Bronchoalveolar Lavage Fluid Galactomannan Research Articles

Aspergillosis coinfection in patients with proven mucormycosis.

Although research on aspergillosis and mucormycosis confection is important to optimize antifungal therapy, data on this issue is scarce. Thus, we systematically investigated aspergillosis coinfection in patients with proven mucormycosis. Medical records of adult patients with proven mucormycosis whose formalin-fixed paraffin-embedded (FFPE) tissue sections were available, in a tertiary hospital from August 2007 to July 2023 were retrospectively reviewed to assess coinfection with aspergillosis. We noted cultures of fungi from sterile and non-sterile sites and performed polymerase chain reaction (PCR) assays on FFPE tissues to detect Aspergillus- and Mucorales-specific DNA. Sixty-seven patients with proven mucormycosis, including 12 (18%) with a positive culture of the mucormycosis agent from sterile site cultures, were enrolled. Fungal cultures from sterile and non-sterile sites revealed Aspergillus spp. growth in nine (13%) of the 67 patients, including two sterile and seven non-sterile cultures. The fungal PCR analysis from the FFPE sections was positive for Aspergillus-specific PCR in five (7%) and positive for both Aspergillus- and Mucorales-specific PCR results in eight (12%). Overall, 21 (31%) of the 67 patients with proven mucormycosis had microbiologic and/or molecular evidence of aspergillosis coinfection. Positive blood or bronchoalveolar lavage fluid galactomannan results were more common in the coinfection group (67% [14/21]) than in the mucormycosis group (37% [17/46], P=.024). No significant difference in mortality between the two groups was observed. Approximately one-third of patients with proven mucormycosis exhibited molecular and/or microbiologic evidence of aspergillosis coinfection. Further research is needed to identify patients with aspergillosis and mucormycosis coinfections, for optimal antifungal therapy.

Prevalence, Risk Factors, and Mortality of Invasive Pulmonary Aspergillosis in Patients with Anti-MDA5+ Dermatomyositis: A Retrospective Study in China.

To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM). A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared. Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P>0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all<0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all<0.05). IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.

The effect of antifungal treatments on bronchoalveolar lavage galactomannan for the diagnosis of invasive fungal infections in patients with hematological malignancy: Single-center experience

Background Invasive fungal infections (IFI) mainly caused by aspergillus species are one of the leading causes of death in patients undergoing immunosuppressive therapy for hematological malignancies. The presence of galactomannan in bronchoalveolar lavage fluid (BAL GM) is an important diagnostic marker. Some of the factors affecting the BAL GM are still unknown. Antifungal treatment administered before or after BAL also affect BAL GM results. Methods To investigate the effect of BAL GM timing on the diagnosis of IFE, 100 patients receiving immunosuppressive therapy with hematological malignancy at the Uludağ University Faculty of Medicine, Hematology Department, and underwent BAL over a 3-year period with the suspicion of IFE as well as 127 BAL procedures of these patients were examined. Results There were 70 patients who started antifungal therapy before BAL and 30 patients who did not. BAL GM was found positive in 33 (47.1%) of the 70 patients who received antifungal therapy compared to 22 (73.3%) of the 30 patients who did not receive antifungal therapy. There was a significant difference between the two groups in terms of BAL GM positivity (p = 0.016). Subsequently, 127 BAL procedures of these 100 patients were evaluated. When the second, third, and subsequent BAL procedures of the same patients were included in the study, BAL GM was positive in 41 (46.6%) of the 88 procedures in patients who received treatment before BAL and in 25 (64.1%) of the 39 procedures in patients who did not receive treatment before BAL. The rate of BAL GM positivity did not differ between groups (p = 0.068). Conclusions The balance between reducing the risk by initiating early antifungal therapy and maximizing the diagnostic value of BAL GM should be evaluated individually for each patient.

