KL-6对急性呼吸窘迫综合征后肺纤维化风险的预测价值

王秀军; 曾令永; 王红嫚

doi:10.16766/j.cnki.issn.1674-4152.004177

KL-6对急性呼吸窘迫综合征后肺纤维化风险的预测价值

doi: 10.16766/j.cnki.issn.1674-4152.004177

遵义医科大学第五附属(珠海)医院呼吸与危重症医学科, 广东珠海 519100

基金项目:

国家自然科学基金项目 81960023

详细信息

通讯作者:
王红嫚，E-mail：2496453591@qq.com

中图分类号: R563.8
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出版历程
- 收稿日期: 2024-09-27
- 网络出版日期: 2025-11-17

Review on the predictive value of KL-6 for the risk of pulmonary fibrosis after ARDS

Department of Respiratory and Critical Care Medicine, the Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University, Zhuhai, Guangdong 519100, China

摘要

摘要: 急性呼吸窘迫综合征(ARDS)是一种严重的呼吸衰竭，病死率较高。其分子机制复杂，常涉及肺部和全身多个系统损伤以及相互作用。ARDS的主要临床特征包括炎症反应、细胞因子大量释放和凝血途径的激活与失调。在临床上该类患者预后方面通常表现出不同程度的肺纤维化，这也是导致ARDS患者预后不良的重要因素。炎症反应在ARDS中起着重要作用，包括促炎途径的下调和抗炎途径的上调。肺纤维化是由于持续的炎症损伤及修复失调导致的胶原蛋白异常沉积，从而促进纤维化的发生。纤维化是一种病理性过程，与肺部组织的瘢痕化和纤维化有关，通常伴随炎症和损伤。研究表明，涎液化糖链抗原-6(KL-6)高分子量黏蛋白样糖蛋白与肺泡上皮损伤程度密切相关，是反映纤维化程度的敏感标志物。在ARDS患者中，KL-6被发现在ARDS及其后续肺纤维化中的水平升高，然而，KL-6的动力学和预后意义尚未得到广泛研究。本文重点探讨KL-6在ARDS后肺纤维化中的预测作用。
- 急性呼吸窘迫综合征 /
- 肺纤维化 /
- 涎液化糖链抗原-6
Abstract: Acute respiratory distress syndrome (ARDS) is a severe respiratory failure with a high degree of mortality. The molecular mechanism is complex, often involving multiple injuries in the lungs and the body and interactions. The main clinical features of ARDS include inflammatory response, massive release of cytokines and activation and dysregulation of coagulation pathways. Clinically, the convenient prognosis of such patients usually shows different degrees of pulmonary fibrosis, which is also an important factor leading to the poor prognosis of ARDS patients. Inflammatory response plays an important role in ARDS, including downregulation of the proinflammatory pathway and upregulation of anti-inflammatory pathways. Pulmonary fibrosis is the abnormal collagen deposition caused by continuous inflammatory damage and repair disorders, which promotes the occurrence of fibrosis. Fibrosis is a pathological process that is associated with scarring and fibrosis of the lung tissue, often accompanied by inflammation and injury. Studies have shown that the Krebs von den Lungen-6 (KL-6) high-molecular-weight mucin-like glycoprotein is closely related to the degree of alveolar epithelial damage and is a sensitive marker reflecting the degree of fibrosis. In ARDS patients, KL-6 was found to be elevated in ARDS and its subsequent pulmonary fibrosis, however, the kinetics and prognostic significance of KL-6 have not been extensively studied, and this paper focuses on the predictive role of KL-6 in pulmonary fibrosis after ARDS.
- Acute respiratory distress syndrome /
- Pulmonary fibrosis /
- Krebs von den Lungen-6

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参考文献(48)

