galactomannan and Pulmonary-Aspergillosis

A clear cutoff value of galactomannan (GM) has not been established for chronic pulmonary aspergillosis (CPA) and is frequently extrapolated from invasive pulmonary aspergillosis. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of serum and bronchoalveolar lavage (BAL) GM, and to propose a cutoff.. We extracted from the studies the cutoff of serum or/and BAL GM associated with true positives, false positives, true negatives, and false negatives. We performed a multi-cutoff model and a non-parametric random effect model. We estimated the optimal cutoff and the area under the curve (AUC) for GM in serum and BAL samples.. Nine studies from 1999 to 2021 were included. Overall, the optimal cutoff of serum GM was 0.96 with a sensitivity of 0.29 (95%CI: 0.14-0.51); specificity of 0.88 (95%CI: 0.73-0.95); and AUC of 0.529 (with a CI: [0.415-0.682] [0.307-0.713]). The AUC for the non-parametric ROC model was 0.631. For BAL GM the cutoff was 0.67 with a sensitivity of 0.68 (95%CI: 0.51-0.82), specificity of 0.84 (95%CI: 0.70-0.92), and AUC of 0.814 (with a CI: [0.696-0.895] [0.733-0.881]). The AUC for the non-parametric model was 0.789.. The diagnosis of CPA requires the assessment of a combination of mycological and serological factors, as no single serum and/or BAL GM antigen test is adequate. BAL GM performed better than serum, with better sensitivity and excellent accuracy.

Topics: Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Humans; Mannans; Pulmonary Aspergillosis; Sensitivity and Specificity

The spectrum of disease caused by Aspergillus spp. is dependent on the immune system of the host, and ranges from invasive aspergillosis (IA) to chronic pulmonary aspergillosis (CPA). Early and reliable diagnosis of Aspergillus disease is important to decrease associated morbidity and mortality. Areas covered: The following review will give an update on current diagnostic strategies for the diagnosis of IA and CPA. Expert commentary: Several new diagnostics for IA (including point-of-care tests) are now available to complement galactomannan testing. In particular, immunoPET/MRI imaging may be a promising approach for diagnosing IA in the near future. Notably, nearly all new biomarkers and tests for IA have been evaluated in the hematology setting only. Validation of biomarkers and tests is therefore needed for the increasing proportion of patients who develop IA outside the hematology setting. As an important first step, reliable definitions of IA are needed for non-hematology settings as clinical presentation and radiologic findings differ in these settings. CPA diagnosis is based on a combination of radiological findings in chest CT, mycological evidence (e.g. by the Aspergillus-specific IgG assay), exclusion of alternative diagnosis and chronicity. ([18F]FDG) PET/CT and immuno PET/MRI imaging are promising new imaging approaches.

Topics: Animals; Aspergillosis; Aspergillus; Biomarkers; Chronic Disease; Galactose; Humans; Magnetic Resonance Imaging; Mannans; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Pulmonary Aspergillosis

The objective of this study was to describe the diagnostic yield and complication rate of bronchoalveolar lavage (BAL) and lung biopsy in the evaluation of pulmonary lesions in patients with cancer and recipients of hematopoietic stem-cell transplantation (HSCT).. We conducted a systematic literature review and performed electronic searches of Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were recipients of HSCT, and if they underwent BAL or lung biopsy for the evaluation of pulmonary lesions. Only English language publications were included.. In all, 14,148 studies were screened; 72 studies of BAL and 31 of lung biopsy were included. The proportion of procedures leading to any diagnosis was similar by procedure type (0.53 v 0.54; P = .94) but an infectious diagnosis was more common with BAL compared with lung biopsy (0.49 v 0.34; P < .001). Lung biopsy more commonly led to a noninfectious diagnosis (0.43 v 0.07; P < .001) and was more likely to change how the patient was managed (0.48 v 0.31; P = .002) compared with BAL. However, complications were more common with lung biopsy (0.15 v 0.08; P = .006), and procedure-related mortality was four-fold higher for lung biopsy (0.0078) compared with BAL (0.0018).. BAL may be the preferred diagnostic modality for the evaluation of potentially infectious pulmonary lesions because of lower complication and mortality rates; thus, choice of procedure depends on clinical suspicion of infection. Guidelines to promote consistency in the approach to the evaluation of lung infiltrates may improve clinical care of patients.

Topics: Adult; Aspergillus; Biomarkers; Biopsy; Bronchoalveolar Lavage; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Lung; Lung Diseases; Lung Neoplasms; Mannans; Neoplasms; Pneumonia; Polymerase Chain Reaction; Pulmonary Aspergillosis

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

Invasive aspergillosis, chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis are the clinical forms of aspergillosis. Although there is a great number of Aspergillus species, Aspergillus fumigatus-complex is the more frequent aetiological agent, regardless of clinical form or baseline condition. The increase in immunosuppressive agents and the higher use of corticosteroids in chronic obstructive pulmonary disease have led to aspergillosis becoming more prominent in recent years. Galactomannan detection and radiological diagnostic images complement the limitations of microbiology cultures in these patients. Voriconazole and liposomal amphotericin B are the gold standard in patients requiring therapy, and posaconazole, itraconazole, caspofungin and other echinocandins are effective alternatives. The prognosis depends of clinical forms and characteristics of the host, but it is particularly poor in the disseminated invasive forms.

Topics: Antifungal Agents; Aspergillosis; Aspergillus; Cross Infection; Drug Resistance, Multiple, Fungal; Endocarditis; Endophthalmitis; Fungemia; Galactose; Humans; Immunocompromised Host; Mannans; Neuroaspergillosis; Postoperative Complications; Pulmonary Aspergillosis; Radiography; Risk Factors; Salvage Therapy; Species Specificity; Vulnerable Populations

A serum galactomannan (GM) assay has been approved for diagnosing invasive aspergillosis (IA). However, the role of the BAL-GM assay has not been well established. Therefore, we conducted a metaanalysis to determine the overall accuracy of BAL-GM in the diagnosis of IA.. After a systematic review of English-language studies, the sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) of BAL-GM for the diagnosis of IA were pooled using a bivariate metaanalysis. Hierarchic summary receiver operating characteristic curves were used to summarize overall test performance. Potential between-study heterogeneity was explored by subgroup analyses. We calculated posttest probability to evaluate clinical usefulness.. Twelve reports, including 13 studies, met our inclusion criteria. The summary estimates of the BAL-GM assay for proven or probable IA were as follows: SEN, 0.90 (95% CI, 0.79-0.96); SPE, 0.94 (95% CI, 0.90-0.96); PLR, 14.87 (95% CI, 8.89-24.90); and NLR, 0.10 (95% CI, 0.04-0.24). The four summary estimates of the BAL-GM assay for proven IA were 0.94 (95% CI, 0.86-0.98), 0.79 (95% CI, 0.68-0.86), 4.41 (95% CI, 2.87-6.77), and 0.07 (95% CI, 0.03-0.09), respectively. Significant heterogeneity was present.. BAL-GM determination is a sensitive and specific test for the diagnosis of proven and probable IA. The measurement of BAL-GM is thus likely to be a useful tool for diagnosing IA. Further studies focused on the impact of treatment agents are needed.

Topics: Biomarkers; Bronchoalveolar Lavage Fluid; Galactose; Humans; Mannans; Predictive Value of Tests; Pulmonary Aspergillosis; ROC Curve; Sensitivity and Specificity

Invasive aspergillosis is a major cause of mortality in allogeneic bone marrow transplant recipients and patients treated for blood malignancies. The diagnostic tools, treatments and preventive strategies, essentially developed for neutropaenic patients, have not been assessed in populations whose immune systems are considered to be competent.. Beside the standard picture of chronic Aspergillus infection, the incidence of invasive aspergillosis is increasing in non neutropaenic patients, such as those with chronic lung diseases or systemic disease treated with long-term immunosuppressive drugs and solid organ transplant recipients. This study reviews the specific features of invasive aspergillosis in non neutropaenic subjects (NNS) and discusses the value of the diagnostic tools and treatment in this population.. A better understanding of the pathophysiology and the epidemiological characteristics of invasive aspergillosis would provide a means of adapting the staging and classification of the disease for NNS.. Invasive aspergillosis is under diagnosed in NNS who may already be colonised when they receive immunosuppressive treatment; this can lead to an adverse outcome in patients who are considered to be a moderate risk population.

