|Year : 2013 | Volume
| Issue : 2 | Page : 54-57
Comparative analysis of pleural fluid biochemical parameters with cholesterol to differentiate transudates from exudates
Rohit Rungta1, Rajendra K Jha2
1 Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India
2 Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India
|Date of Web Publication||18-Dec-2013|
Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, 124 Mukundapur, Kolkata - 700 099, West Bengal
Source of Support: None, Conflict of Interest: None
Background: Light's criteria is the gold standard to differentiate transudative pleural effusion (PE) from exudative PE, but it requires four biochemical estimations which, in developing countries such as India, may not be feasible in every patient due to economic constraints. Aims: To evaluate the comparative usefulness of pleural fluid biochemical parameters with relative usefulness of pleural cholesterol to the traditional Light' criteria. Setting and Design: Prospective institutional based study. Materials and Methods: A total of 56 cases of PE were studied consecutively, of which 34 cases were of tuberculous effusion and 22 cases of nontubercular effusion. The data obtained from the patients were collected, analyzed, and observations noted down. Statistical Analysis: Sensitivity, specificity, positive predictive value and negative predictive value of different biochemical parameters single or in combination were analyzed by SPSS 16 software. Results: According to their etiology, 7 of the effusions were transudates and 49 were exudates. Using a cutoff point of 45 mg for pleural cholesterol and values for protein and lactate dehydrogenase (LDH) of Light et al., the best diagnostic power corresponded to the combination of pleural cholesterol and LDH; cholesterol level over 45 mg/dL and/or LDH over 200 IU/L differentiate exudates from transudates with a sensitivity of 99% and a specificity of 98%. Conclusions: The measurement of pleural cholesterol and LDH permits the separation of pleural exudates from transudates with accuracy similar to the original report of Light et al., with the advantage of requiring only two laboratory determinations and no simultaneous blood sample, especially in a country like India where financial and technical constraints are immense.
Keywords: Cholesterol, exudate, light′s criteria, pleural effusion, transudate
|How to cite this article:|
Rungta R, Jha RK. Comparative analysis of pleural fluid biochemical parameters with cholesterol to differentiate transudates from exudates. J Assoc Chest Physicians 2013;1:54-7
|How to cite this URL:|
Rungta R, Jha RK. Comparative analysis of pleural fluid biochemical parameters with cholesterol to differentiate transudates from exudates. J Assoc Chest Physicians [serial online] 2013 [cited 2019 Mar 24];1:54-7. Available from: http://www.jacpjournal.org/text.asp?2013/1/2/54/123215
| Introduction|| |
Pleural effusion (PE) is of two types depending on the underlying pathophysiology, that is, ''transudates'' and ''exudates.'' Transudates occur when the mechanical factors influence the formation or reabsorption of pleural fluid, like a decrease in plasma oncotic pressure or elevated systemic or pulmonary hydrostatic pressure. Exudate results from inflammation or irritation or other disease process involving the pleura, resulting in increased permeability. 
The first step in determining the etiology of a PE should be to find out whether it is a transudate or an exudate. Light et al., used pleural fluid and serum levels of protein and LDH to establish criteria for differentiating transudates from exudates with a sensitivity and specificity of near 100%. This high diagnostic accuracy made the criteria of Light et al., the 'gold standard' for initial categorization of PE. , However, Light's criteria require four biochemical estimations which, in developing countries such as India, may not be feasible in every patient due to economic constraints. Also, several prospective studies were unable to reproduce the results obtained by Light et al. ,,
The main purpose of this study is to evaluate a large number of PE patients to compare, prospectively, the relative usefulness of pleural concentrations of cholesterol to the traditional criteria of Light et al.,  and their different individual parameters' [pleural lactate dehydrogenase (LDH) concentration, pleural fluid to serum LDH ratio, and pleural fluid to serum protein ratio] for separating exudates from transudates and to determine whether a similar result could be obtained by combining cholesterol with only one or two of the individual indicators of Light et al., thus simplifying the diagnostic procedure and lowering the cost. 
| Materials and Methods|| |
This observational nonrandomized multiple arm prospective study was carried out in a group of new PE cases, admitted between July 2010 and June 2011 in the Department of Medicine at Rajendra Institute of Medical Sciences, Ranchi, Bihar, India. A total of 56 adult patients of both sexes were selected by adhering strictly to certain inclusion and exclusion criteria.
