Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema

AbstractPatients with complicated parapneumonic effusion (CPPE)/empyema have high morbidity and mortality, particularly when adequate management is delayed. We aimed to investigate novel dysregulated cytokines that can be used as biomarkers for infectious pleural effusions, especially for CPPE/empyema. Expression of 40 cytokines in parapneumonic effusions (PPE) was screened in the discovery phase, involving 63 patients, using a multiplex immunobead-based assay. Six cytokines were subsequently validated by enzyme-linked immunosorbent assays (ELISAs). We then used ELISA to further evaluate the diagnostic values and cutoff values of these cytokines as potential biomarkers in an expanded group that included 200 patients with uncomplicated parapneumonic effusion (UPPE), CPPE, empyema, transudates, other exudates, and malignant pleural effusion (MPE). The pleural levels of four cytokines (MIF, MIP-3α, IL-1β, ENA-78) were highest and significantly increased in CPPE/empyema compared with those in other etiologies. According to receiver operating characteristic curve analysis, the four cytokines (MIF, MIP-3α, IL-1β, and ENA-78) had areas under the curve (AUCs) greater than 0.710 for discriminating parapneumonic pleural effusion from noninfectious pleural effusions. In a comparison of nonpurulent CPPE with UPPE, logistic regression analysis revealed that pleural fluid MIF ≥ 12 ng/ml and MIP-3α ≥ 4.3 ng/ml had the best diagnostic value; MIF also displayed the highest odds ratio of 663 for nonpurulent CPPE, with 97.5% specificity, 94.44% sensitivity, and an AUC of 0.950. In conclusion, our results show that elevated MIF and MIP-3α may be used as novel biomarkers for PPE diagnosis, particularly in patients with CPPE/empyema; the findings indicate that dysregulated cytokine expression may provide clues about the pathogenesis of pleural infection.

Download Full-text

The Differential Diagnostic Values of Cytokine Levels in Pleural Effusions

Mediators of Inflammation ◽

10.1155/mi.2005.2 ◽

2005 ◽

Vol 2005 (1) ◽

pp. 2-8 ◽

Cited By ~ 15

Author(s):

Saadet Akarsu ◽

A. Nese Citak Kurt ◽

Yasar Dogan ◽

Erdal Yilmaz ◽

Ahmet Godekmerdan ◽

...

Keyword(s):

Differential Diagnosis ◽

Pleural Effusion ◽

Pleural Fluid ◽

Parapneumonic Effusion ◽

Pleural Effusions ◽

Tuberculous Pleural Effusion ◽

Cytokine Levels ◽

Diagnostic Values

The aim is to examine whether the changes in pleural fluid interleukin (IL)-1β, IL-2, IL-6, and IL-8 levels were significant in differential diagnosis of childhood pleural effusions. IL-1β, IL-2, IL-6, and IL-8 levels in pleural fluids of all 36 patients were measured. The levels of IL-1β, IL-2, IL-6, and IL-8 in pleural fluids were statistically significantly higher in the transudate group compared with those of the exudate group. The levels of IL-1β, IL-6, and IL-8 were also found to be statistically significantly higher in the empyema group compared with both the parapneumonic and the tuberculous pleural effusion groups. The levels of IL-2 and IL-6 were detected to be statistically significantly higher in the tuberculous pleural effusion group in comparison with those of the parapneumonic effusion group. The results showed that pleural fluids IL-1β, IL-2, IL-6, and IL-8 could be used in pleural fluids exudate and transudate distinction.

Download Full-text

Potential diagnostic value of pleural fluid cytokines levels for tuberculous pleural effusion

Scientific Reports ◽

10.1038/s41598-020-79685-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Neda Dalil Roofchayee ◽

Majid Marjani ◽

Neda K. Dezfuli ◽

Payam Tabarsi ◽

Afshin Moniri ◽

...

