Invasive Pulmonary Aspergillosis Group Research Articles

Value Evaluation of Quantitative Aspergillus fumigatus-Specific IgG Antibody Test in the Diagnosis of Non-neutropenic Invasive Pulmonary Aspergillosis.

The role of Aspergillus-specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited. This study aims to evaluate the quantitative test value of Aspergillus fumigatus-specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis. This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of Aspergillus-specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy. The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2±9.6 (33-79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, P=0.027; 33.9% vs 14.7%, P =0.011, respectively). The level of Aspergillus fumigatus-specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1±167.0 vs 62.6±58.0, P<0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 P<0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL. Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and Aspergillus-specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.

Improved diagnostic markers for invasive pulmonary aspergillosis in COPD patients.

The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection. This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients. The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration. Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Different Epidemiology and Characteristics of Invasive Pulmonary Aspergillosis in Acute Lymphoid Leukemia in Comparison with AML: Results of a Prospective Multicentric Observational Study of the Rete Ematologica Lombarda (REL)

Introduction. Invasive pulmonary aspergillosis (IPA) still affects the outcome of acute leukemia (AL) patients (pts). Although this aspect is better defined in acute myeloid leukemia (AML) ( Candoni et al, Mycoses 2020), some reports show a dismal impact also in acute lymphoid leukemia (ALL) ( Cattaneo et al, Leuk Lymphoma 2019). However, data concerning the epidemiology of IPA in adult ALL patients, as well as the best antifungal prophylaxis strategy, are still lacking. Therefore, to describe the incidence of IPA in AL pts and their clinical characteristics, as well as the predisposing factors, we carried out a prospective multicentric observational study within the Rete Ematologica Lombarda (REL). Methods. All consecutive AL patients diagnosed during a 3-year period and treated with curative intent were recorded. Diagnosis of IPA was defined according to EORTC/MSG criteria ( Donnelly et al, Clin Infect Dis 2020). Data concerning age, gender, AL type, chemotherapy (cht) received, complete remission (CR) achievement, antifungal prophylaxis, duration of neutropenia and 30-day mortality were collected. Patient's characteristics were analysed by standard descriptive statistics. The Student's t-test was used to compare continuous values; the Fisher's exact test was used to compare differences in percentage. P values below 0.05 were considered statistically significant. Results. Between 2018 and 2020, 207 AL pts (AML: 165, ALL: 42) were evaluated in five Hospitals participating to the REL. Median age of the whole cohort was 58y, and M/F ratio 112/95. After induction treatment, CR was achieved in 153 of the 200 evaluable pts (76.5%), more frequently in ALL (38/42, 90.5%) than in AML pts (115/158, 72.8%) (p=0.0146). During induction cht, proven/probable (p/p) and possible (poss) IPA were diagnosed in 32/207 pts (15.4%), equally divided in p/p and poss (16 each, 7.7%). P/p IPA were more frequent in ALL than in AML (ALL: 7/42, 16.6% vs AML: 9/165, 5.4%; p= 0.0235); similarly, considering also poss IPA, incidence was higher, even if not significantly (9/42, 21.4% vs 23/165, 13.9%; p=0.2374). Among ALL pts, IPA was more frequent in pts not achieving CR (2/4, 50%) than CR pts (7/38, 18%), whereas in AML CR achievement did not influence IPA frequency (CR group: 15/115, 13%; no CR group: 7/43: 16.5%). ALL pts were uniformly treated with pediatric-like protocols; in AML pts no statistically significant differences in IPA incidence were observed according to cht received (3+7/like: 13/81, 16%; 3+7+midostaurin: 2/27, 7.4%; FLAG-Ida: 3/21, 14.3%; CPX-351: 4/19, 21%). Antimould prophylaxis was protective against IPA in 202 evaluable pts (Yes: 22/171, 12.9%; No: 10/31, 32.3%, p=0.0134). Among ALL pts only 1 out of 15 (6.7%) receiving antimould prophylaxis developed IPA, as compared to 8/27 (29.6%) of those not receiving antimould prophylaxis (p=0.1235). All but two AML pts developing IPA were on posaconazole prophylaxis. Both mean age and duration of neutropenia were significantly lower in ALL than in AML pts (46.02y vs 57.75y, p&amp;lt;0.0001 and 16.66d vs27.96d, p&amp;lt;0.0001); however, an impact of mean duration of neutropenia on IPA incidence was observed only in ALL pts (IPA group: 24.38d; no IPA group: 14.79d, p=0.0359). Only 2 AML pts died at 30d: 1 (3.1%) out of 32 pts with IPA and 1 (0.6%) out of 175 pts without. No early death was observed in ALL pts. Table 1 summarizes the clinical characteristics of AL pts in relation to IPA. Conclusions. Despite younger age, shorter duration of neutropenia and higher percentage of CR achievement, IPA, particularly p/p, was more frequently observed in ALL pts than AML during induction cht. High dose induction cht seems to have no impact in IPA incidence in AML pts. On the other hand, intensive cht ALL protocols, including high doses of dexamethasone, could have a role in IPA development, as well as the lack of antimould prophylaxis, which is confirmed as a predictive factor for IPA. Therefore, studies with antimould agents as prophylaxis against aspergillosis in ALL pts during inductions would be desirable.

