Diagnostic Value of TB-IGRA, PPD, TB-DNA-PCR and TB-Ab in Silicosis Complicated with Tuberculosis

Purpose: The purpose of this article is to investigate the clinical value of TB-IGRA (Tuberculosis-Interferon Gamma Release Assay), PPD (Intradermal Terbuculin Test), TB-DNA-PCR (Tuberculosis-Deoxyribonucleic-Polymerase Chain Reaction) and TB-Ab (Tuberculosis-Antibody) in diagnosing silicosis complicated with pulmonary tuberculosis. Methods: 53 cases of suspected silicosis complicated with pulmonary tuberculosis were selected in the time span ranging from February 2017 to May 2019. TB-IGRA test, PPD test, TB-DNA-PCR and TB-Ab detection were performed. The sensitivity, specificity, positive predictive value and negative predictive value were calculated. Results: Silicosis and pulmonary tuberculosis were diagnosed in 11 cases, with an incidence of 20.75%. The positive rates of TB-IGRA, PPD, TB-DNA-PCR and TB-Ab were 66.04%, 30.19%, 5.67% and 26.42%, respectively. The sensitivity was 90.91%, 81.82%, 27.27% and 54.55% respectively. The specificity was 42.86%, 80.95%, 100% and 80.95% respectively. The positive predictive values were 28.57%, 50%, 100% and 42.86% respectively. The negative predictive values were 94.44%, 91.89%, 84% and 87.18%. The positive rate, sensitivity and negative predictive value of TB-IGRA were the highest, while the specificity of TB-DNA-PCR was the highest yet with low positive rate, sensitivity and positive predictive value. Conclusion: The positive rate and sensitivity of TB-IGRA were high, yet with poor specificity, so it was impossible to judge whether the cases belonged to active pulmonary tuberculosis. The combina-tion of PPD and TB-DNA-PCR could improve the sensitivity, specificity and positive predictive value, and the diagnostic accuracy of active pulmonary tuberculosis, which showed satisfactory clinical value.


Introduction
In recent years, with the economic globalization, the widening gap between the rich and the poor and the increase of rural-urban population flow, the incidence of tuberculosis represents an increasing trend, which has seriously threatened people's physical and mental health. The medical services of our hospital has extended to Hebei, Shanxi, Inner Mongolia three provinces; as we all know that the mining industry and metal smelting industry in the above three provinces are relatively developed, there is a large proportion of mining workers in these three areas, which has resulted in a high incidence of silicosis. Studies have confirmed that silicosis patients are prone to secondary pulmonary tuberculosis, leading to an increase in the incidence of pulmonary tuberculosis [1], Therefore, the situation of tuberculosis prevention and control is still challenging, which has been still considered as the focus of public health issues. The tuberculosis focus is easily wrapped or even overlapped by silicosis nodules, which leads to low positive rate of TB in traditional methods. TB-IGRA technology is the up-to-date in vitro immunodiagnostic method for TB infection worldwide. It has been widely used in North America and Europe. In 2011, it was approved in China [2] [3]. The basic principle is: The T lymphocytes produced by the body infected with Mycobacterium tuberculosis will release γ interferon when stimulated by specific antigen in vitro. Therefore, the quantitative analysis of the γ interferon is capable of determining whether there is a specific T cell response related to Mycobacterium tuberculosis. Large data samples suggested that TB-IGRA had high sensitivity, accuracy and specificity in TB infection diagnosis. However, since the traditional PPD, TB-DNA-PCR, TB-Ab detection methods are low in sensitivity, it is urgent to find faster methods with higher sensitivity, specific for diagnostic of silicosis complicated with tuberculosis [4] [5].

Materials
From February 2017 to May 2019, 53 cases of suspected silicosis complicated with pulmonary tuberculosis were selected.

Inclusion and Exclusion Criteria
Inclusion criteria: 1) The cases were in accordance with GBZ70-2009 "diagnostic criteria for pneumoconiosis" [6]; 2) Recently, the patient had fever, night sweats, cough, hemoptysis, wheezing, pleural effusion and other suspected tuberculosis symptoms; 3) They did not receive Isoniazid or Rifampicin or Rifapentine or Ethambutol or other antituberculosis treatment; 4) The patients agreed to be enrolled in the study and performed active coorperation.

Methods
All patients received four kinds of tuberculosis detection: TB-IGRA,TB-Ab, PPD, TB-DNA-PCR.

