Salimuddin Aziz  ( PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi. )
Farida Agha  ( PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi. )
S.M. Abbas Rizvi  ( PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi. )

Sixty patients of pleural effusion with different aetiology are described. Various microbiological and biochemical parameters were done simultaneously in blood and pleural fluid to differentiate tuberculosis and non-tuberculosis effusions. Some biochemical tests were thought to be helpful in differential diagnosis but no single parameter was found diagnostic. Routine investigations of pleural fluid, sputum and pleural biopsy still remain the best method of diagnosis (JPMA:42, 178, 1992).

Pleural effusion caused by number of diseases, poses a common diagnostic problem^1-4 and a fair number of cases remain undiagnosed inspite of extensive inves­tigations. This is particularly true for cases other than congestive cardiac failure and cirrhosis where cause is evident. Inspite of extensive research the distinction between tuberculosis and non- tuberculosis effusions remain hazy. In Pakistan, where tuberculosis is a com­mon problem, majority of cases are treated as tuber­culosis, not only those that are suggestive of tuberculosis but also those in which no cause can be determined^5,6. This study -was designed to develop a criterion (if possible) to differentiate tuberculosis from non-tuber­culosis effusions by using different microbiological and biochemical parameters.

A total of 60 patients with pleural effusions ad­mitted Centre, Karachi were studied. Their detailed clinical history and relevant demographic data was recorded on a specially designed proforma. The samples of the blood and pleural fluid were drawn simultanously and sub­jected to analysis within the minimum possible time (not exceeding 48 hours). Each specimen was analysed for proteins, lactate dehydrogenase, sugar and alkaline phosphatase. Sputum and pleural fluid was examined for AFB on direct smear and culture. In addition cytology was performed on pleural fluid and blood examined for CP and ESR.

Of 60 patients examined, 40 (66.7%) had tuber­culosis, 9 (15%) malignancy, 8 (13.3%) cirrhosis of the liver and 3 congestive cardiac failure. Sugar levels were low in tuberculosis as compared to malignancy and cirrhosis. Pleural fluid lactate dehydrogenase values were higher than the serum levels in malignant effusions whereas serum lactate dehydrogenase levels were elevated in cirrhosis. Protein levels were higher in tuberculosis and ‘malignancy than in cirrhosis. Alkaline phosphatase levels in blood were low in tuberculosis as compared to cirrhosis and malignancy (Table I).

Pleural fluid/blood ratio for sugar was low (Table II)

in tuber­culosis as compared to malignancy and cirrhosis. Lactate dehydrogenase was higher in tuberculosis than in cir­rhosis and lower than in malignancy. Alkaline phos­phatase ratio was higher in tuberculosis than in malig­nancy and cirrhosis. Sputum examinations were not always positive, nor was AFB seen in pleural fluid in all the tuberculosis patients. Even tuberculin test was not very helpful in confirming the diagnosis.

