Smoking cessation but not inhaled corticosteroids (ICS) can increase histone deacetylase 2 (HDAC2)] in COPD

Introduction: The expression of anti-inflammatory HDAC2 may be reduced in COPD1 due to increased oxidative stress secondary to airway inflammation. This may induce resistance to ICS. Objective: To confirm the extent of suppressed HDAC2 immunostaining within the airways of COPD; its reversibility with ICS or smoking cessation. Methods: Endobronchial biopsies (ebb) from current smoking with COPD (CS; n=15), ex-smokers with COPD (ES; n=17) and normal controls (NC; n=9) were immunostained for HDAC2. COPD subjects entered a double blind randomised controlled trial comparing fluticasone propionate (0.5 mg/twice daily) with placebo for 6 months; ebb were again obtained after treatment and effects of ICS on HDAC2 assessed. Results: Compared to NC there was normal epithelial HDAC2 staining but signif- icant reduction in HDAC2 positive cells in the lamina propria (LP) in CS (p=0.02). However, this was due to a reduction in total LP cells (p = 0.04) and % cell HDAC2 staining was normal. This total cell change strongly negatively correlated to smoking history (R = -0.8, p<0.003). There were significantly more HDAC2 positive cells in ES compared to CS (p=0.04), and this was due to an increase in % cell staining and not increase in total cell numbers. ICS made no difference to HDAC2 staining. Conclusions: Our finding suggests that HDAC2 expression is reduced in CS but due to confounding by changes in cellularity in LP. Quitting does seem to have a real effect on upregulating HDAC2 at a cell level, but is not affected by ICS. Prospective long term smoking cessation studies are needed to confirm these preliminary findings.