Revisiting early intervention in adult asthma

Tari Haahtela; Olof Selroos; Paul M. O'Byrne

doi:10.1183/23120541.00022-2015

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TABLE 1

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.