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Author: Grafiati

Published: 10 March 2023

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1

Jiang, Dingyuan, Huijuan Xiao, Run Dong, Jing Geng, Bingbing Xie, Yanhong Ren, and Huaping Dai. "Krebs von den Lungen‐6 levels in untreated idiopathic pulmonary fibrosis." Clinical Respiratory Journal 16, no. 3 (January 26, 2022): 234–43. http://dx.doi.org/10.1111/crj.13475.

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2

Menon, Balakrishnan, Mani Tiwari, Arya Gopi, Praveen Raj, and Kunj Panwar. "Serum krebs von den lungen-6 (KL-6): a promising biomarker in sarcoidosis." MOJ Current Research & Reviews 1, no. 2 (2018): 45–47. http://dx.doi.org/10.15406/mojcrr.2018.01.00009.

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3

d'Alessandro, Miriana, Paolo Cameli, Laura Bergantini, Federico Franchi, Sabino Scolletta, and Elena Bargagli. "Serum concentrations of Krebs von den Lungen‐6 in different COVID‐19 phenotypes." Journal of Medical Virology 93, no. 2 (August 25, 2020): 657. http://dx.doi.org/10.1002/jmv.26431.

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4

Ko, Ui Won, Eun Jung Cho, Heung-Bum Oh, Hyun Jung Koo, Kyung-Hyun Do, and Jin Woo Song. "Serum Krebs von den Lungen-6 level predicts disease progression in interstitial lung disease." PLOS ONE 15, no. 12 (December 17, 2020): e0244114. http://dx.doi.org/10.1371/journal.pone.0244114.

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Disease progression (DP) in interstitial lung disease (ILD) is variable and difficult to predict. In previous reports, serum Krebs von den Lungen-6 (KL-6) was suggested to be useful in diagnosing and predicting survival in ILD. The aim of our study was to investigate the usefulness of serum KL-6 as a predictor of DP in ILD. Clinical data of 199 patients with ILD (idiopathic pulmonary fibrosis: 22.8%) were prospectively collected and serum KL-6 levels were measured. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, acute exacerbation, or death during follow-up. The median follow-up period was 11.1 months. The mean age of the subjects was 62.2 years, and 59.8% were male. DP occurred in 21.6% of patients. The progressed group showed lower FVC, lower diffusing capacity for carbon monoxide, lower the minimum oxygen saturation during the 6-minute walk test, higher fibrosis scores on high-resolution computed tomography, and higher KL-6 levels (826.3 vs. 629.0 U/mL; p < 0.001) than those of the non-progressed group. In receiver operating characteristic curve analysis, serum KL-6 levels were a significant predictor of DP in ILD (area under the curve = 0.629, p = 0.009, and the optimal cut-off level was 811 U/mL). In multivariable Cox analysis, high serum KL-6 levels (≥ 800 U/mL) were only independently associated with DP in ILD (HR 2.689, 95% CI 1.445–5.004, P = 0.002). Serum KL-6 levels might be useful to predict DP in patients with ILD.

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5

Xue, Mingshan, Chuanxu Cai, Yifeng Zeng, Yifan Xu, Huai Chen, Haisheng Hu, Luqian Zhou, and Baoqing Sun. "Krebs von den Lungen-6 and surfactant protein-A in interstitial pneumonia with autoimmune features." Medicine 100, no. 4 (January 29, 2021): e24260. http://dx.doi.org/10.1097/md.0000000000024260.

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6

Shigemura, Masahiko, Yasuyuki Nasuhara, Satoshi Konno, Chikara Shimizu, Kazuhiko Matsuno, Etsuro Yamaguchi, and Masaharu Nishimura. "Effects of molecular structural variants on serum Krebs von den Lungen-6 levels in sarcoidosis." Journal of Translational Medicine 10, no. 1 (2012): 111. http://dx.doi.org/10.1186/1479-5876-10-111.

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7

Nam, Minjeong, Mina Hur, Hanah Kim, Gun-Hyuk Lee, Mikyoung Park, Han-Sung Kwon, Han-Sung Hwang, and In-Sook Sohn. "Distribution of Presepsin, Krebs von den Lungen 6, and Surfactant Protein A in Umbilical Cord Blood." Diagnostics 12, no. 9 (September 13, 2022): 2213. http://dx.doi.org/10.3390/diagnostics12092213.

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Presepsin is an early indicator of infection, and Krebs von den Lungen 6 (KL-6) and Surfactant Protein A (SP-A) are related to the pathogenesis of pulmonary infection and fibrosis. This study aimed to establish reference intervals (RIs) of presepsin, KL-6, and SP-A levels and to evaluate the possible influence of neonatal and maternal factors on presepsin, KL-6, and SP-A levels in umbilical cord blood (UCB). Among a total of 613 UCB samples, the outliers were removed. The RIs for presepsin, KL-6, and SP-A levels were defined using non-parametric percentile methods according to the Clinical and Laboratory Standards Institute guidelines (EP28-A3C). These levels were analyzed according to neonatal and maternal factors: neonatal sex, gestational age (GA), birth weight (BW), Apgar score, delivery mode, the presence of premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), and pre-eclampsia. Presepsin, KL-6, and SP-A levels showed non-parametric distributions and left-skewed histograms. The RIs of presepsin, KL-6, and SP-A levels were 64.9–428.3 pg/mL, 43.0–172.0 U/mL, and 2.1–36.1 ng/mL, respectively. Presepsin, KL-6, and SP-A levels did not show significant differences according to sex, GA, BW, Apgar score, delivery mode, PROM, GDM, and pre-eclampsia. The median level and 97.5th centile RI of KL-6 showed a slight increase with increased GA. We established RIs for presepsin, KL-6, and SP-A levels in large-scaled UCB samples. Further investigation would be needed to determine the clinical significance.

