Inhaled Corticosteroids as Rescue Medication in Acute Severe Asthma

Gustavo J Rodrigo


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

In This Article

Selected Clinical Evidence on the Use of Inhaled CS in Acute Asthma

A study by Husby et al., published almost 15 years ago, was an important landmark with regard to the use of inhaled CS in the treatment of severe airway diseases.[6] This randomized, controlled trial, which compared the administration of a single dose of 2 mg of inhaled budesonide or placebo to children hospitalized for severe croup, reported rapid clinical improvement (within 2 h of treatment) in patients administered budesonide. A number of subsequent pediatric studies evaluated the effects of inhaled CS in the treatment of asthma exacerbations. These also demonstrated early effects on lung function and clinical variables, which did not seem to be attributable to the action of systemic CS.[7,8]

In the last 10 years, different clinical trials have suggested an early benefit to the use of inhaled CS in both children and adults with acute asthma. Thus, among others, Rodrigo and Rodrigo published a randomized, double-blind trial designed to determine the benefit of very high repeated doses of inhaled flunisolide (1 mg/10 min for 3 h) added to salbutamol, in adult patients with acute severe asthma in the emergency department (ED).[9] 94 patients were assigned to receive flunisolide or placebo, administered through a metered dose inhaler (MDI) and spacer. Flunisolide was associated with a significant benefit in the bronchodilator response, clinical rate and number of hospital admissions, compared with placebo. More importantly, these effects were seen as early as 2 h after the first treatment. Likewise, more recently, Rodrigo compared, in a randomized and double-blinded manner, the effects of repeated doses of inhaled fluticasone (3 mg/h for 3 h via a MDI and spacer) with the standard treatment of systemic CS (a bolus of 500 mg given intravenously) in 106 adults with acute severe asthma.[10] In addition, all patients received inhaled salbutamol and ipratropium. Patients treated with fluticasone showed an early and significant improvement after 90 min of treatment. In addition, the fluticasone-treated group exhibited higher rates of patients who obtained the discharge threshold. This therapeutic benefit was particularly evident in those patients with the most-severe obstructions.

Despite these and other positive pieces of evidence provided by publications in the last decade, inhaled CS have not been considered effective in treating asthma exacerbations. Different state-of-the-art and systematic reviews have concluded that inhaled CS are not effective for the treatment of patients with acute asthma. However, these reviews contain potentially important bias that could affect their validity, including:

  • Omission of relevant studies [11,12]

  • Non distinction between genomic and nongenomic effects [11,13]

  • Pooled analysis of studies with different doses and timing of administration [11,13]

For example, in one meta-analysis, the authors pooled the admission rates of different trials whose protocol duration ranged between 2 and 12 h so they did not distinguish between early and late effects.[13] As a result, these reviews probably underestimated the immediate clinical impact of inhaled CS and, therefore, have conclusions of questionable validity.

On the other hand, some studies have failed to show the beneficial effects of inhaled CS. For example, Schuh et al. performed a double-blind, randomized trial involving 100 children 5 years of age or older with acute severe asthma.[14] All patients were treated with bronchodilators and received one dose of either inhaled fluticasone 2 mg/kg through a MDI and spacer or oral prednisone 2 mg/kg of bodyweight. The degree of improvement in pulmonary function in the initial 4 h among patients treated with prednisone was approximately twice that shown by patients given fluticasone. Furthermore, the rate of hospitalization in the fluticasone group was approximately three-times that of the prednisone group.


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