What Is the Process For Differential Diagnosis of Pleural Effusion?

1. Adenosine deaminase (ADA): It is the most abundant in erythrocytes and T cells. When tuberculous pleurisy (TPE), the activity of T cells is enhanced, so pleural ADA is more than 45 U / L. Helps distinguish tuberculous or cancerous pleural fluid. We have performed a meta-analysis in this regard [1] to more accurately elucidate the diagnostic efficiency of measuring ADA for TPE. The random effect model was used to summarize the sensitivity, specificity, and other indicators of ADA in the diagnosis of TPE in each study, and the working characteristic curves of the subjects were drawn and their diagnostic characteristics were discussed. The results showed that the overall sensitivity of ADA in the diagnosis of TPE: 0.92 (95% CI 0.910.93), specificity: 0.90 (95% CI 0.890.91), positive likelihood ratio: 8.82 (95% CI 7.0511.04), Negative likelihood ratio: 0.10 (95% CI 0.070.14), diagnostic odds ratio: 105.15 (95% CI 68.38167.89). Therefore, the sensitivity and specificity of ADA in the diagnosis of TPE are relatively high. Measuring ADA in PE is helpful for the diagnosis of TPE.

Shi Huanzhong

(Chief physician)

Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University

In recent years, with the advancement of immunology and molecular biology, many new laboratory testing methods have continuously appeared, which has made great progress in the biochemical detection of pleural effusion (PE), providing more evidence for clinical diagnosis and treatment. .

Chinese name

Pleural effusion

category

Means of medical examination

Enzymatic activity determination of pleural effusion

1. Adenosine deaminase (ADA): It is the most abundant in erythrocytes and T cells. When tuberculous pleurisy (TPE), the activity of T cells is enhanced, so pleural ADA is more than 45 U / L. Helps distinguish tuberculous or cancerous pleural fluid. We have performed a meta-analysis in this regard [1] to more accurately elucidate the diagnostic efficiency of measuring ADA for TPE. The random effect model was used to summarize the sensitivity, specificity, and other indicators of ADA in the diagnosis of TPE in each study, and the working characteristic curves of the subjects were drawn and their diagnostic characteristics were discussed. The results showed that the overall sensitivity of ADA in the diagnosis of TPE: 0.92 (95% CI 0.910.93), specificity: 0.90 (95% CI 0.890.91), positive likelihood ratio: 8.82 (95% CI 7.0511.04), Negative likelihood ratio: 0.10 (95% CI 0.070.14), diagnostic odds ratio: 105.15 (95% CI 68.38167.89). Therefore, the sensitivity and specificity of ADA in the diagnosis of TPE are relatively high. Measuring ADA in PE is helpful for the diagnosis of TPE.

2. Lactate dehydrogenase (LDH) and its isoenzymes: Determining the LDH content in pleural effusion is helpful for the differential diagnosis of exudate and exudate. Leakage is <200 U / L, the ratio of pleural fluid to serum content is 200 U / L, and the ratio of pleural fluid to serum content is> 0.6. It is found in pleural fluid caused by pulmonary infarction, lymphoma, and some tumor metastases. LDH is an index reflecting the degree of pleural inflammation. The higher the value, the more obvious the inflammation is. The level of LDH in empyema is significantly increased, which can reach 30 times that of normal serum. Malignant pleural effusions increased LDH and its isoenzyme LDH2, while benign effusions were mainly elevated by LDH4 and LDH5.

3 Amylase (asamyle, AMS): Generally speaking, the AMS level of pleural fluid can refer to the serum value, and the normal serum value is 80 ~ 180U / L. Pleural effusion amylase activity due to pancreatic disease is often increased, which is related to pancreatic enzyme transport along the lymphatic vessels. When the esophagus is ruptured, saliva enters the thorax through the ruptured hole, and at this time, the pleural fluid amylase activity increases. The amylase isoenzyme activity of cancerous pleural effusion (Malignant Pleural Effusion, MPE) is significantly increased, which may be related to the direct synthesis of amylase isoenzymes by tumor cells. The possibility is great.

4 Other enzymatic indicators, such as lysozyme (LZM), and LZM content in TPE> 30 mg / L, were significantly higher than those in cancerous and rheumatic effusions. This term is often measured simultaneously with serum lysozyme and then the ratio is calculated. Normally, those with pleural effusion and serum LZM ratio of 1 are mostly tuberculous [2]. The levels of angiotension converting enzyme (ACE) and superoxide dismutase (SOD) in TPE were significantly increased, while the activity of diamine oxidase in MPE was significantly higher than that in benign thorax Effusion. ^[1-2]

Pleural effusion examination biochemical markers

1. Lung surface-active protein A (SP-A): SP-A is a major phospholipid-associated glycoprotein in lung surfactants. Approximately 70% of malignant pleural effusion (especially lung adenocarcinoma) had significantly increased SP-A levels (500mg / L cutoff), while other types of pleural effusion increased only 3.7% [3]. Therefore, SP-A in pleural fluid can be used as a specific marker of lung adenocarcinoma.