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8

D’Agnano, Vito, Filippo Scialò, Francesco Perna, Lidia Atripaldi, Stefano Sanduzzi, Valentino Allocca, Maria Vitale, Lucio Pastore, Andrea Bianco, and Fabio Perrotta. "Exploring the Role of Krebs von den Lungen-6 in Severe to Critical COVID-19 Patients." Life 12, no. 8 (July 28, 2022): 1141. http://dx.doi.org/10.3390/life12081141.

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COVID-19 encompasses a broad spectrum of clinical conditions caused by SARS-CoV-2 infection. More severe cases experience acute respiratory and/or multiorgan failure. KL-6 is a glycoprotein expressed mainly from type II alveolar cells with pro-fibrotic properties. Serum KL-6 concentrations have been found in patients with COVID-19. However, the relevance of KL-6 in patients with severe and critical COVID-19 has not been fully elucidated. Methods: Retrospective data from consecutive severe to critical COVID-19 patients were collected at UOC Clinica Pnuemologica “Vanvitelli”, A.O. dei Colli, Naples, Italy. The study included patients with a positive rhinopharyngeal swab for SARS-CoV-2 RNA with severe or critical COVID-19. Results: Among 87 patients, 24 had poor outcomes. The median KL-6 value in survivors was significantly lower when compared with dead or intubated patients (530 U/mL versus 1069 U/mL p < 0.001). KL-6 was correlated with body mass index (BMI) (r: 0.279, p: 0.009), lung ultrasound score (LUS) (r: 0.429, p < 0.001), Chung Score (r: 0.390, p < 0.001). KL-6 was associated with the risk of death or oro-tracheal intubation (IOT) after adjusting for gender, BMI, Charlson Index, Chung Score, and PaO2/FIO2 (OR 1.003 95% CI 1.001–1.004, p < 0.001). Serum KL-6 value of 968 has a sensitivity of 79.2%, specificity of 87.1%, PPV 70.4%, NPV 91.5%, AUC: O.85 for risk of death or IOT. Conclusions: The presented research highlights the relevance of serum KL-6 in severe to critical COVID-19 patients in predicting the risk of death or IOT.

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9

Chen, Hao, Rundong Qin, Zhifeng Huang, Wenting Luo, Peiyan Zheng, Huimin Huang, Haisheng Hu, Hui Wang, and Baoqing Sun. "Clinical relevance of serum Krebs von den Lungen-6 levels in patients with coronavirus disease 2019." Cytokine 148 (December 2021): 155513. http://dx.doi.org/10.1016/j.cyto.2021.155513.

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10

Peng, Ding-Hui, Yi Luo, Li-Jun Huang, Fan-Lu Liao, Yan-Yuan Liu, Peng Tang, Han-Ning Hu, and Wei Chen. "Correlation of Krebs von den Lungen-6 and fibronectin with pulmonary fibrosis in coronavirus disease 2019." Clinica Chimica Acta 517 (June 2021): 48–53. http://dx.doi.org/10.1016/j.cca.2021.02.012.

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11

Janssen, Rob, Adrian Kruit, Jan C. Grutters, Henk J. Ruven, Wim B. Gerritsen, and Jules M. van den Bosch. "The Mucin-1 568 Adenosine to Guanine Polymorphism Influences Serum Krebs von den Lungen-6 levels." American Journal of Respiratory Cell and Molecular Biology 34, no. 4 (April 2006): 496–99. http://dx.doi.org/10.1165/rcmb.2005-0151oc.

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12

Okada, Junichi, Eijiro Yamada, Yawara Niijima, Shuichi Okada, and Masanobu Yamada. "Metformin administration attenuates dipeptidyl peptidase-4 inhibitor-induced increases in Krebs von den Lungen-6 (KL-6) levels." Journal of Diabetes 11, no. 1 (October 7, 2018): 95–96. http://dx.doi.org/10.1111/1753-0407.12852.

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13

Kaneko, Yuko, Takahiro Nunokawa, Yoshinori Taniguchi, Yukie Yamaguchi, Takahisa Gono, Kenichi Masui, Atsushi Kawakami, et al. "Clinical characteristics of cancer-associated myositis complicated by interstitial lung disease: a large-scale multicentre cohort study." Rheumatology 59, no. 1 (June 25, 2019): 112–19. http://dx.doi.org/10.1093/rheumatology/kez238.

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Abstract Objective To clarify the incidence, risk factors, and impact of malignancy in patients with PM/DM-associated interstitial lung disease (ILD). Methods This study used data from 497 patients with PM/DM-associated ILD enrolled in a multicentre, retrospective and prospective cohort of incident cases. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after PM/DM diagnosis. Demographic and clinical information was recorded at the time of diagnosis, and data about the occurrence of mortality and malignancy was collected. Results CAM was identified in 32 patients with PM/DM-associated ILD (6.4%). Patients with CAM were older (64 vs 55 years, P < 0.001), presented with arthritis less frequently (24% vs 49%, P = 0.01), and showed a lower level of serum Krebs von den Lungen-6 (687 vs 820 IU/l, P = 0.03) than those without CAM. The distribution of myositis-specific autoantibodies, including anti-melanoma differentiation–associated gene 5, anti-aminoacyl tRNA synthetase, and anti-transcriptional intermediary factor 1-γ antibodies, did not differ between the groups. Survival analysis demonstrated that CAM patients had a poorer survival than non-CAM patients (P = 0.006), primarily due to excess deaths by concomitant malignancy, while mortality due to ILD-related respiratory failure was similar between the groups (P = 0.51). Conclusion Concomitant malignancy can occur in patients with PM/DM-associated ILD, and has significant impact on mortality. Older age, lack of arthritis, and a lower level of serum Krebs von den Lungen-6 at diagnosis are predictors of concomitant malignancy.