Performance of the galactomannan test for the diagnosis of invasive pulmonary aspergillosis using non-invasive proximal airway samples

To diagnose invasive pulmonary aspergillosis (IPA), galactomannan (GM) detection in serum or bronchoalveolar lavage fluid (BALF) is widely used. However, the utility of proximal airway GM test (from induced sputum or tracheal aspirate) has not been well elucidated. In this retrospective cohort study, we evaluated the diagnostic performance of proximal airway GM in diagnosis of IPA including COVID-19 associated pulmonary aspergillosis (CAPA). Between January 2022 and January 2023, patients who had been tested for GM with clinical suspicion or for surveillance from any specimen (serum, induced sputum, tracheal aspirate, and BALF) were screened. IPA was diagnosed using EORTC/MSGERC criteria, and CAPA was diagnosed following the 2020 ECMM/ISHAM consensus criteria. Of 624 patients with GM results, 70 met the criteria for proven/probable IPA and 427 had no IPA. The others included possible IPA and chronic form of aspergillosis. The sensitivities and specificities of serum, proximal airway, and BALF GM for proven/probable IPA versus no IPA were 78.9% and 70.6%, 93.1% and 78.7%, and 78.6% and 91.0%, respectively. Areas under the receiver operating characteristic curve (AUCs) were 0.742 for serum GM, 0.935 for proximal airway GM, and 0.849 for BALF GM (serum GM vs proximal airway GM, p=0.014; proximal airway GM vs BALF GM, p=0.334; serum GM vs BALF GM, p=0.286). This study demonstrates that the performance of GM test from non-invasive proximal airway samples is comparable or even better than those from serum and distal airway sample (BALF).

Clinical utility of metagenomic next-generation sequencing in the diagnosis of invasive pulmonary aspergillosis in acute exacerbation of chronic obstructive pulmonary disease patients in the intensive care unit.

To explore the clinical utility of metagenomic next-generation sequencing (mNGS) in diagnosing invasive pulmonary aspergillosis (IPA) among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the intensive care unit (ICU). A retrospective analysis was conducted on patients with AECOPD admitted to the ICU of Xinxiang Central Hospital in Henan Province, China, between March 2020 and September 2023, suspected of having IPA. Bronchoalveolar lavage fluid (BALF) samples were collected for fungal culture, the galactomannan (GM) test, and mNGS. Based on host factors, clinical features, and microbiological test results, patients were categorized into 62 cases of IPA and 64 cases of non-IPA. Statistical analysis was performed to compare the diagnostic efficacy of fungal culture, the serum and BALF GM test, and mNGS detection for IPA in patients with AECOPD. 1. The sensitivity and specificity of mNGS in diagnosing IPA were 70.9% and 71.8% respectively, with the sensitivity of mNGS surpassing that of fungal culture (29.0%, P<0.01), serum GM test (35.4%, P<0.01), and BALF GM test (41.9%, P<0.05), albeit with slightly lower specificity compared to fungal culture (90.6%, P >0.05), serum GM test (87.5%, P >0.05), and BALF GM test (85.9%, P >0.05).Combining fungal culture with the GM test and mNGS resulted in a sensitivity of 80.6% and a specificity of 92.2%, underscoring a superior diagnostic rate compared to any single detection method. 2.mNGS accurately distinguished strains of the Aspergillus genus. 3.The area under the ROC curves of mNGS was 0.73, indicating good diagnostic performance. 4.The detection duration for mNGS is shorter than that of traditional fungal culture and GM testing. mNGS presents a pragmatic and highly sensitive approach, serving as a valuable complementary tool to conventional microbiological tests (CMT). Our research demonstrated that, compared to fungal culture and GM testing, mNGS exhibits superior diagnostic capability for IPA among patients with AECOPD. Integration of mNGS with established conventional methods holds promise for improving the diagnosis rate of IPA.

Metagenomic next-generation sequencing for detecting Aspergillosis pneumonia in immunocompromised patients: a retrospective study.

The identification of Aspergillus by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary aspergillosis (IPA) in immunocompromised patients (ICP). A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of Aspergillosis and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard. mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, P < 0.001), culture (39.1%, P < 0.001), serum GM (23.9%, P < 0.001) and BALF GM (69.6%, P = 0.031). mNGS was capable of accurately distinguish strains of Aspergillus genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified A. fumigatus, A. flavus, A. terrestris, A. oryzae and Mucor spp. in culture-negative cases. The sequencing reads of Aspergillus by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, P = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with P. jirovecii and cytomegalovirus being the most common co-pathogens. mNGS presents a feasible and remarkably sensitive approach for detecting Aspergillus in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS's ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy.

