Histological evaluation of GR and HDAC expression in endobronchial biopsies of COPD patients with known responsiveness to ICS: Insights from the HISTORIC study

The dysregulated expression of glucocorticoid receptor (GR) and histone deacetylases (HDACs) has been linked to COPD patients’ response to ICS treatment. This study investigates the potential association between the expression of GR and HDACs in endobronchial biopsies (EBB) of COPD patients and their responsiveness to ICS. Tissue expression of GR (including isoforms GRα and GRβ) and HDAC-2, -3, -5 and -8 was evaluated by immunohistochemistry in EBB from 188 patients with COPD, subjects of the HISTORIC study, a randomized, placebo-controlled, double-blind, investigator-initiated trial that proved the hypothesis that high airway smooth muscle cell area in EBB of COPD patients is associated to responsiveness to ICS. Slides were scanned on a Hamamatsu NanoZoomer and marker expression was quantified by digital image analysis using HALOTM (Indica Labs). Patients’ response to ICS was assessed by FEV1 improvement over 12 months. Patients who responded well to ICS exhibited lower expression of total GR in the stroma (p=0.044) and glandular epithelium (p=0.006), and lower overall tissue expression of GRβ (p=0.043) compared with patients who did not respond to ICS. ICS-responsive patients also exhibited higher overall expression of HDAC-2 (p=0.041) and lower expression of HDAC-5 in areas with squamous metaplasia (p=0.036) and of HDAC8 in glandular epithelium (p=0.028). These results suggest that evaluating GR isoforms and HDAC expression in bronchial tissue may help identify COPD patients who would benefit from ICS treatment, potentially leading to more precise and effective medical interventions with reduced side effects and costs.