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ORIGINAL ARTICLE
Year : 2004  |  Volume : 21  |  Issue : 4  |  Page : 46-49 Table of Contents   

Efficacy of pleural fluid alkaline phosphatase and its ratio to serum levels in distinguishing exudates from transudates


1 Department of Tuberculosis & Chest Diseases, Pt. B.D. Sharma Postgraduate Institute of Medical Sciences, Rohtak., India
2 Department of Biochemistry, Pt. B.D. Sharma Postgraduate Institute of Medical Sciences, Rohtak., India

Correspondence Address:
K B Gupta
Department of Tuberculosis & Chest Diseases, Pt. B.D. Sharma Postgraduate Institute of Medical Sciences, Rohtak.
India
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Source of Support: None, Conflict of Interest: None


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   Abstract 

The objective of present study was to evaluate the efficacy of pleural fluid alkaline phosphatase and its ratio to serum levels to classify pleural fluids. A total of 80 patients were divided in transudates and exudates on the basis of extensive clinical, radiological and biochemical evaluation. The efficacy of pleural fluid alkaline phosphatase (P ALP) and pleural fluid / serum alkaline phosphatase ratio (P/S ALP) assessment along with that of Light's criteria to accurately classify transudates and exudates were analyzed. Up to 89% transudates misclassified by Light's criteria were correctly classified by pleural fluid alkaline phosphatase (P ALP) and pleural fluid/serum alkaline phosphatase ratio (P/S ALP) evaluation. Similarly 92% exudates misclassified by Light's criteria were correctly classified by pleural fluid alkaline phosphatase (P ALP) and pleural fluid/serum alkaline phosphatase ratio (P/S ALP) evaluation. By applying a cut off value of 40.0 IU for P ALP, a sensitivity of 85% and specificity of 75% was found. For P/S ALP, applying a cut off value of 0.25 a sensitivity of 85% and specificity of 80% was found. Both P ALP and P/S ALP had a PPV of 92%. However, their respective NPV were 63% and 70%.

Keywords: Light′s criteria, pleural fluid, alkaline phosphatase.


How to cite this article:
Gupta K B, Ghalaut V, Gupta PP, Arora P, Tandon S. Efficacy of pleural fluid alkaline phosphatase and its ratio to serum levels in distinguishing exudates from transudates. Lung India 2004;21:46-9

How to cite this URL:
Gupta K B, Ghalaut V, Gupta PP, Arora P, Tandon S. Efficacy of pleural fluid alkaline phosphatase and its ratio to serum levels in distinguishing exudates from transudates. Lung India [serial online] 2004 [cited 2019 Sep 21];21:46-9. Available from: http://www.lungindia.com/text.asp?2004/21/4/46/44468


   Introduction Top


One of the most frequent disease entity encountered by pulmonologists worldwide is the presence of fluid in pleural space [1],[2] . In a situation where undiagnosed pleural effusion has come across, the first dilemma needed to be solved is whether the fluid is a transudate or exudates [3],[4] . The most frequently used Light's criteria, though still considered as the gold standard; sometimes misclassify a transudate as an exudates [5],[6] . The present study was undertaken to evaluate the efficacy of pleural fluid alkaline phosphatase and its ratio to serum levels in distinguishing pleural fluid transudates and exudates.


   Patients & Methods Top


The present study was carried out at the Department of Tuberculosis & Chest Diseases, and Biochemistry at our Institute. A total of 80 patients with pleural effusions of diverse etiologies attending chest department were included in the study. The patients were divided in two groups : Group A - transudates, and Group B - exudates on the basis of extensive clinical, radiological and biochemical evaluation. [Table 1]

Alkaline phosphatase estimation : Alkaline phosphatase estimation was carried out using method described by Kings et al [7] . Phenol was released by enzymatic hydrolysis of phenyl phosphate under defined conditions of time, temperature and pH which was then estimated calorimetrically.

Light's criteria : According to Light's criteria exudates meet at least one of the following criteria, whereas transudates meet none : (i) pleural fluid protein divided by serum protein greater than 0.5, (ii) pleural fluid LDH divided by serum LDH greater than 0.6 (iii) pleural fluid LDH greater than 2/3rd the upper limit of serum LDH. All patients were evaluated by Light's criteria as well.

