Defining the Effects of an Inhaled Corticosteroid and Long-Acting -Agonist on Therapeutic Targets

The effects of inhaled corticosteroids (ICSs) and long-acting 2-agonists (LABAs) on therapeutic targets have significant clinical relevance regarding optimal management of asthma. Asthma pathophysiology involves two main components: smooth muscle dysfunction and airway inflammation. LABAs and ICSs provide complementary modes of action in that these agents modulate smooth muscle dysfunction/bronchoconstriction and airway inflammation, respectively. Despite the documented benefits of ICSs, they remain underutilized because of a variety of physician- and patient-associated reasons including safety concerns. Underlying these concerns are published reports that suggest systemic effects of high doses of ICSs: skin bruising, reduction of bone mineral density, cataracts, glaucoma, and impaired short-term growth in children. Simple strategies to reduce the potential adverse effects of inhaled steroids include using the lowest effective maintenance dose and optimizing steroid-sparing strategies, specifically combination therapy with a LABA, leukotriene modifier, or theophylline. LABA therapy, when added to ICS therapy, provides clinically significant steroid-sparing effects while at the same time reducing the rate at which asthma exacerbations occur. Available clinical evidence suggests that the combination of ICS plus LABA is the best available option for the management of moderate persistent asthma. Consequently, this combination is the preferred choice for treating moderate persistent asthma based on current National Asthma Education and Prevention Program guidelines for the diagnosis and treatment of asthma.