Keyword(s):

Differential Diagnosis ◽

Pleural Effusion ◽

Diagnostic Accuracy ◽

Pleural Fluid ◽

Diagnostic Value ◽

Parapneumonic Effusion ◽

Pleural Effusions ◽

Tuberculous Pleural Effusion ◽

New Biomarkers ◽

High Level

AbstractPatients with tuberculous pleural effusion (TPE) or malignant pleural effusions (MPE) frequently have similar pleural fluid profiles. New biomarkers for the differential diagnosis of TPE are required. We determined whether cytokine profiles in the PE of patients could aid the differential diagnosis of TPE. 30 patients with TPE, 30 patients with MPE, 14 patients with empyema (EMP) and 14 patients with parapneumonic effusion (PPE) were enrolled between Dec 2018 and 2019. The levels of interleukin (IL)-6, IL-18, IL-27, CXCL8, CCL-1 and IP-10 were determined in PE by ELISA along with measurements of adenosine deaminase (ADA). The best predictors of TPE were combined ADA.IL-27 [optimal cut-off value = 42.68 (103 U ng/l2), sensitivity 100%, specificity 98.28%], ADA [cut off value 27.5 (IU/l), sensitivity 90%, specificity 96.5%] and IL-27 [cut-off value = 2363 (pg/ml), sensitivity 96.7%, specificity 98.3%, p ≤ 0.0001]. A high level of IL-6 [cut-off value = 3260 (pg/ml), sensitivity 100%, specificity 67.2%], CXCL8 [cut-off value = 144.5 (pg/ml), sensitivity 93.3%, specificity 58.6%], CCL1 [cut-off value = 54 (pg/ml), sensitivity 100%, specificity 70.7%] and IP-10 [cut-off value = 891.9 (pg/ml), sensitivity 83.3%, specificity 48.3%] were also predictive of TPE. High ADA.IL-27, ADA and IL-27 levels differentiate between TPE and non-TPE with improved specificity and diagnostic accuracy and may be useful clinically.

Download Full-text

Pleural infection and malignancy

10.1093/med/9780199568741.003.0143 ◽

2018 ◽

Author(s):

Seamus Grundy

Keyword(s):

Pleural Effusion ◽

Malignant Pleural Effusion ◽

Lymphatic Drainage ◽

Parapneumonic Effusion ◽

Malignant Cells ◽

Pleural Effusions ◽

Pleuritic Chest Pain ◽

Systemic Sepsis ◽

Cardiovascular Instability ◽

Pleural Infection

Pleural infection transitions from simple parapneumonic effusion, to complex parapneumonic effusion, to empyema. Primary empyema occurs without an underlying pneumonic process. Pleural infection commonly presents identically to pneumonia with dyspnoea, purulent sputum, and fevers. It may be associated with pleuritic chest pain. Empyema can cause systemic sepsis, leading to cardiovascular instability and multi-organ failure. A malignant pleural effusion arises when malignant cells infiltrate the pleura, resulting in increased production and decreased lymphatic drainage of pleural fluid. Malignant pleural effusions are either metastatic or primary mesothelioma. This chapter discusses pleural infection, malignant pleural effusion, and mesothelioma, focusing on etiology, symptoms, demographics, diagnosis, prognosis, and treatment.

Download Full-text

Assessment of the diagnostic value of CEA, CA125, and CRP and their cut-off point for discrimination of exudative pleural effusions

Bionatura ◽

10.21931/rb/2021.06.03.10 ◽

2021 ◽

Vol 3 (3) ◽

pp. 1944-1947

Author(s):

Hanie Raji ◽

Seyed Hamid Borsi ◽

Mehrdad Dargahi MalAmir ◽

Ahmad Reza Asadollah Salmanpour

Keyword(s):

