Ambresh and Shilpa A: Differentiating transudative and exudative pleural effusion by pleural fluid cholesterol


Introduction

Pleural effusions represent a very common diagnostic task to the physician. A correct diagnosis of the underlying disease is essential to the rational management.1 Normally the pleural space contains only a few millimetres of fluid. Indeed pleural effusion must be regarded as a trivial event but as a sign of major disorder or disease.2

The first diagnostic step is the identification of pleural effusions as either a transudate or exudates. This is useful because it indicates the pathophysiological mechanisms involved. Exudates are secondary to alteration of capillary permeability or lymphatic drainage. Transudates are due to either alterations of hydrostatic and / or osmotic pressure in pleural capillaries or to a fluid passing from the peritoneal cavity via diaphragmatic defects.

If an exudate is present further diagnostic procedures and tests are imperative for definitive diagnosis and specific therapy. On the other hand if the fluid is clearly a transudate one need not worry about manoeuvres directed at the pleura and need to treat only the congestive cardiac failure, nephrosis, cirrhosis or hypoproteinemia.3 Over the years many criteria have been developed by various workers for separation of exudates and transudates.

Objective of the study

To study the diagnostic value of Pleural fluid Cholesterol in differentiating transudative and exudativepleural effusions.

Materials and Methods

Source of data

  1. Data is collected from patients who are attending Medicine OPD and admitted in BLDEU’S Shri B.M.Patil medical college hospital and research centre, Vijayapura.

  2. Period of study is from November 2016 to July 2018

Method of collection of data   

Inclusion criteria

  1. Age >18years

  2. Patients with definite clinical diagnosis and Pleural effusion evidenced by radiological imaging

Exclusion criteria

  1. Age <18years

  2. Patients without definitive clinical diagnosis

  3. Patients previously diagnosed and already on treatment

Type of study

Cross sectional descriptive study

Sample size

Using expected incidence of exudates cases among pleural effusion as 69.4%, expected sensitivity as 88%, expected specificity as 100% and desired precision as +/-10%,

The minimum sample is 60.

This sample size will give the precision of 10%for both sensitivity and specificity.

Formula used:

      N=z2 (1-p)/d2

Z-value of z statistic at 5% level of significance

d-margin of error

p-expected incidence rate

Statistical analysis

Data will be analysed using mean+/-SD Chi square test for association, comparison of means using test, ANOVA for comparison between and within groups and diagrammatic presentation.

Results and Observation

The present study was undertaken in 60 cases of Pleural Effusion over a period of 2 and half years from November 2016 to July 2018, the results of which are given below.

Table 1

Age and sex distribution

Age (years)

Male

Female

p value

N

%

N

%

18-20

1

2.6

0

0.0

0.641

21-30

5

13.2

4

18.2

31-40

8

21.1

7

31.8

41-50

12

31.6

3

13.6

51-60

8

21.1

5

22.7

>60

4

10.5

3

13.6

Total

38

100.0

22

100.0

The age of the patient in this study ranged from 18 years to 75 years. 1 patient was 18 years, 9 patients were under 21-30 years, 15 patients were under 31-40 years, 15 patients were under 41-50 years, 13 patients were under 51-60 years, 7 patients were above 60 years. Out of 60 patients there were 38 males and 22 females.Table 1

Table 2

Distribution of exudates and transudate according to lights criteria

Based on lights criteria

N

%

Exudate

46

76.7

Transudate

14

23.3

Total

60

100

Based on Lights criteria, out of 60 patients 46 were exudates (76.7%) and 14 were transudates (23.3%).Table 2

Table 3

Distribution of exudates and transudate according to pleural fluidcholesterol criteria

Based on cholesterol criteria

N

%

Exudate

45

75

Transudate

15

25

Total

60

100

Based on pleural cholesterol level criteria, out of 60 patients 45(75%) were exudates and 15(25%) were transudates.Table 3

Table 4

Distribution of symptoms in pleural effusion at presentation

Presenting Symptoms

Number (n=60)

