title: Changes in airway histone deacetylase2 in smokers and COPD with inhaled corticosteroids: a randomized controlled trial.
abstract: The expression of HDAC2 is reported as reduced in chronic obstructive pulmonary disease (COPD). We assessed HDAC2 expression within the airways of smokers and subjects with COPD and effects of inhaled corticosteroids (ICS), using immuno-histology to contrast with previous molecular methodology. Endobronchial biopsies (ebb) from current smokers with COPD (COPD-CS; n = 15), ex-smokers with COPD (COPD-ES; n = 17), smokers with normal lung function (NS; n = 16) and normal controls (NC; n = 9) were immunostained for HDAC2. A double-blinded, randomized, placebo-controlled 6 months intervention study assessed effects of ICS on HDAC2 in 34 COPD subjects. There was no difference in epithelial HDAC2 staining in all groups. There was a significant reduction in total cell numbers in the lamina propria (LP) in COPD-CS and NS (p<0.05). LP cellularity correlated inversely with smoking history in COPD-CS (R = -0.8, p<0.003). HDAC2 expression increased markedly in NS (p<0.001); in contrast COPD-CS was associated with suppressed signal (p<0.03), while normal in COPD-ES. ICS did not affect HDAC2 cell staining. Our findings suggest that airway HDAC2 expression is increased in the LP by smoking itself, but is reduced in COPD. Ex-smokers have normalised HDAC2 cell expression, but ICS had no effect. The paper emphasise the pit-falls of relying on molecular data alone to define airway changes.
  
  
  BACKGROUND
  
  The Australian New Zealand Clinical Trials Registry (ANZCTR). REGISTRY NUMBER: ACTRN12612001111864.
authors.affiliation: Breathe Well Centre for Research Excellence in Chronic Respiratory Disease, University of Tasmania School of Medicine, Hobart, Australia. sssohal@utas.edu.au
authors.forename: Sukhwinder Singh
authors.initials: SS
authors.lastname: Sohal
authors.forename: David
authors.initials: D
authors.lastname: Reid
authors.forename: Amir
authors.initials: A
authors.lastname: Soltani
authors.forename: Steven
authors.initials: S
authors.lastname: Weston
authors.forename: Hans Konrad
authors.initials: HK
authors.lastname: Muller
authors.forename: Richard
authors.initials: R
authors.lastname: Wood-Baker
authors.forename: Eugene Haydn
authors.initials: EH
authors.lastname: Walters
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001980:Bronchi / Q000201:enzymology*; D001999:Bronchoscopy; D005260:Female; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000201:enzymology*; D012907:Smoking
chemical_list: D056464:Histone Deacetylase 2