Clinical Relevance of the Serial Measurement of Krebs von den Lungen-6 Levels in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease.
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SUBMITTER: Shirai Y
PROVIDER: S-EPMC8619247 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD).MethodsPatients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm.ResultsBaseline KL-6 and CCL18 levels each correlated with the extent of radiographic fibrosis. Levels of both CCL18 and KL-6 declined significantly at 1 year. In both treatment arms (n = 71 for CYC, n = 62 for MMF), a higher baseline KL-6 level predicted progression of ILD based on the course of FVC (P = 0.024 for CYC; P = 0.005 for MMF) and DLco (P < 0.001 for CYC; P = 0.004 for MMF) over 1 year. A higher baseline CCL18 level predicted progression of ILD based on the course of the FVC (P < 0.001 for CYC; P = 0.007 for MMF) and DLco (P = 0.001 for CYC; P < 0.001 for MMF) over 1 year, as well as mortality (P = 0.0008 for CYC arm only).ConclusionIn a rigorously conducted clinical trial for SSc-related ILD, KL-6 and CCL18 levels correlated with ILD severity and declined with immunosuppression. Patients with higher baseline KL-6 and CCL18 levels were more likely to experience disease progression despite treatment. KL-6 and CCL18 levels could be used to identify patients with a progressive ILD phenotype who may benefit from a more aggressive initial treatment approach.
| S-EPMC6883123 | biostudies-literature
Project description: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.
| S-EPMC7746162 | biostudies-literature
Project description:The clinical relevance of Krebs von den Lungen-6 (KL-6) levels in patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to evaluate the correlation between KL-6 levels, laboratory parameters, and clinical outcomes. We enrolled 364 patients with confirmed COVID-19 who were hospitalized within 1 week of symptom onset. Their serum KL-6 level was measured on admission. Demographic data, symptoms, comorbidities, and laboratory parameters were recorded at the time of admission. Days to nucleic acid conversion and days of hospitalization were defined as clinical outcomes for evaluating the clinical relevance of serum KL-6 levels in COVID-19. Patients with elevated KL-6 levels were significantly older; had more reported instances of fever, cough, fatigue, and wheezing; and a longer hospital stays than those with normal KL-6 levels; the difference was statistically significant (p < 0.001). Furthermore, KL-6 levels was associated with the days of hospitalization and various laboratory parameters that influence the severity and prognosis of COVID-19. Elevated KL-6 levels have also been shown to be an independent risk factor for prolonged hospitalization. Our data suggest that serum KL-6 levels on admission can serve as an indicator for assessing the clinical outcomes of COVID-19.
| S-EPMC7997619 | biostudies-literature
Project description:Acute exacerbation (AE) significantly affects the prognosis of patients with interstitial lung disease (ILD). This study aimed to investigate the best prognostic biomarker for patients with AE-ILD. Clinical data obtained during hospitalization were retrospectively analyzed for 96 patients with AE-ILD at three tertiary hospitals. The mean age of all subjects was 70.1 years; the percentage of males was 66.7%. Idiopathic pulmonary fibrosis accounted for 60.4% of the cases. During follow-up (median: 88 days), in-hospital mortality was 24%. Non-survivors had higher lactate dehydrogenase and C-reactive protein (CRP) levels, lower ratio of partial pressure of oxygen to the fraction of inspiratory oxygen (P/F ratio), and higher relative change in Krebs von den Lungen-6 (KL-6) levels over 1 week after hospitalization than survivors. In multivariable analysis adjusted by age, the 1-week change in KL-6-along with baseline P/F ratio and CRP levels-was an independent prognostic factor for in-hospital mortality (odds ratio 1.094, P = 0.025). Patients with remarkable increase in KL-6 (≥ 10%) showed significantly worse survival (in-hospital mortality: 63.2 vs. 6.1%) than those without. In addition to baseline CRP and P/F ratio, the relative changes in KL-6 over 1 week after hospitalization might be useful for predicting in-hospital mortality in patients with AE-ILD.
| S-EPMC8941048 | biostudies-literature
Project description:Background and objectivesThe 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.MethodsThis 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.ResultsChanges 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.ConclusionsReduced 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.