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14

Benyamine, A., X. Heim, N. Resseguier, D. Bertin, C. Gomez, M. Ebbo, J. R. Harlé, et al. "Krebs von den Lungen-6 (KL-6), un marqueur de fibrose pulmonaire et de sévérité dans la sclérodermie systémique." La Revue de Médecine Interne 39 (June 2018): A67. http://dx.doi.org/10.1016/j.revmed.2018.03.292.

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15

Hara, Hiromichi, Hanae Miyagawa, Jun Araya, Shunsuke Minagawa, Takanori Numata, Yoshinori Umezawa, Akihiko Asahina, Hidemi Nakagawa, and Kazuyoshi Kuwano. "Effect of anti‐interleukin‐17 biologics on Krebs von den Lungen‐6 level in patients with psoriasis." Journal of Dermatology 48, no. 6 (April 16, 2021): 886–93. http://dx.doi.org/10.1111/1346-8138.15895.

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16

Hua, Jian, Masao Hagihara, Morihiro Inoue, and Yasunobu Iwaki. "A case of IgE-multiple myeloma presenting with a high serum Krebs von den Lungen-6 level." Leukemia Research 36, no. 5 (May 2012): e107-e109. http://dx.doi.org/10.1016/j.leukres.2012.02.007.

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17

Tomita, Masaki, Takanori Ayabe, Eiichi Chosa, Naohiro Nose, and Kunihide Nakamura. "Prognostic significance of preoperative serum Krebs von den Lungen-6 level in non-small cell lung cancer." General Thoracic and Cardiovascular Surgery 64, no. 11 (August 11, 2016): 657–61. http://dx.doi.org/10.1007/s11748-016-0706-4.

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18

Takanashi, Satoshi, Naoshi Nishina, Maho Nakazawa, Yuko Kaneko, and Tsutomu Takeuchi. "Usefulness of serum Krebs von den Lungen-6 for the management of myositis-associated interstitial lung disease." Rheumatology 58, no. 6 (January 8, 2019): 1034–39. http://dx.doi.org/10.1093/rheumatology/key420.

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19

Matsumura, Hisako, Hiroyuki Ichiba, Satoshi Ohnishi, Mika Saito, and Haruo Shintaku. "Histologic Chorioamnionitis, Amniotic Fluid Interleukin 6, Krebs von den Lungen 6, and Transforming Growth Factor β1 for the Development of Neonatal Bronchopulmonary Dysplasia." Japanese Clinical Medicine 8 (January 1, 2017): 117906601769607. http://dx.doi.org/10.1177/1179066017696076.

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Background: Chorioamnionitis (CAM) is an important risk factor for the development of bronchopulmonary dysplasia (BPD) in preterm infants. Objectives: To evaluate the effects of CAM on the development of BPD using interleukin 6 (IL-6), Krebs von den Lungen 6 (KL-6), and transforming growth factor β1 (TGF-β1) in the amniotic fluid as markers for inflammation, lung injury, and fibrosis/remodeling, respectively. Methods: Amniotic fluid concentrations of IL-6, KL-6, and TGF-β1 were measured with enzyme-linked immunosorbent assay or electrochemiluminescence immunoassay. Results: Of the 36 preterm infants, 18 were exposed to histologically confirmed CAM. Of these, 12 were later diagnosed as having BPD. The IL-6, KL-6, and TGF-β1 levels in the amniotic fluid significantly increased with increasing histologic severity of CAM. Moreover, these markers were higher in the BPD group with histologic CAM than those without. Conclusions: Our study suggests that CAM is likely to induce inflammatory, injury, and remodeling processes in the fetal lung.

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20

d’Alessandro, Miriana, Laura Bergantini, Paolo Cameli, Lucia Vietri, Nicola Lanzarone, Valerio Alonzi, Maria Pieroni, et al. "Krebs von den Lungen-6 as a biomarker for disease severity assessment in interstitial lung disease: a comprehensive review." Biomarkers in Medicine 14, no. 8 (June 2020): 665–74. http://dx.doi.org/10.2217/bmm-2019-0545.

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Aim: Interstitial lung diseases (ILD) are a group of lung disorders characterized by interstitial lung thickening. Krebs von den Lungen-6 (KL-6) is a molecule that is predominantly expressed by damaged alveolar type II cells and it has been proposed as a potential biomarker of different ILD. Materials & methods: A growing literature about KL-6 has been reviewed and selected to evaluate its role in the clinical management of ILD to predict disease diagnosis, activity, prognosis and treatment response. Results: KL-6 concentrations have been evaluated in fibrotic and granulomatous lung diseases and it was demonstrated to be a biomarker of disease severity useful for clinical follow-up of ILD patients. KL-6 levels differentiated between fibrotic ILD, such as idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis, and nonfibrotic lung disorders, including sarcoidosis and pulmonary alveolar proteinosis. Conclusion: KL-6 is predictive biomarker useful in the clinical management of ILD patients, in particular in patients with severe fibrotic lung disorders.

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21

Chijiwa, C., S. Takeoka, M. Kamata, H. Uchida, S. Fukaya, K. Hayashi, A. Fukuyasu, et al. "Secukinumab decreases serum Krebs von den Lungen 6 (KL-6) level in patients with psoriasis with elevated serum KL-6 level." British Journal of Dermatology 179, no. 6 (September 23, 2018): 1396–97. http://dx.doi.org/10.1111/bjd.16993.

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22

Nam, Minjeong, Mina Hur, Mikyoung Park, and Hanah Kim. "Novel Usefulness of Krebs von den Lungen 6 (KL-6) with Hemoglobin and Lactate Dehydrogenase for Assessing Bone Marrow Fibrosis." Diagnostics 12, no. 3 (March 3, 2022): 628. http://dx.doi.org/10.3390/diagnostics12030628.