Topics: AIDS-Related Opportunistic Infections; Antibodies, Fungal; Antifungal Agents; Aspergillosis; Aspergillus; Chronic Disease; Fungemia; Galactose; Humans; Immunocompromised Host; Immunosuppressive Agents; Lung Diseases; Mannans; Neutropenia; Organ Transplantation; Postoperative Complications; Pulmonary Aspergillosis; Radiography; Respiratory System; Risk Factors; Wound Infection

This review summarizes recent developments in the diagnosis and treatment of fungal pneumonia, with an emphasis on invasive pulmonary aspergillosis.. Improvements in nonculture-based fungal diagnostics, early implementation of pulmonary high resolution, or spiral computed tomography scanning and a recent expansion of the antifungal armamentarium have greatly improved the outcome of immunocompromised patients with invasive aspergillosis. However, the field is changing: new pathogens (such as Zygomycetes) are emerging, and novel risk groups (ICU patients in particular) are being identified.. Galactomannan antigen detection is a valuable tool for evaluating patients at risk for invasive aspergillosis (as a screening assay on serum samples from neutropenic patients or as a confirmatory assay on bronchoalveolar lavage fluid samples, in general), but should be used in conjunction with modern imaging techniques. beta-D-Glucan and PCR assays are still investigational. Voriconazole is the drug of choice for invasive aspergillosis, whereas liposomal amphotericin B at 3 mg/kg per day is the preferred alternative in case of contraindication, drug-related side-effects, or intolerance. Whenever possible, optimal antifungal therapy should be complemented by surgical debridement of necrotic tissue. The added value of combination therapy is still unproven. Therapeutic drug monitoring of mold-active azoles should be implemented in order to minimize toxicity and maximize efficacy. Lipid-based formulations of amphotericin B, and to a lesser extent voriconazole, are the drugs of choice for non-Aspergillus related fungal pneumonia. Although active in prophylaxis, the efficacy of posaconazole in confirmed infections remains controversial.

Topics: Amphotericin B; Antifungal Agents; Fungi; Galactose; Humans; Mannans; Mycoses; Pneumonia; Pulmonary Aspergillosis; Pyrimidines; Radiography, Thoracic; Triazoles; Voriconazole

Chronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA.. The prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit.. A total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5μg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively.. The sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis.. NCT03027089 . Registered 20 January 2017.

Topics: Adult; Aged; Antibodies, Fungal; Aspergillus; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Humans; Immunoglobulin Isotypes; Male; Mannans; Middle Aged; Prospective Studies; Pulmonary Aspergillosis; ROC Curve; Sensitivity and Specificity

An algorithm for distinguishing invasive pulmonary aspergillosis (IPA) in critically ill patients (AspICU) has been proposed but not tested.. This was a prospective observational study applying the AspICU protocol to patients with positive Aspergillus culture (PAC group) and those with negative aspergillus culture but positive galactomannan test in respiratory tract samples (only positive galactomannan (OPG group)). Patients underwent a standardized diagnostic workup with bronchoscopy, computed tomography (CT), and galactomannan determination in serum and bronchoalveolar lavage fluid (BALF).. We included 85 patients in the study. Of these, 43 had positive aspergillus cultures and 42 patients had only a positive galactomannan test. There were no statistically significant differences in baseline characteristics, underlying conditions or ICU scores between the two groups. The galactomannan titre in BALF was significantly higher in the positive aspergillus culture (PAC) group (enzyme immunoassay (EIA) 5.9, IQR 3.2-5.7) than in the OPG group (EIA 1.7, IQR 0.9-4.5) (p < 0.001). Classic features of IPA were detected on CT in 37.5 % and 36.6 % of patients in the PAC and OPG groups, respectively. There were no statistically significant differences between the PAC and the OPG group in relation to AspICU or European Organization for the Research and Treatment of Cancer (EORTC) criteria. A positive aspergillus culture was a stronger trigger for initiating antimycotic treatment than positive BALF galactomannan: 88.4 % of patients in the PAC group were regarded by clinicians as having IPA and received antimycotic treatment as opposed to 59.5 % in the OPG group (p = 0.002). The 180-day mortality was 58.1 % in the PAC group and 59.5 % in the OPG group.. The inclusion of BALF galactomannan as an additional entry criterion for the AspICU clinical algorithm could increase the diagnostic sensitivity for IPA in ICU patients.. The study was registered at ClinicalTrials.gov (registration number NCT01866020 ) on 27 May 2013.

Topics: Aged; Aged, 80 and over; Antifungal Agents; Critical Illness; Galactose; Humans; Intensive Care Units; Mannans; Prospective Studies; Pulmonary Aspergillosis; Therapeutic Irrigation

Diagnosing invasive pulmonary aspergillosis (IPA) remains a challenge in patients with hematological malignancies. The clinical significance of testing bronchoalveolar lavage (BAL) samples both with polymerase chain reaction (PCR) and Aspergillus galactomannan ELISA (GM) is unclear, and the BAL cutoff for GM has not been clearly evaluated yet.. Using a validated nested PCR assay and a GM ELISA, we prospectively examined BAL samples from 87 hematological patients at high risk of IPA. Of 76 (87%) evaluable patients, 29 patients had proven or probable disease.. The receiver operating characteristic (ROC) analysis of GM optical density (OD) cutoff levels yielded a BAL OD of 0.5 to be optimal. We identified 29 probable or proven cases based on this OD. Sensitivity and specificity for BAL GM were 0.79 (95% CI, 0.62-0.9) and 0.96 (95% CI, 0.86-0.99), respectively. For BAL PCR, sensitivity and specificity were 0.59 (95% CI, 0.41-0.75) and 0.87 (95% CI, 0.75-0.94), respectively. Combining BAL GM and PCR for diagnosis showed a sensitivity and specificity rate of 0.55 (95% CI, 0.38-0.72) and 1.0 (95% CI, 0.93-1.0), respectively, if positivity was defined by positive results for both tests. If either positive BAL GM or positive BAL PCR results defined test positivity, the sensitivity was 0.83 (95% CI, 0.65-0.92), and the specificity was 0.83 (95% CI, 0.70-0.91). In terms of optimal sensitivity and specificity, a GM OD cutoff of 0.5 was determined for BAL samples. Positivity for both GM and Aspergillus PCR in BAL makes a pulmonary aspergillosis highly likely.

Topics: Adolescent; Adult; Aged; Aspergillus; Bronchoalveolar Lavage; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Pulmonary Aspergillosis; Sensitivity and Specificity

To prospectively evaluate the utility of detecting bronchoalveolar lavage fluid (BALF) Aspergillus galactomannan antigen (GM) in the diagnosis of pulmonary aspergillosis.. From August 2008 to April 2012, 121 patients suspected of pulmonary aspergillosis were recruited and classified into pulmonary aspergillosis group (n = 57) and non-pulmonary disease group (n = 64) according to the 2008 diagnostic criteria and classification of European Organization for Research and Treatment of Cancer/National Institute of Mycoses Study Group(EORTC/MSG). The absorbency (A) and I value of GM in the patients' serum and BALF were detected by enzyme-linked immunosorbent assay (ELISA). And their values were compared and analyzed.. Twenty cases were confirmed by pathological examinations and 37 cases by clinical diagnosis in the pulmonary aspergillosis group. The mean rank of GM's I value in the serum and BALF samples was 88.21 and 86.49. And they significantly increased compared with the non-pulmonary aspergillosis group (36.77, 38.30) (P < 0.01). At a different serum GM threshold I = 0.5, 0.8, 1.0, the sensitivities were 0.842, 0.649 and 0.228; the specificities 0.906, 0.938, 0.929; the positive predictive values 0.889, 0.902, 0.984 and the negative predictive values 0.866, 0.750, 0.589 respectively. And at a different BALF GM threshold I = 0.5, 0.8, 1.0, the sensitivities were 0.930, 0.657, 0.561; the specificities 0.766, 0.922, 0.969; the positive predictive values 0.779, 0.884, 0.941 and the negative predictive values 0.925, 0.756, 0.713 respectively.. The detection of GM in BALF may be employed for the clinical diagnosis of pulmonary aspergillosis.

