慢性阻塞性肺疾病急性加重的发病机制与生物标志物研究新进展
Recent Advances in the Pathogenesis and Biomarker Research of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
摘要: 慢性阻塞性肺疾病急性加重(Acute Exacerbation of Chronic Obstructive Pulmonary Disease, AECOPD)是驱动慢性阻塞性肺疾病(Chronic Obstructive Pulmonary Disease, COPD)患者疾病进展、住院及死亡的关键事件，其发病机制复杂且异质性强。既往研究多将呼吸道感染视为AECOPD的核心诱因，而近年研究证实，AECOPD发病为多因素、多通路协同调控的复杂病理过程。本文系统综述了AECOPD多维度发病机制的新进展，包括病原微生物感染的触发作用，固有与适应性免疫失调及炎症信号通路的异常激活，以及细胞代谢重编程对炎症与免疫应答的调控。在此基础上，本文进一步总结了对应上述机制的潜在生物标志物，涵盖感染相关指标、免疫炎症分子、信号通路相关分子及代谢产物，并探讨了多指标联合及组学策略在AECOPD精准分型、早期识别及个体化治疗中的临床应用前景。本综述旨在完善AECOPD的发病机制理论体系，为构建精准化生物标志物评估模型、推动AECOPD个体化精准诊疗、改善患者远期预后提供最新的理论参考与研究方向。
Abstract: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a critical event driving disease progression, hospitalization, and mortality in patients with COPD, with complex and highly heterogeneous pathophysiology. Previous studies have predominantly regarded respiratory tract infection as the core trigger of AECOPD; however, emerging evidence has confirmed that AECOPD arises from a complex pathological process involving the synergistic regulation of multiple factors and pathways. This review systematically summarizes recent advances in the multidimensional mechanisms of AECOPD from three aspects: the triggering role of pathogenic infections, dysregulation of innate and adaptive immunity alongside aberrant activation of inflammatory signaling pathways, and the interplay between cellular metabolic reprogramming and inflammatory immune responses. Correspondingly, we discuss potential mechanism-based biomarkers, encompassing infection-related indicators, immuno-inflammatory molecules, signaling pathway-associated molecules, and metabolic products, and further explore the clinical application prospects of multi-marker panels and omics-based strategies for precise phenotyping, early recognition, and individualized therapy in AECOPD. This review aims to refine the theoretical framework of AECOPD pathogenesis, provide updated theoretical references and research directions for constructing precision biomarker assessment models, promoting individualized precision diagnosis and treatment of AECOPD, and improving long-term patient outcomes.
文章引用：王素珍, 陈国峰. 慢性阻塞性肺疾病急性加重的发病机制与生物标志物研究新进展[J]. 临床医学进展, 2026, 16(9): 884-897. https://doi.org/10.12677/acm.2026.1693117

参考文献

[1] 刘升明. 《GOLD 2026报告》关于慢性阻塞性肺疾病诊断、治疗、管理及预防全球策略更新要点解读[J]. 实用医学杂志, 2026, 42(4): 541-550.
[2] Naghavi, M., Kyu, H.H., A, B., Aalipour, M.A., Aalruz, H., Ababneh, H.S., et al. (2025) Global Burden of 292 Causes of Death in 204 Countries and Territories and 660 Subnational Locations, 1990-2023: A Systematic Analysis for the Global Burden of Disease Study 2023. The Lancet, 406, 1811-1872.
https://doi.org/10.1016/s0140-6736(25)01917-8
[3] Qian, Y., Cai, C., Sun, M., Lv, D. and Zhao, Y. (2023) Analyses of Factors Associated with Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Review. International Journal of Chronic Obstructive Pulmonary Disease, 18, 2707-2723.
https://doi.org/10.2147/copd.s433183
[4] Ritchie, A.I. and Wedzicha, J.A. (2020) Definition, Causes, Pathogenesis, and Consequences of Chronic Obstructive Pulmonary Disease Exacerbations. Clinics in Chest Medicine, 41, 421-438.
https://doi.org/10.1016/j.ccm.2020.06.007
[5] Wu, L., Zhang, E., Tu, Y., Chen, Y., Wang, C., Ren, Y., et al. (2025) Inherent Immunity and Adaptive Immunity: Mechanism and Role in AECOPD. Innate Immunity, 31.
