Fluticasone at different doses for chronic asthma in adults and children

Nick P Adams; Janine C Bestall; Paul Jones; Toby J Lasserson; Benedict Griffiths; Christopher J Cates

doi:10.1002/14651858.CD003534.pub3

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Figure 1

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Analysis 1.1

Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 1 Change in FEV1 compared to baseline (litres).

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Analysis 1.2

Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 2 Change in morning PEFR compared to baseline (L/min).

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Analysis 1.3

Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 3 Change in morning PEFR compared to baseline (L/min).

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Analysis 1.4

Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 4 Change in daily asthma symptom score compared to baseline.

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Analysis 1.5

Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 5 Change in number of night‐time awakenings/week compared to baseline.

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Analysis 1.6

Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 6 Change in daily use of beta2 agonist compared to baseline (puffs/d).

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Analysis 1.7

Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 7 Number of patients withdrawn due to lack of efficacy.

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Analysis 2.1

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 1 Change in FEV1 compared to baseline (litres).

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Analysis 2.2

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 2 Change in FVC compared to baseline (litres).

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Analysis 2.3

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 3 Change in FEF25‐75 compared to baseline (L/second).

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Analysis 2.4

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 4 Change in morning PEFR compared to baseline (L/min).

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Analysis 2.5

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 5 Change in evening PEFR compared to baseline (L/min).

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Analysis 2.6

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 6 Change in daily asthma symptom score compared to baseline.

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Analysis 2.7

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 7 Change in number of night‐time awakenings/week compared to baseline.

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Analysis 2.8

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 8 Change in daily use of beta2 agonist compared to baseline (puffs/d).

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Analysis 2.9

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 9 Number of patients withdrawn due to lack of efficacy.

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Analysis 2.10

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 10 Hoarseness or dysphonia (No. of patients).

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Analysis 2.11

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 11 Oral Candidiasis (No. of patients).

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Analysis 2.12

Comparison 2 Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages), Outcome 12 Physician global rated efficacy: ineffective.

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Analysis 3.1

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 1 Change in FEV1 compared to baseline (litres).

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Analysis 3.2

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 2 Change in FEV1 compared to baseline (litres).

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Analysis 3.3

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 3 FEV1 (% predicted).

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Analysis 3.4

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 4 FEV1 (% predicted).

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Analysis 3.5

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 5 FEV1 Litres.

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Analysis 3.6

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 6 PEF (L/min).

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Analysis 3.7

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 7 Change in clinic PEFR compared to baseline (L/min).

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Analysis 3.8

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 8 Change in morning PEFR compared to baseline (L/min).

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Analysis 3.9

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 9 Change in evening PEFR compared to baseline (L/min).

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Analysis 3.10

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 10 Rescue medication usage.

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Analysis 3.11

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 11 Change in daily use of beta2 agonist compared to baseline (puffs/d).

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Analysis 3.12

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 12 Symptom scores.

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Analysis 3.13

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 13 Change in daily asthma symptom score compared to baseline.

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Analysis 3.14

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 14 Change in number of night‐time awakenings/week compared to baseline.

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Analysis 3.15

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 15 Percentage of symptom‐free days.

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Analysis 3.16

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 16 Change in night‐time awakening score compared to baseline.

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Analysis 3.17

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 17 HRQOL: Functional Status IIR questionaire (short version).

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Analysis 3.18

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 18 HRQOL: Sleep Scale Children questionnaire.

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Analysis 3.19

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 19 HRQOL: Quality of Life of Parents of Asthmatic Children questionnaire, burden dimension.

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Analysis 3.20

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 20 HRQOL: Quality of Life of Parents of Asthmatic Children questionnaire, subjective norms dimension.

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Analysis 3.21

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 21 HRQOL: Quality of Life of Parents of Asthmatic Children questionnaire, subjective norms dimension.

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Analysis 3.22

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 22 Physician global rated efficacy: ineffective.

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Analysis 3.23

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 23 Withdrawal due to asthma exacerbation (No. of patients).

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Analysis 3.24

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 24 Withdrawals due to adverse events.

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Analysis 3.25

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 25 Number of patients withdrawn due to lack of efficacy.

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Analysis 3.26

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 26 Oral Candidiasis (No. of patients).

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Analysis 3.27

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 27 Headaches.

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Analysis 3.28

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 28 Sore throat or pharyngitis (No. of patients).

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Analysis 3.29

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 29 Hoarseness or dysphonia (No. of patients).

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Analysis 3.30

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 30 Urinary free cortisol excretion (mcg/24 hours).

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Analysis 3.31

Comparison 3 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages), Outcome 31 Morning plasma cortisol (mcg/dL).

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Analysis 4.1

Comparison 4 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (subgroups), Outcome 1 Change in FEV1 compared to baseline based on study duration(litres) ‐ children.

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Analysis 4.2

Comparison 4 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (subgroups), Outcome 2 Change in FEV1 compared to baseline based on study duration (litres) ‐ adults.

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Analysis 4.3

Comparison 4 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (subgroups), Outcome 3 Change in FEV1 compared to baseline (litres) based on delivery devices ‐ children.

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Analysis 4.4

Comparison 4 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (subgroups), Outcome 4 Change in FEV1 compared to baseline based on delivery devices (litres) ‐ adults.

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Analysis 4.5

Comparison 4 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (subgroups), Outcome 5 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ children.

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Analysis 4.6

Comparison 4 Parallel group studies, no oral steroids: 100 versus 200 mcg/d (subgroups), Outcome 6 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ adults.

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Analysis 5.1

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 1 FEV1 (% predicted).

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Analysis 5.2

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 2 Change in FEV1 compared to baseline (litres).

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Analysis 5.3

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 3 Change in FEV1 compared to baseline (litres ‐ imputed estimates).

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Analysis 5.4

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 4 Change in FVC compared to baseline (litres).

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Analysis 5.5

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 5 Change in FEF25‐75 compared to baseline (L/second).

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Analysis 5.6

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 6 Change in morning PEFR compared to baseline (L/min ‐ imputed/estimated values).

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Analysis 5.7

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 7 Change in morning PEFR compared to baseline (L/min).

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Analysis 5.8

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 8 Change in evening PEFR compared to baseline (L/min).

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Analysis 5.9

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 9 PC20.

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Analysis 5.10

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 10 PD20.

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Analysis 5.11

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 11 Change in daily use of beta2 agonist compared to baseline (puffs/d).

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Analysis 5.12

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 12 Change in number of night‐time awakenings/week compared to baseline.

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Analysis 5.13

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 13 Change in % nights without waking.

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Analysis 5.14

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 14 Change in daily asthma symptom score compared to baseline.

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Analysis 5.15

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 15 Percentage of symptom‐free days.

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Analysis 5.17

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 17 Number of patients withdrawn due to lack of efficacy.

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Analysis 5.18

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 18 Exacerbations requiring oral steroids.

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Analysis 5.19

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 19 Exacerbations requiring hospitalisation.

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Analysis 5.20

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 20 Oral Candidiasis (No. of patients).

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Analysis 5.21

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 21 Sore throat or pharyngitis (No. of patients).

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Analysis 5.22

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 22 Hoarseness or dysphonia (No. of patients).

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Analysis 5.23

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 23 Withdrawals due to adverse events.

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Analysis 5.24

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 24 No. patients with </=18 mcg/dL poststimulation cortisol.

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Analysis 5.25

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 25 AUC serum cortisol.

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Analysis 5.26

Comparison 5 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages), Outcome 26 Change in peak plasma cortisol expression.

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Analysis 6.1

Comparison 6 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (subgroups), Outcome 1 Change in FEV1 compared to baseline based on study duration (litres) ‐ adults.

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Analysis 6.2

Comparison 6 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (subgroups), Outcome 2 Change in FEV1 compared to baseline based on delivery devices (litres) ‐ adults.

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Analysis 6.3

Comparison 6 Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (subgroups), Outcome 3 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ adults.

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Analysis 7.1

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 1 Change in FEV1 compared to baseline (litres).

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Analysis 7.2

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 2 FEV1 (% predicted).

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Analysis 7.3

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 3 Change in morning PEFR compared to baseline (L/min).

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Analysis 7.4

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 4 Change in evening PEFR compared to baseline (L/min).

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Analysis 7.5

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 5 Percentage of symptom‐free days.

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Analysis 7.6

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 6 Change in daily asthma symptom score compared to baseline.

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Analysis 7.7

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 7 Change in number of night‐time awakenings/week compared to baseline.

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Analysis 7.8

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 8 Change in daily use of beta2 agonist compared to baseline (puffs/d).

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Analysis 7.9

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 9 Physician global rated efficacy: ineffective.