Topics: Adult; Aged; Antigens, Fungal; Bronchoalveolar Lavage Fluid; Female; Galactose; Humans; Male; Mannans; Middle Aged; Predictive Value of Tests; Pulmonary Aspergillosis; Sensitivity and Specificity

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

Galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid samples has become an essential tool to diagnose invasive pulmonary aspergillosis (IPA) and is part of diagnostic guidelines. Enzyme-linked immunosorbent assays (ELISAs) (enzyme immunoassays [EIAs]) are commonly used, but they have a long turnaround time. In this study, we evaluated the performance of an automated chemiluminescence immunoassay (CLIA) with BAL fluid samples. This was a multicenter retrospective study in the Netherlands and Belgium. BAL fluid samples were collected from patients with underlying hematological diseases with a suspected invasive fungal infection. Diagnosis of IPA was based on the 2020 European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) consensus definitions. GM results were reported as optical density index (ODI) values. ODI cutoff values for positive results that were evaluated were 0.5, 0.8, and 1.0 for the EIA and 0.16, 0.18, and 0.20 for the CLIA. Probable IPA cases were compared with two control groups, one with no evidence of IPA and another with no IPA or possible IPA. Qualitative agreement was analyzed using Cohen's κ, and quantitative agreement was analyzed by Spearman's correlation. We analyzed 141 BAL fluid samples from 141 patients; 66 patients (47%) had probable IPA, and 56 cases remained probable IPA when the EIA GM result was excluded as a criterion, because they also had positive culture and/or duplicate positive PCR results. Sixty-three patients (45%) had possible IPA and 12 (8%) had no IPA. The sensitivity and specificity of the two tests were quite comparable, and the overall qualitative agreement between EIA and CLIA results was 81 to 89%. The correlation of the actual CLIA and EIA values was strong at 0.72 (95% confidence interval, 0.63 to 0.80). CLIA has similar performance, compared to the gold-standard EIA, with the benefits of faster turnaround because batching is not required. Therefore, CLIA can be used as an alternative GM assay for BAL fluid samples.

Topics: Bronchoalveolar Lavage Fluid; Hematologic Diseases; Humans; Invasive Pulmonary Aspergillosis; Mannans; Pulmonary Aspergillosis; Retrospective Studies; Sensitivity and Specificity

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Topics: Aspergillus; Bronchoalveolar Lavage Fluid; Humans; Invasive Pulmonary Aspergillosis; Mannans; Polymerase Chain Reaction; Pulmonary Aspergillosis; Sensitivity and Specificity

COVID-19-associated pulmonary aspergillosis (CAPA) incidence varies depending on the country. Serum galactomannan quantification is a promising diagnostic tool since samples are easy to obtain with low biosafety issues. A multicenter prospective study was performed to evaluate the CAPA incidence in Argentina and to assess the performance of the lateral flow assay with digital readout (Sōna Aspergillus LFA) as a CAPA diagnostic and screening tool. The correlation between the values obtained with Sōna Aspergillus LFA and Platelia® EIA was evaluated. In total, 578 serum samples were obtained from 185 critically ill COVID patients. CAPA screening was done weekly starting from the first week of ICU stay. Probable CAPA incidence in critically ill patients was 10.27% (19/185 patients when LFA was used as mycological criteria) and 9% (9/100 patients when EIA was used as mycological criteria). We found a very good correlation between the two evaluated galactomannan quantification methods (overall agreement of 92.16% with a Kappa statistic value of 0.721). CAPA diagnosis (>0.5 readouts in LFA) were done during the first week of ICU stay in 94.7% of the probable CAPA patients. The overall mortality was 36.21%. CAPA patients' mortality and length of ICU stay were not statistically different from for COVID (non-CAPA) patients (42.11 vs 33.13% and 29 vs 24 days, respectively). These indicators were lower than in other reports. LFA-IMMY with digital readout is a reliable tool for early diagnosis of CAPA using serum samples in critically ill COVID patients. It has a good agreement with Platelia® EIA.. The incidence of COVID-associated pulmonary aspergillosis (CAPA) in critically-ill Argentinian patients was established (10.27%). Serum galactomannan quantification was useful as a screening tool for this mycosis. A good agreement between Platelia® EIA and Sōna Aspergillus LFA is reported.

Topics: Animals; Argentina; Aspergillus; COVID-19; Critical Illness; Galactose; Humans; Invasive Pulmonary Aspergillosis; Mannans; Prospective Studies; Pulmonary Aspergillosis; Sensitivity and Specificity

Galactomannan Enzyme Immunoassay (GM-EIA) is proved to be a cornerstone in the diagnosis of COVID-19-associated pulmonary aspergillosis (CAPA), its use is limited in middle and low-income countries, where the application of simple and rapid test, including Galactomannan Lateral Flow Assay (GM-LFA), is highly appreciated. Despite such merits, limited studies directly compared GM-LFA with GM-EIA. Herein we compared the diagnostic features of GM-LFA, GM-EIA and bronchoalveolar lavage (BAL) culture for CAPA diagnosis in Iran, a developing country.. Diagnostic performances of GM-LFA and GM-EIA in BAL (GM indexes ≥1) and serum (GM indexes >0.5), i.e. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and areas under the curve (AUC), were evaluated using BAL (n = 105) and serum (n = 101) samples from mechanically ventilated COVID-19 patients in intensive care units. Patients were classified based on the presence of host factors, radiological findings and mycological evidences according to 2020 ECMM/ISHAM consensus criteria for CAPA diagnosis.. The Aspergillus GM-LFA for serum and BAL samples showed a sensitivity of 56.3% and 60.6%, specificity of 94.2% and 88.9%, PPV of 81.8% and 71.4%, NPV of 82.3% and 83.1%, when compared with BAL culture, respectively. GM-EIA showed sensitivities of 46.9% and 54.5%, specificities of 100% and 91.7%, PPVs of 100% and 75%, NPVs of 80.2% and 81.5% for serum and BAL samples, respectively.. Our study found GM-LFA as a reliable simple and rapid diagnostic tool, which could circumvent the shortcomings of culture and GM-EIA and be pivotal in timely initiation of antifungal treatment.

Topics: Antifungal Agents; Bronchoalveolar Lavage Fluid; COVID-19; COVID-19 Testing; Galactose; Humans; Immunoenzyme Techniques; Invasive Pulmonary Aspergillosis; Mannans; Pulmonary Aspergillosis; Sensitivity and Specificity

Studies have confirmed that real-time PCR detection of. The diagnostic criteria of this study were based on the 2015 ESCMID/ERS guidelines for CPA. Seventy-nine patients with CPA and 74 non-CPA patients were enrolled.. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of BALF PCR in the CPA group were 87.18%, 89.80%, 87.18%, 89.80%, and 0.89 (95% CI 0.82-0.95), respectively (. The BALF PCR detection method has good diagnostic value for CPA and combining this method with BALF GM detection can improve diagnostic sensitivity and specificity.

