Inhaled steroids for acute asthma following emergency department discharge

Marcia L Edmonds; Stephen J Milan; Barry E Brenner; Carlos A Camargo Jr; Brian H Rowe

doi:10.1002/14651858.CD002316.pub2

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Figure 1

Study flow diagram.

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Figure 2

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

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Figure 3

Forest plot of comparison: 1 Any ICS plus oral corticosteroid versus oral corticosteroid, outcome: 1.1 Asthma relapse at 7‐10 days.

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Forest plot of comparison: 1 Any ICS plus oral corticosteroid versus oral corticosteroid, outcome: 1.5 Beta2‐agonist use at 20‐24 days.

Figure 4

Forest plot of comparison: 1 Any ICS plus oral corticosteroid versus oral corticosteroid, outcome: 1.5 Beta₂‐agonist use at 20‐24 days.

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Figure 5

Forest plot of comparison: 2 Any ICS versus oral corticosteroid, outcome: 2.1 Asthma relapse at 7‐10 days.

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Figure 6

Forest plot of comparison: 2 Any ICS versus oral corticosteroid, outcome: 2.2 Asthma relapse at 16‐21 days.

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Analysis 1.1

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 1 Asthma relapse at 7‐10 days.

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Analysis 1.2

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 2 Asthma relapse at 20‐24 days.

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Analysis 1.3

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 3 Hospital admission.

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Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 4 Beta2‐agonist use at 7‐10 days.

Analysis 1.4

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 4 Beta₂‐agonist use at 7‐10 days.

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Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 5 Beta2‐agonist use at 20‐24 days.

Analysis 1.5

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 5 Beta₂‐agonist use at 20‐24 days.

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Analysis 1.6

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 6 PEF at 7‐10 days.

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Analysis 1.7

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 7 PEF at 20‐24 days.

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Analysis 1.8

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 8 PEF% at 7‐10 days.

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Analysis 1.9

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 9 PEF% at 20‐24 days.

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Analysis 1.10

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 10 Quality of life at 7‐10 days.

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Analysis 1.11

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 11 Quality of life at 20‐24 days.

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Analysis 1.12

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 12 Cough at 7‐10 days.

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Analysis 1.13

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 13 Cough at 20‐24 days.

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Analysis 1.14

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 14 Wheeze at 7‐10 days.

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Analysis 1.15

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 15 Wheeze at 20‐24 days.

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Analysis 1.16

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 16 Dyspnoea at 7‐10 days.

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Analysis 1.17

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 17 Dyspnoea at 20‐24 days.

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Analysis 1.18

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 18 Hoarseness at 7‐10 days.

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Analysis 1.19

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 19 Hoarseness at 20‐24 days.

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Analysis 1.20

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 20 Sore throat at 7‐10 days.

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Analysis 1.21

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 21 Sore throat at 20‐24 days.

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Analysis 1.22

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 22 Asthma relapse at 7‐10 days ‐ gender subgroups.

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Analysis 1.23

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 23 Asthma relapse at 20‐24 days ‐ gender subgroups.

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Analysis 1.24

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 24 Asthma relapse at 7‐10 days; patients lost to follow‐up excluded.

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Analysis 1.25

Comparison 1 Any ICS plus oral corticosteroid versus oral corticosteroid, Outcome 25 Asthma relapse at 20‐24 days; patients lost to follow‐up excluded.

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Analysis 2.1

Comparison 2 Any ICS versus oral corticosteroid, Outcome 1 Asthma relapse at 7‐10 days.

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Analysis 2.2

Comparison 2 Any ICS versus oral corticosteroid, Outcome 2 Asthma relapse at 16‐21 days.

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Analysis 2.3

Comparison 2 Any ICS versus oral corticosteroid, Outcome 3 Hospital admission.

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Analysis 2.4

Comparison 2 Any ICS versus oral corticosteroid, Outcome 4 PEF at 7‐10 days.

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Analysis 2.5

Comparison 2 Any ICS versus oral corticosteroid, Outcome 5 PEF at 16‐21 days.

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Analysis 2.6

Comparison 2 Any ICS versus oral corticosteroid, Outcome 6 PEF% at 7‐10 days.

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Analysis 2.7

Comparison 2 Any ICS versus oral corticosteroid, Outcome 7 PEF% at 16‐21 days.

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Comparison 2 Any ICS versus oral corticosteroid, Outcome 8 FEV1% pred at 6‐10 days (outcome not pre‐specified in original review).

