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Choi, An, Kim, Kyung, Lee, Park, and Jeong: The Relation of Residual Pleural Thickening with Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases of Pleural Effusion in Patients with Tuberculous Pleuritis
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2008; 65(1): 7-14.

Published online: 31 July 2008

DOI: https://doi.org/10.4046/trd.2008.65.1.7

The Relation of Residual Pleural Thickening with Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases of Pleural Effusion in Patients with Tuberculous Pleuritis

Youngkwon Choi1, Chang Hyeok An, M.D.2, Yu Jin Kim, M.D.2, Sun Young Kyung, M.D.2, Sang Pyo Lee, M.D.2, Jeong Woong Park, M.D.2, Sung Hwan Jeong, M.D.2

1Graduate School of Medicine, Gachon University of Medicine and Science, Incheon, Korea.

2Division of Pulmonology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.

Address for correspondence: Chang Hyeok An, M.D. Division of Pulmonology, Department of Internal Medicine, Gachon University Gil Medical Center, 1198, Guwol-dong, Namdong-gu, Incheon 405-760, Korea. Phone: 82-32-460-3200, Fax: 82-32-469-4320, anch@gilhospital.com

Received 17 February 2008       Accepted 7 July 2008

Copyright © 2008 The Korean Academy of Tuberculosis and Respiratory Diseases

Abstract

Background

Residual pleural thickening (RPT) is the most frequent complication of tuberculous pleurisy (TP), and this can happen despite of administering adequate anti-tuberculous (TB) therapy. Yet there was no definite relation between RPT and other variables. The aim of this study was to examine matrix metalloproteinases (MMPs) and the inhibitors of metalloproteinases (TIMPs) and to identify the factors that can predict the occurrence of RPT.

Methods

The patients with newly-detected pleural effusions were prospectively enrolled in this study from January 2004 to June 2005. The levels of MMP-1, -2, -8 and -9, and TIMP-1 and -2 were determined in the serum and pleural fluid by ELISA. The residual pleural thickness was measured at the completion of treatment and at the point of the final follow-up with the chest X-ray films.

Results

The study included 39 patients with pleural fluid (PF). Twenty-three had tuberculous effusion, 7 had parapneumonic effusion, 7 had malignant effusion and 2 had transudates. For the 17 patients who completed the anti-TB treatment among the 23 patients with TP, 7 (41%) had RPT and 10 (59%) did not. The level of PF TIMP-1 in the patients with RPT (41,405.9±9,737.3 ng/mL) was significantly higher than that of those patients without RPT (29,134.9±8,801.8) at the completion of treatment (p=0.032). In 13 patients who were followed-up until a mean of 8±5 months after treatment, 2 (15%) had RPT and 11 (85%) did not. The level of PF TIMP-2 in the patients with RPT (34.4±6.5 ng/mL) was lower than that of those patients without RPT (44.4±15.5) at the point of the final follow-up (p=0.038).

Conclusion

The residual pleural thickening in TP might be related to the TIMP-1 and TIMP-2 levels in the pleural fluid.

Keywords: Matrix metalloproteinase, Pleural effusion, Residual pleural thickening, Tissue inhibitor of metalloproteinase, Tuberculous pleuritis

Figures and Tables

Figure 1
Gelatin zymograms of pleural effusions from parapneumonic effusions, tuberculous pleuritis, malignanteffusions and transudates. Gelatinolytic bands of 92 kD (proMMP-9), 85 kD (active MMP-9), 72 kD (proMMP-2), 66 kD (active MMP-2) were detected. Intense lytic bands corresponding to the MMP-9 were visible in parapneumonic effusion. MMP: metalloproteinase.
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Figure 2
Pleural fluid TIMP-1 levels according to the RPT in tuberculous pleuritis. The level of TIMP-1 in patients with RPT was significantly higher than that of those without RPT at the completion of treatment. Data are presented as box-plots, where the horizontal line represents the mean. TIMP: tissue inhibitor of metalloproteinase; RPT: residual pleural thickening.
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Figure 3
Pleural fluid TIMP-2 levels according to the RPT in tuberculous pleuritis. The level of TIMP-2 in patients with RPT was lower than that of those without RPT at the point of final follow-up. The mean follow-up period was 8±5 months after treatment. Data are presented as box-plots, where the horizontal line represents the mean. TIMP: tissue inhibitor of metalloproteinase; RPT: residual pleural thickening.
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Table 1
Clinical characteristics of patients with pleural effusions
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Data are presented as mean±standard deviation.

WBC: white blood cells; PF: pleural fluid; P/S ratio: pleural fluid to serum ratio; LDH: lactate dehydrogenase: ADA; adenosine deaminase; ESR: erythrocyte sedimentation rate; CRP: c-reactive protein.

*Kruskal-Wallis test were performed for difference among groups except male:female ratio.

Table 2
Levels of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in serum and pleural effusions
trd-65-7-i002

Data are presented as mean±standard deviation.

*Kruskal-Wallis test were performed for difference among groups.

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