Corticosteroids in the Treatment of Tuberculous Pleurisy : A Double-blind, Placebo-controlled, Randomized Study Christoph Wyser, Gerhard Walzl, Jan P. Smedema, François Swart, Emmerentia M. van Schalkwyk and Bernard W. van de Wal Chest 1996;110;333-338 DOI 10.1378/chest.110.2.333 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/110/2/333 Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1996by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692 Downloaded from chestjournal.chestpubs.org at Dankook University on May 8, 2012 1996 by the American College of Chest Physicians Corticosteroids in the Treatment of Tuberculous Pleurisy* A Double-blind, Placebo-controlled, Randomized Study Christoph Wyser, MD;* Gerhard Walzl, MD; Jan P. Smedema, MD; Frangois Swart, RN; Emmerentia M. van Schalkwyk, MD; and Bernard W. van de Wal, MD Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a stan¬ dard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were compa¬ rable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), betweengroup comparison showed no significant differences at any of the follow-up evaluations. The pro¬ portion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a ben¬ eficial effect on residual pleural thickening. (CHEST 1996; 110:333-38) Key words: computed tomography; lung function testing; prednisone; therapeutic aspiration; thoracoscopy; tuberculous pleurisy Abbreviations: CXR=chest radiograph; HRCT=high-resolution CT; PFT=pulmonary function testing; TB=tuberculosis or tuberculous; TLC=total lung capacity; VAS=visual analog scale of tuberculous (TB) pleurisy have Cjeveral studies that corticosteroid suggested adjuvant therapy may confer beneficial effects. These include a reduced a decrease in residual pleural thickening, morbidity, and more rapid reabsorption of pleural fluid.1"10 Howof Internal Medicine and Stellenbosch DepartmentUnit for Research (SUPUR), University of University PulmonaryTown, South Africa. Stellenbosch, Cape of Internal Medicine, Division of fCurrentiy at the Department Basel, Switzerland. Pulmonology, Kantonspital, Supported by the Tuberculosis 1992 fund, University of Stellen¬ bosch, Capetown, South Africa. received October 9, 1995; revision accepted March 28, Manuscript 1996. requests: Dr. C. Wyser, Department of Internal Medicine, Reprint Division of Pulmonology, Kantonspital, Petersgraben 4, 4031 Basel Switzerland *From the ever, routine corticosteroid therapy in the treatment of TB pleurisy is currently not widely used. One recent study by Lee and coworkers10 suggested that the addition of oral prednisolone to anti-TB che¬ motherapy inin40clinical patients resulted in a more rapid im¬ symptoms and resorption of provement fluid. The same study could not demonstrate that the occurrence of pleural thickening was decreased by the administration of corticosteroids. However, the num¬ ber of patients studied was relatively small and only a small amount of pleural fluid (50 mL) was aspirated To our knowledge, no other placebo-con¬ initially. trolled studies that examine this form of treatment have been published. Furthermore, in the current lit¬ erature, no consensus has been reached about the role Downloaded from chestjournal.chestpubs.org at Dankook University on CHEST May 8,/110 2012 / 2 / AUGUST, 1996 1996 by the American College of Chest Physicians 333 of therapeutic aspiration of the pleural fluid as part of the treatment of TB pleurisy. To examine this further, we conducted a doubleblind, placebo-controlled, randomized study to inves¬ tigate the beneficial effects of prednisone to reduce clinical symptoms and the occurrence of pleural after complete aspiration of the pleural thickening fluid. Materials and Patient Selection Between April 1994 and January Methods 1995, patients with exudative pleural effusions were recruited from the medical admission ward of Tygerberg Hospital, a university teaching hospital in Cape Town, South Africa. Thoracoscopy Thoracoscopy followed by bronchoscopy was performed under general anesthesia using standard methods.1112 Biopsy specimens of the parietal pleura were examined histologically and stained for acid-fast bacilli. Pleural fluid specimens and biopsy specimens sus¬ pended in saline solution were cultured for Mycobacterium tuber¬ culosis. Following thoracoscopy, an intercostal drain was inserted to evacuate any remaining air and fluid, and left in situ for up to 48 h. The macroscopic thoracoscopic findings were graded: type 1, with no or only a few nonspecific inflammation ofthe parietalpleura fibrinous adhesions; type 2, "classic" TB pleurisy13 with an inflamed reddish parietal pleura and multiple grayish-white nodules; and type 3, fibrous inflammation with a thickened parietal pleura and mul¬ tiple fibrous adhesions and/or loculations. At bronchoscopy, bron¬ chial lavage fluid was obtained for M tuberculosis culture. Patients with biopsy specimen proven TB pleurisy were eligible for entry into the study. The diagnosis of TB was confirmed by the presence of caseating granulomas with or without acid-fast bacilli on histologic study and/or a positive M tuberculosis culture. Other causes of pleural exudates such as pneumonia or malignancy were excluded. Patients with contraindications to corticosteroid use, such as diabetes mellitus, uncontrolled hypertension, peptic ulcer dis¬ ease, and empyema were also excluded, as were HIV-seropositive patients and those with neoplastic disease. Written consent was obtained from all subjects and the study was approved by the Uni¬ versity of Stellenbosch and Tygerberg Hospital Ethics Committee. Treatment Protocol All eligible patients were randomly assigned in a double-blind fashion to treatment with either prednisone plus standard anti-TB therapy (prednisone group) or placebo plus standard anti-TB ther¬ apy (placebo group). All patients were prescribed anti-TB treatment Guidelines, consisting of according to10the South African National rifampicin, mg/kg/d, isoniazid, 8 mg/kg/d, and pyrazinamide, 25 mg/kg/d as a fixed combination tablet (Rifater), and pyridoxine, 25 mg/kg/d for 6 months. In addition, prednisone, 0.75 mg/kg/d, or identical placebo tablets were administered. After 2 to 4 weeks, depending on the therapeutic response as assessed by a progressive reduction of symptoms and radiologic improvement, this was gradually reduced over a 2-week period by 5 mg/d in all patients. Follow-up Visits Patients were evaluated on hospital admission, 2 to 3 days after thoracoscopy (baseline of the study), and at 2, 4, 8, 12, 16, and 24 follow-up evaluation included the following: history, physical examination, chest radiograph (CXR) as needed, high-res¬ olution CT (HRCT) of the chest at 24 weeks and pulmonary func¬ tion tests (PFTs) at baseline, 12 weeks, and 24 weeks. weeks. The 334 Morbidity On hospital admission, patients were interviewed and informa¬ tion regarding illness duration, weight loss, pleuritic chest pain, and fever was recorded. Dyspnea, cough, night sweats, tiredness, appetite, pleuritic chest pain, and general well-being were each graded from 0 to 100 using a visual analog scale (VAS). A combined index with a maximum possible score of 700 was calculated.14 The degree of improvement in VAS scores was estimated by subtract¬ ing follow-up from baseline scores and expressed as a percentage of baseline values. New symptoms and clinical signs developing during the treat¬ ment period were documented as possible side effects. Blood glu¬ cose levels, body temperature, weight, and BP were recorded at each visit. CXR/HRCT of the Chest CXRs were performed in the posteroanterior, lateral, and lateral decubitus projection and obtained on hospital admission, after and during the outpatient follow-up visits as long as thoracoscopy, signs of pleural opacification persisted, but in all patients at base¬ line, 2 weeks, and 24 weeks. Two experienced readers, blinded to the clinical history, assessed the initial size and the recurrence of pleural effusion, the pleural thickness (in millimeters), and the ap¬ pearance of the costophrenic angle (sharp <90°, blunted >90°) as well as any pulmonary parenchymal involvement (infiltrate, cavity, scarring). A more than 2-mm pleural thickness (at the point of maximal thickness) at 24 weeks was defined as residual pleural thickening. The amount of pleural fluid at the initial presentation was regarded as small (less than one third of one hemithorax), moderate (between one third and half of one hemithorax), or large (more than half of one hemithorax). HRCT of the chest was obtained at three different levels, namely at the aortic arch, the midhilum, and just above the right hemidiaphragm. Maximal pleural thickness was measured adjacent to a rib.15 Pulmonary Function Tests Spirometry and body