A Simple Method for Differentiating Complicated Parapneumonic Effusion/Empyema from Parapneumonic Effusion Using the Split Pleura Sign and the Amount of Pleural Effusion on Thoracic CT

RESEARCH ARTICLE A Simple Method for Differentiating Complicated Parapneumonic Effusion/ Empyema from Parapneumonic Effusion Using the Split Pleura Sign and the Amount of Pleural Effusion on Thoracic CT Naoki Tsujimoto1‡, Takeshi Saraya1‡*, Richard W. Light2, Yayoi Tsukahara3, Takashi Koide1, Daisuke Kurai1, Haruyuki Ishii1, Hirokazu Kimura4, Hajime Goto1, Hajime Takizawa1 a11111 1 Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan, 2 Division of Allergy/Pulmonary/Critical Care, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 3 Department of Radiology, Kyorin University School of Medicine, Tokyo, Japan, 4 Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan ‡ Naoki Tsujimoto and Takeshi Saraya are double first authors. * OPEN ACCESS Citation: Tsujimoto N, Saraya T, Light RW, Tsukahara Y, Koide T, Kurai D, et al. (2015) A Simple Method for Differentiating Complicated Parapneumonic Effusion/Empyema from Parapneumonic Effusion Using the Split Pleura Sign and the Amount of Pleural Effusion on Thoracic CT. PLoS ONE 10(6): e0130141. doi:10.1371/journal. pone.0130141 Academic Editor: Luis Seijo, Fundación Jimenez Diaz, SPAIN Received: December 16, 2014 Accepted: May 18, 2015 Published: June 15, 2015 Copyright: © 2015 Tsujimoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: The authors received no specific funding for this work. Competing Interests: The authors have declared that no competing interests exist. Abstract Background Pleural separation, the “split pleura” sign, has been reported in patients with empyema. However, the diagnostic yield of the split pleura sign for complicated parapneumonic effusion (CPPE)/empyema and its utility for differentiating CPPE/empyema from parapneumonic effusion (PPE) remains unclear. This differentiation is important because CPPE/ empyema patients need thoracic drainage. In this regard, the aim of this study was to develop a simple method to distinguish CPPE/empyema from PPE using computed tomography (CT) focusing on the split pleura sign, fluid attenuation values (HU: Hounsfield units), and amount of fluid collection measured on thoracic CT prior to diagnostic thoracentesis. Methods A total of 83 consecutive patients who underwent chest CT and were diagnosed with CPPE (n=18)/empyema (n=18) or PPE (n=47) based on the diagnostic thoracentesis were retrospectively analyzed. Results On univariate analysis, the split pleura sign (odds ratio (OR), 12.1; p<0.001), total amount of pleural effusion (30 mm) (OR, 6.13; p<0.001), HU value10 (OR, 5.94; p=0.001), and the presence of septum (OR, 6.43; p=0.018), atelectasis (OR, 6.83; p=0.002), or air (OR, 9.90; p=0.002) in pleural fluid were significantly higher in the CPPE/empyema group than in the PPE group. On multivariate analysis, only the split pleura sign (hazard ratio (HR), 6.70; 95% PLOS ONE | DOI:10.1371/journal.pone.0130141 June 15, 2015 1 / 12 A Simple Method for Detecting the Complicated PPE or Empyema confidence interval (CI), 1.91-23.5; p=0.003) and total amount of pleural effusion (30 mm) on thoracic CT (HR, 7.48; 95%CI, 1.76-31.8; p=0.006) were risk factors for empyema. Sensitivity, specificity, positive predictive value, and negative predictive value of the presence of both split pleura sign and total amount of pleural effusion (30 mm) on thoracic CT for CPPE/empyema were 79.4%, 80.9%, 75%, and 84.4%, respectively, with an area under the curve of 0.801 on receiver operating characteristic curve analysis. Conclusion This study showed a high diagnostic yield of the split pleura sign and total amount of pleural fluid (30 mm) on thoracic CT that is useful and simple for discriminating between CPPE/ empyema and PPE prior to diagnostic thoracentesis. Introduction Before diagnostic thoracentesis, pleural infection should be suspected in all patients with pneumonia persistent fever, and elevation of serum inflammatory markers such as C-reactive protein and white blood cell count. However, those clinical findings do not always indicate complicated parapneumonic effusion (CPPE)/empyema rather than parapneumonic pleural effusion (PPE). Among patients with CPPE/empyema, the frequency of surgery ranges from 15% [1] to 68% [2] and the mortality rate in patients with empyema is 15–20% [3–5]. Rapid recognition of CPPE/empyema is thus crucial to successful treatment. In this regard, thoracic computed tomography (CT) could play a pivotal role in differentiating between CPPE/empyema and PPE. The split pleura sign has been considered a diagnostic sign for empyema. However, no reports have evaluated the use of the split pleura sign to differentiate CPPE/empyema from PPE. These two clinical entities are sequential conditions, which leads to difficulty in assessing the diagnostic yield of the split pleura sign. We therefore undertook a retrospective study to evaluate the utility of the split pleura sign and total amount of pleural effusion on thoracic CT for differentiating between CPPE/empyema and PPE. Materials and Methods This retrospective study was approved by the Ethics Board of Kyorin University (number: H26-032) (Mitaka, Tokyo, Japan). All patients were referred to our respiratory department in outpatient or inpatient settings in Mitaka City, Tokyo, Japan, between May 2006 and May 2014. No informed consent was required for this study, but patient records and information were anonymized and de-identified prior to analysis. The definition of CPPE/empyema was based on Light’s criteria (including only classes 6 and 7) [6] and category 3 or 4 of the American College of Chest Physicians consensus [7]. To be enrolled in the study, patients had to be older than 15 years and show pleural effusion on thoracic CT. This single-institution study retrospectively assessed patients who satisfied at least one of the criteria for CPPE or empyema mentioned above. PPE was defined as a case with clinical and radiological improvement after initiation of antibiotic therapy regardless of the presence of pneumonia and which satisfied none of the criteria for CPPE/empyema. Furthermore, patients with other etiologies for exudative pleural effusion, such as cytologically confirmed malignant pleural effusion (mesothelioma, lung cancer, and other metastatic cancers) and collagen vascular diseases or drugassociated pleural effusion or effusions of unknown etiology were not enrolled in this study. All PLOS ONE | DOI:10.1371/journal.pone.0130141 June 15, 2015 2 / 12 A Simple Method for Detecting the Complicated PPE or Empyema laboratory data including thoracentesis and thoracic CT were obtained within 48 h after admission (...truncated)