迈向过敏性鼻炎的机制性内型分型：用于评估鼻组织证据的状态-部位-时间框架

文献信息

中文摘要

背景： 过敏性鼻炎（AR）的异质性通常通过致敏状态、症状负担或炎症特征来描述，但这些描述并不能确定特定鼻黏膜中发挥作用的机制。本批判性叙述性综述提出一个状态-部位-时间框架，将细胞程序与其解剖环境及暴露相关反应阶段一并评估。该框架区分描述性组织状态、候选机制模块、可测量的机制性内型以及临床可操作的内型。这些是本综述的操作性定义，而非经过验证的分类。文中考察了五个相互重叠的示例：IgE-FcϵRI效应活性、迟发相2型放大、屏障修复功能障碍、可分离的感觉、血管和分泌输出，以及推测的基质维持。作者构建的概念矩阵总结了人类证据、空间定位、时间/复发、匹配扰动、可及测量和临床效用；它不提供证据评分或患者分配规则。人类干预支持IgE通路依赖性，但这并不能确立用于治疗选择的经过验证的鼻组织内型。迟发相细胞因子反应和上皮异常得到人类观察和功能系统的支持，但其稳定性和预测效用仍未完全确立。基质维持仍是一个假设，受到鼻息肉取样和推断性通讯的重要限制。该框架通过识别缺失环节和可检验的替代方案，补充了现有的临床和炎症分类。向临床应用的进展需要在患者内的可重复性、分析验证和外部验证，以及超越常规评估的增量价值；治疗选择主张还需要差异治疗获益的证据。

英文摘要

Allergic rhinitis (AR) heterogeneity is usually described by sensitization, symptom burden, or inflammatory profiles, but these descriptors do not establish which mechanism operates in a particular nasal mucosa. This critical narrative review proposes a State-Place-Time framework that evaluates cellular programs together with their anatomical setting and exposure-related response phase. The framework distinguishes descriptive tissue states from candidate mechanistic modules, measurable mechanistic endotypes, and clinically actionable endotypes. These are operational definitions for this review, rather than a validated classification. Five overlapping examples are examined: IgE-FcϵRI effector activity, late-phase type 2 amplification, barrier-repair dysfunction, separable sensory, vascular, and secretory outputs, and putative stromal maintenance. An author-derived conceptual matrix summarizes human evidence, spatial localization, timing/recurrence, matched perturbation, accessible measurement, and clinical utility; it does not provide an evidence score or patient assignment rule. Human intervention supports IgE-pathway dependence, but this does not establish a validated nasal tissue endotype for treatment selection. Late-phase cytokine responses and epithelial abnormalities are supported by human observations and functional systems, while their stability and predictive utility remain incompletely established. Stromal maintenance remains a hypothesis, with important limits from nasal polyposis sampling and inferred communication. The framework complements existing clinical and inflammatory classifications by identifying missing links and testable alternatives. Progress toward clinical use requires reproducibility within patients, analytical and external validation, and incremental value beyond routine assessment; treatment-selection claims additionally require evidence of differential treatment benefit.