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慢性阻塞性肺疾病的新兴疗法:将创新与可治疗特征相对应

Emerging Therapeutics in COPD: Mapping Innovation to Treatable Traits.

作者信息

Cazzola Mario, McDonald Vanessa M, Stolz Daiana, Rogliani Paola, Matera Maria Gabriella

机构信息

Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome 'Tor Vergata', Rome, Italy.

College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.

出版信息

Lung. 2025 Sep 3;203(1):92. doi: 10.1007/s00408-025-00844-0.

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a complex, heterogeneous condition characterized by diverse clinical phenotypes and underlying pathobiological mechanisms. Traditional "one-size-fits-all" management strategies have limited effectiveness in addressing this heterogeneity. The Treatable Traits (TTs) approach represents a precision medicine paradigm that targets specific, identifiable, and modifiable traits in individual patients, regardless of diagnostic labels. This paper explores the alignment between the TTs framework and emerging pharmacological therapies, with a particular focus on anti-inflammatory agents and bronchodilators currently under investigation. Each drug category is mapped to relevant TTs, such as eosinophilic or neutrophilic inflammation, corticosteroid resistance, chronic bronchitis, and frequent exacerbations. This review highlights the importance of biomarker-driven phenotyping and real-world data in designing TT-based clinical trials. It emphasizes challenges such as trait instability over time, comorbidity clustering, and trial design heterogeneity. Moreover, we advocate for incorporating digital health tools, long-term follow-up, and cost-effectiveness analyses to ensure translational relevance. In conclusion, integrating emerging therapies with the TTs approach holds substantial promise for personalizing COPD management, improving outcomes, and facilitating targeted drug development.

摘要

慢性阻塞性肺疾病(COPD)是一种复杂的异质性疾病,具有多种临床表型和潜在的病理生物学机制。传统的“一刀切”管理策略在应对这种异质性方面效果有限。可治疗特征(TTs)方法代表了一种精准医学模式,该模式针对个体患者的特定、可识别和可改变的特征,而不考虑诊断标签。本文探讨了TTs框架与新兴药物治疗之间的一致性,特别关注目前正在研究的抗炎药物和支气管扩张剂。每个药物类别都与相关的TTs进行了映射,如嗜酸性粒细胞或中性粒细胞炎症、皮质类固醇抵抗、慢性支气管炎和频繁急性加重。本综述强调了生物标志物驱动的表型分析和真实世界数据在设计基于TTs的临床试验中的重要性。它强调了诸如特征随时间的不稳定性、共病聚集和试验设计异质性等挑战。此外,我们主张纳入数字健康工具、长期随访和成本效益分析,以确保转化相关性。总之,将新兴疗法与TTs方法相结合,对于个性化COPD管理、改善预后和促进靶向药物开发具有巨大的前景。

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