Percentage

1. Cough

50

83.3

2. Fever

22

36.7

3. Chest pain

34

56.7

4. Dyspnoea

47

78.3

5. Swelling of limbs

10

16.7

6. Distension of abdomen

10

16.7

7. Facial puffiness

6

10

8. Loss of appetite

60

100

9. Loss of weight

40

66.7

Cough was present in 50 patients (83.3%), fever in 22 patients (36.7%), chest pain in 34 patients (56.7%), dyspnoea in 47(78.3%), swelling of limbs and abdominal distension each in 10 patients (16.7%), facial puffiness in 6 patients, loss of appetite in 60 patients (100%), loss of weight in 40 patients (66.7%).Table 4

Table 5

Distribution of signs in pleural effusion at presentation

Clinical signs

Number (n=60)

Percentage

1. Stony dullness

60

100

2. Absent breath sound

50

83.3

3. Decreased VF/VR

52

86.7

4. Mediastinal shift

50

83.3

5. Pleural rub

4

6.6

6. Crepitations

5

8.3

Stony dullness in 60 patients (100%), Decreased / absent breath sounds in 50 patients (83.3%), Mediastinal shift in 33 patients (83.3%), Decreased VF/VR in 52 patients (86.7%), Pleural rub in 4 patients (6.6%), Crepitations in 5 patients (8.3%).Table 5

Table 6

Pleural effusion right and left side distribution

Side of effusion

Number ( n=60)

Percentage

Right

36

60.0

Left

19

31.7

Bilateral

5

8.3

Out of 60 patients, 36 had right sided effusion, 19 had left sided effusion, 5 patients had bilateral pleural effusion.Table 6

Table 7

Result of sputum AFB

Sputum AFB

Total

P value

N

%

Negative

28

46.7

0.232

Positive

32

53.3

Total

60

100.0

In the study group of 60 patients, sputum AFB was positive in 32 (53.3%) patients and 28 (53.3%) patients had sputum AFB was negative.Table 7

Table 8

Cytology of pleural effusion

Cytology

Total

p value

N

%

Lymphocytes + Mesothelial cells

3

5.0

0.476

Predominantly lymphocytes

42

70.0

Predominantly neutrophils

15

25.0

Total

60

100.0

Out of 60 patients, 3 patients had lymphocytes plus mesothelial cells, 42 patients had predominantly lymphocytes and 15 patients had predominantly neutrophils.Table 8

Table 9

Distribution of pleural protein

Pleural Protein (gram/dl)

Number (n=60)

1-2

6

2-4

16

4-6

34

>6

4

Total

60

The above table shows the values of pleural protein. 6 patients had pleural protein values ranging from 1-2 gram/dl, 16 patients of pleural protein ranging from 2-4 gram/dl, 34 patients ranging from 4-6 gram/dl and 4 patients had protein levels above 6 gram/dl.Table 9

Table 10

Distribution of pleural cholesterol

Pleural Cholesterol

Number (N=60)

<45 mg/dl

15

>45 mg/dl

45

Total

60

15 patients had pleural cholesterol levels less than 45 mg/dl and 45 patients had cholesterol level above 45 mg/dl.Table 10

Table 11

Biochemical analysis of pleural effusion

Parameters

Exudates

Transudate

P value

Mean

SD

Mean

SD

Lights criteria (Transudate=14 Exudate=46)

Serum Protein

5.7

1.0

6.1

1.1

0.215

Pleural Protein (G/DL)

4.7

1.0

2.4

0.9

<0.001*

Pleural Sugar

68.2

40.1

126.7

75.9

<0.001*

Pleural Fluid Protein: Serum Protein

0.8

0.2

0.3

0.1

<0.001*

Pleural cholesterol criteria(transudate=15 Exudate=45)

Pleural cholesterol

78.2

23.7

21.9

9.2

<0.001*

Note: * significant at 5% level of significance (p<0.05).