Diagnosis of invasive pulmonary aspergillosis by lateral flow assay of galactomannan in bronchoalveolar lavage fluid: a meta-analysis of diagnostic performance.

The performance of lateral flow assay (LFA) in diagnosing invasive pulmonary aspergillosis (IPA) has not been well demonstrated. To address this, we conducted a meta-analysis assessing the overall accuracy of LFA in diagnosing IPA using bronchoalveolar lavage fluid (BALF). Over a systematical search and assessment of bias risk, we calculated the pooled specificity, sensitivity, and area under the receiver operating curve (AUC) to assess the diagnostic performance. Our meta-analysis included 11 studies. The combined total sensitivity and specificity for diagnosing IPA were 0.78 (95% confidence interval (CI): 0.71, 0.83) and 0.87 (95% CI: 0.81, 0.91), respectively. The AUC was 0.86 (95% CI: 0.82, 0.89). Our results demonstrate that LFA using galactomannan in BALF exhibits high sensitivity and specificity for diagnosing IPA.

Physicians' knowledge of invasive fungal disease in China.

Invasive fungal disease (IFD) is associated with high morbidity and mortality. Data are lacking regarding physicians' perspectives on the diagnosis and management of IFD in China. To evaluate physicians' perspectives on the diagnosis and management of IFD. Based on current guidelines, a questionnaire was designed and administered to 294 physicians working in haematology departments, intensive care units, respiratory departments and infectious diseases departments in 18 hospitals in China. The total score and subsection scores for invasive candidiasis, invasive aspergillosis (IA), cryptococcosis and invasive mucormycosis (IM) were 72.0 ± 12.2 (maximum = 100), 11.1 ± 2.7 (maximum = 19), 43.0 ± 7.8 (maximum = 57), 8.1 ± 2.0 (maximum = 11) and 9.8 ± 2.3 (maximum = 13), respectively. Although the perspectives of the Chinese physicians were in good overall agreement with guideline recommendations, some knowledge gaps were identified. Specific areas in which the physicians' perspectives and guideline recommendations differed included use of the β-D-glucan test to facilitate the diagnosis of IFD, relative utility of the serum galactomannan test and bronchoalveolar lavage fluid galactomannan test in patients with agranulocytosis, use of imaging in the diagnosis of mucormycosis, risk factors for mucormycosis, indications for initiating antifungal therapy in patients with haematological malignancies, when to start empirical therapy in mechanically ventilated patients, first-line drugs for mucormycosis and treatment courses for IA and IM. This study highlights the main areas that could be targeted by training programs to improve the knowledge of physicians treating patients with IFD in China.

The clinical value of Aspergillus-specific IgG antibody test in the diagnosis of nonneutropenic invasive pulmonary aspergillosis

ObjectivesAspergillus-specific IgG antibody (Asp IgG) has been successfully applied in the diagnosis of chronic pulmonary aspergillosis. We explored its value in nonneutropenic invasive pulmonary aspergillosis (IPA) by a multicenter, prospective, and controlled study. MethodsWe enrolled 372 clinically suspected nonneutropenic patients with IPA from February 2015 to August 2022. After excluding 4 cases with Aspergillus colonization, the remaining 368 cases were finally confirmed as patients with IPA (n = 99), or non-IPA patients (n = 269) consisting of community-acquired pneumonia (n = 206), tuberculosis (n = 22), nontuberculous mycobacteria (n = 5), lung abscess (n = 6), or noninfectious diseases (n = 30). Asp IgG in plasma samples was tested by enzyme-linked immunosorbent assay. ResultsAt cut-off value of ≥80 AU/mL, Asp IgG had much higher sensitivity (59.6% vs. 19.2%, p < 0.0001), but lower specificity (77.0% vs. 96.3%, p < 0.0001) than serum galactomannan (GM) (cut-off value of ≥1.0), and similar sensitivity (59.6% vs. 55.6%, p = 0.611) but lower specificity (77.0% vs. 91.2%, p = 0.001) than bronchoalveolar lavage fluid (BALF) GM (cut-off value of ≥1.0), respectively. Combination diagnosis of either positive for Asp IgG or BALF GM had higher sensitivity (81.0% vs. 55.6%, p = 0.002), but lower specificity (75.2% vs. 91.2%, p = 0.001) than BALF GM alone. The receiver operating characteristic curve showed that Asp IgG had an optimal diagnostic value when the cut-off value was 56.6 AU/ml, and the sensitivity and specificity were 77.8% and 63.9%, respectively. DiscussionsThe diagnostic value of Asp IgG for IPA is superior to serum GM, and a little inferior to BALF GM in nonneutropenic patients with IPA. Considering the convenience of taking blood samples, it is a good screening and diagnostic method for nonneutropenic patients with IPA, especially for those who cannot bear invasive procedures.

