ORIGINAL ARTICLE

A comparative analysis of the biochemical parameters used to

distinguish between pleural exudates and transudates
AnNnN YILMAZ, IxNun KiIi TUNABOYU, EsrN AKKAYA AND BinoI BAYRAMGRLER
Department of Pulmonology, SSK Sreyyapapa Center for Chest Diseases and
Thoracic Surgery, Istanbul, Turkey
A comparative analysis of the biochemical parameters used to distinguish between pleural exu-
dates and transudates
YILMAZ A, TUNABOYU K, AKKAYA E, BAYRAMGRLER B. Respirology 2000; 5: 363367
Objective: The aim of the present study was to compare the various parameters used to identify
exudates.
Methodology: The study included 255 patients with pleural effusions. According to aetiological
diagnosis, 105 pleural effusions were labelled as transudates and 150 were labelled as exudates.
Results: Using the criteria of Light et al., 94.5% of the effusions were correctly classied, yielding
a sensitivity and specicity of 99.3% and 87.6%, respectively. Use of the pleural uid/serum biliru-
bin ratio produced results of 92.9%, 90.7%, and 96.2%, respectively. Using pleural uid cholesterol
level yielded results of 95.7%, 95.3%, and 96.2%, respectively. When the combination of pleural uid
cholesterol level and lactate dehydrogenase (LDH) level was used, the specicity and accuracy were
found to be higher than that using the criteria of Light et al. We found that there was no signicant
difference among the parameters with respect to accuracy.
Conclusion: When the accuracy and cost are considered, differentiation of pleural exudates and
transudates can be achieved only by pleural uid cholesterol level or LDH level; and when two para-
meters were used together, the accuracy and specicity were higher than that using the criteria of
Light et al.
Key words: differentiation, exudates, pleural effusion, transudates.
patients with transudates.
1,57
This cast some doubt
on the universal applicability of these criteria. Several
alternative criteria have been proposed, and some of
these seem to have higher diagnostic accuracy for
identifying transudates. These include use of the
pleural uid total cholesterol concentration, pleural
uid serum albumin gradient, and pleural uid/
serum bilirubin ratio.
2,6,810
Controversy exists as to
which method is more accurate.
1,5,6,9,10
The purpose of
the present study was to evaluate a large number of
patients prospectively to compare the relative utility
of the various parameters in identifying exudates and
nd the most suitable parameter with respect to ef-
ciency and cost.
METHODS
Patient selection
Two hundred and fty-ve pleural effusions from
consecutive patients admitted to SSK Sreyyapapa
Respirology (2000) 5, 363367
INTRODUCTION
Pleural effusions evolve in the course of a variety of
diseases. A correct diagnosis of the underlying disease
is essential to rational management.
1
The rst step in
the diagnosis of pleural effusions is the distinction
between exudates and transudates.
24
The current cri-
teria for differentiating exudates from transudates in
pleural effusions were established by Light et al. in
1972. Sensitivity and specicity, calculated from their
data, were 99% and 98%, respectively.
3
However,
several recent reports have shown that the low speci-
city of the criteria of Light et al. may lead to unwar-
ranted invasive interventions in up to 2030% of
Correspondence: Dr Adnan Yilmaz, Zmrtevler
Atatrk Cad. Abant Apt. No: 30, Kat:281530, Maltepe,
Istanbul, Turkey.
Email: elim@rt.net.tr
Received 13 March 2000; accepted for publication 13
July 2000.
Center for Chest Diseases and Thoracic Surgery,
Istanbul, Turkey, were studied prospectively between
November 1996 and April 1997. Considering the aeti-
ology of the effusions as the gold standard for the
classication of pleural uid,
2,8
105 pleural uid
samples were labelled as transudates and 150 were
labelled as exudates. Among the 105 patients with
transudates, 33 were women and 72 were men, with
an average age of 55.8 (range 2876). Among the 150
patients with exudates, 25 were women and 125 were
men, with an average age of 39.6 (range 1475).
The diagnosis of the disease causing the effusion
was considered to be conrmed when the following
conditions were met:
2,8
1. Congestive heart failure (CHF): presence of an
enlarged heart with clinical or echocardiographic
evidence of cardiac disfunction, and one or more of
the following alterations: elevated venous pressure,
oedema, tachycardia, or ventricular gallop. Patients
suspected of having respiratory infections, pul-
monary emboli, or persistence of the effusion after
adequate treatment of the cardiac insufciency, were
excluded.
