Laidlaw Tanya M
Department of Medicine, the Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Harvard Medical School, Jeff and Penny Vinik Center for Translational Immunology Research, Boston, Massachusetts, USA.
Curr Opin Allergy Clin Immunol. 2025 Feb 1;25(1):41-46. doi: 10.1097/ACI.0000000000001051. Epub 2024 Dec 6.
Aspirin-exacerbated respiratory disease (AERD), a syndrome characterized clinically by asthma, chronic rhinosinusitis with nasal polyposis, and respiratory reactions to aspirin and other cyclooxygenase-1 inhibitors, is an inflammatory condition of the respiratory tract that is often severe and challenging to treat. There have been several recent advances in our understanding of the underlying pathology of the disease. These have been paralleled by welcome advances in the availability of targeted treatment options for patients with AERD.
Spurred in part by results from trials of targeted biologic therapies, along with single cell genomics, there is now clear evidence that the chronic respiratory inflammation in AERD is driven by combination of local tissue factors. These include abnormalities in effector cell populations, with increased accumulation and activation of mast cells and plasma cells in the nasal polyp, along with notable epithelial barrier dysregulation. The key mediators now identified include high levels of both type 2 inflammatory cytokines (IL-4, IL-5, IL-13) and cytokines involved in broader inflammatory pathways (IL-33, TSLP, IL-6, oncostatin M), as well as the overproduction of cysteinyl leukotrienes, and the underproduction of prostaglandin E 2 .
This review covers the latest insights into the immunopathogenesis of and targeted treatment of AERD, including the roles of lipids, effector cells, and inflammatory cytokines, and discusses unanswered questions regarding its pathogenesis and potential future therapies.
阿司匹林加重性呼吸道疾病（AERD）是一种临床上以哮喘、伴有鼻息肉的慢性鼻-鼻窦炎以及对阿司匹林和其他环氧化酶-1抑制剂的呼吸道反应为特征的综合征，是一种常较为严重且治疗具有挑战性的呼吸道炎症性疾病。我们对该疾病潜在病理生理学的理解最近有了多项进展。与此同时，AERD患者靶向治疗选择的可及性也取得了令人欣喜的进展。
部分受靶向生物疗法试验结果以及单细胞基因组学的推动，现在有明确证据表明，AERD中的慢性呼吸道炎症是由多种局部组织因素共同驱动的。这些因素包括效应细胞群体异常，鼻息肉中肥大细胞和浆细胞的积累及活化增加，以及明显的上皮屏障失调。目前确定的关键介质包括高水平的2型炎症细胞因子（IL-4、IL-5、IL-13）和参与更广泛炎症途径的细胞因子（IL-33、TSLP、IL-6、抑瘤素M），以及半胱氨酰白三烯的过度产生和前列腺素E2的产生不足。
本综述涵盖了对AERD免疫发病机制和靶向治疗的最新见解，包括脂质、效应细胞和炎症细胞因子的作用，并讨论了关于其发病机制及潜在未来疗法的未解决问题。