Performance of mNGS in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients.

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT.TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease.

Investigation of predictors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome

Patients with severe fever with thrombocytopenia syndrome (SFTS) had been confirmed to have immune dysfunction and were prone to invasive pulmonary aspergillosis (IPA), which was directly related to the increased mortality. The aim of this study was to investigate the predictors for IPA in SFTS patients, and the results were expected to be helpful for early identification of IPA and initiation of anti-fungal therapy. The study was performed to review laboratory confirmed SFTS patients in two tertiary hospitals in Shandong province (Qilu Hospital of Shandong University and Shandong Public Health Clinical Center) from April 2021 to August 2022. The enrolled patients were further divided into IPA group and non-IPA group. Demographic characteristics, clinical manifestations and laboratory parameters between IPA group and non-IPA group patients were analyzed and compared to identify the independent predictors for IPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent predictors were evaluated by receiver operating characteristic (ROC) curve analysis. In total, 67 SFTS patients were enrolled with an average age of 64.7 (± 8.4) years old. The incidence of IPA was 32.8% (22/67). Mortality of patients in IPA group was 27.3% (6/22), which was significantly higher than that in non-IPA group. Results of univariate analysis showed that uncontrolled diabetes, central nervous system symptoms, platelet < 40 × 109/L, CD4+ T cell < 300/μL and CD8+ T cell < 400/μL were risk factors for development of IPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that uncontrolled diabetes, platelet < 40 × 109/L, CD4+ T cell < 300/μL and CD8+ T cell < 400/μL could be recognized as independent predictors for IPA in SFTS patients. In conclusion, IPA is a serious complication for SFTS patients and increases mortality. It is necessary to early identify predictors of IPA for improving survival of SFTS patients.

Invasive Pulmonary Aspergillosis in Patients with and without SARS-CoV-2 Infection

The recent European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) 2020 consensus classification proposes criteria to define coronavirus 2019 (COVID-19)-associated invasive pulmonary aspergillosis (CAPA), including mycological evidence obtained via non-bronchoscopic lavage. Given the low specificity of radiological findings in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, this criterion makes it difficult to differentiate between invasive pulmonary aspergillosis (IPA) and colonization. This unicenter and retrospective study includes 240 patients with isolates of any Aspergillus species in any respiratory samples during a 20-month study (140 IPA and 100 colonization). Mortality was high in the IPA and colonization groups (37.1% and 34.0%, respectively; p = 0.61), especially in patients with SARS-CoV-2 infection, where mortality was higher in colonized patients (40.7% vs. 66.6.%; p: 0.021). Multivariate analysis confirmed the following variables to be independently associated with increased mortality: age > 65 years, acute or chronic renal failure at diagnosis, thrombocytopenia (<100,000 platelets/µL) at admission, inotrope requirement, and SARS-CoV-2 infection, but not the presence of IPA. This series shows that the isolation of Aspergillus spp. in respiratory samples, whether associated with disease criteria or not, is associated with high mortality, especially in patients with SARS-CoV-2 infection, and suggests an early initiation of treatment given its high mortality rate.