The p value of serum protein is 0.215, pleural protein is <0.001, pleural sugar is <0.001, pleural cholesterol is <0.001, pleural fluid protein: serum protein is <0.001. P value of <0.001 is statistically significant.Table 11

Table 12

Comparison of exudative and transudative pleural effusion according to pleural fluid cholesterol criteria and lights criteria

According to pleural fluid cholesterol criteria (N=60)

According to lights criteria (N=60)

P value

N

%

N

%

Exudate

45

75.0

46

76.66

<0.001*

Transudate

15

25.0

14

23.33

Total

60

100.0

60

100.0

Note: * significant at 5% level of significance (p<0.05)

Based on lights criteria 46 patients were exudate and 14 patients were transudative pleural effusion, based on cholesterol criteria 45 patients were exudative and 15 were transudative pleural effusion.Table 12

The p value is < 0.001 which is statistically significant.

Table 13

Sensitivityanalysis of pleural cholesterol criteria

TP (true positive)

45

FN (false negative)

1

FP (false positive)

0

TN (true negative)

14

Sensitivity

97.8%

Specificity

100.0%

PPV(positive predictive value)

100.0%

NPV(negative predictive value)

93.3%

Accuracy

98.3%

Table 14

Biochemical analysis of pleural effusion

Parameters

Exudates

Transudate

P value

Mean

SD

Mean

SD

Lights criteria (Transudate=14 Exudate=46)

Serum Protein

5.7

1.0

6.1

1.1

0.215

Pleural Protein (G/DL)

4.7

1.0

2.4

0.9

<0.001*

Pleural sugar

68.2

40.1

126.7

75.9

<0.001*

Pleural fluid protein:serum protein

0.8

0.2

0.3

0.1

<0.001*

Pleural cholesterol criteria (Transudate=15 Exudate=45)

Pleural cholesterol

78.2

23.7

21.9

9.2

<0.001*

According to Lights Criteria, the mean serum protein is 5.7±1.0 in exudates and 6.1±1.1 has p value of 0.215. The mean pleural protein is 4.7±1.0 in exudates and 2.4±0.9 has p value of 0.001. The mean pleural sugar is 68.2±40.1 in exudates and 126.7±75.9 has p value of 0.001.The mean pleural protein: serum protein is 0.8±0.2 in exudates and 0.3± 0.1 has p value of 0.001. According to pleural cholesterol criteria, the mean pleural cholesterol is 78.2±23.7 in exudates and 21.9±9.2 and has p value of 0.001 which is statistically significant.Table 14

Pleural fluid cholesterol

Table 15

Comparison of pleural fluid cholesterol values between the studies

S.No

Authors

Sensitivity

Specificity

PPV

NPV

Accuracy

1

Hamm 4

93.5

100

100

91

96

2

Valdes

92.5

87.6

95

80

91.3

3

Ram

96

93

96

92.6

95

4

B N Mohaptra

92

100

100

99

93

5

Burgess

54

92.2

87.3

50

66

6

Present study

97.8

100

100

93.3

98.3

Discussion

A total of 60 patients were taken up for this study. Out of 60, 46 were exudates and 14 were transudates. Among 46 exudates, 40 were tubercular effusions, 5 patients were synpneumonic effusion and 1 patient with malignant effusion.

Among 14 transudative, 7 patients were congestive cardiac failure, 7 patients were cirrhosis.

Age and sex

The age of the patient in this study ranged from 18 years to 75 years. 1 patient was 18 years, 9 patients were between 21-30 years, 15 patients were between 31-40 years, 15 patients were between 41-50 years, 13 patients were between 51-60 years and 7 patients were above 60 years. Out of 60 patients, males were 38 and females were 22.

Presenting symptoms

Cough was present in 50 patients (83.3%), fever in 22 patients (36.7%), chest pain in 34 patients (56.7%), dyspnoea in 47 (78.3%), swelling of limbs and abdominal distension each in 10 patients (16.7%), facial puffiness in 6 patients, loss of appetite in 60 patients (100%), loss of weight in 40 patients (66.7%).

Signs

Mediastinal shift is seen in 50 patients opposite to the pleural effusion. Over affected side of chest, fullness of chest in 48 patients, decreased chest movements in 50 patients, expansion of chest reduced in 50 patients, decreased vocal fremitus in 52 patients, stony dullness in 60 patients, absent breath sounds in 50 patients, decreased vocal resonance in 52 patients, pleural rub in 4 patients and Crepitations in 5 patients.

