Pharmaceuticals (Basel). 2010 Mar 08;3(3):514-540. doi: 10.3390/ph3030514.
Pharmaceuticals (Basel, Switzerland)
Peter J Barnes
PMID: 27713266 PMCID: PMC4033967 DOI: 10.3390/ph3030514
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.
Keywords: eosinophil; epithelial cell; glucocorticoid receptor; histone deacetylase; inflammation; inflammatory gene; long-acting β2-agonist; nuclear factor-κB; pneumonia
