生物标志物指导下的非 T2 炎症表型哮喘患者吸入性皮质类固醇的撤药：一项随机对照试验研究方案。

Biomarker-guided withdrawal of inhaled corticosteroids in asthma patients with a non-T2 inflammatory phenotype - a randomized controlled trial study protocol.

机构信息

Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, Kettegaard Allé 30, Hvidovre, Denmark.

Institute of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen, Denmark.

出版信息

BMC Pulm Med. 2023 Oct 4;23(1):372. doi: 10.1186/s12890-023-02679-y.

DOI:10.1186/s12890-023-02679-y

PMID:37794472

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10552380/

Abstract

BACKGROUND

Non-T2 asthma is characterized by the absence of elevated type 2 inflammatory biomarkers such as blood-eosinophils, total and allergen-specific Immunoglobulin E and Fractional exhaled Nitric Oxide (FeNO). According to guidelines, inhaled corticosteroids (ICS) are the cornerstone of asthma management. However, ICS treatment is associated with a risk of local side effects, including hoarseness and thrush, and long-term high-dose therapy may cause systemic adverse effects. Furthermore, whereas treatment with ICS is highly effective in T2 asthma, studies have shown a markedly reduced ICS efficacy in patients with a lower degree of T2 inflammation, thus posing a clinical challenge in this subgroup of patients. Hence, owing to the ICS dosage step-up approach in current clinical guidelines, patients with low T2 biomarkers are at risk of being exposed to high doses of ICS, and by that at risk of side effects. Thus, an ICS-treatment regime guided by biomarkers that reflects the inflammatory phenotype is warranted in order to reduce the corticosteroid burden in patients with non-T2 asthma. This study combines a panel of non-T2 inflammatory markers (low periostin, low blood-eosinophils, and low FeNO), to determine if this group of patients can maintain asthma control during ICS withdrawal.

METHODS

This is an ongoing prospective multicenter open-label randomized, controlled trial aiming to assess if ICS can be safely tapered in patients with non-T2 asthma. The patients are randomized 1:1 to either standard of care or an ICS tapering regimen (n = 55 in each group) where the initial ICS dose is reduced by 50% for 8 weeks followed by total ICS removal. The primary endpoint is change in asthma control questionnaire (ACQ) from baseline to post-tapered ICS. The secondary endpoints are time from baseline to drop-out caused by loss of asthma control, changes in serum-periostin, blood-eosinophils, FeNO, Forced Expiratory Volume in 1 s (FEV1) and in sputum-eosinophils.

DISCUSSION

This study aims to provide data on ICS tapering in non-T2 asthma patients and to contribute to a more individualized and corticosteroid-sparing treatment regime in this group of patients.

TRIAL REGISTRATION

Clinicaltrials.gov Identifier: NCT03141424. Registration date: May 5, 2017.

摘要

背景

非 T2 哮喘的特征是不存在升高的 2 型炎症生物标志物，如血嗜酸性粒细胞、总 IgE 和过敏原特异性 IgE 以及呼出气一氧化氮分数（FeNO）。根据指南，吸入性皮质类固醇（ICS）是哮喘管理的基石。然而，ICS 治疗与局部副作用风险相关，包括声音嘶哑和鹅口疮，长期高剂量治疗可能会引起全身不良反应。此外，尽管 ICS 治疗在 T2 哮喘中非常有效，但研究表明，在 2 型炎症程度较低的患者中，ICS 的疗效明显降低，因此在该亚组患者中存在临床挑战。因此，由于当前临床指南中的 ICS 剂量递增方法，低 T2 生物标志物患者有暴露于高剂量 ICS 的风险，并因此有副作用的风险。因此，需要一种基于生物标志物的 ICS 治疗方案，该方案反映炎症表型，以减少非 T2 哮喘患者的皮质类固醇负担。本研究结合了一组非 T2 炎症标志物（低骨桥蛋白、低血嗜酸性粒细胞和低 FeNO），以确定该组患者在停用 ICS 期间是否能够维持哮喘控制。

方法

这是一项正在进行的前瞻性多中心开放标签随机对照试验，旨在评估是否可以安全地在非 T2 哮喘患者中逐渐减少 ICS。患者按 1:1 随机分为标准治疗组或 ICS 逐渐减量组（每组 55 例），其中初始 ICS 剂量减少 50%，持续 8 周，然后完全停用 ICS。主要终点是从基线到逐渐减量 ICS 后哮喘控制问卷（ACQ）的变化。次要终点是从基线到因哮喘控制丧失而退出的时间、血清骨桥蛋白、血嗜酸性粒细胞、FeNO、1 秒用力呼气容积（FEV1）和痰嗜酸性粒细胞的变化。