2. Ferritin (Ft): Ferritin (Ft) is a marker of iron storage in the body, and Ft synthesis of some malignant tumor cells is increased. Therefore, it can also be used as a marker of malignant tumors in addition to clinical diagnosis of anemia. In recent years, some studies have found [4] that if the Ft content in pleural effusion is> 500 g / L, the sensitivity of Ft to diagnose malignant pleural effusion is 80% and specificity is 91%; if> 1000 g / L is the boundary, the sensitivity is 76% and the specificity is 94%. The above data suggest that the increased Ft content can also be used as a reference for the differential diagnosis of pleural effusion.

3 Sialic acid (SA) and lipid-bound sialic acid (LSA): SA is the terminal amino acid residue of the sugar chain on the cell surface and participates in various physiological functions of the cell. When the cell becomes cancerous, a series of changes occur on the cell surface, leading to an increase in serum SA. If the lesion causes pleural and ascites fluid, SA in the effusion also increases. Various cancers can cause SA to increase, but lung cancer and ovarian cancer are the most obvious. In addition, some of the SA-associated lipids are called LSA, which is significantly higher in malignant pleural fluid than tuberculous pleural fluid.

4 Lipid determination: Chylous chest produced by thoracic duct rupture contains neutral fat and triglycerides (> 4.5mmol / L), which is cloudy milky, but the cholesterol content does not increase. The level of cholesterol in malignant pleural effusion is significantly higher than that of tuberculous and other infectious pleural effusions, which may be caused by degeneration of pleural epithelial cells, local tissue metabolism disorders, and tissue disintegration during malignant disease response. With a boundary of 2.86 mmol / L, the diagnostic sensitivity of malignant pleural effusion is 85.2% and the specificity is 96.8% [5].

5. C-reactive protein (CRP): CRP is an acute inflammatory response protein, with a detection rate of 100% during acute inflammation. Studies have shown [6] that the CRP level in the exudative effusion group (35.15 ± 4.19mg / L) is significantly higher than in the leaking effusion group (14.19 ± 4.19mg / L). When 30mg / L was used as the cut-off value, it had high sensitivity (93.17%) and specificity (76.15%), and the positive predictive value was 98.14%. There was also a significant difference in pleural fluid / plasma CRP ratio between the two groups. ^[3]

Pleural effusion

Pleural effusion

1. Interferon (IFN): IFN is a type of highly active and multifunctional regulatory protein produced by the relevant biological cells induced by interferon inducers. It is divided into alpha interferon (IFN) according to its antigenicity and different cells. -), interferon beta (IFN-), and interferon gamma (IFN-). Because the concentration of IFN- in tuberculous pleural fluid is> 2U / ml, and other types of pleural fluid are lower than this value, it is considered that the determination of IFN level in pleural fluid has important reference value for the diagnosis of tuberculous pleurisy. To this end, we performed a meta-analysis [7] to clarify the overall diagnostic efficiency of IFN- for TPE. The total sensitivity calculated using the random effects model: 0.89 [95% confidence interval (CI) 0.87-0.92], specificity: 0.97 (95% CI 0.96-0.98), positive likelihood ratio: 24.6 (95% CI 18.0-33.5), negative likelihood ratio: 0.11 (95% CI 0.07-0.16), diagnostic odds ratio: 301.2 (95% CI 159.2-569.9). This result shows that the sensitivity and specificity of IFN- measurement for the diagnosis of tuberculous pleurisy are high. The determination of IFN- concentration in PE is helpful for the diagnosis of tuberculous pleurisy. It can be combined with clinical manifestations and routine test results for comprehensive analysis.

2. Interleukin-2 (IL-2): IL-2 plays an important role in mediating the immune response and can also induce the expression of the IL-2 receptor (IL-2R) on activated effector cells. The levels of IL-2 in tuberculous and malignant pleural fluid were higher than those in peripheral blood.

The level of soluble IL-2 receptor (sIL-2R) in pleural fluid, exudate is higher than leaking fluid, tuberculosis is significantly higher than non-tuberculous, and the ratio of tuberculous pleural sIL-2R / serum sIL-2R is significantly higher than other Patients, it is believed that pleural fluid sIL-2R and its ratio to serum levels are helpful for the differential diagnosis of tuberculous and non-tuberculous pleural effusion. ^[4]

3 Other interleukin families such as IL-1, IL-6, and IL-8 are significantly elevated in the exudate, which helps to distinguish between exudate and leakage. In addition, the levels of IL-1 and IL-6 in TPE were significantly higher than those in MPE. The level of IL-8 in purulent fluid is significantly higher than that caused by other reasons.

