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Diagnostic evaluation of a pleural effusion in adults: Initial testing

John E Heffner, MD
Section Editor
Talmadge E King, Jr, MD
Deputy Editor
Geraldine Finlay, MD


Determining the cause of a pleural effusion is greatly facilitated by analysis of the pleural fluid. Thoracentesis is a simple bedside procedure with imaging guidance that permits fluid to be rapidly sampled, visualized, examined microscopically, and quantified for chemical and cellular content. A systematic approach to analysis of the fluid in conjunction with the clinical presentation should allow the clinician to diagnose the cause of an effusion in about 75 percent of patients at the first clinical evaluation [1]:

A definitive diagnosis, provided by the finding of malignant cells or specific organisms in the pleural fluid, can be established in approximately 25 percent of patients.

A presumptive diagnosis, based on the pre-thoracentesis clinical impression, can be substantiated by pleural fluid analysis in an additional 50 percent of patients.

Even with a nondiagnostic thoracentesis, pleural fluid analysis can be useful in excluding other possible causes, such as infection, or guiding subsequent diagnostic studies. Thus, clinical decision-making information can be gained from pleural fluid analysis in over 90 percent of patients [1].

An approach to pleural fluid analysis will be presented here. Pleural imaging, the technique of thoracentesis, and an approach to pleural effusions of uncertain etiology after the initial evaluation are discussed separately. (See "Imaging of pleural effusions in adults" and "Diagnostic thoracentesis" and "Diagnostic evaluation of pleural effusion in adults: Additional tests for undetermined etiology".)


