epiglucan and Pulmonary-Aspergillosis

Topics: Antigens, Fungal; beta-Glucans; Candidiasis, Invasive; Galactose; Humans; Mannans; Mycoses; Proteoglycans; Pulmonary Aspergillosis; Serologic Tests

Since February 2021 active screening of COVID-19-associated pulmonary aspergillosis (CAPA) has been implemented in our institution.. To evaluate CAPA incidence in our centre and evaluate performance of our screening protocol.. We screened once per week, collecting endotracheal aspirates for fungal culture and galactomannan (GM) and serum for 1,3-ß-D-glucan (BG). In case of positivity (GM more than 4.5, platelia assay, and/or BG >7 pg/ml, wako and/or positive fungal culture), second-level investigations were performed to pursue CAPA diagnosis according to ECMM/ISHAM criteria: bronchoalveolar lavage (BAL) fungal culture and GM, chest computed tomography (CT), serum GM.. A total of 102 patients were screened (median age 64 years, range 39-79; 28 (27.4%) females). Twenty-two patients were diagnosed with CAPA (21%). 12 patients were positive for serum BG, 17 patients were positive for endotracheal aspirates GM and 27 patients were positive for endotracheal aspirates fungal culture. Thirty-two BALs were performed, and 26 patients underwent CT chest. Following the second level investigations 61% of the patients with positive screening tests were diagnosed with CAPA. Serum BG above 20 pg/ml or positive serum GM were always associated with typical CT chest signs of aspergillosis. Compared with 1 single positive test, having 2 positive screening test was significantly more associated with CAPA diagnosis (p = .0004).. Active CAPA screening with serum 1,3-ß-D-glucan and endotracheal aspirates galactomannan and fungal cultures and consequent second level investigations led to high number of CAPA diagnosis. Combining more positive fungal biomarkers was more predictive of CAPA diagnosis.

Topics: Adult; Aged; beta-Glucans; Bronchoalveolar Lavage Fluid; COVID-19; Female; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Pulmonary Aspergillosis; Sensitivity and Specificity

Immune defects in chronic pulmonary aspergillosis (CPA) are poorly characterized. We compared peripheral blood cytokine profiles in patients with CPA versus healthy controls and explored the relationship with disease severity.. Interferon-gamma (IFNγ), interleukin (IL)-17, tumor necrosis factor-α, IL-6, IL-12, and IL-10 were measured after in vitro stimulation of whole blood with lipopolysaccharide (LPS), phytohemagglutinin, β-glucan, zymosan (ZYM), IL-12 or IL-18, and combinations. Clinical parameters and mortality were correlated with cytokine production.. Cytokine profiles were evaluated in 133 patients (57.1% male, mean age 61 years). In comparison to controls, patients with CPA had significantly reduced production of IFNγ in response to stimulation with β-glucan + IL-12 (312 vs 988 pg/mL), LPS + IL-12 (252 vs 1033 pg/mL), ZYM + IL-12 (996 vs 2347 pg/mL), and IL-18 + IL-12 (7193 vs 12 330 pg/mL). Age >60 (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.00-2.91; P = .05) and chronic obstructive pulmonary disease (HR, 1.69; 95% CI, 1.03-2.78; P = .039) were associated with worse survival, whereas high IFNγ production in response to beta-glucan + IL-12 stimulation (HR, 0.48; 95% CI, .25-0.92; P = .026) was associated with reduced mortality.. Patients with CPA show impaired IFNγ production in peripheral blood in response to stimuli. Defective IFNγ production ability correlates with worse outcomes. Immunotherapy with IFNγ could be beneficial for patients showing impaired IFNγ production in CPA.

Topics: beta-Glucans; Cytokines; Female; Humans; Interferon-gamma; Interleukin-12; Interleukin-18; Lipopolysaccharides; Male; Middle Aged; Pulmonary Aspergillosis; Tumor Necrosis Factor-alpha

Topics: beta-Glucans; Bronchoalveolar Lavage Fluid; Europe; Galactose; Humans; Influenza, Human; Intensive Care Units; Mannans; Proteoglycans; Pulmonary Aspergillosis; Surveys and Questionnaires

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Cytarabine; Daunorubicin; Female; Humans; Idarubicin; Leukemia, Myeloid, Acute; Male; Middle Aged; Pulmonary Aspergillosis; Retrospective Studies; Risk Factors; Triazoles; Vidarabine

