Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
Eur Respir J. 2023 Jul 20;62(1). doi: 10.1183/13993003.00218-2023. Print 2023 Jul.
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.
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 (FEV) 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 FEV over 12 months, as compared to ACL/FOR/placebo (p=0.675). However, in patients with HASMC, ACL/FOR/BUD significantly improved FEV, as compared to ACL/FOR/placebo (p=0.020). Over 12 months, the difference of FEV change between the ACL/FOR/BUD group and the ACL/FOR/placebo group was 50.6 mL·year within the group of patients with LASMC and 183.0 mL·year 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.
尽管吸入性皮质类固醇（ICS）在哮喘中非常有效，但在 COPD 中，它们提供了显著但适度的临床益处。在这里，我们检验了这样一个假设，即 COPD 中高支气管气道平滑肌细胞（ASMC）面积与 ICS 反应性相关。
在这项由研究者发起并驱动的、双盲、随机、安慰剂对照试验（HISTORIC）中，190 名 COPD 患者（GOLD 分期 B-D）接受支气管镜检查和支气管内膜活检。患者被分为 A 组和 B 组，分别具有高 ASMC 面积（HASMC：>20%的支气管组织面积）和低 ASMC 面积（LASMC：≤20%的支气管组织面积），并在接受为期 6 周的开放标签三联吸入治疗（aclidinium [ACL]/formoterol [FOR]/budesonide [BUD]，400/12/400μg，每日两次）的情况下进行了预试验期。随后，患者被随机分配接受 ACL/FOR/BUD 或 ACL/FOR/安慰剂治疗，并随访 12 个月。该研究的主要终点是接受或不接受 ICS 的 LASMC 和 HASMC 患者在 12 个月时支气管扩张剂后用力呼气量 1 秒（FEV1）的差异。
在 LASMC 患者中，与 ACL/FOR/安慰剂相比，ACL/FOR/BUD 在 12 个月内并未显著改善 FEV1（p=0.675）。然而，在 HASMC 患者中，与 ACL/FOR/安慰剂相比，ACL/FOR/BUD 显著改善了 FEV1（p=0.020）。在 12 个月内，ACL/FOR/BUD 组与 ACL/FOR/安慰剂组之间的 FEV1 变化差异在 LASMC 患者组中为 50.6 mL·年，在 HASMC 患者组中为 183.0 mL·年。
与 LASMC 患者相比，HASMC 的 COPD 患者对 ICS 的反应更好，这表明这种组织学分析可能预测接受三联疗法的 COPD 患者对 ICS 的反应性。
