Abstract
Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant but modest clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle (ASMC) area in COPD is associated to ICS responsiveness.
In this investigator-initiated and –driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, GOLD stage B-D, underwent bronchoscopy with endobronchial biopsy. Patients divided in groups A and B with high ASMC area (HASMC: >20% of the bronchial tissue area) and with low ASMC area (LASMC: ≤20% of the bronchial tissue area), respectively and followed a run-in period of 6 weeks on open-label triple inhaled therapy with aclidinium/formoterol/budesonide (ACL/FOR/BUD:400/12/400 mcg/bid). Subsequently, patients were randomised to receive either ACL/FOR/BUD or ACL/FOR/Placebo and followed for 12 months. The primary end point of the study was the difference in post-bronchodilator FEV1 over 12 months between patients with LASMC and HASMC receiving or not receiving ICS.
In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV1 over 12 months, as compared to ACL/FOR/placebo p=0.675. In patients with HASMC, however, ACL/FOR/BUD significantly improved FEV1, as compared to ACL/FOR/placebo p=0.020. Over 12 months, the difference of FEV1 change between the group of ACL/FOR/BUD and the group of ACL/FOR/placebo was 50.6 mL·year−1 within the group of patients with LASMC and 183.0 mL·year−1 within the group of patients with HASMC.
COPD patients with ΗASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Daiana Stolz reports support for the present manuscript from Astra Zeneca (unrestricted grant) and University Hospital Basel. Outside the submitted work, Daiana Stolz reports lecture honoraria from CSL Behring, Berlin-Chemie Menarini, Novartis, GlaxoSmithKline, AstraZeneca, Vifor, Merck, Chiesi, Sanofi; advisory board membership with GlaxoSmithKline, CSL Behring.
Conflict of interest: Andrei Μ. Darie reports grants from University Hospital Basel; lecture honoraria from AstraZeneca, GSK; travel support from OrPha Swiss, Janseen; advisory board participation with Gebro Pharma, MSD; outside the submitted work.
Conflict of interest: Matthias J Herrmann reports lecture honoraria from GSK, OM Pharma; travel support from Sanofi; advisory board participation with OM Pharma; outside the submitted work.
Conflict of interest: All other authors have nothing to disclose.
- Received February 9, 2023.
- Accepted May 22, 2023.
- Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org
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