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Corticosteroids for tuberculous pleurisy

  1. Mark E Engel1,*,
  2. Patrice T Matchaba2,
  3. Jimmy Volmink3

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 21 JAN 2009

Assessed as up-to-date: 23 JUL 2007

DOI: 10.1002/14651858.CD001876.pub2

Database Title

Additional Information

How to Cite

Engel ME, Matchaba PT, Volmink J. Corticosteroids for tuberculous pleurisy. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD001876. DOI: 10.1002/14651858.CD001876.pub2.

Author Information

  1. 1

    Faculty of Health Sciences, University of Cape Town, Department of Medicine, Observatory, South Africa

  2. 2

    Novartis Pharmaceuticals Corporation, East Hanover, USA

  3. 3

    University of Stellenbosch, Faculty of Health Sciences, Tygerberg, South Africa

*Mark E Engel, Department of Medicine, Faculty of Health Sciences, University of Cape Town, J47 Old Main Building, Groote Schuur Hospital, Observatory, 7925, South Africa. mark.engel@mrc.ac.za.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 21 JAN 2009

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ARTICLE TOOLS

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It is a major contributor to global morbidity and mortality causing close to an estimated two million deaths each year (WHO 2005). While tuberculosis infection of the lung (pulmonary tuberculosis) is most common, tissues outside of the lungs, such as pericardium (membrane lining the heart) and meninges (membrane lining the brain), may also be infected (extrapulmonary tuberculosis). Extrapulmonary tuberculosis has occurred more frequently in recent years (Harries 1990), and this increase is believed to be attributable to co-infection with human immunodeficiency virus (HIV) (Song 2003; Yang 2004).

 

Definition and incidence

Pleurisy is the name given to an inflammation of the pleura, a semi-permeable membrane covering the lungs and lining the chest wall. The form of pleurisy caused by tuberculosis infection usually results in an abnormal accumulation of fluid in the pleural space between the lungs and chest wall (pleural effusion). Tuberculous pleural effusion is thought to be a delayed hypersensitivity reaction following a recent mycobacterial infection of the pleura (Rossi 1987). Apart from lymph node tuberculosis, tuberculous pleural effusion is the most frequent extrapulmonary manifestation of tuberculosis, representing about 20% of extrapulmonary tuberculosis (Sharma 2004). In one series of 1700 tuberculosis patients, 70 cases of tuberculous pleural effusion were identified (Seibert 1991). Batungwanayo 1993 reported that a high percentage (83%) of people with tuberculous pleural effusion were also HIV infected. This association is thought to be a function of the higher burden of micro-organisms resulting from an impaired host response (Relkin 1994), though detection bias resulting from more opportunity for diagnosis of tuberculous pleural effusion in HIV-positive individuals may also be a contributory factor (Frye 1997).

 

Prognosis

Clinically, tuberculous pleural effusion presents as an acute illness consisting of cough, fever, chest pain, and dyspnoea (Morehead 1998). Although it can resolve spontaneously within a few weeks or months, medical treatment is believed to speed resolution of the effusion and reduce long-term complications such as fibrosis and thickening of the pleura that can further restrict lung function. Therapeutic options for pleural space infections include intravenous antibiotic administration, chest tube drainage, intrapleural administration of a fibrinolytic agent to dissolve fibrous adhesions, thoracotomy to remove fibrinous and infected tissue, and steroid therapy (Chapman 2004). The theoretical basis for using corticosteroids is that they suppress the inflammatory response believed to be responsible for tuberculous pleural effusion. One corticosteroids is prednisone, which is converted in the liver into the active drug, prednisolone. Prednisone or prednisolone is recommended at a daily dose of about 1 mg/kg gradually reducing after one to two weeks, with a total treatment course sometimes being as long as three months (Lemaistre 1951; Mathur 1960; Morehead 1998; Blumberg 2003).