Aspergillus fumigatus is frequently encountered in sputum samples of patients with cystic fibrosis (CF), which traditionally has been interpreted as saprophytic airway colonization. However, this mere bystander role has been challenged by recent data. There is now evidence that Aspergillus fumigatus accelerates the decline of pulmonary function. (1→3)-β-D-glucan (BDG) and galactomannan (GM) are highly sensitive fungal biomarkers that are used to diagnose invasive fungal disease. However, their diagnostic value in CF patients is largely unknown.. We conducted a retrospective cohort study on 104 CF patients to determine whether serum BDG and GM levels correlate with parameters such as Aspergillus-positive sputum cultures and lung function.. Aspergillus fumigatus was persistently detected in 22 of the 104 CF patients (21%). Mean serum BDG and GM levels in the Aspergillus-positive patients were significantly higher than in those without persistent Aspergillus detection (89 versus 40 pg/ml [p = 0.022] and 0.30 versus 0.15 ODI [p = 0.013], respectively). 27 and 7 patients had elevated BDG (≥ 60 pg/ml) or GM levels (> 0.5 ODI), respectivly. BDG and GM levels showed a significant correlation (p = 0.004). Patients with increased serum concentrations of BDG were more frequently Aspergillus-positive (40.7 versus 14.3%, p = 0.004) and had a significantly lower forced expiratory volume in one second (FEV1) than patients with a normal BDG (61.6 versus 77.1%, p = 0.007). In the multivariate analysis, BDG but not GM or the growth of A. fumigatus, proved to be an independent predictor for the FEV1.. CF patients with persistent Aspergillus detection have elevated BDG and GM levels which ranged between healthy and invasively infected patients. Serum BDG may be superior to GM and fungal culture in predicting an impaired lung function in CF patients.

Topics: Adolescent; Adult; Aspergillus fumigatus; beta-Glucans; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Culture Techniques; Cystic Fibrosis; Female; Forced Expiratory Volume; Galactose; Humans; Male; Mannans; Middle Aged; Multivariate Analysis; Proteoglycans; Pulmonary Aspergillosis; Retrospective Studies; Sputum; Young Adult

We evaluated the usefulness of an

Topics: Aged; Aged, 80 and over; Aspergillus; beta-Glucans; Bronchoalveolar Lavage Fluid; Diagnostic Tests, Routine; Female; Galactose; Humans; Immunoassay; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; Proteoglycans; Pulmonary Aspergillosis; Sensitivity and Specificity

We describe a case of a man with ectopic Cushing's syndrome, elevated serum beta-D-glucan, and respiratory cultures with Pseudomonas, Aspergillus, and a partially acid-fast organism. Our case highlights challenges in diagnosis and management of coinfection in an immunocompromised host.

Topics: Aspergillus; beta-Glucans; Bronchoscopy; Cushing Syndrome; Humans; Male; Microscopy; Middle Aged; Nocardia; Pneumonia, Bacterial; Pseudomonas; Pulmonary Aspergillosis; Radiography, Thoracic; Serum; Tomography, X-Ray Computed

The objective of this study was to investigate the prognostic potential of 1,3-beta-d-glucan (BDG) testing in bronchoalveolar lavage fluid (BALF) samples.. A total of 300 BALF samples from 252 patients were investigated for BDG (Fungitell(®) assay). Prognostic potential of BALF BDG was evaluated by using: i.) Kaplan-Meier analysis, and ii.) multivariable Cox hazard regression analyses.. BALF BDG levels were found to be significantly higher in samples with Candida spp. colonization (p < 0.001). A total of 61/252 patients (24.2%) died within 90-days of BALF sampling (18.1% of patients with BALF BDG <200 pg/mL, 32.4% with BALF BDG ≥200 pg/mL). Kaplan-Meier analysis revealed that overall cumulative 90-day mortality was significantly higher in those with BALF BDG levels ≥200 pg/mL when compared to those with levels <200 pg/mL (log-rank p = 0.006, Breslow p = 0.005 and Tarone-Ware p = 0.005). The multivariable Cox regression analysis showed that BALF BDG levels were a strong predictor of 90-day overall mortality, with a hazard ratio of 1.048 (per 100 pg/mL increase of BALF BDG).. False positive BALF BDG results in the presence of Candida spp. colonization of the lower respiratory tract may explain the limited diagnostic potential of BALF BDG testing. In contrast, prognostic potential of BALF BDG may be promising.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Bronchoalveolar Lavage Fluid; Candidiasis, Invasive; Cohort Studies; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Pulmonary Aspergillosis; Risk Factors; Young Adult

