Early Intervention trials of inhaled corticosteroid (ICS) therapy in patients with persistent asthma
| First author or study name [ref.]; study design | Population | Subjects n | ICS and dose | Follow-up period | Comparator(s) | Effect on lung function | Evidence of improved disease control |
| Haahtela [2]; DB in one arm, open in the other | Mild-to-moderate asthma Duration of symptoms <12 months or <12 months + 2 years Mean age 37 years | 74 | Budesonide pMDI +spacer 1200 μg·day−1 | 1 year | Budesonide pMDI+spacer 1200 μg·day−1 with a 2-year delay | Significant improvement in prebronchodilator mPEF, ePEF and FEV1 in both groups but patients treated early achieved better lung function Difference statistically significant between early and delayed therapy (mPEF, p=0.006; ePEF, p=0.004) | Lower airway responsiveness in patients treated without a 2-year delay Difference statistically significant (p=0.027) |
| Agertoft [3]; open, prospective | Children with duration of asthma 0.5–10 years, mean 3.7 years | 278 | Budesonide pMDI +spacer, n=216 | 2–6 years | No ICS therapy (n=62) | Significant negative correlation between duration of asthma and annual improvement in FEV1 (p=0.01) Best improvement in patients with asthma duration <2 years | Lower cumulative dose of budesonide in patients treated early |
| Selroos [4]; open, retrospective | Patients with asthma symptoms of various duration (<6 months, 6–12 months, 1–2 years, 2–5 years and >10 years when starting ICS therapy) | 105 | Budesonide varying doses | 2 years | No | Significant negative correlation between duration of asthma symptoms and maximum improvement in prebronchodilator FEV1 (p=0.0012) and mPEF (p=0.0006) Best PEF improvement in patients with asthma symptom duration <6 months, +110 L·min−1, followed by patients with symptom duration of 6–12 months (+71 L·min−1) and 1–2 years (+69 L·min−1) | |
| Selroos [17]; DB, R, P | Mild-to-moderate asthma Group A: symptoms <12 months Group B: symptoms >24 months Mean age | 81 | Group A: budesonide 100 μg twice daily Group B: budesonide 400 μg twice daily | 12 weeks | Group A: budesonide 100 μg twice daily Group B: budesonide 400 μg twice daily | Group A: no difference between doses in FEV1 and mPEF Group B: higher dose significantly better in improving FEV1 and mPEF | Group A: no difference between doses in asthma symptoms, and use of reliever medication Group B: higher dose significantly better in improving symptoms, and reducing use of reliever medication |
| Selroos [16]; open, prospective | Mild-to-moderate asthma Mean age 37–42 years | 462 | Budesonide varying doses (duration of asthma <2 years) | 5 years | Budesonide varying doses (duration of asthma 2.5–18 years) | Difference in change in mPEF and prebronchodilator FEV1 statistically significantly different in favour of early budesonide therapy (p<0.001 for both) | Lower maintenance dose of budesonide (mean 412 μg, delayed therapy 825 μg; p<0.001) Less additional asthma medications Statistically significantly fewer patients used ≤3 doses of rescue medication per day (p<0.001) Significantly fewer acute exacerbations (p<0.001) Statistically significantly better exercise tolerance (p<0.001) |
| Osterman [19]; DB, P | Mild-to-moderate asthma Duration of asthma <12 months Mean age 33–35 years No ICS therapy within 3 months | 68 | Budesonide 400 μg·day−1 | 1 year (6 months follow-up) | Placebo | Difference in change in mPEF statistically significant in favour of budesonide (p=0.011) | Significantly lower airway responsiveness (PD20) in patients treated with budesonide (p=0.0003) |
| START [20–23]; DB, P, R | Mild persistent asthma <2 years duration Age 5–66 years No previous regular glucocorticosteroid use | 7241 | Budesonide 400 μg·day−1 (200 μg·day−1 in children <11 years) | 3 years | Placebo | Budesonide improved pre- and postbronchodilator FEV1 versus placebo | Budesonide significantly reduced the risk of a severe asthma related event (p<0.0001) and was associated with more symptom-free days (p<0.0001) |
| HEICA [24]; DB, R, active control, open | Newly detected asthma Age 5–10 years No previous regular glucocorticosteroid use | 176 | Budesonide continuous therapy (400 μg twice daily for 1 month, 200 μg twice daily months 2–6, 100 μg twice daily months 7–18); or budesonide as above for months 1–6, thereafter only as needed | 18 months | DSCG 10 mg three times daily | mPEF No differences between the 3 treatment groups at 6 and 18 months FEV1: At 6 months both budesonide groups sign better than DSCG; no difference between groups at 18 months | During the first 6 months, significantly fewer exacerbations in the budesonide groups compared with DSCG; during months 7–18, significantly fewer exacerbations in the continuous budesonide group compared with intermittent budesonide group and DSCG group Median time to first exacerbation: continuous budesonide, 344 days; intermittent budesonide, 268 days; DSCG, 78 days (p<0.001 for both budesonide groups compared with DSCG) Asthma-free days: at 6 months, significant increase (p<0.001) in both budesonide groups compared with DSCG As-needed use of reliever medication: at 6 months, significantly less use in both budesonide groups compared with DSCG (p=0.012) |
DB: double-blind; R; randomised; P: placebo-controlled; pMDI: pressurised metered-dose inhaler; DSCG: disodium cromoglycate; mPEF: morning peak expiratory flow; ePEF: evening peak expiratory flow; FEV1: forced expiratory flow in 1 s; PD20: provocative dose causing a 20% fall in FEV1.