2. Liver cirrhosis (LC): clinical and laboratory evi-
dence of hepatic damage with portal hypertension
or hypoalbuminaemia and an absence of purulent
sputum, malignancy, or pulmonary inltrates.
3. Nephrotic syndrome: It was diagnosed when
there was proteinuria, oedema, and hypoalbu-
minaemia and an absence of purulent sputum,
malignancy, or pulmonary inltrates.
4. Tuberculosis: presence of tuberculous granulo-
mas in pleural biopsy specimen or positive smear or
culture of acid-fast bacilli.
5. Parapneumonic effusion: clinically and radio-
logically conrmed pneumonia with evidence of bac-
terial invasion of the effusion.
6. Empyema: presence of pus cells in the pleural
cavity.
7. Neoplastic: cytological and/or histological
demonstration of pleural involvement.
8. Rheumatoid arthritis: clinical and laboratory
ndings of disease.
Study design
Samples of venous blood and pleural uid in each
patient were obtained on the same day shortly after
hospital admission. Only the results of the rst thora-
centesis were considered. The following biochemical
parameters were determined on samples of the
pleural uid and the venous blood: total protein,
albumin, total cholesterol, total bilirubin, and lactate
dehydrogenase (LDH). Total protein levels were mea-
sured by the biuret method. Lactate dehydrogenase
was measured using a kinetic UV optimized standard
method (the upper normal limit for serum is dened
at 460 IU/L). Cholesterol levels were measured with
enzymatic colorimetric method (CHOD-PAP). Biliru-
bin levels were measured by modied Van den Bergh
and Mller method. For the laboratory classication
of pleural uids, the following criteria were evaluated:
pleural uid (PF) to serum (S) protein ratio > 0.5, PF
to S LDH ratio > 0.6, PF LDH> 307 IU/L (the cut-off
value of pleural uid LDH is two-thirds of the upper
normal limit for the serum LDH), PF cholesterol
> 60 mg/dL, and PF to serum bilirubin ratio > 0.6.
9,11
Three cut-off points ( 0.3, 0.35, and 0.4) were
adopted for PF to S cholesterol ratio.
2
A cut-off
point of 1.2 g/dL was used for pleural uid serum
albumin gradient.
2
Statistical analysis
The usefulness of each biochemical parameter for
identifying exudates was evaluated using Bayesian
methods to measure the following: sensitivity, TP/
(TP+ FN); specicity, TN/(TN+ FP); accuracy (TP+
TN)/(TP+ TN+ FP+ FN); positive predictive value,
TP/TP+ FP; negative predictive value, TN/TN+ FN
where TP is the number of true positive diagnoses, FP
the number of false positive diagnoses, TN the
number of true negative diagnoses, and FN the
number of false negative diagnoses. These indices
were compared using McNemars exact test for cor-
related proportions.
12
RESULTS
According to the causal disease, 105 pleural uid
samples were labelled as transudates and 150 were
labelled as exudates (Table 1).
The criteria of Light et al.
Using these criteria for separating exudates from
transudates, 14 of 255 were misclassied (accuracy
94.5%). Among the 150 exudates, one was misclassi-
ed (sensitivity 99.3%). Clinical diagnosis of this case
was tuberculosis. Thirteen patients with transudates
were not correctly classied (specicity 87.6%).
Among the transudates falsely classied as exudates,
eight were CHF, two were liver cirrhosis, and three
were nephrotic syndrome.
364 A Yilmaz et al.
Table 1 Causes of 255 pleural effusions
Cause No.
Transudates 105
Congestive heart failure 60
Liver cirrhosis 32
Nephrotic syndrome 13
Exudates 150
Tuberculosis 85
Malignant effusion 36
Parapneumonic effusion 22
Empyema 5
Rheumatoid arthritis 2
Ratio of pleural uid protein to serum protein
Using a dividing line of 0.5, 242 of 255 pleural uids
were correctly classied (accuracy 94.9%). Six
patients with exudates were misclassied as transu-
dates (sensitivity 96%). Among the misclassied
exudates, two were tuberculosis, two were parapneu-
monic effusion, and two were neoplastic effusion.
