One of the most common types of extrapulmonary tuberculosis is tuberculous pleural effusion (TPE) which is a primary cause of exudative pleural effusion in high-burden countries.[1] Radiologically TPE has long been viewed as a pure pleural disease, but there is growing evidence that parallel lung parenchymal disease is more frequent than not and that has significant diagnostic, treatment and epidemiological consequences.[2] The standard chest radiography shows that parenchymal lesions in patients with pleural tuberculosis are seen in only one-fifth to two-fifths of non-infectious patients, suggesting that many of them have isolated pleural disease in the past.[3] This notion has since been modified with the growing adoption of computed tomography (CT) and high-resolution CT (HRCT) as more sensitive cross-sectional imaging all the time demonstrates an ever-growing burden of parenchymal abnormalities than implied by chest X-ray alone[4] Coexisting parenchymal abnormalities of the lungs have been observed on plain radiographs in up to 17-40% of patients with TPE, typically on the same side of the effusion and typically in the upper lobes, as per reactivation disease.[5] These lesions comprise exudative or fibroproductive opacities, focal consolidation, cavitation and volume loss, in general, of post-primary pulmonary tuberculosis.[6] However, the chest radiography evidently underestimates actual involvement of the lung as it has been estimated by studies that CT or HRCT revealed parenchymal disease in about 58-87% of patients who had tuberculous pleuritis, nearly doubling the prevalence of these conditions on X-rays.[7] In a CT based series of TPE, underlying parenchymal abnormalities of the lung were detected in approximately 39% of cases, and in other cohorts, which included cross-sectional HRCT, there was active pulmonary TB features in over 80% of patients that had undergone cross-sectional imaging.[8] The CT parenchymal lesions that accompany TPE are wide-range and represent an active and post-infectious lesion.[9] The typical patterns of active disease include segmental or lobar consolidation, nodules which are tree in bud denoting endobronchial spread, centrilobular or confluent nodules, and thick-walled cavities, usually in upper lung zones or superior segments of lower lobes.[10] Micronodules scattered in the subpleural and peribronchovascular interstitium, with interlobular septal thickening are indicative of lymphatic dissemination and have been pointed out as common CT appearances in cases of TB pleuritis.[11] The subtle miliary nodules, bronchiectasis, architectural distortion and fibrotic bands seen in the HRCT are also part of the post-tuberculous sequelae and may be accompanied by the presence of active lesions and the pleural disease. Notably, CT is more sensitive than the chest radiography not only in detecting active parenchymal TB but also in characterising pleural thickening, nodularity and loculation themselves are associated with enhanced microbiological yield of pleural biopsy.[12,13] The identification of the parenchymal lesions among patients with tuberculous pleural effusion is of clinical importance due to various reasons. First, radiological lung involvement raises the chance of finding sputum smear or culture-positivity, hence offering an uninvasive pathway to microbiological verification and drug susceptibility analysis.[14] Second, the presence of parenchymal abnormalities, especially cavitation and tree-in-bud opacities, is a sign of active pulmonary disease and possible transmissibility, and disagrees with the common presumption that patients with seemingly "isolated" pleural TB are non-infectious.[15] Third, CT evidence of active parenchymal TB with pleural effusion helps distinguish between tuberculous pleuritis and other causes of exudative effusions in pleura (malignancy or parapneumonic effusion), which may mimic the patient with tuberculous pleuritis but have dissimilar appearance.[16] Lastly, longitudinal radiographic follow-up has revealed that peripheral nodular opacities could arise during antitubercular therapy of TPE as a paradox and that parenchymal lesions are dynamic, and that interval changes should be interpreted in the context of treatment.[17] It is against this background that a systematic comparison of the parenchymal lesion of the lungs on chest radiography and CT/HRCT in the patients with tuberculous pleural effusion is necessary to help the understanding of the actual prevalence, patterns and clinical correlates of pulmonary involvement in this common extrapulmonary manifestation of tuberculosis.[18]