plethysmography were performed (using the Master-lab; Jaeger; Wuerzburg, Germany). Pulmonary function measurements were performed according to standard protocols and conformed to American Thoracic Society guidelines.16 The pre¬ dicted normal values were those proposed by Schoenberg and col¬ for spirometry, and by Goldman and Becklake18 for lung leagues1' volumes. On completion of treatment, the presence of restriction was defined as decreased total lung capacity (TLC) and FVC ofless than 80% of normal predicted. The degree of improvement for each patient was assessed by subtracting baseline from follow-up results and expressed as a percentage of the baseline values. Statistical Analysis Nonparametric statistical tests were applied because the variables were not normally distributed and the VAS can be considered an ordinal measurement. The significance of differences between baseline and follow-up data within each group was assessed using the Wilcoxon signed rank test (numeric or ordinal data) and the Stuart Maxwell test (ordinal data). For between-group comparisons, we used the Mann-Whitney U test (numeric or ordinal data) and a X2 test with 1 df (dichotomous nominal data). To control for type I error, the p values obtained were multiplied by the number of pairwise comparisons performed (Bonferroni). Significance was defined as p<0.05. Results Baseline Observations A diagnosis of TB pleurisy was made in 74 patients. Four patients were excluded from the efficacy analy- Downloaded from chestjournal.chestpubs.org at Dankook University on May 8, 2012 1996 by the American College of Chest Physicians Clinical Investigations noncompliance with the treat¬ ment, and one because of the detection of an esoph¬ ageal carcinoma at follow-up. Baseline demographic, clinical, and pathologic features of the remaining 70 patients are summarized in Table 1. Thirty-four pa¬ tients were randomized to the prednisone group and 36 to the placebo group. There were no significant differences between the treatment groups with regard to sex, age, duration of illness, size of the effusion, and microbiology results, or the histologic features of the appearance pleura at thoracoscopy. Fewer pa¬ tients in the prednisone group (21.2%) had parenchy¬ mal involvement than the placebo group (44.4%; p=0.06). Thoracoscopy At thoracoscopy, most patients demonstrated the classic macroscopic picture (type 2) of TB pleurisy. The distribution of the three different macroscopic mor¬ phologicafter patterns was similar in the two treatment randomization (Table 1). Reexpansion groups confirmed radiologically, occurred edema, pulmonary after 7 of 68 thoracoscopies (10.3%; 6 patients with effusions and 1 patient with a hydropneumotholarge but rax), resolved within hours of the initiation of ox¬ ygen therapy. Histology and Microbiology sis: three because of In the combined group of 70 patients, caseating granulomas occurred in 64 (92.8%) patients and nonin 5 (7.2%) patients. caseating granulomas occurred Four ofthe latter five patients had positive cultures for M tuberculosis and in one patient, acid-fast bacilli were one patient did not have a histologically. Only the and pleural biopsy, diagnosis of TB pleurisy was based on bilateral pleural lymphocytic exudates and a positive sputum culture for M tuberculosis. Positive M tuberculosis cultures of pleural biopsy specimens were obtained in 54 (78.3%) of 69 patients, and ZiehlNeelsen stains of biopsy specimens were positive in 34 patients (49.3%). In an additional two patients, cul¬ tures were positive in only the sputum and bronchial lavage fluid, respectively. Sixty-one (87.1%) patients had TB pleurisy diagnosed by either acid-fast bacilli on histologictissue. study or positive M tuberculosis cultures of pleural Morbidity A dramatic improvement in the patients' subjective assessment of their general condition was observed fluid as immediately after drainage of the pleural demonstrated by a marked decrease in the median combined VAS index score in both groups (Table 2). Although most patients (77.1%) had an elevated tem¬ than 37.5°C and SD: 38.3± seen perature greater (mean Table and Clinical Features of 1.Demographic Treatment at Baseline Groups Placebo Prednisone p Value No. of patients 36 Male, % 61.2 Race Mixed race, % 47.2 Black, % 52.8 Age, yr, mean±SD Duration of illness, wk, NS* 34 61.8 NS 2.9±2.7 NS NS NS NS 78.8 21.2 NS NS 2.9 14.7 82.4 NS NS NS 77.8 78.8 14.7 NS NS NS 91.7 Caseating granulomata 8.3 Noncaseating granulomata Ziehl-Neelsen positive 47.2 Appearance on thoracoscopy, % Type 1 5.7 Type 2 62.8 Type 3 31.5 93.7 6.1 51.5 NS NS NS 9.0 66.6 30.4 NS NS NS 32.4 67.6 32.8±12.5 32.9±13 prior 3.7±2.2 hospital admission, mean±SD Pleuritis only, % 55.6 Pleuritis and pulmonary TB, % 44.4 Initial size of pleural effusion (CXR), % to Small 0 Moderate 13.9 Large 86.1 TB culture positive, % Pleural fluid 13.9 Pleural biopsy specimen Bronchial lavage 8.6 Histology, % *NS=not significant. 