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Meta-Analysis
. 2014 Sep 1;2014(9):CD001288.
doi: 10.1002/14651858.CD001288.pub4.

Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease

Julia A E Walters  1 , Daniel J Tan, Clinton J White, Peter G Gibson, Richard Wood-Baker, E Haydn Walters
Affiliations
Meta-Analysis

Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease

Julia A E Walters et al. Cochrane Database Syst Rev. .

Abstract

Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity and quality of life. The most common causes are infective, and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti-inflammatory agents.

Objectives: To assess the effects of corticosteroids administered orally or parenterally for treatment of acute exacerbations of COPD, and to compare the efficacy of parenteral versus oral administration.

Search methods: We carried out searches using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials), and checked references of included studies and trials registries. We conducted the last search in May 2014.

Selection criteria: Randomised controlled trials comparing corticosteroids administered orally or parenterally with an appropriate placebo, or comparing oral corticosteroids with parenteral corticosteroids in the treatment of people with acute exacerbations of COPD. Other interventions (e.g. bronchodilators and antibiotics) were standardised for both groups. We excluded clinical studies of acute asthma.

Data collection and analysis: We used standard methodological procedures expected by The Cochrane Collaboration.

Main results: Sixteen studies (n = 1787) met inclusion criteria for the comparison systemic corticosteroid versus placebo and 13 studies contributed data (n = 1620). Four studies (n = 298) met inclusion criteria for the comparison oral corticosteroid versus parenteral corticosteroid and three studies contributed data (n = 239). The mean age of participants with COPD was 68 years, median proportion of males 82% and mean forced expiratory volume in one second (FEV1) per cent predicted at study admission was 40% (6 studies; n = 633). We judged risk of selection, detection, attrition and reporting bias as low or unclear in all studies. We judged risk of performance bias high in one study comparing systemic corticosteroid with control and in two studies comparing intravenous corticosteroid versus oral corticosteroid.Systemic corticosteroids reduced the risk of treatment failure by over half compared with placebo in nine studies (n = 917) with median treatment duration 14 days, odds ratio (OR) 0.48 (95% confidence interval (CI) 0.35 to 0.67). The evidence was graded as high quality and it would have been necessary to treat nine people (95% CI 7 to 14) with systemic corticosteroids to avoid one treatment failure. There was moderate-quality evidence for a lower rate of relapse by one month for treatment with systemic corticosteroid in two studies (n = 415) (hazard ratio (HR) 0.78; 95% CI 0.63 to 0.97). Mortality up to 30 days was not reduced by treatment with systemic corticosteroid compared with control in 12 studies (n = 1319; OR 1.00; 95% CI 0.60 to 1.66).FEV1, measured up to 72 hours, showed significant treatment benefits (7 studies; n = 649; mean difference (MD) 140 mL; 95% CI 90 to 200); however, this benefit was not observed at later time points. The likelihood of adverse events increased with corticosteroid treatment (OR 2.33; 95% CI 1.59 to 3.43). Overall, one extra adverse effect occurred for every six people treated (95% CI 4 to 10). The risk of hyperglycaemia was significantly increased (OR 2.79; 95% CI 1.86 to 4.19). For general inpatient treatment, duration of hospitalisation was significantly shorter with corticosteroid treatment (MD -1.22 days; 95% CI -2.26 to -0.18), with no difference in length of stay the intensive care unit (ICU) setting.Comparison of parenteral versus oral treatment showed no significant difference in the primary outcomes of treatment failure, relapse or mortality or for any secondary outcomes. There was a significantly increased rate of hyperglycaemia in one study (OR 4.89; 95% CI 1.20 to 19.94).

Authors' conclusions: There is high-quality evidence to support treatment of exacerbations of COPD with systemic corticosteroid by the oral or parenteral route in reducing the likelihood of treatment failure and relapse by one month, shortening length of stay in hospital inpatients not requiring assisted ventilation in ICU and giving earlier improvement in lung function and symptoms. There is no evidence of benefit for parenteral treatment compared with oral treatment with corticosteroid on treatment failure, relapse or mortality. There is an increase in adverse drug effects with corticosteroid treatment, which is greater with parenteral administration compared with oral treatment.

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Conflict of interest statement

R Wood‐Baker has undertaken research sponsored by a number of pharmaceutical companies including Marion Merrell Dow, ICI Australia, Pharmacia Upjohn, GlaxoSmithKline, Sanofi‐Synthélabo and Novartis.

E H Walters has undertaken research sponsored by a number of pharmaceutical companies including Glaxo Wellcome, Novartis, Astra, Boehringer, Schering‐Plough and Amgen. He has held consultancies for AstraZeneca, ICI Australia, Pfizer and GlaxoSmithKline.

