Total adenosine deaminase cases as an inflammatory biomarker of pleural effusion syndrome

Table 1 Demographic characteristics and causes of inflammatory and noninflammatory diseases in 157 patients with pleural effusion syndrome in the State of Rio de Janeiro, Brazil, from March 2015 to December 2019, n (%)/median (25^th-75^th percentiles)

Cause	Patient (n)	Prevalence (%)	Age	Female	Male
Non-inflammatory1	33	21.0	76.0 (63.0-86.25)	17.0 (52.0)	16.0 (48.0)
Inflammatory	124	79.0	58.0 (41.5-73.5)	66.0 (53.0)	58.0 (47.0)
Tuberculosis	44	28.0	39.0 (29.7-58.2)	22.0 (50.0)	22.0 (50.0)
Adenoc.	37	24.0	61.0 (45.0-77.0)	25 (68.0)	12 (32.0)
Simple PPE	15	10.0	67.0 (56.0-85.0)	6 (40.0)	9 (60.0)
CPPE/Empiema	8	5.0	52.5 (33.5-78.75)	2 (25.0)	6 (75.0)
Lymphoma	7	4.0	53.0 (47.0-63.0)	0 (0.0)	7 (100.0).
Squamous cell	7	4.0	66.0 (55.0-66.0)	4 (57.0)	3 (43.0)
Other2	6	4.0	73.0 (53.0-79.0)	4 (67.0)	2 (33.0)
Total	157	100.0	58.0 (41.75-73.25)	80 (51.0)	77 (49.0)

¹Transudates: Congestive heart failure (n = 26), chronic renal failure (n = 3), cirrhosis of liver with ascites (n = 3), and serum low total protein levels (n = 1).

²Other exudates: Pseudo-Meigs syndrome (n = 1), Dressler's syndrome (n = 3), chylothorax (n = 1), leukemia (n = 1).

CPPE: Complicated parapneumonic effusions.

Table 2 Levels of pleural adenosine deaminase evaluated in 157 cases of pleural effusion syndrome confirmed with reference standard diagnostic tests¹

Cause	Pleural fluids–sample size (n)	P-ADA (medians) (U/L)	25th-75th percentile
Non-Inflammatory disease (control)
Transudate	33	6.85	2.67-11.26
Inflammatory disease (case)	124	18.4	9.25-41.4
Tuberculosis	44	42.0	32.9-61.9
Adenocarcinoma	37	9.75	6.7-14.9
Simple parapneumonic effusion	15	9.38	5.68-9.97
CPPE and empyema	8	32.9	16.0-61.7
Lymphoma	7	401.2	11.2-990.5
Squamous cell carcinoma	7	13.11	11.0-28.2
Other	6	15.2	7.4-49.0

¹Shapiro-Wilk test for pleural adenosine deaminase (W = 0.347, P < 0.0001). K-W test for pleural adenosine deaminase (H = 81.34, P < 0.0001) and Dunn’s test with P < 0.05: Tuberculosis vs transudates, vs simple PPE, and vs adenocarcinoma, and P > 0.05: CPPE and empyemas, lymphomas, squamous cell carcinoma, and other exudates.

CPPE: Complicated parapneumonic effusions; P-ADA: Pleural adenosine deaminase.

Table 3 Laboratory analysis of adenosine deaminase, proteins, and lactate dehydrogenase in 157 cases of pleural fluids from inflammatory and non-inflammatory pleural effusion syndrome, median (25^th-75^th percentiles)/ mean ± SD¹

Non-inflammatory pleural effusion (control)	Result
Total pleural ADAa	6.85 (2.67–11.26)
Total pleural proteinb	2.64 ± 1.52
Total pleural LDH, medianc	190.5 (100.5–278.8)
Inflammatory pleural effusion (case)
Total pleural ADAa	18.4 (9.25–41.4)
Total pleural proteinb	5.05 (4.47–5.60)
Total pleural LDHc	568.5 (400.3–822.5)

¹The Shapiro–Wilk test (W) rejected the normal data from pleural total adenosine deaminase, and pleural total LDH in exudate cases (P < 0.05), but not pleural total protein in controls (P = 0.0881).

^aP < 0.0001.

^bP < 0.0001, after logarithmic transformation of data.

^cP < 0.0001.

ADA: Adenosine deaminase; LDH: Lactate dehydrogenase; IQR: Interquartile range.

Table 4 Measures of diagnostic parameters of adenosine deaminase following selection of the best cutoff point for pleural inflammatory diseases according to the Youden index in the receiver operating characteristic curve

Diagnostic parameter	Result (%)2	95%CI
Best cutoff (U/L)	≥ 9.00	-
Sensitivity	77.69	69.22-84.75
Specificity	68.75	49.99-83.88
Positive predictive value or precision	90.38	83.03-95.29
Negative predictive value	44.90	30.67-59.77
Positive likelihood ratio1	2.48	2.21-11.2
Negative likelihood ratio1	0.32	0.27-0.51
Diagnostic odds radio	7.65	0.78-18.34
Diagnostic or predictive accuracy1	75.82	68.24-82.37
Disease prevalence1	50.48	44.78-56.17

¹These values are dependent on disease prevalence.

²χ² = 29.5138 (2-Sided P-value= 0.00001). Statnote: The Youden index at the receiver operating characteristic curve is the optimal cutoff value that provides the best tradeoff between sensitivity and specificity.