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度普利尤单抗治疗对非甾体抗炎药加重的呼吸道疾病患者的鼻腔微生物群无影响:一项纵向试点研究。

Dupilumab treatment has no effect on the nasal microbiome in patients with NSAID-exacerbated respiratory disease: a longitudinal pilot study.

作者信息

Bartosik Tina, Pjevac Petra, Séneca Joana, Morgenstern Christina, Arnoldner Tamara, Gangl Katharina, Sinz Christoph, Campion Nicholas James, Tu Aldine, Stanek Victoria, Bangert Christine, Schneider Sven, Eckl-Dorna Julia

机构信息

Department of Otorhinolaryngology, General Hospital and Medical University of Vienna, Vienna, Austria.

Department of Microbiology and Ecosystem Science, Centre for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria.

出版信息

Front Immunol. 2025 May 28;16:1508500. doi: 10.3389/fimmu.2025.1508500. eCollection 2025.

Abstract

BACKGROUND

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) affects up to 10% of patients suffering from nasal polyps and has a severe impact on quality of life. Dupilumab, a monoclonal antibody targeting the IL-4 receptor α chain, leads to symptom relief and reduction in nasal type 2 mediator levels. Here, we investigated the impact of dupilumab treatment on the composition and diversity of the nasal microbiome.

METHODOLOGY

Nasal microbiome was analyzed by 16s rRNA gene amplicon sequencing in 28 patients before, 4, 12, and 24 weeks after dupilumab therapy.

RESULTS

After stringent decontamination and removal of patients whose samples contained less than 500 reads at ≥ one of the four visits, full datasets from 8 out of 28 patients remained for downstream analysis of microbiome data. All 8 patients showed significant reduction in TPS (total polyp score; p=0.0078) and an improvement in SNOT-22 (Sino-nasal outcome test-22, a quality of life questionnaire; p=0.0781) after dupilumab therapy. During 24 weeks of dupilumab therapy, there were no major changes in microbiome diversity or composition observed (Shannon index: V1-V4:p-adj=0.25, Chao 1 Index V1-V4:p-adj=0.31), and only 2 out of 8 patients showed a decrease in staphylococci abundance.

CONCLUSIONS

More than 70% of the samples did not pass quality control, this warrants further refinement of nasal microbiome sampling techniques and mandatory guidelines on stringent quality control for analysis of this low biomass data in future. Furthermore, dupilumab did not have an impact on microbiome diversity or composition.

摘要

背景

非甾体抗炎药诱发的呼吸道疾病(N-ERD)影响高达10%的鼻息肉患者,对生活质量有严重影响。度普利尤单抗是一种靶向白细胞介素-4受体α链的单克隆抗体,可缓解症状并降低鼻腔2型介质水平。在此,我们研究了度普利尤单抗治疗对鼻腔微生物组组成和多样性的影响。

方法

通过16s rRNA基因扩增子测序分析了28例患者在度普利尤单抗治疗前、治疗后4周、12周和24周的鼻腔微生物组。

结果

在进行严格的净化处理并剔除在四次就诊中至少有一次样本读数少于500的患者后,28例患者中的8例的完整数据集留存下来用于微生物组数据的下游分析。所有8例患者在度普利尤单抗治疗后TPS(总息肉评分;p=0.0078)显著降低,SNOT-22(鼻窦结局测试-22,一种生活质量问卷;p=0.0781)有所改善。在度普利尤单抗治疗的24周内,未观察到微生物组多样性或组成有重大变化(香农指数:V1-V4:p校正=0.25,Chao 1指数V1-V4:p校正=0.31),8例患者中只有2例葡萄球菌丰度降低。

结论

超过70%的样本未通过质量控制,这需要进一步完善鼻腔微生物组采样技术,并制定严格的质量控制强制性指南,以便未来分析这种低生物量数据。此外,度普利尤单抗对微生物组多样性或组成没有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d856/12151831/ba4ca2243214/fimmu-16-1508500-g001.jpg

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