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Temas

1 Study flow diagram.
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Figure 1

1 Study flow diagram.

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Risk of bias summary: review authors' judgements about each item for each included study.
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Figure 2

Risk of bias summary: review authors' judgements about each item for each included study.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Forest plot outcome: treatment failure comparing systemic corticosteroids for ≤ 7 days vs > 7 days.
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Figure 4

Forest plot outcome: treatment failure comparing systemic corticosteroids for ≤ 7 days vs > 7 days.

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Forest plot of comparison: 1 Systemic corticosteroids for 7 or fewer days vs longer than seven days, outcome: 1.2 Relapse.
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Figure 5

Forest plot of comparison: 1 Systemic corticosteroids for 7 or fewer days vs longer than seven days, outcome: 1.2 Relapse.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 1 Treatment failure.
Figuras y tablas -
Analysis 1.1

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 1 Treatment failure.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 2 Relapse.
Figuras y tablas -
Analysis 1.2

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 2 Relapse.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 3 Time to re‐exacerbation.
Figuras y tablas -
Analysis 1.3

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 3 Time to re‐exacerbation.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 4 Adverse effect—hyperglycaemia.
Figuras y tablas -
Analysis 1.4

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 4 Adverse effect—hyperglycaemia.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 5 Adverse effect—hypertension.
Figuras y tablas -
Analysis 1.5

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 5 Adverse effect—hypertension.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 6 Other adverse effects—gastrointestinal tract bleeding, symptomatic gastrointestinal reflux, symptoms of congestive heart failure or ischaemic heart disease, sleep disturbance, fractures, depression.
Figuras y tablas -
Analysis 1.6

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 6 Other adverse effects—gastrointestinal tract bleeding, symptomatic gastrointestinal reflux, symptoms of congestive heart failure or ischaemic heart disease, sleep disturbance, fractures, depression.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 7 Mortality.
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Analysis 1.7

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 7 Mortality.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 8 Length of hospitalisation.
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Analysis 1.8

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 8 Length of hospitalisation.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 9 FEV1 (L) (early).
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Analysis 1.9

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 9 FEV1 (L) (early).

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 10 FEV1 % predicted (6 days).
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Analysis 1.10

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 10 FEV1 % predicted (6 days).

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 11 FVC (L) (early).
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Analysis 1.11

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 11 FVC (L) (early).

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 12 FEV1 (L) end of treatment.
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Analysis 1.12

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 12 FEV1 (L) end of treatment.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 13 FEV1 % predicted 30 days.
Figuras y tablas -
Analysis 1.13

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 13 FEV1 % predicted 30 days.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 14 FVC (L) end of treatment.
Figuras y tablas -
Analysis 1.14

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 14 FVC (L) end of treatment.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 15 PaO2 (mmHg) (early).
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Analysis 1.15

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 15 PaO2 (mmHg) (early).

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 16 PaO2 (mmHg) end of treatment.
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Analysis 1.16

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 16 PaO2 (mmHg) end of treatment.

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 17 PaCO2 (mmHg).
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Analysis 1.17

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 17 PaCO2 (mmHg).

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 18 Symptoms—dyspnoea (early).
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Analysis 1.18

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 18 Symptoms—dyspnoea (early).

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 19 Symptoms—dyspnoea (15 days).
Figuras y tablas -
Analysis 1.19

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 19 Symptoms—dyspnoea (15 days).

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 20 Quality of life—overall (6 days).
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Analysis 1.20

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 20 Quality of life—overall (6 days).

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Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 21 Quality of life—overall (30 days).
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Analysis 1.21

Comparison 1 Systemic corticosteroids for 7 or fewer days vs longer than 7 days, Outcome 21 Quality of life—overall (30 days).