Navigating the challenges of invasive pulmonary aspergillosis in lung cancer treatment: a propensity score study.

Invasive pulmonary aspergillosis (IPA) can negatively impact cancer patients' survival. It remains uncertain whether IPA's impact on patient outcomes varies by treatment approach in advanced lung cancer. To explore the association between IPA and outcomes in patients with advanced lung cancer receiving different treatments. A retrospective cohort study. We enrolled patients with advanced-stage lung cancer between 2013 and 2021 at a college hospital in Taiwan and used the 2021 European Organization for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium consensus for IPA diagnosis. Multivariable logistic regression was used to identify the IPA risk factors. We compared overall survival (OS) and postgalactomannan (GM) test survival between the IPA and control groups using multivariable Cox proportional hazards regression and the Kaplan-Meier method with propensity score matching (PSM). Among 2543 patients with advanced-stage lung cancer, 290 underwent a GM test, of which 34 (11.7%) were diagnosed with IPA. Patients undergoing chemotherapy (HR = 4.02, p = 0.027) and immunotherapy [hazard ratio (HR) = 3.41, p = 0.076] tended to have IPA. Compared to the control group, the IPA group had shorter median OS (14.4 versus 9.9 months, p = 0.030) and post-GM test survival (4.5 versus 1.9 months, p = 0.003). IPA was associated with shorter OS (log-rank p = 0.014 and 0.018 before and after PSM, respectively) and shorter 1-year and 2-year survival post-GM test (HR = 1.65 and 1.66, respectively). Patients receiving chemotherapy or immunotherapy had a shorter post-GM test survival if they had IPA. IPA tended to be diagnosed more frequently in patients receiving chemotherapy or immune checkpoint inhibitors. Patients diagnosed with IPA are associated with shorter survival. Larger cohort studies are needed to verify the observations.

Diagnosis values of Dectin-1 and IL-17 levels in plasma for invasive pulmonary aspergillosis in bronchiectasis.

BackgroundAmong immunocompetent patients, patients with bronchiectasis are considered to be a high-risk group for invasive pulmonary aspergillosis (IPA). Early diagnosis and treatment can improve the prognosis of patients.ObjectivesWe aimed to investigate the diagnostic value of Dectin-1 and IL-17 for diagnosing IPA with bronchiectasis.MethodsWe retrospectively collected data on patients with bronchiectasis who had been hospitalized in the Third Affiliated Hospital of Soochow University between September 2018 to December 2021. Dectin-1, IL-17 and GM were measured by enzyme-linked immunosorbent assays.ResultsA total of 129 patients were analyzed in the study, of whom 33 had proven or probable IPA with bronchiectasis. The remaining 96 patients served as controls. The plasma Dectin-1 and IL-17 levels in the IPA group were significantly higher than that in the control group (P=0.005; P<0.001). The plasma GM, BALF GM, plasma Dectin-1 and IL-17 assays had sensitivities of 39.4%, 62.5%, 69.7% and 78.8%, respectively, and specificities of 89.2%, 91.5%, 72.9% and 71.9%, respectively. The sensitivity of Dectin-1 and IL-17 in plasma was higher than that in plasma and BALF GM. while the specificity is lower than that of plasma and BALF GM. The diagnostic sensitivity and specificity of plasma GM combined with IL-17 for IPA in bronchiectasis were greater than 80%. The combination of plasma GM and IL-17 can improve the sensitivity of the GM test, but does not reduce the diagnostic specificity. The plasma Dectin-1 and IL-17 showed positive linear correlations with the bronchiectasis severity Index (BSI) score in linear regression.ConclusionsPlasma Dectin-1 and IL-17 levels were significantly higher in bronchiectasis patients with IPA. The sensitivity of Dectin-1 and IL-17 was superior to that of GM for the diagnosis of IPA in patients with bronchiectasis. The combination of GM and IL-17 in plasma is helpful for the diagnosis of IPA in bronchiectasis patients who cannot tolerate invasive procedures.

