Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Center for Medicine and the Microbiome and.
JCI Insight. 2021 Jul 22;6(14):e141277. doi: 10.1172/jci.insight.141277.
BACKGROUNDThe fungal cell wall constituent 1,3-β-d-glucan (BDG) is a pathogen-associated molecular pattern that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically ill patients may translocate into the systemic circulation and be associated with host inflammation and outcomes.METHODSWe enrolled 453 mechanically ventilated patients with acute respiratory failure (ARF) without invasive fungal infection and measured BDG, innate immunity, and epithelial permeability biomarkers in serially collected plasma samples.RESULTSCompared with healthy controls, patients with ARF had significantly higher BDG levels (median [IQR], 26 pg/mL [15-49 pg/mL], P < 0.001), whereas patients with ARF with high BDG levels (≥40 pg/mL, 31%) had higher odds for assignment to the prognostically adverse hyperinflammatory subphenotype (OR [CI], 2.88 [1.83-4.54], P < 0.001). Baseline BDG levels were predictive of fewer ventilator-free days and worse 30-day survival (adjusted P < 0.05). Integrative analyses of fungal colonization and epithelial barrier disruption suggested that BDG may translocate from either the lung or gut compartment. We validated the associations between plasma BDG and host inflammatory responses in 97 hospitalized patients with COVID-19.CONCLUSIONBDG measurements offered prognostic information in critically ill patients without fungal infections. Further research in the mechanisms of translocation and innate immunity recognition and stimulation may offer new therapeutic opportunities in critical illness.FUNDINGUniversity of Pittsburgh Clinical and Translational Science Institute, COVID-19 Pilot Award and NIH grants (K23 HL139987, U01 HL098962, P01 HL114453, R01 HL097376, K24 HL123342, U01 HL137159, R01 LM012087, K08HK144820, F32 HL142172, K23 GM122069).
真菌细胞壁成分 1,3-β-d-葡聚糖（BDG）是一种与病原体相关的分子模式，可以刺激先天免疫。我们假设，重症患者定植真菌的 BDG 可能会转移到全身循环，并与宿主炎症和结局相关。
我们招募了 453 例机械通气的急性呼吸衰竭（ARF）患者，这些患者没有侵袭性真菌感染，并在连续采集的血浆样本中测量了 BDG、先天免疫和上皮通透性生物标志物。
与健康对照组相比，ARF 患者的 BDG 水平明显更高（中位数[IQR]，26 pg/mL[15-49 pg/mL]，P < 0.001），而 BDG 水平较高（≥40 pg/mL，31%）的 ARF 患者更有可能被分配到预后不良的高炎症亚表型（OR[CI]，2.88[1.83-4.54]，P < 0.001）。基线 BDG 水平可预测更少的无呼吸机天数和更差的 30 天生存率（调整后 P < 0.05）。真菌定植和上皮屏障破坏的综合分析表明，BDG 可能从肺部或肠道腔室转移。我们在 97 例住院 COVID-19 患者中验证了血浆 BDG 与宿主炎症反应之间的关联。
BDG 测量在无真菌感染的重症患者中提供了预后信息。对转移和先天免疫识别和刺激机制的进一步研究可能为危重病提供新的治疗机会。
匹兹堡大学临床与转化科学研究所，COVID-19 试点奖和 NIH 资助（K23 HL139987、U01 HL098962、P01 HL114453、R01 HL097376、K24 HL123342、U01 HL137159、R01 LM012087、K08HK144820、F32 HL142172、K23 GM122069）。
Zotero 插件