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Bone marrow fibrosis (BMF) is manually assessed by reticulin and trichrome stain of bone marrow (BM) biopsy and graded on a semi-quantitative scale. Krebs von den Lungen 6 (KL-6) and Mac-2 binding protein glycosylation isomer (M2BPGi) are known to be associated with lung and liver fibrosis, respectively. We explored the usefulness of KL-6 and M2BPGi to assess BMF. A total of 250 patients who underwent BM biopsy with hematologic or non-hematologic diseases were included, and 42 patients with lung and liver diseases were excluded. The patients’ data, including age, sex, diagnosis, white blood cell, hemoglobin (Hb), platelet, and lactate dehydrogenase (LDH) were collected. Measured KL-6 and M2BPGi levels were compared with reticulin grade (RG) (grade 0–3). KL-6 levels were significantly elevated with an increase in RG, but M2BPGi did not show a significant difference. Hb, LDH, or KL-6 were independent predictors for BMF (odds ratio: 1.96, 2.26, 2.91, respectively), but showed poor predictive ability (area under the curve [AUC] 0.62, 0.61, 0.60, respectively). The combination of Hb, LDH, and KL-6 showed a significantly improved predictive ability for BMF (AUC 0.73; integrated discrimination improvement 0.057; category-free net reclassification improvement 0.625). This is the first study to evaluate the usefulness of KL-6 for assessing BMF. The combination of Hb, LDH, and KL-6 would be an objective and relevant biomarker approach and be applied to risk stratification for BMF.

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23

Letellier, A., C. Rolland-Debord, D. Luque Paz, G. Lefèvre, A. Parrot, L. Piéroni, and J. Cadranel. "Valeur pronostique du KL-6 initial (Krebs von den Lungen 6) au cours de la pneumopathie à SARS-CoV-2." Revue des Maladies Respiratoires Actualités 14, no. 1 (January 2022): 20. http://dx.doi.org/10.1016/j.rmra.2021.11.029.

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24

Ji, Yuan, Stephen J. Bourke, Mark Spears, Louise V. Wain, Gavin Boyd, Phillip P. Lynch, Matthew Cunningham, et al. "Krebs von den Lungen‐6 (KL‐6) is a pathophysiological biomarker of early‐stage acute hypersensitivity pneumonitis among pigeon fanciers." Clinical & Experimental Allergy 50, no. 12 (October 4, 2020): 1391–99. http://dx.doi.org/10.1111/cea.13744.

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25

Tanaka, Sonosuke, Noboru Hattori, Nobuhisa Ishikawa, Hiroyasu Shoda, Atsushi Takano, Ryohei Nishino, Morihito Okada, et al. "Krebs von den Lungen-6 (KL-6) is a prognostic biomarker in patients with surgically resected nonsmall cell lung cancer." International Journal of Cancer 130, no. 2 (April 27, 2011): 377–87. http://dx.doi.org/10.1002/ijc.26007.

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26

Hu, Yang, Liu-Sheng Wang, Yue-Ping Jin, Shan-Shan Du, Yu-Kui Du, Xian He, Dong Weng, et al. "Serum Krebs von den Lungen-6 level as a diagnostic biomarker for interstitial lung disease in Chinese patients." Clinical Respiratory Journal 11, no. 3 (July 7, 2015): 337–45. http://dx.doi.org/10.1111/crj.12341.

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27

Wu, X., L. Wu, C. N. Luo, and Y. M. Shi. "AB1136 THE DIAGNOSTIC VALUE OF SERUM KL-6 IN CONNECTIVE TISSUE DISEASE ASSOCIATED INTERSTITIAL LUNG DISEASE IN THE UYGUR POPULATION OF CHINA." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1858.2–1858. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4860.

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Background:Connective tissue diseases are a group of inflammatory, immune mediated disorders.Interstitial lung disease (ILD) is associated with significant morbidity and mortality.Currently,, scientists are still looking for serum markers to diagnose interstitial lung disease.Althought serum KL-6 level has been studied in ILD of various aetiologies and revealed to be an important serum marker for ILD,but differences in KL-6 expression related to ethnic and/or genetic variants may exist.Objectives:To evaluate the diagnosis of the serum Krebs von den Lungen-6 (KL-6) for CTD-ILD in the Uygur population of China.Methods:117 Patients with CTD-ILD (CTD-ILD group) and 182 patients with CTD (CTD group) who visited the department of rheumatology and immunology of People’s Hospital of Xinjiang Uygur Autonomous Region between January, 2015 and December, 2019 were included. Serum KL-6 levels were measured by chemiluminescent enzyme immunoassay kit.Results:The significantly higher levels of KL-6 were determined in the RA-ILD group than RA group [569(287.5,984)U/ml vs 194(152,266.5)U/ml](P<0.001)(figure 1).The optimal cutoff value of serum KL-6 for diagnosis of RA-ILD was 345.5 U/ml, and the sensitivity and specificity were71.8% and 90.1 %, respectively. Area Under the Curve (AUC) was 0.875.(figure 2)Figure 1.Comparison of serum KL-6 concentrations in CTD-ILD group and CTD group.Fig 2.Receiver-operating characteristic curve(ROC) of KL-6 for the diagnosis of CTD-ILDConclusion:The serum KL-6 is a important biomarker for the diagnosis of CTD-ILD and Serum KL-6 could be a clinically useful biomarker in screening CTD-ILD in the Uygur population of China.References:[1]Woodhead F, Wells A U, Desai S R. Pulmonary Complications of Connective Tissue Diseases[J]. Clinics in Chest Medicine, 2008, 29(29):149–164.Tanaka S, Hattori N, Ishikawa N, et al. Krebs von den Lungen-6 (KL-6) is a progn -ostic biomarker in patients with surgically resected nonsmall cell lung cancer. Int J Cancer 2012; 130:377–87.[2]Ogz E O, Kucuksahin O, Turgay M, et al. Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study. Clinical Rheumatology, 2016, 35(3):663-666.Disclosure of Interests:None declared

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Matuszewski, Michal, Lukasz Szarpak, Zubaid Rafique, Frank W. Peacock, Michal Pruc, Piotr Szwed, Francesco Chirico, Alla Navolokina, Jerzy R. Ladny, and Andrea Denegri. "Prediction Value of KREBS Von Den Lungen-6 (KL-6) Biomarker in COVID-19 Patients: A Systematic Review and Meta-Analysis." Journal of Clinical Medicine 11, no. 21 (November 7, 2022): 6600. http://dx.doi.org/10.3390/jcm11216600.