 

Debates

Studies of adjunctive corticosteroids for the treatment of tuberculous pleural effusion show conflicting results. Non-randomized studies in the pre-HIV era found that corticosteroids led to more rapid resolution of the effusion and reduced likelihood of residual pleural thickening and pleural adhesions (Menon 1964; Singh 1965). An observational study of 165 HIV-positive participants with tuberculous pleural effusion found that prednisolone was associated with decreasing rates of lymphadenopathy and cough as well as improved survival (Elliott 1992; Elliott personal communication).

In contrast, a critical appraisal of published studies demonstrated beneficial effects of corticosteroids on acute symptoms, but it found no benefit for chronic endpoints such as fibrosis, irrespective of dose (Dooley 1997). The authors noted that many of the studies lacked rigour and clinical correlations. Furthermore, the previous version of this Cochrane Review, which included three randomized controlled trials (with a total of 236 participants), concluded that there was insufficient evidence for the effectiveness of adjunctive corticosteroids on lung function, pleural adhesions, residual pleural thickening, residual fluid, and acute clinical symptoms (Matchaba 2000). No HIV-related data were available at the time.

In addition to the uncertainty about benefits of corticosteroid therapy, there is concern about potential risks. In immunocompromized patients, such as those infected with HIV, corticosteroids may further constrain the immune system leading to an increased frequency of opportunistic infections and tumours such as Kaposi sarcoma, a vascular tumour accompanied by numerous unconnected lesions of the skin and thought to be associated with human herpes virus-8 infection (Ensoli 2001). More generally, adverse effects of corticosteroids such as fluid retention and gastrointestinal disturbances have also been documented in people with tuberculosis (Anonymous 1983).

Our review aimed to appraise the existing evidence on the benefits and harms of corticosteroids regardless of HIV status. The study hypothesis was that in people with tuberculous pleurisy, there was no difference in the effects of corticosteroid therapy and placebo on mortality and morbidity.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

To evaluate the effects of adding corticosteroids to drug regimens for tuberculous pleural effusion.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomized and quasi-randomized controlled trials.

 

Types of participants

People diagnosed with tuberculous pleurisy by chest x-ray (as defined by trial authors) plus any of the following: pleural biopsy for histology; Ziehl-Neelsen staining and/or culture of sputum; pleural fluid; or pleural biopsy.

 

Types of interventions

 

Intervention

Any corticosteroid.

 

Control

No treatment, placebo, or other active treatment.

Both groups should receive the same antituberculous drug regimen.

 

Types of outcome measures

 

Primary

  • Death from any cause.
  • Improvement in respiratory function.

 

Secondary

  • Reabsorption of pleural effusion (as defined by authors).
  • Presence of pleural thickening.
  • Presence of pleural adhesions.
  • Improvement in clinical symptoms and signs.
  • Adverse events.
  • HIV-associated events.

 

Search methods for identification of studies

We attempted to identify all relevant trials regardless of language or publication status (published, unpublished, in press, and in progress).

We searched the following databases using the search terms and strategy described in Appendix 1: Cochrane Infectious Diseases Group Specialized Register (May 2007); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (2007, Issue 2); MEDLINE (1966 to May 2007); EMBASE (1974 to May 2007) and LILACS (1982 to May 2007). We also searched Current Controlled Trials (May 2007) using 'tuberculosis' and 'pleur*' as search terms.

We also checked the reference lists of all studies identified with the above methods.

 

Data collection and analysis

 

Selection of studies

ME and JV screened the results of the search for potentially relevant studies. We independently applied eligibility criteria and resolved differences in opinion through discussion. Where the abstracts were unclear or if there was any other reason for uncertainty, we obtained the full article before making a decision on study eligibility. We obtained the assistance of translators when abstracts were not available in English. We excluded studies that did not meet our criteria and stated the reason.

 

Data extraction and management

Using a specially designed data extraction form, ME extracted information for each trial with JV independently cross checking the data. For each trial, we collected information regarding trial characteristics, intervention characteristics, participant characteristics, and outcome measures. We resolved differences in the extracted data by referring to the original articles and through discussion. ME entered the data into Review Manager 5.