Pleural Effusion ◽

Tumor Marker ◽

Pleural Fluid ◽

Tumor Markers ◽

Low Cost ◽

High Specificity ◽

Diagnostic Value ◽

Pleural Effusions ◽

Cross Sectional ◽

The Mean

Pleural effusion is divided into exudative and transudative effusion, and the distinction between exudate and transudate requires multiple investigations of biochemical parameters and their comparison in pleural fluid and serum. This study aimed to assess the diagnostic value of CEA, CA125, and CRP and their cut-off point for discrimination of exudative pleural effusions. This epidemiological and cross-sectional study was performed on 50 patients aged between 18 to 90 years with the diagnosis of exudative pleural effusion referred to Imam Khomeini Hospital in Ahvaz in 2018 and 2019. Demographic and clinical information of patients were collected. The pleural effusion was diagnosed based on physical examination and chest radiography. Pleural effusion was confirmed by thoracentesis. A pleural fluid sample was taken from all patients, and the levels of CEA, CA125, and CRP markers were measured in the pleural fluid. Differentiation of transudate and exudate pleural effusions was performed using Light criteria. The mean CEA and CA125 level of pleural fluid were significantly higher, and the mean CRP level of pleural fluid was significantly lower in patients with malignant diagnoses (P <0.05). Cut-off value with highest sensitivity and specificity in differentiating types of exudative pleural effusions was obtained for CEA tumor marker (greater than 49.8), CA125 tumor marker (greater than 814.02), and CRP marker (less than 7.56). Also, in differentiating types of exudative pleural effusions, CEA tumor marker had sensitivity (89.03%) and specificity (78.42%); CA125 tumor marker had sensitivity (53.18%) and specificity (62.44%), and CRP marker had sensitivity (82.16%), and specificity (89.05%) were. Although the tumor markers had high specificity in the present study, the low sensitivity of some of these tumor markers reduced their diagnostic value. On the other hand, given the numerous advantages of tumor markers, such as low cost and non-invasive, combining them with another can increase the diagnostic value and accuracy.

Download Full-text

Determination of tissue polypeptide-specific antigen in pleural fluid and serum from patients with pleural effusion

The International Journal of Biological Markers ◽

10.1177/172460089501000306 ◽

1995 ◽

Vol 10 (3) ◽

pp. 161-165 ◽

Cited By ~ 1

Author(s):

V. Villena ◽

J. Echave-Sustaeta ◽

A. Lopez-Encuentra ◽

P. Martin-Escribano ◽

J. Estenoz-Alfaro ◽

...

Keyword(s):

Pleural Effusion ◽

Pleural Fluid ◽

Sensitivity And Specificity ◽

Specific Antigen ◽

Diagnostic Value ◽

Pleural Effusions ◽

Malignant Pleural Effusions ◽

Cytologic Analysis

As a tool for differentiating malignant and benign pleural effusions, we evaluated the diagnostic value of the assay of tissue polypeptide-specific antigen (TPS) in pleural fluid and serum, and of the pleural fluid TPS/serum TPS ratio in patients with pleural effusion. We studied prospectively 147 consecutive patients who had pleural effusions: 43 malignant pleural effusions and 104 benign pleural effusions. TPS levels were measured by RIA. The sensitivity and specificity of these measurements were: TPS in pleural fluid (cutoff 20,000 U/L): 0.21 and 0.98; TPS in serum (cutoff 300 U/L): 0.31 and 0.96; pleural fluid TPSI serum TPS ratio (cutoff 1200): 0.07 and 0.99. All these values enhanced the sensitivity of cytologic analysis of pleural fluid. However, we conclude that TPS assay in pleural fluid and serum, and the pleural fluid TPSI serum TPS ratio have limited diagnostic value in patients with pleural effusion.

