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

Amir Soltani,1 Eugene Haydn Walters,1,* David W Reid,1,2 Shakti Dhar Shukla,1 Kaosia Nowrin,1 Chris Ward,3 H Konrad Muller,1 Sukhwinder Singh Sohal1,4,* 1NHMRC Center of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia; 2Iron Metabolism Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia; 3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK; 4School of Health Sciences, University of Tasmania, Launceston, TAS, Australia *These authors contributed equally to this work 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: airway remodeling, bronchial biopsy, COPD, inhaled corticosteroid, vascular remodeling&nbsp