 

Assessment of risk of bias in included studies

ME and JV independently assessed the quality of included trials. We evaluated the generation of the allocation sequence and allocation concealment as adequate, unclear, or inadequate (Jüni 2001). We indicated who was blinded (patients, clinicians, or outcome assessors) in each of the trials. Inclusion of randomized participants was considered adequate if greater than 80% of all participants randomized into the trial were included in the analysis. We presented the results of the quality assessment in a table.

 

Data synthesis

ME analysed the data using Review Manager 5, and JV checked the analysis. We pooled estimates of effect using risk ratio (RR) as a measure of effect for dichotomous outcomes and mean difference (MD) for continuous outcomes, and presented these with 95% confidence intervals (CI). We assessed heterogeneity by visually examining the forest plot and by the statistical chi-square test for heterogeneity using a 10% level of significance. We used the fixed-effect model for the meta-analysis, except for instances of statistical heterogeneity when we used the random-effects model.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

 

Trial selection

Forty-eight studies were screened of which 26 published trials were identified for possible inclusion into the review. Six trials met our inclusion criteria (see 'Characteristics of included studies'). The reasons for excluding studies, initially considered relevant, are provided in the 'Characteristics of excluded studies'.

 

Participants and location

The six trials included 633 participants, with a range of 45 to 197 per trial. They were conducted in Taiwan (1 trial), Spain (1 trial), South Africa (1 trial), Korea (2 trials), and Uganda (1 trial). Participants were adults except in one trial (Galarza 1995), which studied people aged 11 years and older. All trials included participants of both sexes; 59% were male, with a range of 51% to 64% across trials. One trial included only HIV-positive participants (Elliott 2004), two excluded HIV-positive participants (Galarza 1995; Wyser 1996), while the other trials reported HIV status as negative or not determined. In all of the trials, participants with pleural effusion had tuberculosis confirmed by a laboratory diagnosis; in one trial only 63% of participants had a confirmatory pathological or microbiological diagnosis (Galarza 1995).

 

Follow up

The follow-up period varied, ranging from 24 weeks (Wyser 1996) to 46 months (Galarza 1995). Bang 1997 and Lee 1999 did not mention the length of follow up.

 

Interventions

Four trials compared either prednisone or prednisolone with placebo as an adjunct to an established antituberculous regimen containing isoniazid and rifampicin. Bang 1997 and Lee 1999 did not use any comparative treatment.

All but two trials gave corticosteroids orally in different daily doses ranging from 0.75 to 1.0 mg/kg/day for two weeks; Bang 1997 and Lee 1999 used injection but did not clearly state the dosages. Pleural fluid was aspirated before randomization in all but one trial (Galarza 1995) in which aspiration was conducted before patient discharge.

 

Outcomes

None of the trials reported on all eight outcome measures chosen for this review. The outcome measures reported included death from any cause (1 trial), improvement in respiratory function (2 trials), reabsorption of pleural effusion (3 trials examined the outcome at 4 weeks; 4 trials examined the outcome at 8 weeks), presence of pleural thickening (4 trials) and adhesions (2 trials), improvement in clinical symptoms and signs (3 trials), adverse events (6 trials), and HIV-associated events (1 trial).

 

Risk of bias in included studies

See 'Characteristics of included studies' for details of individual trials.

 

Generation of allocation sequence

All trials were reported as randomized. Elliott 2004 explicitly stated that random numbers were computer-generated, which we considered as adequate. The other trials did not indicate how the sequence was generated.

 

Allocation concealment

One trial gave a detailed report the method it used, which we considered to be adequate; briefly, prednisolone and matching placebo tablets were packaged in identical sequentially numbered plastic bags labelled with the randomization code by two people unrelated to the trial (Elliott 2004). The rest did not provide sufficient information to assess this aspect of study quality.

 

Blinding

Four trials were described as double blind and placebo controlled. The remaining two trials did not mention blinding (Bang 1997; Lee 1999). Wyser 1996 and Elliott 2004 specifically mentioned that those assessing outcomes had been blinded.