| S-EPMC8629416 | biostudies-literature
Project description:BACKGROUND: Serum Krebs von den Lungen-6 (KL-6), which is classified as human mucin-1 (MUC1), is used as a marker of sarcoidosis and other interstitial lung diseases. However, there remain some limitations due to a lack of information on the factors contributing to increased levels of serum KL-6. This study was designed to investigate the factors contributing to increased levels of serum KL-6 by molecular analysis. METHODS: Western blot analysis using anti-KL-6 antibody was performed simultaneously on the bronchoalveolar lavage fluid (BALF) and serum obtained from 128 subjects with sarcoidosis. RESULTS: KL-6/MUC1 in BALF showed three bands and five band patterns. These band patterns were associated with the MUC1 genotype and the KL-6 levels. KL-6/MUC1 band patterns in serum were dependent on molecular size class in BALF. Significantly increased levels of serum KL-6, serum/BALF KL-6 ratio and serum soluble interleukin 2 receptor were observed in the subjects with influx of high molecular size KL-6/MUC1 from the alveoli to blood circulation. The multivariate linear regression analysis involving potentially relevant variables such as age, gender, smoking status, lung parenchymal involvement based on radiographical stage and molecular size of KL-6/MUC1 in serum showed that the molecular size of KL-6/MUC1 in serum was significant independent determinant of serum KL-6 levels. CONCLUSIONS: The molecular structural variants of KL-6/MUC1 and its leakage behavior affect serum levels of KL-6 in sarcoidosis. This information may assist in the interpretation of serum KL-6 levels in sarcoidosis.
| S-EPMC3394217 | biostudies-literature
Project description:BackgroundKrebs von den Lungen 6 (KL-6) is a high-molecular-weight mucin-like glycoprotein, which is also known as MUC1. KL-6 is mainly produced by type 2 pneumocytes and bronchial epithelial cells, and, therefore, elevated circulating KL-6 levels may denote disorders of the alveolar epithelial lining. The objective of this study is to verify if KL-6 serum level might support ICU physicians in predicting mortality, risk stratifying and triaging severe COVID-19 patients.MethodsA retrospective cohort study, including all the COVID-19 patients who measured KL-6 serum values at least once during their ICU stay, was performed. The study sample, 122 patients, was divided in two groups, according to the median KL-6 value at ICU admission (median log-transformed KL-6 value: 6.73 U/ml; group A: KL-6 lower than the median and group B: KL-6 higher than the median).ResultsOne-hundred twenty-two ICU patients were included in this study. Mortality was higher in group B than in group A (80 versus 46%; p < 0.001); both linear and logistic multivariate analyses showed ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) significantly and inversely related to KL-6 values.ConclusionAt ICU admission, KL-6 serum level was significantly higher in the most hypoxic COVID-19 patients and independently associated with ICU mortality.
| S-EPMC9391655 | biostudies-literature
Project description:PurposeThe aim of the study was to estimate and compare the diagnostic accuracy of serum Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) for identifying interstitial lung disease (ILD) from non-ILD among connective tissue disease (CTD) patients.Materials and methodsOriginal articles on the diagnostic accuracy of serum KL-6 and SP-D in differentiating CTD-ILD from CTD-nonILD were identified from three public databases. The overall quality of evidence and methodologic quality of each eligible study were assessed by the Grading of Recommendations, Assessment, Development and Evaluation approach and Quality Assessment of Diagnostic Accuracy Studies, respectively. We used the bivariate model to calculate random-effect sensitivity, specificity, likelihood ratios, and area under curve. Furthermore, trial sequential analysis (TSA) was used to determine whether sample sizes incorporated in the meta-analysis were powerful for evaluating the diagnostic utility. Bayesian network analysis was performed to compare the diagnostic accuracy of 2 serum biomarkers in differentiating ILD among CTD patients and various subgroups.ResultsTwenty-nine studies were included in the quantitative synthesis. No threshold effects were observed (all P values >.05). For diagnosis of ILD among CTD patients, overall sensitivity and specificity of serum KL-6 were 0.76 (95% confidence interval [CI]: 0.68-0.82) and 0.89 (95% CI: 0.83-0.93), whereas those for serum SP-D were 0.65 (95% CI: 0.45-0.80) and 0.88 (95% CI: 0.80-0.93). Comprehensive comparison of 2 circulating biomarkers using back-calculated likelihood ratio (LR) demonstrated that serum KL-6 corresponded to a higher LR+ and a lower LR- in comparison to serum SP-D, as well as in SSc-ILD. TSA indicated that evidence for serum KL-6 and SP-D in identifying CTD-ILD is powerful; nonetheless, more trials were needed for validation of serum KL-6 and SP-D in differentiating CTD-ILD subtypes, including different CTD and ethnicities.ConclusionsThis meta-analysis suggested that serum KL-6 had superior diagnostic accuracy to SP-D for differentiating ILD from non-ILD among CTD patients, providing a convenient and non-invasive approach for screening and management of ILD among CTD patients.