Topics: Adult; Aged; Antigens, Bacterial; Aspergillus; Bronchoalveolar Lavage Fluid; Chronic Disease; DNA, Bacterial; Early Diagnosis; Female; Galactose; Humans; Male; Mannans; Middle Aged; Predictive Value of Tests; Prospective Studies; Pulmonary Aspergillosis; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity

Our aim was to evaluate the performance of two galactomannan (GM) assays (Platelia Aspergillus EIA, Bio-Rad. We included critically ill patients, performed GM-EIA and GM-Lateral Flow Assay (GM-LFA) in TA and followed them until development of COVID-19-associated pulmonary aspergillosis (CAPA) or alternate diagnosis. CAPA was defined according to the modified AspICU criteria in patients with SARS-CoV-2 infection. We estimated sensitivity, specificity, positive and negative predictive values for GM-EIA, GM-LFA, the combination of both or either positive results for GM-EIA and GM-LFA. We explored accuracy using different breakpoints, through ROC analysis and Youden index to identify the optimal cut-offs. We described antifungal treatment and 30-day mortality.. We identified 14/144 (9.7%) patients with CAPA, mean age was 50.35 (SD 11.9), the median time from admission to CAPA was 8 days; 28.5% received tocilizumab and 30-day mortality was 57%. ROC analysis and Youden index identified 2.0 OD as the best cut-off, resulting in sensitivity and specificity of 57.1% and 81.5% for GM-EIA and 60% and 72.6% for GM-LFA, respectively.. The diagnostic performance of GM in tracheal aspirates improved after using a cut-off of 2 OD. Although bronchoalveolar lavage testing is the ideal test, centres with limited access to bronchoscopy may consider this approach to identify or rule out CAPA.

Topics: Adult; Antifungal Agents; COVID-19; Diabetes Complications; Female; Galactose; Humans; Male; Mannans; Middle Aged; Obesity; Pulmonary Aspergillosis; Sensitivity and Specificity; Trachea

To evaluate the diagnostic performance of galactomannan (GM) detection in serum and bronchoalveolar lavage fluid (BALF) for invasive pulmonary aspergillosis (IPA) in non-neutropenic patients.. A total of 291 non-neutropenic patients in the Second Xiangya Hospital of Central South University were included. According to the 2019 EORTC/MSG guidelines, all cases were divided into an IPA group (n = 24) and a non-IPA group (n = 267). Receiver operating characteristic (ROC) curves were drawn to compare the diagnostic efficiency of GM detection in BALF and serum.. According to the receiver operating characteristic curves of BALF and serum GM, the areas under the curve were 0.961 and 0.699, respectively. The optimal BALF GM detection was found when the cutoff value was set to 0.87, whereas the sensitivity and specificity were 91.7% and 92.5%, respectively.. BALF GM detection is more sensitive than serum GM detection for diagnosing IPA, and the optimal cutoff value for BALF GM is 0.87.

Topics: Aged; Bronchoalveolar Lavage Fluid; Female; Galactose; Humans; Male; Mannans; Middle Aged; Pulmonary Aspergillosis

The objective of this study was to explore the diagnostic value of the bronchoalveolar lavage fluid galactomannan (BALF GM) test for chronic respiratory disease with pulmonary aspergillosis and to establish the optimal cutoff value. Samples from a total of 309 chronic respiratory disease patients seen at the respiratory medicine department of Peking University Shenzhen Hospital from September 2016 to September 2019 were analyzed. According to the diagnostic criteria, we divided the patients into a case group (

Topics: Adult; Aged; Aspergillus; Biopsy; Bronchoalveolar Lavage Fluid; Bronchoscopy; China; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Humans; Male; Mannans; Middle Aged; Pulmonary Aspergillosis; ROC Curve; Sensitivity and Specificity; Young Adult

Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID-19) associated invasive aspergillosis at a single centre in Cologne, Germany.. A retrospective chart review of all patients with COVID-19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany.. COVID-19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS.. Clinicians caring for patients with ARDS due to COVID-19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co-infection.

Topics: Aged; Antifungal Agents; Bronchoalveolar Lavage Fluid; Coronavirus Infections; COVID-19; Female; Galactose; Germany; Hemorrhage; Hospitals, Teaching; Humans; Intensive Care Units; Lung Diseases; Male; Mannans; Metapneumovirus; Middle Aged; Nitriles; Pandemics; Paramyxoviridae Infections; Pneumonia, Viral; Pulmonary Aspergillosis; Pyridines; Respiratory Distress Syndrome; Retrospective Studies; Thorax; Tomography, X-Ray Computed; Triazoles; Voriconazole

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

Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies.. A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus.. Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung.. A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.

Topics: Antifungal Agents; Aspergillus; Betacoronavirus; Bronchoalveolar Lavage Fluid; Coronavirus Infections; COVID-19; Galactose; Humans; Influenza, Human; Intensive Care Units; Mannans; Pandemics; Pneumonia, Viral; Pulmonary Aspergillosis; SARS-CoV-2

Pathological data of critical ill COVID-19 patients is essential in the search for optimal treatment options.. We performed postmortem needle core lung biopsies in seven patients with COVID-19 related ARDS. Clinical, radiological and microbiological characteristics are reported together with histopathological findings.. Patients age ranged from 58 to 83 years, five males and two females were included. Time from hospital admission to death ranged from 12 to 36 days, with a mean of 20 ventilated days. ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. Chest CT in all patients showed ground glass opacities, commonly progressing to nondependent consolidations. We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia. None of the biopsy specimens showed any signs of invasive aspergillosis.. In this case series common late histopathology in critically ill COVID patients is not classic DAD but heterogeneous with predominant pattern of organizing pneumonia. Postmortem biopsy investigations in critically COVID-19 patients with probable COVID-19 associated pulmonary aspergillosis obtained no evidence for invasive aspergillosis.

Topics: Aged; Aged, 80 and over; Autopsy; Betacoronavirus; Biopsy; Biopsy, Large-Core Needle; Bronchoalveolar Lavage Fluid; Coinfection; Coronavirus Infections; COVID-19; Critical Illness; Female; Galactose; Humans; Lung; Lung Diseases, Interstitial; Male; Mannans; Middle Aged; Pandemics; Phenotype; Pneumonia, Viral; Pulmonary Aspergillosis; Pulmonary Embolism; Respiratory Distress Syndrome; SARS-CoV-2; Tomography, X-Ray Computed

An early diagnosis of chronic pulmonary aspergillosis (CPA) at the stage of simple aspergilloma (SA) remains a challenge in low- and middle-income countries, where imaging may not be routinely available.. We investigate the role of Aspergillus fumigatus-specific IgG in serum, and galactomannan (GM) in bronchoalveolar lavage fluid (BALF) and serum for the diagnosis of SA.. We included 46 consecutive treatment-naïve subjects with SA. The 81 controls were subjects of treated pulmonary tuberculosis with residual radiological abnormality and minimal symptoms; and subjects with pulmonary disorders other than CPA who underwent bronchoscopy. The diagnosis of SA was based on consistent clinical features along with radiological manifestations (cavity with fungal ball).. Using receiver operating characteristic (ROC) curve analysis, the best cut-off value for A fumigatus-specific IgG was 27.3 mgA/L (AUROC, 0.839; sensitivity, 63.5%; specificity, 98.3%). The best cut-off value for serum and BALF-GM was 0.7 (AUROC, 0.636; sensitivity, 32%; specificity, 96.2%) and 2.5 (AUROC, 0.833; sensitivity, 63.7%; specificity, 97.1%), respectively. A combination of A fumigatus-specific IgG (>27 mgA/L) or serum GM (≥0.7) or BALF-GM (≥2.5) had a sensitivity and specificity of 82.6% and 96%, respectively.. A combination of serological tests has the best sensitivity in diagnosing SA. More studies are needed to confirm our findings.

