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Early diagnosis of pulmonary diseases is of great significance for their prevention and treatment. Serum Krebs von den Lungen-6 (KL-6) assay can reflect the damage degree of alveolar epithelium and stromal tissue, and is simple, non-invasive and low-cost. Pervious study showed that the serum KL-6 level was higher in patients with various interstitial lung diseases (e.g. idiopathic pulmonary fibrosis and connective tissue disease, primary Sjögren's syndrome, rheumatoid arthritis, idiopathic inflammatory myopathy and systemic sclerosis combined with interstitial lung disease), non-small cell lung cancer, various pneumonias and chronic obstructive pulmonary disease compared to healthy controls. Therefore, serum KL-6 has good sensitivity and specificity for the early diagnosis of these diseases. Occupational pneumoconiosis is an interstitial lung disease with a well-established etiology. Pervious study has shown that serum KL-6 level was higher in patients with occupational silicosis, occupational asbestosis, and dust-exposed workers compared to healthy controls. However, due to the limited sample size and the inconsistent findings on different studies, further research is needed to study the role of serum KL-6 in the early diagnosis of pneumoconiosis. Future studies should increase the sample size, improve the detection methods for serum KL-6, explore its feasibility as an early diagnostic biomarker for occupational pulmonary diseases, and investigate the efficacy andvalue of its combined application with other biomarkers in the early diagnosis of various pulmonary diseases, including occupational lung diseases, to fully exploit its predictive role in pulmonary diseases.
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{L-End}Objective To analyze the changes of seven potential biomarkers in plasma of patients with occupational silicosis (hereinafter referred to as "silicosis"), and explore their clinical value in determining the stage of silicosis. {L-End}Methods A total of 100 male silicosis patients were selected as the silicosis group (63 cases in stage Ⅰ and 37 cases in stage Ⅱ subgroups), and 100 male healthy individuals were selected as the control group using the 1∶1 matched case-control study. Enzyme-linked immunosorbent assay was used to analyze the level of interleukin-17 (IL-17), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), Krebs von den Lungen-6 (KL-6), connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), and histone H4 in plasma. Their clinical value for diagnosing silicosis was evaluated using receiver operating characteristic (ROC) curve, discriminant analysis stepwise method, and Fisher discriminant function analysis. {L-End}Results The levels of IL-17, MCP-1, MMP-9, KL-6, CTGF, PDGF, and histone H4 in the plasma of the silicosis group, silicosis stage Ⅰ subgroups, and stage Ⅱ subgroups were higher than those in the control group (all P<0.05). The levels of IL-17, MCP-1, and MMP-9 in the plasma of the stage Ⅱ subgroup decreased (all P<0.05), while the levels of KL-6, CTGF and histone H4 increased (all P<0.05) compared with the stage Ⅰ subgroup. The area under the ROC curve for diagnosing silicosis using these seven potential biomarkers ranged from 0.761 to 1.000 (all P<0.01), with the sensitivity of 0.640-1.000, the specificity of 0.840-0.990, and the Youden index of 0.540-0.990. The Fisher discriminant function was formed by stepwise discriminant analysis, and the results showed that the coincidence rate was 99.5%, and the misdiagnosis rate was 0.5% for diagnosing and staging silicosis with these seven potential biomarkers. The coincidence rate of diagnosing control group, silicosis stageⅠsubgroup and the silicosis stage Ⅱ subgroup was 100.0%, 98.4% and 100.0%, respectively. {L-End}Conclusion IL-17, MCP-1, MMP-9, KL-6, CTGF, PDGF and histone H4 in plasma can be used as biomarkers for the diagnosis of silicosis, and the Fisher discriminant function based on the combination of these seven biomarkers can assist in staging silicosis.
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Objective:To explore the correlation between serum krebs von den lungen-6 (KL-6) level and immune function in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD), and provide theoretical basis for clinical diagnosis and treatment.Methods:Eighty-six RA patients were divided into Non-RA-ILD group and RA-ILD group. The serum KL-6 level and immune function (the number of CD3 +, CD4 +, CD8 + and CD4 +/CD8 + ratio) of all subjects were detected. The correlation between serum KL-6) level and immune function was analyzed. The correlation analysis was performed by Pearson or Spearman rank correlation analysis. Results:There were 54 cases of Non-RA-ILD patients and 32 cases of RA-ILD patients in this study. The clinical data showed that RA-ILD patients were mainly male, and the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF) were significantly increased( t=6.382, 7.243 and 7.748, P<0.05). The KL-6 level of RA-ILD patients [(835±72) U/ml] was significantly higher than that of Non-RA-ILD patients [(434±45) U/ml]. And the difference was statistically significant( t=31.670, P<0.05). Meanwhile, the number of CD8 + lymphocyte and CD4 +/CD8 + ratio of RA-ILD patients were significantly increased ( t=3.456 and 4.993, P<0.05). The results of correlation analysis showed that the level of KL-6 in serum was negatively correlated with the level of Ts cells CD8 + ( r=-3.563, P=0.031), and positively correlated with the ratio of CD4 +/CD8 + ( r=4.879, P=0.011). Conclusion:The level of serum KL-6 level is closely related to the abnormal immune function of RA-ILD patients. The serum KL-6 level can be used as an important index to evaluate the immune status of RA-ILD patients.