https://doi.org/10.1177/17534259251322612
[6] Marriott, E., Singanayagam, A. and El-Awaisi, J. (2024) Inflammation as the Nexus: Exploring the Link between Acute Myocardial Infarction and Chronic Obstructive Pulmonary Disease. Frontiers in Cardiovascular Medicine, 11, Article ID: 1362564.
https://doi.org/10.3389/fcvm.2024.1362564
[7] Liu, J., Ran, Z., Wang, F., Xin, C., Xiong, B. and Song, Z. (2020) Role of Pulmonary Microorganisms in the Development of Chronic Obstructive Pulmonary Disease. Critical Reviews in Microbiology, 47, 1-12.
https://doi.org/10.1080/1040841x.2020.1830748
[8] Wu, X., Li, R.F., Lin, Z.S., Xiao, C., Liu, B., Mai, K., et al. (2023) Coinfection with Influenza Virus and Non-Typeable Haemophilus Influenzae Aggregates Inflammatory Lung Injury and Alters Gut Microbiota in COPD Mice. Frontiers in Microbiology, 14, Article ID: 1137369.
https://doi.org/10.3389/fmicb.2023.1137369
[9] Xu, M.M., Kang, J.Y., Wang, Q., Zuo, X., Tan, Y., Wei, Y., et al. (2024) Melatonin Improves Influenza Virus Infection-Induced Acute Exacerbation of COPD by Suppressing Macrophage M1 Polarization and Apoptosis. Respiratory Research, 25, Article No. 186.
https://doi.org/10.1186/s12931-024-02815-0
[10] Tu, Y., Chen, Y., Li, X., Wang, Y., Fang, B., Ren, Y., et al. (2025) Advances in Acute COPD Exacerbation: Clarifying Specific Immune Mechanisms of Infectious and Noninfectious Factors. Therapeutic Advances in Respiratory Disease, 19.
https://doi.org/10.1177/17534666241308408
[11] Moghoofei, M., Azimzadeh Jamalkandi, S., Moein, M., Salimian, J. and Ahmadi, A. (2020) Bacterial Infections in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis. Infection, 48, 19-35.
https://doi.org/10.1007/s15010-019-01350-1
[12] Salama, K.S., Moazen, E.M., Elsawy, S.B., Kotb, S.F., Mohammed, E.M., Tahoun, S.A., et al. (2023) Bacterial Species and Inflammatory Cell Variability in Respiratory Tracts of Patients with Chronic Obstructive Pulmonary Disease Exacerbation: A Multicentric Study. Infection and Drug Resistance, 16, 2107-2115.
https://doi.org/10.2147/idr.s402828
[13] Bhatt, S.P., Agusti, A., Bafadhel, M., Christenson, S.A., Bon, J., Donaldson, G.C., et al. (2023) Phenotypes, Etiotypes, and Endotypes of Exacerbations of Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine, 208, 1026-1041.
https://doi.org/10.1164/rccm.202209-1748so
[14] Daubin, C., Fournel, F., Thiollière, F., Daviaud, F., Ramakers, M., Polito, A., et al. (2021) Ability of Procalcitonin to Distinguish between Bacterial and Nonbacterial Infection in Severe Acute Exacerbation of Chronic Obstructive Pulmonary Syndrome in the ICU. Annals of Intensive Care, 11, Article No. 39.
https://doi.org/10.1186/s13613-021-00816-6
[15] Yu, S., Zhang, H., Wan, L., Xue, M., Zhang, Y. and Gao, X. (2023) The Association between the Respiratory Tract Microbiome and Clinical Outcomes in Patients with COPD. Microbiological Research, 266, Article ID: 127244.
https://doi.org/10.1016/j.micres.2022.127244
[16] Madapoosi, S.S., Cruickshank-Quinn, C., Opron, K., Erb-Downward, J.R., Begley, L.A., Li, G., et al. (2022) Lung Microbiota and Metabolites Collectively Associate with Clinical Outcomes in Milder Stage Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine, 206, 427-439.
