超越症状控制：以缓解作为重症哮喘深度分层治疗目标

文献信息

中文摘要

背景： 重症哮喘的管理已从症状控制转向追求缓解，这一目标借鉴自风湿病学。靶向免疫球蛋白E、白细胞介素-5及其受体、白细胞介素-4受体α亚基以及胸腺基质淋巴细胞生成素的生物制剂，已使许多患者实现持续静息状态成为现实，但根据所用定义的不同，约三分之一患者达到缓解的估计值会相差数十个百分点。本叙述性综述提出两个相互关联的论点。第一，定义的异质性，而非有效药物的缺乏，是将缓解作为治疗目标的核心障碍。第二，缓解最好被理解为一个多维构念，其中临床、功能和生物学静息是彼此独立的轴，可独立达到且常不一致，完全缓解表示这些轴的汇聚，而非某一序列的最后一步。每种生物制剂在2型炎症级联中的作用位置决定了治疗下哪些生物标志物发生变化，并且仅在假设层面决定缓解可达到的深度。结构重塑以及当前药物抑制而非重置炎症的事实限制了该深度，因此缓解仍是一种在治疗下由药物维持的状态。伴鼻息肉的慢性鼻窦炎被视为哮喘缓解的修饰因素，而非独立终点。该框架为概念性且未经验证。优先事项是建立一个协调一致、深度分层的定义，明确治疗负担和以患者为中心的结局，据此评判任何治疗。

英文摘要

The management of severe asthma has shifted from symptom control to the ambition of remission, a goal borrowed from rheumatology. Biologics targeting immunoglobulin E, interleukin-5 and its receptor, the interleukin-4 receptor alpha subunit, and thymic stromal lymphopoietin have made sustained quiescence realistic for many patients, yet estimates that roughly one-third achieve remission shift by tens of percentage points depending on the definition used. This narrative review advances two linked arguments. First, that the heterogeneity of definitions, not any shortage of effective agents, is the central obstacle to using remission as a treatment target. Second, that remission is best read as a multidimensional construct in which clinical, functional and biological quiescence are distinct axes, reached independently and often discordantly, with complete remission denoting their convergence rather than the last step of a sequence. Where each biologic acts within the type 2 cascade determines which biomarkers move under treatment and, only hypothetically, how deep remission can reach. Structural remodeling and the fact that current agents suppress rather than reset inflammation cap that depth, so remission remains a pharmacologically maintained state on treatment. Concomitant chronic rhinosinusitis with nasal polyps is treated as a modifier of asthma remission rather than a separate endpoint. The framework is conceptual and unvalidated. The priority is a harmonized, depth-resolved definition, explicit about treatment burden and patient-centered outcomes, against which any therapy can be judged.