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Summary of findings for the main comparison. SCS treatment for 7 or fewer days compared with SCS treatment for longer than 7 days for acute exacerbations of COPD

SCS treatment for 7 or fewer days compared with SCS treatment for longer than 7 days for acute exacerbations of COPD

Patient or population: patients with acute exacerbations of COPD
Settings: hospital‐initiated treatment
Intervention: SCS treatment for 7 or fewer days
Comparison: SCS treatment for longer than 7 days

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

SCS treatment for longer than 7 days

SCS treatment for 7 or fewer days

Treatment failure
Need for additional treatment
Follow‐up: 10 to 14 days

83 per 1000

61 per 1000
(32 to 117)

OR 0.72
(0.36 to 1.46)

457
(4 studies)

⊕⊕⊕⊝
Moderatea

Equivalent to 22 fewer (95% CI 51 fewer to 34 more)

Relapse
New acute exacerbation or COPD‐related admission
Follow‐up: 14 to 180 days

295 per 1000

304 per 1000
(227 to 395)

OR 1.04
(0.7 to 1.56)

478
(4 studies)

⊕⊕⊕⊝
Moderatea

In one study (Leuppi 2013), hazard ratio for time to re‐exacerbation was 0.95 (95% CI 0.66 to 1.37)

Adverse drug effect—hyperglycaemia
Follow‐up: 3 to 14 days

442 per 1000

439 per 1000
(336 to 548)

OR 0.99
(0.64 to 1.53)

345
(2 studies)

⊕⊕⊕⊝
Moderatea

Adverse drug effects
Gastrointestinal tract bleeding, symptomatic gastrointestinal reflux, symptoms of congestive heart failure or ischaemic heart disease, sleep disturbance, fractures, depression
Follow‐up: 10 to 180 days

84 per 1000

75 per 1000
(40 to 135)

OR 0.88
(0.46 to 1.7)

503
(5 studies)

⊕⊕⊝⊝
Lowa,b

Mortality
Follow‐up: 14 to 180 days

77 per 1000

71 per 1000
(32 to 147)

OR 0.91
(0.4 to 2.06)

336
(2 studies)

⊕⊕⊕⊝
Moderatea

Length of hospitalisation
(days)
Follow‐up: 3 to 14 days

Mean length of hospitalisation in control groups was
10 days

Mean length of hospitalisation in intervention groups was
0.61 lower (1.51 lower to 0.28 higher)

421
(3 studies)

⊕⊕⊕⊝
Moderatea

Lung function (end of treatment)
FEV1 (L)
Follow‐up: 10 to 14 days

Mean FEV1 in control groups ranged from 0.84 to 1.14 L

Mean lung function (end of treatment) in intervention groups was
0.04 lower (0.19 lower to 0.10 higher)

187
(4 studies)

⊕⊝⊝⊝
Very lowa,c,d,e

Health‐related quality of life (QOL)

Overall score (includes activity limitations, symptoms, fatigue, emotional functioning); scale 0 best to 6 worst; minimum important difference 0.5

Follow‐up: 30 days

Mean QOL score in control groups was 1.24

Mean QOL score in intervention groups was 0.06 higher (‐0.16 lower to 0.28 higher)

271 (1 study)

⊕⊕⊕⊝
Moderatea

*The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio.

GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

aWide confidence intervals include significant benefit or harm (‐1 for imprecision).
bParticipants and physicians not blinded to treatment in one study (‐1 for risk of bias).
cParticipants and physicians not blinded to treatment in one study; however risk of bias for the outcome measurement is considered low.
dHigh risk of attrition bias in one study (‐1 for risk of bias).
eSignificant unexplained heterogeneity (‐1 for inconsistency).

Figuras y tablas -
Summary of findings for the main comparison. SCS treatment for 7 or fewer days compared with SCS treatment for longer than 7 days for acute exacerbations of COPD
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Table 1. Study characteristics

Study ID/Setting

Inclusion criteria

AE definition

N participants included/Completing

Mean age, years

% males/ % smokers

Prestudy SCS use, %

SCS ≤ 7 days

SCS > 7 days

Definition of treatment failure

Chen 2005 China/ inpatients

2 years of continuous productive cough, FEV1/FVC post BD < 0.7, FEV1 < 80% predicted. No respiratory failure, diabetes or bronchial asthma

