An Observational Study on Clinical Profiles of Tuberculous Pleural Effusion Patients in A Tertiary Care Teaching Hospital, Dhanmondi, Dhaka, Bangladesh

Background : Mycobacterium tuberculosis has infected around 1.7 billion people around the world so far and has been categorized as one of the top 10 causes of mortality globally. The rate of infection is increasing every year mainly 30 high TB burden countries. Due to high density of population every year the number of Tuberculosis (TB) patients are increasing in Bangladesh. Objective : To analyze the clinical profiles and radiological features of the pleural fluid (PF) among tuberculous pleural effusion (TPE) patients attending Bangladesh Medical College, Dhanmondi, Dhaka, Bangladesh. Methods : This is a hospital-record based cross sectional observational study executed in a tertiary care teaching hospital, Dhanmondi, Dhaka. The study group comprises 182 diagnosed tuberculous pleural effusion patients enrolled in our Bangladesh Medical College Hospital from July 2020 to June 2022. Analysis of data was done by using SPSS 15 software. Results : In our observational study we found that tuberculous pleural effusion was predominant in the male gender (62%) with predominant age group of 31-40 years (36.26%). Among various clinical manifestations the predominant features were fever (89.56%), chest pain (63.19%) and night sweats (51.09%). Duration of TPE patients was 16-30 days (69.78%) when they presented to us. During BMI measurements we found that 56.59% of our patients were within normal BMI range and only 7.14% were undernourished indicating the assumption that low BMI or undernutrition is not a vulnerability factor anymore. 72% of our TPE patients belonged from urban locality. During radiological analysis of pleural fluid through chest x ray we have observed that 60.98% cases were right sided small (65.38%) pleural effusion and 36.81% had loculated pleural effusion. 59.89% of our patients got cured with anti TB medications but we lost follow ups to some of our study populations 15.93%. There were no mortality records during our study period. Conclusion : Most common manifestations of tuberculous pleural effusion were low grade fever and chest pain. TPE was predominant among young adults in our study which we need to be more attentive during our diagnosis and treating patients with pleural effusion.

In TB endemic countries extrapulmonary TB is also very frequent as well as pulmonary TB.After Tuberculous lymphadenitis TBE encounter the most common form of extrapulmonary TB.The accumulation of fluid in the pleural space due to TB is multifactorial.Following a rupture of subpleural caseous focus MTB antigen enters the pleural space which initiates the inflammatory process and increase the permeability from the capillaries.Subsequent obstruction in the lymphatic drainage also decreases the rate of pleural fluid clearance [2]- [4].
As Bangladesh has been listed as one of the high TB burden countries around the world, a large number of TPE cases are encountered in here due to density of population and lack of proper hygiene.In this observational study, we want to focus the clinical profiles of the patients who were diagnosed with TPE attending to Bangladesh Medical College, Dhanmondi, Dhaka.

A. Study Design
A cross sectional observational study was carried out at the Bangladesh Medical College Hospital, Dhanmondi, Dhaka, Bangladesh.

B. Study Population
Patients aged 18 years and above who were admitted to the medicine ward and diagnosed with TPE after meeting the inclusion and exclusion criteria between the period of July 2019 to June 2022 were included as the study population.

C. Study Procedures
We collected demographic features, body mass index (BMI), clinical manifestations, radiological findings (PE size, site, presence or absence of loculation and pulmonary opacities on chest x-ray) and analysis of pleural fluid (microbiological and biochemistry).

D. Pleural Fluid Analysis
Around 20 ml of pleural fluid was collected from each study population and at first physical examination of the pleural fluid was done focusing on color, amount and nature of the fluid.
Pleural fluid was collected in 2 separate test tubes; one for biochemical analysis which includes protein, sugar, LDH and adenosine deaminase (ADA) and other one for total and differential cell count of the PF.Pleural fluid analysis were done within 3-4 hours of the collection at the laboratory.By using Olymopus-AU-400 instrument the estimation of glucose, protein, LDH and ADA done through spectrophotometric method.
In an improved Neubauer's chamber pleural fluid dilution was done with white blood cells (WBC) diluting fluid (Turk's fluid) and after that total leukocyte count (TLC) was estimated.