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Analysis 7.10

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 10 Number of patients withdrawn due to lack of efficacy.

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Analysis 7.11

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 11 Sore throat or pharyngitis (No. of patients).

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Analysis 7.12

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 12 Hoarseness or dysphonia (No. of patients).

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Analysis 7.13

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 13 Oral Candidiasis (No. of patients).

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Analysis 7.14

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 14 Plasma Cortisol (AUC).

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Analysis 7.15

Comparison 7 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages), Outcome 15 Clinic PEF (L/min ‐ change from baseline).

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Analysis 8.1

Comparison 8 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (subgroups), Outcome 1 Change in FEV1 compared to baseline based on study duration (litres) ‐ adults.

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Analysis 8.2

Comparison 8 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (subgroups), Outcome 2 Change in FEV1 compared to baseline based on delivery devices (litres) ‐ adults.

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Analysis 8.3

Comparison 8 Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (subgroups), Outcome 3 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ adults.

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Analysis 9.1

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 1 FEV1 (Change from baseline ‐ litres).

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Analysis 9.2

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 2 Change in morning PEF (L/min).

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Analysis 9.3

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 3 Change in evening PEF (L/min).

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Analysis 9.4

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 4 Change in rescue medication (puffs/d).

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Analysis 9.6

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 6 Change in daily symptoms compared with baseline.

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Analysis 9.8

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 8 Exacerbations requiring hospitalisation.

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Analysis 9.9

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 9 Exacerbations requiring OCS treatment.

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Analysis 9.10

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 10 Withdrawals (total).

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Analysis 9.11

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 11 Withdrawals (adverse events).

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Analysis 9.12

Comparison 9 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages), Outcome 12 Withdrawals (lack of efficacy).

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Analysis 10.1

Comparison 10 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (subgroups), Outcome 1 Change from baseline in FEV1 based on study duration (litres) ‐ adults.

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Analysis 10.2

Comparison 10 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (subgroups), Outcome 2 Change from baseline in FEV1 based on delivery devices (litres) ‐ adults.

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Analysis 10.3

Comparison 10 Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (subgroups), Outcome 3 Change from baseline in FEV1 based on degree of severity (litres) ‐ adults.

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Analysis 11.1

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 1 Change in FEV1 compared to baseline (litres).

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Analysis 11.2

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 2 FEV1 (% predicted).

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Analysis 11.3

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 3 FEV1 (Litres).

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Analysis 11.4

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 4 Change in FVC compared to baseline (litres).

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Analysis 11.5

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 5 FEF25‐75.

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Analysis 11.6

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 6 Change in FEF25‐75 compared to baseline (L/second).

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Analysis 11.7

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 7 am PEF (Litres/min).

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Analysis 11.8

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 8 Change in morning PEFR compared to baseline (L/min).

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Analysis 11.9

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 9 Change in evening PEFR compared to baseline (L/min).

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Analysis 11.10

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 10 Physician global rated efficacy: ineffective.

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Analysis 11.11

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 11 Symptoms.

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Analysis 11.12

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 12 Percentage of symptom‐free days.

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Analysis 11.13

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 13 Change in daily asthma symptom score compared to baseline.

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Analysis 11.14

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 14 Change in number of night‐time awakenings/week compared to baseline.

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Analysis 11.15

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 15 Rescue medication usage.

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Analysis 11.16

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 16 Change in daily use of beta2 agonist compared to baseline (puffs/d).

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Analysis 11.17

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 17 Oral Candidiasis (No. of patients).

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Analysis 11.18

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 18 Hoarseness or dysphonia (No. of patients).

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Analysis 11.19

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 19 Withdrawals (total).

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Analysis 11.20

Comparison 11 Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages), Outcome 20 Number of patients withdrawn due to lack of efficacy.

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Analysis 12.1

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 1 Change in FEV1 compared to baseline (litres).

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Analysis 12.2

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 2 Change in FEV1 compared to baseline (%).

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Analysis 12.3

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 3 Change in FEV1 % predicted.

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Analysis 12.4

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 4 FEV1 (% predicted).

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Analysis 12.5

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 5 Change in morning PEFR compared to baseline (L/min).

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Analysis 12.6

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 6 Change in evening PEFR compared to baseline (L/min).

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Analysis 12.7

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 7 Change in FVC compared to baseline (litres).

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Analysis 12.8

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 8 Change in FEF25‐75 compared to baseline (L/second).

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Analysis 12.9

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 9 PD20.

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Analysis 12.10

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 10 Change in daily asthma symptom score compared to baseline.

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Analysis 12.11

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 11 Change in number of night‐time awakenings/week compared to baseline.

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Analysis 12.12

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 12 Physician global rated efficacy: ineffective.

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Analysis 12.13

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 13 Change in daily use of beta2 agonist compared to baseline (puffs/d).

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Analysis 12.14

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 14 Number of patients withdrawn due to lack of efficacy.

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Analysis 12.15

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 15 Oral Candidiasis (No. of patients).

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Analysis 12.16

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 16 Sore throat or pharyngitis (No. of patients).

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Analysis 12.17

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 17 Hoarseness or dysphonia (No. of patients).

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Analysis 12.18

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 18 Change in peak plasma cortisol compared to baseline (mcg/dL).

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Analysis 12.19

Comparison 12 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages), Outcome 19 Change in morning plasma cortisol compared to baseline (mcg/dL).

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Analysis 13.1

Comparison 13 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (subgroups), Outcome 1 Change in FEV1 compared to baseline based on study duration (litres) ‐ adults.

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Analysis 13.2

Comparison 13 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (subgroups), Outcome 2 Change in FEV1 compared to baseline based on delivery devices (litres) ‐ adults.

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Analysis 13.3

Comparison 13 Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (subgroups), Outcome 3 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ adults.

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Analysis 14.1

Comparison 14 Parallel group studies, no oral steroids: 4‐500 versus 1500‐2000mcg/d (all ages), Outcome 1 FEV1 (Change from baseline ‐ litres).

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Analysis 14.2

Comparison 14 Parallel group studies, no oral steroids: 4‐500 versus 1500‐2000mcg/d (all ages), Outcome 2 Clinic PEF (L/min ‐ change from baseline).

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Analysis 14.3

Comparison 14 Parallel group studies, no oral steroids: 4‐500 versus 1500‐2000mcg/d (all ages), Outcome 3 PC20 (methacholine).

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Analysis 14.4

Comparison 14 Parallel group studies, no oral steroids: 4‐500 versus 1500‐2000mcg/d (all ages), Outcome 4 PC20 AMP.

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Analysis 14.5

Comparison 14 Parallel group studies, no oral steroids: 4‐500 versus 1500‐2000mcg/d (all ages), Outcome 5 Symptoms (change from baseline).

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Analysis 15.1

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 1 Change in daily dose of oral prednisolone compared to baseline (mg).

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Analysis 15.2

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 2 Number of patients unable to discontinue OCS completely.

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Analysis 15.3

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 3 Change in FEV1 compared to baseline (litres).

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Analysis 15.4

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 4 Change in morning PEFR compared to baseline (L/min).

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Analysis 15.5

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 5 Change in evening PEFR compared to baseline (L/min).

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Analysis 15.6

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 6 Change in daily asthma symptom score compared to baseline.

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Analysis 15.7

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 7 Change in rescue beta2 agonist use compared to baseline (puffs/d).

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Analysis 15.8

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 8 Asthma Quality of Life Questionnaire: change in overall score compared to baseline.

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Analysis 15.9

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 9 Asthma Quality of Life Questionnaire: change in activity limitation domain compared to baseline.

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Analysis 15.10

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 10 Asthma Quality of Life Questionnaire: change in symptom domain compared to baseline.

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Analysis 15.11

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 11 Asthma Quality of Life Questionnaire: change in emotional function domain compared to baseline.

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Analysis 15.12

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 12 Asthma Quality of Life Questionnaire: change in environmental exposure domain compared to baseline.

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Analysis 15.13

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 13 Sore throat (No. of patients).

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Analysis 15.14

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 14 Hoarseness/dysphonia (No. of patients).

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Analysis 15.15

Comparison 15 Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d, Outcome 15 Oral Candidiasis (No. of patients).

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Analysis 16.1

Comparison 16 Crossover studies, no oral steroids: 200 versus 1000 mcg (all ages), Outcome 1 FEV1.

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Analysis 16.2

Comparison 16 Crossover studies, no oral steroids: 200 versus 1000 mcg (all ages), Outcome 2 PEF.