P499 A cross-sectional observational to assess the role of Bronchoalveolar lavage fluid galactomannan in the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjective: This study was done to assess the role of Bronchoalveolar lavage fluid (BALF) galactomannan (GM) in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients and to determine the optimal cut-off value of BALF GM for diagnosing IPA in non-neutropenic hosts.MethodsWe conducted a cross-sectional observational study on 96 non-neutropenic patients of age > 18 years with suspected pulmonary infections of fungal etiology. A detailed history of predisposing conditions was obtained and routine laboratory investigations with chest computerized (CT) tomography were performed. Fiberoptic bronchoscopy under local anesthesia and sedation was done using a video bronchoscope. Bronchoalveolar lavage was done from the segment or lobe of interest instilling 60-100 ml of saline withdrawn under low pressure and the sample was tested for a battery of investigations; fungal KOH smear; fungal culture; GM by Platelia Aspergillus enzyme immunoassay; and others required for diagnosis. A protected brush specimen and transbronchial lung biopsy were done wherever feasible. The yield from the BALF GM assay was compared with diagnosis based on definitions given by EORTC/MSG excluding host factors. Patients were classified into three groups namely non-IPA, probable IPA, and proven IPA. For statistical analysis, probable and proven IPA were taken as one group i.e., the IPA group. Mann-Whitney test and Chi-Square test along with Fisher's exact test were performed for inter-group comparison between quantitative and qualitative variables respectively. The receiver operator characteristic curve was used to establish a cut-off point of BALF GM and Serum GM for predicting IPA. Sensitivity, specificity, PPV, and NPV were calculated. The McNemar test was used for the comparison of sensitivity and specificity. Inter-rater kappa agreement was used to find the strength of agreement of BALF GM, BALF culture, and BALF DM.ResultsOut of 96, 1 was diagnosed with proven IPA, 34 were probable IPA cases and 61 were not IPA cases. Chronic kidney disease (CKD) as a risk factor was more common in IPA cases compared to non-IPA cases (25.7% vs. 8.2%, P-value .019). Chest CT showed cavity in a significant number of IPA patients compared to non-IPA cases (60% vs. 29.5%, P-value .003). BALF direct microscopy, culture, and serum GM had sensitivities < 60% but specificities close to 95%. BALF GM showed promising results with a sensitivity of 88.5% and specificity of 85.7% at cutoff value of 0.8.See Figures below.Conclusions: Our study highlights the magnitude of IPA in non-neutropenic hosts with unconventional risk factors like CKD, diabetes, and the need for increased vigilance for diagnosis of IPA in such patients. We suggest a lower cut-off value of BALF GM against 1 as in EORTC/MSG criteria and consider CKD as one of the risk factors for IPA.

A novel algorithm for diagnosis of invasive pulmonary aspergillosis based on pentraxin 3 gene polymorphisms and its adjusted value among autoimmune diseases patients.

BackgroundInvasive pulmonary aspergillosis (IPA) is a rapidly progressive and fatal disease for those with autoimmune diseases. The performance of existing diagnostic tools is unsatisfactory, and a novel algorithm based on pentraxin 3 (PTX3) gene polymorphisms with adjusted PTX3 and galactomannan (GM) values is urgently needed.MethodsLevels of PTX3 and GM were measured in the bronchoalveolar lavage fluid (BALF) and blood samples of patients who had autoimmune diseases with IPA between June 2017 and June 2021. Urea dilution was applied internally to correct the real BALF PTX3 and GM values. Three single-nucleotide polymorphisms (SNPs; rs1840680, rs2305619, and rs3816527) in the PTX3 gene were detected by polymerase chain reaction direct sequencing, and their associations with IPA were evaluated. Receiver operating characteristic (ROC) curves based on different variables were generated to determine the best algorithm for IPA diagnosis.ResultsThis study enrolled 50 patients with IPA and 100 without IPA in the control groups (comprising 50 patients with Aspergillus airway colonization and 50 patients with bacterial pneumonia). The levels of adjusted BALF PTX3 and GM were higher in the IPA group than in the control groups (P<0.05, respectively). For diagnosing IPA, the best adjusted cutoff value for PTX in BALF was 14.5 ng/mL and the best adjusted cutoff value for GM in BALF was 2.5 optical density index (ODI). The SNP rs1840680 AA homozygote was associated with a higher risk of IPA [odds ratio (OR) 18.86, 95% confidence interval (CI): 7.96–44.69; P<0.01], while no genotypic distribution differences were observed for the other 2 SNPs (rs2305619 and rs3816527). Six algorithms were established based on PTX3 gene polymorphisms. The algorithm consisting of PTX3 gene polymorphisms with adjusted BALF PTX3 and BALF GM values demonstrated the best diagnostic performance (sensitivity 90.03%; specificity 97.09%; area under the curve 0.94).ConclusionsIt was revealed that our new algorithm based on PTX3 gene polymorphisms combined with adjusted BALF GM and BALF PTX3 values performed well in diagnosing IPA.

