Tables
- Table 1—
Summary details for included studies
First author [ref.] Patients n Study design Community or hospital Criteria for intervention Interventions Primary outcome variable Duration of OCS therapy Hasegawa 9 20 Randomised, open-label Hospital Hospitalised for acute asthma 1 or 2 weeks of prednisone 0.5 mg·kg−1 after 3 days i.v. CS Morning PEF Jones 10 44 Double-blind Hospital Hospitalised for acute asthma, PEF <65% pred 5 or 10 days of prednisolone Waking PEF and asthma exacerbations Tapering of OCS O'Driscoll 11 35 Double-blind Discharge from hospital Hospitalised for acute asthma, PEF <65% pred OCS 40 mg·day−1 during admission, randomised to abrupt cessation or taperingover 1–2 weeks Morning PEF Hatton 12 35 Double-blind Discharge from hospital Hospitalised for acute asthma; for discharge, PEF at least double cf. admission, variability <15% over 48 h Prednisolone 40 mg·day−1 during admission; post-discharge, 14-day reducing course starting at 40 mg·day−1, or placebo Not stated. PEF, FEV1, FVC and TLC reported Cydulka 13 15 Double-blind Post-ED ED presentation; well enough for discharge 40 mg·day−1 prednisone for 8 days, or tapered over 8 days FEV1 and symptoms on day 12 Karan 14 26 Randomised open-label Post-ED ED presentation; well enough for discharge 40 mg·day−1 prednisone for 8 days, or tapered over 8 days Symptoms of relapse <21 days; FEV1 day 12 and 21; adrenal suppression Doubling ICS FitzGerald 15 290 Double-blind Community Composite criteria for 2 days (symptoms, PEF, healthcare utilisation) Double ICS dose for 14 days or maintain previous dose Failure to regain control (composite criteria) Harrison 7 390 Double-blind Community PEF ↓ by 15% or symptom score ↑ by 1 point from baseline (both permissible during run-in) Double ICS dose for 14 days or maintain previous dose Need for OCS Rice-McDonald 16 22 Double-blind crossover Community Night waking, symptoms reliever use or PEF Placebo or double ICS or dexamethasone 0.1 mg·kg·day−1 for 7 days Treatment failure (3 days) – symptoms, PEF, withdrawal due to asthma or adverse event Higher dose ICS Foresi 17 142# Double-blind Community PEF ↓ by 30% for 2 days Budesonide 200 µg·day−1, plus 800 µg·day−1 or placebo for 7 days Exacerbations = PEF ↓ by 30% for 2 days Levy 18 413 Double-blind Community (primary care offices) Clinician judgement that OCS needed; post-BD PEF 60–90% best or predicted Fluticasone 1 mg b.i.d. or prednisone 40 mg reducing (16 days) Treatment failure (symptoms, PEF) Nana 19 81 Double-blind Post-ED Discharged from ED Budesonide 1600 µg b.i.d. or prednisolone reducing course (7 days) FEV1 after 7 days FitzGerald 20 175 Double-blind Post-ED ED presentation; well enough for discharge (FEV1 >50% pred) Budesonide 600 mcg q.i.d. or prednisolone 40 mg·day−1 (7–10 days) Relapse rate (return to ED) Lee-Wong 21 40 Double-blind Post-admission Admitted for asthma, PEF ≤50% pred Flunisolide 2000 µg b.i.d. or prednisone 40 mg·day−1 for 7 days Not stated. PEF, FEV1, symptom scores reported. Di Franco 22 37 Double-blind Asthma clinic ≥5 days symptoms, FEV1 ≤70% pred and ≤80% recent best Fluticasone 1000 µg b.i.d. or prednisone reducing from 40 mg·day−1; usual ICS ceased Sputum eosinophil percentage at 2 weeks Acute use of ICS in the ED Guttman 23 60 Double-blind ED ED presentation; FEV1 <70% pred; ≥1 criterion for receiving i.v. steroids Two doses i.v. CS, plus inhaled beclomethasone 7000 µg or placebo, divided into five doses over 8 h FEV1 change over 12 h Afilalo 24 54 Double-blind ED ED presentation; FEV1 40–69% pred Inhaled beclomethasone 5000 µg or placebo, over 4 h FEV1 (6-h study) Rodrigo 25 94 Double-blind ED ED presentation; PEF and FEV1 <50% pred Flunisolide 18000 µg or placebo (dosing every 10 min for 3 h) FEV1 (3-h study) Pansegrouw 26 40 Double-blind ED ED presentation with “acute resistant asthma” = FEV1 and FVC <70% pred; misuse of β2-agonist in 2–4 h prior to presentation; lack of response to β2-agonist Single-dose BDP 200 µg or placebo Not stated. Primary aim related to resensitisation of airways to β2-agonist (fenoterol) Rodrigo 27 106 Double-blind ED ED presentation, PEF or FEV1 <50% pred Fluticasone 9000 µg (dosing every 10/60 for 3 h) or 500 mg i.v. hydrocortisone FEV1 or PEF over 3 h; admission rate Single high-dose ICS Leuppi 28 19 Double-blind Exacerbations Induced by ICS reduction Symptoms + PEF >3 sd below baseline mean Double last pre-exacerbation dose, plus budesonide 3200 µg or placebo Not stated Increased dose of budesonide/formoterol – AMD Canonica 29 2358 Open-label Community Step up if 2 consecutive days of reliever ≥3 times·day−1 or night waking Budesonide/formoterol 