上气道作为可治疗特质：哮喘生物制剂选择中的联合气道框架

文献信息

中文摘要

可治疗特质方法将哮喘管理重新聚焦于可测量且可改变的因素，而非诊断标签，并已成为慢性气道疾病精准医学模式的基石。在影响哮喘控制、糖皮质激素负担和治疗反应的特质中，上气道共病既普遍又常被低估。过敏性鼻炎、伴或不伴鼻息肉的慢性鼻窦炎以及嗅觉功能障碍与下气道存在解剖、免疫和临床联系，上气道共病在重度哮喘管理中日益受到考虑。然而，将其系统性地描述为可测量、离散的可治疗特质，并在生物制剂选择时与下气道生物标志物正式整合，在临床实践中仍不一致。在这篇叙述性综述中，我们提出一个概念性的联合气道框架，用于综合评估哮喘患者上气道和下气道的可治疗特质。该框架结合临床表型分析、经过验证的评估工具以及局部和全身炎症生物标志物，以表征上气道疾病并支持而非规定生物制剂选择。我们认为，2型高特质与已获批的、生物标志物指导的单克隆抗体相一致，而上游上皮警报素阻断进一步拓展了治疗格局。Tezepelumab是一种抗TSLP单克隆抗体，现已获批用于CRSwNP，且治疗资格不需要基于生物标志物的2型炎症证据。我们进一步考虑可治疗特质策略如何帮助区分未控制哮喘、难治性哮喘和重度哮喘，如何支持减少糖皮质激素用量，以及如何在肺科-变态反应科-耳鼻喉科整合照护路径中实施。需要前瞻性研究来确定这一概念性方法是否能改善联合气道中的生物制剂选择和患者相关结局。

英文摘要

The treatable traits approach reframes asthma management around measurable and modifiable factors rather than diagnostic labels, and it has become a cornerstone of the precision medicine model in chronic airway disease. Among the traits that shape asthma control, corticosteroid burden and treatment response, upper airway comorbidity is both prevalent and frequently under-recognised. Allergic rhinitis, chronic rhinosinusitis with and without nasal polyps, and olfactory dysfunction share anatomical, immunological and clinical links with the lower airway, and upper-airway comorbidities are increasingly considered in the management of severe asthma. However, their systematic characterisation as measurable, discrete treatable traits and their formal integration with lower-airway biomarkers at the point of biologic selection remain heterogeneous across clinical practice. In this narrative review, we propose a conceptual united-airway framework for the integrated assessment of upper- and lower-airway treatable traits in patients with asthma. The framework combines clinical phenotyping, validated assessment tools and local and systemic inflammatory biomarkers to characterise upper-airway disease and to support, rather than prescribe, biologic selection. We argue that type 2-high traits align with approved, biomarker-guided monoclonal antibodies, while upstream epithelial alarmin blockade has further expanded the therapeutic landscape. Tezepelumab, an anti-TSLP monoclonal antibody, is now approved for CRSwNP and does not require biomarker-based evidence of type 2 inflammation for treatment eligibility. We further consider how a treatable traits strategy helps disentangle uncontrolled from difficult-to-treat and severe asthma, how it supports corticosteroid-sparing, and how it can be operationalised within an integrated pulmonology-allergy-otolaryngology care pathway. Prospective studies are required to determine whether this conceptual approach improves biologic selection and patient-relevant outcomes across the united airway.