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Year : 2019 | Volume : 7 | Issue : 2 | Page : 41 - 44  


Original Articles
To Assess Diagnostic value of Lymphocyte // Neutrophil ratio and Adenosine Deaminase in the Diagnosis of Exudative Tubercular Pleural Effusion

K. Raj Kumar 1, Raghu Vamsi 2, Soumya Rani 3*

Associate Professor, 2, 3 Junior Resident, Department of Pulmonary Medicine, Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar

*Corresponding Author

Dr. Soumya Rani                                                                                                                 

E-mail:  koyyadasoumya711@gmail.com                                                                    

Abstract:

Background: Adenosine deaminase (ADA) is considered a valuable tool in the diagnosis of extra pulmonary tuberculosis.

Objective: To evaluate the role of ADA and L/N ratio in the diagnosis of tuberculous pleural effusion in patients with exudative pleural effusion and to analyze the cause of non tuberculous exudative pleural effusion.

Methods:  This hospital based prospective study was conducted from November 2017 to November 2018 with a total number of 100 patients of exudative pleural effusion who were admitted in medical wards of Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar, India. Patients with transudative pleural effusion, age less than 12years and those who were hemodynamically unstable were excluded from the study.

Results: A total of 100 patients with exudative pleural effusion were analyzed, of which 69 were males and 31 females.  maximum number of cases were seen in age group between 21 and 40 yrs. Total ADA was found to be >40U/L in all cases of TB effusion. All cases of TB effusion were lymphocyte predominant with L/N ratio > 0.75. In case of exudative pleural effusion due to non tuberculous etiology L/N ratio was < 0.75.

Conclusion: 100 cases of exudative pleural effusion were analyzed based on Total ADA and L/N ratio. 80 cases were due to tuberculosis. ADA value of >100 U/L was observed only in tuberculous effusion. L/N ratio was >0.75 in 80 cases of TB effusion and in none of the non tuberculous effusion. Combined use of ADA and L/N ratio is more efficient means for diagnosing tubercular pleural effusion than the use of ADA alone.

Keywords: Adenosine deaminase, lymphocyte/neutrophil ratio, exudative pleural effusion, transudative pleural effusion.

Introduction:

Pleural effusion is the abnormal collection of fluid in the pleural space. It is classified into exudates and transudates based on Lights criteria. 1-3 Tuberculosis is a common infection in India and the commonest cause of exudative pleural effusion. Definitive diagnosis of TB pleural effusion is difficult. Pleural fluid Acid Fast Bacilli (AFB) demonstration is virtually always negative, culture of fluid could be positive in < 25%, histology of pleural biopsy could be positive in 80% whereas HPE and culture of pleural biopsy increases diagnostic efficacy to 90% 4 Because of the non-availability of confirmatory tests (pleural biopsy and HPE) in all centres, the confirmation of diagnosis is difficult. In India, an exudative pleural effusion is considered Tuberculous and started on Anti tuberculous Treatment (ATT).

Adenosine deaminase (ADA) is considered a valuable tool in the diagnosis of extra pulmonary tuberculosis. A Cochrane meta-analysis review of forty articles on ADA in pleural fluid shows that test results for ADA with cut off value >40U/L derived from the summary receptor operator curve (SROC) was 92.2% for both sensitivity and specificity. ADA value > 40 U/L with a lymphocytic effusion and Lymphocyte/Neutrophil (L/N) ratio > 0.75 is considered diagnostic of TB pleural effusion. 5 A TB pleural effusion is typically clear and straw colored; however, it can be turbid or serosanguinous, but is virtually never grossly bloody and effusion is virtually always an exudate. 6-8

Present study was carried out to evaluate the role of ADA and lymphocyte/neutrophil ratio in the diagnosis of tuberculous pleural effusion in patients with exudative pleural effusion and to analyze the cause of non-tuberculous exudative pleural effusion. 

METHODS:

A Hospital based prospective study was carried out at Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar over periods of 1 year from November 2017 to November 2018 among patients attending pulmonary medicine outpatient department and inpatient. Patients with exudative pleural effusion were taken for study. 

Inclusion Criteria

  • Cases of Exudative pleural effusion.
  • Age >12 years. 

Exclusion Criteria

  1. Cases of transudative pleural effusion.
  2. Hemodynamically unstable patients 

Diagnostic Criteria

Lights criteria were used to diagnose exudative pleural effusion. Exudative pleural effusion meets at least one of the following criteria:

  • Pleural fluid protein/serum protein > 0.5
  • Pleural fluid LDH/serum LDH > 0.6
  • Pleural fluid LDH more than two-thirds of normal upper limit for serum. 

Criteria taken for diagnosis of tuberculous pleural effusion

  1. Demonstration of AFB in pleural fluid/sputum and / or
  2. ADA > 40 U/L and / or
  3. L/N ratio > 0.75 in pleural fluid. 

Investigations

Complete Hemogram, ESR, serum Urea, Serum Creatinine, Liver Function Tests, Mantoux, Sputum AFB, Sputum Culture and sensitivity, HIV ELISA. Diagnostic thoracentesis was done, and fluid sent for analysis of glucose, protein, cytology and cell count, LDH, AFB and gram stain, culture and sensitivity and ADA were done. Plain chest X-ray PA view, USG chest and/or CT chest based on affordability. 

Other Investigations

Echocardiogram, pericardial fluid analysis, Serum HBsAg, Anti HCV, OGD scopy, serum ANA, dsDNA, RA factor, aCL antibody, serum thyroid function tests, MRI Brain, 24 hour urine protein, CD4 count, CT guided biopsy. ADA in pleural fluid was done by sensitive Giusti and Galantis colorimetric method, total ADA was done. ADA 1 and 2 isoenzyme was not done. 

Ethics Approval

This study was reviewed and approved by Institutional Ethics Committee (IEC), Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar. Informed oral consent was obtained from all the patients. 

RESULTS: 

A total of 100 patients of exudative pleural effusion were analyzed out of which 69(69%) were males and 31 (31%) were females. They were mostly in the age group of 21-40years. (Table 1) The lowest age was 13 years and highest age was 76 years. ADA was done in all samples of pleural fluid. Total ADA in pleural fluid of more than 40U/L with a pleural fluid L/N ratio of more than 0.75 was useful in differentiating between tuberculous and non-tuberculous pleural effusion. Tuberculosis was the most common cause of pleural effusion. Peak age of tuberculous pleural effusion was 21-30 years. Out of 100 patients of exudative pleural effusion and 80 was tuberculous pleural effusion.

Out of 80 cases of tuberculous pleural effusion, 65 were males and 15 were females. Pleuritic chest pain was noted in 80 cases, followed by fever in 65 cases, dry cough in 55 cases and cough with sputum in 28 cases, hemoptysis in past history of TB was obtained in 5 cases and history of contact with TB patients in 10 cases. Mantoux was reactive (10mm or more) in 44 cases. 50 cases presented with left sided pleural effusion and 54 cases had moderate pleural effusion. Sputum smear for AFB was done in 23 patients who produced sputum and it tested positive only in 3 cases

Total ADA was found to be >40U/L in all the cases with TB effusion (Table 10). All cases of TB effusion were lymphocyte predominant with L/N ratio >0.75. In cases of exudative pleural effusion due to non-tuberculous etiology L/N ratio was <0.75. Other causes of exudative pleural effusion noted are parapneumonic effusion, connective tissue diseases, malignancy, amoebic liver abscess, empyema and hypothyroidism

Table 1Age distribution of 100 cases of exudative plural effusion

Age (years)

Male

Female

Total

N

%

13-20

4

4

8

8

21-30

25

12

37

37

31-40

20

8

28

28

41-50

14

4

18

18

51-60

3

2

5

5

> 60

3

1

4

4

Table 1 shows the age variation was from 13 to 76 years, Majority patients were in the age group of 21-40 years. 

Table 2: Gender distribution

Male

Female

Total

         69 (69%)

           31 (31%)

     100 %

Table 2 shows the present study group consisted of 69 % males and 31 % females 

Table 3: Clinical features symptoms

Symptoms

Total

%

Pleuritic chest pain

80

80

Fever

65

65

Dyspnea

60

60

Cough

55

55

Weight loss

32

32

Appetite loss

40

40

Table 3 shows the pleuritic type of chest pain is the most frequently noted symptom in 80 cases (80%) followed by fever 65 cases (65%), dyspnoea in 60 cases (60%) and cough in 55 cases (55%) respectively. 

Table 4: Total ADA range and mean

ADA Range

Mean

5-239 u/l

89.58 u/l

Table 4 shows total Adenosine Deaminase (ADA) ranged between 5- 239 u/l, with mean 89.58 u/l 

Table 5: Total ADA

 

ADA < 40 u/l

ADA > 40 u/l

No. of cases

17

83

Table 5 shows ADA > 40 u/l which is diagnostic for TB in 83 cases. 

Table 6: L/N ratio

 

l/n ratio > 0.75

l/n ratio < 0.75

No. of cases

80

20

Table 6 shows l/n ratio > 0.75 in 80 cases which is diagnostic for TB 

Table 7: Mantoux and sputum AFB   in tubercular   pleural effusion

 

Tested

Positive

Mantoux

81

44 (54%)

Sputum AFB

23

03 (13%)

Table 7 shows Mantoux positive in 54 % and sputum for AFB positive in 13 % cases. 

Table 8: ADA in exudative effusions

ADA (u/l)

Tuberculous effusion

Non tuberculous effusion

Range

42.19 -239

5-76.5

Mean

153.6

25.6

Table 9:  l/ n ratio in exudative effusion

l/n ratio

Tuberculous effusion

Non tuberculous effusion

> 0.75

80

0

< 0.75

0

20

Table 9 shows all tubercular effusions has l/n ratio > 0.75 

Table 10: ADA and l/n ratio

Etiology

ADA > 40 u/l

l/n ratio > 0.75

Tuberculous

80

80

Non tuberculous

3

0

Table 10 shows ADA > 40 in all tubercular and 3 non tubercular cases, and l/n ratio > 0.75 in all tuberculous effusions. 

DISCUSSION:

Tuberculosis is a common infection in India and the commonest cause of exudative pleural effusion. Because of the non-availability of confirmatory tests like pleural biopsy and HPE in all centers, the confirmation of diagnosis is difficult.

ADA is considered a valuable tool in the diagnosis of extra pulmonary tuberculosis. Pleural fluid Acid Fast Bacilli demonstration is virtually always negative, culture positive in n <25%, histopathology of pleural fluid could be positive in 80% whereas HPE and culture increases diagnostic efficacy to 90%.7 Polymerase chain reaction having a sensitivity of 78% for active disease, has not been found to be an efficient alternative. 9

 Although the rise in ADA in tuberculous effusion was predominantly due to ADA 2, the difference was statistically not significant, and measurement of ADA isoforms is commercially not feasible. 10 An ADA level < 40U/L virtually excludes tuberculosis in lymphocytic pleural effusions. 11

All the 80 cases of lymphocyte predominant pleural effusion with L/N ratio > 0.75 total ADA was found to be > 40U/L. The range of ADA was between 42.19-239U/L with a mean 153.6U/L. These results were in agreement of a study conducted by P. C. Mathur et al. 12

Two cases of exudative pleural effusion due to rheumatoid arthritis were seen. Pleuritic chest pain was noted in both the patients and one patient had cough. Both patients had history of long standing bilateral small joints arthritis. The lowest level of pleural fluid glucose in our study was noted in rheumatoid pleurisy, the value being 13mg/dl. In both the cases pleural fluid LDH level were elevated than plasma levels and Rheumatoid factor (RA) level was > 1:320 in pleural fluid. This is in accordance with the observation of Halla JT et al. 13

The mean ADA value was 42.5 U/L and one case had elevated ADA 69U/L. The effusion was lymphocyte predominant but none of them achieved L/N ratio > 0.75.

4 cases of pneumonia with pleural effusion were analyzed. The presentation was like acute illness and presenting complaints were fever (80%), coughs with sputum production (100%), pleuritic chest pain (60%) and dyspnoea (60%). Haemoptysis was seen in one patient. The mean WBC count was 12,400 and peripheral blood neutrophilia was noted in line with observation of Light RW et al. Pneuomococci was grown in sputum in 2 cases and klebsiella along with E. coli in 2 cases.

This observation is consistent with the study of Varkey B et al, and Barlett JG et al, who stated that pneumococci and S. aureus account for approximately 70% of all aerobic gram-positive isolates and E. coli along with klebsiella species, account for approximately 75% of all aerobic gram-negative empyema. 14, 15

The mean glucose level in pleural fluid was 52mg/dl. The pleural effusion was neutrophil predominant with an L/N ratio <0.75. Culture of plural fluid was negative in all cases. The ADA level was <40U/L in all the cases with a mean value of 21.3 U/L.

Malignant effusion was noted in 3 cases of males. The average age of presentation was 65 years. The most common symptoms noted were anorexia and weight loss in all the 3 cases. One patient presented with hemoptysis. Gross appearance of pleural fluid was bloody in 3 cases. ADA in pleural fluid was less than 40U/L in 2 cases (6.2 and 28 U/L) and 42.6U/L in one case. Mean ADA was 25.6 U/L. The effusion was lymphocyte predominant with mesothelial cells > 10% and L/N ratio < 0.75 in all the three cases.

CONCLUSION: 

In our study, concluded that combined use of the total ADA in pleural fluid of >40U/L with a pleural fluid L/N ratio >0.75 is a more efficient means of diagnosing tuberculous pleural effusion than the use of ADA alone. 

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