 

Inclusion of all randomized participants

The trials included all participants in the analysis (Galarza 1995; Lee 1999) or included most participants (all adequate): 98.8% (Bang 1997), 98.5% (Elliott 2004), 89% (Lee 1988), and 95% (Wyser 1996).

 

Effects of interventions

 

Primary outcomes

 

Death from any cause

Only Elliott 2004 assessed the risk of death, finding no reduction in mortality with corticosteroids (194 participants,  Analysis 1.1).

 

Improvement in respiratory function

Two trials with 191 participants measured improvement in respiratory function and found no difference between the groups. In Galarza 1995, mean forced vital capacity (FVC) was 95% in both the treatment and control groups at the end of treatment. Wyser 1996 reported no significant difference in the degree of improvement in pulmonary function between the prednisone and placebo groups, (total lung capacity: P = 0.39; FVC: P = 0.65) up to six months. A meta-analysis could not be performed due to insufficient reported data.

 

Reabsorption of pleural effusion

 
At 4 weeks

Three trials reported results for this outcome (Galarza 1995; Bang 1997; Elliott 2004). Corticosteroid use resulted in a reduced risk of residual fluid being present at four weeks (RR 0.76, 95% CI 0.62 to 0.94; 394 participants,  Analysis 1.2).

 
At 8 weeks

Given that there was heterogeneity in the effects across the four trials that measured this outcome at eight weeks (chi-squared test = 18.71, P = 0.0003), we used the random-effects model and found no statistically significant benefit with corticosteroids (399 participants,  Analysis 1.3.) In Wyser 1996, complete drainage of pleural fluid was undertaken on admission and effusions did not recur in either group during the course of the study.

 
Presence of pleural thickening

Corticosteroids were associated with a statistically significant reduction in residual pleural thickening (RR 0.69, 95% CI 0.51 to 0.94; 309 participants, 4 trials,  Analysis 1.4).

 
Presence of pleural adhesions

We found no statistically significant reduction in the risk of pleural adhesions (123 participants, 2 trials,  Analysis 1.5).

 
Improvement in clinical symptoms and signs

Time to disappearance of symptoms was significantly shorter in participants receiving corticosteroids (MD -4.32 days, 95% CI -7.44 to -1.20; 123 participants, 2 trials, Analysis 01.06). Furthermore, Lee 1988 demonstrated that fever, chest pain, and dyspnoea were more likely to be resolved by day seven post-treatment in participants on corticosteroids compared to placebo (RR 0.06, 95% CI 0.00 to 0.99; 40 participants,  Analysis 1.7). In this trial, all participants were asymptomatic within 14 days. Wyser 1996 reported no differences in the degree of improvement in symptoms (individual or combined Visual Analogue Scores) or in mean weight gain at regular follow-up evaluations over a 24-week period.

 
Adverse events

Overall, more people in the corticosteroid group experienced adverse events leading to the discontinuation of treatment (RR 2.80, 95% CI 1.12 to 6.98; 586 participants, 6 trials,  Analysis 1.8). In Elliott 2004, nine of 97 participants in the treatment group and two of 97 participants in the placebo group required stoppage of treatment due to hyperglycaemia, hypertension, herpes zoster, or candida infections. Epigastric pain was reported by Wyser 1996 (4/34 participants on corticosteroid therapy and 3/36 on placebo), Lee 1988 (1/21 participants on corticosteroids and 0/19 in the placebo group), and Bang 1997 (1/33 participants on corticosteroids and 0/50 participants in the control group). The same participant in Lee 1988 developed a 'moon' face and lower limb oedema.

 
HIV-associated events

Elliott 2004, which included only HIV-positive participants, reported a trend towards an increase in the incidence of Kaposi's sarcoma in participants receiving corticosteroids (RR 13.00, 95% CI 0.74 to 227.63; 194 participants,  Analysis 1.9). This trial found no evidence of an effect of corticosteroids on HIV-associated infections including cryptococcal meningitis, oesophageal candidiasis, herpes simplex, herpes zoster, oral thrush, and gastroenteritis.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

The evidence base on the effects of corticosteroids administered to people with tuberculous pleurisy remains small, with only six trials evaluating 633 participants.

