A randomized clinical trial on inhaled ciclesonide for managing acute asthma in the emergency room

Abstract

INTRODUCTIONAsthma is a chronic inflammatory disease of the airways that affects approximately 300 million people worldwide. In the United States, between 2001 and 2003, asthma exacerbations caused 4,210 deaths, 504,000 hospitalizations and 1.8 million emergency room visits. 1 Since the mid-1990s, inhaled corticosteroids have been tested for managing asthma exacerbations in emergency-room settings. They have systemic corticosteroid-sparing potential and avoid the need for venipuncture, which is sometimes a difficult procedure. [2][3][4] These drugs exert vasoconstrictor effects on the mucosa by reducing neuronal reuptake of noradrenaline at the neuromuscular junctions of mucosal vessels, thus reducing secretions and facilitating the delivery of beta-2 agonists to their target receptors. Their onset of action is rapid, with peak vasoconstriction occurring in 30 minutes and lasting up to 90 minutes after inhalation. 5,6 Ciclesonide is a prodrug that is activated at the site of action (bronchial cells and lining fluid of the bronchus) by bronchial esterases. These convert ciclesonide to desisobutyryl ciclesonide, which has 100-fold greater affinity for the glucocorticoid receptor than ciclesonide itself. 7Because of this peculiar property, common side effects such as hoarseness, dysphonia, oral candidiasis and suppression of the hypothalamic-pituitary-adrenal axis are much less frequent with ciclesonide than with other high-dose inhaled corticosteroids, as it is inactive outside the lung. [7][8][9][10][11] The anti-inflammatory action of intravenous corticosteroids occurs via a genomic mechanism.This reduces expression of proinflammatory mediators such as interleukins 12 and upregulates