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(Chest. 2006;129:1253-1258.)
© 2006 American College of Chest Physicians

The Prevalence of Pulmonary Parenchymal Tuberculosis in Patients With Tuberculous Pleuritis*

Hee Joung Kim, MD; Hyun Ju Lee, MD; Sung-Youn Kwon, MD; Ho Il Yoon, MD; Hee Soon Chung, MD; Choon-Taek Lee, MD; Sung Koo Han, MD; Young-Soo Shim, MD, FCCP and Jae-Joon Yim, MD

* From the Division of Pulmonary and Critical Care Medicine, Department of Medicine and Lung Institute (Drs. Kim, Han, Shim, and Yim), and Department of Radiology, Institute of Radiation Medicine (Dr. H. J. Lee), Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine (Drs. Kwon, C-T. Lee, and Yoon), Seoul National University Bundang Hospital; and Division of Pulmonology, Department of Internal Medicine (Dr. Chung), Seoul National University Boramae Hospital.

Correspondence to: Jae-Joon Yim, MD, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110–744, South Korea; e-mail: yimjj{at}snu.ac.kr

Abstract

Study objective: To examine the prevalence and characteristics of parenchymal tuberculous pleuritis in adult patients.

Design: Prospective cohort study.

Setting: Three hospitals affiliated with Seoul National University in South Korea.

Patients: All patients > 15 years old with a diagnosis of tuberculous pleuritis were enrolled prospectively between January 1, 2004, and October 31, 2004.

Interventions: Diagnostic thoracocentesis and CT of the chest were done for each patient. Acid-fast bacilli (AFB) smears and cultures for Mycobacterium tuberculosis were requested if patients produced any sputum. A board-certified radiologist reviewed the chest radiographs for the presence and characteristics of any lesions.

Measurements and results: One hundred six patients with tuberculous pleuritis were enrolled (median age, 53 years; range 16 to 89 years). Among them, 33 patients (31%) had sputum or bronchial washing findings positive for AFB smears or for M tuberculosis by culture. Lung parenchymal lesions were observed in 91 of the patients (86%) using chest CT; 39 patients (37%) with parenchymal lesions had radiographic characteristics of active pulmonary tuberculosis. In total, 62 patients (59%) had bacteriologically or radiographically active pulmonary tuberculosis. In addition, 78 patients (74%) had features of reactivated pulmonary tuberculosis.

Conclusions: Lung parenchymal lesions were more common in this series of patients with tuberculous pleuritis than has been reported in previous studies. The patients mostly had radiographic features of reactivated, rather than primary, tuberculosis.

Key Words: pleural tuberculosis • pulmonary tuberculosis • thoracic radiography

Approximately two billion people, nearly one third of the population of the world, have Mycobacterium tuberculosis infection and are at risk for active disease. Among those with latent tuberculosis infection, > 8,000,000 people (140 per 100,000 population) had active disease develop in 2003, of whom 4,000,000 (62 per 100,000) were smear positive and approximately 2,000,000 (28 per 100,000) died.1

Extrapulmonary tuberculosis comprises 9.7 to 46% of all cases of the disease,234 and its proportion has gradually increased in some regions.5 Common organs involved include the lymph nodes, pleura, bones and joints, brain and meninges, liver and other GI organs, genitourinary organs, peritoneum, and pericardium. Tuberculous pleuritis is usually the second most-common form of extrapulmonary tuberculosis after tuberculous lymphadenitis, and remains the most common cause of pleural effusion in areas with a high prevalence of tuberculosis.67

Tuberculous pleuritis can manifest as primary or as reactived disease. In the primary form, pleural effusion is thought to result from penetration of bacilli into the pleural space via rupture of a subpleural caseous focus.8 Protein antigens produced by the tuberculous bacilli induce a delayed hypersensitivity reaction, causing exudation by increased permeability9 or decreased clearance.1011 In addition, tuberculous pleuritis can occur from reactivation of a latent infection.12 In such cases, it is usually associated with parenchymal lesions, such as fibronodular infiltrates or cavitation in one or both upper lung fields.

Although previous studies13141516 reported parenchymal lesions in 18.9 to 46% of patients with tuberculous pleuritis, these were retrospective reviews involving small numbers of cases. The aim of this study was to examine the prevalence and characteristics of parenchymal tuberculosis in adult patients with pleuritis, using a prospectively designed study.