[1]	MEYER N J, GATTINONI L, CALFEE C S. Acute respiratory distress syndrome[J]. Lancet, 2021, 398(10300): 622-637. doi: 10.1016/S0140-6736(21)00439-6
[2]	BOS L D J, WARE L B. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes[J]. Lancet, 2022, 400(10358): 1145-1156. doi: 10.1016/S0140-6736(22)01485-4
[3]	ZHANG T, SHEN P, DUAN C, et al. KL-6 as an immunological biomarker predicts the severity, progression, acute exacerbation, and poor outcomes of interstitial lung disease: a systematic review and meta-analysis[J]. Front Immunol, 2021, 12: 745233. DOI: 10.3389/fimmu.2021.745233.
[4]	HE J, ZHANG J, REN X. Krebs von den lungen-6 as a clinical marker for hypersensitivity pneumonitis: a meta-analysis and bioinformatics analysis[J]. Frontiers in Immunology, 2022, 13: 1041098. DOI: 10.3389/fimmu.
[5]	HE Y Q, ZHOU C C, YU L Y, et al. Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms[J]. Pharmacol Res, 2021, 163: 105224. DOI: 10.1016/j.phrs.2020.105224.
[6]	YE C, XU B, YANG J, et al. Mucin1 relieves acute lung injury by inhibiting inflammation and oxidative stress[J]. Eur J Histochem, 2021, 65(4): 3331. DOI: 10.4081/ejh.2021.3331.
[7]	XIE R, TAN D, LIU B, et al. Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies[J]. MedComm, 2025, 6(2): e70074. DOI: 10.1002/mco2.70074.
[8]	唐敏, 李娜. 急性呼吸窘迫综合征发病机制及相关生物标志物的研究进展[J]. 中国现代医学杂志, 2022, 32(5): 1-6. TANG M, LI N. Pathophysiological mechanism of acute respiratory distress syndrome and research progress on diagnostic biomarkers of ARDS[J]. China Journal of Modern Medicine, 2022, 32(5): 1-6.
[9]	YU H, LIU S, WANG S, et al. The involvement of HDAC3 in the pathogenesis of lung injury and pulmonary fibrosis[J]. Front Immunol, 2024, 15: 1392145. DOI: 10.3389/fimmu.2024.1392145.
[10]	FANG X Z, LI M, WANG Y X, et al. Mechanosensitive ion channel Piezo1 mediates mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis[J]. J Adv Res, 2023, 53: 175-186. doi: 10.1016/j.jare.2022.12.006
[11]	PIAZZA O, SCARPATI G, BOCCIA G, et al. KL-6 in ARDS and COVID-19 patients[J]. Transl Med UniSa, 2022, 24(2): 12-15.
[12]	GRASSELLI G, CALFEE C S, CAMPOROTA L, et al. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies[J]. Intensive Care Med, 2023, 49(7): 727-759. doi: 10.1007/s00134-023-07050-7
[13]	MOKRÁ D. Acute lung injury: from pathophysiology to treatment[J]. Physiol Res, 2020, 69(Suppl 3): S353-S366.
[14]	谢仁雪, 李有霞, 秘乐, 等. HMGB1及相关信号通路在急性呼吸窘迫综合征后肺纤维化中的研究进展[J]. 重庆医学, 2023, 52(11): 1748-1752, 1760. XIE R X, LI Y X, MI L, et al. Research progress of HMGB1 and its signaling pathway in the pulmonary fibrosis after acute respiratory distress syndrome[J]. Chongqing Medicine, 2023, 52(11): 1748-1752, 1760.
[15]	BATTAGLINI D, FAZZINI B, SILVA P L, et al. Challenges in ARDS definition, management, and identification of effective personalized therapies[J]. J Clin Med, 2023, 12(4): 1381. DOI: 10.3390/jcm12041381.
[16]	BHARAT A, HOETZENECKER K. Lung transplantation for acute respiratory distress syndrome[J]. Thorac Surg Clin, 2022, 32(2): 135-142. doi: 10.1016/j.thorsurg.2022.01.005
[17]	KOHNO N, AKIYAMA M, KYOIZUMI S, et al. Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma[J]. Jpn J Clin Oncol, 1988, 18(3): 203-216.
