Performance of Different Pleural Fluid Biomarkers in Tuberculous Pleurisy


Parameter

Tuberculous pleural effusion (TPE)

Non-tuberculous pleural effusion (non-TPE)

p

n = 44

n = 159

Age (years)

51.5 (35.5–71.5)

68 (58–77)

0.0001

Sex F/M

11/33

75/84

0.01a

Site of pleural effusion (left/right/bilateral)

23/21/0

62/94/3

NSa

Body temperature (°C)

38.5 (36.6–39.0)

36.6 (36.6–38.0)

<0.0001

Duration of symptoms (weeks)

4 (2–7)

3 (1–6)

NS

TST (mm)

12 (10–15)

0 (0–9)

<0.001

WBC (109/L)

6.8 (5.3–8.7)

9.6 (7.0–12.9)

<0.0001

Pleural fluid protein concentration (g/dL)

5.0 (4.6–5.9)

4.1 (3.0–4.6)

<0.0001

Pleural fluid/serum protein ratio

0.7 (0.7–0.8)

0.6 (0.5–0.7)

<0.0001

Pleural fluid LDH activity (IU/L)

1,078 (604–2,070)

778 (298–1,795)

<0.05

Pleural fluid/serum LDH ratio

2.5 (1.5–3.8)

1.3 (0.6–3.2)

<0.05

Pleural fluid total cell count (109/L)

1,700 (1,200–3,300)

1,300 (500–3,180)

NS

Pleural fluid lymphocyte percentage

93 (81–96)

63 (36–81)

<0.0001

Pleural fluid ADA (U/L)

58 (44–91)

5 (0–14)

<0.0001

Pleural fluid IFN-γ (pg/mL)

735 (311–1,000)

8 (8–8)

<0.0001

Pleural fluid IL-2sRα (pg/mL)

2,665 (2,065–4,025)

2,116 (1,353–3,514)

<0.05

Pleural fluid IP-10 (pg/mL)

31,660 (21,570–34,399)

1,303 (359–3,400)

<0.001

Pleural fluid IL-12p40 (pg/mL)

621 (392–981)

203 (83–364)

<0.001

Pleural fluid IL-18 (pg/mL)

463 (57–858)

62 (8–185)

<0.001

Pleural fluid TNF-α (pg/mL)

79 (53–194)

13 (5–24)

<0.001

Pleural fluid Fas-ligand (pg/mL)

86 (64–133)

21 (159–32)

<0.001

Pleural fluid human MDC (pg/mL)

753 (523–1,056)

3,631 (281–585)

<0.001

Pleural fluid IL-23 (pg/mL)

1.5 (0.7–3.5)

1.2 (0.1–2.0)

NS


The data were expressed as median with interquartile range; quantitative variables were analyzed with Mann-Whitney U test

n patients number, NS non-significant, TST tuberculin skin test, WBC white blood count, F female, M male, LDH lactate dehydrogenase

aRelationship between qualitative variables was tested in system contingency tables (FREQ) using Chi-square or Fisher test



Table 2 shows the diagnostic performance of various pleural fluid biomarkers differentiating between TPE and non-TPE. The highest diagnostic accuracy was found for IFN-γ. Interferon-induced-protein 10 and Fas-ligand showed only a slightly lower accuracy. AUC of four pleural fluid biomarkers (IFN-γ. IP-10, Fas-ligand, and ADA) was higher than 0.9. Very low diagnostic performance was demonstrated for pleural fluid IL-23, with its sensitivity and specificity below 30 and 60 %, respectively.


Table 2
Sensitivity, specificity, positive and negative predicted value, AUC, and cut-off values of different pleural fluid biomarkers discriminating between tuberculous pleural effusion (TPE) vs. non-tuberculous pleural effusion (non-TPE)




































































































Pleural fluid parameter

Sensitivity

Specificity

PPV

NPV

AUC

Cut-off value

Pleural fluid ADA (U/L)

88.4

92.8

77.6

96.6

0.92

40.0

Pleural fluid IFN-γ (pg/mL)

97.7

98.7

95.5

99.4

0.99

118.7

Pleural fluid IL-2sRα (pg/mL)

79.1

48.4

29.6

89.4

0.63

2,047.7

Pleural fluid IP-10 (pg/mL)

90.7

91.1

73.6

97.3

0.96

11,420.0

Pleural fluid IL-12p40 (pg/mL)

87.2

72.6

45.9

95.5

0.83

296.0

Pleural fluid IL-18 (pg/mL)

61.9

87.6

60.5

88.2

0.77

327.7

Pleural fluid TNF-α (pg/mL)

89.7

79.3

58.3

96.0

0.87

31.6

Pleural fluid Fas-ligand (pg/mL)

94.6

89.6

87.5

95.6

0.95

45.0

Pleural fluid human MDC (pg/mL)

78.4

72.9

69.0

81.4

0.73

520.8

Pleural fluid IL-23 (pg/mL)

29.7

58.3

35.5

51.9

0.39

0.7


The three best results in each column are shown in bold numbers

Significant differences between patients with TPE and patients with non-tuberculous pleural exudates in some clinical and laboratory parameters still persisted after the exclusion of patients with pleural transudates (Table 3). Younger age, higher body temperature, and male predominance characterized patients with TPE as compared with patients with pleural exudates caused by other underlying diseases. No differences in pleural fluid IL-2sRα and IL-23 concentration were noted. However, the activity or concentration of the remaining pleural fluid biomarkers was significantly higher in TPE as compared with all other pleural exudates (Table 3).


Table 3
Comparison of clinical and laboratory variables in patients with tuberculous pleural effusion (TPE) vs. non-tuberculous pleural exudates.































































































Parameter

Tuberculous pleural effusion (TPE)

Non-tuberculous pleural exudates

P

n = 44

n = 129

Age (years)

51.5 (35.5–71.5)

66 (57–74)

0.0008

Sex F/M

11/33

64/65

0.004a

Site of pleural fluid (left/right/bilateral)

23/21/0

59/69/1

NSa

Body temperature (°C)

38.5 (36.6–39.0)

36.6 (36.6–38.0)

<0.001

Duration of symptoms (weeks)

4 (2–7)

3 (1–6)

NS

TST (mm)

12 (10–15)

0 (0–10)

<0.01

WBC (109/L)

6.8 (5.3–8.7)

10.3 (7.8–13.7)

<0.0001

Pleural fluid protein concentration (g/dL)

5.0 (4.6–5.9)

4.3 (3.9–48.0)

<0.0001

Pleural fluid/serum protein ratio

0.7 (0.7–0.8)

0.6 (0.6–0.7)

<0.001

Pleural fluid LDH activity (IU/L)

1,078 (604–2,070)

1,000 (541–2,415)

NS

Pleural fluid/serum LDH ratio

2.5 (1.5–3.8)

1.8 (0.9–4.0)

<0.0001

Pleural fluid total cell count (109/L)

1,700 (1,200–3,300)

1,730 (750–4,670)

NS

Pleural fluid lymphocyte percentage

93 (81–96)

62 (27–79)

<0.0001

Pleural fluid ADA (U/L)

58 (44–91)

8 (2–16)

<0.0001

Pleural fluid IFNγ (pg/mL)

735 (311–1,000)

8 (8–8)

<0.0001

Pleural fluid IL-2sRα (pg/mL)

2,665 (2,065–4,025)
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Jul 2, 2016 | Posted by in RESPIRATORY | Comments Off on Performance of Different Pleural Fluid Biomarkers in Tuberculous Pleurisy

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