"Plasma 1,3-beta-D-glucan levels predict adverse clinical outcomes in critical illness"

作者全名："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; Methe, Barbara A.; Benos, Panayiotis, V; McVerry, Bryan J.; Morris, Alison"

作者地址："[Kitsios, Georgios D.; Yang, Haopu; Britton, Noel; Li, Xiaoyun; Schaefer, Caitlin; Villandre, John J.; Guo, Rui; Evankovich, John W.; Bain, William; Shah, Faraaz; Zhang, Yingze; Methe, Barbara A.; McVerry, Bryan J.; Morris, Alison] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA; [Kitsios, Georgios D.; Yang, Haopu; Britton, Noel; Li, Xiaoyun; Schaefer, Caitlin; Villandre, John J.; Guo, Rui; Evankovich, John W.; Bain, William; Shah, Faraaz; Zhang, Yingze; Methe, Barbara A.; McVerry, Bryan J.; Morris, Alison] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA; [Kitsios, Georgios D.; Britton, Noel; Methe, Barbara A.; McVerry, Bryan J.; Morris, Alison] Univ Pittsburgh, Ctr Med & Microbiome, Pittsburgh, PA USA; [Kitsios, Georgios D.; Evankovich, John W.; Bain, William; Shah, Faraaz; Zhang, Yingze; McVerry, Bryan J.; Morris, Alison] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA USA; [Kotok, Daniel] Cleveland Clin Florida, Weston Hosp, Dept Pulm & Crit Care Med, Weston, FL USA; [Yang, Haopu] Tsinghua Univ, Sch Med, Beijing, Peoples R China; [Yang, Haopu; Benos, Panayiotis, V] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA USA; [Finkelman, Malcolm A.; Zhang, Yonglong] Associates Cape Cod Inc, East Falmouth, MA USA; [Levochkina, Marina S.] Univ Pittsburgh, Ctr Neurosci, Safar Ctr Resuscitat Res, Dept Infect Dis & Microbiol, Pittsburgh, PA 15260 USA; [Levochkina, Marina S.; Wagner, Amy K.] Univ Pittsburgh, Ctr Neurosci, Safar Ctr Resuscitat Res, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA; [Levochkina, Marina S.; Wagner, Amy K.] Univ Pittsburgh, Ctr Neurosci, Safar Ctr Resuscitat Res, Dept Neurosci, Pittsburgh, PA 15260 USA; [Levochkina, Marina S.; Wagner, Amy K.] Univ Pittsburgh, Ctr Neurosci, Safar Ctr Resuscitat Res, Dept Clin & Translat Sci, Pittsburgh, PA 15260 USA; [Guo, Rui] Chongqing Med Univ, Dept Emergency & Crit Care Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Bain, William; Shah, Faraaz] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA; [Morris, Alison] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA"

通信作者："Kitsios, GD (corresponding author), UPMC Montefiore Hosp, Div Pulm Allergy & Crit Care Med, Med, NW628 3459 Fifth Ave, Pittsburgh, PA 15213 USA."

来源：JCI INSIGHT

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000677560000003

JCR分区：Q1

影响因子：8

年份：2021

卷号：6

期号：14

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："BACKGROUND. The fungal cell wall constituent 1,3-beta-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. METHODS. We 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. RESULTS. Compared 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. CONCLUSION. BDG 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."

基金机构："University of Pittsburgh Clinical and Translational Science Institute, COVID-19 Pilot Award; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K23 HL139987, U01 HL098962, P01 HL114453, R01 HL097376, K24 HL123342, U01 HL137159, R01 LM012087, K08HK144820, F32 HL142172, K23 GM122069]"

基金资助正文："University 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)."