Analysis 2.8

Comparison 2 Any ICS versus oral corticosteroid, Outcome 8 FEV₁% pred at 6‐10 days (outcome not pre‐specified in original review).

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Comparison 2 Any ICS versus oral corticosteroid, Outcome 9 FEV1% pred at 16‐21 days (outcome not pre‐specified in original review).

Analysis 2.9

Comparison 2 Any ICS versus oral corticosteroid, Outcome 9 FEV₁% pred at 16‐21 days (outcome not pre‐specified in original review).

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Comparison 2 Any ICS versus oral corticosteroid, Outcome 10 Beta2‐agonist use at 7‐10 days.

Analysis 2.10

Comparison 2 Any ICS versus oral corticosteroid, Outcome 10 Beta₂‐agonist use at 7‐10 days.

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Comparison 2 Any ICS versus oral corticosteroid, Outcome 11 Beta2‐agonist use at 14‐21 days.

Analysis 2.11

Comparison 2 Any ICS versus oral corticosteroid, Outcome 11 Beta₂‐agonist use at 14‐21 days.

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Analysis 2.12

Comparison 2 Any ICS versus oral corticosteroid, Outcome 12 Quality of life at 7‐10 days.

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Analysis 2.13

Comparison 2 Any ICS versus oral corticosteroid, Outcome 13 Cough at 7‐10 days.

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Analysis 2.14

Comparison 2 Any ICS versus oral corticosteroid, Outcome 14 Wheeze at 7‐10 days.

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Analysis 2.15

Comparison 2 Any ICS versus oral corticosteroid, Outcome 15 Wheeze at 16‐21 days.

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Analysis 2.16

Comparison 2 Any ICS versus oral corticosteroid, Outcome 16 Hoarseness at 7‐10 days.

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Analysis 2.17

Comparison 2 Any ICS versus oral corticosteroid, Outcome 17 Hoarseness at 16‐21 days.

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Analysis 2.18

Comparison 2 Any ICS versus oral corticosteroid, Outcome 18 Sore throat at 7‐10 days.

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Analysis 2.19

Comparison 2 Any ICS versus oral corticosteroid, Outcome 19 Sore throat at 16‐21 days.

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Summary of findings for the main comparison. Any ICS plus oral corticosteroid versus oral corticosteroid for acute asthma following emergency department discharge

Any ICS plus oral corticosteroid versus oral corticosteroid for acute asthma following emergency department discharge
Patient or population: predominantly adults with acute asthma following emergency department discharge Settings: community following emergency department discharge Intervention: any ICS plus oral corticosteroid versus oral corticosteroid Comparison: oral corticosteroids
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Any ICS plus oral corticosteroid versus oral corticosteroid
Asthma relapse¹at 20 to 24 days	141 per 1000	100 per 1000 (70 to 143)	OR 0.68 (0.46 to 1.02)	909 (3 studies)	⊕⊕⊕⊕ high²	Predominantly adult patients in Camargo 2000 and adults in Brenner 2000 and Rowe 1999
Hospital admission mean follow‐up period 21 days	22 per 1000	22 per 1000 (9 to 55)	OR 0.99 (0.39 to 2.52)	805 (2 studies)	⊕⊕⊕⊝ moderate³	Predominantly adult patients in Camargo 2000 and adult patients in Rowe 1999
Hoarseness at 20 to 24 days	149 per 1000	95 per 1000 (59 to 150)	OR 0.6 (0.36 to 1.01)	596 (2 studies)	⊕⊕⊕⊝ moderate⁴	Predominantly adult patients in Camargo 2000 and adult patients in Rowe 1999
The basis for the assumed risk* (e.g. the 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.
¹ relapse was defined as "an unscheduled visit for worsening asthma symptoms". ² No point deducted for imprecision as OR = 1.02 was not regarded as a clinically significant increase in risk of admission. ³ Point deducted for imprecision due to wide confidence intervals. ⁴ Point deducted for hoarseness at 20 to 24 days as I² = 55%.

