Effects of a single inhaled budesonide/formoterol dose on glucocorticoid receptor activity in sputum of COPD patients

Background:Combination of inhaled corticosteroids (ICS) and long-acting β2-adrenergic agonists (LABA) offer clinical benefits in COPD compared with ICS alone or LABA alone, especially in reduction of exacerbations. In asthma, LABA enhance glucocorticoid receptor (GR) nuclear translocation in airway macrophages in the presence of corticosteroid, which may explain why low-dose ICS combined with LABA is as effective as high-dose ICS. Whether this mechanism occurs in COPD is not fully studied. Method:In a cross-over study, 35 mild-to-moderate COPD patients inhaled a single dose of budesonide (BUD) 400µg and formoterol (FM) 12µg combination (Symbicort 400/12µg), or BUD/FM 800/24µg (Symbicort 800/24µg), or budesonide (Pulmicort) 800µg, or FM (Oxis) 24µg. Induced sputum was collected after 2h. GR activity and level of inflammatory marker, CXCL8, were analysed in sputum. GR activity was assessed as binding of GR to glucocorticoid response elements (GRE) in sputum macrophages. Data were analysed by non-parametric tests. Results: A single BUD/FM 400/12µg dose enhanced GR-GRE binding to similar extent as BUD 800µg dose and high-dose BUD/FM 800/24µg; 60-90% increase vs basal levels (p<0.05 for all) while FM had no effect. BUD/FM 400/12µg was also as effective in decreasing sputum CXCL8 as BUD 800µg and BUD/FM 800/24µg; 60-70% decrease (p<0.05 for all) while FM had no effect. All treatments were equally effective in improving FEV₁ (p<0.05) and FVC (p<0.05). Conclusions: A single, low inhaled dose of BUD/FM 400/12µg triggers anti-inflammatory effects in the airways and improves lung function in COPD patients as effective as double dose of BUD/FM or BUD alone. Support: AstraZeneca.