Only the trial of HIV-positive people evaluated mortality (Elliott 2004). Due to the small number of events in this trial, the confidence interval around the effect estimate is wide thus precluding firm conclusions about the effect of corticosteroids on death. The other primary outcome we aimed to assess was improvement in respiratory function, but neither trial that focused on this endpoint provided evidence for benefit with corticosteroids, and there was insufficient information to allow us to perform a meta-analysis.

Compared to placebo or no corticosteroids, adjunctive corticosteroids appear to hasten the reabsorption of pleural fluid with trials finding an overall reduction of 24% in the risk of residual fluid four weeks after the start of treatment. Similarly, there is evidence that corticosteroids reduce the likelihood of pleural thickening at the end of treatment. The clinical importance of these findings is unclear particularly in view of the lack of outcome data on respiratory function and the mixed findings with respect to resolution of symptoms and signs in the acute phase of the condition.

Concern has been expressed that corticosteroid-induced immunosuppression may increase the risk of opportunistic infections in HIV-infected participants (Lionakis 2003). To date only one trial has investigated corticosteroid use in this group (Elliott 2004). In this trial there was a trend towards an increase in oesophageal candidiasis, but no statistically important differences were found for any of the opportunistic infections assessed. Also, the risk of Kaposi sarcoma was found to be substantially higher in the corticosteroid group − a potentially important finding that requires confirmation in future trials.

In interpreting the above findings a number of issues need to be kept in mind. Firstly, all six included trials are small and it is possible that clinically significant differences may have been missed. For example, in the trial reporting on mortality (Elliott 2004), 356 participants per study arm would be needed to ensure sufficient power to demonstrate a 10% reduction in mortality from the baseline rate of 39/97. Secondly, while the methodological quality of the available trials seems reasonably good, we did not have sufficient information to assess the completeness of allocation concealment in five of the six trials, a factor known to have a substantial influence on internal validity. A third issue concerns the diagnosis of tuberculous pleural effusion: in the Galarza 1995 trial, one-third of participants had no microbiological confirmation with no indication as to the distribution of unconfirmed diagnoses in the study arms. Fourthly, the optimal dose of adjunctive corticosteroids is not known. Rifampicin induces the liver metabolism of corticosteroids, thus increasing their plasma clearance (McAllister 1983). It has been suggested that higher than usual doses be used to compensate for the reduced availability of corticosteroids to the tissues (Commerford 1991). Finally, all but one of the trials were carried out in the pre-HIV era and thus the generalizability of the current evidence to most participants with tuberculous pleural effusion in low- and middle-income countries who are co-infected with HIV is limited.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

 

Implications for practice

The included randomized controlled trials provide insufficient data to support evidence-based recommendations regarding the use of corticosteroids on risk of death or improvement in lung function in participants with tuberculous pleural effusion, regardless of HIV status. There is also no rigorous evidence to support the use of corticosteroids in people co-infected with HIV, in whom there is some cause for concern that corticosteroids may increase the risk of Kaposi sarcoma.

 
Implications for research

Randomized controlled trials with sufficient statistical power to evaluate the effects of corticosteroids on mortality and key morbidity outcomes are needed. Careful attention should be given to adverse effects, particularly in HIV-positive people.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Vittoria Lutje (Cochrane Infectious Diseases Group) for kindly conducting searches for us and assisting with translation; Lize Van der Merwe (SA Medical Research Council, South Africa) for statistical advice.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
Download statistical data