Seven patients with transudates were falsely classied
as exudates (specicity 93.3%). Of these patients, four
were CHF, two were liver cirrhosis, and one was
nephrotic syndrome.
Pleural uid lactate dehydrogenase
Using 307 IU as a cut-off point for separating exudates
from transudates,
9,11
241 of 255 patients were cor-
rectly classied (accuracy 94.5%). Ten patients with
exudates and four patients with transudates were
falsely classied (sensitivity 93.3%, specicity 96.2%).
Among these, four were tuberculosis, six were neo-
plastic, two were CHF, one was liver cirrhosis, and one
was nephrotic syndrome.
Ratio of pleural uid lactate dehydrogenase to
serum lactate dehydrogenase
Using a dividing line of 0.6, 242 of 255 were correctly
classied (accuracy 94.9%). Five of 150 patients with
exudates were misclassied using this parameter
(sensitivity 96.6%). Among the exudates falsely classi-
ed as transudates, three were tuberculosis and two
were neoplastic. Eight of 105 patients with transu-
dates were mistakenly classied as exudates (speci-
city 92.3%). Among these patients, six were CHF and
two were nephrotic syndrome.
Pleural uid serum albumin gradient
Using a dividing line of 1.2 g/dL, 242 of 255 pleural
uid samples (efciency 94.9%) were obtained. Five
of 150 patients with exudates were falsely classied
(sensitivity 96.6%). Among these patients, two were
tuberculosis, two were neoplastic, and one empyema.
Eight of 105 cases with transudates were misclassied
(specicity 92.3%). Among the misclassied transu-
dates, three were CHF, three were liver cirrhosis, and
two were nephrotic syndrome.
Pleural uid cholesterol
Drawing a dividing line in the concentration
of pleural uid cholesterol of 60 mg/dL, 244 of
255 pleural uid samples were correctly classied
(accuracy 95.7%). Seven of 150 patients with exudates
were misclassied (sensitivity 95.3%). Among seven
patients, two were tuberculosis, one was empyema,
and four were neoplastic. Four of 105 patients with
transudates were falsely classied as exudates (speci-
city 96.2%). All patients were CHF.
Ratio of pleural uid cholesterol to
serum cholesterol
Using a dividing line of 0.3,
2
237 of 255 pleural uid
samples were correctly classied (accuracy 92.9%).
Seven of 150 exudates were mistakenly classied as
transudates (sensitivity 95.3%). Among these falsely
classied exudates, three were tuberculosis, one was
parapneumonic effusion, and three were neoplastic.
Eleven of 105 transudates were misclassied (speci-
city 89.5%). Among the transudates incorrectly clas-
sied were six pleural uids due to CHF, three due to
liver cirrhosis, and due secondary to nephrotic syn-
drome. Using a dividing line of 0.4,
2
230 of 255
patients were correctly classied (accuracy 90.2%).
Twenty-two of 150 exudates were falsely classied
(sensitivity 85.3%). Three of 105 transudates were
incorrectly classied (specicity 97.1%). Among the
pleural uids incorrectly classied, two were CHF,
one was liver cirrhosis, 13 were tuberculosis, four
were parapneumonic, and ve were neoplastic.
Ratio of pleural uid bilirubin to
serum bilirubin
Using a dividing line of > 0.6, 237 of 255 pleural uid
samples were correctly classied (accuracy 92.9%).
Fourteen of 150 exudates were misclassied (sensi-
tivity 90.6%). Among these falsely classied exudates,
seven were tuberculosis, two were parapneumonic,
one was empyema, and four were neoplastic. Four of
105 transudates were falsely classied as exudates
(specicity 96.2%). Of these patients, three were CHF
and one was liver cirrhosis.
Pleural uid cholesterol and pleural uid
lactate dehydrogenase
Using these parameters together, 247 of 255 patients
were correctly classied (accuracy 96.8%). Among the
exudates, one tuberculosis patient was falsely classi-
ed as transudate (sensitivity 99.3). Seven of 105
transudates were misclassied (specicity 93.3%).
Among these patients, ve were CHF, one was liver
cirrhosis, and one was nephrotic syndrome.
