pleural effusion is defined as the accumulation of fluid in the pleural space that exceeds the physiologic amount of 10 - 20 ml . heart failure is the main cause of pleural effusion ( 30 - 40% ) . in the non - cardiac effusion , pneumonia is the most common ( 48% ) ( 1 ) , of which approximately 75% are bacterial . determining the etiology is greatly facilitated by the ability to analyze the pleural fluid via thoracentesis , a simple bedside procedure . the most practical method for differentiating diagnosis is light criteria , which separated transudates from exudates by analyzing protein and lactate dehydrogenase ( ldh ) levels of serum and pleural fluid ( 1 ) . however , only a select number of diagnoses can be established definitively by thoracentesis and results of quantitative cultures are not available until 24 - 72 hr after the procedure . moreover , bacteriological evidence of infection may not develop simultaneously as clinical signs of sepsis and negative results do not exclude sepsis because of poor sensitivity by culture . delays in the administration of adequate antimicrobial treatment increase the risk of mortality ( 2 ) . on the other hand , unnecessary use of antibiotics increases drug resistance , side effects , and expense . since common clinical and laboratory measurements lack the sensitivity and specificity , other tests are needed to identify the infectious cause of a generalized inflammatory response and to allow early diagnosis and appropriate treatment . among the potentially available laboratory parameters , procalcitonin ( pct ) has recently become of interest as a possible marker of the systemic inflammatory response to infection ( 3 ) . it is normally produced in the c - cells of the thyroid gland and is the precursor of calcitonin . a specific protease cleaves pct to calcitonin , katacalcin , and an n - terminal residue . normally , pct is cleaved and none is released into the blood stream such that levels are undetectable ( < 0.1 ng / ml ) in healthy humans . in severe bacterial infections and sepsis , however , intact pct is found in blood . a half - life of approximately 20 - 24 hr is expected for pct after a single , acute stimulus . thus , it has been described as a good predictor of disease severity and antibiotic efficiency ( 4 ) . pct measurements may be helpful in differentiating between infectious or non - infectious causes in patients presenting with a systemic inflammatory response syndrome , and may differentiate between viral and bacterial infections . numerous clinical studies have also proposed pct as a specific marker of bacterial infection or general inflammation ( 5 - 7 ) . however , localized bacterial infections without systemic manifestations , like bacterial parapneumonic effusion ( ppe ) without sepsis , may cause only a small to modest increase ( 0.3 - 1.5 ng / ml ) . therefore , treatment , such as antibiotics , may be necessary despite normal pct levels ( 8) . if pct was measured in body fluids other than serum , conflicting results have been reported . approximately 25% of the plasma concentrations can be detected in the urine ( 9 ) . but alveolar pct does not seem to be a helpful parameter in the early diagnosis of ventilator - associated pneumonia and is not an appropriate marker for predicting mortality ( 10 ) . this study aimed to determine the usefulness and reliability by pct level of pleural fluid in the diagnosis of bacterial ppe . forty - one consecutive patients with ppe from the division of pulmonary / critical care medicine and infectious disease of the department of internal medicine at the st . martin de porres hospital in chiayi from august to december 2006 were included and ppe was diagnosed if they had a score > 6 as assessed by clinical pneumonia infection score ( cpis ) at baseline or 72 hr ( 11 ) , and if ultrasound examination showed pleural effusion . all had undergone diagnostic thoracentesis and venipuncture , with measurement of pct in the pleural fluid and serum , after obtaining ethical research approval from the hospital 's institutional review board and informed consent from the patients . specifically , ppe was categorized as definite bacterial infection if bacterial colonies were identified by blood culture , effusion culture , or quantitative cultures from bronchoscopic broncho - alveolar lavage fluid ( bal ) . the criteria for the diagnosis of non - bacterial ppe were the negative or non - significant growth in culture of the three kinds of specimens . blood and pleural effusion samples were also collected from 9 routine , non - pneumonic effusion patients who acted as the control group . the control group ( non - pneumonic ) was defined with cpis 6 at baseline and 72 hr , and diagnosed as another disease accounting for the chest radiograph abnormality of pleural effusion . all had either congestive heart failure ( n=8 ) or