METHODOLOGY: Following informed consent, in a well ventilated room 3% Hypertonic saline is used for induced sputum because of high success rate and safety. These agents are delivered through ultrasonic nebulizer. Bronchodilatation medication, oxygen supply and resuscitation equipments were available at procedure place. Mechanism: The ultrasonic nebuliser produces a mist of hypertonic saline droplets. The smaller droplets are deposited peripherally in the lung. It is suggested that the hypertonicity of the deposited saline draws interstitial fluid into the lower airways by osmosis. The hypertonic fluid also causes bronchial irritation and this stimulates bronchial secretions. After10-20 minutes of nebulisation the fluid produced mobilize the material in the lower airways. Repeated coughing by the patient help in movement of this material into trachea to facilitate expectoration. After placing a nasal clip, induction is started with 3% hypertonic saline (5 to 7 ml). Patient is asked to expectorate whenever he feels or at every 5 minutes. Saline induction is continued for 15 minutes (3 times, 5 minute each). If sputum sample is inadequate, induction can be continued for another 5 minutes. Meticulous examination sputum smear for AFB by Z−N method and sputum culture for Mycobacterium tuberculosis by conventional Lo¨ wenstein Jensen method was done. None was subjected to any specific antitubercular drug therapy prior to the study. The study was carried out after approval from the ethical committee. Study area and population This prospective, institution-based observational study was conducted in the Department of Respiratory Disease (Pulmonary Medicine), Jawaharlal Nehru Main Hospital & Research Centre, Bhilai, Chhattisgarh. The study population consisted of patients residing in Bhilai and the surrounding areas who were admitted with a diagnosis of tubercular pleural effusion under the care of the Department of Pulmonary Medicine. Study design and duration The study followed a prospective observational design and was carried out over a period of 12 months, from May 2012 to May 2013. All consecutive eligible patients meeting the selection criteria during this period were included until the desired sample size was achieved. Sample size and sampling technique As the exact prevalence of tubercular pleural effusion in the local population was not known, an anticipated prevalence of 50% was assumed for sample size calculation to yield the maximum possible sample size. Using the formula n=4pq/l^2, where p=50, q=100-p=50 and allowable error l=20%" of " p=10, the minimum required sample size was calculated as 100. A total of 100 patients with tubercular pleural effusion who fulfilled the inclusion criteria were therefore enrolled in the study by consecutive sampling. Source of data and data collection Data were obtained from patients with a confirmed diagnosis of tubercular pleural effusion admitted to the chest ward of the Department of Respiratory Disease, Jawaharlal Nehru Main Hospital & Research Centre, Bhilai. Each patient underwent a detailed clinical evaluation including comprehensive history and thorough general and respiratory system examination, with particular attention to symptoms and signs of pleural effusion. Chest radiograph posteroanterior (PA) view was performed in all patients, and a lateral view was obtained when required. Routine laboratory investigations included complete blood count, blood glucose, and simultaneous measurement of serum total protein and lactate dehydrogenase (LDH) to apply Light’s criteria for classification of pleural effusion as exudate or transudate. Pleural fluid analysis and diagnostic work-up Diagnostic thoracentesis was performed in all enrolled patients after obtaining informed written consent. Pleural fluid was sent for cytological examination, total and differential cell counts, biochemical analysis including total protein (g/L), LDH (U/L) and glucose (mg/dL), and for differentiation of transudate versus exudate using Light’s criteria by calculating pleural fluid/serum protein and pleural fluid/serum LDH ratios. Pleural fluid was also subjected to Ziehl–Neelsen staining for acid-fast bacilli, conventional culture for Mycobacterium tuberculosis on Löwenstein–Jensen medium, and measurement of adenosine deaminase (ADA) levels using an autoanalyzer based on the colorimetric end-point method described by Guisti and Galanti. Pleural biopsy After appropriate counseling and written informed consent, closed pleural biopsy using Abram’s pleural biopsy needle was attempted in all patients; however, only 76 patients consented to the procedure. At least three pleural tissue fragments were obtained in each case. The specimens were fixed and stained with hematoxylin and eosin for histopathological examination and were also processed for microbiological evaluation, including Ziehl–Neelsen staining and culture for Mycobacterium tuberculosis. Induced sputum procedure In patients included in the study, induced sputum samples were obtained following informed consent in a well-ventilated room using 3% hypertonic saline delivered via an ultrasonic nebulizer. Standard precautions were taken, with bronchodilator medication, oxygen supply and resuscitation equipment available at the procedure site. The hypertonic saline aerosol, deposited in the peripheral airways, was used to mobilize secretions by osmotic attraction of fluid into the airway lumen and by inducing mild bronchial irritation, thereby stimulating cough. After placement of a nasal clip, nebulization with 3% saline (5–7 mL) was started; patients were instructed to expectorate whenever they felt the urge or at intervals of 5 minutes. Nebulization was continued for 15 minutes (three cycles of 5 minutes each) and extended by an additional 5 minutes if the sample was inadequate. Induced sputum