epiglucan and Respiratory-Insufficiency

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).

Topics: beta-Glucans; Biomarkers; Candida; Capillary Permeability; COVID-19; Critical Illness; Female; Gastrointestinal Microbiome; Humans; Immunity, Innate; Male; Middle Aged; Predictive Value of Tests; Prognosis; Respiration, Artificial; Respiratory Insufficiency; Respiratory System; SARS-CoV-2; Severity of Illness Index; Survival Analysis

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in immunocompromised critically ill patients. New diagnostic strategies for early detection of IPA include the noninvasive biomarkers 1,3-β-d-glucan (BDG), serum, and bronchoalveolar (BAL) fluid galactomannan (GM). The aim of this study was to compare these markers for early detection of IPA in immunosuppressed critically ill patients.. Between December 2014 and December 2015, 49 immunosuppressed patients with respiratory failure were treated at our intensive care unit (ICU). We compared the BDG Fungitell assay with GM Platelia assay in serum and BAL for early detection of IPA. All tests were performed initially after admission at the ICU.. In our study with 49 patients, 13 (26%) had probable IPA. These patients had a higher Acute Physiology And Chronic Health Evaluation II score (28 vs 23, P<.001), Sequential Organ Failure Assessment score (16 vs 14, P<.001), more neutropenia (77% vs 30%, P<.001), worse Horowitz Index (99 vs 73 P<.020), a longer ICU stay (26 vs 17 days, P<.044), and a higher mortality rate (77% vs 58%, P<.001) as compared with patients without probable IPA. The used biomarker BDG presented in patients with probable IPA showed significantly higher levels as compared with patients without probable IPA (375 [103-1000 pg/mL; P<.001] vs 64 [30-105 pg/mL; P < .001]). Comparison of BDG with GM showed that positive serum GM could be detected in only 4 (30%), whereas positive BAL GM could be detected in 12 (92%; mean optical density index, 3.7) of 13 probable IPA cases. These results can be expressed as an overall sensitivity of 88% and a specificity of 82% for probable IPA using the BDG Fungitell assay, a sensitivity of 35% and a specificity of 70% using the serum GM Platelia assay, and a sensitivity of 70% and a specificity of 94% using the BAL GM Platelia assay. The negative predictive values of the used tests were 94% for the BDG Fungitell assay, 94% for the serum GM Platelia assay, and 90% for the BAL GM Platelia assay.. 1,3-β-d-Glucan may be a useful marker for patients under surveillance at risk for IPA. In critically ill patients with immunosuppression, early diagnosis of IPA may be improved by BDG as compared with serum GM. However, diagnostic performance and accuracy increase when BDG is run in parallel with GM from BAL; moreover, the association of the 2 parameters has also the advantage of detecting early and reliable IPA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; APACHE; Aspergillus; Autoimmune Diseases; beta-Glucans; Biomarkers; Bronchoalveolar Lavage Fluid; Critical Illness; Early Diagnosis; Female; Galactose; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Intensive Care Units; Invasive Pulmonary Aspergillosis; Length of Stay; Male; Mannans; Middle Aged; Mortality; Neoplasms; Neutropenia; Organ Dysfunction Scores; Organ Transplantation; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Sensitivity and Specificity; Young Adult

Invasive fungal infection is a fatal complication in liver transplantation and it is very difficult to diagnose at the early stage. The aim of this study was to review our experience with invasive fungal infections in living donor liver transplantation (LDLT) and to analyze the risk factors and the impact of beta-D glucan. From 1991 to 2005, 96 LDLTs were performed in our institution and we measured the serum level of beta-D glucan in order to clarify the diagnosis. Invasive fungal infection was diagnosed based on clinical symptoms, culture, radiological evidence and beta-D glucan. Active fungal infection was treated with fluconazole, amphotericin B, flucytosine and micafungin. Risk factors both pre- and post- LDLT were analyzed. Candida albicans was the most frequently isolated species (70%). The risk factors identified by univariate analysis include the following four conditions: acute blood purification (plasma exchange with or without continuous hemodiafiltration), hepatic vein complications, renal failure and respiratory failure. By logistic regression analysis, hepatic vein complications and respiratory failure were identified as independent risk factors. The risk factors for invasive fungal infection of LDLT in Japan have not been well analyzed and this report will provide valuable information for the prevention of the fungal infection.

Topics: Adolescent; Adult; beta-Glucans; Biomarkers; Child; Child, Preschool; Female; Hepatic Veins; Humans; Infant; Liver Diseases; Liver Transplantation; Living Donors; Male; Middle Aged; Mycoses; Renal Insufficiency; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Sensitivity and Specificity

Pulmonary diseases are important cause of morbidity and mortality in patients with PM/DM. Thirteen (27%) out of 49 PM/DM patients in the study had developed respiratory failure. Respiratory failure resulted form interstitial pneumonitis (i.p.) in 6, pulmonary infection in 2 and both in 5 patients with PM/DM. Respiratory failure was fatal in PM/DM patients with pulmonary diseases and eleven of the 13 patients expired. More importantly, 2 PM/DM patients with respiratory failure had responded to chemotherapy, if it was due to pulmonary infection. Accordingly, it is almost important to distinguish i.p. and infection for the cause of respiratory failure. However, plain chest X-ray as well as standard laboratory tests failed to differentiate i.p. and pulmonary infection. On the other hand, high resolution CT of the lungs, serum endotoxin and serum beta-D-glucan were found to be useful for the differentiation of these conditions associated with respiratory failure in PM/DM patients. And additionally low serum level of IgG and lymphopenia at the onset of respiratory failure may suggest that the patients may have pulmonary infection rather than i.p.

Topics: Adult; beta-Glucans; Biomarkers; Dermatomyositis; Diagnosis, Differential; Endotoxins; Female; Glucans; Humans; Immunoglobulin G; Lung Diseases, Interstitial; Lymphocyte Count; Male; Middle Aged; Pneumonia; Polymyositis; Prognosis; Respiratory Insufficiency; Tomography, X-Ray Computed