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Objective@#To investigate the effects of long-term exposure to silica dust on serum CC16 and KL-6 levels.@*Methods@#The patients with stage I silicosis who were hospitalized in our hospital from April 2016 to April 2017 were treated as silicosis group. The silica dust exposed workers without silicosis who were taken the physical examination in our hospital were taken as a dust-exposed group. The healthy control group comes from in the same period of community physical examination did not touch the dust. The levels of CC16 and KL-6 in serum of all subjects were determined by enzyme-linked immunosorbent assay (ELISA) , and the levels of CC16 and KL-6 in serum were compared in three groups.@*Results@#Compared with the control group, the serum levels of CC16 in the silicosis group (P<0.01) and the dust-exposed group (P<0.01) were significantly lower. Compared with the control group, the level of serum KL-6 in the silicosis group was significantly decreased (P<0.01) compared with the control group, while the level of KL-6 in the serum of the dust-exposed group was significantly increased (P<0.01) . The ROC area of CC16 for diagnosis of silicosis was 0.92 (P<0.01) , with a sensitivity of 81.37%, specificity of 92.63% and Kappa value of 0.74.@*Conclusion@#Long-term exposure to silica dust may lead to a decrease in serum CC16 levels. Reduced serum CC16 levels may be useful in identifying the diagnosis of silicosis.
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Objective To determine the levels and significance of Krebs von den lungen-6(KL-6), pulmonary surfactant protein A (SP-A), SP-D and interleukin (IL)-6 in patients with connective tissue disease interstitial lung disease (CTD-ILD). Methods The serum KL-6, SP-A, SP-D and IL-6 in all subjects were detected and the imaging and pulmonary function were recorded t test, χ2 test, non-parametric test, ANOVA and correlation analysis were used for data analysis. Results ① The levels of serum KL-6, SP-A, SP-D, IL-6 in the CTD-ILD group [551.4 (428.2, 883.5) U/ml, 938.4(435.2, 2324.7) pg/ml, 90.7 (80.7, 100.3) ng/ml and 30.4 (22.9, 41.7) pg/ml; P all<0.05] was significantly higher than that in the CTD group [192.9 (139.2, 266.2) U/ml; 458.0 (372.6, 529.0) pg/ml; 80.0 (71.2, 98.3) ng/ml; 18.6 (4.9, 31.0) pg/ml, Z=-5.383, -3.76, -2.123,-3.903, P all <0.05]; and higher than healthy controls (n=30) [183.2(141.9, 216.6) U/ml; 229.0(162.0, 248.0) pg/ml;50.8(26.1, 96.4) ng/ml;7.1(3.7, 8.7) pg/ml, Z=-5.801,-8.13, 2.272, 3.266;P all<0.05].②The levels of KL-6 in pulmonary HRCT for active ILD group was significantly higher than the non-active ILD group [998.5 (640.3, 1293.3) U/ml vs 565.0(434.0, 799.5) U/ml, Z=2.182, P=0.023], there was no statistical difference in the levels of SP-A, SP-D, IL-6 between the 2 groups. ③ Spearman correlation analysis showed that KL-6 was negatively correlated with forced vital capacity (FVC%);SP-D, IL-6 and diffusing capacity of carbon monoxide (DLCO %). ④ Logistic multiple regression analysis showed that KL-6 [OR=1.017, P=0.002, 95%CI (1.006, 1.028)], SP-A [OR=1.023, P=0.009, 95%CI (1.006, 1.041)], SP-D [OR=1.175, P=0.009, 95%CI (1.075, 1.264)], IL-6[OR=1.213, P=0.001, 95%CI(1.088, 1.354)] were the risk factors for ILD. Conclusion Serum KL-6, SP-A, SP-D and IL-6 are significantly increased and correlate with CTD-ILD. KL-6 is related to the pulmonary inflammatory disease and vital capacity, while SP-D and IL-6 are related to diffusion function.
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Objective To evaluate the serum Krebs von den Lungen (KL)-6 for the diagnosis of interstitial lung disease (ILD) associated with connective tissue diseases (CTD) and its lung-CT subtypes.Methods Seventy-five CTD patients were employed for this study,44 CTD with ILD and 31 ILD without ILD.The 44 CTD patients with ILD were further divided into different subgroups based on lung-CT imaging and clinical indexes.The enzyme-linked immune sorbent assay (ELISA) was used to measure the serum KL-6 level.For those data that was abnormally distributed,the differences between groups was compared with independent samples nonparametric tests.Results The level of serum KL-6 in the CTD with ILD was significantly higher than that without ILD [(1 118±877) U/ml vs (253±144) U/ml] (Z=-6.047,P＜0.01).By using a criterion of 500 U/ml,our data suggested that the serum KL-6 level was useful for the ILD-CTD diagnosis;the sensitivity,specificity,positive and negative predictive values were 72.7％,87.1％,88.9％ and 69.2％,respectively.The serum KL-6 level,however,showed no statistical differences between ILD subtypes,i.e.,usual interstitial pneumonia (UIP),nonspecific interstitial pneumonia (NSIP) and indeterminate [(1 104±843) U/ml,(1 242±1 039) U/ml,(815±400) U/ml,respectively] (x2=0.35,P=0.84).Our data further showed that the KL-6 level was significantly higher in CTD-ILD patients with intensive lung lesions than those with limited lung lesions [(1 910±918) U/ml vs (459±268) U/ml] (Z=-4.364,P＜0.01).In addition,the KL-6 level was significantly higher in active ILDs than in inactive ILDs[(1 478±917) U/ml vs (598±475) U/ml] (Z=-3.915,P＜0.01).Conclusion The serum KL-6 is a valuable biomarker for CTD-ILD diagnosis and even for the assessment of the extent and activity of lung damage.