0.83°C), only 1 patient had an elevated temperature 3 days after drainage of the pleural fluid and before the initiation of treatment with the trial medication. Improvement in the individual VAS and combined VAS index scores became statistically significantly dif¬ ferent from baseline for the first time at 8 weeks in the prednisone group and at 12 weeks in the placebo group. However, differences in the degree of improve¬ ment in VAS scores between the 2 groups were not statistically significant at any of the follow-up evalua¬ tions (Table 2). Furthermore, the most dramatic Table 2.Morbidity.VAS* No. of patients Admission Baseline 2 wk 4 wk 8 wk 12 wk 16 wk 24 wk Placebo Prednisone 36 434 (298-584) 57 (14-150)* 55 (0-115) 40 (9-97) 20 (0-65) 2 (0-65)* 0 (0-12)* 0 (0-0)* 34 449 (340-610) 58 (18-133)f 51 (11-85) 11 (0-105) 3 (0-43)* 0 (0-15)* 0 (0-20)* 0 (0-0)* p Value J NS NS NS NS NS NS NS NS Visual analog scale (median combined index score of well-being, ap¬ petite, night sweats, pleuritic chest pain, tiredness, dyspnea, and cough) at different evaluation time points. NS=not significant; /=comparison between placebo and prednisone group. admission. *p<0.0001 comparedto tobaseline. *p<0.05 compared * Downloaded from chestjournal.chestpubs.org at Dankook University on CHEST May 8,7110/2/ 2012 AUGUST, 1996 1996 by the American College of Chest Physicians 335 Table 3.Pleural Thickening 10.4±5.8 8.4±6.3 8.2±7.0 8.4±7.6 2.5±3.7 4.3±5.1 17(53.1) 14(41.1) NS NS NS NS 9.4J 4.2 6.3d 3.3 5.6J 4.3 5.1d 4.3 2.U :2.7 3.0±3.' NS NS NS NS NS NS 34 17 (50) 36 18 (50) 21 (60) 10 (27.8) No. of patients Residual pleural thickening (%) (CXR) Residual pleural thickening (%) (CT scan) Blunted costophrenic angle (%) (CXR) Pleural thickness, mm, mean±SD (CXR) At baseline At 2 wk At4wk At 8 wk At 24 wk Pleural thickness at 24 wk, mm p Value Prednisone Placebo (33)* (19)* (23)* (17)* (mean±SD) on CT scan * Number of patients in whom CXRs were taken. improvements in the VAS scores were observed after complete drainage of the effusion, before randomiza¬ tion. Body weight at 4, 8, and 24 weeks after initiation of treatment showed a significant but comparable in¬ crease in the 2 groups (mean weight gain at 24 weeks: 5.3 kg in the placebo group and 5.8 kg in the group). prednisone At 6 months, all patients were cured according to clinical and radiologic data and treatment was subse¬ Drug resistance necessitating a quently instopped. treatment was not observed in the anti-TB change any patient. Radiography and HRCT of the Chest At baseline, only one patient had bilateral pleural more than one half the effusions. In 59 cases (84.3%), volume of the hemithorax was involved, and in 24 (34.3%) cases coexisting pulmonary lesions could be seen. The pulmonary involvement included patchy infiltrates with or without small cavitation or scarring. One patient had a hydropneumothorax on hospital admission. CXR at 24 weeks revealed residual pleural thicken¬ ing on the lateral chest wall in 17 (50%) of the 34 patients and 18 (50%) of the 36 prednisone-treated with treated placebo (Table 3). HRCT of the patients chest showed residual pleural thickening in 17 (53.1%) of 32 patients in the prednisone group and 21 (60%) of 35 patients in the placebo group. Three patients did not have a HRCT at 24 weeks. There was no statisti¬ difference in the degree of residual cally significant thickness on CXR and HRCT (p=0.52). pleural In patients with thoracoscopic findings of acute in¬ flammation (type 1 and 2), residual pleural thickening occurred in 10 of 21 patients (42.8%) in the prednisone group and in 14 of 24 placebo-treated patients (58.8%). Seven of 10 patients (70%) in the prednisone group and 6 of 10 patients (60%) in the placebo group with thoracoscopic evidence of fibrous inflammation (type 336 3) showed