Rapid Effects of Inhaled Corticosteroids in Acute Asthma: An Evidence-Based Evaluation

Rodrigo GJ. Chest . 2006;130:1301–1311 PURPOSE OF THE STUDY. To analyze available evidence on the early (1–4 hours) clinical impact of inhaled corticosteroids (ICSs) for adults and children with an acute asthma exacerbation in the emergency department (ED). STUDY POPULATION. A total of 470 adults (≥18 years old) and 663 children (6 months to 17 years old) seen in the ED or an equivalent care setting with a diagnosis of acute asthma. METHODS. A search was conducted of Medline (1966 to February 2006) and Embase (1974 to February 2006) databases, the Cochrane Controlled Trials Register, bibliographic reviews of primary research, review articles, and citations from texts. Randomized, double-blind, placebo-controlled trials conducted in the ED or equivalent care setting comparing ICSs to placebo or systemic corticosteroids were analyzed. Primary outcome measures included hospital admission and ED discharge rates. Secondary outcomes were spirometric measures, clinical symptoms, heart and respiratory rates, oxygen saturation, and adverse effects, all measured from 1 to 4 hours of the protocol. RESULTS. Fifty articles were identified on the initial search, and 17 of these randomized, double-blind, placebo-controlled studies (6 included adults and 11 included children) met the above-stated criteria. Eight studies compared ICSs with placebo, 3 compared ICSs plus systemic corticosteroids (SCSs) with SCSs, and 6 compared ICSs with SCSs. ICS doses used in the trials ranged from 400 μg to 2 mg dispensed by inhaler or nebulizer, and the ICSs used included fluticasone (3 studies), budesonide (8), flunisolide (2), dexamethasone (1), and beclomethasone (3). “Multiple-dose” protocols administered ≥3 doses of ICS at ≤30-minute intervals, and “single-dose” protocols administered ≤2 doses at ≤30-minute intervals or ≥1 dose at >30-minute intervals. Six studies examined the discharge rates 2 to 3 hours after multidose ICS treatment and found that a significantly greater proportion of ICS-treated patients were discharged early from the ED compared with those treated with either placebo or SCS (odds ratio: 4.7). Patients who received multiple ICS doses along with β agonists also had improvement in spirometric and clinical scores, with evidence of a dose-response relationship. There was a significantly lower admission rate in the patients treated with multiple-dose ICSs. The number of patients needed to treat with ICSs to prevent 1 hospital admission was 10. CONCLUSIONS. This study suggests that ICS treatment provides early beneficial effects (1–2 hours) when they were used in multiple-dose amounts administered in time intervals of ≤30 minutes. REVIEWER COMMENTS. This meta-analysis suggests that ICSs given early in multiple doses with β agonists may have a place in the ED for treatment of acute exacerbations of asthma. Previous studies have shown that asthmatic patients have a significant increase in airway mucosal blood flow compared with nonasthmatic patients. Repeated high doses of ICSs could work by decreasing airway blood flow, leading to enhanced bronchodilator action when administered simultaneously with β agonists. Additional study is needed to determine the most effective dose and delivery system in different patient populations to obtain an optimal effect.