Background

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.

Objective

We sought to identify differences in the upper airway inflammatory signature between CRSwNP and AERD and determine whether endotypic subtypes of AERD may exist.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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阿司匹林加重呼吸系统疾病的炎症异质性

背景

阿司匹林加重呼吸系统疾病 (AERD) 是一种机制上不同的慢性鼻窦炎伴鼻息肉 (CRSwNP) 亚型。尽管经常与 2 型炎症相关，但描述 AERD 中炎性细胞因子和脂质介质环境的文献一直存在矛盾。

客观的

我们试图确定 CRSwNP 和 AERD 之间上气道炎症特征的差异，并确定是否可能存在 AERD 的内型亚型。

方法

在来自 109 名 CRSwNP 患者、30 名 AERD 患者和 64 名非 CRS 对照的鼻粘液中测量了代表 1 型、2 型和 3 型炎症的 7 种细胞因子和 21 种脂质介质的水平。确定了组间炎症介质的差异，并通过层次聚类分析确定了AERD患者的炎症模式。

结果

AERD 与 CRSwNP 的区别在于 IL-5、IL-6、IL-13 和 IFN-γ 的显着升高；然而，患者之间存在显着的异质性。分层聚类分析确定了 3 种 AERD 炎症亚内型，其特征是（1）低炎症负荷，（2）高 2 型细胞因子，和（3）相对较低的 2 型细胞因子和高水平的 1 型和 3 型细胞因子。几种脂质介质与哮喘和鼻窦疾病严重程度相关；然而，脂质介质的变异性低于细胞因子。

结论

AERD 与 2 型细胞因子（IL-5 和 IL-13）和 1 型细胞因子 IFN-γ 的升高有关。在AERD患者中，炎症特征是异质的，支持该疾病的亚内型。应进一步澄清AERD免疫特征的变异性，因为这可以预测针对2型炎症的生物药物的临床反应。