[Table 4] demonstrates the pleural fluid alkaline phosphatase (P ALP) levels and pleural fluid/serum alkaline phosphatase ratios (P/S ALP) in transudates and exudates. The alkaline phosphatase concentration in pleural fluid was found to be higher in the exudates than that compared to transudates. The difference in means of transudates and exudates was statistically significant (p<0.05) for pleural fluid alkaline phosphatase level and also for pleural fluid/serum alkaline phosphatase ratio.

Statistical analysis : The statistical differences between the means of various parameters of two groups were estimated by student's unpaired "t" test. The usefulness of each biochemical parameter was evaluated by Bayesian method including sensitivity, specificity, positive predictive value, and negative predictive value.


   Results Top


Out of 80 patients, there were 63 males; the male/ female ratio in the transudate group and exudate group being 2.33 and 4.45; respectively. The nonsmoker/ smoker ratios in transudate group and exudate group were 2:3 and 1:3, respectively. [Table 2] shows the etiology of pleural fluid in these patients. [Table 3] illustrates the radiological appearance of pleural fluid in these patients.

[Table 5] shows the number of cases misclassified by Light's criteria but correctly classified by pleural fluid alkaline phosphatase ( P ALP) and pleural fluid/ serum alkaline phosphatase ratio (P/S ALP) evaluation. Up to 89% transudates misclassified by Light's criteria were correctly classified by pleural fluid alkaline phosphatase (PALP) and pleural fluid/serum alkaline phosphatase ratio (P/S ALP) evaluation. Similarly, 92% exudates misclassified by Light's criteria were correctly classified by pleural fluid alkaline phosphatase (P ALP) and pleural fluid/serum alkaline phosphatase ratio (P/S ALP) evaluation.

[Table 6] reveals sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of pleural fluid alkaline phosphatase (P ALP) and pleural fluid/serum alkaline phosphatase ratio (P/ S ALP) estimation in these patients. By applying a cut off value of 40.0 IU for P ALP, a sensitivity of 85% and specificity of 75% was found. For P/S ALP, applying a cut off value of 0.25, a sensitivity of 85% and specificity of 80% was found. Both P ALP and P/S ALP had a PPV of 92%. However, their respective NPV were 63% and 70%.


   Discussion Top


For decades, the Light's criteria have been used far more frequently than any other single criteria for diagnosing transudates or exudates and considered as a gold standard. Over the last few years, various workers have noted that even Light's criteria misclassify a significant percentage of pleural effusions in certain clinical circumstances [8],[9],[10],[11] . The results from these studies have shown that none of various parameters could be used as a sole criterion to diagnose transudate or exudates in all clinical scenarios with an infallible accuracy. This has resulted in active search of some better parameters - alkaline phosphates estimation being one of them.

Alkaline phosphatase catalyzes the alkaline hydrolysis of a large variety of naturally occuring and synthetic substrates, but the natural substances on which they act in the body are not known [12] . The enzyme is present in all tissues of the body at or in the cell membranes, and particularly occurs in high concentrations in the intestinal epithelium, kidney tubules, bone, liver and placenta. The predominant types present in normal serum can be characterized as that of liver and bone variety [12] . Although the precise metabolic function of the enzyme is not yet known, it appears that the enzyme is associated with lipid transport in intestinal epithelium and with calcification process in bone.

As noted in various previous studies [13],[14],[15],[16] also; exudates have a high concentration of alkaline phosphatase in pleural effusion when compared to that of transudates and the same feature has been used in distinguishing transudates and exudates successfully. By applying a cut off value of 40.0 IU for P ALP, a sensitivity of 85% and specificity of 75% was found. For P/S ALP, applying a cut off value of 0.25 a sensitivity of 85% and specificity of 80% was found. Both P ALP and P/S ALP had a PPV of 92% NPV of P ALP evaluation was 63%; whereas NPV of P/S ALP was 70%. The percentage of misclassification by using pleural alkaline phosphatase criteria was similar to that by Light's criteria in case of transudates and better than Light's criteria in cases with exudates. Moreover, a significant number of the patients misclassified by Light's criteria were accurately picked up by pleural fluid alkaline phosphatase and its ratio to serum levels.