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The SARS-CoV-2 (COVID-19) pandemic is a major issue that necessitates the use of cutting-edge disease prediction models. The aim of the study was to assess the existing evidence regarding association between Krebs von den Lungen-6 levels and COVID-19 severity. A literature search was performed on Web of Science, PubMed, Scopus and Cochrane Central Register of Controlled Trials databases from 1 January 2020 up to 2 August 2022. The electronic database search was supplemented by searching Google Scholar. In addition, reference lists of relative articles were also reviewed. KL-6 levels among COVID-19 positive vs. negative patients varied and amounted to 443.37 ± 249.33 vs. 205.73 ± 86.8 U/mL (MD = 275.33; 95%CI: 144.57 to 406.09; p < 0.001). The KL-6 level was 402.82 ± 261.16 U/mL in the severe group and was statistically significantly higher than in the non-severe group (297.38 ± 90.46 U/mL; MD = 192.45; 95%CI: 118.19 to 266.72; p < 0.001). The KL-6 level in the mild group was 272.28 ± 95.42 U/mL, compared to 268.04 ± 55.04 U/mL in the moderate COVID-19 group (MD = −12.58; 95%CI: −21.59 to −3.57; p = 0.006). Our meta-analysis indicates a significant association between increased KL-6 levels and SARS-CoV-2 infection. Moreover, KL-6 levels are significantly higher in patients with a more severe course of COVID-19, indicating that KL-6 may be a useful predictor to identify patients at risk for severe COVID-19.

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29

Naderi, Nadereh, and Mahsa Rahimzadeh. "Krebs von den Lungen-6 (KL-6) as a clinical marker for severe COVID-19: A systematic review and meta-analyses." Virology 566 (January 2022): 106–13. http://dx.doi.org/10.1016/j.virol.2021.11.006.

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30

Yamaya, Takafumi, Eri Hagiwara, Tomohisa Baba, Takaaki Kitayama, Kota Murohashi, Katsuyuki Higa, Yozo Sato, et al. "Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019." Respiratory Investigation 59, no. 5 (September 2021): 596–601. http://dx.doi.org/10.1016/j.resinv.2021.04.002.

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31

Asakura, Takanori, Yoshifumi Kimizuka, Tomoyasu Nishimura, Shoji Suzuki, Ho Namkoong, Yohei Masugi, Yasunori Sato, Makoto Ishii, and Naoki Hasegawa. "Serum Krebs von den Lungen‐6 level in the disease progression and treatment of Mycobacterium avium complex lung disease." Respirology 26, no. 1 (June 29, 2020): 112–19. http://dx.doi.org/10.1111/resp.13886.

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32

Volkmann, Elizabeth R., Donald P. Tashkin, Masataka Kuwana, Ning Li, Michael D. Roth, Julio Charles, Faye N. Hant, et al. "Progression of Interstitial Lung Disease in Systemic Sclerosis: The Importance of Pneumoproteins Krebs von den Lungen 6 and CCL18." Arthritis & Rheumatology 71, no. 12 (November 2019): 2059–67. http://dx.doi.org/10.1002/art.41020.

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33

Hammoda, Rasha, Haitham Salah-ElDin, Nermin EL-Gharbawy, and Dina Ragab. "Krebs von den Lungen‐6, a promising marker in evaluating the severity of interstitial lung disease in Egyptian rheumatoid arthritis patients." Egyptian journal of Immunology 28, no. 4 (October 1, 2021): 241–49. http://dx.doi.org/10.55133/eji.280425.

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Krebs von den Lungen-6 (KL-6) is one of the mucins associated with interstitial lung disease. We aimed to assess the value of KL-6 as a marker for detecting the presence of interstitial lung disease in Egyptian rheumatoid arthritis patients and to evaluate its ability to assess severity in different grades of interstitial lung disease. The study included 89 rheumatoid arthritis patients; 64 patients with interstitial lung disease and 25 patients without interstitial lung disease. Serum levels of KL-6 were assessed using enzyme linked immunosorbent assay. Levels of KL-6 were higher in patients with interstitial lung disease compared to patients without interstitial lung disease (P< 0.001). KL-6 levels were significantly higher in grade 4 patients than those in grades 1 and 2. Also, KL-6 levels were significantly higher in grade 3 patients than those in grades 1 and 2. Kl-6 levels were also higher in grade 2 patients compared to grade 1 patients. Finally, no difference was observed between grade 4 patients and grade 3 patients. KL-6 levels were significantly higher in usual interstitial pneumonia pattern compared other patterns (P=0.015). In conclusion, KL-6 is a potential circulating biomarker that may have a substantial role in detecting the presence and evaluating the severity of interstitial lung disease among rheumatoid arthritis patients.

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Cho, Eun-Jung, Kyoung-Jin Park, Dae-Hyun Ko, Hyun Jung Koo, Sang Min Lee, Jin Woo Song, Woochang Lee, et al. "Analytical and Clinical Performance of the Nanopia Krebs von den Lungen 6 Assay in Korean Patients With Interstitial Lung Diseases." Annals of Laboratory Medicine 39, no. 3 (May 1, 2019): 245–51. http://dx.doi.org/10.3343/alm.2019.39.3.245.

