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

• Published in: International journal of chronic obstructive pulmonary disease Vol. 11; no. 1; pp. 2359 - 2367
• Main Authors: Soltani, Amir, Walters, Eugene Haydn, Reid, David W, Shukla, Shakti Dhar, Nowrin, Kaosia, Ward, Chris, Muller, H Konrad, Sohal, Sukhwinder Singh
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2016; Dove Medical Press Ltd; Dove Medical Press
• Subjects: Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - adverse effects; Adult; Aged; airway remodeling; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Antibodies; Asthma; Australia; Biopsy; bronchial biopsy; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - adverse effects; Bronchoscopy; Cancer therapies; Care and treatment; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cloning; COPD; Corticosteroid drugs; Demographics; Double-Blind Method; Female; Fluticasone - administration & dosage; Fluticasone - adverse effects; Glucocorticoids; Growth factors; Humans; Inhaled corticosteroid; Lung - blood supply; Lung - drug effects; Lung - physiopathology; Lung cancer; Male; Middle Aged; Original Research; 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; Spirometry; Steroids; Time Factors; Transforming Growth Factor beta1 - metabolism; Treatment Outcome; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; vascular remodeling; Vascular Remodeling - drug effects; United Kingdom > UK; United States > US; vascular remodeling; inhaled corticosteroid; airway remodeling; bronchial biopsy; COPD
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S113176

This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD). 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. 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. 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.