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Literature review current through: Sep 2016. | This topic last updated: Dec 2, 2015.
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  1. Collins TR, Sahn SA. Thoracocentesis. Clinical value, complications, technical problems, and patient experience. Chest 1987; 91:817.
  2. Sahn SA, Huggins JT, San Jose E, et al. The art of pleural fluid analysis. Clin Pulm Med 2013; 20:77.
  3. Ali HA, Lippmann M, Mundathaje U, Khaleeq G. Spontaneous hemothorax: a comprehensive review. Chest 2008; 134:1056.
  4. Bouros D, Pneumatikos I, Tzouvelekis A. Pleural involvement in systemic autoimmune disorders. Respiration 2008; 75:361.
  5. Ferreiro L, Alvarez-Dobaño JM, Valdés L. Systemic diseases and the pleura. Arch Bronconeumol 2011; 47:361.
  6. Murin S, Wiedemann HP, Matthay RA. Pulmonary manifestations of systemic lupus erythematosus. Clin Chest Med 1998; 19:641.
  7. Hunder GG, Pierre RV. In vivo LE cell formation in synovial fluid. Arthritis Rheum 1970; 13:448.
  8. Funauchi M, Ikoma S, Yu H, et al. A case of progressive systemic sclerosis complicated by massive pleural effusion with elevated CA125. Lupus 2000; 9:382.
  9. Toworakul C, Kasitanon N, Sukitawut W, et al. Usefulness of pleural effusion antinuclear antibodies in the diagnosis of lupus pleuritis. Lupus 2011; 20:1042.
  10. Porcel JM, Ordi-Ros J, Esquerda A, et al. Antinuclear antibody testing in pleural fluid for the diagnosis of lupus pleuritis. Lupus 2007; 16:25.
  11. Khare V, Baethge B, Lang S, et al. Antinuclear antibodies in pleural fluid. Chest 1994; 106:866.
  12. Wang DY, Yang PC, Yu WL, et al. Serial antinuclear antibodies titre in pleural and pericardial fluid. Eur Respir J 2000; 15:1106.
  13. Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972; 77:507.
  14. Heffner JE, Brown LK, Barbieri CA. Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Primary Study Investigators. Chest 1997; 111:970.
  15. Gonlugur U, Gonlugur TE. The distinction between transudates and exudates. J Biomed Sci 2005; 12:985.
  16. Kummerfeldt CE, Chiuzan CC, Huggins JT, et al. Improving the predictive accuracy of identifying exudative effusions. Chest 2014; 145:586.
  17. Porcel JM, Peña JM, Vicente de Vera C, et al. Bayesian analysis using continuous likelihood ratios for identifying pleural exudates. Respir Med 2006; 100:1960.
  18. Heffner JE, Highland K, Brown LK. A meta-analysis derivation of continuous likelihood ratios for diagnosing pleural fluid exudates. Am J Respir Crit Care Med 2003; 167:1591.
  19. Chakko SC, Caldwell SH, Sforza PP. Treatment of congestive heart failure. Its effect on pleural fluid chemistry. Chest 1989; 95:798.
  20. Shinto RA, Light RW. Effects of diuresis on the characteristics of pleural fluid in patients with congestive heart failure. Am J Med 1990; 88:230.
  21. Romero-Candeira S, Fernández C, Martín C, et al. Influence of diuretics on the concentration of proteins and other components of pleural transudates in patients with heart failure. Am J Med 2001; 110:681.
  22. Roth BJ, O'Meara TF, Cragun WH. The serum-effusion albumin gradient in the evaluation of pleural effusions. Chest 1990; 98:546.
  23. Porcel JM. Utilization of B-type natriuretic peptide and NT-proBNP in the diagnosis of pleural effusions due to heart failure. Curr Opin Pulm Med 2011; 17:215.
  24. Winterbauer RH, Riggins RC, Griesman FA, Bauermeister DE. Pleuropulmonary manifestations of Waldenstrom's macroglobulinemia. Chest 1974; 66:368.
  25. Rodríguez JN, Pereira A, Martínez JC, et al. Pleural effusion in multiple myeloma. Chest 1994; 105:622.
  26. Light RW, Girard WM, Jenkinson SG, George RB. Parapneumonic effusions. Am J Med 1980; 69:507.
  27. Pettersson T, Klockars M, Hellström PE. Chemical and immunological features of pleural effusions: comparison between rheumatoid arthritis and other diseases. Thorax 1982; 37:354.
  28. Johnson JR, Falk A, Iber C, Davies S. Paragonimiasis in the United States. A report of nine cases in Hmong immigrants. Chest 1982; 82:168.
  29. Horowitz ML, Schiff M, Samuels J, et al. Pneumocystis carinii pleural effusion. Pathogenesis and pleural fluid analysis. Am Rev Respir Dis 1993; 148:232.
  30. Garcia-Pachon E, Padilla-Navas I. Urinothorax: case report and review of the literature with emphasis on biochemical diagnosis. Respiration 2004; 71:533.
  31. Staats BA, Ellefson RD, Budahn LL, et al. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc 1980; 55:700.
  32. Sahn SA. Pathogenesis and clinical features of diseases associated with a low pleural fluid glucose. In: The Pleura in Health and Disease, Chretien J, Bignon J, Hirsch A (Eds), Marcel Dekker, New York 1985. p.267-285.
  33. Carr DT, McGuckin WF. Pleural fluid glucose. Serial observation of its concentration following oral administration of glucose to patients with rheumatoid pleural effusions and malignant effusions. Am Rev Respir Dis 1968; 97:302.
  34. Taryle DA, Good JT Jr, Sahn SA. Acid generation by pleural fluid: possible role in the determination of pleural fluid pH. J Lab Clin Med 1979; 93:1041.
  35. Good JT Jr, Taryle DA, Sahn SA. The pathogenesis of low glucose, low pH malignant effusions. Am Rev Respir Dis 1985; 131:737.
  36. Sahn SA, Reller LB, Taryle DA, et al. The contribution of leukocytes and bacteria to the low pH of empyema fluid. Am Rev Respir Dis 1983; 128:811.
  37. Cheng DS, Rodriguez RM, Rogers J, et al. Comparison of pleural fluid pH values obtained using blood gas machine, pH meter, and pH indicator strip. Chest 1998; 114:1368.
  38. Bowling M, Lenz P, Chatterjee A, et al. Perception versus reality: the measuring of pleural fluid pH in the United States. Respiration 2012; 83:316.
  39. Sahn SA. Pleural fluid pH in the normal state and in diseases affecting the pleural space. In: The Pleura in Health and Disease, Chretien J, Bignon J, Hirsch A (Eds), Marcel Dekker, New York 1985. p.253.
  40. Sahn SA, Willcox ML, Good JT Jr, et al. Characteristics of normal rabbit pleural fluid: physiologic and biochemical implications. Lung 1979; 156:63.
