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
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ISSN:0012-3692
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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
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May 8,/110
2012
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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-
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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
*
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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
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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
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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
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