specimens were examined by Ziehl–Neelsen staining for acid-fast bacilli and cultured for Mycobacterium tuberculosis on Löwenstein–Jensen medium. None of the patients received antitubercular therapy prior to the diagnostic evaluation. Selection criteria Inclusion criteria Age >14 years. Exudative pleural effusion as defined by Light’s criteria. Diagnosis of tubercular pleural effusion established by at least one of the following: Pleural fluid smear positive for acid-fast bacilli and/or culture positive for Mycobacterium tuberculosis. Pleural biopsy showing histopathological features consistent with tuberculosis and/or culture positivity. Pleural fluid ADA level ≥40 IU/L in an exudative, lymphocyte-predominant effusion, in the absence of alternative diagnosis. Exclusion criteria Patients with pleural effusion who did not provide informed consent. Patients with transudative pleural effusion. Patients aged >85 years. Ethical considerations The study protocol was reviewed and approved by the Institutional Ethical and Scientific Committee of Jawaharlal Nehru Main Hospital & Research Centre, Bhilai. All participants were informed about the nature and purpose of the study, and written informed consent was obtained prior to inclusion and before performing invasive procedures such as thoracentesis, pleural biopsy and induced sputum collection. Data management and statistical analysis All collected data were checked for completeness and internal consistency before entry. Data were compiled using Microsoft Excel and analysed using an online statistical calculator (MedCalc). Descriptive statistics were expressed as proportions and ratios as appropriate. Association between categorical variables was assessed using the Chi-square (χ²) test. The χ² statistic was calculated as χ^2=∑▒ (O-E)^2/E, where O denotes observed frequency and E denotes expected frequency, with degrees of freedom calculated as (number of rows − 1) × (number of columns − 1). A p value <0.05 was considered statistically significant.

In a study of 100 patients with tubercular pleural effusion, chest X-ray revealed parenchymal lesions in 35% (n=35) and no lesions in 65% (n=65). Demographic patterns showed lesions more prevalent among males (69% of lesion-positive cases vs 65% lesion-negative; n=24/35 vs 42/65) and younger patients under 55 years (86% vs 88%; n=30/35 vs 57/65), aligning with the overall study population where males predominated (66%) and most cases (87%) were under 55 years. Table 1: Distribution of Parenchymal Lesions by Demographics Characteristic Lesion Present (n=35) Lesion Absent (n=65) Total Male 24 (69%) 42 (65%) 66 Female 11 (31%) 23 (35%) 34 Age <55 years 30 (86%) 57 (88%) 87 Age ≥55 years 5 (14%) 8 (12%) 13 This suggests parenchymal involvement follows similar demographic trends as pleural effusion alone, though dedicated statistical testing for these subgroups was not performed. Significant associations emerged between parenchymal lesions and markers of pulmonary tuberculosis. Lesions strongly correlated with induced sputum ZN smear positivity (9/35 present vs 6/65 absent; p=0.027), indicating higher AFB detection in lesion-positive cases. Table 2: Lesions vs Induced Sputum ZN Smear Chest X-ray Lesion ZN Smear Positive ZN Smear Negative Total Present 9 26 35 Absent 6 59 65 Total 15 85 100 Even stronger was the link with induced sputum LJ culture positivity (25/35 present vs 21/65 absent; p=0.00018), where over 70% of lesion-positive patients had culture-confirmed TB compared to 32% without lesions. Table 3: Lesions vs Induced Sputum LJ Culture Chest X-ray Lesion LJ Positive LJ Negative Total Present 25 10 35 Absent 21 44 65 Total 46 54 100 In contrast, no significant correlations existed with pleural-based diagnostics. Parenchymal lesions showed weak association with pleural fluid ZN smear (2/65 present vs 1/35 absent; p=0.94) and culture positivity (similar non-significant distribution; p>0.05), highlighting that pleural effusion diagnostics poorly predict concurrent lung parenchymal disease. These findings underscore the value of sputum evaluation over pleural fluid analysis when radiographic parenchymal lesions suggest active pulmonary involvement in tubercular pleural effusion. Table 4: Lesions vs Pleural Fluid ZN Smear Chest X-ray Lesion ZN Positive ZN Negative Total Present 2 63 65 Absent 1 34 35 Total 3 97 100 Table 5: Lesions vs Pleural Fluid Culture Chest X-ray Lesion Culture Positive Culture Negative Total Present 2 63 65 Absent 1 34 35 Total 3 97 100

