Circulating 1,3-Beta-D-Glucan is Associated with Lung Function, Respiratory Symptoms, and Mediators of Matrix Degradation in Chronic Obstructive Pulmonary Disease

Gorgone, Matthew; Singhvi, Deepti; Nouraie, Mehdi; Finkelman, Malcolm; Zhang, Yonglong; Pu, Jiantao; Chandra, Divay; Zhang, Yingze; Kitsios, Georgios D; Morris, Alison; Sciurba, Frank C.; Bon, Jessica

doi:10.15326/jcopdf.2022.0290

Cited by 2 publications

(3 citation statements)

References 58 publications

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“…To date, definition of an appropriate cut‐off for fungal translocation is lacking. 4 Thus, relying upon a high cut‐off value, such as 80 pg/mL, provides a more conservative estimate of the utility of the BDG titre where a significant relationship with outcome, symptom severity or another biomarker was also observed in various other non‐fungal infection disease states [e.g., CKD, inflammatory bowel disease, COPD, Lupus 21 , 22 , 23 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Fungal translocation measured by serum 1,3‐ß‐D‐glucan correlates with severity and outcome of liver cirrhosis—A pilot study

Egger

Horvath

Prüller

et al. 2023

Liver International

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Background & AimsOn a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host–pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier.MethodsIncluding 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3‐β‐D‐glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease.ResultsPatients with cirrhosis Child–Pugh class (CPC)‐B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2–25.2) compared to patients with cirrhosis CPC‐A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon‐gamma‐induced protein). Mortality differed significantly between patients with positive versus negative BDG (log‐rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8–26.3).DiscussionWe observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in‐depth knowledge about (fungal‐)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host–pathogen interactions and potentially introduce points of application for therapeutic interventions.

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Section: Methodsmentioning

confidence: 99%

Fungal translocation measured by serum 1,3‐ß‐D‐glucan correlates with severity and outcome of liver cirrhosis—A pilot study

Egger

Horvath

Prüller

et al. 2023

Liver International

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“…Patients with COPD have distinct gut microbiome profiles from healthy controls, with plausible causal mechanisms involving alternations of microbial metabolism [6 ▪ ]. Clinical observations also implicate translocation in severe COPD, as patients with acute exacerbations have increased small intestinal permeability, while plasma levels of 1,3-β- d -glucan (BDG), a fungal cell-wall constituent, potentially signifying translocating fungi from the gut), correlate with lung matrix degradation markers and worse lung function [7 ▪ ,8].…”

Section: Gut–lung Axis In Chronic Lung Diseasesmentioning

confidence: 99%

“…The prototypical PAMP is lipopolysaccharide (LPS), the endotoxin found on the outer cell wall of gram-negative bacteria, which causes increased neutrophil migration, higher myeloperoxidase activity, and cytokine levels in the lungs leading to epithelial cell damage and permeability alveolar edema [42,43]. Among critically ill patients without evidence of invasive fungal infection, plasma levels of the fungal PAMP BDG were significantly associated with the marker of intestinal permeability intestinal fatty acid binding protein-2, the hyper-inflammatory subphenotype of systemic host responses, higher mortality and longer times for liberation from mechanical ventilation [7 ▪ ,44 ▪▪ ]. Such studies provide indirect evidence of the role of gut-origin circulating PAMPs on lung physiology and outcomes.…”

Section: Translocation Of Microbial Components and Metabolitesmentioning

confidence: 99%

Gut–lung crosstalk during critical illness

Nath

Kitsios

Bos

2023

Current Opinion in Critical Care

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Purpose of reviewStudy of organ crosstalk in critical illness has uncovered complex biological communication between different organ systems, but the role of microbiota in organ crosstalk has received limited attention. We highlight the emerging understanding of the gut–lung axis, and how the largest biomass of the human body in the gut may affect lung physiology in critical illness.Recent findingsDisruption of healthy gut microbial communities and replacement by disease-promoting pathogens (pathobiome) generates a maladaptive transmitter of messages from the gut to the lungs, connected via the portal venous and the mesenteric lymphatic systems. Gut barrier impairment allows for microbial translocation (living organisms or cellular fragments) to the lungs. Host-microbiota interactions in the gut mucosa can also impact lung physiology through microbial metabolite secretion or host-derived messengers (hormones, cytokines or immune cells). Clinical examples like the prevention of ventilator-associated pneumonia by selective decontamination of the digestive tract show that the gut–lung axis can be manipulated therapeutically.SummaryA growing body of evidence supports the pathophysiological relevance of the gut–lung axis, yet we are only at the brink of understanding the therapeutic and prognostic relevance of the gut microbiome, metabolites and host-microbe interactions in critical illness.

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Circulating 1,3-Beta-D-Glucan is Associated with Lung Function, Respiratory Symptoms, and Mediators of Matrix Degradation in Chronic Obstructive Pulmonary Disease

Cited by 2 publications

References 58 publications

Fungal translocation measured by serum 1,3‐ß‐D‐glucan correlates with severity and outcome of liver cirrhosis—A pilot study

Fungal translocation measured by serum 1,3‐ß‐D‐glucan correlates with severity and outcome of liver cirrhosis—A pilot study

Gut–lung crosstalk during critical illness

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