Abstract
Background 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 cell (ASMC) area in COPD is associated with ICS responsiveness.
Methods In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, Global Initiative for Chronic Obstructive Lung Disease stage B–D, underwent bronchoscopy with endobronchial biopsy. Patients were divided into groups A and B, with high ASMC area (HASMC: >20% of the bronchial tissue area) and 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 (ACL)/formoterol (FOR)/budesonide (BUD) (400/12/400 μg twice daily). 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 forced expiratory volume in 1 s (FEV1) over 12 months between patients with LASMC and HASMC receiving or not receiving ICS.
Results In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV1 over 12 months, as compared to ACL/FOR/placebo (p=0.675). However, in patients with HASMC, 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 ACL/FOR/BUD group and the ACL/FOR/placebo group 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.
Conclusion 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.
Tweetable abstract
Airway smooth muscle area in endobronchial biopsies can be used as a predictive biomarker to identify COPD patients who belong to a specific COPD endotype that responds better to triple therapy with LAMA/LABA/ICS https://bit.ly/3BSLYIS
Footnotes
This article has been revised according to the correction published in the October 2023 issue of the European Respiratory Journal.
This clinical trial was prospectively registered with the ISRCTN registry as ISRCTN11017699. Individual participant data will not be made available. Protocol details may be available upon request to corresponding author.
This article has an editorial commentary: https://doi.org/10.1183/13993003.00956-2023
Conflict of interest: D. Stolz reports support for the present manuscript from AstraZeneca (unrestricted grant) and University Hospital Basel; outside the submitted work, D. Stolz reports lecture honoraria from CSL Behring, Berlin-Chemie Menarini, Novartis, GlaxoSmithKline, AstraZeneca, Vifor, Merck, Chiesi and Sanofi, and advisory board membership with GlaxoSmithKline and CSL Behring. A.M. Darie reports grants from University Hospital Basel, lecture honoraria from AstraZeneca and GSK, travel support from OrPha Swiss and Janssen, and advisory board participation with Gebro Pharma and MSD, outside the submitted work. M.J. Herrmann reports lecture honoraria from GSK and OM Pharma, travel support from Sanofi, and advisory board participation with OM Pharma, outside the submitted work. All other authors have no potential conflicts of interest to disclose.
Support statement: This study was funded by an unrestricted grant from AstraZeneca and the Clinic of Pneumology, University Hospital Basel, Switzerland. AstraZeneca had no influence on study design or interpretation of the data. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received February 9, 2023.
- Accepted May 22, 2023.
- Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org
LIBRARY USERS
Log in through your institution
Purchase access
