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Randomized Controlled Trial
. 2023 Jul 20;62(1):2300218.
doi: 10.1183/13993003.00218-2023. Print 2023 Jul.

Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial

Daiana Stolz  1   2   3   4 , Eleni Papakonstantinou  5   2   3   4 , Maria Pascarella  5 , Kathleen Jahn  5 , Aline Siebeneichler  5 , Andrei M Darie  5 , Matthias J Herrmann  5 , Werner Strobel  5 , Anna Salina  5 , Leticia Grize  5 , Spasenija Savic Prince  6 , Michael Tamm  5   2
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Free article
Randomized Controlled Trial

Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial

Daiana Stolz et al. Eur Respir J. .
Free article

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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.

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Conflict of interest statement

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.

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