Rethinking Blood Eosinophils for Assessing Inhaled Corticosteroids Response in COPD: A Post Hoc Analysis From the FLAME Trial.

IF 9.5 1区 医学 Q1 CRITICAL CARE MEDICINE
Chest Pub Date : 2024-11-01 Epub Date: 2024-07-09 DOI:10.1016/j.chest.2024.06.3790
Alexander G Mathioudakis, Sebastian Bate, Pradeesh Sivapalan, Jens-Ulrik Stæhr Jensen, Dave Singh, Jørgen Vestbo
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引用次数: 0

Abstract

Background: The varied treatment response to inhaled corticosteroids (ICS) in patients with COPD and the associated increased risk of pneumonia necessitate a personalized ICS therapeutic approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. However, BEC appears to change in response to ICS treatment.

Research question: Does (1) BEC measured on ICS treatment (2) BEC measured off ICS treatment, or (3) the change in BEC during ICS treatment best predict treatment response to ICS in COPD?

Study design and methods: The Fluticasone Salmeterol on COPD Exacerbations Trial (FLAME), a 52-week, double-blind randomized controlled trial compared long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs) with LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing BEC before and after the run-in period to represent BEC on and off ICS, respectively. In this post hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS-containing regimen.

Results: Our study showed that LABA/LAMA combination was superior, or at least noninferior, to LABA/ICS in curbing exacerbations for most FLAME participants. However, higher BEC off ICS, higher BEC on ICS, and significant BEC suppression during ICS treatment corresponded to superior response to LABA/ICS in terms of exacerbation rate, time to first exacerbation, and time to first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment (≥ 200 cells/μL), and higher BEC on ICS did not predict ICS treatment response. For these patients, BEC off ICS and BEC change proved more predictive. Excess pneumonia risk associated with ICS appeared to be confined to patients who do not benefit from this treatment. BEC was not predictive of treatment effects on lung function and health status.

Interpretation: This exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response.

Clinical trial registration: ClinicalTrials.gov; No.: NCT01782326; URL: www.

Clinicaltrials: gov.

重新思考用于评估慢性阻塞性肺病 ICS 反应的血液嗜酸性粒细胞:FLAME 的事后分析。
背景:慢性阻塞性肺病(COPD)患者对吸入式皮质类固醇(ICS)的治疗反应各不相同,而且肺炎风险增加,因此有必要采用个性化的 ICS 治疗方法。血液嗜酸性粒细胞计数(BEC)可预测 ICS 的治疗反应。然而,嗜酸性粒细胞计数似乎会随着 ICS 治疗而发生变化:研究设计和方法:FLAME是一项为期52周的双盲RCT研究,比较了LABA/LAMA与LABA/ICS。在为期 4 周的磨合期内,禁止使用皮质类固醇。我们选择了之前服用过 ICS 的患者,从而使磨合期前和磨合期后的 BEC 分别代表服用和停用 ICS 时的 BEC。在这项事后分析中,我们重新研究了结果数据,探讨了三种 BEC 生物标志物如何与含 ICS 方案的治疗反应相互影响:结果:我们的研究证实,对于大多数 FLAME 参与者而言,LABA/LAMA 组合在遏制病情恶化方面优于或至少不劣于 LABA/ICS。然而,在ICS治疗期间,停用和使用ICS时的BEC值较高,且BEC值明显受到抑制,这与LABA/ICS在病情恶化率、首次病情恶化时间和首次肺炎时间方面的优越反应相对应。在包括 9% 的参与者在内的一个亚组中,BEC 在 ICS 治疗期间发生了显著变化(≥ 200 cells/μL),服用 ICS 时较高的 BEC 并不能预测 ICS 治疗反应。对这些患者来说,使用 ICS 后的 BEC 和 BEC 的变化更具预测性。与 ICS 相关的过高肺炎风险似乎仅限于不能从这种治疗中获益的患者。BEC不能预测治疗对肺功能和健康状况的影响:这项探索性分析主张优先使用ICS治疗后的BEC或ICS治疗期间的BEC变化来指导ICS治疗决策。临床试验注册:NCT01782326:临床试验注册:NCT01782326。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Chest
Chest 医学-呼吸系统
CiteScore
13.70
自引率
3.10%
发文量
3369
审稿时长
15 days
期刊介绍: At CHEST, our mission is to revolutionize patient care through the collaboration of multidisciplinary clinicians in the fields of pulmonary, critical care, and sleep medicine. We achieve this by publishing cutting-edge clinical research that addresses current challenges and brings forth future advancements. To enhance understanding in a rapidly evolving field, CHEST also features review articles, commentaries, and facilitates discussions on emerging controversies. We place great emphasis on scientific rigor, employing a rigorous peer review process, and ensuring all accepted content is published online within two weeks.
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