[18]	INAGAKI Y, XU H, NAKATA M, et al. Clinicopathology of sialomucin: MUC1, particularly KL-6 mucin, in gastrointestinal, hepatic and pancreatic cancers[J]. Biosci Trends, 2009, 3(6): 220-232.
[19]	D'ALESSANDRO M, BERGANTINI L, CAMELI P, et al. Krebs von den Lungen-6 as a biomarker for disease severity assessment in interstitial lung disease: a comprehensive review[J]. Biomark Med, 2020, 14(8): 665-674. doi: 10.2217/bmm-2019-0545
[20]	KOHNO N, INOUE Y, HAMADA H, et al. Difference in sero-diagnostic values among KL-6-associated mucins classified as cluster 9[J]. Int J Cancer Suppl, 1994, 8: 81-83.
[21]	WANG Y, CHEN S, LIN Z, et al. Imaging and serum biomarkers in connective tissue disease-associated interstitial lung diseases: correlation between lung ultrasound B-lines and KL-6 levels[J]. Ann Rheum Dis, 2019, 78(4): 573-575. doi: 10.1136/annrheumdis-2018-214098
[22]	MOSTAFA A I, SALEM A E, AHMED H A M, et al. Role of Krebs von den Lungen-6 (KL-6) in assessing hypersensitivity pneumonitis[J]. Tuberc Respir Dis(Seoul), 2021, 84(3): 200-208. doi: 10.4046/trd.2020.0122
[23]	D'ALESSANDRO M, GANGI S, PAGGI I, et al. Diagnostic performance of CLEIA versus FEIA for KL-6 peripheral and alveolar concentrations in fibrotic interstitial lung diseases: a multicentre study[J]. J Clin Lab Anal, 2024, 38(19-20): e25108. DOI: 10.1002/jcla.25108.
[24]	JI Y, BOURKE S J, SPEARS M, et al. Krebs von den Lungen-6 (KL-6) is a pathophysiological biomarker of early-stage acute hypersensitivity pneumonitis among pigeon fanciers[J]. Clin Exp Allergy, 2020, 50(12): 1391-1399. doi: 10.1111/cea.13744
[25]	WANG C, WANG Q, LIU T, et al. Krebs von den Lungen-6 (KL-6) as a diagnostic marker for pulmonary fibrosis: a systematic review and meta-analysis[J]. Clin Biochem, 2023, 114: 30-38. doi: 10.1016/j.clinbiochem.2023.01.010
[26]	JIANG D, XIAO H, DONG R, et al. Krebs von den Lungen-6 levels in untreated idiopathic pulmonary fibrosis[J]. Clin Respir J, 2022, 16(3): 234-243. doi: 10.1111/crj.13475
[27]	D'ALESSANDRO M, CONTICINI E, BERGANTINI L, et al. Krebs von den Lungen-6 as biomarker of the new progressive fibrotic phenotype of interstitial lung disease[J]. Tissue Cell, 2024, 90: 102516. DOI: 10.1016/j.tice.2024.102516.
[28]	MILLAN-BILLI P, CASTELLVÍ I, MARTINEZ-MARTINEZ L, et al. Diagnostic value of Krebs von den Lungen (KL-6) for interstitial lung disease: a European prospective cohort[J]. Arch Bronconeumol, 2024, 60(6): 350-355. doi: 10.1016/j.arbres.2024.03.028
[29]	HAN L, WANG S, MA J, et al. Expression and significance of serum KL-6 in patients with acute respiratory distress syndrome[J]. J Thorac Dis, 2023, 15(12): 6988-6995. doi: 10.21037/jtd-23-1787
[30]	BENEGAS URTEAGA M, RAMÍREZ RUZ J, SÁNCHEZ GONZÁLEZ M. Idiopathic pulmonary fibrosis[J]. Radiologia Vol, 2022, 64(3): 227-239.
[31]	D'ALESSANDRO M, BERGANTINI L, CAVALLARO D, et al. Krebs von den Lungen-6 as disease severity marker for COVID-19 patients: analytical verification and quality assessment of the Tosoh AIA-360 compared to Lumipulse G600Ⅱ[J]. Int J Environ Res Public Health, 2022, 19(4): 2176. DOI: 10.3390/ijerph19042176.
[32]	GORMAN E A, O'KANE C M, MCAULEY D F. Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management[J]. Lancet, 2022, 400(10358): 1157-1170. doi: 10.1016/S0140-6736(22)01439-8