Fungal Tracheobronchitis in Lung Transplant Recipients: Incidence and Utility of Diagnostic Markers.

Fungal tracheobronchitis caused by Aspergillus and Candida spp. is a recognized complication after lung transplantation, but knowledge of the incidence of Candida tracheobronchitis is lacking. The diagnosis relies on fungal cultures in bronchoalveolar lavage fluid (BALF), but cultures have low specificity. We aimed to evaluate the one-year incidence of fungal tracheobronchitis after lung transplantation and to assess the utility of diagnostic markers in serum and BALF to discriminate fungal tracheobronchitis from colonization. Ninety-seven consecutively included adult lung-transplant recipients were prospectively followed. BALF and serum samples were collected at 1, 3 and 12 months after transplantation and analyzed for betaglucan (serum and BALF), neutrophils (BALF) and galactomannan (BALF). Fungal tracheobronchitis was defined according to consensus criteria, modified to include Candida as a mycologic criterion. The cumulative one-year incidence of Candida and Aspergillus tracheobronchitis was 23% and 16%, respectively. Neutrophils of &gt;75% of total leukocytes in BALF had 92% specificity for Candida tracheobronchitis. The area under the ROC curves for betaglucan and galactomannan in BALF to discriminate Aspergillus tracheobronchitis from colonization or no fungal infection were high (0.86 (p &lt; 0.0001) and 0.93 (p &lt; 0.0001), respectively). To conclude, the one-year incidence of fungal tracheobronchitis after lung transplantation was high and dominated by Candida spp. Diagnostic markers in BALF could be useful to discriminate fungal colonization from tracheobronchitis.

Diagnostic value of bronchoalveolar lavage fluid galactomannan assay for invasive pulmonary aspergillosis in adults: A meta-analysis.

To analyse the diagnostic accuracy of bronchoalveolar lavage fluid galactomannan (BALF-GM) assay for invasive pulmonary aspergillosis (IPA) in adults to determine the optimal diagnostic cut-off by meta-analysis. PubMed, Embase, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI), and China Wanfang databases were searched to collect relevant studies on the diagnostic value of BALF-GM for IPA from inception to March 2022. The summary receiver operating characteristic (SROC) curve was drawn to determine the optimal diagnostic cut-off. Nineteen articles (56 data sets) were included. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.79 (95% CI: 0.72-0.84), 0.92 (95% CI: 0.88-0.94), 9.25 (95% CI: 6.84-12.52), 0.23 (95% CI: 0.18-0.30), 39.44 (95% CI: 29.55-52.65), and 0.92 (95% CI: 0.90-0.94), respectively. The area under the curves (AUCs) were 0.92, 0.86, 0.93, 0.89, 0.88, and 0.94 when the cut-off values were 0.5, 0.8, 1.0, 1.5, 2.0, and 3.0, respectively. Sixteen studies were included in the combined analysis when the cut-off value was 0.5. The results showed that the pooled sensitivity, specificity, PLR, NLR and DOR of BALF-GM (cut-off 0.5) for the diagnosis of IPA were 0.89 (95% CI: 0.83-0.93), 0.79 (95% CI: 0.71-0.86), 4.33 (95% CI: 3.04-6.16), 0.14 (95% CI: 0.09-0.22), and 31.51 (95% CI: 17.43-56.98). The AUC was 0.92 (95% CI: 0.89-0.94). BALF-GM has excellent diagnostic accuracy for adult IPA, which can be diagnosed early and treated early to reduce the mortality rate. Considering the sensitivity, specificity, PLR and NLR, the recommended diagnostic cut-off of BALF-GM for adult IPA is 0.5.

