Inhaled corticosteroid normalizes some but not all airway vascular remodeling in COPD

Int J Chron Obstruct Pulmon Dis. 2016 Sep 22;11:2359-2367. doi: 10.2147/COPD.S113176. eCollection 2016.


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.

Conclusion: 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.

Keywords: COPD; airway remodeling; bronchial biopsy; inhaled corticosteroid; vascular remodeling.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects
  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / adverse effects
  • Australia
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Double-Blind Method
  • Female
  • Fluticasone / administration & dosage*
  • Fluticasone / adverse effects
  • Humans
  • Lung / blood supply*
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Phosphorylation
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Remodeling / drug effects*


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fluticasone