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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 3  |  Page : 923-927

Diagnostic value of soluble triggering receptor expressed on myeloid cells-1 in pleural effusion


1 Department of Chest Diseases and Tuberculosis, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Departments of Chest Diseases, El-Mahallah Chest Hospital, Gharbia, Egypt

Date of Submission06-Sep-2016
Date of Acceptance03-Oct-2016
Date of Web Publication15-Nov-2017

Correspondence Address:
Mohamed E Ibrahim
El-Mahallah Chest Hospital, El-Mahallah El-Koubra, Gharbia, 31951
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.218282

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  Abstract 

Objectives
The aim of this study was to assess the value of the pleural fluid soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the diagnosis of the etiology of pleural effusion.
Background
The accurate diagnosis of pleural effusion remains a challenging problem even after thoracocentesis and closed pleural biopsy. TREM-1 is a recently described molecule that plays an important role in myeloid cell-activated inflammatory responses.
Patients and methods
We measured sTREM-1 levels from 20 patients with transudative effusion, 20 patients with malignant effusion, 20 patients with tuberculous effusion, and 20 patients with parapneumonic effusion using a specific enzyme-linked immunosorbent assay technique.
Result
sTREM-1 levels were significantly higher in parapneumonic effusion (45.50 ± 13.21 ng/l) than tuberculous effusion (34.90 ± 10.51 ng/l) and in malignant effusion (15.37 ± 5.01 ng/l) than transudative effusion (6.75 ± 3.35 ng/l).
Conclusion
Our study suggests that sTREM-1 can differentiate between infectious effusions (parapneumonic and tuberculous) and noninfectious effusions (malignant and transudative effusions).

Keywords: parapneumonic effusion, pleural effusion, soluble triggering receptor expressed on myeloid cells-1


How to cite this article:
Bakr RM, El-Mahallawy II, Abdelmotaleb TM, Ibrahim ME. Diagnostic value of soluble triggering receptor expressed on myeloid cells-1 in pleural effusion. Menoufia Med J 2017;30:923-7

How to cite this URL:
Bakr RM, El-Mahallawy II, Abdelmotaleb TM, Ibrahim ME. Diagnostic value of soluble triggering receptor expressed on myeloid cells-1 in pleural effusion. Menoufia Med J [serial online] 2017 [cited 2018 Jul 23];30:923-7. Available from: http://www.mmj.eg.net/text.asp?2017/30/3/923/218282


  Introduction Top


Pleural effusion is the abnormal accumulation of fluid in the pleural space. The first step in the evaluation of pleural effusion is a detailed assessment of history and physical examination. The importance of the assessment of history and physical examination arises from the fact that a significant percentage of pleural effusions have no definitive diagnostic features on pleural fluid analysis or pleural biopsy. Diagnosis of the cause of pleural effusion is made on the basis of the clinical setting and exclusion of other alternative causes. The next step is sampling of the pleural fluid and categorization as a transudate or an exudate [1].

Several biological markers have been proposed for the differential diagnosis of these disease entities. The soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a recently discovered cell surface molecule that is selectively expressed on blood neutrophils and a subset of monocytes. It is a member of the immunoglobulin superfamily and is upregulated in the presence of microbial products [2],[3].

The initial characterization of sTREM-1 showed that its expression is upregulated in response to lipopolysaccharide and other microbial products [4].

Therefore, the sTREM is used in the diagnosis of empyema and other types of pleural effusion [5].


  Patients and Methods Top


This study was carried out in El Mehala Chest Hospital; it included 80 patients with pleural effusions of different etiologies.

The study protocol was approved by the Ethical Committee Faculty of Medicine, Menoufia University. The patients were classified into four groups:

Group 1: 20 patients with transudative pleural effusion.

Group 2: 20 patients with malignant pleural effusion.

Group 3: 20 patients with tuberculous pleural effusion.

Group 4: 20 patients with parapneumonic pleural effusion.

A consent was obtained from participants, and an assessment of full clinical history, clinical examination, and routine laboratory investigations were performed. For example, complete blood picture, erythrocyte sedimentation rate, blood urea and serum creatinine, fasting and postprandial blood sugar, and liver function tests, especially albumin, and radiological examination were performed.

Plain chest radiography posteroanterior and lateral views were obtained and, when required, the following was performed.

Computed tomography scan of the chest, abdominal ultrasonography, and echocardiography.

Tuberculin skin test, sputum examination for acid-fast bacilli by Ziehl–Neelsen stain on 3 successive days, serum protein and lactate dehydrogenase (LDH), and diagnostic thoracocentesis were performed.

Collection and processing of the pleural fluid samples were performed. The pleural fluid obtained was subjected to the following examination.

Physical examination including (aspect, color, odor, specific gravity) and chemical examination including the following:

Protein level, glucose level, and adenosine deaminase level when tuberculous effusion was suspected and LDH level.

Bacteriological examination, cytological examination, differential leukocytic count, and cytological examination were performed for malignant cells and assessment of the level of sTREM-1 was performed using an enzyme-linked immunosorbent assay.

