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; Eleni Papakonstantinou; Maria Pascarella; Kathleen Jahn; Aline Siebeneichler; Andrei M. Darie; Matthias J. Herrmann; Werner Strobel; Anna Saliņa; Leticia Grize; Spasenija Savic Prince; Michael Tamm

doi:10.1183/13993003.00218-2023

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^*
, Eleni Papakonstantinou
, Maria Pascarella
, Kathleen Jahn
, Aline Siebeneichler
, Andrei M. Darie
, Matthias J. Herrmann
, Werner Strobel
, Anna Saliņa
, Leticia Grize
, Spasenija Savic Prince
, Michael Tamm

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

3 Downloads (Pure)

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.

Original language	English
Article number	2300218
Journal	European Respiratory Journal
Volume	62
Issue number	1
DOIs	https://doi.org/10.1183/13993003.00218-2023
Publication status	Published - 2023
Externally published	Yes

Field of Science*

3.2 Clinical medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1183/13993003.00218-2023

Airway smooth muscle areaFinal published version, 694 KB

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Stolz, D., Papakonstantinou, E., Pascarella, M., Jahn, K., Siebeneichler, A., Darie, A. M., Herrmann, M. J., Strobel, W., Saliņa, A., Grize, L., Prince, S. S., & Tamm, M. (2023). Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial. European Respiratory Journal, 62(1), Article 2300218. https://doi.org/10.1183/13993003.00218-2023

@article{11f3bd9decea41329e6e5bf1a2b5ed85,

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

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.",

author = "Daiana Stolz and Eleni Papakonstantinou and Maria Pascarella and Kathleen Jahn and Aline Siebeneichler and Darie, \{Andrei M.\} and Herrmann, \{Matthias J.\} and Werner Strobel and Anna Saliņa and Leticia Grize and Prince, \{Spasenija Savic\} and Michael Tamm",

note = "Publisher Copyright: Copyright {\textcopyright} The authors 2023.",

year = "2023",

doi = "10.1183/13993003.00218-2023",

language = "English",

volume = "62",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "1",

}

Stolz, D, Papakonstantinou, E, Pascarella, M, Jahn, K, Siebeneichler, A, Darie, AM, Herrmann, MJ, Strobel, W, Saliņa, A, Grize, L, Prince, SS & Tamm, M 2023, 'Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial', European Respiratory Journal, vol. 62, no. 1, 2300218. https://doi.org/10.1183/13993003.00218-2023

Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial. / Stolz, Daiana; Papakonstantinou, Eleni; Pascarella, Maria et al.
In: European Respiratory Journal, Vol. 62, No. 1, 2300218, 2023.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC)

T2 - a randomised, placebo-controlled, double-blind, investigator-initiated trial

AU - Stolz, Daiana

AU - Papakonstantinou, Eleni

AU - Pascarella, Maria

AU - Jahn, Kathleen

AU - Siebeneichler, Aline

AU - Darie, Andrei M.

AU - Herrmann, Matthias J.

AU - Strobel, Werner

AU - Saliņa, Anna

AU - Grize, Leticia

AU - Prince, Spasenija Savic

AU - Tamm, Michael

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85165521728

U2 - 10.1183/13993003.00218-2023

DO - 10.1183/13993003.00218-2023

M3 - Article

C2 - 37385657

AN - SCOPUS:85165521728

SN - 0903-1936

VL - 62

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 1

M1 - 2300218

ER -

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

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