识别和治疗皮质类固醇难治性联合气道疾病中的中性粒细胞性炎症：一种可治疗特征方法。

文献信息

中文摘要

背景： 中性粒细胞性炎症在难以控制的哮喘、伴鼻息肉的慢性鼻窦炎（CRSwNP）和过敏性鼻炎中日益被认识到，但其临床解读仍然具有挑战性。中性粒细胞增多可与2型（T2）炎症共存，也可由感染、吸烟、环境暴露、肥胖、治疗效应或短暂性加重生物学引起；因此，不应自动将其等同于稳定的非T2内型或皮质类固醇抵抗。本综述聚焦于临床医生如何在整个联合气道中识别并处理具有临床意义的中性粒细胞性可治疗特征。直接气道评估，特别是哮喘中的诱导痰以及上气道疾病中的鼻细胞学或组织评估，提供了局部炎症表型的最接近测量，而外周血和可溶性生物标志物仍为支持性而非可互换的替代指标。在赋予中性粒细胞增多治疗意义之前，可重复性、临床背景和排除继发性原因至关重要。目前尚无针对哮喘、CRSwNP或过敏性鼻炎的中性粒细胞特异性生物制剂获批。大环内酯类药物在选定患者中提供了最明确的临床可用桥梁，但治疗反应并非由经验证的中性粒细胞截断值定义。靶向CXCR1/2或IL-17通路的试验表明，减少中性粒细胞性炎症并不一定转化为有意义的临床获益，而NET和cGAS-STING导向的策略仍处于研究阶段。一种实用的可治疗特征方法应整合经验证的共存T2特征、在可行时进行直接气道表型分析、基于证据或试验的治疗选择，以及对炎症表型和临床结局的纵向重新评估。

英文摘要

Neutrophilic inflammation is increasingly recognized in difficult-to-control asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and allergic rhinitis, but its clinical interpretation remains challenging. Neutrophilia may coexist with type 2 (T2) inflammation and can also arise from infection, smoking, environmental exposure, obesity, treatment effects, or transient exacerbation biology; therefore, it should not be equated automatically with a stable non-T2 endotype or corticosteroid resistance. This review focuses on how clinicians can identify and act on a clinically meaningful neutrophilic treatable trait across the united airway. Direct airway assessment, particularly induced sputum in asthma and nasal cytology or tissue assessment in upper-airway disease, provides the closest measure of local inflammatory phenotype, whereas peripheral blood and soluble biomarkers remain supportive rather than interchangeable surrogates. Reproducibility, clinical context, and exclusion of secondary causes are essential before assigning therapeutic significance to neutrophilia. No neutrophil-specific biologic is currently approved for asthma, CRSwNP, or allergic rhinitis. Macrolides provide the clearest clinically available bridge in selected patients, but treatment response is not defined by a validated neutrophil cutoff. Trials targeting CXCR1/2 or IL-17 pathways demonstrate that reducing neutrophilic inflammation does not necessarily translate into meaningful clinical benefit, whereas NET- and cGAS-STING-directed strategies remain investigational. A practical treatable-trait approach should integrate validated coexisting T2 traits, direct airway phenotyping where feasible, evidence-based or trial-based treatment selection, and longitudinal reassessment of both inflammatory phenotype and clinical outcomes.