Figures
- FIGURE 1
PRISMA flow diagram for the study selection process. ICS: inhaled corticosteroid.
- FIGURE 2
Cochrane Collaboration Tool (randomised controlled trials): risk of bias assessments for each included study.
- FIGURE 3
Forest plot comparison (randomised controlled trials): change in pre-bronchodilator forced expiratory volume in 1 s (% predicted) stratified by age. ICS: inhaled corticosteroid.
- FIGURE 4
Forest plot comparison (randomised controlled trials): change in post-bronchodilator forced expiratory volume in 1 s (% predicted) stratified by age. ICS: inhaled corticosteroid.
Tables
- TABLE 1
Study characteristics of the included randomised controlled trials
First author [ref.] Age group Duration years Asthma definition Asthma severity ICS intervention Sample size Mean age years Female % Pre-BD FEV1 L % pred Beasley [17] Adults 1 Physician-diagnosed asthma; treatment with SABA only last 3 months Mild Budesonide 200 µg twice daily# 225 34.9 57 90.3 No placebo (open-label) 223 35.8 51 89.2 Becker [18] Children 1 Physician-diagnosed asthma; ≥6 months of symptoms, FEV1 >75% pred Mild Beclomethasone 200µg twice daily¶ 119 7.6 32.8 1.39 91.3 Placebo, twice daily 121 7.7 34.7 1.42 92.0 Boulet [19] Adults 1 Physician-diagnosed asthma; BHR and FEV1 >70% pred Mild Fluticasone 100–250µg daily# 35 27 54.2 3.55 97.2 Placebo daily 34 26 69.7 3.33 98.5 den Otter [20] Adults 2 Symptoms typical of asthma; BHR or BDR; FEV1 decline ≥80 mL·year−1 No restriction Fluticasone 250 µg daily# 23 Placebo daily 22 Jonasson [21] Children 2.3 Physician-diagnosed asthma; ≥1 exacerbation in last 12 months or ≥3 exacerbations ever Mild Budesonide 200 µg daily# 32 10.0 46.9 2.23 102.1 Placebo daily 34 9.4 35.3 2.04 104.6 Juniper [22] Adults 1 Physician-diagnosed asthma; BHR and FEV1 >70% pred No restriction Budesonide 200 µg twice daily# 16 42.4 62.5 89.9 Placebo twice daily 16 35.1 56.3 92.1 Merkus [23] Children 2–3 Physician-diagnosed asthma; BHR and FEV1 55–90% pred or FEV1/FVC 50–75% pred Moderate-severe Budesonide 100 µg three times daily¶ 34 11.4 62.9 72.2 Placebo three times daily 20 10.9 76.7 73.5 O'Byrne [24] Mostly adults 1 Physician-diagnosed asthma; BHR Mild Budesonide 200 µg twice daily# 1282 39.0 62.2 84.2 Placebo, twice daily 1277 40.0 60.4 84.1 Osterman [25] Adults 1 Physician-diagnosed asthma diagnosed within the last year; BHR No restriction Budesonide 200 µg twice daily# 38 33.0 57.9 3.31 93.1 Placebo twice daily 37 35.0 54.1 3.23 88.7 Pauwels [3] Adults and children 3 Physician-diagnosed asthma; recent onset ≤2 years; variable airflow limitation Mild Budesonide 200–400 µg daily# 3597 24.0 54.2 86.3 Placebo daily 3568 24.0 54.0 86.6 Simons [26] Children 1 Physician-diagnosed asthma; BHR and BDR and FEV1>70% pred Mild Beclomethasone 200 µg twice daily¶ 81 9.6 41.0 1.89 92.0 Placebo twice daily 80 9.5 45.0 1.88 96.0 Tonascia [27] Children 4.3 Physician-diagnosed asthma; BHR Mild-moderate Budesonide 200 µg twice daily¶ 311 9.0 41.8 93.6 Placebo, twice daily 418 9.0 44.0 94.2 Ward [12] Adults 1 Physician-diagnosed asthma; positive skin prick testing to ≥3 common aeroallergens Mild-moderate Fluticasone 750 µg twice daily+ 17 96.0 Placebo twice daily 18 94.0 ICS: inhaled corticosteroid; BD: bronchodilator; FEV1: forced expiratory volume in 1 s; SABA: short-acting β2-agonist; BHR: bronchial hyperresponsiveness; BDR: bronchodilator reversibility; FVC: forced vital capacity. #: low-dose ICS; ¶: medium-dose ICS; +: high-dose ICS.
