New biomarkers for the diagnosis of pleural effusion

Abstract
Background
Persistent undiagnosed effusion is present in approximately 15% of all causes of exudative effusion. Pleural effusion caused by immunoglobulin G4 (IgG4) is a new type of pleural effusion. Tumor markers such as Carcinoembryonic antigen (CEA) may play a role in the diagnosis of malignant pleural effusion. This study aimed to evaluate the use of serum Immunoglobulin G4 and carcinoembryonic antigen in diagnosing pleural effusion.

Methods
This observational descriptive cross-sectional study comprised 89 individuals with exudative pleural effusion who visited the Assiut university hospital's chest department. All patients were examined and asked about their medical history. Also, chest X-ray, MSCT chest, transthoracic ultrasonography, pleural fluid analysis and cytology, serum level of carcinoembryonic antigen, and immunoglobulin G4 were performed. In addition, pleural biopsy, bronchoscopy, and thoracoscopy were performed when required.

Results
In comparison to another diagnosis, the level of serum IgG 4 was observed to be substantially greater in individuals with IgG4-associated effusion (725± 225.45). Patients with malignant mesothelioma (70± 16.24) and metastatic adenocarcinoma (93.52± 19.34) had lower levels of IgG4. In contrast, the serum level of CEA was significantly higher in individuals with malignant mesothelioma (79.50± 29.47) and metastatic adenocarcinoma (68.71± 28.98). Patients with para-pneumonic effusion had a minor serum level of CEA (0.36 ± 0.26). At cutoff point > 152 mg/dl serum IgG-4 had 100% sensitivity and 94% specificity in the diagnosis of IgG4 related pleural effusion with an overall accuracy of 95.3% and area under the curve of 0.97. At the cutoff point > 5 ng/ml serum CEA had 77% sensitivity and 100% specificity in diagnosing malignant pleural effusion with an overall accuracy of 91.1% and area under the curve of 0.88.

Conclusion
Serum IgG4 higher than 152 mg/dl has good diagnostic accuracy in cases of undiagnosed pleural effusion. Carcinoembryonic antigen aids in diagnosing malignant pleural effusion with a cutoff point higher than 5 ng/ml in serum.

Trial registration
ClinicalTrials.gov registration ID NCT03260088