Download Full-text

Protein Profiling of Pleural Effusions to Identify Malignant Pleural Mesothelioma Using SELDI-TOF MS

Technology in Cancer Research & Treatment ◽

10.1177/153303460900800502 ◽

2009 ◽

Vol 8 (5) ◽

pp. 323-332 ◽

Cited By ~ 23

Author(s):

Joost P.J.J. Hegmans ◽

Joris D. Veltman ◽

Eric T. Fung ◽

Thorsten Verch ◽

Curtis Glover ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Characteristic Curve ◽

Diagnostic Value ◽

Exchange Chromatography ◽

Protein Profiling ◽

Cytokeratin 19 ◽

Pleural Mesothelioma ◽

Pleural Effusions ◽

Proteinchip Array ◽

Potential Biomarker

Diagnosis of malignant pleural mesothelioma (MM) is limited. Novel proteomic technologies can be utilized to discover changes in expression of pleural proteins that might have diagnostic value. The objective of this study was to detect protein profiles that could be used to identify malignant pleural mesothelioma with surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS). Pleural effusions were collected from patients with confirmed mesothelioma (n = 41) and from patients with effusions due to other causes ([n = 48] cancerous and non-cancerous). Samples were fractionated using anion exchange chromatography and bound to different types of ProteinChip array surfaces. All samples were also subjected to other commercially available immunoassays (human epididymes protein 4 [HE4], osteopontin [OPN], soluble mesothelin-related proteins [SMRP], and the cytokeratin 19 fragment [CYFRA 21–1]). Peak intensity data obtained by SELDI-TOF were subjected to classification algorithms in order to identify potential classifier peaks. A protein peak at m/z 6614 was characterized as apolipoprotein (Apo) CI. In this setting, the sensitivity and specificity of this potential biomarker was 76 % and 69 %, respectively. The area under the receiver operating characteristic curve (AUC) for Apo CI was 0.755, thereby outperforming OPN, HE4, and CYFRA 21–1. SMRP performed best with an AUC of 0.860 with a sensitivity of 83% and specificity of 74%. Our study validates the use of SMRP as a diagnostic marker for pleural mesothelioma and furthermore suggests that Apo CI levels could be used in the future to discriminate pleural mesothelioma from other causes of exudates.

Download Full-text

The Diagnostic Value of the Pleural Fluid C-Reactive Protein in Parapneumonic Effusions

Disease Markers ◽

10.1155/2016/7539780 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Shimon Izhakian ◽

Walter G. Wasser ◽

Benjamin D. Fox ◽

Baruch Vainshelboim ◽

Mordechai R. Kramer

Keyword(s):

Heart Failure ◽

Pleural Effusion ◽

Pleural Fluid ◽

Predictive Value ◽

Medical Center ◽

Diagnostic Value ◽

Parapneumonic Effusion ◽

C Reactive Protein ◽

Reactive Protein ◽

Sensitivity Specificity

Purpose. The aim of this study was to evaluate the sensitivity of pleural C-reactive protein (CRP) biomarker levels in identifying parapneumonic effusions.Methods. A single-center, retrospective review of 244 patients diagnosed with pleural effusions was initiated among patients at the Rabin Medical Center, Petah Tikva, Israel, between January 2011 and December 2013. The patients were categorized into 4 groups according to their type of pleural effusion as follows: heart failure, malignant, post-lung transplantation, and parapneumonic effusion.Results. The pleural CRP levels significantly differentiated the four groups (p<0.001) with the following means: parapneumonic effusion,5.38±4.85 mg/dL; lung transplant,2.77±2.66 mg/dL; malignancy,1.19±1.51 mg/dL; and heart failure,0.57±0.81 mg/dL. The pleural fluid CRP cut-off value for differentiating among parapneumonic effusions and the other 3 groups was 1.38 mg/dL. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.2%, 71.5%, 37%, and 95%, respectively. A backward logistic regression model selected CRP as the single predictor of parapneumonic effusion (OR = 1.59, 95% CI = 1.37–1.89).Conclusions. Pleural fluid CRP levels can be used to distinguish between parapneumonic effusions and other types of exudative effusions. CRP levels < 0.64 mg/dL are likely to indicate a pleural effusion from congestive heart failure, whereas levels ≥ 1.38 mg/dL are suggestive of an infectious etiology.