| S-EPMC7220682 | biostudies-literature
Project description:AimHypersensitivity pneumonitis (HP), also referred to as exogenous allergic alveolitis, is one of the most common interstitial lung diseases (ILDs). A potential immune biomarker, Krebs von den lgen-6 (KL-6) characterizes the progression and severity of HP. The meta-analysis in this study was conducted to elucidate the variations in the concentrations of KL-6 in different types of HP.MethodsA systematic search of various databases such as EMBASE, Pubmed, CNKI, VIP, Web of Science, and WanFang was carried out to find relevant published articles between January 1980 and August 2022 that explored the relationship between KL-6 and allergic pneumonia. Standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect sizes for comparison among different groups. The GSE47460 and GSE150910 datasets were downloaded to extract and validate the differences in KL-6 mRNA expression between HP lung tissue and healthy controls. Furthermore, the single-cell sequencing dataset GSE135893 was downloaded to extract KL-6 mRNA expression in type II alveolar epithelial cells to validate the differences between HP and healthy controls. Two researchers evaluated the quality of the included studies by employing Newcastle-Ottawa Scale. All the qualified studies were subjected to statistical analyses carried out utilizing RevMan 5.2, Stata 11.0, and R software 4.1.3.ResultsTwenty studies aligned perfectly with the inclusion criteria of the meta. The concentrations of KL-6 were substantially higher in the blood of HP patients as compared to the control group. Subgroup analyses were carried out in accordance with the allergen source and the results revealed that patients with different allergens had higher blood KL-6 concentrations than healthy controls. Additionally, different subgroups of subjects were created for meta-analysis as per the fibrosis status, race, measurement method, and sample type. The concentration of KL-6 in blood was much higher in all HP subgroups than in healthy control groups. Moreover, the bioinformatics analysis revealed that KL-6 mRNA expression was higher in HP lung tissue and type II alveolar epithelial cells as compared to healthy controls.ConclusionThe present meta-analysis and bioinformatics analysis suggested that the concentration levels of KL-6 varied between HP patients and healthy individuals, and the KL-6 concentrations may be higher in the blood samples of HP patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, CRD42022355334.
| S-EPMC9748086 | biostudies-literature
Project description:Aims/introductionDiabetes mellitus is reported as a risk factor for increased coronavirus disease 2019 (COVID-19) severity and mortality, but there have been few reports from Japan. Associations between diabetes mellitus and COVID-19 severity and mortality were investigated in a single Japanese hospital.Materials and methodsPatients aged ≥20 years admitted to Osaka City General Hospital for COVID-19 treatment between April 2020 and March 2021 were included in this retrospective, observational study. Multivariable logistic regression analysis was carried out to examine whether diabetes mellitus contributes to COVID-19-related death and severity.ResultsOf the 262 patients included, 108 (41.2%) required invasive ventilation, and 34 (13.0%) died in hospital. The diabetes group (n = 92) was significantly older, more obese, had longer hospital stays, more severe illness and higher mortality than the non-diabetes group (n = 170). On multivariable logistic regression analysis, age (odds ratio [OR] 1.054, 95% confidence interval [CI] 1.023-1.086), body mass index (OR 1.111, 95% CI 1.028-1.201), history of diabetes mellitus (OR 2.429, 95% CI 1.152-5.123), neutrophil count (OR 1.222, 95% CI 1.077-1.385), C-reactive protein (OR 1.096, 95% CI 1.030-1.166) and Krebs von den Lungen-6 (OR 1.002, 95% CI 1.000-1.003) were predictors for COVID-19 severity (R2 = 0.468). Meanwhile, age (OR 1.104, 95% CI 1.037-1.175) and Krebs von den Lungen-6 (OR 1.003, 95% CI 1.001-1.005) were predictors for COVID-19-related death (R2 = 0.475).ConclusionsDiabetes mellitus was a definite risk factor for COVID-19 severity in a single Japanese hospital treating moderately-to-severely ill patients.
| S-EPMC9114902 | biostudies-literature