To conclude, though Light's criteria remains as gold standard to differentiate transudates and exudates, in cases where there is a mismatch between clinical diagnosis and the outcome from Light's criteria, especially cases having pleural fluid protein level between 2.5 to 3.5 g%, pleural fluid alkaline phosphatase (P ALP) and pleural fluid / serum alkaline phosphatase ratio (P/S ALP) evaluation may add to diagnostic accuracy. It is by no way going to replace the Light's criteria but can be used as a complementary to Light's criteria in borderline cases to further enhance the diagnostic accuracy.

 
   References Top

1.Storey DD, Dines DE, Coles DT. Pleural effusion : a diagnostic dilemma. JAMA 1976 ; 236 : 2183-6  Back to cited text no. 1    
2.McLean AN, Bicknell SR, McAlpine LG, Peacock AJ. Investigation of pleural effusion. Chest 1998 ; 114 : 150-3  Back to cited text no. 2    
3.Heffner JE, Sahn SA, Brown LK. Multilevel likelihood ratios for identifying exudative pleural effusion. Chest 2002; 121 : 1916-20  Back to cited text no. 3    
4.Burgess LJ, Martiz FJ, Taljaard JJF, et al. Comparative analysis of the biochemical parameters used to distinguish between pleural transudates and exudates. Chest 1995; 107 : 1604-09.  Back to cited text no. 4    
5.Porcel JM, Vives M, de Vera MCV, et al. Useful tests on pleural fluids that distinguish transudates from exudates. Ann Clin Biochem 2001; 38 : 671-5.  Back to cited text no. 5    
6.Porcel NK, Vives M. Classic, abbreviated, and modified Light's criteria: the end of the story ? Chest 1999 ; 116 : 1833-34.  Back to cited text no. 6    
7.King EJ, Armstrong AR. Estimation of alkaline phosphatase. Canad Med Assoc J 1934 ; 311 : 152-56.  Back to cited text no. 7    
8.Hamm H, Broham U, Bohmer R, et al. Cholesterol in pleural effusions : a diagnostic aid. Chest 1987 ; 92 : 296-302.  Back to cited text no. 8    
9.Gupta KB, Sindhwani G, Gahlaut VS, Parkash Prem, Tandon S, et al. Evaluation of pleural fluid and serum MDA levels in differentiating transudative from exudative pleural effusions. Indian J Tub 2002 ; 49 : 97 - 102.  Back to cited text no. 9    
10.Gupta KB, Ghaluat V, Gupta R, Tandon S, Parkash P, et al. Estimation of serum and pleural fluid amylase and isoenzymes in cases of malignant pleural effusion. Indian J Tub 2001; 48: 87-89.  Back to cited text no. 10    
11.Roth BT, O' Meara TF, Cragun WH, et al. The serum effusion albumin gradient in the evaluation of pleural effusion. Chest 1990; 98 : 546-49.  Back to cited text no. 11    
12.Moss DW, Handersson AR. Teitz text book of clinical chemistry. 3rd ed. Philadelphia : WB Saunders Co. 1999 ; p 617-721.  Back to cited text no. 12    
13.Sarojini B, Ramakrishan R. Enzymes in biofluids for diagnosis of diseases. Indian J Clin Biochem 1991; 6 : 14348.  Back to cited text no. 13    
14.Syablo NC. Use of pleural alkaline phosphatase content to diagnose tubercular effusions. Chest 1991; 99 : 522-3.  Back to cited text no. 14    
15.Gazquez I, Porcel JM, Vives M. Pleural alkaline phosphatase in separation of transudative and exudative pleural effusion. Chest 1997; 112 : 569-70.  Back to cited text no. 15    
16.Metinatas M, Alatas O, Alatas F, et al. Comparative analysis of biochemical parameters for differentiation of pleural exudates from transudates - Light's criteria, cholesterol, bilirubin, albumin gradient, alkaline phosphatase, creatinine kinase, and uric acid. Clin Chim Acta 1997; 264 : 149-62.  Back to cited text no. 16    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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