residual pleural thickening. These differ¬ ences were not statistically significant. After complete aspiration, no patient experienced a recurrence of pleural fluid in either treatment group, as assessed by CXR (posteroanterior, lateral, and lateral decubitus projections). The intrapulmonary le¬ sions, when present, appeared to resolve more slowly than the pleural abnormalities. Lung Function Testing At baseline, both groups had mild to moderate lung impairment (Fig 1); mean±SD TLC was 76.7±12% of predicted normal values in the pred¬ nisone group and 77.8±22.9% of predicted normal values in the placebo group; FVC was 59.1 ± 16.7% and 57.9±12.8%, respectively. A significant improvement of TLC in the respective groups was noted after 3 function months (p<0.0001 prednisone group; p=0.009 placebo and 6 months (p<0.0001 for both groups). A group) similar response was observed in FVC. The groups did not differ significantly with respect to the degree of improvement in PFT results (p=0.39 for TLC and p=0.65 for FVC). At 24 weeks, the difference in the proportions of patients with restrictive PFT results (33.3% prednisone group; 39.4% placebo group) was not significant (p=0.72). Side Effects No serious side effects observed except for prednisone group epigastric pain (four patients and three patients in the placebo group). None of the patients had evidence of impaired glucose tolerance. were in the Discussion Our study shows that oral prednisone does not have beneficial effect on residual pleural thickening in the treatment of TB pleurisy. This is in accordance with the study by Lee and coworkers,10 who had conducted a similar study, with the exception of the complete a Downloaded from chestjournal.chestpubs.org at Dankook University on May 8, 2012 1996 by the American College of Chest Physicians Clinical Investigations CHANGE IN TLC WITH TREATMENT 12 WEEKS BASELINE 24 WEEKS CHANGE IN FVC WITH TREATMENT 3100 I 70 u. 50 h 12 WEEKS BASELINE Figure 1. pleural effusion is best managed by complete drainage. In our opinion, thoracoscopy presents the best approach for both diagnosis and simultaneous complete drainage of the effusion of TB pleurisy. In the absence of thoracoscopy facilities, drainage should be attempted as completely as possible by needle tho¬ racentesis. The incidence of residual pleural thicken¬ ing in our sample was comparable to that of previous reports.219 In contrast to research by Hulnick and coworkers,20 HRCT was not found to be more sensitive than CXR in diagnosing pleural thickening, since the difference in diagnostic yield of the two methods was not statistically significant. Assessment of residual pleural thickening by HRCT or CXR failed to reveal any beneficial effect of additional prednisone in pre¬ venting this complication. The final radiologic outcome of patients with the various macroscopic pleural appearances at thoracos¬ copy showed no significant difference between pred¬ nisone- and placebo-treated patients either for the acute inflammatory (type 1 and 2) or fibrous inflam¬ matory (type 3) types. Clinically and functionally significant sequelae of pleural thickening are rare when TB pleurisy is treated with standard anti-TB chemotherapy and drained neither of our treatment completely. It is of note that recurrence of their pleural groups experienced any effusions. Lung function impairment as a result of pleural is an occasional sequela of TB pleural thickening effusion. In keeping with research on children by Filler and Porter,21 our study found that the addition of did not influence the final PFT result out¬ prednisone come of the disease in an adult sample. Both groups demonstrated a significant improvement in all PFT parameters after 3 and 6 months, but group differences were not significant. Both groups demonstrated a sig¬ in with a restrictive nificant number of a in 70 patients Changes in TLCareand FVC withastreatment expressed mean±SD. with TB pleurisy. Results fluid on hospital admission. In that drainagetheofaddition pleuralofcorticosteroids resulted in a more study, in clinical rapid improvement symptoms. We also ob¬ served a statistically significant improvement in the VAS scores compared with baseline occurring earlier in the prednisone group. However, there was no sig¬ nificant difference between the two groups at any of the follow-up evaluations. We therefore believe that the statistically