The role of pentraxin3 in plasma and bronchoalveolar lavage fluid in COPD patients with invasive pulmonary aspergillosis

BackgroundThe use of galactomannan (GM) testing in plasma and bronchoalveolar lavage fluid (BALF) has improved the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD); however, the high false-positive rate leads to overdiagnosis. Pentraxin 3 (PTX3) as an indicator of inflammation plays an important role in resistance to Aspergillus infections. This study aimed to investigate the diagnostic value of PTX3 for diagnosing IPA with COPD.MethodsWe retrospectively collected data on patients with suspected COPD and IPA who had been hospitalized in the Third Affiliated Hospital of Soochow University between September 2017 and November 2020. PTX3 and GM were measured using enzyme-linked immunosorbent assays.ResultsA total of 165 patients were included in the study, of whom 35 had confirmed or probable IPA. The remaining 130 patients served as controls. The median plasma and BALF PTX3 levels were significantly higher in patients with IPA than in control patients (3.74 ng/mL vs. 1.29 ng/mL, P < 0.001; and 3.88 ng/mL vs. 1.58 ng/mL, P < 0.001 in plasma and BALF, respectively). The plasma GM, plasma PTX3, BALF GM, and BALF PTX3 assays had sensitivities of 60.0%, 77.1%, 78.6%, and 89.3%, respectively, and specificities of 73.8%, 69.2%, 80.7%, and 77.1%, respectively. The sensitivity of PTX3 in plasma and BALF was higher than that of GM. However, the specificity of PTX3 and GM did not differ significantly between the IPA group and the control group. The specificity of the assays for the diagnosis of IPA was > 90% in patients who were PTX3-positive and GM-positive in plasma and BALF.ConclusionsBALF and plasma PTX3 levels were significantly higher in COPD patients with IPA. The sensitivity of PTX3 was superior to that of GM for diagnosing IPA in patients with COPD. The combination of GM and PTX3 is useful for the diagnosis of IPA in patients with COPD.

Diagnosis values of IL-6 and IL-8 levels in serum and bronchoalveolar lavage fluid for invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Among immunologically normal hosts, patients with chronic obstructive pulmonary disease (COPD) are considered to be at high risk of invasive pulmonary aspergillosis (IPA), and early diagnosis and treatment are the...

Early-Warning Immune Predictors for Invasive Pulmonary Aspergillosis in Severe Patients With Severe Fever With Thrombocytopenia Syndrome.