Principle of the assay

The kit assay human triggering receptor expressed on myeloid cells (TREM) level in the sample use purified human TREM antibody to coat microtiter plate wells, make solid-phase antibody, then add TREM to wells, combined TREM antibody which with enzyme labeled, become antibody–antigen–enzyme–antibody complex, after washing completely, add substrate, substrate becomes blue color at horseradish peroxidase enzyme-catalyzed, reaction is terminated by the addition of a sulfuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450 nm. The concentration of TREM in the samples was then determined by comparing the optic density of the samples with the standard curve. The materials provided with the kit:




  Results Top


There were no statistically significant differences in terms of the sex distribution in the different groups of patients with pleural effusion [Table 1].
Table 1: Comparison of the sex distribution in the different groups of patients with pleural effusion

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On comparing the mean values of age (years) in all groups, there were no statistically significant differences between groups [Table 2].
Table 2: Comparison of the age distribution in the different groups of patients with pleural effusion

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sTREM-1 levels were significantly higher in parapneumonic effusion (45.50 ± 13.21 ng/l) than tuberculous effusion (34.90 ± 10.51 ng/l) and in malignant effusion (15.37 ± 5.01 ng/l) than transudative effusion (6.75 ± 3.35 ng/l) [Table 3] and [Figure 1].
Table 3: Comparison of the soluble triggering receptor expressed on myeloid cells-1 level (ng/l) in the different groups of patients with pleural effusion

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Figure 1: Comparison of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) level (ng/l) in the different patient groups with pleural effusion.

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sTREM-1 levels showed highly significant differences on comparison of transudative and exudative pleural effusions [Table 4].
Table 4: Comparison of the soluble triggering receptor expressed on myeloid cells-1 level (ng/l) between transudative and exudative pleural effusions

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sTREM-1 levels showed highly significant differences on comparison of malignant and infectious pleural effusions [Table 5].
Table 5: Comparison of the soluble triggering receptor expressed on myeloid cells-1 level (ng/l) between malignant and infectious pleural effusions

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There was a positive correlation between sTREM-1 (ng/l) and protein (g/dl), between sTREM-1 (ng/l) and LDH (U/dl), and between protein (g/dl) and LDH (U/dl) [Table 6] and [Figure 2], [Figure 3], [Figure 4].
Table 6: Pearson's correlations between lactate dehydrogenase, protein, and soluble triggering receptor expressed on myeloid cells-1 in all the groups studied

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Figure 2: Correlation between soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) (ng/l) and protein (g/dl).

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Figure 3: Correlation between soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) (ng/l) and lactate dehydrogenase (LDH) (U/dl).

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Figure 4: Correlation between protein (g/dl) and lactate dehydrogenase (LDH) (U/dl).

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sTREM-1 in pleural effusion has a cut-off point 13.75, a sensitivity of 100%, and a specificity of 87% to differentiate between infectious and noninfectious pleural effusions [Figure 5].
Figure 5: Receiver-operating characteristic (ROC) curve between infectious (3+4) and noninfectious (1+2) groups.

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  Discussion Top


Pleural infection is a common clinical problem. Its successful treatment depends on a rapid diagnosis and early initiation of antibiotics. The measurement of sTREM-1 level in pleural effusions has proven to be a valuable diagnostic tool for differentiating bacterial effusions from effusions of other etiologies [6].

TREM-1 is a recently identified molecule that is involved in monocytic activation and in the inflammatory response. It belongs to a family related to the natural killer cell receptors and is expressed on neutrophils, mature monocytes, and macrophages [7].

In the present study, the mean value of sTREM-1 in pleural fluid was low in noninfectious effusion (transudative and malignant effusions, respectively) and significantly higher in infectious effusion (parapneumonic and tuberculous effusions, respectively). The highest mean value was observed in patients with parapneumonic effusion (the mean value was 45.50 ± 13.21 ng/l), followed by tuberculous effusion (the mean value was 34.90 ± 10.51 ng/l). However, the mean value of malignant pleural effusion was low (15.37 ± 5.01 ng/l) and the lowest mean value was found for transudate effusion (6.75 ± 3.35 ng/l).

These results were in agreement with Kim et al. [8], who concluded that the sTREM-1 expression is significantly higher in parapneumonic effusions, suggesting its potential role as an additional diagnostic marker for pleural effusions.

Also, Faisal et al. [9] studied pleural fluid in forty patients and included 10 parapneumonic patients, 10 malignant patients, 10 patients with congestive heart failure, and 10 patients with post- coronary artery bypass grafting. They concluded that the levels of sTREM-1 were increased in parapneumonic effusions and may prove to be a diagnostic marker and aid in distinguishing parapneumonic effusions from other exudative pleural effusions.

In the study carried out by Klensy-Tait et al. [10], 74 patients with pleural effusions of varying etiologies were investigated. They concluded that sTREM-1 expression in pleural fluid was higher in parapneumonic, tuberculosis, and neoplastic effusions, but low in transudative effusion. In infectious effusions, a high concentration of sTREM-1 may exclude other causes of pleural effusion.

