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Review |

Corticosteroid Therapy in Pulmonary Sarcoidosis:  A Systematic Review FREE

Shanthi Paramothayan, PhD, MRCP; Paul W. Jones, PhD, FRCP
JAMA. 2002;287(10):1301-1307. doi:10.1001/jama.287.10.1301.
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Published online

Context  Corticosteroids are used in pulmonary sarcoidosis to reduce symptoms and minimize long-term damage. Spontaneous recovery is a common feature. Both the decision to initiate therapy and the treatment response may be influenced by disease severity, so trials need to use a randomized controlled design.

Objective  To assess the effect of oral and inhaled corticosteroids on chest radiograph results, symptoms, pulmonary function, and long-term outcome in pulmonary sarcoidosis.

Data Sources  MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled Trials Register were searched all years through December 2001. Bibliographies of review articles and retrieved articles were searched, and pharmaceutical companies and authors of identified trials were contacted for other studies. There was no language restriction.

Study Selection  Trials were randomized and included a control group. Participants were adults with histologic evidence of pulmonary sarcoidosis. Treatments included the use of oral and inhaled corticosteroids for at least 8 weeks. The search identified 150 studies; 9 met the inclusion criteria, but only 8 provided usable data.

Data Extraction  Two reviewers assessed trial quality using the Jadad score, which evaluates the quality of randomization, blinding, and reasons for withdrawal. Data were extracted and sent to primary authors for verification.

Data Synthesis  In patients with stage 2 and 3 disease, oral corticosteroids improved findings on the chest radiograph after 6 to 24 months (Peto odds ratio, 2.54; 95% confidence interval [CI], 1.69-3.81; P<.001). Forced vital capacity improved with oral corticosteroids (weighted mean difference [WMD], 4.2% predicted; 95% CI, 0.4%-7.9% predicted) and diffusing capacity also improved (WMD, 5.7% predicted; 95% CI, 1.0%-10.5% predicted). In 2 small studies of inhaled corticosteroids, there was no effect on chest radiograph and inconsistent effects on lung function in one and only a small improvement in symptoms in the other. There were no data following corticosteroid withdrawal to assess any disease-modifying effect.

Conclusions  Oral corticosteroids improved results on the chest radiograph following 6 to 24 months of treatment and produced a small improvement in vital capacity and diffusing capacity. Trials of inhaled corticosteroids were small and results too inconsistent to make firm conclusions concerning their efficacy. There are no data to suggest that corticosteroid therapy alters long-term disease progression.

Sarcoidosis is a common multisystem granulomatous disorder. The lungs are frequently involved and pulmonary fibrosis may result. Black American and Afro-Caribbean populations have a higher incidence of the disease and may exhibit a more relentless course with higher morbidity and mortality.1 The severity of lung involvement is assessed on the basis of symptoms (particularly dyspnea and cough), changes on chest radiograph (which are staged from 1-4), and lung function. Spontaneous resolution can occur without treatment.2 Corticosteroids are given to reduce symptoms and speed resolution and in the hope of minimizing long-term effects (ie, modify progression of the disease). There is no consensus as to when corticosteroid therapy should be initiated, the dose, or treatment duration. Studies in sarcoidosis must take into account the spontaneous resolution that occurs frequently and the possibility that steroid responsiveness may vary by baseline severity. It is important to ensure that treatment and control groups share the same baseline characteristics and receive the same clinical management. This can be achieved only by randomization and blinding of the trialists to treatment allocation. Many studies have failed to minimize selection and treatment bias in this way. Furthermore, recent studies3 appear to have been designed on the premise that evidence for the efficacy of corticosteroids was so clear that randomization to treatment or control could not be justified. This review aims to synthesize all available data obtained from randomized controlled trials (RCTs) to provide a least-biased estimate of the efficacy of corticosteroid therapy in pulmonary sarcoidosis.

