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Plasma 1,3-β-d-glucan levels predict adverse clinical outcomes in critical illness
Georgios D Kitsios1,2,3, Daniel Kotok4, Haopu Yang1,5,6
1Division 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.
Abstract:
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).
Insights
Elevated 1,3-β-d-glucan (BDG) in critically ill patients without fungal infections indicates a higher risk of severe inflammation and poorer outcomes. This fungal marker may translocate from the lungs or gut, impacting host immunity.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Immunology
Background:
- 1,3-β-d-glucan (BDG) is a fungal cell wall component and pathogen-associated molecular pattern.
- BDG can stimulate the innate immune system.
- The role of BDG translocation in critically ill patients is not fully understood.
Purpose of the Study:
- To investigate if BDG translocates into systemic circulation in mechanically ventilated patients with acute respiratory failure (ARF).
- To determine the association between plasma BDG levels and host inflammation and clinical outcomes.
- To explore potential sources of BDG translocation.
Main Methods:
- Enrolled 453 mechanically ventilated patients with ARF without invasive fungal infection.
- Measured plasma BDG, innate immunity biomarkers, and epithelial permeability.
- Analyzed associations between BDG levels, inflammatory subphenotypes, ventilator-free days, and 30-day survival.
Main Results:
- Patients with ARF had significantly higher plasma BDG levels compared to healthy controls.
- High BDG levels (≥40 pg/mL) were associated with an increased likelihood of the hyperinflammatory subphenotype.
- Baseline BDG levels predicted fewer ventilator-free days and worse 30-day survival.
Conclusions:
- Plasma BDG measurement provides prognostic information in critically ill patients, even without diagnosed fungal infections.
- BDG translocation from the lung or gut may contribute to host inflammation.
- Further research into BDG translocation mechanisms and immune recognition could reveal new therapeutic targets.