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Cho, Eun-Jung, Kyoung-Jin Park, Dae-Hyun Ko, Hyun Jung Koo, Sang Min Lee, Jin Woo Song, Woochang Lee, et al. "Analytical and Clinical Performance of the Nanopia Krebs von den Lungen 6 Assay in Korean Patients With Interstitial Lung Diseases." Annals of Laboratory Medicine 39, no. 3 (2019): 245. http://dx.doi.org/10.3343/alm.2019.39.3.251.

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Benyamine, Audrey, Xavier Heim, Noémie Resseguier, Daniel Bertin, Carine Gomez, Mikaël Ebbo, Jean-Robert Harlé, et al. "Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease." Rheumatology International 38, no. 5 (February 17, 2018): 813–19. http://dx.doi.org/10.1007/s00296-018-3987-3.

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Shirai, Yuichiro, Ryosuke Fukue, Yuko Kaneko, and Masataka Kuwana. "Clinical Relevance of the Serial Measurement of Krebs von den Lungen-6 Levels in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease." Diagnostics 11, no. 11 (October 28, 2021): 2007. http://dx.doi.org/10.3390/diagnostics11112007.

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Krebs von den Lungen-6 (KL-6) levels measured at baseline have been reported as a circulating biomarker useful for the detection, evaluation of severity and assessment of risk of the progression of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). In this retrospective study, longitudinal changes in serum KL-6 levels over 2 years were examined in 110 patients with SSc using prospectively collected cohort data. Serum KL-6 levels fluctuated in a significant proportion of the patients but remained stable in the remaining patients. A wide range of variability of longitudinal KL-6 levels was associated with the presence of ILD, diffuse cutaneous SSc, positive anti-topoisomerase I antibodies, negative anticentromere antibodies, increased ILD extent on high-resolution computed tomography, extensive disease, low pulmonary function parameters, high KL-6 levels at baseline and immunomodulatory treatment. Extensive disease was consistently identified as an independent factor associated with variability in KL-6 levels in different models of multiple regression analysis. We failed to demonstrate correlations between trends for KL-6 level changes during the 6 months after SSc diagnosis and ILD progression over 2 years in patients with SSc-ILD. Serum KL-6 levels fluctuate in SSc patients with ILD, especially in those with extensive disease, but the clinical utility of a serial KL-6 level measurement remains uncertain.

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Lobo Prat, D., I. Castellví, D. Castillo, S. Orozco, A. Mariscal, L. Martínez-Martínez, A. M. Millán Arciniegas, et al. "AB0666 PROGNOSTIC VALUE OF SERUM KREBS VON DEN LUNGEN-6 GLYCOPROTEIN CIRCULATING LEVELS IN COVID-19 PNEUMONIA: A PROSPECTIVE COHORT STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1365.1–1365. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1359.

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Background:Currently, there are no biomarkers to predict respiratory worsening in patients with Coronavirus infectious disease, 2019 (COVID- 19) pneumonia.Objectives:We aimed to determine the prognostic value of Krebs von de Lungen-6 circulating serum levels (sKL-6) predicting COVID- 19 evolving trends.Methods:We prospectively analyzed the clinical and laboratory characteristics of 375 COVID- 19 patients with mild lung disease on admission. sKL-6 was obtained in all patients at baseline and compared among patients with respiratory worsening.Results:45.1% of patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were higher in patients who had respiratory worsening (median [IQR] 303 [209-449] vs. 285.5 [15.8-5724], P=0.068). The best sKL-6 cut-off point was 408 U/mL (area under the curve 0.55; 33% sensitivity, 79% specificity). Independent predictors of respiratory worsening were sKL-6 serum levels, age >51 years, time hospitalized, and dyspnea on admission. Patients with baseline sKL-6 ≥ 408 U/mL had a 39% higher risk of developing respiratory aggravation seven days after admission. In patients with serial determinations, sKL-6 was also higher in those who subsequently worsened (median [IQR] 330 [219-460] vs 290.5 [193-396]; p<0.02).Conclusion:sKL-6 has a low sensibility to predict respiratory worsening in patients with mild COVID-19 pneumonia. Baseline sKL-6 ≥ 408 U/mL is associated to a higher risk of respiratory worsening. sKL-6 levels are not useful as a screening tool to stratify patients on admission but further research is needed to investigate if serial determinations of sKL-6 may be of prognostic use.References:[1]Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. 5.[2]Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, Sigurslid HH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020.[3]Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020;20(1):519.Disclosure of Interests:None declared.

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Zheng, Peiyan, Xiaomao Zheng, Hasegawa Takehiro, Zhangkai Jason Cheng, Jingxian Wang, Mingshan Xue, Quanming Lin, et al. "The prognostic value of Krebs von den Lungen-6 and surfactant protein-A levels in the patients with interstitial lung disease." Journal of Translational Internal Medicine 9, no. 3 (September 1, 2021): 212–22. http://dx.doi.org/10.2478/jtim-2021-0040.

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Abstract Background and Objectives The highly variable clinical course of interstitial lung disease (ILD) makes it difficult to predict patient prognosis. Serum surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) are known prognostic biomarkers. However, the clinical or pathophysiological differences in patients with these biomarkers have not been well evaluated. We investigated the clinical and pathophysiological differences through the comparison of SP-A and KL-6 levels before and after treatment. Methods This study included retrospective data from 91 patients who were treated for ILD between August 2015 and September 2019. Serum SP-A and KL-6 levels were measured before and after treatment. The patients were followed up for 3 months. Results Changes in the serum biomarkers (Delta SP-A and Delta KL-6) were found to be significantly correlated (rs = 0.523, P < 0.001); Delta SP-A and Delta KL-6 were inversely correlated with changes in pulmonary function (% predicted values of diffusing capacity for carbon monoxide [DLCO], forced vital capacity [FVC], and forced expiratory volume in 1 s [FEV1]). Patients were divided into four groups based on their Delta SP-A and Delta KL-6 levels in a cluster analysis (G1, G2, G3, and G4). Both SP-A and KL-6 were elevated in the G1 group, with all the patients enrolled classified as progressive or unchanged, and 86.4% of patients showed improved disease activity in the G4 group, where both SP-A and KL-6 levels were reduced. In the G2 group, only SP-A levels decreased post-treatment, indicating an improvement in respiratory function; the patients were not at the end stage of the disease. Only the SP-A levels increased in the G3 group with immunosuppressive treatment. Conclusions Reduced serum SP-A and/or KL-6 levels are associated with improved lung function in patients with ILD. Some patients only showed a decrease in SP-A levels could prognosis an improvement in respiratory function. When only SP-A is increased, it may imply that the patients are at an early stage of disease progression. As a result, for proper disease monitoring, measuring both markers is important.