[33]	ASCHNER Y, CORRELL K A, BEKE K M, et al. PTPα promotes fibroproliferative responses after acute lung injury[J]. Am J Physiol Lung Cell Mol Physiol, 2022, 323(1): L69-L83. doi: 10.1152/ajplung.00436.2021
[34]	RAMASAMY S, SUBBIAN S. Critical determinants of cytokine storm and type Ⅰ interferon response in COVID-19 pathogenesis[J]. Clin Microbiol Rev, 2021, 34(3): e00299-20. DOI: 10.1128/CMR.00299-20.
[35]	LAMERS M M, HAAGMANS B L. SARS-CoV-2 pathogenesis[J]. Nat Rev Microbiol, 2022, 20(5): 270-284. doi: 10.1038/s41579-022-00713-0
[36]	马刚, 冯珂, 马汉宁, 等. 方舱医院新冠肺炎普通型患者临床和CT特征与住院时间关系的研究[J]. 中华全科医学, 2021, 19(2): 316-319. doi: 10.16766/j.cnki.issn.1674-4152.001798 MA G, FENG K, MA H N, et al. A study on the relationship between clinical and CT features and length of stay of general type novel coronavirus pneumonia patients in mobile cabin hospital[J]. Chinese Journal of General Practice, 2021, 19(2): 316-319. doi: 10.16766/j.cnki.issn.1674-4152.001798
[37]	HAN X, FAN Y, ALWALID O, et al. Six-month follow-up chest CT findings after severe COVID-19 pneumonia[J]. Radiology, 2021, 299(1): E177-E186. doi: 10.1148/radiol.2021203153
[38]	MOHAMMADI A, BALAN I, YADAV S, et al. Post-COVID-19 pulmonary fibrosis[J]. Cureus, 2022, 14(3): e22770. DOI: 10.7759/cureus.22770.
[39]	KATTNER S, SUTHARSAN S, BERGER M M, et al. Serum KL-6 as a candidate predictor of outcome in patients with SARS-CoV-2 pneumonia[J]. J Clin Med, 2023, 12(21): 6772. DOI: 10.3390/jcm12216772.
[40]	SCARPATI G, BALDASSARRE D, BOFFARDI M, et al. Krebs von den Lungen 6 (KL-6) levels in COVID-19 ICU patients are associated with mortality[J]. J Anesth Analg Crit Care, 2022, 2(1): 37. DOI: 10.1186/s44158-022-00064-5.
[41]	D'ALESSANDRO M, BERGANTINI L, CAMELI P, et al. Serial KL-6 measurements in COVID-19 patients[J]. Intern Emerg Med, 2021, 16(6): 1541-1545. doi: 10.1007/s11739-020-02614-7
[42]	LIN H, LIU Q, ZHAO L, et al. Circulating pulmonary-originated epithelial biomarkers for acute respiratory distress syndrome: a systematic review and meta-analysis[J]. Int J Mol Sci, 2023, 24(7): 6090. DOI: 10.3390/ijms24076090.
[43]	ARNOLD D T, DONALD C, LYON M, et al. Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks[J]. PloS One, 2021, 16(4): e0249607. DOI: 10.1371/journal.pone.0249607.
[44]	PARK M, HUR M, KIM H, et al. Usefulness of KL-6 for Predicting clinical outcomes in hospitalized COVID-19 patients[J]. Medicina, 2022, 58(10): 1317. DOI: 10.3390/medicina58101317.
[45]	ISHIZAKA A, MATSUDA T, ALBERTINE K H, et al. Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome[J]. Am J Physiol Lung Cell Mol Physiol, 2004, 286(6): L1088-L1094. doi: 10.1152/ajplung.00420.2002
[46]	KONDO T, HATTORI N, ISHIKAWA N, et al. KL-6 concentration in pulmonary epithelial lining fluid is a useful prognostic indicator in patients with acute respiratory distress syndrome[J]. Respir Res, 2011, 12: 32. DOI: 10.1186/1465-9921-12-32.
[47]	ZHU W, LIU C, TAN C, et al. Predictive biomarkers of disease progression in idiopathic pulmonary fibrosis[J]. Heliyon, 2024, 10(1): e23543. DOI: 10.1016/j.heliyon.2023.e23543.
[48]	LI X N, LIN Y P, HAN M M, et al. Modulating fibrotic mechanical microenvironment for idiopathic pulmonary fibrosis therapy[J]. Adv Mater, 2024, 36(50): e2407661. DOI: 10.1002/adma.202407661.