Materials and Methods

Participants and Study Procedures
All patients > 15 years old with a diagnosis of tuberculous pleuritis were enrolled prospectively between January 1, 2004, and October 31, 2004, at three hospitals affiliated with Seoul National University, South Korea: Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul National University Boramae Hospital. All potential enrollees underwent a standardized interview and physical examination, and underwent simple chest radiographs in the posteroanterior and decubitus positions. Diagnostic thoracocentesis was performed, and laboratory measurements were made of WBC counts and the levels of protein, lactate dehydrogenase, glucose, and adenosine deaminase. The pleural fluids were examined cytologically for malignant cells; smears for acid-fast bacilli (AFB) and samples for M tuberculosis cultures were obtained. If the possibility of tuberculous pleuritis was present, the smears and cultures of sputa were done up to three times, if the patient was able to produce sputum. CT scans of the chest were performed in every patient. Noncontrast chest CT scans were normally recommended; however, contrast-enhanced CT could be done if clinically needed. Any patient with bacterial growth from the pleural fluid other than M tuberculosis, or with malignant cells in the pleural fluid, was excluded from the study. The protocol of this study was approved by the institutional review board of Seoul National University Hospital, and written permission was obtained from each enrollee.

Diagnosis of Tuberculous Pleuritis
The diagnosis of tuberculous pleuritis was based on the following criteria: (1) demonstration of AFB or the growth of M tuberculosis in pleural fluid or tissue; or (2) presence of caseating granulomas in pleural tissue; or (3) a lymphocyte-predominant exudative effusion with an adenosine deaminase level > 40 IU/L. The pleural effusion was considered as an exudate if the fluid met the criteria described by Light.17 The positive predictive value of lymphocyte predominant exudates with an adenosine deaminase level > 40 IU/L is 100% in the Korean population.18 Definition of the presence of pulmonary parenchymal tuberculosis was a positive AFB smear findings or a positive M tuberculosis culture finding from sputum, or the presence of a radiographic lesion compatible with the pulmonary form of the disease.

Classification of Parenchymal Lesions
Radiographs were reviewed blindly by a board-certified radiologist, who evaluated the radiographs for the presence of the parenchymal pulmonary tuberculous lesions and, if any were present, classified them as patchy, linear, nodular, mass-like, cavitary, fibrotic, or calcified. In addition, the extent of each lesion was categorized into multilobar, unilobar, or segmental. The radiologist also checked whether hilar or mediastinal lymphadenopathy were present.

Determination of Radiographic Activities of Lung Parenchymal Tuberculosis
Radiographic activities were classified based on previously published criteria192021: definitely inactive, with no evidence of lung lesions; probably inactive, with lesions appearing mainly as calcified nodules or fibrotic bands; indeterminate activity, with lesions appearing mainly as noncalcified well-circumscribed nodules; probably active, showing a "tree-in-bud" appearance or multiple noncalcified poorly circumscribed nodules without a cavity; and definitely active lesions including a cavity.

Statistical Analysis
Univariate comparisons between the culture-positive group and culture-negative group were performed using Pearson {chi}2 test or Fisher Exact Test for categorical variables and Student t test for continuous variables. All tests of significance were two sided, and p < 0.05 was considered statistically significant. Statistical software (version 11.0; SPSS; Chicago, IL) was used for all analysis.

Results

One hundred six patients with tuberculous pleuritis were enrolled: 34 patients from Seoul National University Hospital, 37 patients from Seoul National University Bundang Hospital, and 35 patients from Seoul National University Boramae Hospital. Of the patients, 64 were male (60%). The median age was 53 years (range, 16 to 89) and with two peaks at 20 to 29 years and 70 to 79 years, respectively. Twenty patients (19%) had a history of previous tuberculosis. The most common symptoms were cough, dyspnea, and fever. Pleural effusions were present on the right side in 59 patients (56%), on the left side in 38 patients (36%), and on both sides in 9 patients (8.5%). Forty-nine patients (46%) received a diagnosis of tuberculous pleuritis by bacteriology or pathology; clinical diagnoses were made in the other 57 patients (54%). No patient was HIV seropositive (Table 1 ).


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  		Table 1.. Demographic and Clinical Characteristics of Patients With Tuberculous Pleuritis (n = 106)*

 
Sputum AFB smears and M tuberculosis cultures were obtained from 89 patients. Among these, 33 patients (31%) had positive sputum or bronchial washing fluid results. Lung parenchymal lesions were observed in simple chest radiographs of 71 patients (67%). In addition, parenchymal lesions were demonstrated by chest CT scans in 20 patients without parenchymal lesions noted on simple chest radiographs. In total, 91 of 106 patients (86%) had parenchymal lesions in chest CT scans. Surprisingly, two patients with positive sputum culture findings for M tuberculosis had no abnormalities detected in their chest CT scans. Nodular (64%) and patchy lesions or infiltrations (57%) were the most common form of parenchymal lesion, and cavitary lesions were found in 17 patients (19%). Upper-lobe-dominant lesions were more frequent (n = 58, 64%). In 16 patients (18%), hilar or mediastinal lymphadenopathy was observed (Table 2 ). Thirty-nine of the 106 patients (37%) had definitely or probably active pulmonary tuberculosis in terms of radiographic characteristics, 33 patients (31%) had bacteriologically active pulmonary disease, and 62 patients (59%) had bacteriologically or radiographically active pulmonary disease (Fig 1 ).


