RESEARCH JOURNAL #4

Name: Jayhan Q. Ambrocio Date: November 8,2019

Gr./Sec.: 8-Amaryllis Group #:4

Improved early diagnosis of difficult cases of tuberculous pleural effusion by combination of

thoracoscopy with immunological tests

Abstract

Although pleural effusion is a common clinical manifestation, the differential diagnosis of the cause of
pleural effusion is often challenging, especially in the early differentiation of tuberculous pleurisy (TP)
from other pleural effusion. The aim of this study was to evaluate the performance of commonly used
laboratory tests for the early diagnosis of difficult cases of pleural effusion.

Acknowledgement

Patients with undiagnosed pleural effusion were enrolled and subjected to five laboratory tests
including thoracoscopy, pleural fluid adenosine deaminase assay (ADA), Medford, J.A. Bennett, serum
tuberculosis antibody test (TB-antibody), tuberculin skin test (TST), and T-SPOT.TB assay. The diagnosis
of TP was established based on pleural histology and mycobacterial culture. The different tests were
compared for diagnostic performance. R.C. She, C.M. Litwin.

Introduction

Tuberculosis (TB) remains one of the most severe bacterial infectious diseases globally, posing a great
threat to the public health of seven billion people (Dabernat et al., 2014). The World Health
Organization estimated that TB caused 1.7 million deaths and 10.4 million incident cases worldwide in
2016, including 0.9 million incident cases in China (World Health Organization, 2017). Although the
global TB mortality rate showed a decline of 3% per year and the TB incidence decreased about 2% per
year in 2016 compared to 2015, TB remains one of the top 10 causes of death worldwide (GBD
Tuberculosis Collaborators, 2018). Tuberculous pleural effusion, also known as tuberculous pleurisy (TP),
is a common manifestation of extrapulmonary TB, which accounts for about 3–25% of all TB cases (Light,
2010, Kataria and Khurshid, 2001).

The early diagnosis of TP is crucial for initiating timely effective treatment and promoting favorable
outcomes. However, in clinical practice, distinguishing TP from other causes of pleural effusion is often
challenging. The definite diagnosis of TP still depends primarily on the demonstration of positive
Mycobacterium tuberculosis culture in pleural tissue or fluid samples (Gopi et al., 2007, Harada et al.,
2008). This method not only lacks sensitivity but is also time-consuming, often leading to a missed or
delayed diagnosis. (Light, 1999, World Health Organization, 2015, Udwadia and Sen, 2010). Alternative
methods include pleural biopsy via thoracoscopy (Wang et al., 2015), pleural fluid adenosine deaminase
assay (ADA) (Liang et al., 2008), tuberculosis antibody test (TB-antibody) (Steingart et al., 2011),
tuberculin skin test (TST) (Kunter et al., 2003), and the T-SPOT.TB assay (Chung et al., 2011). These
methods have improved the diagnosis of TP, particularly the speed of diagnosis. However, these
methods, when used individually, still lack sufficient sensitivity or specificity to be useful for the
differential diagnosis of TP (Liang et al., 2008, Liu et al., 2016, Sriram et al., 2011, Diacon et al., 2003).
Given that each of these methods has advantages and disadvantages, it was hypothesized that a
combination of different methods may offer greater diagnostic capability than is offered by a single
method. To test this hypothesis, a single-center retrospective case-series study was conducted to
evaluate the diagnostic performance of several common laboratory tests for the diagnosis of TP when
used either individually or in different combinations, and to determine the optimal scheme for improved
early diagnosis of TP.

Statement of the Problem

Patients with undiagnosed pleural effusion were enrolled and subjected to five laboratory tests
including thoracoscopy, pleural fluid adenosine deaminase assay (ADA), serum tuberculosis antibody
test (TB-antibody), tuberculin skin test (TST), and T-SPOT.TB assay. The diagnosis of TP was established
based on pleural histology and mycobacterial culture. The different tests were compared for diagnostic
performance.
Significance of the Study

This study aimed to evaluate the laboratory tests for the early diagnosis of difficult cases of pleural
effusion. Different combinations of laboratory tests for tuberculous pleurisy were compared in a high
tuberculosis burden country. Thoracoscopy combined with the tuberculin skin test or TB-antibody
showed optimal for tuberculous pleurisy.

Scope and Delimitation of the Study

This study has the following limitations. First, the study was conducted in a single hospital with a
relatively small sample size; thus, the results may not be generalized to other populations. Second, the
patient population involved in this study came from a region with a high TB burden; thus the results may
not be applicable to other areas, especially those with a low TB burden. Third, the patients enrolled in
this study were all difficult cases with an uncertain diagnosis, which may have given rise to an under-
estimation of the true sensitivity and specificity of the diagnostic tests.

