Performance of mNGS in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients
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PROVIDER: S-EPMC10644336 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC7249715 | biostudies-literature
Project description:BackgroundInvasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplantation. Early diagnosis and therapy has been shown to improve outcomes, but reaching a definitive diagnosis quickly can be problematic. Recently, galactomannan testing of bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA, but widespread experience and consensus on optical density (OD) cut-offs remain lacking.MethodsWe performed a prospective case-control study to determine an optimal BAL galactomannan OD cutoff for IPA in at-risk patients with hematological diagnoses. Cases were subjects with hematological diagnoses who met established definitions for proven or probable IPA. There were two control groups: subjects with hematological diagnoses who did not meet definitions for proven or probable IPA and subjects with non-hematological diagnoses who had no evidence of aspergillosis. Following bronchoscopy and BAL, galactomannan testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions.ResultsThere were 10 cases and 52 controls. Cases had higher BAL fluid galactomannan OD indices (median 4.1, range 1.1-7.7) compared with controls (median 0.3, range 0.1-1.1). ROC analysis demonstrated an optimum OD index cutoff of 1.1, with high specificity (98.1%) and sensitivity (100%) for diagnosing IPA.ConclusionsOur results also support BAL galactomannan testing as a reasonably safe test with higher sensitivity compared to serum galactomannan testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid over-diagnosis of IPA, and a standardized method of collection should be established before results can be compared between centers.
| S-EPMC2837869 | biostudies-literature
Project description:BackgroundThe pathogenesis of invasive aspergillosis (IA) is still unknown, but its progression is rapid and mortality rate remains high. Bronchoalveolar lavage fluid (BALF) galactomannan (GM) analysis has been used to diagnose IA. This study is aimed at making an accurate estimate of the whole accuracy of BALF-GM in diagnosing IA.MethodsAfter a systematic review of the study, a bivariate meta-analysis was used to summarize the specificity (SPE), the sensitivity (SEN), the positive likelihood ratios (PLR), and the negative likelihood ratios (NLR) of BALF-GM in diagnosing IA. The overall test performance was summarized using a layered summary receiver operating characteristic (SROC) curve. Subgroup analysis was performed to explore the heterogeneity between studies.ResultsA total of 65 studies that are in line with the inclusion criteria were included. The summary estimates of BALF-GM analysis are divided into four categories. The first is the proven+probable vs. possible+no IA, with an SPE, 0.87 (95% CI, 0.85-0.98); SEN, 0.81 (95% CI, 0.76-0.84); PLR, 9.78 (5.78-16.56); and NLR, 0.20 (0.14-0.29). The AUC was 0.94. The BALF-GM test for proven+probable vs. no IA showed SPE, 0.88 (95% CI, 0.87-0.90); SEN, 0.82 (95% CI, 0.78-0.85); PLR, 6.56 (4.93-8.75); and NLR, 0.24 (0.17-0.33). The AUC was 0.93. The BALF-GM test for proven+probable+possible vs. no IA showed SPE, 0.82 (95% CI, 0.79-0.95); SEN, 0.59 (95% CI, 0.55-0.63); PLR, 3.60 (2.07-6.25); and NLR, 0.31 (0.15-0.61). The AUC was 0.86. The analyses for others showed SPE, 0.85 (95% CI, 0.83-0.87); SEN, 0.89 (95% CI, 0.86-0.91); PLR, 6.91 (4.67-10.22); and NLR, 0.18 (0.13-0.26). The AUC was 0.94.ConclusionsThe findings of this BALF-GM test resulted in some impact on the diagnosis of IA. The BALF-GM assay is considered a method for diagnosing IA with high SEN and SPE. However, the patients' underlying diseases may affect the accuracy of diagnosis. When the cutoff is greater than 1, the sensitivity will be higher.
| S-EPMC7723495 | biostudies-literature
Project description:We studied patients diagnosed with aspergillosis based on positive bronchoalveolar lavage (BAL) Aspergillus galactomannan (GM) who had follow-up BAL sampling within 180 days. GM trend and clinical outcome were concordant in only 60% (30/50). While useful for the initial diagnosis, BAL GM trending does not always correlate with treatment response.
| S-EPMC10977621 | biostudies-literature
Project description:BackgroundThe Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits.MethodsWe performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany.ResultsCases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval [CI] .815-.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers.ConclusionsIn this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.
| S-EPMC8492156 | biostudies-literature
Project description:ObjectiveTo assess the diagnostic efficacy of metagenomic next generation sequencing (mNGS) for proven invasive pulmonary aspergillosis (IPA).MethodsA total of 190 patients including 53 patients who had been diagnosed with proven IPA were retrospectively analyzed. Using the pathological results of tissue biopsy specimens as gold standard, we ploted the receiver operating characteristic (ROC) curve to determine the optimal cut-off value of mNGS species-specific read number (SSRN) of Aspergillus in bronchoalveolar lavage fluid (BALF)for IPA. Furthermore, we evaluated optimal cut-off value of mNGS SSRN in different populations.ResultsThe optimal cut-off value of Aspergillus mNGS SSRN in BALF for IPA diagnosis was 2.5 for the whole suspected IPA population, and 1 and 4.5 for immunocompromised and diabetic patients, respectively. The accuracy of mNGS was 80.5%, 73.7% and 85.3% for the whole population, immunocompromised and diabetic patients, respectively.ConclusionsThe mNGS in BALF has a high diagnostic efficacy for proven IPA, superioring to Aspergillus culture in sputum and BALF and GM test in blood and BALF. However, the cut-off value of SSRN should be adjusted when in different population.