Aspergillus-related disease was confirmed to be associated with immune disorders in patients, severe patients with severe fever with thrombocytopenia syndrome (SFTS) infected by novel phlebovirus were confirmed to have severe immune damage including cellular immunosuppression and cytokine storms. Secondary invasive pulmonary aspergillosis (IPA) in severe SFTS patients can increase fatality rate. This study investigated early-warning predictive factors of secondary IPA in severe SFTS patients. Receiver operating characteristic analysis was used to assess the value of immune parameters to predict IPA in SFTS patients. The cut-off values of CD4+ and CD8+ T-cell counts to predict IPA were 68 and 111 cells/mm3, with sensitivities of 82.6% and 72%, and specificities of 56.7% and 83.3%, respectively. Cut-off values of IL-6, TNF-α, IL-8, and IL-10 to predict IPA incidence in critically ill SFTS patients were 99 pg/mL, 63 pg/mL, 120 pg/mL, and 111 pg/mL, with sensitivities of 90.0%, 86.7%, 83.3% and 90.0% and specificities of 80.4%, 71.7%, 82.6% and 65.2%, respectively. Lower CD4+ and CD8+ T-cells counts, higher levels of IL-6, TNF-α, IL-8 and IL-10, higher incidence of pancreatic and renal damage, early antibacterial therapy of carbapenems, and intensive care unit admission were risk factors of IPA in SFTS patients. Multivariate logistic regression analysis indicated counts of CD4+ T-cells <68 cells/mm3 combined with CD8+ T-cells <111 cells/mm3 (odds ratio [OR] 0.218, 95% confidence interval [CI] 0.059–0.803, p=0.022), IL-6 >99 pg/ml combined with IL-10 >111 pg/ml (OR 17.614, 95% CI 2.319–133.769, p=0.006), and brain natriuretic peptide level >500 pg/ml (OR 13.681, 95% CI 1.994–93.871, p=0.008) were independent risk factors for IPA in SFTS patients. The mortality in the IPA group was significantly higher than in the non-IPA group (p=0.001). Early antifungal treatment of IPA patients was significantly associated with improved survival (log-rank, p=0.022). Early diagnosis of IPA and antifungal treatment can improve the prognosis of SFTS patients. Besides, we speculate SFTS may be as a host factor for IPA.

The diagnostic performance of galactomannan detection in invasive pulmonary aspergillosis with severe and critically ill influenza

Objective: To analyze the diagnostic performance of serum and bronchoalveolar lavage fluid (BALF) galactomannan (GM) test in invasive pulmonary aspergillosis(IPA) with severe and critically ill influenza. Methods: A retrospective study was performed for 157 patients with severe and critically ill influenza admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from December 2017 to April 2019.Clinical characteristics and serum and BALF GM values were collected. The patients were divided into an IPA group (n=18) and a non-IPA group (n=139). The definition of IPA modified from AspICU algorithm taken as the gold standard (The corresponding clinical manifestations, imaging manifestations and microbiological diagnostic criteria should be met simultaneously), the performance of serum and BALF GM test and their combination to IPA with influenza were analyzed respectively and receiver operating characteristic curve (ROC) was drawn. Results: A total of 157 cases were enrolled, 95 were critically ill, and the mortality of IPA with influenza was 55.6%(10/18). The APACHE Ⅱ score, PSI score, urea nitrogen, influenza severity (Percentage of critically ill influenza) and invasive ventilator in IPA group were (16±6), (110±31), 10.7 (8.4, 17.8) mmol/L, 88.9% and 66.7%, respectively, which were significantly higher than those in non-IPA group [(10±5), (83±30), 5.2 (3.6, 7.6) mmol/L, 56.8% and 24.5%, P<0.05]. All patients received serum GM test and 32 patients performed BALF GM test at the same time. When the cut-off valve of serum GM test was 0.5 μg/L, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 66.7% (12/18), 95.0% (132/139), 63.2% (12/19) and 95.7% (132/138) respectively. When the cut-off value of BALF GM test was 1.0 μg/L, the sensitivity, specificity, PPV and NPV were 80%(8/10),86.4%(19/22),72.7%(8/11)and 90.5%(19/21)respectively. The BALF GM cut-off value of 0.88 μg/L showed the highest diagnostic efficacy for IPA, for which the sensitivity and specificity were 90%(9/10) and 86.4%(19/22). The areas under the ROC curve of serum GM, BALF GM, and the combination of them were 0.81, 0.85, and 0.94 respectively. The difference was statistically significant (P<0.05) and the combined diagnosis efficiency was higher. Conclusions: Critically ill influenza patients should be alert for IPA. The sensitivity of serum GM test in the diagnosis of IPA with influenza was low, while the NPV was high. The optimum BALF GM cut-off value was 0.88 μg/L. The combination with BALF and serum GM test can improve the diagnostic performance.

Comparing the diagnostic value of bronchoalveolar lavage fluid galactomannan, serum galactomannanan, and serum 1,3-β-d-glucan in non-neutropenic respiratory disease patients with invasive pulmonary aspergillosis.