200/6 or 100/6 AMD or FMD; AMD included step-up to four puffs b.i.d. until symptoms resolved or 14 days Exacerbations (asthma-related SAE, hospitalisation/ED, OCS ≥5 days; asthma-related withdrawal) Ind 30 1539 Open-label Community Step up if 2 consecutive days of reliever ≥3 times·day−1 or night waking Budesonide/formoterol 200/6 or 100/6 AMD or FMD; AMD included step-up to four puffs b.i.d. until symptoms resolved or for 14 days Treatment successes (NHLBI criteria for asthma severity) and treatment failures (serious asthma exacerbation, OCS ≥5 days, hospitalisation, emergency treatment, asthma-related withdrawal) Leuppi 31 127 Open-label Community Step up if 2 consecutive days of reliever ≥3 times·day−1 or night waking or PEF <80% baseline mean Budesonide/formoterol 200/6 AMD or FMD; AMD included step-up to 2–4 puffs b.i.d. for 7–14 days Treatment successes (NHLBI criteria for asthma severity) and treatment failures (serious asthma exacerbation, OCS ≥5 days, hospitalisation, emergency treatment, asthma-related withdrawal) Buhl 32 4025 Open-label Community Step up if reliever ≥3 times·day−1 or night waking or PEF <80% baseline mean Budesonide/formoterol 200/6 AMD or FMD; AMD included step-up to two puffs b.i.d. for 7 days, +/- step up to four puffs b.i.d. for further 7 days Asthma-related quality of life over 12 weeks Stallberg 33 1034 Open-label Community 2 consecutive days of: reliever ≥3 times·day−1, or night waking or PEF <85% baseline mean Budesonide/formoterol 200/6 or 100/6 AMD or FMD; AMD included step-up to four puffs b.i.d. for 7–14 days Exacerbations (OCS, medical care unit, asthma-related SAE, asthma-related withdrawal) FitzGerald 34 995 Open-label Community 2 consecutive days of: reliever ≥3 times·day−1, or night waking or PEF <85% baseline mean Budesonide/formoterol 200/6 or 100/6 AMD or FMD; AMD included step-up to four puffs b.i.d. for 7–14 days Exacerbations (OCS or extra ICS, ED visit, asthma-related SAE, asthma-related withdrawal) Acute use of budesonide/formoterol Balanag 35 103 Double-blind ED ED presentation, FEV1 30–60% pred Budesonide/formoterol 1600/48 µg in two doses or salbutamol 1600 µg MDI+spacer in two doses Mean FEV1 up to 3 h Use of LABA for exacerbations Turner 36 34 Double-blind Community Mild exacerbations of at least 2 weeks duration, post-BD FEV1 ≥75% pred or personal best, sputum eosinophils >4% Salmeterol 50 µg b.i.d. or beclomethasone 500 µg b.i.d. or placebo (3 weeks) Sputum eosinophils Boonsawat 37 88 Double-blind ED ED presentation, FEV1 30–60% pred Formoterol 54 µg by Turbuhaler® cf. with 2400 µg salbutamol MDI+spacer, as three doses over 1 h FEV1 at 75 min Studies not specifically of exacerbations, but relevant to self-management Treatment of sputum eosinophilia Gibson 38 26 Double-blind crossover Induced by ICS cessation for 4 days No exacerbations required – sputum eosinophilia only Single dose budesonide 2400 µg or placebo Sputum eosinophils at 6 h SMART Symbicort® studies¶ Scicchitano 39 1890 Double-blind Community As-needed for symptoms including during early stages of exacerbations (Budesonide 400 µg b.i.d. + terbutaline prn or Budesonide/formoterol 200/6 2 od + Symbicort® 200/6 1 puff prn) Time to first severe exacerbation (hospitalisation or ED, OCS or PEF ↓30% for 2 consecutive days) O'Byrne 40 2760 Double-blind Community As-needed for symptoms including during early stages of exacerbations (Budesonide 400 µg b.i.d. + terbutaline prn or Budesonide/formoterol 100/6 2 puffs b.i.d. + terbutaline prn or Budesonide/formoterol 100/6 b.i.d. + Budesonide/formoterol 100/6 prn) Time to first severe exacerbation (hospitalisation or ED, OCS or PEF ↓ 30% for 2 consecutive days) -
OCS: oral corticosteroids; ICS: inhaled corticosteroid; ED: Emergency Department; AMD: adjustable maintenance dosing (see text for explanation); LABA: long-acting β2-agonist; SMART: (Symbicort® Maintenance And Reliever Therapy) Symbicort® studies; i.v.: intravenous; CS: corticosteroids; PEF: peak expiratory flow; % pred: % predicted; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; TLC: total lung capacity; BD: bronchodilator; BDP: beclomethasone dipropionate; FMD: fixed maintenance dosing (see text for explanation); SAE: serious adverse event; NHLBI: National Heart, Lung and Blood Institute; MDI: metered dose inhaler; od: one daily; prn: as needed. #: Groups 2 and 3 of the study by Foresi et al. 17. ¶: These studies did not specifically examine the management of exacerbations, but as-needed use of the study medication would have included periods of mild-to-moderate exacerbations.
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