Dataset Information

Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion.

ABSTRACT:

Background

The simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains difficult. This study aimed to determine the accuracy of hepatocyte growth factor (HGF) in the diagnosis of TPE.

Methods

We quantified the expression of HGF, adenosine deaminase (ADA), and interferon gamma (IFN-γ) in pleural effusion (PE) in 97 TPE subjects and 116 non-TPE subjects using an enzyme-linked immunosorbent assay (ELISA) or a fully automatic biochemical analyzer. The diagnostic performance of these three biomarkers was evaluated using a receiver operating characteristic (ROC) curve of subjects by age and gender.

Results

We discovered that the TPE group had much higher levels of HGF than the non-TPE group, regardless of age or gender, and that there was no statistically significant difference between the two groups' levels of HGF expression in peripheral plasma. In female TPE patients aged ≤65 years, the AUCs of TPE and non-TPE diagnosed by HGF, ADA or IFN-γ were 0.988, 0.964, and 0.827, respectively. HGF plus ADA had the highest diagnostic efficacy in female TPE patients aged ≤65 years. With HGF plus ADA having a cut-off value of 0.219 for distinguishing TPE from non-TPE, the area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 0.998 (95% confidence interval [CI], 0.993-1.000), 100 (95% CI, 89.997-100.000), 96.667 (95% CI, 82.783-99.916), 97.222 (95% CI, 83.594-99.586), and 100.

Conclusion

This study confirmed that HGF plus ADA has high diagnostic efficacy in younger female TPE patients and has the potential to be an excellent biomarker.

SUBMITTER: Zheng SC

PROVIDER: S-EPMC10359098 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion.

Zheng Sheng-Cai SC Huang Zhong-Yin ZY Zhai Kan K Shi Huan-Zhong HZ Shao Ming-Ming MM

Frontiers in microbiology 20230706

<h4>Background</h4>The simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains difficult. This study aimed to determine the accuracy of hepatocyte growth factor (HGF) in the diagnosis of TPE.<h4>Methods</h4>We quantified the expression of HGF, adenosine deaminase (ADA), and interferon gamma (IFN-γ) in pleural effusion (PE) in 97 TPE subjects and 116 non-TPE subjects using an enzyme-linked immunosorbent assay (ELISA) or a fully automatic biochemical analyzer. The diagn ...[more]

PMID: 37485530

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Project description:BACKGROUNDCurrent diagnostic tools for tuberculous pleural effusion (TPE) are often inadequate, making accurate diagnosis challenging. Effective identification of TPE is critical for ensuring proper treatment and preventing tuberculosis relapse. This study explored the potential of granzyme A (GZMA) as a biomarker for TPE.METHODSPatients with TPE, malignant pleural effusion (MPE), and parapneumonic pleural effusion (PPE) were recruited into discovery and validation cohorts. The discovery cohort consisted of 200 patients with TPE and 100 patients with MPE, while the validation cohort included 167 patients with TPE, 84 patients with MPE, and 69 patients with PPE.RESULTSIn the discovery cohort, GZMA levels were significantly elevated in TPE compared with MPE, demonstrating 90% sensitivity and 91% specificity at a cutoff of 102.29 ng/mL for effectively distinguishing between the two conditions. In the validation cohort, GZMA maintained high diagnostic performance, distinguishing TPE from MPE with 87% sensitivity and 87% specificity and from PPE with 87% sensitivity and 84% specificity. Incorporating GZMA, lactate dehydrogenase (LDH), and adenosine deaminase (ADA) into a random forest model further improved diagnostic accuracy. In the discovery cohort, this model achieved 92% sensitivity and 100% specificity, and in the validation cohort, it distinguished TPE from MPE with 87% sensitivity and 94% specificity and from PPE with 87% sensitivity and 91% specificity.CONCLUSIONOverall, GZMA is a promising biomarker for diagnosing TPE, with improved accuracy when combined with LDH and ADA, providing a robust tool for timely identification and effective management of patients with TPE.FUNDINGThe study was supported by Science and Technology Project of Shenzhen (KCXFZ20211020163545004, KQTD20210811090219022, JCYJ20220818095610021, JSGG20220822095200001, JCYJ20210324094614038), Shenzhen Medical Research Funding (B2302035, A2302004), Provincial Natural Science Foundation of Guangdong (2022A1515220034), and Shenzhen Third People's Hospital Research Foundation (G2022155).

Project description:BackgroundAdenosine deaminase (ADA) is a sensitive marker of tuberculous pleural effusion (TBPE). However, in pleural effusion (PE), the detection of ADA alone cannot be used to determine whether the increase in the ADA level is caused by the rising proportion of macrophages and lymphocytes in the cell components or by the increase in the total cell number. The diagnostic precision of ADA is probably restricted due to the false positive and negative results. Thus, we explored the clinical value of the ratio of PE ADA to lactate dehydrogenase (LDH) in differentiating between TBPE and non-TBPE.MethodsPatients hospitalized with PEs between January 2018 and December 2021 were retrospectively recruited for this study. We analyzed the values of ADA, LDH, and 10× ADA/LDH in the patients with TBPE and non-TBPE. We also determined the sensitivity, specificity, Youden index, and area under the curve for 10× ADA/LDH at different ADA levels and evaluated its diagnostic accuracy.ResultsIn total, 382 patients with PEs were included in the study. Among whom, 144 were diagnosed with TBPE, this supposes a "pre-test probability" >40%. It is quite high, 134 with malignant PEs, 19 with parapneumonic PEs, 43 with empyema, 24 with transudate PEs, and 18 with other types of PE of a known etiology. The ADA levels were positively correlated with the LDH levels in TBPE. LDH levels usually increase in response to cell damage or cell death. The 10× ADA/LDH level was significantly increased in the TBPE patients. In addition, the 10× ADA/LDH level increased as the ADA level increased in TBPE. To differentiate between TBPE and non-TBPE, the optimal cut-off value of 10× ADA/LDH at different ADA levels was assessed using receiver operating curves. At an ADA level >20 U/L, 10× ADA/LDH showed the best diagnostic performance, and had a specificity and sensitivity of 0.94 (95% CI: 0.84-0.98) and 0.95 (95% CI: 0.88-0.98), respectively.ConclusionsThe 10× ADA/LDH dependent diagnostic index can be used to distinguish TBPE from non-TBPE and could be used to guide future clinical decisions.