Chan et al. [11] studied 67 patients with pleural effusion because of transudative (14), malignancy (15), tuberculous pleuritis (16), parapneumonic effusion (10), and empyema (12). sTREM-1 was measured by enzyme-linked immunosorbent assay and expressed as pg/ml. They concluded that sTREM-1 is useful in differentiating noninfectious effusion from tuberculous pleuritis. Also, they concluded that soluble and surface TREM-1 are valuable markers in establishing the etiology of pleural effusions.

In the study carried out by Bediwy et al. [12] serum and pleural fluid sTREM-1 were measured in 68 patients with parapneumonic and transudative pleural effusion. Pleural fluid sTREM-1 concentrations were significantly higher in complicated parapneumonic effusions than in uncomplicated parapneumonic effusions. Serum and pleural fluid sTREM-1 levels were higher in parapneumonic than in transudative groups. They concluded that high concentrations of pleural fluid sTREM-1 enable early diagnosis and differentiation of complicated parapneumonic effusions from uncomplicated parapneumonic effusions.

Summah et al. [6] found that sTREM-1 has a good diagnostic accuracy and concluded that it may provide a useful adjunctive tool for the diagnosis of bacterial pleural effusions.

In the study carried out by Ghoneim et al. [13], it was concluded that sTREM-1 could be useful in differentiating between nonpurulent complicated and noncomplicated parapneumonic pleural effusion and hence early pleural drainage in patients with complicated parapneumonic effusion.


  Conclusion Top


Measurement of levels of sTREM-1 in pleural fluid is useful in differentiation between infectious effusion (parapneumonic and tuberculous) and noninfectious effusion (malignant and transudative effusions). In parapneumonic effusion, the sTREM-1 level was higher than that in tuberculous, malignant, and transudative effusions. In tuberculous effusion, the sTREM-1 level was higher than that in malignant effusions and transudative effusions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Martin ML. Non malignant pleural effusion. In: Fishman AP, Elias JA, Fishman JA, et al. editors. Fishman's pulmonary diseases and disorders, 4th ed. New York: McGraw-Hill; 2008. 1987–1988.  Back to cited text no. 1
    
2.
Gibot S, Le Renard PE, Bollaert PE, Kolopp-Sarda MN, Béné MC, Faure GC, Lévy B. Surface triggering receptor expressed on myeloid cells 1 expression patterns in septic shock. Intensive care Med 2005; 31: 594–597.  Back to cited text no. 2
    
3.
Light RW. Pleural diseases. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2007. 211–224.  Back to cited text no. 3
    
4.
Routsi C, Giamarellos-Bourboulis EJ, Antonopolou A, Kollias S, Siasiakou S, Koronaios A, et al. Does soluble triggering receptor expressed on myeloid cells-1 play any role in the pathogenesis of septic shock? Clin Exp Immunol 2005; 142:62–67.  Back to cited text no. 4
    
5.
Leibowitz S, Kennedy L. The tuberculin reaction in pleural cavity and its suppression by anti lymphocyte serum. Br J Exp Pathol 1973; 54:152–162.  Back to cited text no. 5
    
6.
Summah H, Tao L-L, Zhu Y-G, Jiang H-N, Qu J-M. Pleural fluid soluble triggering receptor expressed on myeloid cells-1 as a marker of bacterial infection: a meta-analysis. BMC Infect Dis 2011; 11:280.  Back to cited text no. 6
    
7.
Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 2001; 410:1103–1107.  Back to cited text no. 7
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8.
Kim JH, Park EY, Kim WH, Park W, Jeong HC, Lee JH, et al. Soluble triggering receptor expressed on myeloid cells-1. Role in the diagnosis of pleural effusions. Tuberc Respir Dis 2007; 62:290–298.  Back to cited text no. 8
    
9.
Faisal MB, Barnette R, Magdalena O, Richard L, Ruxana TS. MRCP soluble TREM-1 (triggering receptor expressed on myeloid cells) in pleural effusions. A marker of infectious disease. Am Coll Chest Physicians 2007; 132:462–463.  Back to cited text no. 9
    
10.
Klensy-Tait J, Turnbull IR, Colonna M. The TREM receptor family and signal integration. Nat Immunol 2006; 7:1266–1273.  Back to cited text no. 10
    
11.
Chan MC, Chang KM, Chao WC, Lin LY, Kuo BI, Hsu JY, Wu CL. Evaluation of a new inflammatory molecule (triggering receptor expressed on myeloid cells-1) in the diagnosis of pleural effusion. Respirology 2007; 12:333–338.  Back to cited text no. 11
    
12.
Bediwy AS, Elkholy MG, Elbedewy M, Hasane MA. Pleural fluid soluble triggering receptor expressed on myeloid cells-1 in complicated and uncomplicated parapneumonic pleural effusions. ISRN Pulmonol 2011; 2011:689–691.  Back to cited text no. 12
    
13.
Ghoneim AHA, Sheble ER, Elshora AE, Salah AA. Diagnostic utility of soluble triggering receptor expression on myeloid cells-1 in complicated parapneumonic pleural effusion. Egypt J Chest Dis Tuberc 2013; 62:593–597.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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