Sharma OP. Sarcoidosis.  Dis Mon.1990;36:469-535.
Lynch JP. Pulmonary sarcoidosis: current concepts and controversies.  Compr Ther.1997;23:197-216.
Gibson GJ, Prescott RJ, Muers MF.  et al.  British Thoracic Society sarcoidosis study: effects of long term corticosteroid treatment.  Thorax.1996;51:238-247.
Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials.  JAMA.1995;273:408-412.
Jadad A, Moore RA, Carroll D.  et al.  Assessing the quality of reports of randomized controlled trials: is blinding necessary?  Control Clin Trials.1996;17:1-12.
Eule E, Roth I, Ehrke I, Weinecke W. Corticosteroid therapy of intrathoracic sarcoidosis stages 1 and 2: results of a controlled clinical trial.  Z Erkr Atmungsorgane.1977;149:142-147.
Milman N, Graudal N, Grode G, Munch E. No effect of high-dose inhaled corticosteroids in pulmonary sarcoidosis: a double-blind, placebo-controlled study.  J Intern Med.1994;236:285-290.
Selroos O, Sellergren TL. Corticosteroid therapy of pulmonary sarcoidosis: a prospective evaluation of alternate day and daily dosage in stage 2 disease.  Scand J Respir Dis.1979;60:215-221.
James DG, Carstairs LS, Trowell J, Sharma OP. Treatment of sarcoidosis: report of a controlled therapeutic trial.  Lancet.1967;2:526-528.
Zaki MH, Lyons HA, Leilop L, Huang CT. Corticosteroid therapy in sarcoidosis: a 5 year controlled follow-up study.  N Y State J Med.1987;87:496-499.
Pietinalho A, Tukiainen P, Haahtela T.  et al.  Oral prednisolone followed by inhaled budesonide in newly diagnosed pulmonary sarcoidosis.  Chest.1999;116:424-431.
Israel HL, Fouts DW, Beggs RA. A controlled trial of prednisone treatment of sarcoidosis.  Am Rev Respir Dis.1973;107:609-614.
DuBois RM, Greenhalgh PM, Southcott AM.  et al.  Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study.  Eur Respir J.1999;13:1345-1350.
Alberts C, Van der Mark TW, Jansen HM. Inhaled budesonide in pulmonary sarcoidosis: a double-blind, placebo-controlled study.  Eur Respir J.1995;8:682-688.
Erkkila S, Froseth B, Hellstrom PE.  et al.  Inhaled budesonide influences cellular and biochemical abnormalities in pulmonary sarcoidosis.  Sarcoidosis.1988;5:106-110.
Khan KS, Daya S, Jadad AR. The importance of quality of primary studies in producing unbiased systematic reviews.  Arch Intern Med.1996;156:661-666.

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References

Sharma OP. Sarcoidosis.  Dis Mon.1990;36:469-535.
Lynch JP. Pulmonary sarcoidosis: current concepts and controversies.  Compr Ther.1997;23:197-216.
Gibson GJ, Prescott RJ, Muers MF.  et al.  British Thoracic Society sarcoidosis study: effects of long term corticosteroid treatment.  Thorax.1996;51:238-247.
Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials.  JAMA.1995;273:408-412.
Jadad A, Moore RA, Carroll D.  et al.  Assessing the quality of reports of randomized controlled trials: is blinding necessary?  Control Clin Trials.1996;17:1-12.
Eule E, Roth I, Ehrke I, Weinecke W. Corticosteroid therapy of intrathoracic sarcoidosis stages 1 and 2: results of a controlled clinical trial.  Z Erkr Atmungsorgane.1977;149:142-147.
Milman N, Graudal N, Grode G, Munch E. No effect of high-dose inhaled corticosteroids in pulmonary sarcoidosis: a double-blind, placebo-controlled study.  J Intern Med.1994;236:285-290.
Selroos O, Sellergren TL. Corticosteroid therapy of pulmonary sarcoidosis: a prospective evaluation of alternate day and daily dosage in stage 2 disease.  Scand J Respir Dis.1979;60:215-221.
James DG, Carstairs LS, Trowell J, Sharma OP. Treatment of sarcoidosis: report of a controlled therapeutic trial.  Lancet.1967;2:526-528.
Zaki MH, Lyons HA, Leilop L, Huang CT. Corticosteroid therapy in sarcoidosis: a 5 year controlled follow-up study.  N Y State J Med.1987;87:496-499.
Pietinalho A, Tukiainen P, Haahtela T.  et al.  Oral prednisolone followed by inhaled budesonide in newly diagnosed pulmonary sarcoidosis.  Chest.1999;116:424-431.
Israel HL, Fouts DW, Beggs RA. A controlled trial of prednisone treatment of sarcoidosis.  Am Rev Respir Dis.1973;107:609-614.
DuBois RM, Greenhalgh PM, Southcott AM.  et al.  Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study.  Eur Respir J.1999;13:1345-1350.
Alberts C, Van der Mark TW, Jansen HM. Inhaled budesonide in pulmonary sarcoidosis: a double-blind, placebo-controlled study.  Eur Respir J.1995;8:682-688.
Erkkila S, Froseth B, Hellstrom PE.  et al.  Inhaled budesonide influences cellular and biochemical abnormalities in pulmonary sarcoidosis.  Sarcoidosis.1988;5:106-110.
Khan KS, Daya S, Jadad AR. The importance of quality of primary studies in producing unbiased systematic reviews.  Arch Intern Med.1996;156:661-666.
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