E. Microbiological Testing
PF samples underwent Gram stain and Ziehl-Nelson (ZN) staining.The Gene Xpert MTB/RIF technique was applied over PF to detect the results in the earlier periods [5].
As TB is very common in our country so we didn't proceed towards the invasive investigations like pleural biopsy for histopathology or culture to reach our diagnosis.

F. Radiological Data
An expert thoracic Radiologist has reviewed all the chest X-rays.According to the radiological findings TPE considered large if they occupied half or more than half of the hemithorax and small if they occupied less than half of hemithorax.Massive TPE was categorized when there is complete opacification in the hemithorax.Pleural effusion that is located to one or more fixed pockets in the pleural space showing a convex form facing in the pulmonary parenchyma can be defined as loculated TPE.Pulmonary opacity was defined as an area of increased pulmonary attenuation caused by intraparenchymal or airspace diseases, including cavitation or cystic spaces or any previous fibrotic lesions [6].

I. Sampling Techniques
Consecutive convenient (purposive) sampling method was applied in here.

J. Statistical Analysis
In our study we have used descriptive statistics to summarize the various parameters regarding demographic profiles, clinical features, pleural fluid characteristics and radiological findings.The normally distributed data and results are described with mean and standard deviation (SD).Categorical data were summarized using frequencies and percentages as well.Statistical analysis was done by using appropriate statistical tool like 'chi-square' test, student 't' test, where applicable.A p-value of <0.05 was statistically significant and p-value of > 0.05 was considered not significant statistically.All kinds of Data were recorded into semi-structured pre-tested pro forma.It was entered into Microsoft Excel and analyzed using SPSS v 24.0 (IBM Corp., Armonk, NY, USA).Informed consent was taken in all the cases and the records were kept confidentially.

K. Ethical Clearance and Informed Consent
The study was carried out after obtaining approval from the Institutional Ethical Committee.The participants were briefed about the purpose of the study and informed consent was obtained prior to the data collection.

III. RESULTS
272 patients with pleural effusion were reviewed among them 182 patients have completed the diagnostic and exclusion criteria and then became a part of the study population.Majority (62.09%) of the patients were males with the age group ranging from 31-40 years (36.26%)among both genders.

C. Clinical Manifestations of TPE Patients
Among various clinical manifestations the most common features were fever (89.56%), chest pain (63.19%) and night sweats (51.09%) which were observed in our TPE patients.69.78% patients presented to us after 16-30 days of their clinical manifestations.

F. Area Wise Distribution of the Study Group
Our TPE patients were mostly (72%) belonged from the urban group.

G. Chest X-ray Data Interpretation
During radiological analysis of TPE patient we have found that most (60.98%) of our TPE patients had Right sided pleural effusion with occupying less than half of hemithorax (65.38%).Among these cases 36.81%patients had loculated pleural effusion.

H. Progress of our TPE Patients
Majority (59.89%) of our patients got cured with the anti TB medications following 6 months however we lost to follow up (15.93%) some of our cases.We had 0% mortality rate among our study group due to TPE so far.

IV. DISCUSSION
Tuberculous pleural effusion is usually considered as a paucibacillary infection.There are certain factors which determine the diagnosis of TPE.Those include adequate clinical history, radiological features consistent with pleural effusion, findings of pleural fluid such as predominant lymphocyte count, increased pleural protein level, high LDH levels, low glucose level and more than 35 IU/L of ADA level [7].
The confirmatory diagnosis of the pleural TB still depends upon proper identification of the causative organism either on direct microscopic examination or culture of the pleural fluid.In case of invasive procedures, we can introduce pleural biopsy followed by its histopathology and culture which will provide us confirmation around 90-97% of cases [7], [8].
As a high TB burden and poor resourceful country, we usually don't proceed to the invasive procedures at the first instance.Clinical profiles and adequate pleural fluid analysis are still our pivotal steps for diagnosis of TPE.