The incidence of invasive pulmonary aspergillosis (IPA) is increasing higher in non-neutropenic patients. This study aimed to assess the diagnostic performance of bronchoalveolar lavage fluid (BALF). Galactomannan (GM), serum GM, and 1,3-β-d-glucan (BDG) in non-neutropenic respiratory disease patients with IPA.A total of 333 non-neutropenic patients suspected IPA were recruited from Xiamen University Zhong Shan hospital between January 2016 and February 2019. One, 33, and 92 cases were diagnosed with proven, and possible IPA.BALF and serum GM were both elevated in the possible IPA group and the probable/proven IPA group (p < 0.001). BALF and serum GM showed a fair correlation in the possible IPA group (r = 0.286, p = 0.008), and moderate correlation in the probable/proven IPA group (r = 0.466, p = 0.005). When the cutoff value was 0.5, the sensitivity and negative likelihood ratio of BALF GM were superior to serum GM (78.3% vs 47.8%, 96.7% vs 91.6%). The specificity and positive likelihood ratio of BALF GM were slightly weaker than serum GM (91.8% vs 95.4%, 56.7% vs 85.0%). When the cutoff value was 1.0, the sensitivity and negative predictive value of BALF GM were better than serum GM (73.9% vs 26.1%, 94.5% vs 88.8%), and the specificity of were equivalent (99.2%). The optimal cutoff value of BALF GM was 0.6, wherein the sensitivity reached 78.3% and the specificity reached 95.4%. Given the extremely low sensitivity of serum BDG at different cutoff values (≥10 μg/mL = 5.3%, ≥20 μg/mL = 2.1%), it cannot be used as a preferred biomarker.The diagnostic performance of BALF GM was superior to other biomarkers and the optimal cutoff value was 0.6.

Assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis in severe patients

To evaluate the assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis (IPA) in severe patients. A retrospective study was conducted. The patients with suspected IPA admitted to intensive care unit (ICU) of Affiliated Hospital of Binzhou Medical College from January 2015 to December 2019 were enrolled. The diagnosis, clinical diagnosis and suspected diagnosis were made according to the grading criteria of Guidelines for the diagnosis and treatment of invasive fungal infection in severe patients (2007). Those who met the criteria were enrolled in the IPA group, and those who did not meet the criteria or other pathogens were enrolled in the non-IPA group. The general data of the patients were collected, and the changes of tracheal and bronchial mucosa under tracheal microscope before and after treatment were recorded, as well as the results of galactomannan (GM) test and aetiology culture of bronchoalveolar lavage fluid (BALF). The baseline, bronchoscopy and pulmonary CT manifestations and their dynamic changes were compared in each group. A total of 142 patients with suspected IPA were finally enrolled. Among them, 12 were pathologically proven IPA, 77 were probable IPA, 22 were possible IPA, and 31 were undefined IPA. Of the 142 patients, 60 had typical manifestations of mucosal injury under bronchoscopy, including 7 proven IPA patients (58.3%), 52 probable IPA patients (67.5%), and 1 possible IPA patient (4.5%), but none undefined IPA patient. The patients undergoing lung CT scan were 12 proven IPA patients (100%), 73 probable IPA patients (94.8%), and 21 possible IPA patients (95.5%), respectively. Most of the Chest CT showed patchy or strip density increasing and other non-specific manifestations. There were 3 proven IPA patients (25.0%), 7 probable IPA patients (9.0%), and 0 possible IPA patient (0%) who had typical IPA CT manifestations (halo sign and cavity or crescent sign). Among the patients of proven IPA and probable IPA (89 cases), there were a total of 35 cases with endoscopic airway mucosal injury and tracheoscopy reexamination ≥ 3 times. All the 35 patients received anti-aspergillus treatment, among which 16 survived and 19 died. Among the 16 patients who survived, the microscopic appearance of mucosal injury was gradually reduced and the clinical manifestations were gradually improved. Of the 19 patients who died, 16 had deteriorated endoscopic airway mucosal injury. The specific manifestations of severe patients with bronchial mucosal injury are of great significance in the diagnosis of IPA. In the case of severe patients who cannot receive pathological examination or chest CT in time, dynamic observation of the changes of airway mucosal injury is a simple auxiliary method to discover the changes of patients' condition in time, evaluate the effect of antifungal therapy and the prognosis of IPA.

