重症肺炎的肺部炎症具有分区和机理上不同的亚型特征

M Jeffrey, J Bartholdson Scott, RJ White, E Higginson, M Maes, S Forrest, J Pereira-Dias, S Parmar, E Heasman-Hunt, MD Curran, P Polgarova, J Herre, EE Davenport, S Baker, G Dougan, V Navapurkar, A Conway Morris
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引用次数: 0

摘要

肺炎是全球头号传染病杀手,通常需要接受重症监护。尽管肺炎很普遍,但人们对重症肺炎的生物学基础仍不完全了解。我们对支气管肺泡转录组、细胞因子、微生物学和临床特征进行了多方面的评估,对一组疑似重症肺炎患者进行了生物学剖析。我们的数据揭示了三种肺限制性转录定义的重症肺炎内型(称为 "肺炎型"(Pn))。所有这三种肺炎型的临床表现和呼吸衰竭的严重程度相当,但关键是结果不同。最常见的 Pn1 型的特点是肺泡细胞因子含量低、耐受性巨噬细胞增大和上皮损伤。Pn3 的特征是中性粒细胞-单核细胞浸润、IL-6-STAT3 激活和较长的机械通气时间。Pn2 的缓解速度最快,表现出平衡的免疫反应和上皮-内皮修复特征。我们的研究发现了疑似肺炎和急性肺损伤患者肺部不同的机理表型,为个性化治疗提供了新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes
Pneumonia is the leading infectious disease killer worldwide and commonly requires admission to critical care. Despite its prevalence, the underpinning biology of severe pneumonia remains incompletely understood. We performed multifaceted assessments of bronchoalveolar transcriptome, cytokines, microbiology, and clinical features to biologically dissect a cohort of patients with suspected severe pneumonia. Our data revealed three lung-restricted transcriptionally defined severe pneumonia endotypes (termed ‘Pneumotypes’ (Pn)). All three Pneumotypes had comparable clinical presentations and severity of respiratory failure but critically had divergent outcomes. Pn1, the most common, was characterised by low alveolar cytokines, expanded tolerogenic macrophages and epithelial damage. Pn3 was characterised by neutrophil-monocyte infiltration, IL-6-STAT3 activation and longer duration of mechanical ventilation. Pn2 displayed the fastest resolution, exhibiting a balanced immune response and epithelial-endothelial repair signatures. Our work has identified mechanistically distinct phenotypes in the lungs of patients with suspected pneumonia and acute lung injury, providing new targets for personalised therapy.
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