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Almuntashiri, Sultan, Chelsea James, Xiaoyun Wang, Budder Siddiqui, and Duo Zhang. "The Potential of Lung Epithelium Specific Proteins as Biomarkers for COVID-19-Associated Lung Injury." Diagnostics 11, no. 9 (September 8, 2021): 1643. http://dx.doi.org/10.3390/diagnostics11091643.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was first reported in Wuhan, China, and was declared a pandemic by the World Health Organization (WHO) on 20 March 2020. The respiratory system is the major organ system affected by COVID-19. Numerous studies have found lung abnormalities in patients with COVID-19, including shortness of breath, respiratory failure, and acute respiratory distress syndrome. The identification of lung-specific biomarkers that are easily measurable in serum would be valuable for both clinicians and patients with such conditions. This review is focused on the pneumoproteins and their potential to serve as biomarkers for COVID-19-associated lung injury, including Krebs von den Lungen-6 (KL-6), surfactant proteins (SP-A, SP-B, SP-C, SP-D), and Clara cell secretory protein (CC16). The current findings indicate the aforementioned pneumoproteins may reflect the severity of pulmonary manifestations and could serve as potential biomarkers in COVID-19-related lung injury.

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OKADA, JUNICHI, SHUICHI OKADA, and MASANOBU YAMADA. "151-LB: High Risk of Krebs Von Den Lungen-6 (kL-6) Elevation when Dipeptidyl Peptidase-4 Inhibitors and Amiodarone Are Prescribed Simultaneously." Diabetes 68, Supplement 1 (June 2019): 151—LB. http://dx.doi.org/10.2337/db19-151-lb.

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Zhang, Zhansai, Yanfang Zhao, Gang Chen, Ruoming Li, Jun Yang, and Daoyuan Sun. "Study of lung toxicity in rats exposed to silica powder with different hard metal constituents." Toxicology and Industrial Health 34, no. 7 (April 18, 2018): 449–57. http://dx.doi.org/10.1177/0748233718758586.

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The objective of this study was to assess the lung toxicity induced by the inhalation of different hard metal constituents and silica powder and screen for potential toxicity biomarkers. Rats were randomly divided into saline, cobalt, tungsten carbide, silica, and hard metal (HM) groups and were administered a single 10-mg dose of the respective treatments. After 8 weeks, the lung tissue structure in the HM group was deformed, numerous nucleated giant and epithelial-like cells appeared in the stroma, and the computed tomography scanning images appeared abnormal. Krebs von den Lungen-6 (KL-6), transforming growth factor (TGF)-β1, and TGF-β2 expression in bronchoalveolar lavage fluid (BALF) significantly differed between the groups ( p < 0.05). Serum KL-6 and TGF-β1, but not TGF-β2, levels significantly differed between some groups ( p < 0.05). We observed multinucleated giant cells in the rat lung tissue. While the serum and BALF levels of KL-6 and TGF-β2 are not highly specific, TGF-β1 may be a valuable reference diagnostic marker in HM lung disease.

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Witarto, Andro Pramana, Bendix Samarta Witarto, Achmad Januar Er Putra, Shidi Laras Pramudito, and Alfian Nur Rosyid. "Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19 Lung Injury: A Systematic Review and Meta-Analysis." Iranian Biomedical Journal 25, no. 6 (October 1, 2021): 381–89. http://dx.doi.org/10.52547/ibj.25.6.381.

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Zhong, Danli, Chanyuan Wu, Jingjing Bai, Chaojun Hu, Dong Xu, Qian Wang, and Xiaofeng Zeng. "Comparative diagnostic efficacy of serum Krebs von den Lungen-6 and surfactant D for connective tissue disease-associated interstitial lung diseases." Medicine 99, no. 16 (April 2020): e19695. http://dx.doi.org/10.1097/md.0000000000019695.

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Qin, H., X. P. Xu, J. Zou, X. J. Zhao, H. W. Wu, Q. F. Zha, S. Chen, Y. Kang, and H. D. Jiang. "Krebs von den Lungen-6 associated with chest high-resolution CT score in evaluation severity of patients with interstitial lung disease." Pulmonology 25, no. 3 (May 2019): 143–48. http://dx.doi.org/10.1016/j.pulmoe.2018.05.008.

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Wakamoto, Hiroyuki, Nozomi Sano, Yoshiaki Yano, Shinya Sakai, Takanori Kikuchi, Mitsumasa Fukuda, Takehiko Morimoto, and Eiichi Ishii. "Clinical Usefulness of Serum Krebs von den Lungen-6 for Detecting Chronic Aspiration in Children with Severe Motor and Intellectual Disabilities." Journal of Pediatrics 167, no. 5 (November 2015): 1136–42. http://dx.doi.org/10.1016/j.jpeds.2015.08.030.