Over the past hundred years various chemical tests have been described to distinguish tuberculosis from non-tuberculosis effusions. Historically based on the protein levels and specific gravity, the pleural fluid effusions were classified into transudates and cx­udates^7,8. Laullen and Carr found that 72% patients of congestive cardiac failure had specific gravity below 1.0 16 whereas 73% of the tuberculosis and malignancy above 1.016⁹. Later protein levels of 3.0 gram per 100 ml were taken as a dividing line and was found slightly better in differentiating transudates and exudates¹⁰. Furabashi and Sarkar¹¹ have suggested pH measurements of less than 7.28 in the non-malignant and inflammatory ef­fusions. Pleural fluid and serum protein ratio was suggested by Luetschers¹². Higher pleural fluid lactate dehydrogenase values than serum were reported by Wrobeiski and Wrobeiski¹³. Light and co-workers developed a criterion for the diagnosis of exudates as pleural fluid to serum protein ratio of more than 0.5 pleural fluid lactate dehydrogenase levels of more than 200 units per litre and pleural fluid to serum lactate dehydrogenase ratio of above 0.6 which has become a standard¹⁴. Pleural fluid and serum bilirubin ratio of over 0.6 has also been suggested¹⁵. Though the differentiation between transudates and exudates narrows such pos­sibilities, distinction between tuberculosis and non-tuberculosis effusions is still not clear. Lower levels of sugar among tuberculosis effusions as compared to serum but normal in malignancy and cirrhosis, are consistent with the previous studies Pleural fluid lactate dehydrogenase levels were elevated in both tuberculosis and malignancy but levels in malignancy were much higher which in the presence of normal or low level of proteins is also consistent with the malignant effusions¹⁴. Elevated lactate dehydrogenase levels in malignant pleural fluid than in serum is in agreement with Wrobeiski¹³. Pleural fluid/serum ratio for lactate dehydrogenase in tuberculosis is higher in com­parison to cirrhosis and low in malignancy. The alkaline phosphatase ratio in tuberculosis is higher as compared to malignancy and cirrhosis. Though this study compares well with the previous studies, the parameters studied do not confirm the diagnosis. The determination of lactate dehydrogenase and alkaline phosphatase may help to differentiate tuberculosis from malignant effusions but are not diag­nostic. The pleural fluid/blood ratio for lactate dehydrogenase and alkaline phosphatase may also con­tribute. In the absence of any diagnostic parameter, the routine investigations of pleural fluid, sputum and pleural biopsy for direct smear and culture remains important in the workup of tuberculosis effusions. Some encouraging results have been reported when all inves­tigations are undertaken¹⁶. Recent advances in molecular biology of the DNA hybridization with polymerase chain reaction promises to be a great advance, but is not yet available for the routine laboratory investigations¹⁷.

1. Hirsch, A., Ruffle, P., Nebur., M., Bignon, .1. and Chretein, J. Pleural effusions; laboratory tests in 300 cases. Thorax. 1979; 34:106-12.
2. Storey, D.D., Dines, D.E. and Coles, D.T. Pleural effusions. A diagnostic dilcma. JAMA, 1976; 236:2183-86.
3. Light, R.W. Pleural diseases. Philadelphia, Lea and Febiger, 1983, pp.61-7.
4. Lowell, J.R. Pleural effusions. A comprehensive review. Baltimore, University Park Presa, 1977, p. 64.
5. Falk, A. The prognostic significance of the idiopathic pleural effuaiona. Dis. Chest, 1950; 18:542-61.
6. Ropper, W.H. and Waring. J.J. Primary serolibrinous pleural effusions in military personnel. Am. Rev. Tuberc., 1955; 71:616.34.
7. Paddock, F.K. The diagnostic significance of serous fluids in disease. N.Engl. 3. Med., 1940; 223:1010-15.
8. Paddock, F.K. The relationship between specific gravity and the protein content in human serous effusions. Am.J. Mcd., Sci. 1941; 201:569-74.
9. Leuallen, E.G and Csrr, D.T. Pleural effusiuns. A statistical study of 436 patients. N. Engl. 3. Med., 1955; 252:79-83.
10. Carr, D.T. and Power, M.H. Clinical value of measurement ofconcentration of proteins in pleural fluid, N. Engl. 3. Med., 1958;259:9.26-27.
11. Furabashi, A., Sarkar, T.K. and Korey, R.G Respiratory gas and pH measurementa of pleural fluid. N. EngI. 3. Med., 1959; 108:1266.
12. Luetscher, J.A. Electrophoretic analysis of the proteins of plasma and serous effusions. 3. din. Invest., 1941; 20:90-106.
13. Wrobleiwski, F. and Wrobleiwski, Ft. The clinical significance of lactic dehydrogenase activity of aerous effusiona. Ann. Intern. Med.. 1958; 48:813-22.
14. Light, ltW., Isabelle MacGregor, M.1., Luchsinger, P.C. and Ball, W.C Pleural effusions; the diagnostic separation of transudates and exudates. Ann. Intern. Med., 1972; 77:507-13.
15. Meisel, 5., Shamiss, A.B., Thaler, M., Nuasinovitch, N. and Roscuthal, T. Pleural fluid to serum bilirubin concentration ratio for separation of transudates from exudates. Chest, 1990,98:141-44.
16. Siebert, A.F., Haynes, J., Middleton, ft. and Bass, T.B. Tuberculous pleural effusion. Twenty year experience. Chest, 1991; 99:883-86.
17. Grange, J.M. Recent developments of molecular biology of mycobacteria. Bull, lot. Union Tuberc, Lung Dis., 1990; 65:19-22.