title: Sex Differences in Airway Remodeling in a Mouse Model of Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  After adjustment for the amount of smoking, women have a 50% increased risk of chronic obstructive pulmonary disease (COPD) compared with men. The anatomic basis and/or mechanism(s) of these sex-related differences in COPD are unknown.
  
  
  OBJECTIVE
  To characterize the impact of female sex hormones on chronic cigarette smoke-induced airway remodeling and emphysema in a mouse model of COPD.
  
  
  METHODS
  Airway remodeling and emphysema were determined morphometrically in male, female, and ovariectomized mice exposed to 6 months of cigarette smoke. Antioxidant- and transforming growth factor (TGF)-β-related genes were profiled in airway tissues. The selective estrogen receptor modulator tamoxifen was also administered during smoke exposure in a short-term model. Airway wall thickness of male and female human smokers at risk of or with mild COPD was measured using optical coherence tomography.
  
  
  RESULTS
  Small airway wall remodeling was increased in female but not male or ovariectomized mice and was associated with increased distal airway resistance, down-regulation of antioxidant genes, increased oxidative stress, and activation of TGF-β1. These effects were prevented by ovariectomy. Use of tamoxifen as a therapeutic intervention mitigated smoke-induced increase in oxidative stress in female mice. Compared with male human smokers, female human smokers had significantly thicker airway walls.
  
  
  CONCLUSIONS
  The excess risk of small airway disease in female mice after chronic smoke exposure was associated with increased oxidative stress and TGF-β1 signaling and also was related to the effects of female sex hormones. Estrogen receptor antagonism might be of value in reducing oxidative stress in female smokers.
authors.affiliation: 1 Centre for Heart Lung Innovation, St. Paul's Hospital.|2 Department of Medicine, and.
authors.forename: Anthony
authors.initials: A
authors.lastname: Tam
authors.affiliation: 3 Department of Pathology, University of British Columbia, Vancouver, BC, Canada; and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Churg
authors.affiliation: 3 Department of Pathology, University of British Columbia, Vancouver, BC, Canada; and.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Wright
authors.affiliation: 3 Department of Pathology, University of British Columbia, Vancouver, BC, Canada; and.
authors.forename: Steven
authors.initials: S
authors.lastname: Zhou
authors.affiliation: 1 Centre for Heart Lung Innovation, St. Paul's Hospital.|2 Department of Medicine, and.
authors.forename: Miranda
authors.initials: M
authors.lastname: Kirby
authors.affiliation: 1 Centre for Heart Lung Innovation, St. Paul's Hospital.|2 Department of Medicine, and.
authors.forename: Harvey O
authors.initials: HO
authors.lastname: Coxson
authors.affiliation: 4 British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.affiliation: 1 Centre for Heart Lung Innovation, St. Paul's Hospital.|2 Department of Medicine, and.
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
authors.affiliation: 1 Centre for Heart Lung Innovation, St. Paul's Hospital.|2 Department of Medicine, and.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D012737:Sex Factors
keywords: cigarette smoke; emphysema; estrogen; oxidative stress; small airway remodeling