Download Full-text

Th1/Th2 cytokine profiles differentiating tuberculous from malignant pleural effusions: A systematic review and meta-analysis

10.37766/inplasy2022.1.0005 ◽

2022 ◽

Author(s):

Yulin Zeng ◽

◽

Liwei Wang ◽

Hai Zhou ◽

Yu Qi

Keyword(s):

Pleural Effusion ◽

Immune Responses ◽

Meta Analysis ◽

Diagnostic Value ◽

Pleural Effusions ◽

Cytokine Profiles ◽

Th2 Cytokine ◽

Different Types ◽

Review Question ◽

Th1 And Th2

Review question / Objective: To clarify which one has a different predominance of Th1 and Th2 immune responses in malignant and tuberculous pleural effusions. We did a meta-analysis of the results published previously to assess the levels of Th1/Th2 cytokines in two types of pleural effusion and evaluated its ability to distinguish TPE from MPE. Condition being studied: Malignant and tuberculous pleural effusions are the two most common types of exudative pleural effusions, both of which can be seen with the typical accumulation of lymphocytes. Immune responses mediated by either the Th1 or Th2 subset dominate, depending on different types of pleural effusion. Thus, we performed a meta-analysis of all available studies to quantitatively evaluate the levels of Th1/Th2 cytokine profiles in TPE and MPE, as well as to assess the potential diagnostic value of these cytokines in discriminating TPE from MPE.

Download Full-text

Diagnostic value of pleural fluid and serum procalcitonin levels in the diagnosis of parapneumonic pleural effusion

Tuberkuloz ve Toraks ◽

10.5578/tt.5334 ◽

2013 ◽

Vol 61 (2) ◽

pp. 103-109 ◽

Cited By ~ 4

Author(s):

Canan DOĞAN ◽

Semra BİLAÇEROĞLU ◽

Ali Kadri ÇIRAK ◽

Ayşe ÖZSÖZ ◽

Defne ÖZBEK

Keyword(s):

Pleural Effusion ◽

Pleural Fluid ◽

Diagnostic Value ◽

Parapneumonic Pleural Effusion

Download Full-text

Score for Differentiating Pleural Tuberculosis from Malignant Effusion

Medical Sciences ◽

10.3390/medsci7030036 ◽

2019 ◽

Vol 7 (3) ◽

pp. 36 ◽

Cited By ~ 3

Author(s):

Alejandra González ◽

Mariano Fielli ◽

Adrián Ceccato ◽

Carlos Luna

Keyword(s):

Lactic Acid ◽

Pleural Effusion ◽

White Cell Count ◽

Characteristic Curve ◽

Area Under The Curve ◽

Wald Test ◽

Daily Practice ◽

Final Diagnosis ◽

Pleural Effusions ◽

Two Samples

Differential diagnosis of lymphocytic pleural effusions between tuberculous (TBE) and malignant (ME) effusion is usually difficult in daily practice. Our aim was to develop a score to differentiate TBE from ME effusions. A cohort of 138 consecutive patients with pleural effusion was prospectively studied from May 2014 through June 2017. Glucose, lactate dehydrogenase (LDH), proteins, white cell count, lactic acid, and pH in the pleural fluid were measured. Pleural effusions other than lymphocytic, patients with a final diagnosis other than tuberculosis or malignancy, and patients who met Light’s criteria for transudate were excluded. Eighty-two samples (47 TBE and 35 ME) were included in the analysis. Using logistic regression analysis and Wald test, we developed a score including age, glucose, proteins, and lactic acid. The receiver operating characteristic curve (ROC) for the score was determined, and the area under the curve (AUC) was calculated. A cutoff of eight points was required to achieve 93.5% sensitivity, 78% specificity, and a likelihood ratio of 4.26 to distinguish tuberculosis from malignant pleural effusion. The AUC of the score was 0.915 (95% CI = 0.82–0.96).

Download Full-text