Eosinophilic inflammation in COPD: from an inflammatory marker to a treatable trait.
Eosinophilic inflammation in COPD: from an inflammatory marker to a treatable trait.
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COPD中的嗜酸性粒细胞炎症：从炎症标志物到可治疗特征。
DOI：
10.1136/thoraxjnl-2020-215167
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发表时间：
2021-03
期刊：
影响因子：
10
通讯作者：
De Soyza A
中科院分区：
文献类型：
--
作者：
David B;Bafadhel M;Koenderman L;De Soyza A
慢性阻塞性肺疾病（COPD）的异质性带来了许多诊断、预后、治疗和管理方面的挑战，因为COPD的发病机制非常复杂，并且对潜在的细胞和分子机制仍知之甚少。一个可靠的，易于测量的，临床相关的生物标志物将是非常宝贵的改善患者的结果。COPD的国际和国家指南建议使用血液嗜酸性粒细胞计数作为生物标志物，以帮助估计对吸入性皮质类固醇（ICS）的可能反应性，并可能有助于有效的管理策略。然而，由于高嗜酸性粒细胞水平与ICS效应之间相关性的机制尚不清楚，因此呼吸界对COPD患者血嗜酸性粒细胞计数的使用仍存在广泛争议。2018年11月和2019年3月，在葛兰素史克（GlaxoSmithKline plc）的推动和资助下，举行了两次涉及呼吸医学专家、免疫学家以及初级和二级护理临床医生的国际会议。这些会议的目的是探讨嗜酸性粒细胞在COPD疾病过程中的作用以及作为预后和诊断标志物，并确定需要进一步研究的知识不足领域。在这篇综述文章中总结了与会者对关键主题的共识观点，结合当前文献，旨在帮助正在进行的COPD疾病过程研究和生物标志物的开发，以帮助临床管理。在某些情况下，嗜酸性粒细胞可以被招募到肺部，越来越多的证据支持嗜酸性粒细胞炎症在某些COPD患者中的作用。免疫调节细胞、细胞因子和趋化因子的作用促进嗜酸性粒细胞穿过支气管血管上皮浸润进入气道，其中嗜酸性粒细胞介导的炎症由促炎介质的释放驱动。多项研究和两项荟萃分析表明，外周血嗜酸性粒细胞可能与ICS降低COPD急性加重获益的可能性增加呈正相关。然而，这些研究在设计和持续时间上各不相同，嗜酸性粒细胞水平被视为ICS反应的预测因素。通常，当嗜酸性粒细胞水平为100-300个细胞/微升（或更高）时观察到反应，传统上认为该水平在正常范围内。白细胞介素-5靶向治疗的一些成功表明，嗜酸性粒细胞表型可能是一种可治疗的性状。生物标志物的使用有助于对COPD进行分层治疗，其目的是改善患者的预后。一些证据支持嗜酸性粒细胞作为COPD可治疗特征的潜在生物标志物，尽管仍然缺乏，研究正在进行中。认为最重要的是要达成统一的共识，并找到一种实用、方便和负担得起的方法来利用COPD的任何生物标志物。围绕其利用的挑战可能包括为生物标志物驱动的治疗提供明确和务实的理由，指导初级和二级护理之间的ICS戒断，以及缺乏支持临床实践中广泛应用的经济激励措施。未来的治疗应该更有针对性，而不是假设原发性疾病标签（COPD或哮喘）将定义治疗反应。
The heterogeneity of chronic obstructive pulmonary disease (COPD) creates many diagnostic, prognostic, treatment and management challenges, as the pathogenesis of COPD is highly complex and the underlying cellular and molecular mechanisms remain poorly understood. A reliable, easy-to-measure, clinically relevant biomarker would be invaluable for improving outcomes for patients. International and national guidance for COPD suggests using blood eosinophil counts as a biomarker to help estimate likely responsiveness to inhaled corticosteroids (ICS) and, potentially, to aid effective management strategies. However, with the mechanism underlying the association between higher eosinophil levels and ICS effect unknown, use of the blood eosinophil count in COPD continues to be widely debated by the respiratory community. Two international meetings involving respiratory medicine specialists, immunologists and primary and secondary care clinicians were held in November 2018 and March 2019, facilitated and funded by GlaxoSmithKline plc. The aims of these meetings were to explore the role of eosinophils in the disease processes of COPD and as prognostic and diagnostic markers, and to identify areas of deficient knowledge that warrant further research. The consensus views of the attendees on key topics, contextualised with current literature, are summarised in this review article, with the aim of aiding ongoing research into the disease processes of COPD and the development of biomarkers to aid clinical management. Under certain conditions, eosinophils can be recruited to the lung, and increasing evidence supports a role for eosinophilic inflammation in some patients with COPD. Infiltration of eosinophils across the bronchial vascular epithelium into the airways is promoted by the actions of immunoregulatory cells, cytokines and chemokines, where eosinophil-mediated inflammation is driven by the release of proinflammatory mediators. Multiple studies and two meta-analyses suggest peripheral blood eosinophils may correlate positively with an increased likelihood of exacerbation reduction benefits of ICS in COPD. The studies, however, vary in design and duration and by which eosinophil levels are viewed as predictive of an ICS response. Generally, the response was seen when eosinophil levels were 100–300 cells/µL (or higher), levels which are traditionally viewed within the normal range. Some success with interleukin-5-targeted therapy suggests that the eosinophilic phenotype may be a treatable trait. The use of biomarkers could help to stratify treatment for COPD—the goal of which is to improve patient outcomes. Some evidence supports eosinophils as a potential biomarker of a treatable trait in COPD, though it is still lacking and research is ongoing. A unified consensus and a practical, accessible and affordable method of utilising any biomarker for COPD was thought to be of most importance. Challenges around its utilisation may include presenting a clear and pragmatic rationale for biomarker-driven therapy, guidance on ICS withdrawal between primary and secondary care and a lack of financial incentives supporting broad application in clinical practice. Future treatments should, perhaps, be more targeted rather than assuming the primary disease label (COPD or asthma) will define treatment response.
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影响因子：
9
作者：
Caramori G;Casolari P;Barczyk A;Durham AL;Di Stefano A;Adcock I
通讯作者：
Adcock I
影响因子：
7.3
作者：
Davoine F;Lacy P
通讯作者：
Lacy P
影响因子：
168.9
作者：
Brightling, CE;Monteiro, W;Pavord, ID
通讯作者：
Pavord, ID
影响因子：
24.3
作者：
Doyle, Alfred D.;Mukherjee, Manali;Jacobsen, Elizabeth A.
通讯作者：
Jacobsen, Elizabeth A.
DOI：
10.1164/rccm.201108-1553oc
发表时间：
2012-07-01
影响因子：
24.7
作者：
Bafadhel, Mona;McKenna, Susan;Brightling, Christopher E.
通讯作者：
Brightling, Christopher E.