Long-acting β2-agonists unlock corticosteroid insensitivity in chronic obstructive pulmonary disease

Published Online September 25, 2013

The addition of long-acting β2-agonist (LABA) to inhaled corticosteroid (ICS) achieves better disease control than ICS monotherapy in asthma and chronic obstructive pulmonary disease (COPD). Current concerns on LABA safety in asthma support fixed-dose combinations of LABA/ICS from a single inhaler. Unlike asthma, COPD is a relatively corticosteroid insensitive disease where ICS monotherapy has modest impact on lung function decline. However, LABA/ICS combination treatment significantly improves clinical outcomes in COPD patients. At the cellular level, reduced nuclear translocation of the glucocorticoid receptor (GR) contributes to corticosteroid insensitivity.

In an original research article published recently in The Journal of Allergy and Clinical Immunology (JACI), Haque et al investigated whether LABA treatment could enhance activated GR translocation to improve corticosteroid insensitivity in airway cells isolated from COPD patients. Using inhaled drug doses routinely prescribed in clinical practice, they observed combination LABA/ICS therapy had a greater anti-inflammatory effect than ICS alone and was also steroid sparing.

The authors found that addition of LABA to low-dose ICS enhanced activated GR nuclear translocation equivalent to that seen with a five-fold higher dose of ICS in sputum macrophages. The authors’ findings suggest that this biological mechanism may partly account for the superior clinical effects observed in COPD of combination LABA/ICS treatment.

The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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