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Table 2. Data not included in the meta‐analysis

Study ID	Data
Allen 2000	Steroid consumption Side effects Unclear reporting (no response from trialists)
Ayres 1995	Symptom free days and nights Rescue beta2 agonist free days and nights Daytime and night‐time symptom scores Above outcomes analysed by investigators using non‐parametric statistics Change in FEV1 compared to baseline Change in FVC compared to baseline Change in morning PEFR compared to baseline Change in evening PEFR compared to baseline Change in diurnal variability in PEFR compared to baseline Change in clinic PEFR compared to baseline No SD values available for above outcomes Morning plasma cortisol Data log transformed and reported using geometric means by investigators: log transformed values not available
Boner 1999	Methacholine BHR (PC20 FEV1) Log transformed data not available FEV1 No SD values available Overnight urinary cortisol No numerical data available
Bukovskis 2002	FEV1 change from baseline Unclear reporting (no response from trialists)
Chervinsky 1994	Change in urinary free cortisol compared to baseline Change in urinary 17‐hydroxy steroids compared to baseline Change in morning plasma cortisol compared to baseline Change in plasma cortisol 60 min post co‐syntropin No SD values available for above outcomes
Chetta 2002	FEV1 Unclear reporting (no response from trialists)
Dahl 1993	Morning plasma cortisol Plasma cortisol 30 min post 250 mcg ACTH Diurnal variation in PEFR FVC Daily beta2 agonist use (puffs/day) No SD values available for above outcomes
Derom 1999	Cortisol suppression Unclear reporting (no response from trialists)
Derom 2001	Cortisol suppression PC20 Unclear reporting (no response from trialists)
Gershman 2000	PC20 ECP Data reported as medians
Hofstra 2000	PD20 No SDs presented.
Ind 2003	Medication usage Symptoms Data presented as medians
Katz 1998	Change in FEV1 compared to baseline Change in FVC compared to baseline Change in FEF25‐75 compared to baseline Change in evening PEFR compared to baseline Change in night‐time awakening score compared to baseline No SD values available for above outcomes
Meijer 1999	FEV1 PEF Symptoms Medication usage Cortisol Data presented as medians
Nieto 2001	PC20 Unclear reporting (no response from trialists)
Noonan 1998	Change in log e methacholine bronchial responsiveness PD20 FEV1 Error bars plotted on graphical display of results, but unclear whether these represent SD or SEM values
Pauwels 2002	Cortisol suppression PC20 Unclear reporting (no response from trialists)
Pearlman 1997	Change in evening PEFR compared to baseline Medical Outcomes Study Short Form (SF‐36A) Living with asthma questionnaire No SD values available for above outcomes Morning serum cortisol No numerical data available for above outcome Physician rated global assessment of efficacy Data not presented in a form suitable for meta‐analysis
SAM40012	% symptom free days rescue medication usage Data reported as medians.
Verona 2003	Medication usage Symptoms Data reported as medians
Wallin 2003	am PEF/pm PEF Data reported as medians
Wasserman 1996	Physician‐rated global assessment of effectiveness Data not presented in a form suitable for meta‐analysis
Wolfe 1996	Change FEV1 compared to baseline No SD values available for above outcome Change in morning PEFR compared to baseline Change in evening PEFR compared to baseline Daily wheeze, cough, shortness of breath scores Daily beta2 agonist use Morning plasma cortisol No numerical data available for above outcomes

Table 2. Data not included in the meta‐analysis

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Table 3. Methods of imputations and estimates

Outcome	WMD/GIV	Study	Method
07:03	WMD	Pinnas 2005	Published means. SDs based on other studies.
07:07	GIV	Pinnas 2005	Published means. SDs based on other studies.
07:07	GIV	Wolfe 1996	Published P values (versus placebo), assumed same SEM between two FP groups.
20:01	WMD	Pinnas 2005	Published means. SDs based on other studies.
20:03	WMD	Ind 2003; Pinnas 2005	Published means. SDs based on other studies.

Table 3. Methods of imputations and estimates

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Table 4. Search History Detail

Date	N included/excluded
All Years searching to March 1999	Initial version of the review (All Years searching to March 1999): 6494 citations retrieved, 2162 unique citations imported to Inhaled Steroid Register. From this a fluticasone register was created consisting of 258 citations. 180 excluded on basis of abstract: 150 not RCT; 30 not chronic asthma in humans; 78 papers retrieved in full text form; 57 excluded on basis of full paper: 6 not RCT; 1 infants; 3 delivery device comparison; 1 treatment period < 1 week; 46 not a comparison of 2 or more doses of FP; 21 publications meeting inclusion criteria; 16 unique studies meeting inclusion criteria One study (Raphael 1999) was identified by Glaxo Wellcome. This study was published after the date of the final electronic search (March 1999). Three studies (Boner 1999, Hofstra 2000, Ind 2003) were identified as a result of searching respiratory society meeting abstracts.
Update (March 1999‐January 2005)	From hand searching the updated inhaled steroids search results (additional 1301 references), a 'fluticasone' register was created consisting of 196 citations (121 references excluded from abstracts as irrelevant comparisons). Forty‐six references pertaining to 34 studies were retrieved in full for this review. One study reported findings from two data‐sets and these studies have been given two identifiers (Sorkness 1999; Sorkness 1999a). We excluded 11 studies for the following reasons: Wrong comparator (9), outcomes not relevant (2) and varying dose of FP (1). 24 new studies met the inclusion criteria for the review (Allen 2000; Bukovskis 2002; Casale 2001; Chetta 2002; Derom 1999; Derom 2001; Falcoz 2000; Gershman 2000; Giannini 2003; Kemp 2004; Li 1999; Meijer 1999; Nathan 2000; Nielsen 2002; Nieto 2001; O'Sullivan 2002; Pauwels 2002; Pearlman 1999; Pearlman 2002; SAM40012; Sorkness 1999; Sorkness 1999a; Verona 2003; Wallin 2003). Data for two studies previously included as abstracts were published in full text form (Hofstra 2000; Ind 2003). One study was identified from an online repository of unpublished clinical trials (SAM40012).
January 2005‐January 2006	References identified: 411 Number assessed for further scrutiny: 55

Table 4. Search History Detail

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Table 5. Asthma severity: characteristics of included patients at baseline