Rural 28%
After introducing the anti TB medication if we don't get adequate response from the patient's general status then we proceed towards invasive procedures moreover it is costly and not easily available in all the health care centers in our country.
There are various cut-off values to identify TPE through the pleural fluid ADA level.These values usually depend upon the age of the patients [9], [10].Tay and Tee have been classified the pleural fluid ADA level according to the age group.They have proposed to positive ADA level 72 IU/L in patients with aged <55 years and 26 IU/L with aged >55 years.It usually signifies the diagnostic accuracy around 95% in both the cases [9].However, in our study only 15.93% patients aged >50 years so it may create an impact on lack of association between age and ADA values.The production of ADA and subsequently activation of lymphocytes usually depend on the degree of inflammation going on.Usually elevated pleural LDH level indicates inflammation [11].
Although CT chest is not routinely indicated the diagnosis of pleural fluid TB, but pulmonary opacities can be visualized more accurately than standard chest x-ray [5], [12].
In our routine clinical practice patients with TPE along with parenchymal involvement usually consider as an infectious cases.In our research we usually have taken the cases which have no features of parenchymal involvement in the routine chest X-ray.Reference [13] had shown the sputum examination for AFB in patients with TPE without parenchymal involvement on the chest x-ray and observed that 22.2% patients had positive sputum either on AFB stain and/or culture [13].Another study has performed on the induced sputum examination among TPE patients which found that 55% patients had positive sputum culture without any parenchymal involvement in the chest X-ray [14].
Majority of our TPE patients were males 62% compared to the female group.There are also several studies where they also found male predominance among TPE patients [15], [16].In this study, the TPE patients is predominant in the age group of 31-40 years and progressively declined along with aging which carries the different picture from the western world as there TPE occurs at the later age group due to low endemicity.Parikh P and co-researchers also found the TPE prevalence more in the age group between 31-40 years [17].
Our study populations had got more (60.98%)right sided pleural effusion than left sided and very few cases of bilateral pleural effusions (3.84%).Although these findings varied in different studies.

V. LIMITATIONS
As pleural biopsy is an invasive and costly procedure so we couldn't be able to do pleural biopsy in all patients followed by histopathology and culture sensitivity.As high TB burden country the clinical findings and pleural fluid analysis still play a pivotal role in our management strategy.As our current research has done on a tertiary care teaching hospital in the urban location so it doesn't reflect the exact picture of the entire nation.Moreover, we have not done Gene Xpert of TB on the sputum sample in all the patients which need to be done in the near future.More ongoing research need to be accomplished to bring a definitive conclusion in this communicable disease.

VI. CONCLUSION
TPE was found more frequent in the young healthy male adults in our study.Moreover, very few patients were underweight, indicating the assumption that low BMI or undernutrition is not a vulnerability factor anymore even in a high TB burden country like Bangladesh.Although invasive procedures are not routinely practiced in our country to diagnose TB, but we recommend that we should perform Gene Xpert for TB on the sputum sample invariably all patients with extrapulmonary TB whether there is presence or absence of parenchymal lesions on chest X-ray.

ACKNOWLEDGMENT
The authors wish to thank the Ethical Committee of Bangladesh Medical College for approving and providing the opportunities to complete the research work and grateful to the Radiology and Pathology laboratory staff for their help during this study.The authors also acknowledge the cooperation of the study population who participated in this study.

CONFLICT OF INTEREST
Authors declare that they do not have any conflict of interest.
A diagnosis was made by observing the following criteria: a) Clinical features consistent with TPE b) Exudative pleural effusion based on Light's criteria c) Pleural fluid ADA level 35 U/l or more d) Resolution of PF and improvement of patient's well being followed by anti TB medications e) A positive microbiological test was defined as mycobacterium tuberculosis identified in the PF sample by microscopy or Gene Xpert method f) Exclusion of other potential differentials during the routine follow ups of the TPE patients.H. Exclusion Criteria a) Patients having parenchymal lesions on chest X ray b) Except TPE other confirmed diagnosis of extrapulmonary TB c) Pulmonary TB d) Pregnant women e) Patients not willing to participate in the study f) Alteration in higher psychic function in critically ill patients.

Fig. 2 .
Fig. 2. Area wise distribution of the study group.

TABLE I :
AGE WISE DISTRIBUTION OF STUDY POPULATION

TABLE II :
CLINICAL MANIFESTATIONS OF TPE PATIENTS D. Duration of Symptoms among TPE Patients

TABLE III :
DURATION OF SYMPTOMS OF TPE PATIENTS

TABLE IV :
DISTRIBUTION OF BMI AMONG STUDY GROUP BMI (kg/m 2 )

TABLE V :
CHEST X RAY DATA INTERPRETATION OF TPE PATIENTS

TABLE VI :
PROGRESSION OF TPE PATIENTS