(i) Age ≥14 years of both sexes; (ii) patients with definite clinical diagnosis and PE evidenced by radiological imaging, where thoracentesis yield a sufficient good quantity of pleural fluid for examination; (iii) patients of PE who have not received any therapy for his/her present disease; and (iv) patients giving consent.
(i) Patients with history of PE due to trauma (penetrating or nonpenetrating); (ii) patients previously diagnosed and already on treatment; (iii) patients without definite clinical diagnosis; and (iv) patients not willing to participate in the study.
All the PE patients after admission in the emergency, detailed history taking and clinical examination were performed. Patient was assessed for the history of fever, productive or dry cough, night sweats, hemoptysis, chest pain, lower extremity edema, orthopnea, paroxysmal nocturnal dyspnea, decreased urine output, and other relevant symptoms. Clinical assessment including general survey and systemic examination was done. Patient was investigated for parameters like routine blood examination, serum cholesterol, serum LDH, chest x-ray, electrocardiography, echocardiography, renal function tests, liver function tests, biochemical and cytological examination of pleural fluid (cell count, cell type, specific gravity, protein, sugar, LDH, adenosine deaminase (ADA), cholesterol, acid fast bacilli, malignant cells, mycobacterial culture), sputum for acid fast bacilli, ultrasonography of thorax, and computed tomography of thorax (in selected patients) for evaluation of PE.
The PEs were classified as exudative and transudative on the basis of etiological diagnosis, Light's criteria, and pleural fluid cholesterol (a pleural fluid value >45 mg/dL and ratio of pleural fluid and serum cholesterol of >0.3 taken to define exudates). , According to Light's criteria if any one of the following is present, then the fluid was classified as an exudate: (1) pleural fluid to serum total protein ratio greater than 0.5, (2) pleural fluid to serum LDH ratio greater than 0.6, and/or (3) pleural fluid LDH greater than 200 IU/L. 
Sensitivity, specificity, positive predictive value and negative predictive value of different biochemical parameters single or in combination were analyzed by SPSS 16 software.
Strict confidentiality of the study reports was maintained and all the queries and apprehensions of the patients and their families were addressed with utmost care. Prior to initiating the study, counseling of the patients and their families were done and an informed written consent was taken.
| Results|| |
A total of 56 patients with PE were studied of which 34 (60.52%) were cases of tuberculous effusion and 22 (39.48%) were cases of nontuberculous effusion. The remaining 22 cases were of malignant effusion (eight cases), transudative effusion (seven cases), synpneumonic effusion (five cases), and two cases of empyema. There were a greater number of male patients than female patients in this study with 69.42% males and 30.58% females. The present study comprised of patients aged from 18 years to 74 years (mean age: 40.16 ± 14.50 years). The mean age in case of tuberculous effusion was 33.9 ± 9.49 years, with the maximum number of patients between 20 and 50. The mean ages in case of malignant, synpneumonic, and transudative effusions were 62.4 ± 7.019 years, 32 ± 13.32 years, and 46.6 ± 8.23 years, respectively. Out of the 56 patients with PE 30 patients had a right-sided effusion and 20 patients had a left-sided effusion and 6 patients had bilateral effusion. Empyema was detected in two cases, both were on right side.