Review of Related Literature

Diagnostic criteria, a definite diagnosis of TP was based on a positive culture of M. tuberculosis, or a

histopathological demonstration of granulomas in pleural tissue biopsy, or a good response to anti-TB
chemotherapy over at least 1 year of follow-up (Kataria and Khurshid, 2001, Villena Garrido et al., 2014).
The degree of pleural effusion was divided into three grades: large with a fluid volume ≥1500 ml;
moderate with a volume of 500–1500 ml; minimal with a volume of ≤500 ml. Thoracoscopy procedures
was performed by qualified respiratory physicians using a semi-rigid pleuroscope (Olympus LTF240) in a
thoracoscope chamber. Prior to thoracoscopy, patients with contraindications (such as acute coronary
syndrome, significant bleeding tendency, severe respiratory distress syndrome, etc.) were excluded
based on preoperative assessment. The preoperative assessment included vital signs, exercise tolerance,
routine blood test, coagulation function test, liver and kidney function tests, arterial blood gas analysis,
myocardial injury markers, and electrocardiogram. During the thoracoscopy procedure, patients were
closely monitored for blood pressure, heart rate, respiratory rate, and arterial oxygenation, and were
given constant supplemental oxygen via nasal catheter. The incision was usually made between the
fourth and eighth intercostal space of the axillary line. After moderate sedation and local anesthesia, a
semi-rigid pleuroscope was inserted into the pleural cavity through the small incision in the chest wall.
The visceral, diaphragmatic, and parietal pleura were carefully inspected, with all possible abnormalities
recorded. The quantity and characteristics of pleural effusion were recorded. Pleural biopsies were
implemented with flectional biopsy forceps in all suspected areas under direct visual control. Pleural
effusion specimens were collected for M. tuberculosis culture, biochemistry, and cytological
examination. Prior to incision closure, a chest drainage tube was inserted to drain fluid and air in the
pleural cavity. Chest radiography was done routinely until the removal of the chest drainage tube.

Methodology

Study population, this research project was approved by the Human Research Ethics Committee of
the First Affiliated Hospital of Chongqing Medical University, China. Written informed consent was
obtained from all patients for participation in this study. A chart review was conducted of all
hospitalized patients with a suspected diagnosis of TP between January 2014 and December 2016 at the
First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Although all patients
received comprehensive laboratory tests, including chest computed tomography (CT), TST, acid-fast
staining of respiratory tract samples, pleural biochemical and cytological examinations, and serum
pleural carcinoembryonic antigen assays, the cause of the pleural effusion was uncertain.Patients were
included in this study if they met all of the following criteria: (1) either sex and age ≥18 years; (2)
presence of symptoms resembling TB, including cough, night sweats, fever, loss of weight, chest pain,
and hemoptysis; (3) presence of pleural effusion on chest X-ray; (4) not confirmed to have TP. Patients
were excluded if they met any of the following criteria: (1) presence of active pulmonary TB and/or
under anti-TB therapy; (2) under immunosuppression therapy; and (3) HIV-seropositive.

Results and Findings

 All patients TB patients Non-TB patients p-
Clinical characteristics
(n = 106) (n = 72) (n = 34) Value

Age (years) 53.1 ± 16.5 50 ± 16.7 59.8 ± 13.7 0.003

Male 75 (70.8%) 53 (73.6%) 22 (64.7%) 0.352

BMI (kg/m2) 22.3 ± 3.4 22.1 ± 3.0 22.7 ± 4.0 0.586

Smoker 53 (50.0%) 34 (47.2%) 19 (55.9%) 0.410

HIV infection 0 (0%) 0 (0%) 0 (0%)

Close contact with TB 7 (6.6%) 7 (9.7%) 0 (0%) 0.007

Symptoms

Cough 63 (59.4%) 44 (61.1%) 19 (55.9%) 0.613

Chest pain 38 (35.8%) 27 (37.5%) 11 (32.4%) 0.610

Fever 28 (26.4%) 18 (25.0%) 10 (29.4%) 0.634

Dyspnea 14 (13.2%) 8 (11.1%) 6 (17.6%) 0.358

Night sweats 5 (4.7%) 4 (5.6%) 1 (2.9%) 0.558

Hemoptysis 2 (1.9%) 1 (1.4%) 1 (2.9%) 0.588

Weight loss 2 (1.9%) 0 (0%) 2 (5.9%) 0.160

Duration of symptoms
46.4 ± 56.1 36.9 ± 48.8 66.4 ± 64.7 0.024
(days)

Count of thoracocentesis 2.1 ± 1.2 1.9 ± 1.2 2.5 ± 1.2 0.050

Results

A total of 106 patients were enrolled; their mean age was 53 years and 70.8% were male. Seventy-
two (68%) of them were confirmed to have TP. When used individually, the five laboratory tests showed
highly variable performance parameters, including sensitivity ranging from 46% to 92% and specificity
ranging from 33% to 82%. When used in different combinations, thoracoscopy combined with TST or TB-
antibody showed the optimal performance parameters, with a sensitivity of 80.8% and a specificity of
85.7%.

Conclusions

In conclusion, the diagnostic performances of five relatively rapid laboratory tests for TP were
evaluated using a panel of 106 patients with suspected TP. When used individually, the tests showed
highly variable performance parameters. When used in different combinations, thoracoscopy combined
with TST or TB-antibody showed the optimal performance parameters, suggesting its potential as a
valuable tool for the early diagnosis of TP. The results of this study suggest that the combination of
thoracoscopy with TST or TB-antibody test is the best choice for the early diagnosis of difficult cases of
TP in high TB burden countries.

Recommendations

The authors declare that no funding was received for this study. This work was approved by the
Institutional Review Board of the First Affiliated Hospital of Chongqing Medical University. The authors
confirm that the patient data in the text remained confidential and unidentified. No competing interests
exist in this study.

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