Affiliations: University of Oxford, Oxford, UK,
Vanderbilt University, Nashville, TN
Correspondence to: Y. C. Gary Lee, PhD, FCCP, Oxford Centre for Respiratory Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK; e-mail: email@example.com
The primary aim of the physician investigating the patient with an undiagnosed pleural effusion is to establish the correct diagnosis with a minimum number of investigations. For > 30 years, the first step in this process is to determine whether the fluid is a transudate or an exudate, which dictates further investigations and management. One consequence of this is the relentless search to find “better” indexes to differentiate transudates from exudates. This letter expresses our view that research efforts directed to this end would be better channeled into identifying disease-specific diagnostic markers.
Simple criteria such as the effusion/serum ratio of protein and lactate dehydrogenase (ie, “Light’s criteria”), have proved to be robust in separating transudates from exudates1with a diagnostic accuracy of 96%.2 This is as near to perfect as is practically possible because the “gold standard” for comparison is clinical diagnosis, which itself carries a small but definite error rate. Even if superior diagnostic criteria were theoretically possible, to establish the superiority of any new proposed criteria over Light’s criteria a sample size of > 13,000 subjects is required (α, 0.05; desired power, 0.90).
Exudates are defined by a higher effusion/serum level of proteins; hence, the levels of most proteins will be higher in exudative effusions, without the proteins necessarily having any specific diagnostic accuracy. Substantial resources can be expended assessing whether a novel marker is a better marker of the transudate-vs-exudate differentiation for little return.
Novel technologies such as global gene profiling and proteomics are now available to improve on this by identifying “fingerprints” for specific diagnoses. Success in this area will help in identifying the cause for an exudate and would be of great clinical value for patients with pleural effusions. We believe that the search for a better marker of a pleural fluid exudate should now be abandoned and that resources should be focused on identifying specific disease markers and improving clinical management.3
None of the authors have a financial relationship with a commercial entity that has an interest in the subject of this article.
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