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  		Table 2.. Radiographic Patterns of Lung Parenchymal Lesions in Patients With Tuberculous Pleuritis and Any Lesions on Chest CT Scans (n = 91)

 

Figure 1
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  		Figure 1.. Presumptive radiographic activities among 106 patients with tuberculous pleuritis. M.TB = M tuberculosis.

 
We tentatively classified the patients with tuberculous pleuritis into primary or reactivated tuberculosis based on their radiographic characteristics, and evaluated the differences between the two groups. We classified 28 patients (26%) without any parenchymal lesion, or with infiltrations in the lower lobe, or with mediastinal lymphadenopathy as having primary tuberculosis. In addition, we regarded 78 patients (74%) with cavitary, fibrotic, or calcified lesions mainly in the upper lobe as having reactivated disease. Of the latter group, 19 patients (24%) had a history of previous tuberculosis; however, only 1 of the 28 patients with the primary form reported having had tuberculosis previously (p = 0.04). Men were more common in the group with reactivated tuberculosis (p = 0.009). The mean level of adenosine deaminase was higher in patients with reactivated vs primary tuberculosis (86.1 ± 34.7 IU/L vs 73.2 ± 20.3 IU/L, p = 0.02) and the presence of tuberculous bacilli in sputa was more common (46.2% vs 12.5%, p = 0.004; Table 3 ).


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  		Table 3.. Demographic and Clinical Features of Patients With Primary or Reactivated Tuberculosis Based on Chest CT Scans*

 
Discussion

Tuberculous pleuritis is a major treatable cause of exudative pleural effusion and one of the common manifestations of extrapulmonary tuberculosis. It may occur at any stage of active infection and may develop as both a primary and a reactivated disease. In the primary form, effusions typically develop 6 to 12 weeks after infection,11 and are believed to result from a hypersensitivity response to small amounts of tuberculoprotein released into the pleural space.13

Unlike previous reports,13141516 we found that 86% of these 106 patients had radiographic evidence of lung parenchymal tuberculosis when evaluated with chest CT scans. Among these, 31% had positive AFB smear or M tuberculosis culture findings indicating active pulmonary disease, and 37% had definitely or probably active pulmonary tuberculosis in terms of radiographic characteristics. In all, 59% of the patients had bacteriologically or radiographically active pulmonary tuberculosis. In addition, only 28 of 91 patients with parenchymal lesions showed the characteristic radiographic features of primary tuberculosis, such as lower-lobe dominance or mediastinal lymphadenopathy. This prevalence is much higher than in previous reports,13141516 in which the presence of parenchymal lesions was probably underestimated because of the low sensitivity of simple chest radiographs, or because of selection bias caused by retrospective design. Chest CT scanning is known to be much more sensitive in detecting lung parenchymal lesions than simple chest radiography.2223 In our study, chest CT scans revealed the evidence of parenchymal tuberculosis in 20 patients without any parenchymal lesions visible on simple chest radiographs. Considering the high prevalence of active pulmonary parenchymal tuberculosis, as high as 59%, in patients with tuberculous pleuritis, the patients suspected of having tuberculous pleuritis should be placed in isolation until a thorough evaluation for the presence of active pulmonary tuberculosis is negative.

In addition to the high prevalence of parenchymal lesions in patients with tuberculous pleuritis in our study, most of the 91 patients (86%) with lung parenchymal lesions had characteristic radiographic features of reactivated disease, such as cavitation, fibrosis, or calcified lesions mainly in the upper lobe, although some reports2425 have denied the association of these radiographic characteristics with reactivated tuberculosis. This proportion of lung parenchymal lesions among patients with tuberculous pleuritis is much higher than the 27%26 or 46%13 reported previously. The high prevalence of reactivated disease in our study could be due to the striking decrease in the annual risk of infection in Korea, which has decreased from 5.3% in 1958 to 0.5% in 1988.27 In this situation, patients with latent tuberculosis infections are more common than newly infected patients; therefore, encountering patients with reactivated disease is more likely. In conclusion, lung parenchymal lesions were more common in this series of patients with tuberculous pleuritis than has been reported previously, and the patients usually had radiographic features of reactivated rather than primary tuberculosis.

Acknowledgements

We acknowledge the insightful contributions of Dr. Young Whan Kim (Seoul National University Hospital), Dr. Chul-Gyu Yoo (Seoul National University Hospital), Dr. Sang Min Lee (Seoul National University Hospital), Dr. Chang-Hoon Lee (Korea Center for Disease Control and Prevention), and Dr. Young AE Kang (Seoul National University Hospital).

Footnotes

Abbreviation: AFB = acid-fast bacilli

Drs. Kim and H. J. Lee contributed equally to this work.

Received for publication August 23, 2005. Accepted for publication November 18, 2005.

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