TABLE 2.
Overview of clinical trials examining worsenings (mild exacerbation days/days with symptoms) and severe exacerbations
| Study | Description | Definition of severe exacerbation | Patients with severe exacerbations, % | Definition of asthma worsening* | Patients with worsenings, % |
|---|---|---|---|---|---|
| Pauwels et al, 2003 (19) | 3-year, randomized, double-blind trial 7241 patients (aged 5–66 years) with mild persistent asthma Bud vs placebo for 3 years |
Asthma-related event requiring hospital admission or emergency treatment, or death due to asthma | Bud: 3.3 Placebo: 5.5 |
Days with symptoms (opposite of symptom-free days) | Placebo vs bud: Year 1: 15% vs 11 Year 2: 12% vs 11 Year 3: 12% vs 10 |
| Price et al, 2003 (20) | 16-week, double-blind, randomized, parallel group, non-inferiority study 889 adults (aged 15–75 years) with inadequately controlled asthma Mont + bud vs double-dose bud |
A day with a >20% decrease from baseline in morning PEF; an increase in SABA use of >70% (minimum increase of two puffs), or an increase in symptom score of ≥50%, or an asthma attack (worsening of asthma requiring an unscheduled physician or ED visit, admission to hospital, or treatment with oral corticosteroids) | Mont + bud: 1.6 Double-dose bud: 2.3 |
Opposite of asthma-free days (defined as any day free of oral corticosteroid use, emergency care, nocturnal awakenings, with use of <2 puffs of SABA) | Mont + bud: 13.3 Double-dose bud: 17.8 |
| O’Byrne et al, 2005 (14) | 1-year, randomized, double-blind trial 2760 patients (aged 4–80 years) treated with ICS and a history of ≥1 exacerbation in the last year Treatment groups: ;Bud/form M + R Bud/form + SABA Bud + SABA |
Deterioration in asthma resulting in hospitalization/ED treatment, oral steroid treatment or morning PEF ≤70% of baseline on 2 consecutive days | Bud/form M + R: 16 Bud/form + SABA: 27 Bud + SABA: 28 |
Mild exacerbation days: any day with awakening caused by asthma, with as-needed medication use of ≥2 inhalations above baseline mean value, or with morning PEF ≤80% of baseline mean value | Bud/form M + R: 17 Bud/form + SABA: 23 Bud + SABA: 20 |
| Lundbäck et al, 2006 (21) | 1-year, randomized, double-blind parallel-group study 282 patients (aged 18–70 years) with mild to moderate asthma Treatment groups: ;Salm/flutic Flutic alone Salm alone |
Deterioration in asthma requiring an increase in rescue medication use over that used during run-in period of >6 puffs/day for ≥2 consecutive days, or an increase of ≥2 doses/day in regular inhaled medication (study medication or additional ICS) for ≥2 days by the patient’s own decision, or ≥2 days when asthma symptoms prevented work or normal activities | % of patients experiencing ≥2 exacerbations: Salm/flutic: 4.2 Flutic: 17.4 Salm: 40.0 |
Days with symptoms (opposite of symptom-free days) | Salm/flutic: 33 Flutic: 32.1 Salm: 55.5 |
| Rabe et al, 2006 (22) | 12-month, randomized, double-blind, parallel-group study 3394 asthma patients (aged ≥12 years) using bud/form maintenance therapy Designed to evaluate the additional benefits of the following as-needed therapies: Bud/form Form Terbut |
Deterioration in asthma resulting in emergency treatment or hospitalization or the need for oral steroids ≥3 days | Bud/form prn: 12 Form prn: 17 Terbut prn: 22 |
Mild exacerbation days: any night with an awakening due to asthma, morning PEF ≥20% below baseline or as-needed medication use of ≥2 inhalations in 24 h above baseline | Bud/form prn: 74 Form prn: 77 Terbut prn: 78 |
| Boulet et al, 2007 (24) | 12-week, randomized, open-label study 474 patients (aged 12–75 years) with moderate, persistent asthma Ciclesonide vs flutic |
Deterioration of asthma requiring treatment with oral steroids | Ciclesonide: 1.3 Flutic: 2.1 |
Days with asthma symptoms and with rescue medication use | Ciclesonide: 15 Flutic: 16 |
| Bousquet et al, 2007 (8) | 6-month, double-blind, randomized study 2309 patients (aged ≥12 years) with symptomatic asthma (FEV1 ≥50% predicted) who had experienced an asthma exacerbation in the previous year Treatment groups: Bud/form M + R Salm/flutic + SABA |
Deterioration in asthma leading to hospitalization/ED treatment and/or oral corticosteroid treatment ≥3 days | Bud/form M + R: 9.4 Salm/flutic + SABA: 11.3 |
Opposite of asthma control days (defined as a day and night with no asthma symptoms, no awakenings due to asthma and no as-needed medication use) | Before treatment: Bud/form M + R: 93.7 Salm/flutic + SABA: 94.2 On treatment: Bud/form M + R: 56 Salm/flutic + SABA: 55.1 |
| Kuna et al, 2007 (23) | 6-month, randomized, double-blind study 3335 symptomatic adults and adolescents (≥12 years) with asthma Treatment groups: Bud/form M + R Bud/form + SABA Salm/flutic + SABA |
Deterioration in asthma resulting in hospitalization or ED treatment, or need for oral steroids for ≥3 days | Bud/form M + R: 9 Bud/form + SABA: 11 Salm/flutic + SABA: 12 |
Two consecutive mild exacerbation days (defined as a day with any one of the following: morning PEF ≥20% below baseline, daily as-needed medication use ≥2 inhalations above baseline or a night with an asthma-related awakening) | Bud/form M + R: 61 Bud/form + SABA: 63 Salm/flutic + SABA: 59 Average number of worsenings/patient/6 months: Bud/form M + R: 27 Bud/form + SABA: 29 Salm/flutic + SABA: 27 |
| Bateman et al, 2008 (25) | 6-month, randomized, open-label, parallel-group study 528 patients (aged ≥12 years and <80 years) with a 6-month history of bronchial asthma Ciclesonide vs flutic |
Worsening asthma symptoms or a reduction in lung function requiring treatment with oral steroids | Ciclesonide: 2.3 Flutic: 2.5 |
Days with asthma symptoms and with rescue medication use | Ciclesonide: 26 Flutic: 27 |
*
As per Asthma Worsenings Working Group considerations. Bud Budesonide; ED Emergency department; FEV1 Forced expiratory volume in 1 s; flutic Fluticasone; form Formoterol; M + R Maintenance plus relief; mont Montelukast; PEF Peak expiratory flow; SABA Short-acting beta-2 agonist; salm Salmeterol; terbut Terbutaline; vs Versus