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贝那鲁肽可降低重度嗜酸性粒细胞性哮喘和伴有鼻息肉的慢性鼻-鼻窦炎患者的嗜酸性粒细胞和炎症标志物:一项真实世界的初步研究。

Benralizumab reduces eosinophils and inflammatory markers in patients with severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: A pilot real-life study.

机构信息

Department of Sense Organs, Sapienza University of Rome, Rome, Italy.

Department of Biosciences and Territory, University of Molise, Pesche, IS, Italy.

出版信息

Immunol Lett. 2022 Aug;248:70-77. doi: 10.1016/j.imlet.2022.06.009. Epub 2022 Jun 23.

DOI:10.1016/j.imlet.2022.06.009
PMID:35752279
Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) and Severe Eosinophilic Asthma (SEA) are both frequently sustained by eosinophilic inflammation and are probably the manifestation of a unique disease of upper and lower respiratory tract. We retrospectively observed 11 patients with severe CRSwNP and concomitant SEA under add-on therapy with benralizumab evaluating symptoms using Sino Nasal Outcome Test-22 (SNOT-22), Visual Analogue Scale (VAS), and Asthma Control Test (ACT) and Nasal polyp size by endoscopic and radiological score by Nasal Polyp Score (NPS) and Lund-Mackay Score (LMS). At 6 and 12 months, the expression of cationic eosinophil protein (ECP), Interleukin 17 (IL-17), Interferon gamma (INF-γ), and vascular endothelial growth factor (VEGF) was measured by nasal scraping to assess mucosal inflammation. After 12 months of benralizumab treatment, SNOT-22 decreased from 45 (23-97) to 14 (5-53) (p < 0.05), total VAS of rhinologic symptoms decreased from 30 (17-44) to 9 (5-37) (p ≤ 0.01) and ACT score increased from 10 (5-15) to 24 (20-25) (p ≤ 0.01). NPS decreased from 5 (3-6) to 3 (2-4) after 6 months (p < 0.05) and to 2 (2-3) after one year respectively (p <  0.05) and LMS total score from 21 (15-24) to 17 (8-21) (p ≤ 0.01) after 12 months from starting treatment. Nasal mucosa scraping found differences in INF-γ and VEGF expression in patients compared to 10 healthy subjects, with a normalization of these markers during eosinophils depletion induced by benralizumab. This is the first pilot real-life study conducted with an anti-IL5R monoclonal antibody in severe eosinophilic asthma and severe CRSwNP patients showing that this treatment can induce benefit both diseases not only from the clinical, but also from the inflammatory point of view. Moreover, our research pointed out that INF-γ and VEGF may represent potential response biomarker.

摘要

慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)和重度嗜酸性粒细胞性哮喘(SEA)均由嗜酸性粒细胞炎症持续存在,可能是上下呼吸道的一种独特疾病的表现。我们回顾性观察了 11 例重度 CRSwNP 伴 SEA 患者,他们在接受 benralizumab 附加治疗时,使用 Sino Nasal Outcome Test-22(SNOT-22)、视觉模拟量表(VAS)和哮喘控制测试(ACT)评估症状,并通过内镜和放射学评分评估鼻息肉大小,使用鼻息肉评分(NPS)和 Lund-Mackay 评分(LMS)。在 6 和 12 个月时,通过鼻刮取物测量阳离子嗜酸性粒细胞蛋白(ECP)、白细胞介素 17(IL-17)、干扰素 γ(INF-γ)和血管内皮生长因子(VEGF)的表达,以评估黏膜炎症。在接受 benralizumab 治疗 12 个月后,SNOT-22 从 45(23-97)降至 14(5-53)(p<0.05),鼻症状总 VAS 从 30(17-44)降至 9(5-37)(p≤0.01),ACT 评分从 10(5-15)升至 24(20-25)(p≤0.01)。NPS 在 6 个月时从 5(3-6)降至 3(2-4)(p<0.05),1 年后分别降至 2(2-3)(p<0.05),LMS 总分从 21(15-24)降至 17(8-21)(p≤0.01)。与 10 名健康受试者相比,在接受 benralizumab 治疗后,患者的 INF-γ 和 VEGF 表达存在差异,在嗜酸性粒细胞耗竭后这些标志物趋于正常。这是首例在重度嗜酸性粒细胞性哮喘和重度 CRSwNP 患者中用抗 IL-5R 单克隆抗体进行的真实生活研究,表明这种治疗不仅能从临床角度,还能从炎症角度为这两种疾病带来获益。此外,我们的研究指出,INF-γ 和 VEGF 可能是潜在的反应生物标志物。

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