The current research has indicated that 35% of patients who had a tubercular pleural effusion exhibited radiographic lung parenchymal involvement which is in line with the past literature indicating the frequent but inconsistently reported parenchymal disease in pleural tuberculosis. Seiscento et al. [4] found pulmonary involvement in one-quarter of patients on chest radiograph and two-thirds on HRCT, and tomography evidence of active pulmonary tuberculosis in a quarter of the cases, which has underscored that standard radiography underestimates accompanying lung disease. In the same manner, Yilmaz et al.[19] showed underlying lung parenchymal abnormalities in 39% of patients with tuberculous pleurisy on CT, which is similar to the 35% lesion rate of the chest X-ray seen in the current cohort. In further support of the notion that pleural tuberculosis is in most instances a continuum of pulmonary tuberculosis but not a discrete pleural process, narrative reviews by Zhai et al. have pointed to the fact that CT is able to detect parenchymal disease in 40-85% of TPE cases. The fact that the present study has a similar demographic distribution in lesion-positive and lesion-negative groups with the majority of the participants being males and younger adults is consistent with the overall epidemiological characteristics of pleural TB in these series and the idea that the parenchymal involvement represents the same underlying disease burden but not a different clinical subset. The close connection between parenchymal lesions of the chest X-rays and induced microbiological positivity in the sputum of patients in this study is consistent with previous literature that demonstrated patients with pleural TB and concomitant lung involvement are an important source of transmission. Seiscento et al. [4] stressed that pulmonary lesions revealed by HRCT in pleural TB have a significant epidemiological implication as these patients can be among the most significant carriers of infection despite an initial appearance of isolated pleural disease. Recent reviews of tuberculous pleural effusion have also reported that parenchymal disease and airways involvement enhances chances of sputum smarter positivity or culture positivity especially the occurrence of radiographic abnormalities like consolidation, cavitation or tree-in-bud opacities. These findings are further expanded in the present study, which illustrates that despite induced sputum, the rate of culture positivity is greater than 70 percent in the lesion-positive patients, significantly high compared to those without radiographic involvement of the lung parenchyma, which points to the diagnostic utility of the systematic solicitation of sputum samples when pulmonary lesions are observed. Such a finding is particularly applicable in resource constrained and high burden environments, in which induced sputum is less invasive and more readily available than thoracoscopy or image-guided pleural biopsy to confirm microbiological and perform drug susceptibility analysis. Conversely, the insignificant correlation between parenchymal lesions and presence of ZN smear or culture-positivepleural fluid in the current study is similar to earlier findings that indicate that pleural tuberculosis is generally paucibacillary in the pleural space. Many series have been described as having low yields of mycobacterium in pleural fluid with culture sensitivity strongly linked to the methodology and often worse than sputum or pleural biopsy despite the use of liquid culture systems (Zhai et al.[20], Porcel et al.[1]). The radiological loculation and certain pleural fluid features as opposed to parenchymal lesions have been found to be the determinants of mycobacterial recovery in effusion by studies of predictors of pleural fluid culture positivity including the work by Ryu et al. [17]on loculated TPE. Here, the current results can be linked to the idea that pleural and pulmonary compartments are not fully associated in terms of bacillary load: radiographic lung disease is an indicator of sputum positivity but not the yield of pleural fluid culture, whereas the features of pleural fluid and loculation seem to be more appropriate when predicting the outcome of effusion culture. These findings combined with results of large cohorts of pleural TB patients who show a better culture sensitivity with the use of a combination of pleural and sputum specimens indicate that an integrated diagnostic method should be considered that utilizes sputum examination in case of the presence of parenchymal lesions but does not depend on only the use of pleural fluid smear or culture to rule out active pulmonary infection. Further research that includes HRCT, quantitative bacteria and fine phenotyping of fluid in pleura could further refine the process of risk stratification, and could also be used to shape diagnostic algorithms used to diagnose tubercular pleural effusion in endemic areas.

This paper shows that 35 per cent of patients with tubercular pleural effusion have chest X-ray parenchymal lesion and are strongly associated with induced sputum ZN smear (p=0.027) and LJ culture positivity (p=0.00018), as well as a higher pulmonary bacillary load and infectivity in this subgroup. On the contrary, the pleural fluid diagnostics did not demonstrate a significant correlation with the radiographic lung involvement, indicating the paucibacillary character of pleural space and the necessity of complementary assessment of sputum. All TPE patients, especially the ones with parenchymal abnormalities, are advised to undergo a routine chest radiography with directed induced sputum testing to optimize microbiological validation and inform infection management. Prospective studies that include the use of HRCT can be further utilized in the future to explain the actual prevalence and trends of lung involvement in tubercular pleural effusion.

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