 
Comparison 1. Corticosteroids versus control (placebo or no steroids)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Death from any cause1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
 2 Residual fluid at 4 weeks3394Risk Ratio (M-H, Fixed, 95% CI)0.76 [0.62, 0.94]
 3 Residual fluid at 8 weeks4399Risk Ratio (M-H, Random, 95% CI)0.72 [0.46, 1.12]
 4 Presence of pleural thickening4309Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.51, 0.94]
 5 Presence of pleural adhesions2123Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.51, 1.11]
 6 Days to improvement in symptoms2123Mean Difference (IV, Fixed, 95% CI)-4.32 [-7.44, -1.20]
 7 Clinical symptoms after 7 days1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 8 Adverse events leading to treatment discontinuation6586Risk Ratio (M-H, Fixed, 95% CI)2.80 [1.12, 6.98]
 9 HIV-associated events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    9.1 Cryptococcal meningitis
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    9.2 Oesophageal candidiasis
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    9.3 Gastroenteritis
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    9.4 Herpes simplex
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    9.5 Herpes zoster
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    9.6 Kaposi sarcoma
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    9.7 Oral thrush
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Appendix 1. Search methods: detailed search strategies

Search setCIDG SRaCENTRALMEDLINEbEMBASEbLILACSb
1tuberculosistuberculosisTUBERCULOSISTUBERCULOSIStuberculosis
2TBsteroidstuberculosistuberculosisTB
3steroidscorticosteroidsTBTB1 or 2
4corticosteroidsglucocorticoids1 or 2 or 31 or 2 or 3steroids
5dexamethasonehydrocortisonesteroid*steroidshydrocortisone
6hydrocortisoneprednisoloneSTEROIDSSTEROIDSdexamethasone
7prednisolonedexamethasonecorticosteroidscorticosteroidsprednisolone
8—2 or 3 or 4 or 5 or 6 or 7glucocorticoidsglucocorticoids4 or 5 or 6 or 7
9—1 and 8hydrocortisonehydrocortisone3 and 8
10——dexamethasonedexamethasone—
11——prednisoloneprednisolone—
12——prednisonemethylprednisone—
13——methylprednisone5 or 6 or 7 or 8 or 9 or 10 or 11 or 12—
14——5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 134 and 13—
15——4 and 14Limit 13 to human—
16——Limit 15 to human——


aCochrane Infectious Diseases Group Specialized Register.
bSearch terms used in combination with the search strategy for retrieving trials developed by The Cochrane Collaboration (Higgins 2006); upper case: MeSH or EMTREE heading; lower case: free text term.

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Last assessed as up-to-date: 23 July 2007.

DateEventDescription
10 September 2008AmendedConverted to new review format with minor editing.


 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Protocol first published: Issue 4, 1997
Review first published: Issue 3, 1998

DateEventDescription
24 July 2007New citation required and conclusions have changedReview title changed from 'Steroids for treating tuberculous pleurisy'; search updated to May 2007; general updates and modifications were made to most sections with the methods and results sections of the review entirely revised; 'Types of interventions' modified to include any corticosteroid used in combination with antituberculos treatment; 'Types of outcome measures' modified to evaluate death from any cause and improvement in respiratory function as primary outcomes, secondary outcomes updated to include HIV-associated events, "worsening of the parenchymal disease" excluded, and adverse drug effects changed to adverse events. Three new trials added, one of which consisted exclusively of HIV-positive participants. Despite all this, the conclusions remain unchanged.
28 April 2006AmendedNew studies sought but none found.
28 February 2005AmendedNew studies found and included or excluded.


 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Mark Engel (ME) took responsibility for the update of this review. ME developed the data extraction forms with Jimmy Volmink (JV) providing input. ME and JV selected the trials for inclusion in the review, extracted the data, and assessed trial quality. ME contacted authors for additional information. ME entered the data and conducted the analysis. ME wrote the first draft of the review with JV contributing to the final text and analysis. Patrice Matchaba (PM) contributed to the discussion. ME and JV are responsible for maintaining the review.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Internal sources

  • South African Medical Research Council, South Africa.
  • University of Cape Town, South Africa.

 

External sources

  • Department for International Development, UK.