Study ID	FEV1: incl. criteria	Basline FEV1	Symptom frequency	OCS treatment	ICS treatment	Author opinion	Overall estimation
Agertoft 1997	Not stated	Not stated	No	No	Not stated	Mild	Mild
Allen 1998	>60	88‐89%	Not stated	No	Approx. 50% patients ICS naive at baseline, 50% previous regular ICS use	Mild to moderate	Mild to moderate
Allen 2000	Not stated	61%	Not stated	Yes (non‐OCS dependents excluded)	Not stated	Severe	Severe
Ayres 1995	Not stated	Mean baseline morning PEFR 73‐77 (% predicted)	Need for 2 or more doses beta2 agonist on 2 out of 7 days of run in period	Proportion of patients using OCS (<10 mg/d)	Yes: BDP 1‐2 mg/d or BUD 0.8‐1.6 mg/d	moderate to severe	Moderate to severe
Boner 1999	Not stated	Not stated	Not stated	No	Not stated	Not stated	Unclear
Bukovkis 2002	Not stated	Not stated	Not stated	Not stated	Not stated	Not stated	Unclear
Casale 2001	>/=65%	3‐3.2 L	Not stated	No	Not stated	Mild to moderate	Mild to moderate
Chervinsky 1994	60‐90	71‐73%	Not stated	No	Yes: at least 1 month regular treatment with BDP prior to study	Mild to moderate	Mild to moderate
Chetta 2002	>70%	100‐110%	Well documented history of asthma	No	Not stated	Mild to moderate	Mild
Dahl 1993	Not stated	73‐75%	daytime wheezing or night‐time symptoms on at least 4 days of 7 day run‐in period or PEFR variability 20% or greater	No	Yes: BDP 1000 mcg/d or less	Moderate	Moderate
Derom 1999	>/=40%	80%	Not stated	No	Not within 6 months	Not stated	Mild
Derom 2001	Not stated	Not stated	Not stated	Not stated	Not stated	Unclear	Unclear
Falcoz 2000	50‐80%	Not stated	Not stated	Not stated	Not stated	Mild‐to‐moderate	Unclear
FAP30001	>/=45%	74‐5%	Not stated	No	Yes	Not stated	Moderate
FLIC15	>/=60% predicted	Not stated	Not stated	No	No	Mild to moderate	Mild
FLIP01/a	Not reported	Not reported	Not reported	No	Yes	Not reported	Moderate
FLIP39	Not reported	Not reported	Perennial symptoms requiring ICS	No	Yes ‐ up to 400mcg/d	Not stated	Moderate
FLTA3014	50‐85%	Not reported	Not reported	No	Yes	Not stated	Unclear
FLTA3020/a	60‐90%	Not reported	Not reported	No	No (low dose ceased 30 days prior to study entry)	Not stated	Mild to moderate
FLTA3022/a	40‐85% predicted	Not reported	Not stated	Yes	Yes	Not stated	Severe
FLTA4030	50‐80%	Not stated	Stable during 7 day run‐in, controlled with SABA alone	No	No	Not stated	Mild to moderate
Galant 1996	45‐75	60‐62%	> 8 puffs/d beta2 agonist or 2‐4 night‐time awakenings in week run‐in	No	No	Mild to moderate	Moderate
Gershman 2000	Not stated	66‐69%	Not stated	Not stated	Not stated	Not stated	Unclear
Giannini 2003	Not stated	3.23 L	Requirement for beta‐agonist treatment during run‐in	Not stated	Not stated	Moderate	Mild to moderate
Hofstra 2000	Not stated	96.6‐93.2%	Not stated	No	No	Not stated	Unclear
Ind 2003	FEV1 not stipulated at inclusion	No details	Symptomatic despite ICS treatment. History of exacerbations	No	Yes: 1000‐1600 mcg/d of BDP or BUD	Moderate‐severe	Moderate‐severe
Katz 1998	Not stated	PEFR 75 (% predicted) or less	Asthma symptoms on at least 4 out of 10 days of run in period or at least one night‐time awakening in 10 days or 4 or puffs beta2 agonist on at least 4 days	No	No	Not stated	Moderate
Kemp 2004	50‐100% predicted	82‐85% predicted	Mild stable asthma	No	No	Mild	Mild
Lawrence 1997	50‐80	65‐68%	"Mean beta2 agonist use 3.2 ‐ 4.2 puffs/d "	No	Yes: 3 months treatment or longer prior to study	Not stated	Moderate
Li 1999	FEV1 </=50% predicted	82.5‐88.2%	Not stated	No	No	Not stated	Mild
Lumry 2006	45‐80%	65.3‐65.5	Not stated	No	Yes	Not stated	Moderate
Meijer 1999	Not stipulated	79‐81%	Participants who exacerbated needing OCS during run‐in were excluded	No	Yes ‐ treatment tapered prior to randomisation	Mild‐moderate	Mild to moderate
Nathan 2000	45‐75% predicted	63.3‐64.3	Not stated	No	Yes	Moderate	Moderate
Nelson 1999	40‐80	60‐62%	Not stated	Yes	Almost 100% of patients receiving ICS	Severe	Severe
Nieto 2001	Not stated	Not stated	Not stated	Not stated	Not stated	Not stated	Unclear
Noonan 1998	60‐85	73‐76%	"No more than 12 puffs/d beta2 agonist and no more than 3 nights with awakening due to asthma"	No	No	Mild to moderate	Moderate
Noonan 1995	40‐80	56‐57.4%	Requirement for rescue beta2 agonist for 2 weeks prior to study due to symptoms	Yes	87% of patients receiving ICS	Severe	Severe
O'Sullivan 2002	>/=60%	79‐86%	Not stated	No	No	Mild‐moderate	Mild to moderate
Pauwels 2002	Not stated	Not stated	Not stated	Not stated	Not stated	Not stated	Unclear
Pearlman 1997	50‐80	66‐67%	"Mean beta2 agonist use 3.4‐4.1 puffs/dNo more than 12 puffs/d beta2 agonist and no more than 2 nights with awakening due to asthma symptoms in last 7 days"	No	Yes: at least 3 months	Moderate	Moderate
Pearlman 1999	50‐80%	65‐69%	Not stated	No	No	Mild‐moderate	Mild to moderate
Peden 1998	50‐85	72‐73%	"No more than 12 puffs/d beta2 agonist and no more than 3 nights with awakening due to asthmaMean awakenings per night due to asthma 0.05 to 0.09Mean beta2 agonist use 1.4 to 2.0 puffs/d"	No	Some patients: amount and type of ICS not stated	Not stated	Moderate
Pinnas 2005	45‐80	67%	'during the week before randomization, patients could not have had more than 3 days in which more than 12 inhalations of albuterol were used, more than 3 nights with awakenings due to asthma requiring albuterol, or asthma exacerbations requiring systemic corticosteroids and/or hospitalization.'	No	No	Moderate to severe	Moderate
Raphael 1999	45‐65	64.7‐65.7%	> 8 puffs/week beta 2 agonist or diurnal variability in PEFR > 20% during run‐in if FEV > 65‐80 (% predicted)	No	Yes: BDP or TA 8‐12 puffs/d	mild/moderate and severe	mild/moderate and severe
SAM40012	Not stated	Not stated	Symptom score greater than 2 on at least 3 of previous 7 days	Not stated	Yes	Not stated	Moderate
Sheffer 1996	45‐75	62‐64%	"During 7 day run‐in:> 2 night‐time awakenings due to asthma in last 7 days20% or greater PEFR diurnal variability at least one day in which 8 puffs beta2 agonist used "	No	No	Mild to moderate	Moderate
Sorkness 1999a	>/=50%	86‐88%	Not stated	No	No	Mild to moderate	Mild to moderate
Sorkness 1999	>/=50%	83‐88%	Not stated	No	No	Mild to moderate	Mild to moderate
Verona 2003	Not stated	Not stated	Exacerbation in last year requiring hospitalisation	No	Yes	Moderate to severe	Moderate to severe
Wallin 2003	Not stated	91‐2%	Symptomatoic during run‐in period despite medication	Not stated	Yes	Mild to moderate	Mild to moderate
Wasserman 1996	50‐80%	Not stated	"Mean beta2 agonist use 3.1 to 3.3 puffs/dDuring last 7 days run‐in no more than 12 puffs/d beta2 agonist and no more than 2 nights with awakening due to asthma"	No	No	Not stated	Moderate
Wolfe 1996	50‐80%	64‐66%	During 2 week run‐in period no more than 12 puffs/d beta2 agonist and no more than 2 nights with awakening due to asthma	No	Yes: dose not stated	Moderate	Moderate

Table 5. Asthma severity: characteristics of included patients at baseline

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Table 6. Criteria for withdrawal due to lack of efficacy

Study ID	FEV1	PEFR	Beta2 agonist use	Night‐time awakening	Exacerbations
Chervinsky 1994	20% or greater decrease compared to baseline	20% decrease in morning or evening PEFR on 4 or more days out of 7 in week prior to clinic visit	12 or more puffs on 3 or more days out of 7 in week prior to clinic visit	2 or more nights with 2 awakening out of 7 in week prior to clinic visit	Any clinical exacerbation requiring emergency treatment, hospital admission or additional asthma medication other than rescue beta 2 agonist
Galant 1996	15% or greater decrease compared to baseline	20% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	12 or more puffs on 3 or more days out of 7 in week prior to clinic visit	3 or more awakening in week prior to clinic visit
Katz 1997	15% or greater decrease compared to baseline	15% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	8 or more puffs on 2 or more days out of 7 in week prior to clinic visit	2 or more nights with awakening out of 7 in week prior to clinic visit
Lawrence 1997	20% or greater decrease compared to baseline	20% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	12 or more puffs on 2 or more days out of 7 in week prior to clinic visit	2 or more nights with awakening out of 7 in week prior to clinic visit	any clinical exacerbation requiring emergency treatment, hospital admission or additional asthma medication other than rescue beta 2 agonist
Nathan 2000	20% or greater decrease compared to baseline	20% or greater decrease compared to baseline	12 or more puffs on 2 or more days out of 7 in week prior to clinic visit	2 or more awakening in week prior to clinic visit	Any clinical exacerbation requiring emergency treatment, hospital admission or additional asthma medication other than rescue beta 2 agonist
Pearlman 1997	20% or greater decrease compared to baseline	20% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	12 or more puffs on 2 or more days out of 7 in week prior to clinic visit	2 or more awakening in week prior to clinic visit	Any clinical exacerbation requiring emergency treatment, hospital admission or additional asthma medication other than rescue beta 2 agonist
Peden 1997	15% or greater decrease compared to baseline	20% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	12 or more puffs on 3 or more days out of 7 in week prior to clinic visit	3 or more awakening in week prior to clinic visit	Any clinical exacerbation requiring emergency treatment, hospital admission or additional asthma medication other than rescue beta 2 agonist
Raphael 1999	20% or greater decrease compared to baseline	20% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	12 or more puffs on 3 or more days out of 7 in week prior to clinic visit	3 or more nights with awakening out of 7 in week prior to clinic visit
Sheffer 1996	15% or greater decrease compared to baseline	20% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	12 or more puffs on 3 or more days out of 7 in week prior to clinic visit	3 or more nights with awakening out of 7 in week prior to clinic visit	Any clinical exacerbation requiring emergency treatment, hospital admission or additional asthma medication other than rescue beta 2 agonist
Wasserman 1996	20% or greater decrease compared to baseline	20% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	12 or more puffs on 3 or more days out of 7 in week prior to clinic visit	2 or more nights with awakening out of 7 in week prior to clinic visit	any clinical exacerbation requiring emergency treatment, hospital admission or additional asthma medication other than rescue beta 2 agonist
Wolfe 1996	20% or greater decrease compared to baseline	20% or greater decrease in morning PEFR on 3 or more days out of 7 in week prior to clinic visit	12 or more puffs on 3 or more days out of 7 in week prior to clinic visit	2 or more nights with awakening out of 7 in week prior to clinic visit	Any clinical exacerbation requiring emergency treatment, hospital admission or additional asthma medication other than rescue beta 2 agonist

