Abstract
Background: Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the underlying molecular mechanisms of hyperinflation, an important aspect of COPD pathophysiology, and how inhaled corticosteroids (ICS) affect it.
Objectives: To investigate the effects of extra-fine and standard sized ICS/long-acting β2-agonist (LABA) treatment on both hyperinflation and the upper airway epithelial gene expression profile in severe COPD.
Methods: Sixty patients entered a 1-month run-in period on low dose standard sized ICS/LABA, budesonide/formoterol (BUD/F) 200/6 b.i.d. Thereafter, patients were randomly and double-blind assigned to 3-month treatment with higher and BUD-equivalent doses of 1) extra-fine particle ICS/LABA, beclomethasone/formoterol (BDP/F) 100/6 (n=31), or 2) standard sized BUD/F200/6 (n=29), 2 inhalations b.i.d. Lung function and upper airway epithelial gene expression were assessed before and after 1 and 3-month ICS/LABA treatment.
Results: Three-month combination treatment with both extra-fine and standard-sized ICS/LABA reduced hyperinflation (RV/TLC%predicted, p<0.05). We identified an upper airway epithelial gene expression signature that associated with higher RV/TLC%predicted. This signature for RV/TLC%predicted was enriched for genes associated with increased p53 mediated apoptosis, which was decreased by ICS/LABA treatment after 3- but not yet after 1-month treatment.
Conclusions: ICS/LABA treatment improves RV/TLC%predicted in severe COPD, in association with decreased expression of genes involved in the signal transduction by p53 class mediator resulting in induction of apoptosis pathway.
- Copyright ©the authors 2016