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Revisiting early intervention in adult asthma

Tari Haahtela, Olof Selroos, Paul M. O'Byrne
ERJ Open Research 2015 1: 00022-2015; DOI: 10.1183/23120541.00022-2015
Tari Haahtela
1Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
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  • For correspondence: tari.haahtela@haahtela.fi
Olof Selroos
2Semeco AB, Ängelholm, Sweden and Helsinki University, Helsinki, Finland
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Paul M. O'Byrne
3Firestone Institute for Respiratory Health, St Joseph's Hospital and McMaster University, Hamilton, ON, Canada
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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 designPopulationSubjects nICS and doseFollow-up periodComparator(s)Effect on lung functionEvidence of improved disease control
    Haahtela [2];  DB in one arm, open in the otherMild-to-moderate asthma Duration of symptoms  <12 months or  <12 months + 2 years Mean age 37 years74Budesonide pMDI  +spacer  1200 μg·day−11 yearBudesonide  pMDI+spacer  1200 μg·day−1  with a 2-year delaySignificant 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, prospectiveChildren with duration  of asthma 0.5–10 years,  mean 3.7 years278Budesonide pMDI  +spacer, n=2162–6 yearsNo 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 yearsLower cumulative dose  of budesonide in patients  treated early
    Selroos [4];  open, retrospectivePatients with asthma  symptoms of various  duration (<6 months,  6–12 months,  1–2 years, 2–5 years  and >10 years when  starting ICS therapy)105Budesonide  varying doses2 yearsNoSignificant 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, PMild-to-moderate asthma Group A: symptoms  <12 months Group B: symptoms  >24 months Mean age81Group A: budesonide  100 μg twice daily Group B: budesonide  400 μg twice daily12 weeksGroup A: budesonide  100 μg twice daily Group B: budesonide  400 μg twice dailyGroup A: no difference  between doses in FEV1  and mPEF Group B: higher dose  significantly better  in improving FEV1  and mPEFGroup 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, prospectiveMild-to-moderate  asthma Mean age 37–42 years462Budesonide varying  doses (duration  of asthma  <2 years)5 yearsBudesonide 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, PMild-to-moderate  asthma Duration of asthma  <12 months Mean age 33–35 years No ICS therapy within  3 months68Budesonide  400 μg·day−11 year (6 months follow-up)PlaceboDifference 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, RMild persistent  asthma <2 years  duration Age 5–66 years No previous regular  glucocorticosteroid  use7241Budesonide  400 μg·day−1  (200 μg·day−1  in children  <11 years)3 yearsPlaceboBudesonide improved  pre- and  postbronchodilator  FEV1 versus placeboBudesonide 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, openNewly detected asthma Age 5–10 years No previous regular  glucocorticosteroid  use176Budesonide  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 needed18 monthsDSCG 10 mg  three times dailymPEF 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 monthsDuring 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.

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Revisiting early intervention in adult asthma
Tari Haahtela, Olof Selroos, Paul M. O'Byrne
ERJ Open Research May 2015, 1 (1) 00022-2015; DOI: 10.1183/23120541.00022-2015

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Revisiting early intervention in adult asthma
Tari Haahtela, Olof Selroos, Paul M. O'Byrne
ERJ Open Research May 2015, 1 (1) 00022-2015; DOI: 10.1183/23120541.00022-2015
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  • Article
    • Abstract
    • Abstract
    • Introduction
    • What is meant by early intervention?
    • Early intervention studies
    • Reducing or discontinuing ICS
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    • Preventing exacerbations
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  • Asthma and allergy
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  • The “vicious circle” of chronic cough
  • Non-response and response to biologics for severe asthma
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