https://doi.org/10.1164/rccm.202110-2241oc
[17] Su, L., Qiao, Y., Luo, J., Huang, R., Li, Z., Zhang, H., et al. (2022) Characteristics of the Sputum Microbiome in COPD Exacerbations and Correlations between Clinical Indices. Journal of Translational Medicine, 20, 76-86.
https://doi.org/10.1186/s12967-022-03278-x
[18] Xue, Q., Xie, Y., He, Y., Yu, Y., Fang, G., Yu, W., et al. (2023) Lung Microbiome and Cytokine Profiles in Different Disease States of COPD: A Cohort Study. Scientific Reports, 13, Article No. 5715.
https://doi.org/10.1038/s41598-023-32901-0
[19] Xiao, W., Chen, Y., Du, L., Wu, J., Wang, Z., Mao, B., et al. (2024) Bacterial Interactome Disturbance in Chronic Obstructive Pulmonary Disease Clinical Stability and Exacerbations. Respiratory Research, 25, Article No. 173.
https://doi.org/10.1186/s12931-024-02802-5
[20] An, Y., Xu, M., Kang, Y., Fang, J. and Zhang, X. (2025) Tripartite Exacerbation Stratification in AECOPD Suggests a Gradient of Lower Airway Dysbiosis: A Metagenomic Transition from Commensal Taxa to Pseudomonadota Dominance. Frontiers in Microbiology, 16, Article ID: 1588029.
https://doi.org/10.3389/fmicb.2025.1588029
[21] Pragman, A.A., Hodgson, S.W., Wu, T., Zank, A., Reilly, C.S. and Wendt, C.H. (2024) Sputum Microbiome α-Diversity Is a Key Feature of the COPD Frequent Exacerbator Phenotype. ERJ Open Research, 10, Article ID: 00595-2023.
https://doi.org/10.1183/23120541.00595-2023
[22] Xie, S., Wang, K., Zhang, W., Xiao, K., Yan, P., Li, Y., et al. (2018) Immunodeficiency in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Inflammation, 41, 1582-1589.
https://doi.org/10.1007/s10753-018-0830-7
[23] Ge, L., Wang, N., Chen, Z., Xu, S. and Zhou, L. (2024) Expression of Siglec-9 in Peripheral Blood Neutrophils Was Increased and Associated with Disease Severity in Patients with AECOPD. Cytokine, 177, Article ID: 156558.
https://doi.org/10.1016/j.cyto.2024.156558
[24] Xiong, X., Zhu, M., Wu, H., Wu, Z., Fan, L. and Cheng, D. (2025) T-Cell Immune Status in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Case-Control Study. Frontiers in Medicine, 12, Article ID: 685400.
https://doi.org/10.3389/fmed.2025.1433844
[25] Xue, W., Ma, J., Li, Y. and Xie, C. (2022) Role of CD4+ T and CD8+ T Lymphocytes-Mediated Cellular Immunity in Pathogenesis of Chronic Obstructive Pulmonary Disease. Journal of Immunology Research, 2022, Article ID: 1429213.
https://doi.org/10.1155/2022/1429213
[26] Jiang, M., Cai, R., Wang, J., Li, Z., Xu, D., Jing, J., et al. (2021) ILC2 Cells Promote Th2 Cell Differentiation in AECOPD through Activated Notch-GATA3 Signaling Pathway. Frontiers in Immunology, 12, Article ID: 685400.
https://doi.org/10.3389/fimmu.2021.685400
[27] Xiong, X., Zhu, M., Wu, H., Fan, L. and Cheng, D. (2022) Immunophenotype in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study. Respiratory Research, 23, 137-147.
https://doi.org/10.1186/s12931-022-02058-x
[28] Miralles, C., Miñana, M.D., Nieto, M.L., del Carmen Aguar, M., Domínguez-Márquez, V. and Soler-Cataluña, J.J. (2026) Inflammatory Phenotype Drives Different Immunosuppressive Response in COPD Exacerbations. BMC Pulmonary Medicine, 26, Article No. 86.
