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Plasma 1,3-ß-d-glucan levels predict adverse clinical outcomes in critical illness.
Kitsios, Georgios D; Kotok, Daniel; Yang, Haopu; Finkelman, Malcolm A; Zhang, Yonglong; Britton, Noel; Li, Xiaoyun; Levochkina, Marina S; Wagner, Amy K; Schaefer, Caitlin; Villandre, John J; Guo, Rui; Evankovich, John W; Bain, William; Shah, Faraaz; Zhang, Yingze; Methé, Barbara A; Benos, Panayiotis V; McVerry, Bryan J; Morris, Alison.
  • Kitsios GD; 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.
  • Kotok D; Center for Medicine and the Microbiome and.
  • Yang H; Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Finkelman MA; Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Florida, Weston Hospital, Weston, Florida, USA.
  • Zhang Y; 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.
  • Britton N; School of Medicine, Tsinghua University, Beijing, China.
  • Li X; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Levochkina MS; Associates of Cape Cod Inc., East Falmouth, Massachusetts, USA.
  • Wagner AK; Associates of Cape Cod Inc., East Falmouth, Massachusetts, USA.
  • Schaefer C; 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.
  • Villandre JJ; Center for Medicine and the Microbiome and.
  • Guo R; 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.
  • Evankovich JW; Department of Infectious Diseases and Microbiology and.
  • Bain W; Departments of Physical Medicine and Rehabilitation, Neuroscience, and Clinical and Translational Science, Center for Neuroscience, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Shah F; Departments of Physical Medicine and Rehabilitation, Neuroscience, and Clinical and Translational Science, Center for Neuroscience, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Zhang Y; 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.
  • Methé BA; 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.
  • Benos PV; 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.
  • McVerry BJ; Department of Emergency and Critical Care Medicine, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • Morris A; 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.
JCI Insight ; 6(14)2021 07 22.
Article in English | MEDLINE | ID: covidwho-1341362
ABSTRACT
BACKGROUNDThe fungal cell wall constituent 1,3-ß-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).
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiration, Artificial / Candida / Beta-Glucans / COVID-19 / Immunity, Innate Type of study: Prognostic study Limits: Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: Jci.insight.141277

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiration, Artificial / Candida / Beta-Glucans / COVID-19 / Immunity, Innate Type of study: Prognostic study Limits: Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: Jci.insight.141277