chronic renal failure ( n=1 ) but not pneumonia . none of the 50 patients had received systemic or topical antimicrobial therapy 3 days before the study , none had smoked at least one cigarette per day for 1 yr , and none had a diagnosed thyroid disease or small cell lung cancer . blood samples were obtained by venipuncture and specimens were collected in tubes containing ethylenediamine tetraacetic acid ( edta ) , centrifuged at 3,000 rpm for 10 min at 4 , and the supernatants were stored at -20 for later determination of pct if the patient was enrolled after 72 hr . the quantitative determination of pct was performed with lumi test pct , an immunoluminometric assay manufactured by b.r.a.h.m.s diagnostica gmbh , hennigsdorf / berlin ( 12 ) . bal fluid was obtained from fiberoptic bronchoscope olympus with 200 ml warm sterile saline administrated to the involved lobe . samples were then plated onto dishes : trypticase soy agar 5% sb , chocolate ii agar , eosin methylene blue agar , and columbia colistin - nalidoxic acid agar . sensitivity and specificity were expressed in percentages . after confirming normally distributed data , demographic data was compared using the independent t test or the chi - square test when appropriate . the non - parametric kruskal - wallis tests or the bonferroni criteria of mann - whitney u tests for continuous variables were used to compare pct level among groups . the receiver - operating characteristic ( roc ) curves were analyzed to define the optimal cut - off value and used to compare diagnostic accuracy . sensitivity , specificity , and area under the roc curve ( auc ) were estimated using a standard formula . forty - one consecutive patients with ppe from the division of pulmonary / critical care medicine and infectious disease of the department of internal medicine at the st . martin de porres hospital in chiayi from august to december 2006 were included and ppe was diagnosed if they had a score > 6 as assessed by clinical pneumonia infection score ( cpis ) at baseline or 72 hr ( 11 ) , and if ultrasound examination showed pleural effusion . all had undergone diagnostic thoracentesis and venipuncture , with measurement of pct in the pleural fluid and serum , after obtaining ethical research approval from the hospital 's institutional review board and informed consent from the patients . specifically , ppe was categorized as definite bacterial infection if bacterial colonies were identified by blood culture , effusion culture , or quantitative cultures from bronchoscopic broncho - alveolar lavage fluid ( bal ) . the criteria for the diagnosis of non - bacterial ppe were the negative or non - significant growth in culture of the three kinds of specimens . blood and pleural effusion samples were also collected from 9 routine , non - pneumonic effusion patients who acted as the control group . the control group ( non - pneumonic ) was defined with cpis 6 at baseline and 72 hr , and diagnosed as another disease accounting for the chest radiograph abnormality of pleural effusion . all had either congestive heart failure ( n=8 ) or chronic renal failure ( n=1 ) but not pneumonia . none of the 50 patients had received systemic or topical antimicrobial therapy 3 days before the study , none had smoked at least one cigarette per day for 1 yr , and none had a diagnosed thyroid disease or small cell lung cancer . blood samples were obtained by venipuncture and specimens were collected in tubes containing ethylenediamine tetraacetic acid ( edta ) , centrifuged at 3,000 rpm for 10 min at 4 , and the supernatants were stored at -20 for later determination of pct if the patient was enrolled after 72 hr . the quantitative determination of pct was performed with lumi test pct , an immunoluminometric assay manufactured by b.r.a.h.m.s diagnostica gmbh , hennigsdorf / berlin ( 12 ) . bal fluid was obtained from fiberoptic bronchoscope olympus with 200 ml warm sterile saline administrated to the involved lobe . samples were then plated onto dishes : trypticase soy agar 5% sb , chocolate ii agar , eosin methylene blue agar , and columbia colistin - nalidoxic acid agar . were expressed in percentages . after confirming normally distributed data , demographic data was compared using the independent t test or the chi - square test when appropriate . the non - parametric kruskal - wallis tests or the bonferroni criteria of mann - whitney u tests for continuous variables were used to compare pct level among groups . the receiver - operating characteristic ( roc ) curves were analyzed to define the optimal cut - off value and used to compare diagnostic accuracy . sensitivity , specificity , and area under the roc curve ( auc ) were estimated using a standard formula . the study population was composed of 50 patients ( 35 males and 15 females ) with a median age of 67 yr . of these , 25 had bacterial ppe , 16 had non - bacterial ppe , and 9 made up the control group . table 1 showed demographic and clinical data of the ppe patients divided into two subgroups and showed the underlying medical disease . the diagnosis of bacterial ppe was established in 25 cases : 8 patients had gram - negative bacilli , 13 had gram - positive cocci , and 4 had polymicrobial growth . overall , pleural fluid culture findings were positive in 9 of 25 patients , bronchoscopic bal quantitative culture was positive in 16 patients , and 4 had positive blood cultures . the median pct levels in pleural fluid were significantly higher in the bacterial ppe ( 0.24 ng / ml ) than in the non - bacterial ppe ( 0.09 ng / ml ) and the control groups ( 0.08 ng / ml , p<0.001 ) , but no statistical difference was found in serum concentrations among the three groups ( p=0.205 , table 2 ) . regarding non - bacterial ppe diagnosis , no significant differences occurred in the non - bacterial ppe group compared to the control group for pleural pct ( fig . 1 ) . others , ldh and glucose levels of pleural fluid also demonstrated significant differences among the three groups , but pleural protein level did not ( table 2 ) . the cut - off value of pleural fluid pct for diagnosis of bacterial ppe ( from the roc curve ; auc=0.84 ) was 0.17 ng / ml ( fig . this corresponded to 80% sensitivity and 76% specificity , in contrast to 72% sensitivity and 94% specificity with a well - known serum cut - off value ( 0.5 ng / ml ) for bacterial infection ( table 3 ) ( 13 ) . ppe occurs in approximately 10% of patients with community - acquired pneumonia ( 14 ) and most bacterial ppe will resolve with antibiotic treatment alone . thus , limitations and inaccuracies in clinical decision - making have motivated the development of techniques to establish the diagnosis of bacterial ppe and guide treatment decisions to significantly reduced antibiotic administration or avoid neglecting bacterial infections . gram stain and cultures of tracheal secretions have been commonly used but are non - specific and lack the sensitivity for establishing the presence of bacterium partly because of oro - pharyngeal colonization and difficulties in obtaining definite pathogens from an inadequately expectorated specimen . several methods have been developed in an attempt to improve their diagnostic accuracy , including c - reactive protein ( crp ) and bacterial antibody assays . crp levels are usually lower in viral and superficial bacterial infections than in deep bacterial infections ( 15 ) but their role in the etiologic diagnosis of respiratory infections is not well established and their usefulness in distinguishing between bacterial and viral pneumonia have conflicting results ( 16 ) . clinical analysis of antibody - coated bacteria is not sensitive enough for the exclusion of bacterial pneumonia . also its routine use is limited due to the cost and unavailability in clinical laboratory ( 17 ) . among these chemical parameters in our study , ldh and glucose in pleural fluid showed significant differences between the three groups , but pleural protein level did not . we believed that the difference of glucose level came from patients with empyema in bacterial ppe group . for the ldh level , the transudative nature of the control group might contribute the statistical difference by light 's criteria for pleural effusion . however , to our knowledge , these parameters could not be a guideline for diagnosis or treatment at present , when they were used in a single . pct , a circulating serum calcitonin precursor , is a 116 amino - acid protein stimulated by bacterial inflammation and produced by neuro - endocrine cells of different organs , including the lungs ( 18 ) . thus , patients with small cell lung cancer and thyroid disease were excluded for the neurocrine nature in our study . to our knowledge , elevated serum levels of pct have been found in several diseases such as sepsis syndrome , inhalation burn injury , and infectious pneumonitis ( 19 ) . it is important that pct is elevated in bacterial infections but remain low in viral infections ( 20 ) . it also deserved our attention because that the measurement of pct with lumi test is easy and can be completely within two hours . we could absolutely get the information of bacterial infection much more quickly as compared with identifying bacteria by culture . furthermore , its serum concentration is more sensitive and specific than crp , interleukin-6 ( il-6 ) or white blood cell count for differentiating bacterial and viral causes of community - acquired pneumonia ( cap ) ( 12 ) and is utilized to guide treatment decisions to significantly reduce antibiotic use and costs without adverse effects on outcomes ( 21 ) . however , localized bacterial infections or infections without systemic manifestations cause only a small to modest increases