Table 6. Criteria for withdrawal due to lack of efficacy

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Comparison 1. Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline (litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Change in morning PEFR compared to baseline (L/min) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Change in morning PEFR compared to baseline (L/min) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Change in daily asthma symptom score compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Change in number of night‐time awakenings/week compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Change in daily use of beta2 agonist compared to baseline (puffs/d) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

6.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Number of patients withdrawn due to lack of efficacy Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

7.1 Children	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Adults	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages)

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Comparison 2. Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline (litres) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Adults	2	313	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐0.16, 0.08]
2 Change in FVC compared to baseline (litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Change in FEF25‐75 compared to baseline (L/second) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Change in morning PEFR compared to baseline (L/min) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Adults	2	313	Mean Difference (IV, Fixed, 95% CI)	‐7.49 [‐17.31, 2.33]
5 Change in evening PEFR compared to baseline (L/min) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	2	313	Mean Difference (IV, Fixed, 95% CI)	‐7.95 [‐17.24, 1.34]
6 Change in daily asthma symptom score compared to baseline Show forest plot	2	313	Std. Mean Difference (IV, Fixed, 95% CI)	0.32 [0.10, 0.54]

6.1 Children	0	0	Std. Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Adults	2	313	Std. Mean Difference (IV, Fixed, 95% CI)	0.32 [0.10, 0.54]
7 Change in number of night‐time awakenings/week compared to baseline Show forest plot	2	313	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.02, 0.16]

7.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Adults	2	313	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.02, 0.16]
8 Change in daily use of beta2 agonist compared to baseline (puffs/d) Show forest plot	2	313	Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.37, 0.51]

8.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.2 Adults	2	313	Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.37, 0.51]
9 Number of patients withdrawn due to lack of efficacy Show forest plot	2	313	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.48 [0.88, 2.46]

9.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Adults	2	313	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.48 [0.88, 2.46]
10 Hoarseness or dysphonia (No. of patients) Show forest plot	2	322	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.52 [0.14, 1.97]

10.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Adults	2	322	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.52 [0.14, 1.97]
11 Oral Candidiasis (No. of patients) Show forest plot	2	322	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.27 [0.05, 1.35]

11.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 Adults	2	322	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.27 [0.05, 1.35]
12 Physician global rated efficacy: ineffective Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

12.1 Children	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Adults	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Parallel group studies, no oral steroids: 50 versus 200 mcg/d (all ages)

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Comparison 3. Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline (litres) Show forest plot	10		Litres (Fixed, 95% CI)	Subtotals only

1.1 Children	4	656	Litres (Fixed, 95% CI)	‐0.04 [‐0.09, 0.01]
1.2 Adults	6	887	Litres (Fixed, 95% CI)	0.03 [‐0.02, 0.07]
2 Change in FEV1 compared to baseline (litres) Show forest plot	10		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 Children	4	656	Mean Difference (IV, Fixed, 95% CI)	‐0.03 [‐0.08, 0.02]
2.2 Adults	6	887	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.05, 0.07]
3 FEV1 (% predicted) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 Children	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 FEV1 (% predicted) Show forest plot	2	432	% (Fixed, 95% CI)	‐0.52 [‐3.83, 2.79]

4.1 Children	1	179	% (Fixed, 95% CI)	‐2.0 [‐6.00, 2.00]
4.2 Adults	1	253	% (Fixed, 95% CI)	2.70 [‐3.19, 8.59]
5 FEV1 Litres Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 PEF (L/min) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

6.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Change in clinic PEFR compared to baseline (L/min) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 Children	2	351	Mean Difference (IV, Fixed, 95% CI)	3.00 [‐6.84, 12.84]
7.2 Adults	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Change in morning PEFR compared to baseline (L/min) Show forest plot	11		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

8.1 Children	4	710	Mean Difference (IV, Fixed, 95% CI)	‐3.67 [‐9.81, 2.46]
8.2 Adults	7	1148	Mean Difference (IV, Fixed, 95% CI)	‐7.04 [‐11.87, ‐2.20]
9 Change in evening PEFR compared to baseline (L/min) Show forest plot	6		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

9.1 Children	2	351	Mean Difference (IV, Fixed, 95% CI)	‐4.50 [‐11.77, 2.77]
9.2 Adults	4	648	Mean Difference (IV, Fixed, 95% CI)	‐7.04 [‐12.66, ‐1.43]
10 Rescue medication usage Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

10.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Change in daily use of beta2 agonist compared to baseline (puffs/d) Show forest plot	9	1409	Mean Difference (IV, Fixed, 95% CI)	0.14 [‐0.09, 0.37]

11.1 Children	3	522	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.14, 0.49]
11.2 Adults	6	887	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐0.21, 0.42]
12 Symptom scores Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

12.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
13 Change in daily asthma symptom score compared to baseline Show forest plot	8	1252	Std. Mean Difference (IV, Fixed, 95% CI)	0.04 [‐0.07, 0.15]

13.1 Children	3	522	Std. Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.17, 0.18]
13.2 Adults	5	730	Std. Mean Difference (IV, Fixed, 95% CI)	0.06 [‐0.08, 0.21]
14 Change in number of night‐time awakenings/week compared to baseline Show forest plot	4	661	Mean Difference (IV, Fixed, 95% CI)	0.05 [0.01, 0.09]

14.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14.2 Adults	4	661	Mean Difference (IV, Fixed, 95% CI)	0.05 [0.01, 0.09]
15 Percentage of symptom‐free days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

15.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
16 Change in night‐time awakening score compared to baseline Show forest plot	6	921	Std. Mean Difference (IV, Fixed, 95% CI)	0.17 [0.04, 0.30]

16.1 Children	2	351	Std. Mean Difference (IV, Fixed, 95% CI)	0.17 [‐0.04, 0.38]
16.2 Adults	4	570	Std. Mean Difference (IV, Fixed, 95% CI)	0.17 [0.01, 0.34]
17 HRQOL: Functional Status IIR questionaire (short version) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

17.1 Children	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18 HRQOL: Sleep Scale Children questionnaire Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

18.1 Children	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
19 HRQOL: Quality of Life of Parents of Asthmatic Children questionnaire, burden dimension Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

19.1 Children	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
19.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
20 HRQOL: Quality of Life of Parents of Asthmatic Children questionnaire, subjective norms dimension Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

20.1 Children	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
20.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
21 HRQOL: Quality of Life of Parents of Asthmatic Children questionnaire, subjective norms dimension Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

21.1 Children	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
21.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
22 Physician global rated efficacy: ineffective Show forest plot	2	357	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.37 [0.77, 2.44]

22.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
22.2 Adults	2	357	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.37 [0.77, 2.44]
23 Withdrawal due to asthma exacerbation (No. of patients) Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

23.1 Children	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
23.2 Adults	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
24 Withdrawals due to adverse events Show forest plot	3	627	Odds Ratio (M‐H, Fixed, 95% CI)	1.16 [0.54, 2.47]

24.1 Children	0	0	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
24.2 Adults	3	627	Odds Ratio (M‐H, Fixed, 95% CI)	1.16 [0.54, 2.47]
25 Number of patients withdrawn due to lack of efficacy Show forest plot	9	1657	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.01 [0.76, 1.35]

25.1 Children	3	522	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.25 [0.79, 1.97]
25.2 Adults	6	1135	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.88 [0.61, 1.28]
26 Oral Candidiasis (No. of patients) Show forest plot	6	1150	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.98 [0.46, 2.08]

26.1 Children	2	391	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.33 [0.30, 5.90]
26.2 Adults	4	759	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.88 [0.37, 2.11]
27 Headaches Show forest plot	3	511	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.62 [0.15, 2.60]