https://doi.org/10.1186/s12890-025-04020-1
[29] Ditz, B., Kistemaker, L., van den Berge, M., Vonk, J., Gosens, R. and Kerstjens, H. (2021) Responsivity and Reproducibility of Sputum Inflammatory Biomarkers during COPD Exacerbation and Stable Phases—A Pilot Study. International Journal of Chronic Obstructive Pulmonary Disease, 16, 3055-3064.
https://doi.org/10.2147/copd.s326081
[30] Barta, I., Paska, C. and Antus, B. (2022) Sputum Cytokine Profiling in COPD: Comparison between Stable Disease and Exacerbation. International Journal of Chronic Obstructive Pulmonary Disease, 17, 1897-1908.
https://doi.org/10.2147/copd.s364982
[31] Ji, S., Dai, M., Huang, Y., Ren, X., Jiang, M., Qiao, J., et al. (2022) Influenza a Virus Triggers Acute Exacerbation of Chronic Obstructive Pulmonary Disease by Increasing Proinflammatory Cytokines Secretion via NLRP3 Inflammasome Activation. Journal of Inflammation, 19, Article No. 8.
https://doi.org/10.1186/s12950-022-00305-y
[32] Ji, S., Bai, Q., Wu, X., Zhang, D., Wang, S., Shen, J., et al. (2020) Unique Synergistic Antiviral Effects of Shufeng Jiedu Capsule and Oseltamivir in Influenza a Viral-Induced Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Biomedicine & Pharmacotherapy, 121, Article ID: 109652.
https://doi.org/10.1016/j.biopha.2019.109652
[33] Reimer, J., Page, J., Saha, P., Shen, S., Zhu, X., Qian, S., et al. (2025) Leveraging Dynamic Stability to Infer Regulation in Protein-Protein Interaction Networks: A Study of Infectious Vulnerability in COPD. PLOS ONE, 20, e0326062.
https://doi.org/10.1371/journal.pone.0326062
[34] Cardenas, V.J., Seashore, J.B., Tapryal, N., Ameri, M., Rivera, R., Sharma, K., et al. (2025) Low Levels of DNA Repair Enzyme NEIL2 May Exacerbate Inflammation and Genomic Damage in Subjects with Stable COPD and during Severe Exacerbations. Respiratory Research, 26, Article No. 165.
https://doi.org/10.1186/s12931-025-03251-4
[35] Fan, X., Gao, Y., Hua, C., Peng, L. and Ci, X. (2023) Daphnetin Ameliorates PM2.5-Induced Airway Inflammation by Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis in CS-Exposed Mice. Biomedicine & Pharmacotherapy, 165, Article ID: 115047.
https://doi.org/10.1016/j.biopha.2023.115047
[36] Xiao, C., Cheng, S., Li, R., Wang, Y., Zeng, D., Jiang, H., et al. (2021) Isoforskolin Alleviates AECOPD by Improving Pulmonary Function and Attenuating Inflammation Which Involves Downregulation of Th17/IL-17A and NF-κB/NLRP3. Frontiers in Pharmacology, 12, Article ID: 721273.
https://doi.org/10.3389/fphar.2021.721273
[37] Yu, Y., Miao, T., Xiao, W., Mao, B., Du, L., Wang, Y., et al. (2024) Andrographolide Attenuates NLRP3 Inflammasome Activation and Airway Inflammation in Exacerbation of Chronic Obstructive Pulmonary Disease. Drug Design, Development and Therapy, 18, 1755-1770.
https://doi.org/10.2147/dddt.s445788
[38] Li, R., Deng, H., Han, Y., Tong, Y., Hou, Y., Huang, T., et al. (2024) Therapeutic Effects of Lianhua Qingke on COPD and Influenza Virus-Induced Exacerbation of COPD Are Associated with the Inhibition of NF-κB Signaling and NLRP3 Inflammasome Responses. International Immunopharmacology, 142, Article ID: 113213.
https://doi.org/10.1016/j.intimp.2024.113213
[39] Ou, G., Zhu, M., Huang, Y., Luo, W., Zhao, J., Zhang, W., et al. (2022) HSP60 Regulates the Cigarette Smoke-Induced Activation of TLR4-NF-κB-MyD88 Signalling Pathway and NLRP3 Inflammasome. International Immunopharmacology, 103, Article ID: 108445.
