Pleural effusion(PE) is a common medical problem with various causes. The differential diagnosis for PE is often challenging. This consensus was generated by members of the academic group of the pleural and mediastinal diseases(preparatory) of Chinese Thoracic Society and some external experts. The members convened in virtual meetings and conducted an extensive literature investigation and assessed the quality of the evidence using a modified grading of recommendations assessment, development, and evaluation(GRADE) approach. This consensus included three chapters: the initial evaluation of PE, the diagnosis of PE with common causes, and the diagnosis of PE with uncommon causes.

The main recommendations of Chapter Ⅰ were as follows:(1) For patients suspected of PE according to medical history and clinical manifestations, thoracic CT or ultrasound is recommended to confirm the presence or absence of PE.(2) Ultrasound-guided thoracentesis is recommended when available. Recommended tests for all sampled pleural effeusions include total protein, lactate dehydrogenase (LDH), adenosine deaminase (ADA), differential cell count, and cytological examination.(3) It is recommended to use Light′s criteria to distinguish exudate and transudate. When PE is classified to be exudates with heart failure, it is recommended to detect N-terminal pro-brain natriuretic peptide of PE or serum-pleural fluid albumin gradient to assist the judgment.(4) Pleural biopsy is recommended for patients for whom the causes of PE cannot be identified by the detection of PE samples, and CT or ultrasound-guided pleural biopsy is more accurate. Thoracoscopy is recommended for patients whose etiology cannot be identified by laboratory tests of PE and/or pleural biopsy histopathology.

The main recommendations of Chapter Ⅱ were as follows:(1)It is suggested to obtain more samples or use immunocytochemistry to assist the diagnosis and cell typing when initial cytopathology examination shows atypical cells, suspicious malignant or malignant cells. (2) Liquid medium for Mycobacterium tuberculosis culture is recommended to improve the positive rate. Molecular diagnosis (nucleic acid amplification or Xpert MTB/RIF) is recommended when tuberculous PE is suspected. For suspected tuberculous PE where the examination of PE is inconclusive. CT or ultrasound-guided pleural biopsy or thoracoscopy is recommended to obtain pleural tissue for acid-fast staining, Mycobacterium tuberculosis nucleic acid amplification and culture.(3)C-reactive protein (CRP) of PE is recommended to distinguish uncomplicated PPE from complicated PPE. It is suggested to inoculate pleural effusion into blood culture bottles or culturing specimens from ultrasound-guided pleural biopsy to increase the positive rate.

The main recommendations of Chapter Ⅲ were as follows:(1) It is recommended to comprehensively analyze the patients′ medical history, clinical manifestations, effusion characteristics, and biopsy pathological results to indentify uncommon causes.(2) It is recommended to detect the presence of chylomicrons or cholesterol crystals, with testing of the levels of triglyceride and cholesterol in PE for clinical suspicion of chylothorax or pseudochylothorax. (3) PE may be the result of a combination of various causes, and it is recommended to screen factors such as heart failure, hypoalbuminemia, and thoracic infection for critical patients.(4) For patients with PE whose cause has not been identified by thoracoscopic pleural biopsy, close follow-up for at least 2 years is recommended to exclude malignant diseases.