At least 2 of 3 symptoms: increased sputum or dyspnoea or purulent sputum

86/81

71

75/44

Not stated

Prednisolone 30 mg 7 days

Prednisolone 30 mg/d 10 days + 15 mg/d 5 days

Not known

Gomaa 2008 (abstract only)

FEV1 < 50% predicted, no respiratory acidosis

Not stated

42/Not known

Not stated

Not stated

Not stated

Prednisolone 30 mg 7 days

Prednisolone 30 mg 15 days

Outcome not reported

Leuppi 2013 Switzerland/5 sites

Age > 40 years, smoking history ≥ 20 pack‐years

At least 2 of the following: change in baseline dyspnoea, cough or sputum quantity/purulence

314/296

69

60/45

20

5 days: days 1 to 4 methylprednisolone 40 mg, days 2 to 5 oral prednisolone 40 mg

14 days: days 1 to 4 methylprednisolone 40 mg, days 2 to 14 oral 40 mg prednisolone

Received open‐label glucocorticoids during index exacerbation

Rahman 2004 (abstract only) Bangladesh/1 site

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Prednisolone 30 mg 7 days

Prednisolone 30 mg 14 days

Outcome not reported

Salam 1998 (abstract only) USA/Unknown sites

Not stated

Not stated

21/Not known

Not stated

Not stated

None in previous month

IV CS 3 days

IV CS 3 days + 7 days OCS

Outcome not reported

Sayiner 2001 Turkey/1 site

FEV1 < 35% predicted, PYH > 20, no respiratory failure requiring ventilation

Not stated, requiring admission

36/34

65

94/Not stated

None in previous month

IV methylprednisone 0.5 mg/kg qds 3 days

IV methylprednisone 0.5 mg/kg qds 3 days, bd 3 days, od 4 days

Required open‐label steroid treatment

Sirichana 2008 (abstract and author data) Thailand/1 site

Age > 40 years, symptoms > 24 hours

Increase in at least 2 of 3 symptoms—dyspnoea, sputum volume, sputum purulence; requiring admission

48/42

73

88/Not stated

None in previous month

Prednisolone 30 mg 5 days

Prednisolone 30 mg 10 days

Outcome not reported

Wood‐Baker 1997 (abstract and author data) Australia & New Zealand/2 sites

Age > 40 years; > 10 pack‐year smoking history; FEV1 < 50% predicted

Not stated, requiring admission

38/28

71

63/Not stated

None for current AEs, no long‐term OS > 5 mg/d

Prednisolone 2.5 mg/kg orally daily for 3 days

Prednisolone 0.6 mg/kg orally daily for 7 days followed by prednisolone 0.3 mg/kg orally daily for 7 days

Lack of progress according to attending physician during treatment
Figuras y tablas -
Table 1. Study characteristics
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Table 2. Sensitivity analyses

Excluding Sirichana (not blinded)

All studies

Relapse

1.01 (0.66 to 1.55)

1.04 (0.70 to 1.56)

FEV1 early

‐0.09 (‐0.22 to 0.05)

‐0.07 (‐0.19 to 0.05)

FEV1 end

‐0.06 (‐0.23 to 0.11)

‐0.04 (‐0.19 to 0.10)

FVC early

‐0.00 (‐0.25 to 0.25)

0.01 (‐0.20 to 0.22)

FVC end

‐0.14 (‐0.38 to 0.09)

‐0.12 (‐0.33 to 0.09)

Adverse event—other

0.94 (0.48 to 1.82)

0.89 (0.46 to 1.69)

Excluding Sayiner (IV SCS)

All studies

Treatment failure

0.66 (0.32 to 1.37)

0.72 (0.36 to 1.46)

Relapse

1.02 (0.67 to 1.56)

1.04 (0.70 to 1.56)

Adverse event—hyperglycaemia

0.99 (0.63 to 1.54)

0.99 (0.64 to 1.53)

Adverse event—other

0.89 (0.46 to 1.69)

0.89 (0.46 to 1.69)

FEV1 early

‐0.02 (‐0.19 to 0.16)