- TABLE 2
Meta-analysis of randomised controlled trials for pre-bronchodilator (BD) outcomes stratified by age group
Outcome or subgroup Studies n Participants n Statistical method Effect estimate p-value I2 GRADE ΔPre-BD FEV1 % pred 8 8332 MD (Random, 95% CI) 2.22 (1.32–3.12) <0.0001 41% Moderate# Adults 5 4181 MD (Random, 95% CI) 2.47 (1.64–3.29) <0.0001 0% High Children 4 4151 MD (Random, 95% CI) 2.08 (0.71–3.44) 0.003 64% Moderate# ΔPre-BD FEV1 mL 4 3603 MD (Random, 95% CI) 74.14 (54.47–93.81) <0.0001 87% Moderate# Adults 2 2634 MD (Random, 95% CI) 108.82 (84.40–133.23) <0.0001 0% High Children 2 969 MD (Random, 95% CI) 10.00 (−23.21–43.21) 0.56 0% Moderate# ΔPre-BD FEV1 SMD 10 11131 SMD (Random, 95% CI) 0.21 (0.12–0.30) <0.0001 68% Moderate# Adults 6 6740 SMD (Random, 95% CI) 0.28 (0.15–0.41) <0.0001 63% Moderate# Children 5 4391 SMD (Random, 95% CI) 0.16 (0.04–0.28) 0.008 60% Moderate# ΔPre-BD FVC % pred 2 804 MD (Fixed, 95% CI) 0.10 (−1.23–1.43) 0.88 0% Moderate# Adults 1 75 MD (Fixed, 95% CI) 2.30 (−2.29–6.89) 0.33 Low#,¶ Children 1 729 MD (Fixed, 95% CI) −0.10 (−1.49–1.29) 0.89 Low#,¶ ΔPre-BD FVC mL 2 804 MD (Random, 95% CI) −12.84 (−149.33–123.65) 0.85 53% Moderate# Adults 1 75 MD (Random, 95% CI) 90.00 (−100.51–280.51) 0.35 Low#,¶ Children 1 729 MD (Random, 95% CI) −60.00 (−124.87–4.87) 0.07 Low¶,¶ ΔPre-BD FVC SMD 2 804 SMD (Fixed, 95% CI) 0.01 (−0.13–0.15) 0.86 0% Moderate# Adults 1 75 SMD (Fixed, 95% CI) 0.23 (−0.23–0.68) 0.33 Low#,¶ Children 1 729 SMD (Fixed, 95% CI) −0.01 (−0.16–0.14) 0.89 Low#,¶ ΔPre-BD FEV1/FVC % pred 0 0 MD (Fixed, 95% CI) Adults 0 0 MD (Fixed, 95% CI) Children 0 0 MD (Fixed, 95% CI) ΔPre-BD FEV1/FVC ratio 1 729 MD (Fixed, 95% CI) 1.60 (0.64–2.56) 0.001 Moderate# Adults 0 0 MD (Fixed, 95% CI) Children 1 729 MD (Fixed, 95% CI) 1.60 (0.64–2.56) 0.001 Moderate# ΔPre-BD FEV1/FVC SMD 1 729 SMD (Fixed, 95% CI) 0.25 (0.10–0.39) 0.001 Moderate# Adults 0 0 SMD (Fixed, 95% CI) Children 1 729 SMD (Fixed, 95% CI) 0.25 (0.10–0.39) 0.001 Moderate# FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; MD: mean difference; SMD: standardised mean difference. #: GRADE score downgraded for heterogeneity or inconsistency of results between studies; ¶: GRADE score downgraded for imprecision, 95% CI includes important benefit and potential harm.
