A Holy Grail of asthma management: toward understanding how long-acting beta(2)-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids

Br J Pharmacol. 2008 Mar;153(6):1090-104. doi: 10.1038/sj.bjp.0707627. Epub 2007 Dec 10.


There is unequivocal evidence that the combination of an inhaled corticosteroid (ICS) -- i.e. glucocorticoid -- and an inhaled long-acting beta(2)-adrenoceptor agonist (LABA) is superior to each component administered as a monotherapy alone in the clinical management of asthma. Moreover, Calverley and colleagues (Lancet 2003, 361: 449-456; N Engl J Med 2007, 356: 775-789) reporting for the 'TRial of Inhaled STeroids ANd long-acting beta(2)-agonists (TRISTAN)' and 'TOwards a Revolution in COPD Health (TORCH)' international study groups also demonstrated the superior efficacy of LABA/ICS combination therapies over ICS alone in the clinical management of chronic obstructive pulmonary disease. This finding has been independently confirmed indicating that the therapeutic benefit of LABA/ICS combination therapies is not restricted to asthma and may be extended to other chronic inflammatory diseases of the airways. Despite the unquestionable benefit of LABA/ICS combination therapies, there is a vast gap in our understanding of how these two drugs given together deliver superior clinical efficacy. In this article, we review the history of LABA/ICS combination therapies and critically evaluate how these two classes of drugs might interact at the biochemical level to suppress pro-inflammatory responses. Understanding the molecular basis of this fundamental clinical observation is a Holy Grail of current respiratory diseases research as it could permit the rational exploitation of this effect with the development of new 'optimized' LABA/ICS combination therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Agonists / therapeutic use
  • Asthma / drug therapy*
  • Controlled Clinical Trials as Topic
  • Drug Combinations
  • Drug Synergism
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Humans
  • Pulmonary Disease, Chronic Obstructive / drug therapy*


  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Drug Combinations
  • Glucocorticoids