Topics: Adult; Antibodies, Fungal; Aspergillus fumigatus; Bronchoalveolar Lavage Fluid; Female; Galactose; Humans; Immunoglobulin G; Male; Mannans; Middle Aged; Pulmonary Aspergillosis; ROC Curve; Sensitivity and Specificity; Serologic Tests; Tomography, X-Ray Computed

Bronchoalveolar lavage galactomannan (BAL-GM) is a mycological criterion for diagnosis of probable invasive aspergillosis (IA) per European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORT-MSG) consensus criteria, but its real-world positive predictive value (PPV) has not been well-studied. Our aim was to estimate the PPV of BAL-GM in a contemporary cohort of patients with positive BAL-GM.. We identified consecutive patients with ≥1 positive BAL-GM value (index ≥ 0.5) at Brigham and Women's Hospital from 11/2009 to 3/2016. We classified patients as having no, possible, probable, or proven IA, excluding BAL-GM as mycological criterion.. We studied 134 patients: 54% had hematologic malignancy (HM), and 10% were solid organ transplant (SOT) recipients. A total of 42% of positive (≥0.5) BAL-GM results were falsely positive (PPV 58%). The number of probable IA cases was increased by 23% using positive BAL-GM as mycologic criterion alone. PPV was higher in patients with HM or SOT (P < 0.001) and with use of higher thresholds for positivity (BAL-GM ≥ 1 vs 1-0.8 vs 0.8-0.5: P = 0.002).. 42% of positive BAL-GM values were falsely positive. We propose a critical reassessment of BAL-GM cutoff values in different patient populations. Accurate noninvasive tests for diagnosis of IA are urgently needed.

Topics: Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; Clinical Laboratory Techniques; False Positive Reactions; Female; Galactose; Hematologic Neoplasms; Humans; Mannans; Middle Aged; Organ Transplantation; Predictive Value of Tests; Pulmonary Aspergillosis; Retrospective Studies; Young Adult

The value of serum and bronchoalveolar lavage fluid galactomannan (BALF-GM) in diagnosing chronic pulmonary aspergillosis (CPA) remains unclear. Here, we study the diagnostic efficacy of GM in the diagnosis of CPA. We included consecutive treatment-naive subjects with CPA. For calculating the specificity of serum GM, we enrolled diseased controls (minimally symptomatic subjects previously treated for pulmonary tuberculosis, not meeting the criteria for CPA). To calculate the specificity of BALF-GM, subjects with pulmonary disorders other than CPA who underwent bronchoscopy were included. We determined the cutoff of serum and BALF-GM levels using receiver operating characteristic (ROC) curve analysis. We enrolled 243 consecutive treatment-naive subjects (53.5% males) of CPA with a mean (standard deviation) age of 43.6 (14.7) years. Forty-five (60% males; age, 46.7 [15.7] years) and 27 (59.3% males; age, 52.6 [12.8] years) subjects served as controls for serum and BALF-GM, respectively. The best cutoff value for serum and BALF-GM was 0.55 (area under the ROC curve [AUROC], 0.605; sensitivity, 38%; specificity, 87%) and 1.375 (AUROC, 0.836; sensitivity, 68%; specificity, 93%), respectively. At a cutoff value of 2.5, BALF-GM had a sensitivity and specificity of 50% and 100%, respectively. BALF-GM performs better than serum GM and may be helpful in the diagnosis of CPA in selected patients. More studies are required to confirm our findings.

Topics: Adult; Aspergillus; Bronchoalveolar Lavage Fluid; Chronic Disease; Female; Fungal Polysaccharides; Galactose; Humans; Male; Mannans; Middle Aged; Prospective Studies; Pulmonary Aspergillosis; ROC Curve; Sensitivity and Specificity; Serum

The treatment response in chronic pulmonary aspergillosis (CPA) is usually assessed based on the improvement in clinical and imaging findings. Herein, we evaluate serum Aspergillus fumigatus-specific IgG, serum galactomannan, weight change, and lung function for assessing treatment response in subjects with CPA.. We categorized treatment response as favourable (improved or stable clinical response with radiologically improved or stable disease) or unfavourable (worsening of symptoms or radiological progression) after 6 months of treatment with antifungal azoles. We measured A. fumigatus-specific IgG, serum galactomannan, weight, and lung function at baseline, 3 months, and 6 months in those with favourable and unfavourable treatment response.. One hundred and twenty-six consecutive treatment-naïve subjects (53.2% (67/126) males; mean ± SD age, 42.3 ± 14.7 years) with CPA were included. One hundred and six and 20 were classified as having favourable and unfavourable response, respectively. After 6 months of treatment, the decline in serum A. fumigatus-specific IgG (n = 119) was similar in those with favourable or unfavourable response (mean ± SD, -26.3 ± 45.5 mgA/L vs. -3.4 ± 65.6 mgA/L; p 0.20). There was no significant change in the serum galactomannan (favourable vs. unfavourable: mean ± SD, -0.11 ± 2.8 vs. -0.62 ± 2; p 0.92) or FEV1 (favourable vs. unfavourable: mean ± SD, 24 ± 250 mL vs. -62 ± 154 mL; p 0.19) after 6 months of treatment. There was significant loss of weight (mean ± SD, -2.5 ± 4.5 kg) in subjects with unfavourable response.. Serum A. fumigatus-specific IgG and serum galactomannan inconsistently decrease following treatment and may not be useful indicators for monitoring treatment response in CPA. Similarly, there is little change in pulmonary function following treatment. A gain in body weight is seen in those with favourable response.

Topics: Adult; Antibodies, Fungal; Antifungal Agents; Azoles; Body Weight; Chronic Disease; Female; Follow-Up Studies; Galactose; Humans; Immunoglobulin G; Lung; Male; Mannans; Middle Aged; Prospective Studies; Pulmonary Aspergillosis; Treatment Outcome

To improve the quality of invasive pulmonary aspergillosis (IPA) management for intensive care unit (ICU) patients using a practical diagnostic scoring model.. This nested case-control study aimed to determine the incidence of IPA in 405 ICU patients, between July 2012 and June 2014, at 6 hospitals in Jakarta, Indonesia. Phenotypic identifications and galactomannan (GM) tests of sera and lung excreta were performed in mycology laboratory, Parasitology Department, Faculty of Medicine, Universitas Indonesia in Jakarta, Indonesia.. The incidence of IPA in the ICUs was 7.7% (31 of 405 patients). A scoring model used for IPA diagnosis showed 4 variables as the most potential risk factors: lung excreta GM index (score 2), solid organ malignancy (score 2), pulmonary tuberculosis (score 2), and systemic corticosteroids (score 1). Patients were included in a high-risk group if their score was greater than 2, and in a low-risk group if their score was less than 2.. This study provides a novel diagnosis scoring model to predict IPA in ICU patients. Using this model, a more rapid diagnosis and treatment of IPA may be possible. The application of the diagnosis scoring should be preceded by specified pre-requisites.

Topics: Adrenal Cortex Hormones; Case-Control Studies; Galactose; Humans; Incidence; Indonesia; Intensive Care Units; Mannans; Middle Aged; Neoplasms; Predictive Value of Tests; Pulmonary Aspergillosis; Risk Factors; Tuberculosis, Pulmonary

The growing emergence of azole-resistant Aspergillus fumigatus strains worldwide is a major concern for current systemic antifungal treatment. Here we report antifungal activities of a novel inhaled triazole, PC1244, against a collection of multi-azole-resistant A. fumigatus strains.. MICs of PC1244 were determined for A. fumigatus carrying TR34/L98H (n = 81), TR46/Y121F/T289A (n = 24), M220 (n = 6), G54 (n = 11), TR53 (n = 1), TR463/Y121F/T289A (n = 2), G448S (n = 1), G432C (n = 1) and P216S (n = 1) resistance alleles originating from either India, the Netherlands or France. The effects of PC1244 were confirmed in an in vitro model of the human alveolus and in vivo in temporarily neutropenic, immunocompromised mice.. PC1244 exhibited potent inhibition [geometric mean MIC (range), 1.0 mg/L (0.125 to >8 mg/L)] of growth of A. fumigatus strains carrying cyp51A gene mutations, showing much greater potency than voriconazole [15 mg/L (0.5 to >16 mg/L)], and an effect similar to those on other azole-susceptible Aspergillus spp. (Aspergillus flavus, Aspergillus terreus, Aspergillus tubingensis, Aspergillus nidulans, Aspergillus niger, Aspergillus nomius, Aspergillus tamarii) (0.18-1 mg/L). In TR34/L98H and TR46/Y121F/T289A A. fumigatus-infected in vitro human alveolus models, PC1244 achieved superior inhibition (IC50, 0.25 and 0.34 mg/L, respectively) compared with that of voriconazole (IC90, >3 mg/L and >10 mg/L, respectively). In vivo, once-daily intranasal administration of PC1244 (0.56-70 μg/mouse) to the A. fumigatus (AF91 with M220V)-infected mice reduced pulmonary fungal load and serum galactomannan more than intranasal posaconazole.. PC1244 has the potential to become a novel topical treatment of azole-resistant pulmonary aspergillosis.

