J Korean Med Assoc.  2007 Oct;50(10):894-902. 10.5124/jkma.2007.50.10.894.

Inhaled Corticosteroids in Asthma

• Lee JM

• KMID: 2065001
• DOI: http://doi.org/10.5124/jkma.2007.50.10.894

Abstract

Asthma is characterized by airway inflammation, hyperresponsiveness, and remodeling, which are responsible for the variable airway obstruction and respiratory symptoms. Although a number of anti-asthma drugs have been developed, none has succeeded in managing symptoms and underlying airway inflammation as effectively as corticosteroids. However, systemic effects of the drugs were a major obstacle to use them in asthma therapy. A significant breakthrough in asthma therapy occurred when corticosteroids became available as inhaled preparations, reducing the potential for systemic effects while achieving excellent therapeutic efficacy. The first inhaled corticosteroid (ICS) having such characteristics was beclomethasone-17alpha, 21-dipropionate, which was introduced in the early 1970s. With growing information on their efficacy and the recognition of chronic inflammation as a fundamental component of asthma, ICSs have become the cornerstone of asthma therapy since the early 1990s. The potent anti-inflammatory effect of ICSs seems to be resulted mainly from the reduction of the number and activation of inflammatory cells in the bronchial mucosa and through their inhibitory effects on the synthesis of various mediators and cytokines. In addition, the airway selectivity is thought to come from a high hepatic first-pass inactivation rate of the drugs. A number of ICSs are currently on the market, and some drugs are available as the combination of an ICS and a long-acting beta2 agonist in a single inhaler. The present paper comprises a short background behind the development of ICSs, their pharmacologic and clinical profiles, and the current positions in asthma treatment.

Keyword

Inhaled corticosteroid; Asthma

MeSH Terms

Adrenal Cortex Hormones*
Airway Obstruction
Asthma*
Cytokines
Inflammation
Mucous Membrane
Nebulizers and Vaporizers
Adrenal Cortex Hormones
Cytokines

Figure

• 

  Figure 1 The mechanism by which inhaled drug particles deposit in the airway lumen

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  Figure 2 Schematic overview of pharmacokinetics of inhaled steroid. Each steroid has a different rate of the hepatic first-pass deactivation.

• 

  Figure 3 Action mechanism of corticosteroid (Modified from Am J Respir Crit Care Med 1998; 157: 51-53): Glucocorticoids enter the cell and bind to a glucocorticoid receptor (GR), which is complexed with two molecules of the 90 kDa heat shock protein (hsp90) and with p59 protein. Upon ligand binding, GR dissociates from hsp90 and translocates to the nucleus, where it binds as a dimer to a glucocorticoid response element (GRE) located within the promoter of target genes. GR can also interact as a monomer, via direct protein-protein interaction, with transcription factors such as NFkB and AP-1, activated by cytokines and other pro-inflammatory stimuli. The resulting mutual repression prevents both GR and the other transcription factors from binding to theirrespective DNA response elements (RE).

• 

  Figure 4 Biological effects of corticosteroids on inflammatory cells and structural cells in the airways.

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