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Plasma (1-3)-β-d-glucan levels are associated with host inflammatory responses and predict adverse clinical outcomes in critical illness

By Georgios D Kitsios, Daniel Kotok, Haopu Yang, Malcolm Finkelman, Yonglong Zhang, Noel Britton, Rui Guo, John W Evankovich, William Bain, Faraaz Shah, Yingze Zhang, Panayiotis V. Benos, Bryan J. McVerry, Alison Morris

Posted 12 Jun 2020
medRxiv DOI: 10.1101/2020.06.11.20128264

Background: The fungal cell-wall constituent (1,3)-beta-d-glucan (BDG) is a pathogen-associated molecular pattern (PAMP) that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically-ill patients may translocate into the systemic circulation and thus be associated with host inflammatory responses and outcomes. Methods: We enrolled 453 mechanically-ventilated patients with acute respiratory failure with no evidence of invasive fungal infection (IFI). From serial plasma samples, we measured BDG, innate immunity and epithelial permeability biomarkers. From lower respiratory tract and stool samples we quantified bacterial and fungal DNA load using culture-independent techniques. Results: A positive BDG test (>60pg/ml) at baseline was detected in 19% of patients. BDG levels were significantly associated with markers of innate immunity (interleukin-6, tumor necrosis factor receptor-1 and procalcitonin), epithelial barrier disruption (receptor for advanced glycation end-products and fatty-acid binding protein-2, for lung and gut respectively) and with higher probability of classification in an adverse prognosis hyperinflammatory subphenotype (all p<0.05). No differences in fungal or bacterial DNA load were found by BDG test positivity. Positive BDG testing was associated with higher incidence of acute kidney injury, fewer ventilator free days and worse 30-day survival (adjusted p<0.05). Patients with positive BDG test on follow-up sampling (>3 days from intubation) had higher mortality than patients with persistently negative test on follow-up (p<0.05). Conclusions: This is the first study to demonstrate the prognostic role of BDG in critically ill patients with no evidence of IFI. Translocation of BDG into systemic circulation may contribute to inflammation and clinical outcomes.

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