Sex Differences in Airway Remodeling in a XXXX Model of @entity1030 .

@entity1 @entity172 @entity440 @entity19 @entity641 @entity2415 @entity1030
RATIONALE: After adjustment for the amount of smoking, @entity1 have a 50% increased risk of @entity1030 ( @entity1030 ) compared with @entity1 . The anatomic basis and/or mechanism(s) of these sex-related differences in @entity1030 are unknown. OBJECTIVES: To characterize the impact of female sex hormones on chronic cigarette smoke-induced airway remodeling and @entity2415 in a @entity19 model of @entity1030 . METHODS: Airway remodeling and @entity2415 were determined morphometrically in male, female, and ovariectomized @entity19 exposed to 6 months of cigarette smoke. Antioxidant- and transforming growth factor (TGF)-b-related genes were profiled in airway tissues. The selective @entity172 receptor modulator @entity440 was also administered during smoke exposure in a short-term model. Airway wall thickness of male and female @entity1 smokers at risk of or with mild @entity1030 was measured using optical coherence tomography. MEASUREMENTS AND MAIN RESULTS: Small airway wall remodeling was increased in female but not male or ovariectomized @entity19 and was associated with increased distal airway resistance, down-regulation of antioxidant genes, increased oxidative stress, and activation of @entity641 . These effects were prevented by ovariectomy. Use of @entity440 as a therapeutic intervention mitigated smoke-induced increase in oxidative stress in female @entity19 . Compared with male @entity1 smokers, female @entity1 smokers had significantly thicker airway walls. CONCLUSIONS: The excess risk of small airway disease in female @entity19 after chronic smoke exposure was associated with increased oxidative stress and @entity641 signaling and also was related to the effects of female sex hormones. @entity172 receptor antagonism might be of value in reducing oxidative stress in female smokers.