Summary of findings for the main comparison. Any ICS plus oral corticosteroid versus oral corticosteroid for acute asthma following emergency department discharge

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Summary of findings 2. Any ICS versus oral corticosteroid for acute asthma following emergency department discharge

Any ICS versus oral corticosteroid for acute asthma following emergency department discharge
Patient or population: patients with acute asthma following emergency department discharge Settings: Intervention: any ICS versus oral corticosteroid
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Any ICS versus oral corticosteroid
Asthma relapse¹at 16 to 21 days	215 per 1000	257 per 1000 (180 to 353)	OR 1.26 (0.8 to 1.99)	425 (2 studies)	⊕⊕⊕⊝ moderate²	Adults in 1 study Levy 1996 and children in the other Volovitz 1998
Hospital admission mean follow‐up period: 9 to 10 days	8 per 1000	3 per 1000 (0 to 61)	OR 0.31 (0.01 to 7.95)	254 (3 studies)	⊕⊕⊕⊝ moderate²	Adults in 1 study Fitzgerald 2000 and children in the other two Nakanishi 2003 and Volovitz 1998
Hoarseness at 16 to 21 days	24 per 1000	39 per 1000 (13 to 112)	OR 1.62 (0.52 to 5.05)	412 (1 study)	⊕⊕⊝⊝ low^2,3	Adults in 1 study Levy 1996
The basis for the assumed risk* (e.g. the 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.
¹ Relapse was defined in the largest study, Levy, as "treatment failure". Patients were categorised as a treatment failure if (a) PEF fell below 60% of the best/predicted value on two consecutive occasions, or (b) a symptom score of 3 (indicating the symptoms were the same or worse than on entry to the study) was recorded on three or more consecutive days, or (c) the patient withdrew because of uncontrolled symptoms or an adverse event related to asthma. In the other two studies relapse was defined as need for additional oral corticosteroid therapy or an unscheduled visit for asthma symptoms. ² Point deducted for imprecision due to wide confidence intervals. ³ Point deducted for hoarseness at 16 to 21 days as data contributed by only one study.

Summary of findings 2. Any ICS versus oral corticosteroid for acute asthma following emergency department discharge

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Table 1. Summary of included studies comparing ICS plus oral corticosteroids to oral corticosteroids alone

Study

ICS + oral corticosteroids

Corticosteroids

Age

Location

Duration and delivery for ICS + corticosteroids

Duration and delivery for placebo + corticosteroids

Standard of care

Brenner 2000

Adults

Flunisolide 1 mg twice daily by MDI and aerochamber for 24 days

Placebo twice daily by MDI and aerochamber

Oral prednisone 40 mg daily for 5 days, and used albuterol MDI as needed

Camargo 2000

257

260

Predominantly adults

250 μg inhaled fluticasone by Diskhaler twice daily for 20 days

Placebo by Diskhaler twice daily for 20 days

Oral prednisone 50 mg daily for 5 days, and inhaled albuterol as needed

Rowe 1999

Adults

Canada

Inhaled budesonide Turbuhaler 800 μg twice daily for 3 weeks

Inhaled placebo Turbuhaler twice daily for 3 weeks

Both treatment and control groups received prednisone 50 mg PO x 7 days and prn salbutamol by MDI after discharge

ICS: inhaled corticosteroids; MDI: metered‐dose inhaler; PO: oral.

Table 1. Summary of included studies comparing ICS plus oral corticosteroids to oral corticosteroids alone

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Table 2. Summary of included studies comparing ICS alone to oral corticosteroid alone