The amount of proteins in the pleural fluid ranged from 1.2 to 6.2 g/dL. The mean protein level in tuberculous effusion was 4.1 ± 0.8 g/dL, in malignant effusion was 4.8 ± 0.2 g/dL, in synpneumonic effusion was 4.7 ± 0.3 g/dL, in empyema it was 4.7 ± 0.2, and in case of transudate it was 2 ± 0.7 g/dL. The pleural fluid and serum protein ratio was >0.5 g% in tubercular, malignant, synpneumonic, and empyema but <0.5 g% in transudative PE [Table 1] and [Table 2]. The glucose level in the pleural fluid ranged from 48 to 148 mg%. Low glucose levels were associated with tuberculous effusions, synpneumonic, empyema and malignant effusion, and high glucose levels were seen in transudate. In our study, the mean values of pleural fluid glucose were: Tuberculous effusion 61 ± 9.2 mg%, malignant effusion 50 ± 4 mg%, synpneumonic effusion 48 ± 15 mg %, empyema 27 ± 3.5 mg%, and in case of transudate 84 ± 11 mg % [Table 1] and [Table 2]. The mean levels of ADA in the pleural fluid in the various groups of effusions were estimated. In tuberculous effusions, the mean ADA level was 78.7 ± 19.9 IU/L, in malignant effusion the mean ADA level was 42.6 ± 9.3 IU/L and in transudates, the mean ADA level was 28.4 ± 8.2 IU/L [Table 1] and [Table 2]. The average LDH value in tubercular effusion 236.2 ± 37.5, malignant 340 ± 46.5, transudative 95 ± 24.5, synpneumonic 530 ± 80, and empyema 1225 ± 125. The mean LDH in exudate effusion was higher as compared to transudative effusions which was highly significant [Table 1] and [Table 2]. By taking ratio of pleural and serum LDH >0.6 cutoff, the activity of LDH exhibited 85.4% sensitivity and 75% specificity. By taking pleural fluid LDH 200U/L as cutoff point, it exhibited 79.1% sensitivity and 75% specificity [Table 3].
|Table 3: Sensitivity, specificity, positive predictive value and negative predictive value of various biochemical parameters of pleural fluid in isolation or combination|
Click here to view
The average pleural fluid cholesterol in tubercular effusion 72.4 ± 9.2, malignant 76.1 ± 10.2, transudative 36.9 ± 5.2, synpneumonic 74.2 ± 4.2, and empyema 74.5 ± 4.5 [Table 1] and [Table 2]. The mean pleural fluid in exudates was significantly higher compared with transudates. By taking pleural fluid cholesterol of <45 mg% as the cutoff value, the pleural fluid cholesterol test exhibited 90% sensitivity and 99% specificity for diagnosis of transudative effusions [Table 3].
| Discussion|| |
According to the causal disease, 7 (12.5%) pleural fluid samples were labeled as transudates and 49 (87.5%) were labeled as exudates. It may be observed that 2 of the 49 exudates were misclassified as transudates (sensitivity 98%) and 1 of the 7 transudates was erroneously labeled as exudates (specificity 87%). The two misclassified exudates corresponded to complicated parapneumonic effusions and of the erroneously classified transudates, one was secondary to congestive heart failure. When the concentration of cholesterol in pleural fluid, with a cutoff point of 45 mg/dL, was used for classification, 5 of the 49 exudates were misclassified with a sensitivity of 90%, while all the transudates were correctly labeled (specificity 100%). If the cutoff point of 60 mg/dL as proposed by Hamm et al.,  was used, sensitivity fell to 73% and specificity remained 100%.
All the transudates that were erroneously classified by the criteria of Light et al., were correctly identified through cholesterol level and, inversely, all exudates that were misclassified by cholesterol were correctly identified by the measurements of Light et al.
[Table 3] shows the sensitivity and specificity calculated for the criteria of Light et al., for cholesterol alone and for all the possible combinations of cholesterol and the individual components of the set of Light et al. It may be observed that cholesterol has a higher sensitivity (P < 0.05) but a lower specificity (P < 0.01) than the criteria of Light et al., and that their combined use improves sensitivity (99%) but not specificity (95%).
Of the six alternatives that combine cholesterol and one or two of the indicators of Light et al., only that of cholesterol level greater than 45 mg/dL and LDH level greater than 200 U/L exhibit a better diagnostic yield than the triad of Light et al., and this is due to a significantly higher specificity (P < 0.02). Our results show that the combination of an increased concentration of cholesterol level greater than 45 mg/dL and/or LDH level greater than 200 U/L in pleural fluid constitutes a useful tool for separating exudates from transudates. , The diagnostic yield of this combination is similar to that obtained by Light et al., in their original investigation and superior to those reported by other authors. ,
Our initial assumption, that the simultaneous use of the criteria of Light et al., and cholesterol would be complementary, was not confirmed, since the specificity of this combination was, in our patients, as low as that of the criteria of Light et al., alone. This could be interpreted as a lack of a contributory effect of cholesterol, but [Table 3] shows that the combinations which include pleural-serum protein ratio were the ones that exhibit the lowest specificity, while the combination of cholesterol and LDH shows the highest.  This misleading effect of protein ratio is present in all the studies that report low specificities. Most of the errors were observed in congestive heart failure and protein ratio was the deceiving index in most cases. This aspect has been recently addressed by Chakko et al.,  who demonstrated that the treatment of heart failure may change the chemistry of pleural fluid probably by withdrawing water and, thus, concentrating proteins. If this is so, the interpretation of protein ratio in heart failure would depend on previous treatment, which is a variable that is difficult to standardize. This would mean that this indicator is not suitable in patients with heart failure and, probably, in those with liver cirrhosis in whom diuretics have been used. As most transudates considered for differential diagnosis correspond to those etiologies, it seems reasonable to abandon this low-specificity indicator. Roth et al.,  showed that this limitation of the criteria of Light et al., could be overcome by measuring the serum-effusion albumin gradient which, when over 1.2 mg/dL, indicated a transudate. Replacing the serum PE protein ratio by this other indicator undoubtedly increases the specificity of the criteria of Light et al., but a simultaneous blood sample is still required.
