Pneumologie 2025; 79(S 01): S111
DOI: 10.1055/s-0045-1804789
Abstracts
D2 – Grundlagen- und translationale Lungenforschung

ICS responsiveness and GR expression in endobronchial biopsies of COPD patients

D Soriano
1   Klinik für Pneumologie, Universitätsklinik Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Deutschland; Universitätsklinikum Freiburg; Klinik für Pneumologie
,
E Papakonstantinou
2   Department of Pneumology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.; Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital, 4031 Basel, Switzerland.
,
M Nowak
3   University Hospital Zürich
,
L Grieze
4   University Hospital Basel; University Hospital Basel; Clinic of Respiratory Medicine and Pulmonary Cell Research
,
S Savic
5   University Hospital Basel; Universitiy Hospital Basel; Department of Pathology
,
V Kölzer
6   University Hospital Basel
,
D Stolz
7   Universitätsklinikum Freiburg; Klinik für Pneumologie, Department Innere Medizin, Medizinische Fakultät, Albert Ludwigs Universität, Freiburg, Deutschland; Clinic of Respiratory Medicine and Pulmonary Cell Research
› Author Affiliations
› Further Information
Also available ateRef
 

The responsiveness to inhaled corticosteroids (ICS) in COPD patients is not well understood. The expression of glucocorticoid receptor (GR) and its two isotypes GR alpha (the active isotype) and beta (the repressing counterpart) may be linked to patients’ response to treatment. We investigated the association between the expression of the total GR, GR alpha and GR beta in endobronchial biopsies (EBB) of COPD patients with known responsiveness to ICS-therapy.

The expression of GR in total, GR alpha and GR beta was evaluated by immunochemistry in endobronchial biopsies from 188 subjects with COPD. The subjects were treated within the HISTORIC study, a randomized, placebo-controlled, double-blind, investigator-initiated trial that proved the hypothesis that high airway smooth muscle cell (ASMC) area in EBB of COPD patients is associated to responsiveness to ICS. A total of 1624 slides were scanned on a Hamamatsu NanoZoomer and marker expression was quantified by digital image analysis using HALO (Indica Labs). Patients’ response to ICS was assessed by FEV1 improvement over 12 months.

The expression of the total GR receptor did not differ between responders and non-responders. However, the overall expression of GR beta was decreased in the tissue of the EBB from responders compared to non-responders (p=0.04). In responders GR alpha expression was decreased in the stroma (p=0.04), in the glandular epithelium (p=0.006), and the bronchial epithelium (p=0.006), however the expression of GR beta was decreased in airway smooth muscle cells (p=0.04) which makes the predominant part of the mucosa of responders. Patients treated with ICS before the first biopsie exhibited a lower expression of total GR in the stroma (p=0.0002), the bronchial epithelium (p=0.0009) and the ASMC (p=0.0007).

These results suggest that the difference in expression of the GR and its isotypes may help to identify responders to ICS-therapy in COPD patients. It appears that the ICS therapy itself changes the expression of the GR within the endobronchial mucosa.



Publication History

Article published online:
18 March 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany