全面剖析难治性哮喘揭示 T2 低表型近乎缺失。
Comprehensive Characterization of Difficult-to-Treat Asthma Reveals Near Absence of T2-Low Status.
机构信息
School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research, Southampton Biomedical Research Centre at University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom; Respiratory Medicine Department, University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom.
School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Biomedical Science, Faculty of Sport, Health, and Social Sciences, Solent University Southampton, Southampton, United Kingdom.
出版信息
J Allergy Clin Immunol Pract. 2023 Sep;11(9):2812-2821.e4. doi: 10.1016/j.jaip.2023.05.028. Epub 2023 May 26.
BACKGROUND
Asthma is conventionally stratified as type 2 inflammation (T2)-high or T2-low disease. Identifying T2 status has therapeutic implications for patient management, but a real-world understanding of this T2 paradigm in difficult-to-treat and severe asthma remains limited.
OBJECTIVES
To identify the prevalence of T2-high status in difficult-to-treat asthma patients using a multicomponent definition and compare clinical and pathophysiologic characteristics between patients classified as T2-high and T2-low.
METHODS
We evaluated 388 biologic-naive patients from the Wessex Asthma Cohort of difficult asthma (WATCH) study in the United Kingdom. Type 2-high asthma was defined as 20 parts per billion or greater FeNO , 150 cells/μL or greater peripheral blood eosinophils, the need for maintenance oral corticosteroids, and/or clinically allergy-driven asthma.
RESULTS
This multicomponent assessment identified T2-high asthma in 93% of patients (360 of 388). Body mass index, inhaled corticosteroid dose, asthma exacerbations, and common comorbidities did not differ by T2 status. Significantly worse airflow limitation was found in T2-high compared with T2-low patients (FEV/FVC 65.9% vs 74.6%). Moreover, 75% of patients defined as having T2-low asthma had raised peripheral blood eosinophils within the preceding 10 years, which left only seven patients (1.8%) who had never had T2 signals. Incorporation of sputum eosinophilia 2% or greater into the multicomponent definition in a subset of 117 patients with induced sputum data similarly found that 96% (112 of 117) met criteria for T2-high asthma, 50% of whom (56 of 112) had sputum eosinophils 2% or greater.
CONCLUSIONS
Almost all patients with difficult-to-treat asthma have T2-high disease; less than 2% of patients never display T2-defining criteria. This highlights a need to assess T2 status comprehensively in clinical practice before labeling a patient with difficult-to-treat asthma as T2-low.
背景
哮喘传统上分为 2 型炎症（T2）高或 T2 低疾病。确定 T2 状态对患者管理具有治疗意义，但对于难以治疗和严重的哮喘，对这种 T2 范式的实际理解仍然有限。
目的
使用多组分定义确定难以治疗的哮喘患者中 T2 高状态的患病率，并比较分类为 T2 高和 T2 低的患者的临床和病理生理特征。
方法
我们评估了英国威塞克斯哮喘队列中 388 名生物初治的难治性哮喘患者（WATCH 研究）。T2 高哮喘定义为 FeNO≥20 皮克/毫升、外周血嗜酸性粒细胞≥150 个/μL、需要维持口服皮质类固醇和/或由过敏引起的哮喘。
结果
这种多组分评估方法在 388 名患者中的 93%（360 名）中确定了 T2 高哮喘。T2 状态与体重指数、吸入皮质类固醇剂量、哮喘加重和常见合并症无关。与 T2 低患者相比，T2 高患者的气流受限明显更差（FEV/FVC 65.9%比 74.6%）。此外，75%的 T2 低哮喘患者在过去 10 年内有过外周血嗜酸性粒细胞升高，这使得只有 7 名患者（1.8%）从未出现过 T2 信号。在有诱导痰数据的 117 名患者亚组中，将痰嗜酸性粒细胞 2%或更高纳入多组分定义中，同样发现 96%（117 名中的 112 名）符合 T2 高哮喘的标准，其中 50%（112 名中的 56 名）的痰嗜酸性粒细胞为 2%或更高。
结论
几乎所有难治性哮喘患者都有 T2 高疾病；只有不到 2%的患者从未出现过 T2 定义标准。这凸显了在将难以治疗的哮喘患者标记为 T2 低之前，临床上需要全面评估 T2 状态的必要性。
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