonary Disease, 18, 1783-1802. [Google Scholar] [CrossRef
[50] Alupo, P., Katagira, W., Mukunya, D., et al. (2024) The Neutrophil-to-Lymphocyte Ratio as a Predictor of Acute Exacerbations among Patients with COPD in Uganda. Chronic Obstructive Pulmonary Disease, 11, 187-195.
[51] Gómez-Rosero, J.A., Cáceres-Galvis, C., Ascuntar, J., Atencia, C., Vallejo, C.E. and Jaimes, F. (2021) Biomarkers as a Prognostic Factor in COPD Exacerbation: A Cohort Study. COPD: Journal of Chronic Obstructive Pulmonary Disease, 18, 325-332. [Google Scholar] [CrossRef] [PubMed]