Study	ICS N	Corticosteroids N	Age	Location	Duration and delivery for ICS	Duration and delivery for corticosteroids	Standard of care
Di Franco 2006	18	19	Adults	Italy	Inhaled fluticasone propionate (FP) 2000 mg/daily (4 puffs of 250 mg in the morning and in the evening with a large spacer) and oral prednisone placebo for 2 weeks	Oral prednisone 40 mg/day tapered to 10 mg/day by reducing the dose by 5 mg every other day and inhaled placebo for 2 weeks. Patients held their usual regular ICS treatment but continued to use their previous regular bronchodilator treatment (including oral theophylline), during the study period
Fitzgerald 2000	90	85	Adults	Canada	Budesonide 600 μg 4 times daily by Turbuhaler for 7 to 10 days (mean 7.5 days)	Oral prednisone, 40 mg daily, for 7 to 10 days (mean 7.5 days)	Participants used inhaled terbutaline as needed and pre‐existing asthma medications were continued
Francis 1997	37	19	Children	Multicentre study based in the UK	Inhaled fluticasone propionate, 1 mg twice daily by nebuliser, and placebo oral suspension for 7 days	Inhaled placebo twice daily, and oral prednisolone 2 mg/kg/day for 4 days, then 1 mg/kg/day for 3 days	Both groups received salbutamol as needed, by nebuliser or MDI with babyhaler. Concurrent medications were continued (4 patients only)
Levy 1996	200	203	Adults	UK	Fluticasone 1 mg twice daily via a Volumatic for a period of 16 days	Reducing course of oral prednisolone, starting at 40 mg and reducing by 5 mg every 2 days, for a period of 16 days	All concurrent asthma medications, including existing ICS, were continued
Manjra 2000	158	151	Children	multicentre study based in the UK	Fluticasone propionate, 1 mg twice daily by nebuliser for 7 days and oral placebo	Inhaled placebo, and oral prednisolone, 2 mg/kg/day for 4 days, then 1 mg/kg/day for 3 days	Both groups received inhaled salbutamol as needed, and concurrent medications were continued
Nakanishi 2003	29	28	Children	US	Flunisolide, 4 inhalations (1 mg) twice daily for 7 days, and daily placebo tablets	Oral prednisone, 2 mg/kg (maximum of 60 mg/day) for 7 days and inhaled placebo twice daily. Outpatient inhalations were given with a pressurised MDI with valved holding chamber
Nana 1998	42	42	Adults	Thailand	Inhaled budesonide by Turbuhaler, 1600 mg twice daily for 7 days, and oral placebo	Oral prednisolone initially 40 mg per day and decreasing by 5 mg/day for 7 days, and inhaled placebo	Both groups received 1 dose of oral prednisolone 60 mg PO while in the emergency department, and inhaled terbutaline by Turbuhaler as needed. Other asthma medications were continued during the study (48 patients were on oral xanthines and 49 patients were on oral beta₂‐agonists)
Verona 1998	62	74	Children	Multicentre study based in the UK	Fluticasone propionate (FP) 500 μg twice daily by MDI with spacer for 7 days, and placebo tablets	Prednisolone tablets, 2 mg/kg/day for 4 days, 1 mg/kg/day for 3 days, and placebo MDI inhaler	All patients received Ventolin as needed, and continued all regular asthma medications
Volovitz 1998	11	11	Children	Israel	Single‐dose budesonide 1600 μg by turbohaler	Prednisolone 2 mg/kg PO	Both groups received terbutaline 5 mg by nebuliser or 0.5 mg by turbohaler at the start of trial. Intervention 1 group was discharged on budesonide 200 μg 4 times daily by turbohaler, reduced by 25% every second day, and placebo tablets. From the eighth day, they continued on 200 μg twice daily for 2 weeks. Intervention 2 group was discharged on prednisolone 2 mg/kg/day, reduced by 25% every second day, and placebo Tubohaler
ICS: inhaled corticosteroid; MDI: metered‐dose inhaler; PO: oral.

Table 2. Summary of included studies comparing ICS alone to oral corticosteroid alone

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Comparison 1. Any ICS plus oral corticosteroid versus oral corticosteroid

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Asthma relapse at 7‐10 days Show forest plot	3	909	Odds Ratio (M‐H, Fixed, 95% CI)	0.72 [0.48, 1.10]

