Anti-inflammatory Effects of High-Dose Inhaled Fluticasone Versus Oral Prednisone in Asthma Exacerbations

Belda J, Margarit G, Martinez C, et al. Eur Respir J . 2007;30(6):1143–1149 PURPOSE OF THE STUDY. There have been reports that parenteral corticosteroids have no bronchodilator effect within the first few hours of an acute asthma exacerbation and that their effect occurs within the first 6 to 8 hours after administration. Inhaled corticosteroids have been suggested to work faster than oral or parenteral corticosteroids in the emergency setting. This study was undertaken to investigate the mechanism through which inhaled steroids may act faster than oral steroids for acute asthma. STUDY POPULATION. The study included patients aged 16 to 65 years who were treated in the emergency department for moderate asthma exacerbations. Inclusion criteria included a previous diagnosis of asthma and no use of intravenous or oral steroid in the 4 weeks preceding the study. METHODS. This study was a randomized, double-blind, placebo-controlled prospective trial. There were 39 patients aged 16 to 65 years assigned to receive fluticasone and placebo prednisone (19 patients) or prednisone and placebo fluticasone (20 patients). The medication was administered via a metered-dose inhaler and spacer (16 puffs, 4000 μg/day or placebo) plus 1 pill (prednisone 30 mg/day or placebo). Spirometry and induced sputum for differential cell counts and albumin, α2-macroglobulin and blood eosinophil, interleukin 5, and granulocyte-macrophage colony-stimulating factor levels were obtained before treatment and 2, 4, 6, and 24 hours after treatment. RESULTS. Clinical symptoms (moderate-to-severe dyspnea) improved after 24 hours in both groups. Airway obstruction was similar between groups at baseline in peak expiratory flow and forced expiratory flow in 1 second, improving progressively during the first 6 hours and decaying slightly after 24 hours. There were no significant differences between treatment groups. Eosinophil counts in sputum also improved over time in both groups. The effect was faster with fluticasone than with prednisone but was partially lost at 24 hours. In contrast, prednisone reduced blood eosinophil counts more strongly than fluticasone, although no more rapidly. Plasma protein in sputum and eosinophil count in blood both decreased until 24 hours, with no significant differences between the groups. CONCLUSIONS. Both treatments resulted in improved symptoms, airway obstruction and inflammation, and plasma protein leakage at 24 hours. Prednisone seemed to have reduced blood eosinophil counts, whereas fluticasone reduced airway eosinophils, suggesting a less systemic antiinflammatory effect of inhaled fluticasone. REVIEWER COMMENTS. The role of inhaled steroids during an acute asthma exacerbation is unclear. There is insufficient evidence that inhaled steroids alone are as effective as systemic corticosteroids for treatment of acute asthma. The authors showed that there was no significant difference between high-dose fluticasone and oral prednisone in reducing airway obstruction and treatment of symptoms. This is particularly interesting, because inhaled steroids are less systemically active as compared with either intravenous or oral steroids and may confer fewer adverse effects. Of note, however, is the tremendously high dose of fluticasone used in the study. All study subjects had a 3-week follow-up visit, yet the authors failed to mention any relapses or continued morbidity of the subjects’ asthma symptoms. It would be of great importance to observe whether patients treated only with inhaled steroids are able to regain control of their asthma symptoms in the same manner as those patients treated with systemic steroids. Moreover, further investigations are warranted to elucidate whether lower doses of fluticasone can produce similar effects on symptoms of asthma exacerbations and airway obstruction.