https://doi.org/10.1016/j.intimp.2021.108445
[40] Jiang, J., Chen, S., Li, H., Xie, Q. and Yang, Y. (2021) TLR3 Inhibitor and Tyrosine Kinase Inhibitor Attenuate Cigarette Smoke/Poly I:C-Induced Airway Inflammation and Remodeling by the EGFR/TLR3/MAPK Signaling Pathway. European Journal of Pharmacology, 890, Article ID: 173654.
https://doi.org/10.1016/j.ejphar.2020.173654
[41] Tao, L., Lu, X., Fu, Z., Tian, Y., Liu, X., Li, J., et al. (2023) Tong Sai Granule Improves AECOPD via Regulation of MAPK-SIRT1-NF-κB Pathway and Cellular Senescence Alleviation. Journal of Ethnopharmacology, 314, Article ID: 116622.
https://doi.org/10.1016/j.jep.2023.116622
[42] Liu, X., Zhang, H., Si, Y., Du, Y., Wu, J. and Li, J. (2022) High-Coverage Lipidomics Analysis Reveals Biomarkers for Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Journal of Chromatography B, 1201, Article ID: 123278.
https://doi.org/10.1016/j.jchromb.2022.123278
[43] Gai, X., Guo, C., Zhang, L., Zhang, L., Abulikemu, M., Wang, J., et al. (2021) Serum Glycerophospholipid Profile in Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Frontiers in Physiology, 12, Article ID: 646010.
https://doi.org/10.3389/fphys.2021.646010
[44] Arshad, H., Siokis, A., Franke, R., Habib, A., Alfonso, J.C.L., Poliakova, Y., et al. (2022) Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease. Cells, 11, Article No. 2283.
https://doi.org/10.3390/cells11152283
[45] Kim, H.Y., Lee, H.S., Kim, I.H., Kim, Y., Ji, M., Oh, S., et al. (2022) Comprehensive Targeted Metabolomic Study in the Lung, Plasma, and Urine of PPE/LPS-Induced COPD Mice Model. International Journal of Molecular Sciences, 23, Article No. 2748.
https://doi.org/10.3390/ijms23052748
[46] Wei, Y.Y., Ye, J.J., Zhang, D.W., Hu, L., Wu, H. and Fei, G. (2024) Melatonin Rescues Influenza a Virus-Induced Cellular Energy Exhaustion via OMA1‐OPA1‐S in Acute Exacerbation of COPD. Journal of Pineal Research, 76, e12991.
https://doi.org/10.1111/jpi.12991
[47] Cazzola, M., Page, C.P., Wedzicha, J.A., Celli, B.R., Anzueto, A. and Matera, M.G. (2023) Use of Thiols and Implications for the Use of Inhaled Corticosteroids in the Presence of Oxidative Stress in COPD. Respiratory Research, 24, Article No. 194.
https://doi.org/10.1186/s12931-023-02500-8
[48] Liu, J., Huang, J., Liu, H., Chen, C., Xu, J. and Zhong, L. (2021) Elevated Serum 4HNE plus Decreased Serum Thioredoxin: Unique Feature and Implications for Acute Exacerbation of Chronic Obstructive Pulmonary Disease. PLOS ONE, 16, e0245810.
https://doi.org/10.1371/journal.pone.0245810
[49] Zhang, C., Su, D., Wang, X., Cao, P., Li, M. and Fu, L. (2025) Plasma 4-Hydroxynonenal Estimates Severity and Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Scientific Reports, 16, Article No. 758.
https://doi.org/10.1038/s41598-025-30368-9
[50] Roca, C., Hemphill, C.C., Speen, A.M., Jaspers, I., Wolfgang, M.C. and Drummond, M.B. (2026) Dysbiosis of the Nasal Microbiome Is Associated with Prospective Acute Exacerbation of COPD. Microbiome, 14, Article No. 120.
https://doi.org/10.1186/s40168-026-02357-1
[51] Pázmány, P., Soós, A., Hegyi, P., Dohos, D., Kiss, S., Szakács, Z., et al. (2021) Inflammatory Biomarkers Are Inaccurate Indicators of Bacterial Infection on Admission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease—A Systematic Review and Diagnostic Accuracy Network Meta-Analysis. Frontiers in Medicine, 8, Article ID: 639794.
