Original Contribution
The use of pleural fluid procalcitonin and C-reactive protein in the diagnosis of parapneumonic pleural effusions: a systemic review and meta-analysis

https://doi.org/10.1016/j.ajem.2012.04.004Get rights and content

Abstract

Background

We aimed to perform a systematic review and meta-analysis of the diagnostic performance of pleural fluid procalcitonin (PCT) or C-reactive protein (CRP) in differentiating parapneumonic effusion in patients with pleural effusion.

Methods

We searched the EMBASE, MEDLINE, and Cochrane database in December 2011. Original studies that reported the diagnostic performance of PCT alone or compared with that of other biomarkers for differentiating the characteristics of pleural effusion were included.

Results

We found 6 qualifying studies including 780 patients with suspected parapneumonic effusion and 306 confirmed cases of parapneumonic effusion. Six studies examined the diagnostic performance of pleural fluid PCT, 3 also tested for serum PCT, and another 3 tested for serum CRP. The bivariate pooled sensitivity and specificity were as follows 0.67 (95% confidence interval [CI], 0.54-0.78) and 0.70 (95% CI, 0.63-0.76), respectively, for pleural fluid PCT; 0.65 (95% CI, 0.55-0.74) and 0.68 (95% CI, 0.62-0.74), respectively, for serum PCT; and 0.54 (95% CI, 0.47-0.61) and 0.77 (95% CI, 0.72-0.81), respectively, for serum CRP. There was evidence of significant heterogeneity (I2 = 55.0%) for pleural fluid or serum PCT but not for CRP (I2 = 0.0%).

Conclusion

The existing literature suggests that both pleural fluid and serum PCT tests have low sensitivity and specificity for differentiating parapneumonic effusion from other etiologies of pleural effusion. Compared with PCT, serum CRP has higher specificity and a higher positive likelihood ratio, and thus, it has a higher rule-in value than PCT.

Introduction

Approximately 20% of patients with pneumonia may develop a parapneumonic pleural effusion, of whom 35% have empyema and 5.3% will ultimately need surgical intervention. Among those with parapneumonic effusion requiring surgical intervention, a mortality rate as high as 20% has been reported [1], [2], [3], [4], [5].

The diagnosis of a parapneumonic pleural effusion is not always straightforward, especially when patients have coexisting heart failure or malignancy [4], [6]. Conventional leukocyte counts, effusion cell and differential counts, and Light criteria did not provide adequate information [1], [2], [3], [4], [7], [8]. Microbiologic studies can provide more definitive results; however, the yield rate is only approximately 60%, and the long turnaround time may result in delayed diagnosis [3], [4], [9]. By contrast, unselective administration of broad-spectrum empirical antibiotics will result in the overuse of antibiotics and possible antibiotic resistance or Clostridium difficile infection.

Biomarkers of infection or inflammation, such as procalcitonin (PCT) and C-reactive protein (CRP), have been recently used to improve the diagnosis of parapneumonic effusion. C-reactive protein is an acute-phase reactant produced primarily by hepatocytes. Its production is induced by systemic inflammation of either infectious or noninfectious origin. The production of PCT, unlike that of CRP, is elevated only in response to bacterial infection but not to noninfectious inflammation or nonbacterial infection [10], [11]. The usefulness of PCT has been widely demonstrated in the diagnosis of sepsis and in the management of antibiotic use among patients with lower respiratory tract infection [12].

Only a few studies have investigated the diagnostic role of pleural fluid PCT or CRP in the etiology of pleural effusion, and these studies had relatively small sample sizes [3], [13], [14], [15], [16], [17]. To summarize current evidence on the use of pleural fluid PCT or CRP in the diagnosis of parapneumonic effusion, we performed a systemic review and meta-analysis.

Section snippets

Search strategy and selection criteria

We searched 3 electronic databases (MEDLINE, EMBASE, and Cochrane database) for studies published through December 2011 with the following Medical Subject Heading terms and free text: “pleural effusion,” “pleural fluid,” “pleurisy,” “biomarker,” and “procalcitonin.” We did not set any time or language restrictions for these searches. We checked the reference lists of relevant review articles. For comparison of diagnostic performance of pleural fluid PCT and CRP, we only include studies that

Identification of studies and their quality

Our initial search yielded 34 citations, of which 18 were excluded after abstract and title screening. We retrieved 16 studies for full-text reading, of which 6 met our inclusion criteria (Fig. 1). The 6 included studies were published from 3 countries between 2009 and 2011, and the studies included 780 patients (median, 74.5 [range, 41-308]) [3], [13], [14], [15], [16], [17]. Parapneumonic effusion was confirmed in 306 patients (overall prevalence, 39.2% [range, 12.0-67.3%]). Six [3], [13],

Discussion

Using pooled data from 6 studies comprising 760 patients, we found an only low-to-moderate diagnostic accuracy of pleural fluid PCT levels (AUROC = 0.71; 95% CI, 0.67-0.75) in predicting parapneumonic effusion among patients with pleural effusion of unknown origin. Pleural fluid CRP, although still having a low-to-moderate diagnostic value, appeared to have better diagnostic accuracy than PCT (AUROC = 0.83; 95% CI, 0.76-0.90), notably regarding its rule-in value (PCT LR+: 3.25 vs CRP LR+: 2.24).

Conclusion

The available evidence examining the diagnostic accuracy of pleural fluid PCT levels as a predictor of parapneumonic effusion is limited and does not allow for a firm conclusion. The pooled accuracy estimates of 6 different studies indicated only a low-to-moderate diagnostic value of pleural fluid PCT. Serum PCT appeared to have comparable diagnostic value with pleural fluid PCT, whereas pleural fluid CRP appeared to have a superior rule-in value to PCT in predicting infectious parapneumonic

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    Conflict of interest: None declared.

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