27.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
27.2 Adults	3	511	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.62 [0.15, 2.60]
28 Sore throat or pharyngitis (No. of patients) Show forest plot	5	841	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.87 [0.71, 4.93]

28.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
28.2 Adults	5	841	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.87 [0.71, 4.93]
29 Hoarseness or dysphonia (No. of patients) Show forest plot	7	1365	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.65 [0.27, 1.57]

29.1 Children	2	391	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.00 [0.20, 4.99]
29.2 Adults	5	974	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.54 [0.19, 1.55]
30 Urinary free cortisol excretion (mcg/24 hours) Show forest plot	2	228	Mean Difference (IV, Fixed, 95% CI)	‐0.70 [‐3.73, 2.32]

30.1 Children	2	228	Mean Difference (IV, Fixed, 95% CI)	‐0.70 [‐3.73, 2.32]
30.2 Adults	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
31 Morning plasma cortisol (mcg/dL) Show forest plot	3	377	Mean Difference (IV, Fixed, 95% CI)	‐0.06 [‐1.01, 0.89]

31.1 Children	2	333	Mean Difference (IV, Fixed, 95% CI)	‐0.07 [‐1.14, 0.99]
31.2 Adults	1	44	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐2.09, 2.09]

Comparison 3. Parallel group studies, no oral steroids: 100 versus 200 mcg/d (all ages)

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Comparison 4. Parallel group studies, no oral steroids: 100 versus 200 mcg/d (subgroups)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline based on study duration(litres) ‐ children Show forest plot	3	490	Litres (Fixed, 95% CI)	‐0.01 [‐0.07, 0.05]

1.1 1‐4 weeks	0	0	Litres (Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 1‐5 months	3	490	Litres (Fixed, 95% CI)	‐0.01 [‐0.07, 0.05]
1.3 6 months or more	0	0	Litres (Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Change in FEV1 compared to baseline based on study duration (litres) ‐ adults Show forest plot	6		Litres (Fixed, 95% CI)	0.03 [‐0.02, 0.07]

2.1 1‐4 weeks	0		Litres (Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 1‐5 months	6		Litres (Fixed, 95% CI)	0.03 [‐0.02, 0.07]
2.3 6 months or more	0		Litres (Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Change in FEV1 compared to baseline (litres) based on delivery devices ‐ children Show forest plot	3		Litres (Fixed, 95% CI)	‐0.01 [‐0.07, 0.05]

3.1 MDI	0		Litres (Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 DPI	3		Litres (Fixed, 95% CI)	‐0.01 [‐0.07, 0.05]
4 Change in FEV1 compared to baseline based on delivery devices (litres) ‐ adults Show forest plot	6		Litres (Fixed, 95% CI)	0.03 [‐0.02, 0.07]

4.1 MDI	3		Litres (Fixed, 95% CI)	0.02 [‐0.08, 0.12]
4.2 DPI	3		Litres (Fixed, 95% CI)	0.03 [‐0.02, 0.08]
5 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ children Show forest plot	3		Litres (Fixed, 95% CI)	‐0.01 [‐0.07, 0.05]

5.1 Mild to moderate	0		Litres (Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Moderate	3		Litres (Fixed, 95% CI)	‐0.01 [‐0.07, 0.05]
6 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ adults Show forest plot	6		Litres (Fixed, 95% CI)	0.03 [‐0.02, 0.07]

6.1 Mild to moderate	0		Litres (Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Moderate	6		Litres (Fixed, 95% CI)	0.03 [‐0.02, 0.07]

Comparison 4. Parallel group studies, no oral steroids: 100 versus 200 mcg/d (subgroups)

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Comparison 5. Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FEV1 (% predicted) Show forest plot	4	551	Mean Difference (IV, Fixed, 95% CI)	‐0.96 [‐3.45, 1.53]

1.1 Children	2	114	Mean Difference (IV, Fixed, 95% CI)	‐2.48 [‐8.60, 3.64]
1.2 Adults	2	437	Mean Difference (IV, Fixed, 95% CI)	‐0.66 [‐3.39, 2.06]
2 Change in FEV1 compared to baseline (litres) Show forest plot	9	1283	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.06, 0.04]

2.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Adults	9	1283	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.06, 0.04]
3 Change in FEV1 compared to baseline (litres ‐ imputed estimates) Show forest plot	11	1720	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.05]

3.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	11	1720	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.05]
4 Change in FVC compared to baseline (litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Change in FEF25‐75 compared to baseline (L/second) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Change in morning PEFR compared to baseline (L/min ‐ imputed/estimated values) Show forest plot	13		Litres/min (Fixed, 95% CI)	Subtotals only

6.1 Children	2	876	Litres/min (Fixed, 95% CI)	‐7.92 [‐12.93, ‐2.91]
6.2 Adults	11	1713	Litres/min (Fixed, 95% CI)	‐1.97 [‐5.77, 1.82]
7 Change in morning PEFR compared to baseline (L/min) Show forest plot	13		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 Children	2	876	Mean Difference (IV, Fixed, 95% CI)	‐7.92 [‐12.93, ‐2.91]
7.2 Adults	11	1703	Mean Difference (IV, Fixed, 95% CI)	‐4.84 [‐9.37, ‐0.31]
8 Change in evening PEFR compared to baseline (L/min) Show forest plot	7		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

8.1 Children	2	874	Mean Difference (IV, Fixed, 95% CI)	‐9.36 [‐14.37, ‐4.35]
8.2 Adults	5	776	Mean Difference (IV, Fixed, 95% CI)	‐3.76 [‐9.18, 1.66]
9 PC20 Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

9.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 PD20 Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

10.1 Children	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Change in daily use of beta2 agonist compared to baseline (puffs/d) Show forest plot	7	931	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.08, 0.43]

11.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 Adults	7	931	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.08, 0.43]
12 Change in number of night‐time awakenings/week compared to baseline Show forest plot	2	334	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.05, 0.04]

12.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Adults	2	334	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.05, 0.04]
13 Change in % nights without waking Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

13.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
13.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14 Change in daily asthma symptom score compared to baseline Show forest plot	7	930	Std. Mean Difference (IV, Fixed, 95% CI)	0.11 [‐0.02, 0.24]

14.1 Children	0	0	Std. Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14.2 Adults	7	930	Std. Mean Difference (IV, Fixed, 95% CI)	0.11 [‐0.02, 0.24]
15 Percentage of symptom‐free days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

15.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
16 Health related quality of life ‐ AQLQ (absolute scores)	0		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
16.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
16.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17 Number of patients withdrawn due to lack of efficacy Show forest plot	7	1294	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.41 [1.01, 1.98]

17.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
17.2 Adults	7	1294	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.41 [1.01, 1.98]
18 Exacerbations requiring oral steroids Show forest plot	2	883	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.21 [0.72, 2.05]

18.1 Children	2	883	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.21 [0.72, 2.05]
18.2 Adults	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
19 Exacerbations requiring hospitalisation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

19.1 Children	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
19.2 Adults	0		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
20 Oral Candidiasis (No. of patients) Show forest plot	8	1752	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.87 [0.47, 1.61]

20.1 Children	1	528	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.65 [0.19, 2.27]
20.2 Adults	7	1224	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.95 [0.47, 1.95]
21 Sore throat or pharyngitis (No. of patients) Show forest plot	8	1825	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.98 [0.60, 1.63]

21.1 Children	2	883	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.34 [0.58, 3.08]
21.2 Adults	6	942	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.83 [0.44, 1.55]
22 Hoarseness or dysphonia (No. of patients) Show forest plot	7	1693	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.76 [0.40, 1.46]

22.1 Children	1	528	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.30 [0.29, 5.79]
22.2 Adults	6	1165	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.67 [0.32, 1.38]
23 Withdrawals due to adverse events Show forest plot	5	1161	Odds Ratio (M‐H, Fixed, 95% CI)	0.65 [0.22, 1.92]

23.1 Children	1	528	Odds Ratio (M‐H, Fixed, 95% CI)	0.98 [0.14, 6.99]
23.2 Adults	4	633	Odds Ratio (M‐H, Fixed, 95% CI)	0.55 [0.15, 2.03]
24 No. patients with </=18 mcg/dL poststimulation cortisol Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

24.1 Children	0		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
24.2 Adults	2		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
25 AUC serum cortisol Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

25.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
25.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
26 Change in peak plasma cortisol expression Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

26.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
26.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 5. Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (all ages)

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Comparison 6. Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (subgroups)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline based on study duration (litres) ‐ adults Show forest plot	11	1720	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.05]