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Sato, Seidai, Masaki Hanibuchi, Asami Fukuya, Youhei Yabuki, Hiroki Bando, Terumi Yoshijima, Hisatsugu Goto, Hirohisa Ogawa, and Yasuhiko Nishioka. "Idiopathic Pleuroparenchymal Fibroelastosis is Characterized by an Elevated Serum Level of Surfactant Protein-D, but Not Krebs Von Den Lungen-6." Lung 192, no. 5 (June 1, 2014): 711–17. http://dx.doi.org/10.1007/s00408-014-9599-0.

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Arnold, David T., Charmaine Donald, Max Lyon, Fergus W. Hamilton, Anna J. Morley, Marie Attwood, Alexandra Dipper, and Shaney L. Barratt. "Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks." PLOS ONE 16, no. 4 (April 29, 2021): e0249607. http://dx.doi.org/10.1371/journal.pone.0249607.

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Introduction Acute presentations of COVID-19 infection vary, ranging from asymptomatic carriage through to severe clinical manifestations including acute respiratory distress syndrome (ARDS). Longer term sequelae of COVID-19 infection includes lung fibrosis in a proportion of patients. Krebs von den Lungen 6 (KL-6) is a mucin like glycoprotein that has been proposed as a marker of pulmonary epithelial cell injury. We sought to determine whether KL-6 was a marker of 1) the severity of acute COVID-19 infection, or 2) the persistence of symptoms/radiological abnormalities at medium term follow up. Methods Prospective single centre observational study. Results Convalescent KL-6 levels were available for 93 patients (male 63%, mean age 55.8 years) who attended an 12-week follow up appointment after being admitted to hospital with COVID-19. For 67 patients a baseline KL-6 result was available for comparison. There was no significant correlations between baseline KL-6 and the admission CXR severity score or clinical severity NEWS score. Furthermore, there was no significant difference in the baseline KL-6 level and an initial requirement for oxygen on admission or the severity of acute infection as measured at 28 days. There was no significant difference in the 12-week KL-6 level and the presence or absence of subjective breathlessness but patients with abnormal CT scans at 12 weeks had significantly higher convalescent KL-6 levels compared to the remainder of the cohort (median 1101 IU/ml vs 409 IU/ml). Conclusions The association between high KL-6 levels at 12 weeks and persisting CT abnormalities (GGO/fibrosis), is a finding that requires further exploration. Whether KL-6 may help differentiate those patients with persisting dyspnoea due to complications rather than deconditioning or dysfunctional breathing alone, is an important future research question.

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Shrestha, Abhigan Babu, Pashupati Pokharel, Harendra Singh, Sajina Shrestha, and Fioni. "Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19: A Systematic Review, Meta-Analysis, and Trial Sequence Analysis." Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine 17 (January 2023): 117954842311523. http://dx.doi.org/10.1177/11795484231152304.

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OBJECTIVE This systematic review and meta-analysis aimed to find the association between serum Krebs von den Lungen-6 (KL-6) and the severity of Coronavirus disease 2019 (COVID-19) infection. DATA SOURCES Databases of Embase, PubMed, Web of Science, Science Direct, and Google Scholar were searched for studies reporting KL-6 levels in COVID-19 patients, published between January 2020 and September 30 2022. DATA SYNTHESIS For comparison between the groups, standard mean difference (SMD) and 95% confidence intervals (CI) were computed as the effect sizes. Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were measured to assess the diagnostic power of KL-6. In addition, the summary receiver operating characteristics curve (sROC) was constructed to summarize the true positive (TP), and false positive (FP) rates. To validate the findings of meta-analysis, Trial Sequential Analysis (TSA) was conducted. RESULTS Altogether 497 severe COVID-19 patients and 934 non-severe (mild to moderate) COVID-19 patients were included. Pooling of 12 studies indicated that the serum KL-6 level had significant association with severity of COVID-19 infection: standard mean difference = 1.18 (95% CI: 0.93-1.43), p = 0.01; I2: 58.56%]. Pooled diagnostic parameters calculated from eight studies were: sensitivity 0.53 (95% CI: 0.47-0.59); specificity 0.90 (95% CI: 0.88-0.93); positive likelihood ratio 4.80 (95% CI: 3.53-6.53); negative likelihood ratio 0.46 (95% CI: 0.32-0.68); and area under curve: 0.8841. Additionally, TSA verified the adequacy of sample size and robustness of the meta-analysis. CONCLUSION Serum KL-6 level has a moderate degree of correlation with the severity of COVID-19 infection but has low sensitivity. So, it is not recommended as a screening test for severe COVID-19 infection.

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Firmansyah, Zam Zam, Tri Wahju Astuti, and Garinda Alma Duta. "Increased Serum KL-6/MUC1 Level, Neutrophils and Lymphocytes Sputum in Malang Splendid Bird Market Workers." Jurnal Respirologi Indonesia 40, no. 2 (April 30, 2020): 75–81. http://dx.doi.org/10.36497/jri.v40i2.103.

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Backgrounds: People who work in the bird market have a high exposure risk of air pollution in large numbers, particulate pollutans including organic dust, loose feathers, insects or ticks, food aerosol particles, bird’s excreta (amonia) and various of gram bacteria, fungal and virus. Exposure to particles will stimulate the immune system against harmful pathogens in the form of an inflammatory response. An infection or injury will stimulate secretion of KL-6/MUC1 (Krebs von den Lungen-6 is a high molecular weight, mucin-like glycoprotein in human (MUC1)) by AEC type II and bronchial epithelial cells in response to cell damage and regeneration. Methods: This was an observational analytic cross-sectional study on 35 subjects, which examined and analyzed the characteristics of workers, percentage count of neutrophils, lymphocytes in induced sputum and KL-6/MUC1 serum levels using ELISA sandwich. Results: Mean KL-6/MUC1 serum levels in the bird market workers increased (1152.67+583.92 U/ml) from normal levels (105.3-401.2 U/ml). There was a significant positive correlation between the length of exposure and KL-6/MUC1 serum levels (r=0.624; P

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