in pct levels . treatment , such as antibiotics , may therefore be necessary in patients with pneumonia despite normal pct levels . in previous studies , since pneumonia is generally an organ related infection , pct values are usually low even in the presence of marked clinical symptoms or radiographic findings ( 22 ) . in the demographic data , a significant difference occurred in the variables of cpis and diabetes mellitus between the bacterial and non - bacterial ppe group . our findings warrant further studies that will take into consideration the association of diabetes mellitus and pct levels . pct has been measured in body fluids other than serum in only few papers and with conflicting results ( 9 ) . in 2005 , ( 23 ) reported that serum and pleural fluid pct concentrations were statistically different between tuberculous and nontuberculous pleurisy groups , even though they were not elevated up to the cut - off level of 0.5 ng / ml . this study was to verify whether pct levels measured in pleural effusion could be a marker of bacterial ppe and present with a more sensitive or specific parameter than serum levels to identify non - septic bacterial infection and prevent the unnecessary use of broad - spectrum therapy . based on the results here , pct measurement in pleural effusion represents a potential adjunct to the diagnosis of bacterial ppe despite the lack of statistical difference among the three groups in terms of serum levels . to our knowledge , bal fluid pct concentrations remained undetectable in previous studies due to the hypothesis that the alveolar membrane could be a strong filter to circulating cytokines ( 24 ) . the low alveolar pct release could be the same with some local mediators , like tumor necrosis factor (25 ) . otherwise , pct has been proposed as an indicator of severe generalized infections or sepsis , while localized infections or infections without systemic manifestations cause only a limited increase ( 26 ) . pct induction is consequently generally slight in isolated pneumonia due to the organ - related nature of the infection . in our study , the severity of ppe was not taken into consideration and pneumonic severity index score demonstrated a non - significant difference between the bacterial and non - bacterial ppe groups . thus , we could regard the ppe as a localized infection and our cases might not be so serious to cause sepsis . then we consequently found that the serum pct levels in our study were almost lower than the current cutoff value of 0.5 ng / ml and it was not significantly increased in the bacterial ppe group as compared with the non - bacterial or control group . at the time , we believed that pleural fluid might play a role for diagnosis in such the localized infection , like ppe . first , the gold standard for evaluating the diagnosis of pneumonia remains the open lung biopsy instead of the cpis score , although the appropriateness of studying a diagnostic test only among dead patients is debatable . second , a lower threshold value ( 0.01 ng / ml ) of the quantitative determination by homogeneous immunoassay may be inappropriate for detecting low , meaningful concentrations . lastly , some bacterial pneumonia , such as chlamydia , mycoplasma pathogens , or legionnaires ' disease , could not be cultured easily in traditional media . on the other hand , this study shows that the pleural fluid pct levels in bacterial ppe are significantly different from those of the non - bacterial and control groups . however , both the serum and pleural fluid pct levels in patients with bacterial ppe are below the current cut - off level of 0.5 ng / ml . in a patient with a pleural fluid pct concentration of < 0.17 ng / ml , other confusing reasons of bacterial ppe can be ruled out with a 76% probability . if pleural fluid pct > 0.17 ng / ml , bacterial ppe can be diagnosed with an 80% probability .
this study evaluated the value of procalcitonin ( pct ) levels in pleural effusion to differentiate the etiology of parapneumonic effusion ( ppe ) . 
 forty - one consecutive ppe patients were enrolled and were divided into bacterial and non - bacterial ppe . 
 blood and pleural effusion samples were collected for pct measurement on admission and analyzed for diagnostic evaluation . 
 pct of pleural fluid was significantly increased in the bacterial ppe group ( 0.24 ng / ml ) compared to the non - bacterial ppe group ( 0.09 ng / ml ) , but there was no significant difference for serum pct . 
 a pct concentration of pleural fluid > 0.174 ng / ml ( best cut - off value ) was considered positive for a diagnosis of bacterial ppe ( sensitivity , 80% ; specificity , 76% ; auc , 0.84 ) . 
 pleural effusion pct in the bacterial ppe is significantly different from those of the non - bacterial ppe and control groups , so the diagnostic use of pct still warrants further investigation .