Topics: Animals; Antifungal Agents; Aspergillus; Colony Count, Microbial; Disease Models, Animal; France; Galactose; Humans; India; Lung; Mannans; Mice; Microbial Sensitivity Tests; Netherlands; Pulmonary Aspergillosis; Treatment Outcome; Triazoles

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

Aspergillus fumigatus-specific IgG is pivotal in making the diagnosis of chronic pulmonary aspergillosis (CPA). However, the cut-off value for A. fumigatus-specific IgG remains unknown. We included consecutive treatment-naïve subjects with chronic cavitary pulmonary aspergillosis (CCPA, cases). The controls were subjects with treated pulmonary tuberculosis, who had residual radiological abnormality and minimal symptoms. The diagnosis of CCPA was based on consistent clinicoradiological features along with demonstration of Aspergillus infection (growth of Aspergillus in sputum or bronchoalveolar lavage fluid [BALF] culture; serum or BALF galactomannan index >0.5 and >1, respectively). For determining the cut-off of A. fumigatus-specific IgG (Phadia), subjects were randomly classified as derivation (two-thirds) and validation (one-third) cohort. One hundred and thirty-seven cases and 50 controls were included. The best cut-off value for A. fumigatus-specific IgG (derivation cohort) was 27.3 mgA/L (AUROC, 0.976) at a sensitivity and specificity of 95.6% and 100%, respectively. Using a cut-off of 27 mgA/L, the sensitivity and specificity in the validation cohort was 91.3% and 100%, respectively. In contrast, the sensitivity of Aspergillus precipitins was only 25.5%. At a cut-off value of 27 mgA/L, A. fumigatus-specific IgG is a reliable test with high sensitivity and specificity in the diagnosis of CPA. More studies are required to confirm our findings.

Topics: Adult; Aged; Antibodies, Fungal; Aspergillus fumigatus; Chronic Disease; Female; Galactose; Humans; Immunoglobulin G; Male; Mannans; Middle Aged; Prospective Studies; Pulmonary Aspergillosis; Radiography, Thoracic; ROC Curve; Sensitivity and Specificity

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

Galactomannan (GM) and Aspergillus DNA detection are useful tools for the diagnosis of invasive pulmonary aspergillosis (IPA), primarily in blood and bronchoscopy samples. This study aimed to evaluate the utility of both markers for detection of Aspergillus in sputum from patients with allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA).. ABPA or CPA demographic patient data were retrieved. This retrospective observational audit included 159 patients with at least one sputum pair. 223 sputum sample pairs were analysed, as well as six control samples for GM only. Real time PCR was performed following sputum DNA extraction using the MycAssay™ Aspergillus kit and cycle thresholds were subtracted from 38 to give positive values (transformed Ct, TCt).. The mean age of the patients was 61.81years (SD: ±11.06; range 29-100). One hundred and twenty-six (79.2%) had CPA. Cultures were positive for fungi in 13.1% of the samples, and A. fumigatus was the commonest (11.9%) fungus isolated. Receiver operating characteristic (ROC curve) analysis of sputum GM comparing TCt of >0.0, and >2.0 to derive GMI cut-off values showed a cut-off of 6.5. About 50% of sputa with strongly positive PCR values had GM values>6.5. Two of six (33%) control samples had GM indices>6.5.. It is not clear that GM determinations in sputum are useful for diagnosis of either CPA or ABPA, or following therapy.

Topics: Adult; Aged; Aged, 80 and over; Aspergillosis, Allergic Bronchopulmonary; Aspergillus; Biomarkers; Bronchoalveolar Lavage Fluid; Chronic Disease; DNA, Fungal; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Humans; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Pulmonary Aspergillosis; Retrospective Studies; ROC Curve; Sputum

Topics: Antigens, Fungal; Bronchoalveolar Lavage Fluid; False Negative Reactions; Galactose; Humans; Mannans; Pulmonary Aspergillosis; Specimen Handling

A steroid-immunosuppressed rat model of invasive pulmonary aspergillosis was use to examine the usefulness of galactomannan enzyme immunoassay (GM) and quantitative real time PCR (RT-PCR) in evaluating the association between response and exposure after a high dose of prophylactic posaconazole.. Two different strains of Aspergillus fumigatus with different in vitro posaconazole susceptibility were used.. Serum concentrations demonstrated similar posaconazole exposure for all treated animals. However, response to posaconazole relied on the in vitro susceptibility of the infecting strain. After prophylaxis, galactomannan index and fungal burden only decreased in those animals infected with the most susceptible strain.. This study demonstrated that both biomarkers may be useful tools for predicting efficacy of antifungal compounds in prophylaxis.

Topics: Animals; Antifungal Agents; Biomarkers; Galactose; Immunoenzyme Techniques; Mannans; Pulmonary Aspergillosis; Rats; Real-Time Polymerase Chain Reaction; Triazoles

In recent years, infections caused by Aspergillus sp. have become an emerging focus of clinical microbiology and infectious disease, as the number of patients infected with Aspergillus sp. has increased markedly. Although chronic pulmonary aspergillosis (CPA) is considered a 'semi-invasive' or 'intermediate' disease, little data are available for the direct comparison of CPA with invasive pulmonary aspergillosis (IPA) and pulmonary aspergilloma (PA) to quantify invasiveness. In this study, we compared the characteristics of CPA with those of IPA and PA among hospitalized patients over a 10-year period. A total of 29, 51 and 31 cases of CPA, IPA and PA, respectively, were included. An increasing trend in galactomannan antigen seropositivity rate from PA (24.1%) to CPA (35.7%) to IPA (54.9%) and an opposite trend for anti-Aspergillus antibody (PA (71.0%) to CPA (45.8%) to IPA (7.1%)) were observed. Eight percent of CPA patients were infected with more than one Aspergillus sp. The survival rate of the CPA group also fell between the survival rate of PA and IPA, confirming the intermediate severity of CPA. The survival rate of the CPA group became significantly higher than that of the IPA group from day 180 onwards until 2 years after admission (P<0.05). The survival rate of the CPA group remained lower than that of the PA group from day 30 onwards until 2 years after admission. Poor prognostic factors for CPA included older age (P=0.019), higher total leukocyte count (P=0.011) and higher neutrophil count (P=0.012) on admission. This study provided clinical and laboratory evidence for the semi-invasive properties of CPA.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Fungal; Aspergillus; Child; Chronic Disease; Female; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Microbiological Techniques; Middle Aged; Prognosis; Pulmonary Aspergillosis; Survival Rate; Time Factors; Young Adult

Topics: Antigens; Biomarkers; Bronchoalveolar Lavage Fluid; Chromatography, Affinity; Cryptococcosis; Galactose; Humans; Latex Fixation Tests; Mannans; Polysaccharides; Pulmonary Aspergillosis

Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus, Aspergillus flavus, or Aspergillus niger is associated with high mortality. We evaluated the efficacy and compared the therapeutic effect differences of voriconazole (VRC) in combination with caspofungin (CAS) in transiently neutropenic rats infected by A. fumigatus, A. flavus, or A. niger.. Treatment groups consisted of VRC (10 mg/kg q12 h) monotherapy, CAS (1 mg/kg/day) monotherapy, combination of VRC (10 mg/kg q12 h) + CAS (1 mg/kg/day), and no drug for 10 consecutive days. The efficacy and the difference in the treatments were evaluated through prolongation of survival, reduction in serum galactomannan levels and residual fungal burden, and histological studies.. For all the strains, the combination of VRC and CAS led to significant prolongation in survival (P < 0.05) and reduction in residual fungal burden (P < 0.05) compared with CAS alone, and decrease in serum galactomannan levels (P < 0.05) compared with either agent alone. The survival in the combined therapy groups was significantly improved compared to VRC monotherapy for the strains of A. flavus and A. niger (P < 0.05), but no significant difference for the strains of A. fumigatus (P > 0.05).. Combination of VRC and CAS was synergistic in IPA by A. flavus and A. niger, but small efficacy benefits in IPA by A. fumigatus.