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Bang 1997 {published data only}
  • Bang JS, Kim MS, Kwak SM, Cho CH. Evaluation of steroid therapy in tuberculous pleurisy - A prospective, randomized study. Tuberculosis and Respiratory Disease 1997;44(1):52-8.
Elliott 2004 {published and unpublished data}
  • Elliott AM, Luzze H, Quigley MA, Nakiyingi J, Kyaligonza S, Namujju PB, et al. A randomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis. Journal of Infectious Diseases 2004;190(5):869-78.
Galarza 1995 {published data only}
Lee 1988 {published data only}
Lee 1999 {published data only}
  • Lee BH, Jee HS, Choi JC, Park YB, An CH, Kim JY, et al. Therapeutic effect of prednisolone in tuberculous pleurisy - A prospective study for the prevention of the pleural adhesion. Tuberculosis and Respiratory Disease 1999;46(4):481-8.
Wyser 1996 {published data only}
  • Wyser C, Walzl G, Smedema JP, Swart F, van Schalkwyk EM, van de Wal BW. Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study. Chest 1996;110(2):333-8.

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Aspin 1958 {published data only}
Bilaceroglu 1999 {published data only}
  • Bilaceroglu S, Perim K, Buyuksirin M, Celikten E. Prednisolone: a beneficial and safe adjunct to antituberculosis treatment? A randomized controlled trial. International Journal of Tuberculosis and Lung Disease 1999;3(1):47-54.
Cherednikova 1973 {published data only}
  • Cherednikova GV. Immediate and late results of treatment with corticosteroid hormones of children with tuberculosis [Blizhaishie i otdalennye rezul'taty lecheniia kortikosteroidnymi gormonami detei, bol'nykh tuberkulezom]. Problemy Tuberkuleza 1973;51(12):46-9.
Cisneros 1996 {published data only}
Damany 1968 {published data only}
  • Damany SJ, Shah KT. Treatment of pleural effusion with and without triamcinolone in addition to usual antituberculosis chemotherapy. Journal of the Indian Medical Association 1968;51(8):391-3.
Filler 1963 {published data only}
  • Filler J, Porter M. Physiologic studies of the sequelae of tuberculous pleural effusion in children treated with antimicrobial drugs and prednisone. American Review of Respiratory Disease 1963;88:181-8.
Fleishman 1960 {published data only}
  • Fleishman SI, Coetzee AM, Mindel S, Berjak J, Lichter AI. Antituberculous therapy combined with adrenal steroids in the treatment of pleural effusions: a controlled therapeutic trial. Lancet 1960;23(1):199-201.
Grewal 1969 {published data only}
  • Grewal KS, Dixit RP, Sil DR. A comparative study of therapeutic regimens with and without corticosteroids in the treatment of tuberculous pleural effusion. Journal of the Indian Medical Association 1969;52(11):514-6.
Khomenko 1990 {published data only}
  • Khomenko IS, Chukanov VI, Gergert VI, Utkin VV. Effectiveness of antitubercular chemotherapy combined with corticosteroids and immunomodulators [Effektivnost' protivotuberkuleznoi khimioterapii v sochetanii s kortikosteroidami i immunomoduliatorami]. Problemy Tuberkuleza 1990;1:24-8.
Manresa 1997 {published data only}
Mathur 1960 {published data only}
  • Mathur KS, Prasad R, Mathur JS. Intrapleural hydrocortisone in tuberculous pleural effusion. Tubercle 1960;41:358-62.
Mathur 1965 {published data only}
  • Mathur KS, Mathur JS, Sapru RP. Treatment of tuberculosis pleural effusion with local instillation of hydrocortisone. Diseases of the Chest 1965;47:303-9.
Mayanja-Kizza 2005 {published data only}
  • Mayanja-Kizza H, Jones-Lopez E, Okwera A, Wallis R, Ellner J, Mugerwa R, Whalen C, for the Uganda-Case Western Research Collaboration. Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: a phase 2 clinical trial in Uganda. Journal of Infectious Diseases 2005;191(6):856-65.
Menon 1964 {published data only}
  • Menon NK. Steroid therapy in tuberculous effusion. Tubercle 1964;45:17-20.
Paheco 1973 {published data only}
  • Pacheco CR, Valdez-Ochoa S, Naranjo F, Alvarez H, Aguilar M, Saavedra M. Clinical study of a new synthetic steroid in the treatment of pleural tuberculosis [Estudio clinico de un nuevo esteroide de sintesis en el tratamiento de la pleuresia tuberculosa]. Gaceta Medica de Mexico 1973;106(3):249-55.
Paley 1959 {published data only}
  • Paley SS, Mihaly JP, Mais EL, Gittens SA, Lupini B. Prednisolone in the treatment of tuberculous pleural effusions. American Review of Tuberculosis 1959;79:307-14.
Porsio 1966 {published data only}
  • Porsio A, Borgia M. Controlled clinical trials of the use of a new anabolic agent in a Sanatorium. La Clinica Terapeutica 1966;37(6):502-18.
Singh 1965 {published data only}
  • Singh D, Yesikar SS. Role of intrapleural corticosteroids in tuberculous pleural effusion: a clinicotherapeutic trial of 50 cases. Journal of the Indian Medical Association 1965;45(6):306-9.
Starostenko 1989 {published data only}
  • Starostenko EV, Novoselova VP. Indications for the use of prednisolone in tuberculosis. Problemy Tuberkuleza 1989;1:44-7.
Tani 1964 {published data only}
  • Tani P, Poppius H, Makipaja J. Cortisone therapy for exudative tuberculous pleurisy in the light of a follow-up study. Acta Tuberculosea Scandinavica 1964;44:303-9.
Tanzj 1965 {published data only}
  • Tanzj PL, Andreini E. On therapeutic use of corticosteroids in pleuro-pulmonary tuberculosis. Archivio di Tisiologia e delle Malattie dell'Apparato Respiratorio 1965;20(5):331-57.

