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

conference contribution
posted on 2023-05-24, 10:43 authored by Sukhwinder SohalSukhwinder Sohal, Reid, D, Soltani, A, Weston, S, Muller, HK, Wood-Baker, R, Eugene WaltersEugene Walters
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.

History

Publication title

The European Respiratory Journal

Pagination

785s

Department/School

Menzies Institute for Medical Research

Event title

The European Respiratory Journal

Date of Event (Start Date)

2010-01-01

Date of Event (End Date)

2010-01-01

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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