Topics: Animals; Antifungal Agents; Aspergillus flavus; Aspergillus fumigatus; Aspergillus niger; Caspofungin; Disease Models, Animal; Drug Therapy, Combination; Echinocandins; Galactose; Humans; Lipopeptides; Male; Mannans; Microbial Sensitivity Tests; Neutropenia; Pulmonary Aspergillosis; Pyrimidines; Rats; Rats, Sprague-Dawley; Treatment Outcome; Triazoles; Voriconazole

A serum galactomannan (GM) antigen test has been widely used to diagnose invasive pulmonary aspergillosis. However, there are limited data on the use of the serum GM antigen test for the serologic diagnosis of chronic pulmonary aspergillosis (CPA).. Data were collected from all consecutive patients with a clinical suspicion of CPA who underwent a serum GM antigen test.. In total, 334 patients who were suspected to have CPA were eligible for this study and 168 (50%) patients were finally diagnosed with CPA. The serum GM antigen test was positive in 38 (23%) patients with CPA and in 25 (15%) patients without CPA. The sensitivity of the serum GM antigen test was 23% (95% confidence interval [CI], 17-30%), and its specificity was 85% (95% CI, 79-90%), with positive and negative predictive values of 60% (95% CI, 47-72%) and 52% (95% CI, 46-58%), respectively. The accuracy of the test was 54%. The area under the receiver operating characteristic curve was 0.538 (95% CI, 0.496-0.580).. The serum GM antigen test could not be used for the serologic diagnosis of CPA.

Topics: Aged; Antigens, Fungal; Biomarkers; Chronic Disease; Female; Galactose; Humans; Male; Mannans; Middle Aged; Predictive Value of Tests; Pulmonary Aspergillosis; Sensitivity and Specificity; Serologic Tests; Serum

The diagnosis of pulmonary aspergillosis is difficult because the sensitivity of the conventional methods for the detection of Aspergillus such as culture and cytology, is poor. To improve the sensitivity for Aspergillus detection, the detection of galactomannan antigen has been investigated. The serum galactomannan (GM) antigen has been recognized to be a useful tool for the diagnosis of invasive pulmonary aspergillosis. However, the utility of the galactomannan antigen for the diagnosis of pulmonary aspergillosis other than invasive pulmonary aspergillosis (IPA) has been unclear.. The GM antigen using serum and bronchial washing (BW) using bronchofiberscopy for the diagnosis of pulmonary aspergillosis other than IPA were measured.. In 45 enrolled patients, 7 patients had pulmonary aspergillosis, 5 of these patients had chronic necrotizing pulmonary aspergillosis and 2 patients had allergic bronchopulmonary aspergillosis. The area under the receiver operating characteristic (ROC) curve was 0.89 for the BW GM antigen detection test, and 0.41 for the serum GM antigen detection test, suggesting that the BW GM antigen detection test exhibits a better diagnostic performance than the serum GM antigen detection test. The BW GM antigen detection test had a sensitivity of 85.7% and a specificity of 76.3% at a cut-off level of ≥0.5, which was the optimal cut-off level obtained by the ROC curve.. The BW GM antigen detection test is thought to be a promising test for the diagnosis of pulmonary aspergillosis other than IPA.

Topics: Aged; Antigens, Fungal; Aspergillosis, Allergic Bronchopulmonary; Aspergillus; Biomarkers; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchoscopy; Female; Galactose; Humans; Male; Mannans; Middle Aged; Pulmonary Aspergillosis; Sensitivity and Specificity

Fungal infections of lung have become increasingly common during the last few decades. Aspergillosis and the role of aflatoxins in various chronic lung diseases have not been extensively studied. Bronchoalveolar lavage (BAL) samples and sera from 40 patients of chronic lung diseases were analyzed for galactomannan antigen (GM) and aflatoxin by enzyme-linked immunosorbent assay. Direct microscopy and culture of BAL samples were also done to detect the Aspergillus species. Results revealed that 15 (37.5 %) of the 40 patients had growth of Aspergillus on BAL culture. Out of these culture-positive cases, 13 (86.7 %) patients were positive for galactomannan antigen also. About 62.5 % cases did not show growth of Aspergillus in BAL culture. However, galactomannan antigen could be detected in 20 % of these patients. Overall, 20 % patients were diagnosed as proven invasive fungal disease (IFD), 32.5 % were of probable IFD, 17.5 % of possible IFD. Aspergillus growth was observed in 100 % of proven and 53.8 % of probable IFD cases. Galactomannan antigen was found in 100 % cases of proven and 76.9 % of probable IFD. Ten (25 %) patients were found to be positive for aflatoxins. It was detected in 6 (40 %) of culture-positive cases. About 62.5 % of the cases with proven IFD and 46.1 % of probable IFD had aflatoxin in their samples. Aflatoxin positivity was found to be more in patients with proven IFD than in probable IFD, and higher level of aflatoxins was detected in cases with proven IFD. Significant difference was observed in aflatoxin positivity among food grain workers when compared to other occupations.

Topics: Aflatoxins; Aspergillus; Bronchoalveolar Lavage Fluid; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Humans; Male; Mannans; Microbiological Techniques; Microscopy; Middle Aged; Pulmonary Aspergillosis; Serum

To describe and estimate the rate of breakthrough invasive mould diseases (IMD) in patients receiving caspofungin.. Retrospective, non-interventional study conducted in three University Hospitals.. Nineteen breakthrough infections have been identified including 13 aspergillosis, 2 mucormycosis, a fusariosis, a Hormographiella aspergillata infection and 2 possible IMD. Cases were equally distributed between the centres. Fourteen patients had a haematologic malignancy, four were transplant recipients (allogeneic haematopoietic stem cells in three, liver in one) and one had hepatic cirrhosis. Caspofungin has been prescribed as prophylaxis (n = 3), empirical therapy (n = 9) or directed therapy for candidemia (n = 5) or aspergillosis (n = 2). Aspergillus galactomannan was positive in serum or in bronchoalveolar lavage fluid in 10 of the 13 aspergillosis. Median duration of caspofungin treatment before breakthrough IMD was 15 days. Nine patients died within twelve weeks. Rate of breakthrough IMD in onco-haematology patients has been estimated to 7.3% for all mould infections and to 4.2% when restricted to documented aspergillosis.. Our data call for Aspergillus galactomannan monitoring and close clinical and radiological examination in case of persistence or recurrence of infection signs in high-risk patients receiving caspofungin.

Topics: Adult; Aged; Antifungal Agents; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; France; Fusariosis; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hospitals, University; Humans; Lipopeptides; Male; Mannans; Middle Aged; Mucormycosis; Pulmonary Aspergillosis

Diagnosing chronic pulmonary aspergillosis (CPA) is complicated, and there are limited data available regarding the identification of galactomannan (GM) in clinical specimens to assist the detection of this infection. The purpose of this study was to evaluate the detection of GM in bronchoalveolar lavage fluid (BALF) and serum and to assess its utility for diagnosing CPA. We retrospectively reviewed the diagnostic and clinical characteristics of 144 patients, with and without CPA, in Nagasaki University Hospital, Japan, whose BAL and serum specimens were examined for the presence of GM. The Platelia Aspergillus enzyme immunoassay (PA EIA) was performed according to the manufacturer's instructions. The mean values of BALF GM antigen were 4.535 (range, 0.062-14.120) and 0.430 (range, 0.062-9.285) in CPA (18) and non-CPA (126) patients, respectively. The mean values of serum GM antigen were 1.557 (range, 0.232-5.397) and 0.864 (range, 0.028-8.956) in CPA and non-CPA patients, respectively. PA EIA of BALF is superior to the test with serum, with the optimal cut-off values for BALF and serum of 0.4 and 0.7, respectively. The sensitivity and specificity of PA EIA in BALF at a cut-off of 0.4 were 77.2% and 77.0%, respectively, whereas with serum at a cut-off of 0.7, they were 66.7% and 63.5%, respectively. GM testing using BALF showed reasonable sensitivity and specificity as compared to that using serum. Thus, assessing GM levels in BALF may enhance the accuracy of diagnosing CPA.