2 Asthma relapse at 20‐24 days Show forest plot	3	909	Odds Ratio (M‐H, Fixed, 95% CI)	0.68 [0.46, 1.02]

3 Hospital admission Show forest plot	2	805	Odds Ratio (M‐H, Fixed, 95% CI)	0.99 [0.39, 2.52]

4 Beta₂‐agonist use at 7‐10 days Show forest plot	3	672	Mean Difference (IV, Fixed, 95% CI)	0.51 [‐0.44, 1.47]

5 Beta₂‐agonist use at 20‐24 days Show forest plot	3	602	Mean Difference (IV, Random, 95% CI)	‐0.14 [‐2.35, 2.06]

6 PEF at 7‐10 days Show forest plot	2	205	Mean Difference (IV, Fixed, 95% CI)	‐0.88 [‐28.49, 26.72]

7 PEF at 20‐24 days Show forest plot	2	172	Mean Difference (IV, Fixed, 95% CI)	‐4.55 [‐35.91, 26.81]

8 PEF% at 7‐10 days Show forest plot	2	206	Mean Difference (IV, Random, 95% CI)	‐1.79 [‐11.04, 7.46]

9 PEF% at 20‐24 days Show forest plot	2	172	Mean Difference (IV, Random, 95% CI)	‐2.34 [‐9.44, 4.77]

10 Quality of life at 7‐10 days Show forest plot	2	613	Mean Difference (IV, Fixed, 95% CI)	0.19 [‐0.01, 0.39]

11 Quality of life at 20‐24 days Show forest plot	2	559	Mean Difference (IV, Random, 95% CI)	0.33 [‐0.36, 1.01]

12 Cough at 7‐10 days Show forest plot	2	620	Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.57, 0.07]

13 Cough at 20‐24 days Show forest plot	2	571	Mean Difference (IV, Random, 95% CI)	‐0.47 [‐1.25, 0.31]

14 Wheeze at 7‐10 days Show forest plot	2	622	Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.48, 0.12]

15 Wheeze at 20‐24 days Show forest plot	2	571	Mean Difference (IV, Random, 95% CI)	‐0.43 [‐1.31, 0.45]

16 Dyspnoea at 7‐10 days Show forest plot	2	620	Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.92, 0.33]

17 Dyspnoea at 20‐24 days Show forest plot	2	571	Mean Difference (IV, Random, 95% CI)	‐0.43 [‐1.31, 0.45]

18 Hoarseness at 7‐10 days Show forest plot	2	612	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.53, 1.46]

19 Hoarseness at 20‐24 days Show forest plot	2	596	Odds Ratio (M‐H, Fixed, 95% CI)	0.60 [0.36, 1.01]

20 Sore throat at 7‐10 days Show forest plot	2	612	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.43, 1.24]

21 Sore throat at 20‐24 days Show forest plot	2	596	Odds Ratio (M‐H, Fixed, 95% CI)	0.64 [0.35, 1.16]

22 Asthma relapse at 7‐10 days ‐ gender subgroups Show forest plot	3	720	Odds Ratio (M‐H, Random, 95% CI)	0.76 [0.38, 1.52]

22.1 Male	3	296	Odds Ratio (M‐H, Random, 95% CI)	0.96 [0.21, 4.43]
22.2 Female	3	424	Odds Ratio (M‐H, Random, 95% CI)	0.79 [0.34, 1.82]
23 Asthma relapse at 20‐24 days ‐ gender subgroups Show forest plot	3	761	Odds Ratio (M‐H, Random, 95% CI)	0.71 [0.37, 1.35]

23.1 Male	3	315	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.22, 1.62]
23.2 Female	3	446	Odds Ratio (M‐H, Random, 95% CI)	0.78 [0.30, 1.99]
24 Asthma relapse at 7‐10 days; patients lost to follow‐up excluded Show forest plot	3	725	Odds Ratio (M‐H, Fixed, 95% CI)	0.72 [0.47, 1.10]

25 Asthma relapse at 20‐24 days; patients lost to follow‐up excluded Show forest plot	3	768	Odds Ratio (M‐H, Fixed, 95% CI)	0.70 [0.46, 1.05]

Comparison 1. Any ICS plus oral corticosteroid versus oral corticosteroid

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Comparison 2. Any ICS versus oral corticosteroid

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Asthma relapse at 7‐10 days Show forest plot	4	684	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.66, 1.52]

2 Asthma relapse at 16‐21 days Show forest plot	2	425	Odds Ratio (M‐H, Fixed, 95% CI)	1.26 [0.80, 1.99]

3 Hospital admission Show forest plot	3	254	Odds Ratio (M‐H, Fixed, 95% CI)	0.31 [0.01, 7.95]

4 PEF at 7‐10 days Show forest plot	6	1047	Mean Difference (IV, Fixed, 95% CI)	10.95 [‐0.84, 22.73]

5 PEF at 16‐21 days Show forest plot	4	792	Mean Difference (IV, Fixed, 95% CI)	15.21 [1.53, 28.89]

6 PEF% at 7‐10 days Show forest plot	2	376	Mean Difference (IV, Fixed, 95% CI)	‐0.74 [‐3.12, 1.64]

7 PEF% at 16‐21 days Show forest plot	2	347	Mean Difference (IV, Fixed, 95% CI)	0.58 [‐2.07, 3.23]

8 FEV₁% pred at 6‐10 days (outcome not pre‐specified in original review) Show forest plot	1	55	Mean Difference (IV, Fixed, 95% CI)	‐17.80 [‐26.98, ‐8.62]

9 FEV₁% pred at 16‐21 days (outcome not pre‐specified in original review) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

10 Beta₂‐agonist use at 7‐10 days Show forest plot	3	128	Mean Difference (IV, Fixed, 95% CI)	0.08 [‐0.47, 0.64]

11 Beta₂‐agonist use at 14‐21 days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

12 Quality of life at 7‐10 days Show forest plot	2	231	Std. Mean Difference (IV, Fixed, 95% CI)	0.14 [‐0.12, 0.40]

13 Cough at 7‐10 days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

14 Wheeze at 7‐10 days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

15 Wheeze at 16‐21 days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

16 Hoarseness at 7‐10 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

17 Hoarseness at 16‐21 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

18 Sore throat at 7‐10 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

19 Sore throat at 16‐21 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. Any ICS versus oral corticosteroid

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