A Holy Grail of asthma management: toward understanding how long‐acting β2‐adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids

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Abstract
There is unequivocal evidence that the combination of an inhaled corticosteroid (ICS)—i.e. glucocorticoid—and an inhaled long‐acting β2‐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 β2‐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. British Journal of Pharmacology (2008) 153, 1090–1104; doi:10.1038/sj.bjp.0707627; published online 10 December 2007