| S-EPMC10484620 | biostudies-literature
Project description:Background: Invasive pulmonary aspergillosis (IPA) is an infection that primarily affects immunocompromised hosts, including hematological patients and stem-cell transplant recipients. The diagnosis of IPA remains challenging, making desirable the availability of new specific biomarkers. High-throughput methods now allow us to interrogate the immune system for multiple markers of inflammation with enhanced resolution. Methods: To determine whether a signature of alveolar cytokines could be associated with the development of IPA and used as a diagnostic biomarker, we performed a nested case-control study involving 113 patients at-risk. Results: Among the 32 analytes tested, IL-1β, IL-6, IL-8, IL-17A, IL-23, and TNFα were significantly increased among patients with IPA, defining two clusters able to accurately differentiate cases of infection from controls. Genetic variants previously reported to confer increased risk of IPA compromised the production of specific cytokines and impaired their discriminatory potential toward infection. Collectively, our data indicated that IL-8 was the best performing cytokine, with alveolar levels ≥904 pg/mL predicting IPA with elevated sensitivity (90%), specificity (73%), and negative predictive value (88%). Conclusions: These findings highlight the existence of a specific profile of alveolar cytokines, with IL-8 being the dominant discriminator, which might be useful in supporting current diagnostic approaches for IPA.
| S-EPMC5712575 | biostudies-literature
Project description:Galactomannan detection in bronchoalveolar lavage (BAL) fluid samples (GM test) is currently considered the gold standard test for diagnosing invasive pulmonary aspergillosis (IPA). The limitations, however, are the various turnaround times and availability of testing. We compared the performance of GM testing with that of conventional culture, an Aspergillus lateral-flow-device (LFD) test, a beta-d-glucan (BDG) test, and an Aspergillus PCR assay by using BAL fluid samples from immunocompromised patients. A total of 78 BAL fluid samples from 78 patients at risk for IPA (74 samples from Graz and 4 from Mannheim) collected between December 2012 and May 2013 at two university hospitals in Austria and Germany were included. Three patients had proven IPA, 14 probable IPA, and 17 possible IPA, and 44 patients had no IPA. The diagnostic accuracies of the different methods for probable/proven IPA were evaluated. The diagnostic odds ratios were the highest for the GM, PCR, and LFD tests. The sensitivities for the four methods (except culture) were between 70 and 88%. The combination of the GM (cutoff optical density index [ODI], >1.0) and LFD tests increased the sensitivity to 94%, while the combination of the GM test (>1.0) and PCR resulted in 100% sensitivity (specificity for probable/proven IPA, 95 to 98%). The performance of conventional culture was limited by low sensitivity, while that of the BDG test was limited by low specificity. We evaluated established and novel diagnostic methods for IPA and found that the Aspergillus PCR, LFD, and GM tests were the most useful methods for diagnosing the disease by using BAL fluid samples. In particular, the combination of the GM test and PCR or, if PCR is not available, the LFD test, allows for sensitive and specific diagnosis of IPA.
| S-EPMC4042784 | biostudies-literature
Project description:PCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic review assessing the diagnostic accuracy of PCR in BAL fluid with a direct comparison versus galactomannan (GM) in BAL fluid. We included prospective and retrospective cohort and case-control studies. Studies were included if they used the EORTC/MSG consensus definition criteria of IPA and assessed ?80% of patients at risk for IPA. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Nineteen studies published between 1993 and 2012 were included. The summary sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for reference standard definitions, the summary sensitivity and specificity values (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively. Antifungal treatment before bronchoscopy significantly reduced sensitivity. The diagnostic performance of PCR was similar to that of GM in BAL fluid using an optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a positive result, the pooled sensitivity was higher than that of GM alone, with similar specificity. We conclude that the diagnostic performance of PCR in BAL fluid is good and comparable to that of GM in BAL fluid. Performing both tests results in optimal sensitivity with no loss of specificity. Results are dependent on the reference standard definitions.
| S-EPMC3486225 | biostudies-literature
Project description:Comprehensive proteomic analysis of the protein expression landscape of bronchoalveolar lavage fluid during invasive pulmonary aspergillosis in murine and human samples. 38 murine BALF samples (10 Aspergillus fumigatus infected mice without immunosuppression and without invasive pulmonary aspergillosis (IPA), 19 immunosuppressed and infected mice with IPA and 9 immunosuppressed animals without infection) were analysed for their global protein expression. In addition, 54 human BALF specimen from patients with probable IPA (23 samples), proven IPA (4 cases) and 27 control samples from patients with unrelated pulmonary diseases were analysed for their global protein composition. Host responses and Aspergillus fumigatus-specific proteins detectable in BALF were studied.
2020-10-14 | PXD016664 | Pride