Inhaled Corticosteroids as Rescue Medication in Acute Severe Asthma

Gustavo J Rodrigo


Expert Rev Clin Immunol. 2008;4(6):723-729. 

In This Article

Analysis of the Clinical Evidence in Agreement With the Characteristics of Nongenomic Fffects

The analysis of evidence confirmed that the clinical trials using repeated doses of inhaled CS in short time intervals (three or more doses administered in at least 30-min intervals for 90-120 min) showed early benefits (1-2 h onset) in terms of clinical and spirometric variables.[28] Of the eight studies that compared inhaled CS to placebo, four involved multiple doses of CS administered at short intervals (every 10-30 min) ( Table 1 ).[9,29,30,31] All showed rapid (after 2 h of treatment) and significant benefits favoring inhaled CS in terms of pulmonary function, clinical index, oxygen saturation and hospitalizations. Two other studies for which no significant effects were observed used multiple doses of inhaled CS at substantially lengthier administration intervals (every 60 min).[32,33] Finally, a single dose of inhaled CS was administered in two studies and an early effect on lung function (after 60 min) was observed in one of the studies,[7] whereas no difference between groups was observed in the other.[34]

Inhaled and systemic CS used to treat severe asthma were compared in a total of six clinical trials, five involving children and adolescents [14,35,36,37,38]and one involving adults only.[10] Analysis of the three studies in which multiple doses of inhaled CS were administered (at 10-30-min intervals) revealed significant early effects (after 2 h of treatment) in the variables studied (lung function, symptoms and signs, discharges and admissions) ( Table 2 ).[10,35,36] Of the three studies based on inhaled CS single-dose protocols, no significant differences in the different study variables were observed between groups in two of the studies.[37,38] The third study, however, merits special attention.[14] This well-designed study of children and adolescents with moderate-to-severe acute asthma compared the administration of a single dose of inhaled fluticasone (2 mg) with a standard dose of oral prednisone (2 mg/kg), each administered at the commencement of the protocol. The patients treated with prednisone experienced significantly greater increases in spirometric values and their hospitalization rates were significantly lower. As the only study of those analyzed demonstrating systemic CS to be superior to inhaled CS, it is noteworthy that the protocol was based on a single dose of inhaled CS, and the earliest measurement of the variables was 4 h after protocol was begun. Prednisone superiority, therefore, may be explained by the fact that the genomic or anti-inflammatory effects of the drug may have already been triggered by the time the variables were measured.

More recently, a systematic review with a meta-analysis was performed to analyze the best available evidence on the early (1-4 h) clinical and objective impact of inhaled CS for patients with acute asthma in the ED setting.[39] In total, 17 studies met criteria for inclusion in the review (470 adults and 663 children and adolescents). After 2-4 h of the protocol, a greater reduction in admission rates was observed with trials that used multiple doses of inhaled CS (odds ratio [OR]: 0.30; 95% confidence interval [CI]: 0.16-0.55), especially when CS were compared with placebo. Patients treated with inhaled CS also displayed a faster clinical improvement compared with those administered placebo or systemic CS, increasing the probability of an early ED discharge by almost five-times (OR: 4.70; 95% CI: 2.97-7.42). The advantage of using inhaled CS was also demonstrated in spirometric and clinical measures as early as 60 min. These benefits were obtained only when patients received multiple doses of inhaled CS along with β2-agonists compared with placebo or systemic CS. This is a very relevant finding, since hospital admissions count for the largest part of the direct health costs for asthma. A second finding of this review was that patients who received inhaled CS in multiple doses displayed a faster improvement compared with patients receiving placebo or systemic CS, increasing the probability of an early ED discharge. On the contrary, those trials that used single doses of inhaled CS or multiple doses in very prolonged intervals presented smaller beneficial effects or no differences between groups. Therefore, the most important parameter would not be the total dose administered, but rather the relationship between the dose and the timing of administration.


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