- TABLE 3
Meta-analysis of randomised controlled trials for post-bronchodilator (BD) outcomes stratified by age group
Outcome or subgroup Studies n Participants n Statistical method Effect estimate p-value I2 GRADE ΔPost-BD FEV1 % pred 2 7894 MD (Random, 95% CI) 0.61 (−0.31–1.54) 0.19 71% Moderate# Adults 1 3970 MD (Random, 95% CI) 1.54 (0.87–2.21) <0.0001 Moderate# Children 2 3924 MD (Random, 95% CI) 0.20 (−0.49–0.90) 0.57 12% High ΔPost-BD FEV1 mL 1 729 MD (Fixed, 95% CI) −40.00 (−115.38–35.38) 0.30 Moderate# Adults 0 0 MD (Fixed, 95% CI) Children 1 729 MD (Fixed, 95% CI) −40.00 (−115.38–35.38) 0.30 Moderate# ΔPost-BD FEV1 SMD 2 8894 SMD (Random, 95% CI) 0.06 (−0.03–0.15) 0.18 69% Moderate# Adults 1 3970 SMD (Random, 95% CI) 0.14 (0.08–0.21) <0.0001 Moderate# Children 2 4924 SMD (Random, 95% CI) 0.02 (−0.05–0.09) 0.57 15% High ΔPost-BD FVC % pred 1 729 MD (Fixed, 95% CI) −0.20 (−1.40–1.00) 0.74 Low#,¶ Adults 0 0 MD (Fixed, 95% CI) Children 1 729 MD (Fixed, 95% CI) −0.20 (−1.40–1.00) 0.74 Low#,¶ ΔPost-BD FVC mL 1 729 MD (Fixed, 95% CI) −60.00 (−119.99– −0.03) 0.05 Low#,¶ Adults 0 0 MD (Fixed, 95% CI) Children 1 729 MD (Fixed, 95% CI) −60.00 (−119.99– −0.03) 0.05 Low#,¶ ΔPost-BD FVC SMD 1 729 SMD (Fixed, 95% CI) −0.02 (−0.17–0.13) 0.77 Low#,¶ Adults 0 0 SMD (Fixed, 95% CI) Children 1 729 SMD (Fixed, 95% CI) −0.02 (−0.17–0.13) 0.77 Low#,¶ ΔPost-BD FEV1/FVC % pred 0 0 MD (Fixed, 95% CI) Adults 0 0 MD (Fixed, 95% CI) Children 0 0 MD. (Fixed, 95% CI) ΔPost-BD FEV1/FVC ratio 1 729 MD (Fixed, 95% CI) 0.70 (−0.08–1.48) 0.08 Low#,¶ Adults 0 0 MD (Fixed, 95% CI) Children 1 729 MD (Fixed, 95% CI) 0.70 (−0.08–1.48) 0.08 Low#,¶ ΔPost-BD FEV1/FVC SMD 1 729 SMD (Random, 95% CI) 0.13 (−0.01–0.28) 0.07 Low#,¶ Adults 0 0 SMD (Random, 95% CI) Children 1 729 SMD (Random, 95% CI) 0.13 (−0.01–0.28) 0.07 Low#,¶ FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; MD: mean difference; SMD: standardised mean difference. #: GRADE score downgraded for heterogeneity or inconsistency of results between studies; ¶: GRADE score downgraded for imprecision, 95% CI includes important benefit and potential harm.
Supplementary Material
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Supplementary_tables ERR-0185-2020_Supplementary_tables
