A Holy Grail of asthma management: toward understanding how long-acting beta(2)-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids.
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.
Giembycz
M A
MA
Department of Pharmacology and Therapeutics, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. giembycz@ucalgary.ca
Kaur
M
M
Leigh
R
R
Newton
R
R
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D018849:Controlled Clinical Trials as Topic; D004338:Drug Combinations; D004357:Drug Synergism; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004338:Drug Combinations; D005938:Glucocorticoids