Inhaled Corticosteroids

Abstract

Inhaled corticosteroids (ICS) are the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2). Through suppression of airway inflammation ICS reduce airway hyperresponsiveness and control asthma symptoms. ICS are now first-line therapy for all patients with persistent asthma, controlling asthma symptoms and preventing exacerbations. Inhaled long-acting β2-agonists added to ICS further improve asthma control and are commonly given as combination inhalers, which improve compliance and control asthma at lower doses of corticosteroids. By contrast, ICS provide much less clinical benefit in COPD and the inflammation is resistant to the action of corticosteroids. This appears to be due to a reduction in HDAC2 activity and expression as a result of oxidative stress. ICS are added to bronchodilators in patients with severe COPD to reduce exacerbations. ICS, which are absorbed from the lungs into the systemic circulation, have negligible systemic side effects at the doses most patients require, although the high doses used in COPD has some systemic side effects and increases the risk of developing pneumonia.

A Review on the Safety and Efficacy of Inhaled Corticosteroids in the Management of Asthma

“…The steroid-receptor complex then translocates into the nucleus and binds to glucocorticoid-response elements (GRE) in the promoter region of steroid-sensitive genes, which may encode anti-inflammatory proteins [14]. The overall effect is suppression of activated inflammatory genes and increased transcription of anti-inflammatory genes.…”

“…Smoking asthmatics and patients with severe asthma appear to be relatively corticosteroid-resistant, unlike patients with chronic obstructive pulmonary disease (COPD) where steroid responsiveness is generally poor [14]. In these patient populations, there is a reduction in histone deacetylase-2 (HDAC2) activity and expression, which prevents corticosteroids from switching off activated inflammatory genes [18][19][20].…”

“…Activated GR normally recruits HDAC2, which reduces histone acetylation induced by proinflammatory transcription factors such as nuclear factor kappa B (NFkB), thereby switching off activated inflammatory genes. Oxidative stress generated from cigarette smoke and intense inflammation in severe asthma and COPD impairs the activity of HDAC2 and reduces the anti-inflammatory effect of corticosteroids [14].…”

“…The fraction of ICS that reaches the systemic circulation is absorbed from the airway, alveolar surface, and the gut after the oropharyngeal deposits are swallowed [14]. The systemic bioavailability depends on gastrointestinal bioavailability and the amount of ICS that enters the systemic circulation via lungs.…”

“…Systemic side effects of ICS depend on several factors: the dose delivered, delivery device used, site of delivery, and individual differences in response to the corticosteroid [14]. The systemic effect of an ICS depends on the amount of the drug absorbed into the systemic circulation.…”