‐0.07 (‐0.19 to 0.05)

FEV1 end

0.03 (‐0.06 to 0.12)

‐0.04 (‐0.19 to 0.10)

FVC early

0.12 (‐0.18 to 0.42)

0.01 (‐0.20 to 0.22)

FVC end

‐0.06 (‐0.34 to 0.22)

‐0.12 (‐0.33 to 0.09)
Figuras y tablas -
Table 2. Sensitivity analyses
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Comparison 1. Systemic corticosteroids for 7 or fewer days vs longer than 7 days

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Treatment failure Show forest plot

4

457

Odds Ratio (M‐H, Fixed, 95% CI)

0.72 [0.36, 1.46]

2 Relapse Show forest plot

4

478

Odds Ratio (M‐H, Fixed, 95% CI)

1.04 [0.70, 1.56]

3 Time to re‐exacerbation Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Subtotals only

4 Adverse effect—hyperglycaemia Show forest plot

2

345

Odds Ratio (M‐H, Fixed, 95% CI)

0.99 [0.64, 1.53]

5 Adverse effect—hypertension Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6 Other adverse effects—gastrointestinal tract bleeding, symptomatic gastrointestinal reflux, symptoms of congestive heart failure or ischaemic heart disease, sleep disturbance, fractures, depression Show forest plot

5

503

Odds Ratio (M‐H, Fixed, 95% CI)

0.89 [0.46, 1.69]

7 Mortality Show forest plot

2

336

Odds Ratio (M‐H, Fixed, 95% CI)

0.91 [0.40, 2.06]

8 Length of hospitalisation Show forest plot

3

421

Mean Difference (IV, Fixed, 95% CI)

‐0.61 [‐1.51, 0.28]

9 FEV1 (L) (early) Show forest plot

3

96

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.19, 0.05]

9.1 FEV1 absolute

2

75

Mean Difference (IV, Fixed, 95% CI)

‐0.08 [‐0.22, 0.06]

9.2 FEV1 change

1

21

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.27, 0.19]

10 FEV1 % predicted (6 days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

11 FVC (L) (early) Show forest plot

3

97

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.20, 0.22]

11.1 FVC measured

2

75

Mean Difference (IV, Fixed, 95% CI)

‐0.05 [‐0.29, 0.19]

11.2 FVC change from baseline

1

22

Mean Difference (IV, Fixed, 95% CI)

0.23 [‐0.23, 0.69]

12 FEV1 (L) end of treatment Show forest plot

4

187

Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.19, 0.10]

12.1 FEV1 measured

3

164

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.25, 0.16]

12.2 FEV1 change from baseline

1

23

Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.23, 0.14]

13 FEV1 % predicted 30 days Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

14 FVC (L) end of treatment Show forest plot

3

99

Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.33, 0.09]

14.1 FVC measured

2

77

Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐0.39, 0.11]

14.2 FVC change from baseline

1

22

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.44, 0.29]

15 PaO2 (mmHg) (early) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

16 PaO2 (mmHg) end of treatment Show forest plot

2

121

Mean Difference (IV, Fixed, 95% CI)

‐1.38 [‐4.96, 2.21]

17 PaCO2 (mmHg) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

17.1 3 days of follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

17.2 10 days of follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

18 Symptoms—dyspnoea (early) Show forest plot

2

320

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.08 [‐0.29, 0.14]

19 Symptoms—dyspnoea (15 days) Show forest plot

4

404

Std. Mean Difference (IV, Fixed, 95% CI)

0.16 [‐0.03, 0.36]

19.1 Change

3

133

Std. Mean Difference (IV, Fixed, 95% CI)

0.25 [‐0.09, 0.60]

19.2 Absolute

1

271

Std. Mean Difference (IV, Fixed, 95% CI)

0.12 [‐0.12, 0.36]

20 Quality of life—overall (6 days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

21 Quality of life—overall (30 days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Figuras y tablas -
Comparison 1. Systemic corticosteroids for 7 or fewer days vs longer than 7 days
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