1.1 1‐4 weeks	2	293	Mean Difference (IV, Fixed, 95% CI)	0.09 [‐0.01, 0.19]
1.2 1‐5 months	8	1237	Mean Difference (IV, Fixed, 95% CI)	‐0.03 [‐0.08, 0.02]
1.3 6 months or longer	1	190	Mean Difference (IV, Fixed, 95% CI)	0.08 [‐0.03, 0.19]
2 Change in FEV1 compared to baseline based on delivery devices (litres) ‐ adults Show forest plot	11	1720	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.05]

2.1 MDI	8	1226	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.03, 0.07]
2.2 DPI	3	494	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.11, 0.06]
3 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ adults Show forest plot	11	1720	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.05]

3.1 Mild to moderate	3	194	Mean Difference (IV, Fixed, 95% CI)	‐0.05 [‐0.18, 0.08]
3.2 Moderate	6	1136	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.05, 0.06]
3.3 Mixed	1	200	Mean Difference (IV, Fixed, 95% CI)	‐0.05 [‐0.19, 0.09]
3.4 Unclear	1	190	Mean Difference (IV, Fixed, 95% CI)	0.08 [‐0.03, 0.19]

Comparison 6. Parallel group studies, no oral steroids: 200 versus 400‐500 mcg/d (subgroups)

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Comparison 7. Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline (litres) Show forest plot	3	351	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.10, 0.09]

1.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Adults	3	351	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.10, 0.09]
2 FEV1 (% predicted) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Change in morning PEFR compared to baseline (L/min) Show forest plot	3	593	Mean Difference (IV, Fixed, 95% CI)	‐7.97 [‐14.58, ‐1.35]

3.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	3	593	Mean Difference (IV, Fixed, 95% CI)	‐7.97 [‐14.58, ‐1.35]
4 Change in evening PEFR compared to baseline (L/min) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Percentage of symptom‐free days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Change in daily asthma symptom score compared to baseline Show forest plot	2	194	Std. Mean Difference (IV, Fixed, 95% CI)	0.31 [0.03, 0.60]

6.1 Children	0	0	Std. Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Adults	2	194	Std. Mean Difference (IV, Fixed, 95% CI)	0.31 [0.03, 0.60]
7 Change in number of night‐time awakenings/week compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

7.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Change in daily use of beta2 agonist compared to baseline (puffs/d) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

8.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Physician global rated efficacy: ineffective Show forest plot	2	400	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.25 [0.81, 1.93]

9.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Adults	2	400	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.25 [0.81, 1.93]
10 Number of patients withdrawn due to lack of efficacy Show forest plot	2	454	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.30 [0.90, 5.90]

10.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Adults	2	454	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.30 [0.90, 5.90]
11 Sore throat or pharyngitis (No. of patients) Show forest plot	3	615	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.02 [0.29, 3.56]

11.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 Adults	3	615	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.02 [0.29, 3.56]
12 Hoarseness or dysphonia (No. of patients) Show forest plot	3	615	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.28 [0.08, 0.92]

12.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Adults	3	615	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.28 [0.08, 0.92]
13 Oral Candidiasis (No. of patients) Show forest plot	3	615	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.89 [0.32, 2.49]

13.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
13.2 Adults	3	615	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.89 [0.32, 2.49]
14 Plasma Cortisol (AUC) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

14.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15 Clinic PEF (L/min ‐ change from baseline) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

15.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 7. Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (all ages)

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Comparison 8. Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (subgroups)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline based on study duration (litres) ‐ adults Show forest plot	3	351	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.10, 0.09]

1.1 1‐4 weeks	1	23	Mean Difference (IV, Fixed, 95% CI)	‐0.45 [‐0.88, ‐0.02]
1.2 1‐5 months	2	328	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.08, 0.11]
1.3 6 months or longer	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Change in FEV1 compared to baseline based on delivery devices (litres) ‐ adults Show forest plot	3	351	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.10, 0.09]

2.1 MDI	1	23	Mean Difference (IV, Fixed, 95% CI)	‐0.45 [‐0.88, ‐0.02]
2.2 DPI	2	328	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.08, 0.11]
3 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ adults Show forest plot	3	351	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.10, 0.09]

3.1 Mild to moderate	1	23	Mean Difference (IV, Fixed, 95% CI)	‐0.45 [‐0.88, ‐0.02]
3.2 Moderate	2	328	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.08, 0.11]

Comparison 8. Parallel group studies, no oral steroids: 100 versus 400‐500 mcg/d (subgroups)

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Comparison 9. Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FEV1 (Change from baseline ‐ litres) Show forest plot	5	900	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.06, 0.04]

1.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Adults	5	900	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.06, 0.04]
2 Change in morning PEF (L/min) Show forest plot	4	905	Mean Difference (IV, Fixed, 95% CI)	‐2.30 [‐7.94, 3.35]

2.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Adults	4	905	Mean Difference (IV, Fixed, 95% CI)	‐2.30 [‐7.94, 3.35]
3 Change in evening PEF (L/min) Show forest plot	2	505	Mean Difference (IV, Fixed, 95% CI)	5.83 [‐2.94, 14.60]

3.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	2	505	Mean Difference (IV, Fixed, 95% CI)	5.83 [‐2.94, 14.60]
4 Change in rescue medication (puffs/d) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Health‐related quality of life ‐ AQLQ (absolute scores)	0		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Change in daily symptoms compared with baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

6.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Nocturnal awakenings (awakenings per night)	0		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Adults	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Exacerbations requiring hospitalisation Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

8.1 Children	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.2 Adults	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Exacerbations requiring OCS treatment Show forest plot	2	363	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.24 [0.77, 1.98]

9.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Adults	2	363	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.24 [0.77, 1.98]
10 Withdrawals (total) Show forest plot	5	1039	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.27 [0.88, 1.83]

10.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Adults	5	1039	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.27 [0.88, 1.83]
11 Withdrawals (adverse events) Show forest plot	4	841	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.46 [0.17, 1.25]

11.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 Adults	4	841	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.46 [0.17, 1.25]
12 Withdrawals (lack of efficacy) Show forest plot	2	537	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.67 [0.73, 3.81]

12.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Adults	2	537	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.67 [0.73, 3.81]
13 Drug‐related adverse events	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected
13.1 Children	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
13.2 Adults	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
14 HPA function data (am cortisol <5mcg/dL)	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected
14.1 Children	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
14.2 Adults	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 9. Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (all ages)

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Comparison 10. Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (subgroups)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change from baseline in FEV1 based on study duration (litres) ‐ adults Show forest plot	5	900	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.06, 0.04]

1.1 1‐4 weeks	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 1‐5 months	3	435	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.09, 0.05]
1.3 6 months or longer	2	465	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.07, 0.07]
2 Change from baseline in FEV1 based on delivery devices (litres) ‐ adults Show forest plot	5	900	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.06, 0.04]

2.1 MDI	3	435	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.09, 0.05]
2.2 DPI	2	465	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.07, 0.07]
3 Change from baseline in FEV1 based on degree of severity (litres) ‐ adults Show forest plot	5	900	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.06, 0.04]

3.1 Mild to moderate	1	38	Mean Difference (IV, Fixed, 95% CI)	0.1 [‐0.08, 0.28]
3.2 Moderate	3	575	Mean Difference (IV, Fixed, 95% CI)	‐0.03 [‐0.10, 0.04]
3.3 Moderate to severe	1	287	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.09, 0.09]

Comparison 10. Parallel group studies, no oral steroids: 400‐500 versus 800‐1000 mcg/d (subgroups)

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Comparison 11. Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline (litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 FEV1 (% predicted) Show forest plot	2	283	Mean Difference (IV, Fixed, 95% CI)	‐0.43 [‐5.72, 4.87]

2.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Adults	2	283	Mean Difference (IV, Fixed, 95% CI)	‐0.43 [‐5.72, 4.87]
3 FEV1 (Litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Change in FVC compared to baseline (litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 FEF25‐75 Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Change in FEF25‐75 compared to baseline (L/second) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

6.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 am PEF (Litres/min) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

7.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Change in morning PEFR compared to baseline (L/min) Show forest plot	2	419	Mean Difference (IV, Fixed, 95% CI)	‐21.86 [‐29.19, ‐14.53]

8.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.2 Adults	2	419	Mean Difference (IV, Fixed, 95% CI)	‐21.86 [‐29.19, ‐14.53]
9 Change in evening PEFR compared to baseline (L/min) Show forest plot	2	419	Mean Difference (IV, Fixed, 95% CI)	‐12.66 [‐19.32, ‐5.99]

9.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Adults	2	419	Mean Difference (IV, Fixed, 95% CI)	‐12.66 [‐19.32, ‐5.99]
10 Physician global rated efficacy: ineffective Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

