title: Inhaled corticosteroid normalizes some but not all airway vascular remodeling in COPD.
abstract: BACKGROUND
  This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months. Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3. This clinical trial has been registered and allocated with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with reference number ACTRN12612001111864.
  
  
  RESULTS
  There were no significant baseline differences between treatment groups. With ICS, vessels and angiogenic factors did not change in hypervascular reticular basement membrane, but in the hypovascular lamina propria (LP), vessels increased and this had a proportionate effect on lung air trapping. There was modest evidence for a reduction in LP vessels staining for VEGF with ICS treatment, but a marked and significant reduction in p-SMAD 2/3 expression.
  
  
  CONCLUSIONS
  Six-month high-dose ICS treatment had little effect on hypervascularity or angiogenic growth factors in the reticular basement membrane in COPD, but normalized hypovascularity in the LP, and this was physiologically relevant, though accompanied by a paradoxical reduction in growth factor expression.
authors.affiliation: NHMRC Center of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Amir
authors.initials: A
authors.lastname: Soltani
authors.affiliation: NHMRC Center of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Eugene Haydn
authors.initials: EH
authors.lastname: Walters
authors.affiliation: NHMRC Center of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia; Iron Metabolism Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Reid
authors.affiliation: NHMRC Center of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Shakti Dhar
authors.initials: SD
authors.lastname: Shukla
authors.affiliation: NHMRC Center of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Kaosia
authors.initials: K
authors.lastname: Nowrin
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Ward
authors.affiliation: NHMRC Center of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia.
authors.forename: H Konrad
authors.initials: HK
authors.lastname: Muller
authors.affiliation: NHMRC Center of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia; School of Health Sciences, University of Tasmania, Launceston, TAS, Australia.
authors.forename: Sukhwinder Singh
authors.initials: SS
authors.lastname: Sohal
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001315:Australia; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008168:Lung / Q000098:blood supply* / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068298:Fluticasone
keywords: COPD; airway remodeling; bronchial biopsy; inhaled corticosteroid; vascular remodeling