Figures
- Fig. 1.—
Process of inclusion of studies in the meta-analysis. RCT: randomised controlled trial.
- Fig. 2.—
Dose-response curve of inhaled budesonide in adult asthma, based on negative exponential model for four clinical outcome measures: a) morning peak expiratory flow (PEF), b) evening PEF, c) forced expiratory volume in one second (FEV1), and d) β‐agonist use
- Fig. 3.—
Modified Forest plot for standardised difference in forced expiratory volume in one second (FEV1) comparing 400 µg·day−1 with doses of ≥800 µg·day−1. Pooled data=0.05 (−0.12–0.22).
- Fig. 4.—
Modified Forest plot for standardised difference in morning peak expiratory flow comparing 400 µg·day−1 with doses of ≥800 µg·day−1. Pooled data=0.07 (−0.11–0.25).
Tables
- Table 1—
Summary of studies used in the meta-analysis
First author [ref.] Subjects n Study duration weeks Doses of bud used µg·day−1 Device FEV1 % pred range (mean) or PEF Age yrs range (mean) Baseline ICS usage FEV1 Morning PEF Evening PEF β‐agonist use Exacerbations Symptom score Busse 11 473 12 200,400, 800, 1600 Turbuhaler 40–75 (65) 18–70 (44) 300–1000 BDP·day−1 Yes Yes Yes Yes Yes Yes Miyamoto 13 267 6 200, 400, 800 Turbuhaler 50–80 Adult (51) Not for 1/12 Yes Yes Yes No Yes Yes Kemp 12 273 12 400, 800 Turbuhaler 50–80 (67) 18–70 (39) Not for 6/12 Yes Yes Yes Yes Yes Yes Lorentzson 14 103 6 200,400 MDI+spacer 80 16–59 (32) 0 No Yes Yes Yes No Yes O'Byrne 15 57 16 400,800 MDI+spacer ≥18 (35) 0 No Yes Yes Yes No Pirozynski 16 262 4 200,800 Turbuhaler (82) (36) 0 Yes Yes Yes No No No -
FEV1: forced expiratory volume in one second
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PEF: peak expiratory flow
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ICS: inhaled corticosteroid
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MDI: metered-dose inhaler
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bud: budesonide
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BDP: beclomethasone dipropionate
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- Table 2—
Doses of budesonide (µg·day−1) at which 80 and 90% of the maximum effect is achieved, as derived from a negative exponential model
Outcome measure 80% of max. effect achieved 90% of max. effect achieved FEV1 315 450 Morning PEF 230 329 Evening PEF 412 589 β‐agonist use 204 293 -
The effect obtained with 1600 µg·day−1 budesonide was considered to be the “maximum effect” for the purposes of this analysis
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FEV1: forced expiratory volume in one second
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PEF: peak expiratory flow
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- Table 3—
Estimates of dose of budesonide (µg·day−1) giving peak effect and effect on mean change in outcome measure
Outcome measure R2 % Fixed-effects model Random-effects model Dose of peak effect Mean change (95% CI) Dose of peak effect Mean change (95% CI) FEV1 L 39 1084 0.29 (0.19–0.40) 1090 0.30 (0.15–0.45) Morning PEF L·min−1 39 881 58.2 (45–72) 976 61.8 (35.4–88.1) Evening PEF L·min−1 50 926 36.6 (25–48.2) 1050 40.2 (11.7–68.8) β‐agonist use puffs·day−1 52 965 −2.54 (−0.78–−4.35) 1038 −2.76 (−6.33–−0.81) -
CI: confidence interval
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FEV1: forced expiratory volume in one second
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PEF: peak expiratory flow
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- Table 4—
The number of withdrawals and withdrawals due to asthma according to budesonide dose in the three studies
First author [ref.] Dose Subjects n Total withdrawals n (%) Withdrawals due to asthma n (%) Busse 11# Placebo 92 55 (60) 52 (56) 200 µg 91 24 (26) 16 (18) 400 µg 93 17 (18) 10 (11) 800 µg 99 16 (16) 9 (9) 1600 µg 98 13 (13) 7 (7) Kemp 12 Placebo 89 18 (20) 14 (16) 400 µg 93 9 (10) 5 (5) 800 µg 91 5 (6) 0 (0) Miyamoto 13 Placebo 70 18 (26) 3 (4) 200 µg 63 7 (11) 0 (0) 400 µg 67 12 (18) 1 (2) 800 µg 67 6 (9) 1 (2) O'Byrne 15 Placebo 20 6 (30) 2 (10) 400 µg 17 4 (24) 0 (0) 800 µg 20 8 (40) 0 (0) -
#: the withdrawal data from this study was measured from the graph of discontinuations from the study (fig. 1⇑)
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this data does not correspond to that stated in the text (withdrawal due to worsening asthma: 61% of placebo group
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20% of 200 µg·day−1 group
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11% of 400 µg·day−1 group
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8% of 800 µg·day−1 group
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and 7% of 1600 µg·day−1 group)
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