https://doi.org/10.3389/fmed.2021.639794
[52] Ye, Y., Zhao, H., Kang, T., Zhao, L., Li, N., Chen, J., et al. (2022) Optimal Cut-Off Value of Serum Procalcitonin in Predicting Bacterial Infection Induced Acute Exacerbation in Chronic Obstructive Pulmonary Disease: A Prospective Observational Study. Chronic Respiratory Disease, 19.
https://doi.org/10.1177/14799731221108516
[53] Ruiz-González, A., Sáez-Huerta, E., Martínez-Alonso, M., Bernet-Sánchez, A. and Porcel, J.M. (2022) A Simple Scoring System to Differentiate Bacterial from Viral Infections in Acute Exacerbations of COPD Requiring Hospitalization. International Journal of Chronic Obstructive Pulmonary Disease, 17, 773-779.
https://doi.org/10.2147/copd.s356950
[54] Hsu, C.W., Suk, C.W., Hsu, Y.P., Chang, J., Liu, C., Huang, S., et al. (2022) Sphingosine-1-Phosphate and CRP as Potential Combination Biomarkers in Discrimination of COPD with Community-Acquired Pneumonia and Acute Exacerbation of COPD. Respiratory Research, 23, Article No. 63.
https://doi.org/10.1186/s12931-022-01991-1
[55] Schumann, D.M., Papakonstantinou, E., Kostikas, K., Grize, L., Tamm, M. and Stolz, D. (2023) Variability of Fractional Exhaled Nitric Oxide Is Associated with the Risk and Aetiology of COPD Exacerbations. Respirology, 28, 445-454.
https://doi.org/10.1111/resp.14439
[56] Ellingsen, J., Janson, C., Bröms, K., Hårdstedt, M., Högman, M., Lisspers, K., et al. (2024) CRP, Fibrinogen, White Blood Cells, and Blood Cell Indices as Prognostic Biomarkers of Future COPD Exacerbation Frequency: The TIE Cohort Study. Journal of Clinical Medicine, 13, Article No. 3855.
https://doi.org/10.3390/jcm13133855
[57] 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.
https://doi.org/10.1186/s12890-021-01650-z
[58] Liao, Q.Q., Mo, Y.J., Zhu, K.W., Gao, F., Huang, B., Chen, P., et al. (2024) Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), and Eosinophil-to-Lymphocyte Ratio (ELR) as Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). International Journal of Chronic Obstructive Pulmonary Disease, 19, 501-518.
https://doi.org/10.2147/copd.s447519
[59] 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.
https://doi.org/10.2147/copd.s416869
[60] Chen, X., Liu, S., Luo, Y., Wei, H., Ge, H., Liu, H., et al. (2025) Systemic Immune-Inflammation Index Is Associated with Adverse Outcomes in Patients Hospitalized for AECOPD: A Multicenter Cohort Study. Respiration, 104, 648-666.
https://doi.org/10.1159/000545267
[61] Wei, T., Wang, X., Lang, K., Chen, C., Song, Y., Luo, J., et al. (2022) Low Eosinophil Phenotype Predicts Noninvasive Mechanical Ventilation Use in Patients with Hospitalized Exacerbations of COPD. Journal of Inflammation Research, 15, 1259-1271.
https://doi.org/10.2147/jir.s343918
[62] Kwok, W.C., Tam, T.C.C., Chau, C.H., Lam, F.M. and Ho, J.C.M. (2025) Differences in Blood Eosinophil Level during Stable Disease and during Exacerbation of COPD and Exacerbation Risks. Lung, 203, Article No. 37.
https://doi.org/10.1007/s00408-025-00792-9
[63] 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.
https://doi.org/10.1590/1519-6984.231134
[64] Jung, A.L., Han, M., Griss, K., Bertrams, W., Nell, C., Greulich, T., et al. (2023) Novel Protein Biomarkers for Pneumonia and Acute Exacerbations in COPD: A Pilot Study. Frontiers in Medicine, 10, Article ID: 1180746.