earlier symptom relief in our pred¬ nisone group was clinically irrelevant. The main factor responsible for symptomatic im¬ provement in all patients was the complete early drainage of the effusion at the time of the thoracos¬ copy. Although a "placebo" effect attributable to the contribute to the diagnostic procedure per sewecould symptomatic improvement, believe that the evac¬ uation of the effusion was the principal reason. This is supported by the observation that the body tempera¬ ture normalized in most patients before initiation of therapy. The reabsorption of pleural fluid in TB pleu¬ risy can take up to a year10 if complete drainage is not performed. In the study by Lee and coworkers,10 the average reabsorption rates of pleural effusions were 54.5 days in prednisolone-treated patients and 123.2 days in placebo-treated patients. Better assessment of the underlying lung parenchyma after drainage is a further consideration in favor of the complete removal of pleural fluid. Taken together, these data suggest that TB patients pattern PFT results at 6 months. Whether this reflects resid¬ ual pleural disease or other factors is not clear. A con¬ tinued follow-up of all patients is being conducted at 6-monthly intervals to detect the development of late fibrothorax or relapse of active TB. Side effects ascribed to prednisone are well recog¬ nized and occurred in few patients in both treatment groups, the most important being epigastric pain. Body increased significantly in both groups during weight treatment. Withdrawal of prednisone therapy due to adverse effects was not necessary in any patient. A of the addition of corticosteroid potential concern be the dissemination or progression of therapy might TB. This was not observed in any of our patients, which is in accordance with earlier studies.22'23 We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment Downloaded from chestjournal.chestpubs.org at Dankook University on May 2012 / 2 / AUGUST, 1996 CHEST8,/110 1996 by the American College of Chest Physicians 337 of TB pleurisy. The addition of short-term oral pred¬ nisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural diickening. The question whether achievement of early drainage is superior to no drain¬ age for the long-term outcome has not been answered by our study and would necessitate further controlled studies. ACKNOWLEDGMENTS: We acknowledge the help and encour¬ T.R. Joubert and Drs. H. Welke and R. Gie in the agement of Prof. of this project. We are indebted to Z. Buttner, M. development and J. Mouton for their tireless work as research assistants, Plaatjies, to M. Engelbrecht for randomization and drug preparation, to Prof. P.G. Bardin and Drs. C. Corbett, }.}. Jansen, andt.T. Bolliger for and to Dr. N. Smuts Tor re¬ their critical review of this porting the HRCT. manuscript References Aspin J, O'Hara H. Steroid-treated tuberculous pleural effusions. Br J Tuber 1958; 52:81-3 2 Grewal KS, Dixit RP. A comparative study of therapeutic regimens with and without corticosteroids in the treatment of tuberculous pleural effusion. J Indian Med Assoc 1969; 52:514-16 3 Damany SJ, Shah KT. Treatment of pleural effusion with and without triamcinolone in addition to usual antituberculosis che¬ motherapy. J Indian Med Assoc 1968; 51:391-93 4 Mathur KS, Prasad R, Mathur JS. Intrapleural hydrocortisone in tuberculous pleural effusion. Tubercle I960; 40:358-62 5 Mathur KS, Mathur JS, Sapru RP. Treatment of tuberculous Scand 1964; 44:303-09 10 Lee CH, Wang WJ, Lan RS, et al. 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Chest 1995; 107:1621-30 Downloaded from chestjournal.chestpubs.org at Dankook University on May 8, 2012 1996 by the American College of Chest Physicians Clinical Investigations Corticosteroids in the Treatment of Tuberculous Pleurisy : A Double-blind, Placebo-controlled, Randomized Study Christoph Wyser, Gerhard Walzl, Jan P. Smedema, François Swart, Emmerentia M. van Schalkwyk and Bernard W. van de Wal Chest 1996;110; 333-338 DOI 10.1378/chest.110.2.333 This information is current as of May 8, 2012 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/110/2/333 Cited Bys This article has been cited by 12 HighWire-hosted articles: http://chestjournal.chestpubs.org/content/110/2/333#related-urls Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. 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