Figures

1
1
Study flow diagram for 2008‐2014 literature searches.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
4
4
5
5
6
6
1.1
1.1. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 1 Treatment failure.
1.2
1.2. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 2 Rate of relapse to 30 days.
1.3
1.3. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 3 Relapse.
1.4
1.4. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 4 Mortality.
1.5
1.5. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 5 Early FEV1 (L) ‐ absolute or change.
1.6
1.6. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 6 Early FEV1 (% predicted).
1.7
1.7. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 7 Early FVC (L) ‐ absolute or change.
1.8
1.8. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 8 Early FVC (% predicted).
1.9
1.9. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 9 Early FEV1/FVC (%).
1.10
1.10. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 10 Early PEF (L/minute) ‐ absolute or change.
1.11
1.11. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 11 Early dyspnoea score.
1.12
1.12. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 12 Early PaO2 (mmHg) ‐ absolute or change.
1.13
1.13. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 13 Early PaCO2 (mmHg) ‐ absolute or change.
1.14
1.14. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 14 FEV1 (L) ‐ absolute or change.
1.15
1.15. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 15 FEV1 (% predicted).
1.16
1.16. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 16 FVC (L) ‐ absolute or change.
1.17
1.17. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 17 FVC (% predicted).
1.18
1.18. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 18 FEV1/FVC (%).
1.19
1.19. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 19 PEF (L/minute) ‐ absolute.
1.20
1.20. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 20 Transitional dyspnoea index (change).
1.21
1.21. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 21 Dyspnoea score walking (change, VAS).
1.22
1.22. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 22 Overall dyspnoea score.
1.23
1.23. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 23 PaO2 (mmHg) ‐ change or absolute.
1.24
1.24. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 24 PaCO2 (mmHg) ‐ absolute.
1.25
1.25. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 25 Overall quality of life score (CRQ) (change).
1.26
1.26. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 26 Physical capacity (m) (6‐minute walk distance).
1.27
1.27. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 27 Length of stay (days).
1.28
1.28. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 28 Duration of mechanical ventilation (days).
1.29
1.29. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 29 Adverse drug effects.
1.30
1.30. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 30 Adverse effect ‐ hyperglycaemia (30 days).
1.31
1.31. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 31 Adverse effect ‐ hypertension.
1.32
1.32. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 32 Adverse effect ‐ gastrointestinal bleeding.
1.33
1.33. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 33 Adverse effect ‐ dyspepsia.
1.34
1.34. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 34 Adverse effect ‐ weight gain.
1.35
1.35. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 35 Adverse effect ‐ depression.
1.36
1.36. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 36 Adverse effect ‐ anxiety.
1.37
1.37. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 37 Adverse effect ‐ psychiatric disorder.
1.38
1.38. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 38 Adverse effect ‐ insomnia.
1.39
1.39. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 39 Adverse effect ‐ delirium.
1.40
1.40. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 40 Adverse effect ‐ secondary infection.
1.41
1.41. Analysis
Comparison 1 Systemic corticosteroid (SCS) versus placebo, Outcome 41 Adverse effect ‐ ventilator‐associated pneumonia.
2.1
2.1. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 1 Treatment failure.
2.2
2.2. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 2 Relapse.
2.3
2.3. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 3 Mortality after discharge (1‐3 months).
2.4
2.4. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 4 Early FEV1 (L).
2.5
2.5. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 5 Early FVC (L).
2.6
2.6. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 6 Early dyspnoea score (VAS).
2.7
2.7. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 7 Early cough score (VAS).
2.8
2.8. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 8 Early sputum volume score (VAS).
2.9
2.9. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 9 FEV1 (L) ‐ absolute or change.
2.10
2.10. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 10 FVC (L) ‐ absolute.
2.11
2.11. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 11 FEV1/FVC ratio.
2.12
2.12. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 12 Dyspnoea score (VAS) at 7‐10 days.
2.13
2.13. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 13 Cough score (VAS) at 7 days.
2.14
2.14. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 14 Sputum volume score (VAS) at 7 days.
2.15
2.15. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 15 PaO2 (mmHg) at 7 days.
2.16
2.16. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 16 PaCO2 (mmHg) at 7 days.
2.17
2.17. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 17 Health status: Clinical COPD Questionnaire (change at 1 week).
2.18
2.18. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 18 Quality of life: SGRQ (change at 7 days).
2.19
2.19. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 19 Quality of life: CRQ Dyspnoea (change at 4 weeks).
2.20
2.20. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 20 Quality of life: CRQ Fatigue (change at 4 weeks).
2.21
2.21. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 21 Quality of life: CRQ Mastery (change at 4 weeks).
2.22
2.22. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 22 Quality of life: CRQ Emotion (change at 4 weeks).
2.23
2.23. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 23 Duration of hospitalisation (days).
2.24
2.24. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 24 Adverse effect ‐ hyperglycaemia.
2.25
2.25. Analysis
Comparison 2 Intravenous corticosteroid (IVCS) versus oral corticosteroid (OCS), Outcome 25 Adverse effect ‐ hypertension.
See this image and copyright information in PMC

Update of

Comment in

References

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