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Anonymous 1983
  • Anonymous. Study of chemotherapy regimens of 5 and 7 months' duration and the role of corticosteroids in the treatment of sputum-positive patients with pulmonary tuberculosis in South India. Tubercle 1983;64(2):73-91.
Batungwanayo 1993
Blumberg 2003
  • Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. American Journal of Respiratory and Critical Care Medicine 2003;167(4):603-62.
Chapman 2004
Commerford 1991
  • Commerford PJ, Strang JIG. Tuberculous pericarditis. In: Coovadia HM, Benatar SR editor(s). A century of tuberculosis: South African perspectives. Cape Town: Oxford University Press, 1991:123-36.
Dooley 1997
Elliott 1992
  • Elliott AM, Halwiindi B, Bagshawe A, Hayes RJ, Luo N, Pobee JO, et al. Use of prednisolone in the treatment of HIV-positive tuberculosis patients. Quarterly Journal of Medicine 1992;85(307-8):855-60.
Ensoli 2001
Frye 1997
Harries 1990
Higgins 2006
  • Higgins JPT, Green S. Highly sensitive search strategies for identifying reports of randomized controlled trials in MEDLINE. Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 [updated September 2006]; Appendix 5b. www.cochrane.org/resources/handbook/hbook.htm (accessed 1 May 2007).
Jüni 2001
Lemaistre 1951
  • Lemaistre CA, Tompsett R, Muschenheim C, Moore JA, McDermott W. Effects of adrenocorticotropic hormone and cortisone in patients with tuberculosis. Journal of Clinical Investigation 1951;30(5):445-56.
Lionakis 2003
McAllister 1983
Morehead 1998
Relkin 1994
Review Manager 5
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Rossi 1987
  • Rossi GA, Balbi B, Manca F. Tuberculous pleural effusions. Evidence for selective presence of PPD-specific T-lymphocytes at site of inflammation in the early phase of the infection. American Review of Respiratory Disease 1987;136(3):575-9.
Seibert 1991
Sharma 2004
Song 2003
  • Song AT, Schout D, Novaes HM, Goldbaum M. Clinical and epidemiological features of AIDS/tuberculosis comorbidity. Revista do Hospital das Clinicas 2003;58(4):207-14.
WHO 2005
  • World Health Organization. Global tuberculosis control: surveillance, planning, financing. WHO report 2005 [WHO/HTM/TB/2005.349]. Geneva: World Health Organization, 2005.
Yang 2004
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