Project description:Background: The diagnostic value of pleural effusion mononuclear cells count for tuberculous pleurisy (TBP) is unclear. We aimed to evaluate the diagnostic value of pleural effusion mononuclear cells count and its combination with adenosine deaminase (ADA) in TBP patients. Methods: We initially analyzed 296 patients with unknown pleural effusion from the Department of Respiratory Medicine at Provincial People's Hospital during January 2014 to February 2018. Ultimately, 100 tuberculous pleurisy (TBP) patients and 105 non-tuberculous pleurisy (non-TBP) patients with pleural effusion were investigated in the current study. Meanwhile, pleural effusion mononuclear cells count and ADA test were performed to evaluate the diagnostic value for TBP. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), accuracy and area under the receiver operating characteristic (ROC) curve (AUC) of pleural effusion mononuclear cells count only and its combination with ADA for TBP diagnosis were investigated. Results: (i) The best cut-off value of pleural effusion mononuclear cells count for TBP diagnosis was 969.6 × 106/L, with the sensitivity, specificity and accuracy of 76, 57, and 66%, respectively. (ii) Combination of pleural effusion mononuclear cells count and ADA test suggested diagnostic value for TBP. Specifically, serial test showed the sensitivity, specificity, accuracy of 65, 90, 78%, respectively, whereas parallel test revealed the sensitivity, specificity, accuracy of 92, 45, 68%, respectively. The sensitivity of parallel test (92%) was significantly higher than pleural effusion mononuclear cells count alone (76%) (X2 = 23.19, p < 0.001). (iii) The area under the ROC of pleural effusion mononuclear cells count and it combined with ADA were 0.66 (95% CI, 0.59-0.72) and 0.83 (95% CI, 0.78-0.89), respectively, with statistically significant difference (Z = 3.46, p < 0.001). Conclusion: This retrospective case-control study demonstrated that pleural effusion mononuclear cells count is relatively useful for TBP diagnosis. Furthermore, the pleural effusion mononuclear cells count in combination with ADA can further improve the diagnostic accuracy of TBP.

Project description:BackgroundIncreased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we compare various disease characteristics in patients with high-ADA pleural effusion.MethodsWe retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors.ResultsThe most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range [IQR] 67.2-104.1), higher than those of patients with pleural infection (median 60.9 [IQR 45.3-108.0], p = 0.004), malignant pleural effusion (median 54.1 [IQR 44.8-66.7], p < 0.001), or autoimmune diseases (median 48.5 [IQR 45.9-58.2], p = 0.008), with no significant difference from NTM (p = 1.000) or ML (p = 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively.ConclusionCases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases.

Project description:Accurate differential diagnosis is the key to choosing the correct treatment for pleural effusion. The present study aimed to assess whether interleukin 32 (IL-32) could be a new biomarker of tuberculous pleural effusion (TPE) and to explore the biological role of IL-32 in TPE. IL-32 levels were evaluated in the pleural effusions of 131 patients with undetermined pleural effusion from Wuhan and Beijing cohorts using an enzyme-linked immunosorbent assay method. Macrophages from TPE patients were transfected with IL-32-specific small interfering RNA (siRNA), and adenosine deaminase (ADA) expression was determined by real-time PCR and colorimetric methods. With a cutoff value of 247.9 ng/mL, the area under the curve of the receiver operating characteristic (ROC) curve for IL-32 was 0.933 for TPE, and the sensitivity and specificity were 88.4% and 93.4%, respectively. A multivariate logistic regression model with relatively good diagnostic performance was established. IL-32-specific siRNA downregulated ADA expression in macrophages, and IL-32γ treatment significantly induced ADA expression. Our results indicate that IL-32 in pleural effusion may be a novel biomarker for identifying patients with TPE. In addition, our multivariate model is acceptable to rule in or rule out TPE across diverse prevalence settings. Furthermore, IL-32 may modulate ADA expression in the tuberculosis microenvironment. (This study has been registered at ChiCTR under registration number ChiCTR2100051112 [https://www.chictr.org.cn/index.aspx].) IMPORTANCE Tuberculous pleural effusion (TPE) is a common form of extrapulmonary tuberculosis, with manifestations ranging from benign effusion with spontaneous absorption to effusion with pleural thickening, empyema, and even fibrosis, which can lead to a lasting impairment of lung function. Therefore, it is of great significance to find a rapid method to establish early diagnosis and apply antituberculosis therapy in the early stage. This study indicates that interleukin 32 (IL-32) in pleural effusion is a new high-potency marker to distinguish TPE from pleural effusions with other etiologies. A multivariate model combining age, adenosine deaminase (ADA), lactic dehydrogenase, and IL-32 may reliably rule in TPE in intermediate- or high-prevalence areas. Additionally, we observed that IL-32 might regulate ADA expression in macrophages in the tuberculosis microenvironment. Therefore, this study provides new insights into the role of IL-32 in the tuberculosis microenvironment.

Dataset Information

Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion.

Background

Methods

Results

Conclusion

Publications

Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion.

Similar Datasets

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