The statistical results of these parameters are sum-
marized in Table 2. When these indices were com-
pared using McNemars exact test, there was no
signicant difference among the parameters with
respect to accuracy.
DISCUSSION
Separation of exudates from transudates remains a
useful initial step in determining the cause of a
pleural effusion.
2
Historically, specic gravity was
used to separate these two entities.
13
Later, a pleural
uid protein level of 30 g/L was used.
14
Many mis-
classications were made resulting in patients endur-
ing unnecessary investigations. Chandrasekhar et al.
The differentiation of pleural uids 365
thus proposed the use of absolute values of pleural
uid LDH in making this distinction.
15
A combination
of two parameters was used by Light et al. in 1972.
Sensitivity and specicity, calculated from their data,
were 99 and 98%, respectively.
3
Recently, however,
several prospective studies were unable to reproduce
the excellent results obtained by Light et al. In most
of them, using the criteria of Light et al., the sensitiv-
ity remained high, greater than 95%, but the speci-
city did not surpass 78%.
1,5,6
Roth et al. showed that limitation of the criteria of
Light et al. could be overcome by measuring the
serumeffusion albumin gradient.
6
In this study, a
sensitivity and specicity of 95% and 100%, respec-
tively, was demonstrated. Burgess et al., however, did
not agree with these results.
2
From the results of this
study, the sensitivity and specicity were 87% and
92%, respectively. Hamm et al.
1
and Valdes et al.
5
sug-
gested the use of cholesterol levels in distinguishing
between transudates and exudates. The sensitivity
and specicity for cholesterol level were found as
100% and 95%, respectively.
1
Romero et al., however,
did not agree with these results.
9
Sensitivity and
specicity, calculated from these data, were 72% and
85%, respectively. Meisel et al. investigated the pleural
uid/serum bilirubin ratio and yielded a sensitivity
and specicity of 96% and 83%, respectively.
10
In the
study by Burgess et al., a sensitivity and specicity of
81% and 61%, respectively, were obtained.
2
From the results of the present study, the criteria of
Light et al. remain the most sensitive (99.3%) for exu-
dates. However, unlike the results obtained by Light et
al.
3
in their initial study, the specicity was much
lower at 87.6%. Using one of the proposed alternative
criteria, the pleural uid cholesterol level, we found
that the specicity was higher than when using the
criteria of Light et al. However, sensitivity of this cri-
teria was lower than when using the criteria of Light
et al. Using the combination of pleural uid choles-
terol and pleural uid LDH obtained higher sensitiv-
ity than using either alone. The specicity and
accuracy of this combination were found to be higher
than when using the criteria of Light et al. When
the ratio of pleural uid/serum bilirubin level was
used, the sensitivity and accuracy were lower than
when using the criteria of Light et al. However, these
criteria had higher specicity. When it was compared
with pleural uid cholesterol level, it had a lower sen-
sitivity and accuracy but specicity was similar. The
present results showed that there was no signicant
difference among the parameters with respect to
accuracy.
We conclude that differentiation of pleural exu-
dates and transudates can be achieved only by pleural
uid cholesterol or LDH level measurement. When
pleural uid cholesterol and LDH level measurement
were used together, this combination has an ef-
ciency higher than that achieved by the criteria of
Light et al. The proposed combination has advan-
tages in that a contemporary blood sample is not
required and that chemical tests are reduced, thereby
lowering the cost of the diagnostic procedure.
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Table 2 Summary of statistical results
Sensitivity Specicity Accuracy Positive Negative
predictive predictive
value value
Pleural uid/serum protein 96.0 93.3 94.9 95.3 94.2
Pleural uid lactate dehydrogenase 93.3 96.2 94.5 97.2 91.0
Pleural uid/serum lactate dehydrogenase 96.7 92.4 94.9 94.8 95.1
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Serum/pleural uid albumin 96.7 92.4 94.9 94.8 95.1
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Pleural uid cholesterol 95.3 96.2 95.7 97.3 93.5
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Pleural uid/serum cholesterol 0.35 92.0 93.3 92.5 95.2 89.1
Pleural uid/serum cholesterol 0.4 85.3 97.1 90.2 97.7 82.3
Pleural uid cholesterol + pleural uid lactate dehydrogenase 99.3 93.3 96.9 95.5 99.0
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The differentiation of pleural uids 367