4 Tumor necrosis factor (TNF): TNF is a peptide growth factor that has a wide range of biological functions and is closely related to the occurrence and development of various diseases. The level of TNF in tuberculous pleural fluid is five times its serum level, while the level of TNF in non-tubular pleural fluid is significantly reduced.

5. Epidermal growth factor (EGF): EGF has a stimulating effect on epidermal growth, and has a strong mitogenic effect on epithelial cells of various tissues, which may be a wound healing factor. There is a large amount of EGF in patients with tuberculous pleurisy, which plays a positive protective role in the healing outcome of inflammation. The EGF content of tuberculous pleural effusion was significantly higher than that of malignant pleural effusion.

6. Vascular endothelial growth factor (VEGF): VEGF in pleural effusion has biological activity and can stimulate tumor growth and chemotactic. VEGF is present in various pleural effusions, the VEGF in exudate is higher than the effusion, and the VEGF level in malignant pleural effusion is higher than that in benign pleural effusion. ^[5]

Pleural effusion for tumor markers

1. Carcinoembryonic antigen (CEA): CEA is a large molecular weight glycoprotein, originally found in human colon cancer extracts, and can be found in fetal and adult colon mucosa, lungs and breasts. The normal value is between 5 and 15 g / L. CEA levels in malignant pleural fluid are higher than those in serum, which can be used to distinguish benign and malignant pleural fluid. We performed a systematic review [8] to determine the overall diagnostic efficiency of CEA for MPE, and found that the total sensitivity of CEA concentration to diagnose MPE was 0.54 (95% CI 0.52-0.55), specificity: 0.94 (95% CI 0.93 0.95), positive likelihood ratio: 9.52 (95% CI 6.97 13.01), negative likelihood ratio: 0.49 (95% CI 0.44 0.54), diagnostic odds ratio: 22.5 (95% CI 15.6 32.5) . In general, CEA measurement of pleural fluid may be helpful for the diagnosis of MPE. Further analysis also found that CEA is helpful for the differential diagnosis of malignant pleural mesothelioma and metastatic lung cancer. However, it must be noted that CEA alone cannot establish a diagnosis of MPE.

2. Carbohydrate Antigens CA125, CA 15-3, CA 19-9 and CYFRA (Cytokeratin Fragment) 21-1: Diagnosis of MPE with Carbohydrate Antigens CA125, CA 15-3, CA 19-9 and CYFRA 21-1 There are also many reports of efficiency studies, but the results vary widely. We conducted a systematic review of the English literature [9] and used random effect models to summarize the overall diagnostic efficiency of the above-mentioned tumor marker concentrations or their combined detection for MPE diagnosis in each study. The results showed that the total sensitivity and specificity of the above-mentioned tumor marker concentrations in the diagnosis of MPE were: CA125, 0.48 / 0.85; CA 15-3, 0.51 / 0.96; CA 19-9, 0.25 / 0.96; CYFRA 21-1, 0.55 /0.910.54. Summarizing the receiver operating characteristic curve showed that the pleural effusion CA125 and CA19-9 had lower diagnostic efficacy for MPE, while CA 15-3 and CYFRA 21-1 had higher diagnostic efficacy. When two or more of the above tumor markers are used in combination, the diagnostic sensitivity and specificity are improved to different degrees. In general, the existing evidence does not support the diagnosis of MPE with a single tumor marker, but the combined use of two or more tumor markers has a higher diagnostic sensitivity. The results of tumor marker determination should also be comprehensively analyzed in combination with clinical manifestations and other routine test results.

3 Other markers: other test items such as tumor-associated protein-mucin-like cancer-associated antigen (MCA), tissue peptide-specific antigen, telomerase, 2-microglobulin (2-MG), human villi -human chorionic gonadotrophin (-HCG), cytokerain 19 fragments (CYFRA2121), neuron specific enolase (NSE), and squamous cell antigen (SCC), etc. have more or less reference value for the differential diagnosis of benign and malignant PE. The combined detection of multiple indicators can improve the positive detection rate. ^[6]

PPD-IgG Pleural effusion test anti-PPD-IgG

PPD (purified protein derivative) is a tuberculin-purified protein. After being infected with Mycobacterium tuberculosis, the body can produce antibodies, namely anti-PPD-IgG. High titer antibodies can be detected in the serum and pleural fluid of tuberculosis patients, which is helpful for the diagnosis of tuberculosis. Using 0.55 as the defining value, the positive rate of tuberculous pleural effusion is 85%, while other pleural effusions are only 19%. ^[7]

Other indicators of pleural effusion

Detection of complement, rheumatoid factor (RF), antinuclear antibody (ANA), etc. in pleural fluid can help to identify pleural effusion caused by rheumatic diseases. Increased ANA titer. ^[8-9]