https://doi.org/10.3389/fmed.2023.1180746
[65] Zhang, Y., Ren, L., Sun, J., Han, F. and Guo, X. (2021) Increased Serum Soluble Interleukin-2 Receptor Associated with Severity of Acute Exacerbation of Chronic Obstructive Pulmonary Disease. International Journal of Chronic Obstructive Pulmonary Disease, 16, 2561-2573.
https://doi.org/10.2147/copd.s321904
[66] Gu, Y., Li, P., Xiao, Y., Zhang, J. and Su, X. (2023) The Diagnostic and Assessment Value of Plasma Pentraxin 3 in Acute Exacerbation of Chronic Obstructive Pulmonary Disease. International Journal of Chronic Obstructive Pulmonary Disease, 18, 1391-1400.
https://doi.org/10.2147/copd.s402463
[67] Ma, K.S., Li, L.N., Ma, Y.C., Fan, R., Chen, G., Zhao, H., et al. (2025) Serum Osteopontin as a Prognostic Biomarker in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Frontiers in Immunology, 16, Article ID: 1708595.
https://doi.org/10.3389/fimmu.2025.1708595
[68] Wei, B., Tian, T. and Liu, Y. (2020) IL-10 Combined with NGAL Has Diagnostic Value for AECOPD Combined with AKI. International Journal of Chronic Obstructive Pulmonary Disease, 15, 637-644.
https://doi.org/10.2147/copd.s245541
[69] Zhou, J., Du, W., Huang, H., Chen, Y., Chen, L. and Zheng, M. (2025) Association of CALLY Index and CLR with COPD Risk in Middle-Aged and Older Americans: Evidence from NHANES 2017-2020. Frontiers in Medicine, 12, Article ID: 1535415.
https://doi.org/10.3389/fmed.2025.1535415
[70] Ding, Y., Liu, Y., Yu, J., Cai, C., Fu, L., Zhu, J., et al. (2025) The Association between the CALLY Index and All-Cause Mortality in Patients with COPD: Results from the Cohort Study of NHANES 2007-2010. International Journal of Chronic Obstructive Pulmonary Disease, 20, 159-169.
https://doi.org/10.2147/copd.s485036
[71] Jung, A.L., Møller Jørgensen, M., Bæk, R., Griss, K., Han, M., Auf Dem Brinke, K., et al. (2020) Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease. The Journal of Infectious Diseases, 221, 325-335.
https://doi.org/10.1093/infdis/jiz460
[72] Wang, F., Yang, B., Qiao, J., Bai, L., Li, Z., Sun, W., et al. (2023) Serum Exosomal microRNA-1258 May as a Novel Biomarker for the Diagnosis of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Scientific Reports, 13, Article No. 18332.
https://doi.org/10.1038/s41598-023-45592-4
[73] Kim, S.H., Ahn, H.S., Park, J.S., Yeom, J., Yu, J., Kim, K., et al. (2021) A Proteomics-Based Analysis of Blood Biomarkers for the Diagnosis of COPD Acute Exacerbation. International Journal of Chronic Obstructive Pulmonary Disease, 16, 1497-1508.
https://doi.org/10.2147/copd.s308305
[74] Bertrams, W., Wilhelm, J., Veeger, P., Hanko, C., Brinke, K.a.d., Klabunde, B., et al. (2024) A mRNA Panel for Differentiation between Acute Exacerbation or Pneumonia in COPD Patients. Frontiers in Medicine, 11, Article ID: 1234068.
https://doi.org/10.3389/fmed.2024.1234068
[75] Bertrams, W., Griss, K., Han, M., Seidel, K., Klemmer, A., Sittka-Stark, A., et al. (2020) Transcriptional Analysis Identifies Potential Biomarkers and Molecular Regulators in Pneumonia and COPD Exacerbation. Scientific Reports, 10, Article No. 241.
https://doi.org/10.1038/s41598-019-57108-0
[76] Yang, J., Zhang, Q., Zhang, J., Ouyang, Y., Sun, Z., Liu, X., et al. (2022) Exploring the Change of Host and Microorganism in Chronic Obstructive Pulmonary Disease Patients Based on Metagenomic and Metatranscriptomic Sequencing. Frontiers in Microbiology, 13, Article ID: 818281.
https://doi.org/10.3389/fmicb.2022.818281

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