Aspergillus fumigatus (A. fumigatus) is one of the most common fungi to cause diseases in humans. Recent evidence has demonstrated that airway epithelial cells play an important role in combating A. fumigatus through inflammatory responses. Human airway epithelial cells have been proven to synthesize the active vitamin D, which plays a key role in regulating inflammation. The present study was conducted to investigate the impact of A. fumigatus infection on the activation of vitamin D and the role of vitamin D activation in A. fumigatus-elicited antifungal immunity in normal human airway epithelial cells. We found that A. fumigatus swollen conidia (SC) induced the expression of 1α-hydroxylase, the enzyme catalyzing the synthesis of active vitamin D, and vitamin D receptor (VDR) in 16HBE cells and led to increased local generation of active vitamin D. Locally activated vitamin D amplified SC-induced expression of antimicrobial peptides in 16HBE cells but attenuated SC-induced production of cytokines in an autocrine fashion. Furthermore, we identified β-glucan, the major A. fumigatus cell wall component, as the causative agent for upregulation of 1α-hydroxylase and VDR in 16HBE cells. Therefore, activation of vitamin D is inducible and provides a bidirectional regulation of the responses to A. fumigatus in 16HBE cells.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Antifungal Agents; Aspergillus fumigatus; beta-Glucans; Bronchi; Cell Line; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Gene Expression Regulation; Humans; Inflammation; Pulmonary Aspergillosis; Real-Time Polymerase Chain Reaction; RNA Interference; Spores, Fungal; Vitamin D

Infection by the human fungal pathogen Aspergillus fumigatus induces hypoxic microenvironments within the lung that can alter the course of fungal pathogenesis. How hypoxic microenvironments shape the composition and immune activating potential of the fungal cell wall remains undefined. Herein we demonstrate that hypoxic conditions increase the hyphal cell wall thickness and alter its composition particularly by augmenting total and surface-exposed β-glucan content. In addition, hypoxia-induced cell wall alterations increase macrophage and neutrophil responsiveness and antifungal activity as judged by inflammatory cytokine production and ability to induce hyphal damage. We observe that these effects are largely dependent on the mammalian β-glucan receptor dectin-1. In a corticosteroid model of invasive pulmonary aspergillosis, A. fumigatus β-glucan exposure correlates with the presence of hypoxia in situ. Our data suggest that hypoxia-induced fungal cell wall changes influence the activation of innate effector cells at sites of hyphal tissue invasion, which has potential implications for therapeutic outcomes of invasive pulmonary aspergillosis.

Topics: Anaerobiosis; Animals; Aspergillus fumigatus; beta-Glucans; Cell Wall; Cytokines; Disease Models, Animal; Hyphae; Immunity, Innate; Lectins, C-Type; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Pulmonary Aspergillosis

A case of invasive pulmonary aspergillosis caused by Aspergillus terreus is described. The diagnosis was based on demonstration of branched septate hyphae in a sputum specimen and isolation of the fungus in culture. The diagnosis was further supported by detection of A. terreus-specific DNA, galactomannan (GM) and (1→3)-β-D-glucan (BDG) in consecutive serum specimens. The patient was treated for about 10 weeks with voriconazole. The decreasing levels of GM and BDG in serum samples were accompanied by symptomatic and radiological improvement. The report highlights the value of surrogate markers in the diagnosis and for monitoring the course of invasive aspergillosis during therapy.

Topics: Antifungal Agents; beta-Glucans; Child; Galactose; Humans; Lung Diseases, Fungal; Male; Mannans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proteoglycans; Pulmonary Aspergillosis; Pyrimidines; Triazoles; Voriconazole

In order to establish the reliable cut-off value of galactomannan (GM) antigen as well as that for beta-D-glucan for CNPA diagnosis, we conducted the following study. From 2001 to 2008, in a total of 1511 patients we measured GM and anti-aspergillus antibody simultaneously. These patients had chronic pulmonary disease including old tuberculosis, nontuberculous mycobacteriosis, COPD, and had bullous lung, interstitial lung disease or were suspected to have suspected to have interstitial lung disease. We designated cases as probable CNPA when the sample represented a positive anti-aspergillus antibody. We then analyzed the sensitivity and specificity according to various GM antigen values. When using the GM antigen cut-off value at 0.5, the sensitivity and specificity for CNPA were 63.4% and 68.6% respectively. Using 1.0 for cut-off value resulted in the better specificity for CNPA diagnosis. Similar analysis was performed on beta-D-glucan for CNPA diagnosis. When using D-glucan cut-off value as 20 pg/ml, the sensitivity and specificity for CNPA. These results indicate that the cut-off value of serological examination for infectious disease should be considered by the type of disease.

Topics: Antigens, Bacterial; beta-Glucans; Chronic Disease; Galactose; Humans; Mannans; Necrosis; Proteoglycans; Pulmonary Aspergillosis; Sensitivity and Specificity