TB-IGRA
In the early morning, 6 -10 mL of fasting peripheral venous blood was extracted and was anticoagulated with heparin, and peripheral monocytes were isolated. 50

TB-Ab
Colloidal gold immunochromatography was performed to determine serum tuberculosis antibody. The reagent was provided by Shanghai Aopu biological company, and the operation was carried out according to the instruction of the kit.

PPD
After subcutaneous injection of 5 IU tuberculosis protein derivative into the inner site of left forearm for 72 hours, the average diameter of induration was observed and calculated by (transverse diameter + longitudinal diameter)/2. When there is no induration or the average diameter of induration is less than 10 mm, the result will be regarded as negative (−); and the result will be regarded as positive = (+) when the diameter exceeds 10 mm.

Sputum or Pleural Effusion TB-DNA-PCR
After

Statistical Method [7] [8]
Spss20.0 statistical software was used to process the data. Measurement data was presented by x ± S; Count data was expressed in %.

General Results
There were 52 males and 1 female in 53 cases of suspected silicosis complicated with pulmonary tuberculosis, aged from 42 to 86 years old, with an average age of (61.85 1 ± 11.32). 11 cases were diagnosed as pulmonary tuberculosis, and the incidence rate was 20.75%, 42 cases were ruled out of tuberculosis, and the 11 cases were given anti tuberculosis drugs intervention (Table 1).

Positive and Negative Rates of TB-IGRA, PPD, TB-DNA-PCR and TB-Ab
A total of 53 cases were included in this study, among which 11 cases were diagnosed as pulmonary tuberculosis, and 42 cases were ruled out of tuberculosis.

Sensitivity, Specificity, Positive Predictive Value and Negative Predictive Value of TB-IGRA, PPD, TB-DNA-PCR and TB-Ab
Sensitivity, specificity, positive predictive value and negative predictive value of

Discussion
Tuberculosis is the most common complication of silicosis. Meta analysis [9] conducted by mirsadraee et al. showed that mobidity of tuberculosis in pneumoconiosis patients was 22.50%, which was significantly higher than that of normal people (6.3%). At present Silicosis is a common occupational disease in   Table 3. Sensitivity, specificity, positive predictive value and negative predictive value of the four tuberculosis detection indexes %. manifestations which permits early diagnosis and has become popular in Europe and America. The mechanism of TB-IGRA detection [10] is that upon infection of Mycobacterium tuberculosis, T-lymphocytes were stimulated to produce. When physically stimulated by the tuberculin again, interferon will be secreted immediately. ELISPOT is used to count interferon-γ peripheral blood mononuclear cells, and then diagnostic conclusion was drawn. 11 cases of pulmonary tuberculosis were diagnosed in this study, with the incidence of 20.75%. Positive rates of TB-IGRA, PPD, TB-DNA-PCR and TB-Ab were 66.04%, 30.19%, 5.67% and 26.42%, with the sensitivity of 90.91%, 81.82%, 27.27% and 54.55%, the specificity of 42.86%, 80.95%, 100% and 80.95%. The positive predictive values of 28.57%, 50%, 100% and 42.86% and the negative predictive values of 94.44%, 91.89%, 84% and 87.18%, respectively. TB-IGRA was highest in positive rate, sensitivity and negative predictive value, while TB-DNA-PCR had the highest specificity, with low positive rate, sensitivity and positive predictive value. The values of PPD and TB-Ab were between the two. PPD was high in sensitivity and specificity, but clinical strong positive value is low and is relatively high in false-positive rate and false-negative rate.
To sum up, TB-IGRA is high in positive rate and sensitivity, which is better than the traditional sputum examination of tuberculosis. Yet with poor specificity, it's unable to judge whether the case is active tuberculosis, which is limited in clinical diagnosis. However, it can be used as an auxiliary diagnostic item. Combination of PPD and TB-DNA-PCR can improve the sensitivity, specificity and positive predictive value, and also improve the diagnostic accuracy of active tuberculosis, which can make up for each other's shortcomings, thus has favorable clinical value in the auxiliary diagnosis of active tuberculosis.

Project Name
The project name is 2018 key project plan of medical science research in Hebei Province 20180869 Comparison between TB-IGRA detection and bronchoalveolar lavage fluid tuberculosis detection in the diagnosis of silicosis with pulmonary tuberculosis.

Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this paper.