Diagnostic value of galactomannan in serum and bronchoalveolar lavage fluid for invasive pulmonary aspergillosis in non-neutropenic patients

Objective: 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. Methods: 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. Results: 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. Conclusions: BALF GM detection is more sensitive than serum GM detection for diagnosing IPA, and the optimal cutoff value for BALF GM is 0.87.

Potential value of serum Aspergillus IgG antibody detection in the diagnosis of invasive and chronic pulmonary aspergillosis in non-agranulocytic patients

BackgroundAt present, serum Aspergillus IgG and IgM antibody detection is mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but its value in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. IgM can be used as a marker of acute infection to help diagnose acute infection-related diseases. IgG is a marker of long-term infection and is used to assist in the diagnosis of pre-existing or chronic infection-related diseases. The aim of this study was to investigate and compare the value of serum Aspergillus IgG and IgM antibody detection in the diagnosis of IPA and CPA in non-agranulocytic patients.MethodsFifty-eight cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of community-acquired bacterial pneumonia and 50 cases in the healthy control group were collected. The serum (1,3)-β-D-glucan test (G test) was performed with a chromogenic method, and the galactomannan test (GM test) and Aspergillus IgG and IgM antibody detection were performed by commercial enzyme-linked immunosorbent assay (ELISA) in all patients. The sensitivity and specificity, cut-off value and area under the curve (AUC) of Aspergillus IgG and IgM antibodies were further obtained by receiver operating characteristic (ROC) curves.ResultsThe positive rate of the G test, Aspergillus IgG antibody detection and the GM test also showed notable differences among the IPA, CPA, community-acquired bacterial pneumonia and healthy groups (P = 0.006, P < 0.001 and P = 0.217, respectively). Only the positive rate of the GM test showed a significant difference between the IPA and CPA groups (P = 0.04). ROC curves indicated that Aspergillus IgG antibody detection had a higher specificity in the IPA group than in the CPA group (0.952). The detection of Aspergillus IgG antibody can preferably distinguish IPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.923, specificity = 0.459, cut-off value = 134.46, AUC = 0.727). It can also distinguish CPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut-off value = 75.46, AUC = 0.873).ConclusionsSerum Aspergillus IgG antibody detection may have certain clinical value in the diagnosis of IPA and CPA in non-agranulocytic patients.

Comparison of Clinical Manifestation, Diagnosis, and Outcomes of Invasive Pulmonary Aspergillosis and Pulmonary Mucormycosis.

Objects: Invasive pulmonary mold infection usually has devastating outcomes. Timely differentiation between invasive pulmonary aspergillosis (IPA) from pulmonary mucormycosis (PM) is critical for treatment decision-making. However, information on IPA and PM differentiation is limited. Methods: We conducted a retrospective, multicenter, observational study, with proven and probable IPA and PM patients from January 2004 to December 2017. Demographics, clinical manifestations, image reports, histopathological findings, and outcomes were analyzed. Results: A total of 46 IPA (33 proven and 13 probable) and 19 PM (18 proven and one probable) cases were analyzed. The majority of tissues (81% in IPA and 61% in PM) were obtained using bronchoscopy. Prior influenza infection was a predisposing factor for IPA, and abscess formation in CT scan was associated with PM (p = 0.0491, p = 0.0454, respectively). The positive culture rate for PM was lower than that for IPA (37% vs. 67%, p = 0.0294). The galactomannan (GM) level from serum and bronchoalveolar lavage (BAL) fluid was significantly higher in IPA than in PM (3.3 ± 0.5 vs. 0.8 ± 0.6, p = 0.0361; 4.0 ± 0.6 vs. 0.59 ± 0.1, p = 0.0473, respectively). The overall mortality rate was 65%, which was similar among IPA and PM groups. Systemic steroid exposure and high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on admission were independently correlated to mortality in IPA (p = 0.027, p = 0.026, respectively). However, there was no predictor for mortality found in PM patients. Conclusions: Influenza infection, abscess formation in CT scan, and GM level may help physicians to differentiate IPA and PM. Bronchoscopy-guided biopsy and lavage specimen provide timely and definite diagnosis. The prognosis of IPA is associated with systemic steroid exposure and higher APACHE II scores on admission.