  41. Good JT Jr, Antony VB, Reller LB, et al. The pathogenesis of the low pleural fluid pH in esophageal rupture. Am Rev Respir Dis 1983; 127:702.
  42. Sahn SA, Good JT Jr. Pleural fluid pH in malignant effusions. Diagnostic, prognostic, and therapeutic implications. Ann Intern Med 1988; 108:345.
  43. Burrows CM, Mathews WC, Colt HG. Predicting survival in patients with recurrent symptomatic malignant pleural effusions: an assessment of the prognostic values of physiologic, morphologic, and quality of life measures of extent of disease. Chest 2000; 117:73.
  44. Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of survival for patients with malignant pleural effusions. Chest 2000; 117:79.
  45. Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of pleurodesis failure: analysis of primary data. Chest 2000; 117:87.
  46. Heffner JE, Heffner JN, Brown LK. Multilevel and continuous pleural fluid pH likelihood ratios for draining parapneumonic effusions. Respiration 2005; 72:351.
  47. Jiménez Castro D, Díaz Nuevo G, Sueiro A, et al. Pleural fluid parameters identifying complicated parapneumonic effusions. Respiration 2005; 72:357.
  48. Joseph J, Viney S, Beck P, et al. A prospective study of amylase-rich pleural effusions with special reference to amylase isoenzyme analysis. Chest 1992; 102:1455.
  49. Piras MA, Gakis C, Budroni M, Andreoni G. Adenosine deaminase activity in pleural effusions: an aid to differential diagnosis. Br Med J 1978; 2:1751.
  50. Riantawan P, Chaowalit P, Wongsangiem M, Rojanaraweewong P. Diagnostic value of pleural fluid adenosine deaminase in tuberculous pleuritis with reference to HIV coinfection and a Bayesian analysis. Chest 1999; 116:97.
  51. Liang QL, Shi HZ, Wang K, et al. Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis. Respir Med 2008; 102:744.
  52. Ogata Y, Aoe K, Hiraki A, et al. Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis? Acta Med Okayama 2011; 65:259.
  53. Burgess LJ, Maritz FJ, Le Roux I, Taljaard JJ. Combined use of pleural adenosine deaminase with lymphocyte/neutrophil ratio. Increased specificity for the diagnosis of tuberculous pleuritis. Chest 1996; 109:414.
  54. Porcel JM, Esquerda A, Bielsa S. Diagnostic performance of adenosine deaminase activity in pleural fluid: a single-center experience with over 2100 consecutive patients. Eur J Intern Med 2010; 21:419.
  55. Liu YC, Shin-Jung Lee S, Chen YS, et al. Differential diagnosis of tuberculous and malignant pleurisy using pleural fluid adenosine deaminase and interferon gamma in Taiwan. J Microbiol Immunol Infect 2011; 44:88.
  56. Kalantri Y, Hemvani N, Chitnis DS. Evaluation of real-time polymerase chain reaction, interferon-gamma, adenosine deaminase, and immunoglobulin A for the efficient diagnosis of pleural tuberculosis. Int J Infect Dis 2011; 15:e226.
  57. Kolditz M, Halank M, Schiemanck CS, et al. High diagnostic accuracy of NT-proBNP for cardiac origin of pleural effusions. Eur Respir J 2006; 28:144.
  58. Tomcsányi J, Nagy E, Somlói M, et al. NT-brain natriuretic peptide levels in pleural fluid distinguish between pleural transudates and exudates. Eur J Heart Fail 2004; 6:753.
  59. Porcel JM, Vives M, Cao G, et al. Measurement of pro-brain natriuretic peptide in pleural fluid for the diagnosis of pleural effusions due to heart failure. Am J Med 2004; 116:417.
  60. Porcel JM, Martínez-Alonso M, Cao G, et al. Biomarkers of heart failure in pleural fluid. Chest 2009; 136:671.
  61. Zhou Q, Ye ZJ, Su Y, et al. Diagnostic value of N-terminal pro-brain natriuretic peptide for pleural effusion due to heart failure: a meta-analysis. Heart 2010; 96:1207.
  62. Porcel JM, Chorda J, Cao G, et al. Comparing serum and pleural fluid pro-brain natriuretic peptide (NT-proBNP) levels with pleural-to-serum albumin gradient for the identification of cardiac effusions misclassified by Light's criteria. Respirology 2007; 12:654.
  63. Long AC, O'Neal HR Jr, Peng S, et al. Comparison of pleural fluid N-terminal pro-brain natriuretic peptide and brain natriuretic-32 peptide levels. Chest 2010; 137:1369.
  64. Janda S, Swiston J. Diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac origin: a systematic review and meta-analysis. BMC Pulm Med 2010; 10:58.
  65. Light RW. Tumor markers in undiagnosed pleural effusions. Chest 2004; 126:1721.
  66. Liang QL, Shi HZ, Qin XJ, et al. Diagnostic accuracy of tumour markers for malignant pleural effusion: a meta-analysis. Thorax 2008; 63:35.
  67. Porcel JM, Vives M, Esquerda A, et al. Use of a panel of tumor markers (carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions. Chest 2004; 126:1757.
  68. Hassan R, Remaley AT, Sampson ML, et al. Detection and quantitation of serum mesothelin, a tumor marker for patients with mesothelioma and ovarian cancer. Clin Cancer Res 2006; 12:447.
  69. Light RW. Pleural diseases, 3rd ed, Williams & Wilkins, Baltimore 1995.
  70. Yam LT. Diagnostic significance of lymphocytes in pleural effusions. Ann Intern Med 1967; 66:972.
  71. Adelman M, Albelda SM, Gottlieb J, Haponik EF. Diagnostic utility of pleural fluid eosinophilia. Am J Med 1984; 77:915.
  72. Spriggs AI, Boddington NM. The Cytology of Effusions, 2nd ed, Grune and Stratton, New York 1968.
  73. Rubins JB, Rubins HB. Etiology and prognostic significance of eosinophilic pleural effusions. A prospective study. Chest 1996; 110:1271.
  74. Martínez-García MA, Cases-Viedma E, Cordero-Rodríguez PJ, et al. Diagnostic utility of eosinophils in the pleural fluid. Eur Respir J 2000; 15:166.
  75. Fatimi SH, Deedar-Ali-Khawaja R. Catamenial pneumothorax associated with ascites, eosinophilic pleural effusion, and relatively low glucose content. Am Surg 2010; 76:E212.
  76. Light RW, Erozan YS, Ball WC Jr. Cells in pleural fluid. Their value in differential diagnosis. Arch Intern Med 1973; 132:854.
  77. Hurwitz S, Leiman G, Shapiro C. Mesothelial cells in pleural fluid: TB or not TB? S Afr Med J 1980; 57:937.