阿司匹林诱发的呼吸系统疾病的脱敏治疗：分子机制的新见解。
Aspirin desensitization in aspirin-exacerbated respiratory disease: New insights into the molecular mechanisms.
机构信息
Department of Pulmonology and Allergy, Hospital Clinic Barcelona- Institute for Health Research (IdiBAPS), Spain.
Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain; Spanish Network of Centers for Biomedical Research on Respiratory Diseases (CIBERES), Spain.
出版信息
Respir Med. 2018 Oct;143:39-41. doi: 10.1016/j.rmed.2018.08.009. Epub 2018 Aug 23.
BACKGROUND
Aspirin desensitization (AD) has been the only available modifying treatment in aspirin-exacerbated respiratory disease (AERD). The mechanisms of AD are nonetheless poorly understood. Though very effective, AD is limited by its risks and side-effects.
OBJECTIVE
Moving forward to the targeted biologicals era, the aim of this study was to characterize the airway inflammatory response to long-term AD, including TSLP dynamics, in order to assess potential new targets in AERD.
PATIENTS AND METHODS
Adult patients with aspirin challenge-confirmed AERD underwent an oral AD followed by daily ingestion of aspirin for at least 6 months. Clinical data and inflammatory biomarkers were measured and compared, before and after AD. Induced sputum analyses were performed at baseline, one and six months after AD (differential cell count and levels of sputum supernatant leukotriene C4, prostaglandin D2 and E2, and TSLP).
RESULTS
AD was followed by significant clinical improvement, as quantified by all monitored parameters. The good clinical outcomes of AD in our study are supported by overall changes observed in the arachidonic acid metabolites (decreased PGD2 over a constant LTC4/PGE2). TSLP increased (mean baseline 0.1 ± 0.03; 1 month 3.68 ± 7; 6 months 212.2 ± 44 pg/ml; p < 0.01).
CONCLUSIONS
Our findings suggest that new biologicals blocking TSLP might have a clinical benefit in AERD, by cutting down the TSLP-induced PGD2 generation.
背景
阿司匹林脱敏（AD）是治疗阿司匹林加重性呼吸系统疾病（AERD）的唯一可行的修饰治疗方法。然而，AD 的机制仍未被充分理解。尽管 AD 非常有效，但由于其风险和副作用，其应用受到限制。
目的
在靶向生物制剂时代，本研究旨在描述 AD 后气道炎症反应的特征，包括 TSLP 动力学，以评估 AERD 中的潜在新靶点。
患者和方法
经口服阿司匹林激发试验证实的成年 AERD 患者接受 AD 治疗，随后至少每日口服阿司匹林 6 个月。在 AD 前后测量和比较临床数据和炎症生物标志物。在 AD 前、AD 后 1 个月和 6 个月进行诱导痰分析（差异细胞计数和痰上清液白三烯 C4、前列腺素 D2 和 E2 以及 TSLP 水平）。
结果
AD 后所有监测参数均显著改善，表明临床症状明显改善。AD 在我们的研究中取得良好的临床效果，这得到了观察到的花生四烯酸代谢物整体变化的支持（PGD2 降低，LTC4/PGE2 不变）。TSLP 增加（基线时平均为 0.1±0.03；1 个月时为 3.68±7；6 个月时为 212.2±44 pg/ml；p<0.01）。
结论
我们的发现表明，阻断 TSLP 的新型生物制剂可能通过减少 TSLP 诱导的 PGD2 生成，在 AERD 中具有临床获益。
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