Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tenn.
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
J Allergy Clin Immunol. 2021 Apr;147(4):1318-1328.e5. doi: 10.1016/j.jaci.2020.11.001. Epub 2020 Nov 12.
Aspirin-exacerbated respiratory disease (AERD) is a mechanistically distinct subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Although frequently associated with type 2 inflammation, literature characterizing the milieu of inflammatory cytokines and lipid mediators in AERD has been conflicting.
We sought to identify differences in the upper airway inflammatory signature between CRSwNP and AERD and determine whether endotypic subtypes of AERD may exist.
Levels of 7 cytokines representative of type 1, type 2, and type 3 inflammation, and 21 lipid mediators were measured in nasal mucus from 109 patients with CRSwNP, 30 patients with AERD, and 64 non-CRS controls. Differences in inflammatory mediators were identified between groups, and patterns of inflammation among patients with AERD were determined by hierarchical cluster analysis.
AERD could be distinguished from CRSwNP by profound elevations in IL-5, IL-6, IL-13, and IFN-γ; however, significant heterogeneity existed between patients. Hierarchical cluster analysis identified 3 inflammatory subendotypes of AERD characterized by (1) low inflammatory burden, (2) high type 2 cytokines, and (3) comparatively low type 2 cytokines and high levels of type 1 and type 3 cytokines. Several lipid mediators were associated with asthma and sinonasal disease severity; however, lipid mediators showed less variability than cytokines.
AERD is associated with elevations in type 2 cytokines (IL-5 and IL-13) and the type 1 cytokine, IFN-γ. Among patients with AERD, the inflammatory signature is heterogeneous, supporting subendotypes of the disease. Variability in AERD immune signatures should be further clarified because this may predict clinical response to biologic medications that target type 2 inflammation.
阿司匹林加重性呼吸系统疾病（AERD）是一种与慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）在机制上明显不同的亚型。尽管常与 2 型炎症相关，但描述 AERD 中炎症细胞因子和脂质介质环境的文献一直存在争议。
我们旨在确定 CRSwNP 和 AERD 之间上呼吸道炎症特征的差异，并确定 AERD 是否存在表型亚型。
测量了 109 例 CRSwNP 患者、30 例 AERD 患者和 64 例非 CRS 对照者鼻黏液中 7 种代表 1 型、2 型和 3 型炎症的细胞因子和 21 种脂质介质的水平。比较各组之间炎症介质的差异，并通过层次聚类分析确定 AERD 患者的炎症模式。
通过显著升高的 IL-5、IL-6、IL-13 和 IFN-γ，AERD 可与 CRSwNP 区分开；然而，患者之间存在显著的异质性。层次聚类分析确定了 AERD 的 3 种炎症亚表型，特征为（1）低炎症负担，（2）高 2 型细胞因子，和（3）相对较低的 2 型细胞因子和较高水平的 1 型和 3 型细胞因子。一些脂质介质与哮喘和鼻-鼻窦疾病严重程度相关；然而，脂质介质的变异性小于细胞因子。
AERD 与 2 型细胞因子（IL-5 和 IL-13）和 1 型细胞因子 IFN-γ升高有关。在 AERD 患者中，炎症特征存在异质性，支持该疾病的亚表型。AERD 免疫特征的变异性应进一步阐明，因为这可能预测针对 2 型炎症的生物药物的临床反应。