Side of pleural effusion

Out of 60 patients, 36 had right side effusion, 19 had left side effusion, and 5 patients had bilateral pleural effusion.

Sputum AFB analysis

In the study group of 60 patients, sputum AFB was positive in 32 (53.3%) patients and 28 (53.3%) patients had sputum AFB was negative.

Colour of pleural effusion distribution

Colour of pleural effusion 36 patients had amber colour, 18 patients had clear fluid, 4 patients had haemorrhagic and straw colour in 2 patients.

Cytology of pleural effusion

Out of 60 patients, 3 patients had predominantly lymphocytes plus mesothelial cells, 42 patients had predominantly lymphocytes and 15 patients had predominantly neutrophils.

USG analysis

In the study group of 60 patients, cirrhosis was present in 7 patients, hepatomegaly in 1 patient, ascites in 1 patient, and normal in 39 patients.

Biochemical analysis of pleural effusion

Hammfirst used pleural cholesterol as a parameter. In his study of 150 patients he found excellent results (Sensitivity 93%, Specificity 100%, Accuracy 96%). Following Hamm’s, 5 Valdes 6 aimed to validate this parameter. In his study of 74 patients pleural cholesterol had good resultsas shown in the above table. Similar results were obtained from studies by Ram7 in 100 patients and B N Mohaptra 8 in his study of 132 patients. The studies of Burgess and Remeroof 124 patients, results were in favour of lights criteria but they had less sensitivity, specificity and accuracy. As a result the present study of 60 patients which contains Pleural Cholesterol criteria has more sensitivity, specificity and accuracy when compared to other studies done by Burgess 9 and Remero4 which contains Lights criteria. The study shows that pleural fluid cholesterol criteria (cholesterol >45 mg/dl - exudate and cholesterol <45 mg/dl – transudate) constitute a useful tool for the separation of pleural effusions.

Conclusion

The pleural fluid cholesterol criteria were found to be the most efficient criteria.

Since this parameter involves the measurement of only pleural fluid values of cholesterol, it has following advantages

  1. Economically, it reduces number of biochemical tests

  2. Simpler, as there is no need to take simultaneous blood sample at the time of thoracocentesis.

It is concluded that the determination of pleural fluid cholesterol criteria can be included in routine analysis of pleural fluid samples in place of presently used Lights Criteria.

Summary

This was a cross sectional descriptive study of 60 cases of pleural effusion. The parameter pleural fluid cholesterol levels are used in comparison with Lights criteria to distinguishing transudative and exudative pleural effusion. The following results were obtained in the present study.

  1. True positive in 45 cases

  2. False negative 1 case

  3. False positive 0 case

  4. True negative 14 case

  5. Sensitivity 97 8%

  6. Specificity 100%

  7. Positive predictive value 100%

  8. Negative predictive value 93 3%

  9. Accuracy 98 3%

Source of Funding

No financial support was received for the work within this manuscript.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

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DD Dorey R A Defronzo E Ferrannini Pleural effusion- A Diagnostic dilemmaJAMA1976121836

2 

E Hampson D Chisholm X Pi-Sunyer Complications of Pleural effusion .Needle biopsy of parietal pleura in the diagnosis of pleural effusionQ J Med19613410612

3 

R Light Approach to Management of Pleural effusionAnn Int Med19666434151

4 

H Hamm JD Tobin R Andres Cholesterol in pleural effusion- A diagnostic aidChest198792296301

5 

F K Paddock Z Keen The relationship between the specific gravity and the protein content in human serous effusionsAm J Med Sci194120156974

6 

C E Leuallen K L Zii Pleural effusion. A statistical study of 436 patientsNEJM19552527983

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DT Carr H M Giles W H Giles Dietz WHClinical value of measurement of protein in pleural fluidNEJM19582599267

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J Chandrasekhar N Vikram Pleural effusion LDH activity and protein content its value in diagnosisArch NT Med19691284850

9 

R W Light A Candela L Hernandez Pleural Effusions: The Diagnostic Separation of Transudates and ExudatesAnn Int Med19727745071310.7326/0003-4819-77-4-507



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