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Comparative diagnostic efficacy of serum Krebs von den Lungen-6 and surfactant D for connective tissue disease-associated interstitial lung diseases: A meta-analysis.

ABSTRACT: PURPOSE:The 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 METHODS:Original 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. RESULTS:Twenty-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. CONCLUSIONS:This 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.

SUBMITTER: Zhong D

PROVIDER: S-EPMC7220682 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Comparative diagnostic efficacy of serum Krebs von den Lungen-6 and surfactant D for connective tissue disease-associated interstitial lung diseases: A meta-analysis.

Zhong Danli D Wu Chanyuan C Bai Jingjing J Hu Chaojun C Xu Dong D Wang Qian Q Zeng Xiaofeng X

Medicine 20200401 16

<h4>Purpose</h4>The 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.<h4>Materials and methods</h4>Original 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 methodolog ...[more]

PMID: 32311947

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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.

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.

Dataset Information

Comparative diagnostic efficacy of serum Krebs von den Lungen-6 and surfactant D for connective tissue disease-associated interstitial lung diseases: A meta-analysis.

Publications

Comparative diagnostic efficacy of serum Krebs von den Lungen-6 and surfactant D for connective tissue disease-associated interstitial lung diseases: A meta-analysis.

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