Topics: Adult; Aged; Aged, 80 and over; Aspergillus; Bronchoalveolar Lavage Fluid; Chronic Disease; Clinical Laboratory Techniques; Female; Galactose; Humans; Immunoenzyme Techniques; Japan; Male; Mannans; Middle Aged; Pulmonary Aspergillosis; Retrospective Studies; Sensitivity and Specificity; Serum; Young Adult

This study evaluated the pharmacological activity of PTX3, administered in combination with voriconazole, in a rat model of pulmonary aspergillosis. The data indicated additive therapeutic activities of these compounds, as demonstrated by the amelioration of respiratory function changes, reduction of lung fungal burden, and increased survival. Overall, we provide clear evidence that the combination of PTX3 with a suboptimal dose of voriconazole might represent a therapeutic option under those clinical conditions where the use of voriconazole alone is not warranted for efficacy and tolerability reasons.

Topics: Animals; Antifungal Agents; Body Burden; C-Reactive Protein; Colony Count, Microbial; Cortisone; Drug Combinations; Galactose; Immunosuppressive Agents; Kaplan-Meier Estimate; Lung; Mannans; Organ Size; Pulmonary Aspergillosis; Pyrimidines; Rats; Respiratory Function Tests; Serum Amyloid P-Component; Survival; Triazoles; Voriconazole

The sensitivities of the serum and bronchoalveolar lavage galactomannan (GM) assays in 48 patients with pulmonary aspergilloma were 38% (13 of 34; 95% confidence interval [CI], 22%-56%) and 92% (33 of 36; 95% CI, 78%-98%), respectively. The positivity of serum GM assays was significantly higher in patients with hemoptysis than in those without hemoptysis (52% vs 9%; P=.02).

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Clinical Laboratory Techniques; Female; Galactose; Humans; Male; Mannans; Middle Aged; Pulmonary Aspergillosis; Sensitivity and Specificity; Serum

Culture-independent molecular techniques such as real-time PCRs offer the potential for early diagnosis of invasive aspergillosis (IA), thereby reducing the disease-associated mortality rate. PCR-based testing is presently excluded from disease-defining consensus criteria due to lack of standardization and clinical validation. A single-center prospective study was conducted to investigate the performance of the commercially available MycAssay Aspergillus test for detecting Aspergillus DNA in patients with suspicion of IA. To this end, a total of 158 bronchoalveolar lavage (BAL) fluid specimens that were consecutively collected from hematology (n = 68) and intensive care unit (n = 90) patients were examined. Sixteen of 17 (94.1%) specimens from patients with proven/probable IA were MycAssay positive, and 15 of these 16 patients were also positive by an "in-house" PCR assay. A total of 139 of 141 (98.6%) specimens from patients without proven/probable IA were MycAssay negative. Fifteen of 16 (94.1%) MycAssay-positive patients were also positive for BAL fluid galactomannan (GM) at an index cutoff of ≥1.0 (index range, 1.1 to 8.3), as were 3 patients without IA but with pulmonary fusariosis. Interestingly, in seven of the PCR-positive BAL specimens that tested culture positive for Aspergillus species, cycle threshold values were earlier than those of specimens with a culture-negative result. In conclusion, the MycAssay Aspergillus PCR appears to be a sensitive and specific molecular test for the diagnosis of IA, and its performance is comparable to that of the GM assay. However, more large studies are necessary to firmly establish its clinical utility in high-risk settings.

Topics: Aspergillus; Bacteriological Techniques; Bronchoalveolar Lavage Fluid; Galactose; Humans; Immunoenzyme Techniques; Mannans; Molecular Diagnostic Techniques; Prospective Studies; Pulmonary Aspergillosis; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity

Invasive pulmonary aspergillosis (IPA) is difficult to diagnose. The detection of galactomannan (GM) in serum samples is useful for diagnosing IPA. A positive test for GM antigen in BAL has also been proposed as a criterion of IPA, although it has not been fully validated. The aim of our study was to evaluate the contribution of GM antigen detection in BAL to the diagnosis of IPA in hematologic patients.. One hundred one consecutive patients treated for hematologic malignancy were explored by bronchoscopy and BAL for new pulmonary infiltrates. Both BAL fluid and serum samples were evaluated for GM using an enzyme-linked immunosorbent assay test, with an optical density index >or= 0.5 considered positive. Respiratory samples were also examined for the presence of fungi.. IPA was diagnosed in 33 patients according to European Organization for Research and Treatment of Cancer and Mycoses Study Group consensus group criteria (six proven, 23 probable, four possible). Nineteen of these 33 patients had a positive BAL GM test, whereas three patients without IPA had false-positive results. GM detection in BAL had a sensitivity of 57.6% (95% CI, 40.8%-72.8%) and a specificity of 95.6% (95% CI, 87.8%-98.5%). Among the 19 patients with IPA whose BAL was positive for GM, 15 also had a positive serum GM test. In 11 of these 19 patients, Aspergillus was identified in the respiratory samples.. Detection of GM in BAL is complementary of serum GM testing and mycologic evaluation of the respiratory samples for the diagnosis of IPA. Positive GM BAL was the sole microbiologic criterion in two of 33 patients studied.

Topics: Adult; Antigens; Bronchoalveolar Lavage Fluid; Bronchoscopy; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Pulmonary Aspergillosis; Reproducibility of Results; Retrospective Studies; Severity of Illness Index

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

We studied the antifungal activity of anidulafungin (AFG) in combination with voriconazole (VRC) against experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits and further explored the in vitro and in vivo correlations by using Bliss independence drug interaction analysis. Treatment groups consisted of those receiving AFG at 5 (AFG5 group) and 10 (AFG10 group) mg/kg of body weight/day, VRC at 10 mg/kg every 8 h (VRC group), AFG5 plus VRC (AFG5+VRC group), and AFG10 plus VRC (AFG10+VRC group) and untreated controls. Survival throughout the study was 60% for the AFG5+VRC group, 50% for the VRC group, 27% for the AFG10+VRC group, 22% for the AFG5 group, 18% for the AFG10 group, and 0% for control rabbits (P < 0.001). There was a significant reduction of organism-mediated pulmonary injury, measured by infarct scores, lung weights, residual fungal burdens, and galactomannan indexes, in AFG5+VRC-treated rabbits versus those treated with AFG5 and VRC alone (P < 0.05). In comparison, AFG10+VRC significantly lowered only infarct scores and lung weights in comparison to those of AFG10-treated animals (P < 0.05). AFG10+VRC showed no significant difference in other outcome variables. Significant Bliss synergy was found in vivo between AFG5 and VRC, with observed effects being 24 to 30% higher than expected levels if the drugs were acting independently. These synergistic interactions were also found between AFG and VRC in vitro. However, for AFG10+VRC, only independence and antagonism were observed among the outcome variables. We concluded that the combination of AFG with VRC in treatment of experimental IPA in persistently neutropenic rabbits was independent to synergistic at a dosage of 5 mg/kg/day but independent to antagonistic at 10 mg/kg/day, as assessed by Bliss independence analysis, suggesting that higher dosages of an echinocandin may be deleterious to the combination.

Topics: Anidulafungin; Animals; Antifungal Agents; Area Under Curve; Bronchoalveolar Lavage Fluid; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Echinocandins; Female; Galactose; Humans; Mannans; Pulmonary Aspergillosis; Pyrimidines; Rabbits; Triazoles; Voriconazole