10.1 Children	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Adults	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Symptoms Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

11.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12 Percentage of symptom‐free days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

12.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
13 Change in daily asthma symptom score compared to baseline Show forest plot	1		Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected

13.1 Children	0		Std. Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
13.2 Adults	1		Std. Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14 Change in number of night‐time awakenings/week compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

14.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15 Rescue medication usage Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

15.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
16 Change in daily use of beta2 agonist compared to baseline (puffs/d) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

16.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
16.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17 Oral Candidiasis (No. of patients) Show forest plot	2	433	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.32 [0.11, 0.97]

17.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
17.2 Adults	2	433	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.32 [0.11, 0.97]
18 Hoarseness or dysphonia (No. of patients) Show forest plot	2	433	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.18 [0.05, 0.59]

18.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
18.2 Adults	2	433	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.18 [0.05, 0.59]
19 Withdrawals (total) Show forest plot	2	294	Peto Odds Ratio (Peto, Fixed, 95% CI)	5.29 [1.59, 17.60]

19.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
19.2 Adults	2	294	Peto Odds Ratio (Peto, Fixed, 95% CI)	5.29 [1.59, 17.60]
20 Number of patients withdrawn due to lack of efficacy Show forest plot	2	427	Peto Odds Ratio (Peto, Fixed, 95% CI)	5.31 [2.18, 12.96]

20.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
20.2 Adults	2	427	Peto Odds Ratio (Peto, Fixed, 95% CI)	5.31 [2.18, 12.96]

Comparison 11. Parallel group studies, no oral steroids: 50‐100 versus 800‐1000 mcg/d (all ages)

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Comparison 12. Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline (litres) Show forest plot	3	489	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.19, ‐0.04]

1.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Adults	3	489	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.19, ‐0.04]
2 Change in FEV1 compared to baseline (%) Show forest plot	1		Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.1 Children	0		Std. Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Adults	1		Std. Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Change in FEV1 % predicted Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 FEV1 (% predicted) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Change in morning PEFR compared to baseline (L/min) Show forest plot	4	763	Mean Difference (IV, Random, 95% CI)	‐8.32 [‐18.02, 1.37]

5.1 Children	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	4	763	Mean Difference (IV, Random, 95% CI)	‐8.32 [‐18.02, 1.37]
6 Change in evening PEFR compared to baseline (L/min) Show forest plot	2	424	Mean Difference (IV, Fixed, 95% CI)	‐7.81 [‐14.66, ‐0.95]

6.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Adults	2	424	Mean Difference (IV, Fixed, 95% CI)	‐7.81 [‐14.66, ‐0.95]
7 Change in FVC compared to baseline (litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

7.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Change in FEF25‐75 compared to baseline (L/second) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

8.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 PD20 Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

9.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 Change in daily asthma symptom score compared to baseline Show forest plot	2	291	Std. Mean Difference (IV, Fixed, 95% CI)	0.06 [‐0.17, 0.29]

10.1 Children	0	0	Std. Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Adults	2	291	Std. Mean Difference (IV, Fixed, 95% CI)	0.06 [‐0.17, 0.29]
11 Change in number of night‐time awakenings/week compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

11.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12 Physician global rated efficacy: ineffective Show forest plot	2	400	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.34 [0.85, 2.12]

12.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Adults	2	400	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.34 [0.85, 2.12]
13 Change in daily use of beta2 agonist compared to baseline (puffs/d) Show forest plot	2	291	Mean Difference (IV, Fixed, 95% CI)	0.11 [‐0.29, 0.50]

13.1 Children	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
13.2 Adults	2	291	Mean Difference (IV, Fixed, 95% CI)	0.11 [‐0.29, 0.50]
14 Number of patients withdrawn due to lack of efficacy Show forest plot	4	554	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.32 [0.73, 2.40]

14.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
14.2 Adults	4	554	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.32 [0.73, 2.40]
15 Oral Candidiasis (No. of patients) Show forest plot	5	618	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.33 [0.16, 0.70]

15.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.2 Adults	5	618	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.33 [0.16, 0.70]
16 Sore throat or pharyngitis (No. of patients) Show forest plot	4	452	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.49 [0.18, 1.39]

16.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
16.2 Adults	4	452	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.49 [0.18, 1.39]
17 Hoarseness or dysphonia (No. of patients) Show forest plot	4	561	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.51 [0.24, 1.08]

17.1 Children	0	0	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
17.2 Adults	4	561	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.51 [0.24, 1.08]
18 Change in peak plasma cortisol compared to baseline (mcg/dL) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

18.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
19 Change in morning plasma cortisol compared to baseline (mcg/dL) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

19.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
19.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 12. Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (all ages)

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Comparison 13. Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (subgroups)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in FEV1 compared to baseline based on study duration (litres) ‐ adults Show forest plot	3	489	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.19, ‐0.04]

1.1 1‐4 weeks	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 1‐5 months	3	489	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.19, ‐0.04]
1.3 6 months or longer	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Change in FEV1 compared to baseline based on delivery devices (litres) ‐ adults Show forest plot	3	489	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.19, ‐0.04]

2.1 MDI	2	357	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.19, ‐0.02]
2.2 DPI	1	132	Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐0.32, 0.02]
3 Change in FEV1 compared to baseline based on degrees of severity (litres) ‐ adults Show forest plot	3	489	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.19, ‐0.04]

3.1 Mild to moderate	1	159	Mean Difference (IV, Fixed, 95% CI)	‐0.12 [‐0.26, 0.02]
3.2 Moderate	2	330	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.20, ‐0.02]

Comparison 13. Parallel group studies, no oral steroids: 200 versus 800‐1000 mcg/d (subgroups)

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Comparison 14. Parallel group studies, no oral steroids: 4‐500 versus 1500‐2000mcg/d (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FEV1 (Change from baseline ‐ litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Clinic PEF (L/min ‐ change from baseline) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 PC20 (methacholine) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 PC20 AMP Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Symptoms (change from baseline) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 Children	0		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Adults	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 14. Parallel group studies, no oral steroids: 4‐500 versus 1500‐2000mcg/d (all ages)

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Comparison 15. Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in daily dose of oral prednisolone compared to baseline (mg) Show forest plot	4	274	Mean Difference (IV, Fixed, 95% CI)	1.00 [‐0.45, 2.45]

2 Number of patients unable to discontinue OCS completely Show forest plot	4	274	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.53 [0.88, 2.68]

3 Change in FEV1 compared to baseline (litres) Show forest plot	4	274	Mean Difference (IV, Fixed, 95% CI)	‐0.13 [‐0.24, ‐0.01]

4 Change in morning PEFR compared to baseline (L/min) Show forest plot	4	274	Mean Difference (IV, Fixed, 95% CI)	‐19.63 [‐34.98, ‐4.27]

5 Change in evening PEFR compared to baseline (L/min) Show forest plot	4	274	Mean Difference (IV, Fixed, 95% CI)	‐21.58 [‐35.20, ‐7.97]

6 Change in daily asthma symptom score compared to baseline Show forest plot	4	274	Std. Mean Difference (IV, Fixed, 95% CI)	0.15 [‐0.09, 0.39]

7 Change in rescue beta2 agonist use compared to baseline (puffs/d) Show forest plot	4	274	Mean Difference (IV, Fixed, 95% CI)	‐0.14 [‐1.05, 0.78]

8 Asthma Quality of Life Questionnaire: change in overall score compared to baseline Show forest plot	3	187	Mean Difference (IV, Fixed, 95% CI)	‐0.12 [‐0.48, 0.23]

9 Asthma Quality of Life Questionnaire: change in activity limitation domain compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

10 Asthma Quality of Life Questionnaire: change in symptom domain compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

11 Asthma Quality of Life Questionnaire: change in emotional function domain compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

12 Asthma Quality of Life Questionnaire: change in environmental exposure domain compared to baseline Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

13 Sore throat (No. of patients) Show forest plot	2	141	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.70 [0.15, 3.18]

14 Hoarseness/dysphonia (No. of patients) Show forest plot	2	141	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.92 [0.28, 2.99]

15 Oral Candidiasis (No. of patients) Show forest plot	2	141	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.96 [0.41, 2.24]

Comparison 15. Parallel studies, oral steroid treated: 1000‐1500 versus 2000 mcg/d

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Comparison 16. Crossover studies, no oral steroids: 200 versus 1000 mcg (all ages)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FEV1 Show forest plot	1		Litres (Fixed, 95% CI)	Totals not selected

2 PEF Show forest plot	1		Litres/min (Fixed, 95% CI)	Totals not selected

Comparison 16. Crossover studies, no oral steroids: 200 versus 1000 mcg (all ages)

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