Long-acting beta-agonists: anti-inflammatory properties and synergy with corticosteroids in asthma

Contemporary asthma management calls for combination inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) for patients with moderate to severe persistent asthma. This combination has consistently shown superior clinical efficacy compared with monotherapy with higher doses of ICS. It is unclear whether ICS and LABA act additively because of their complementary mechanisms of action, or whether they act synergistically based on possible favorable interactions between them. The purpose of this review is to summarize research findings on the anti-inflammatory activity of LABA published since October 2002 and to speculate on how these findings will affect future asthma management recommendations.

Combination ICS plus LABA consistently demonstrates superiority over ICS monotherapy in clinical outcomes such as pulmonary function, symptoms, and exacerbation rates, and is consistent with definitive data published before the review period. However, investigations into possible effects of LABA on inflammatory mediators are preliminary. Positive effects of LABA on some serum and bronchial inflammatory measures have been observed, but the clinical importance of these findings has not been established.

Current asthma treatment recommendations are based on clinical trials demonstrating improved clinical outcomes of combination ICS plus LABA over ICS alone. Whether LABA possesses clinically important benefits beyond bronchodilation remains to be established. Distinguishing anti-inflammatory activity of LABA will help define optimal long-term treatment regimens for asthma that not only improve pulmonary function, symptoms, and exacerbation rates but also protect against airway remodeling.