| Conclusion|| |
The measurement of pleural cholesterol and LDH permits the separation of pleural exudates from transudates with accuracy similar to the original report of Light et al., with the advantage of requiring only two laboratory determinations and no simultaneous blood sample, especially in a country like India where financial and technical constraints are immense.
| References|| |
|1.||Seaton A. The Pleura. In: Seaton A, Leitch AG, Seaton D, editors. Crofton and Douglas's Respiratory Diseases. 5th ed. Vol 2. USA: Wiley-Blackwell; 2000. p. 1152-81. |
|2.||Udwadia FE. History of Respiratory Medicine. In: Jindal SK, Shankar PS, Raoof S, Gupta D, Aggarwal AN Agarwal R, editors. Textbook of Pulmonary and Critical Care Medicine. 1 st ed., Vol 1. New Delhi: Jaypee Brothers; 2011. p. 3 8. |
|3.||Light RW. Disorders of the pleura, mediastinum, diaphragm and chest wall. In: Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscazlo J, editors. Harrison's Principles of Internal Medicine. 18 th ed. USA: McGraw-Hill Professional; 2011. p. 1565-9. |
|4.||Hamm H, Brohan U, Bohmer R, Missmahl HP. Chest 1987;92:296-302. |
|5.||Gil Suay V, Martínez Moragon E, Cases Viedma E, Perpiñá TM, León FM, Sanchis Aldas J. Pleural cholesterol in differentiating transudates and exudates. A prospective study of 232 cases. Respiration 1995;62:57-63. |
|6.||Bartter T, Santarelli R, Akers SM, Pratter MR. The evaluation of pleural effusion. Chest 1994;106:1209-14. |
|7.||Vives M, Porcel JM, Vicente de Vera M, Ribelles E, Rubio M. A study of Light's criteria and possible modifications for distinguishing exudative from transudative pleural effusions. Chest 1996;109:1503-7. |
|8.||Heffner JE, Sahn SA, Brown LK. Multilevel likelihood ratios for identifying exudative pleural effusions(*). Chest 2002;121:1916-20. |
|9.||Valdés L, Pose A, Suàrez J, Gonzalez-Juanatey JR, Sarandeses A, San José E, et al. Cholesterol: A useful parameter for distinguishing between pleural exudates and transudates. Chest 1991;99:1097-102. |
|10.||Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusions: The diagnostic separation of transudates and exudates. Ann Intern Med 1972;77:507-13. |
|11.||Costa M, Quiroga T, Cruz E. Measurement of pleural fluid cholesterol and lactate dehydrogenase. A simple and accurate set of indicators for separating exudates from transudates. Chest 1995;108:1260-3. |
|12.||Walshe AD, Douglas JG, Kerr KM, McKean ME, Godden DJ. An audit of the clinical investigation of pleural effusion. Thorax 1992;47:734-7. |
|13.||Prabhudesai PP, Mahashur AA, Mehta N, Ajay R. Exudative pleural effusion in patients over forty years of age: An analysis of seventy six patients. J Postgrad Med 1993;39:190-3. |
|14.||Chakko SC, Caldwell SH, Sforza PP. Treatment of congestive heart failure. Its effect on pleural fluid chemistry. Chest 1989;95:798-802. |
|15.||Roth BJ, O'Meara TF, Cragun WH. The serum-effusion albumin gradient in the evaluation of pleural effusions. Chest 1990;98:546-9. |
[Table 1], [Table 2], [Table 3]