TUMOR NECROSIS FACTOR (TNF) ALPHA INHIBITORS, ASPERGILLOSIS, AND GALACTOMANNAN: THE PERILS OF BEING MISLED BY AN INSENSITIVE TEST

TUMOR NECROSIS FACTOR (TNF) ALPHA INHIBITORS, ASPERGILLOSIS, AND GALACTOMANNAN: THE PERILS OF BEING MISLED BY AN INSENSITIVE TEST

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.

Evaluation of the diagnostic accuracy of galactomannan from the bronchoalveolar lavage fluid of patients with suspected invasive pulmonary aspergillosis

BackgroundSeveral studies to evaluate the accuracy of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) as a diagnostic tool have been carried out; however, there are still controversies about the optimal cut-off point of BALF GM. AimsThe objective of this study was to determine the diagnostic accuracy and the optimal cut-off point on BALF GM from patients with suspected invasive pulmonary aspergillosis (IPA) in a tertiary care hospital. MethodsA cross-sectional study with 188 patients (≥18 years) that had undergone a bronchoscopy with BAL due to suspected IPA was carried out. IPA was diagnosed according to the EORTC/MSG guidelines. ResultsThe optimal optical density cut-off point for BALF GM was 0.67, with sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 70%, 32.3%, and 100%, respectively. ConclusionsBALF GM detection proved to be a useful supplementary technique in the early diagnosis of IPA in both neutropenic and non-neutropenic patients.

Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Post Hoc Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study.

ABSTRACTCritically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a post hoc analysis of a previous multicenter, multinational observational study with the aim of assessing the differential prognostic impact of BALF mycological tests, namely, positive (optical density index of ≥1.0) BALF galactomannan (GM) and positive BALF Aspergillus culture alone or in combination for critically ill patients with COVID-19. Of the 592 critically ill patients with COVID-19 enrolled in the main study, 218 were included in this post hoc analysis, as they had both test results available. CAPA was diagnosed in 56/218 patients (26%). Most cases were probable CAPA (51/56 [91%]) and fewer were proven CAPA (5/56 [9%]). In the final multivariable model adjusted for between-center heterogeneity, an independent association with 90-day mortality was observed for the combination of positive BALF GM and positive BALF Aspergillus culture in comparison with both tests negative (hazard ratio, 2.53; 95% CI confidence interval [CI], 1.28 to 5.02; P = 0.008). The other independent predictors of 90-day mortality were increasing age and active malignant disease. In conclusion, the combination of positive BALF GM and positive BALF Aspergillus culture was associated with increased 90-day mortality in critically ill patients with COVID-19. Additional study is needed to explore the possible prognostic value of other BALF markers.

Clinical Features, Diagnostic Test Performance, and Prognosis in Different Subtypes of Chronic Pulmonary Aspergillosis

ObjectiveThe aim of this study was to describe clinical features in different subtypes of chronic pulmonary aspergillosis (CPA)-simple aspergilloma (SA), chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN), and subacute invasive aspergillosis (SAIA), respectively, and identify long-term prognosis of CPA.MethodsWe reviewed patients diagnosed with different subtypes of CPA from 2002 to 2020 at Nanjing Jinling Hospital, China. We analyzed the clinical and survival information of five different subgroups. A Cox regression model was used to explore proper antifungal duration and long-term survival factors of CCPA and SAIA.ResultsA total of 147 patients with CPA were included, consisting of 11 SA, 48 CCPA, 5 CFPA, 12 AN, and 71 SAIA. The most common underlying pulmonary disease was pulmonary tuberculosis (n = 49, 33%), followed by bronchiectasis (n = 46, 31.3%) and chronic obstructive pulmonary disease (COPD) or emphysema (n = 45, 30.6%), while in SAIA and CFPA groups, the most common was COPD or emphysema (45.1 and 100%). Cough (85%), expectoration (70.7%), hemoptysis (54.4%), and fever (29.9%) were common symptoms, especially in CCPA, CFPA, and SAIA groups. The common imaging manifestations included cavitation (n = 94, 63.9%), fungal ball (n = 54, 36.7%), pleural thickening (n = 47, 32.0%), and bronchiectasis (n = 46, 31.3%). SAIA and CFPA groups had a lower value of hemoglobin (HB) and serum albumin (ALB) with higher C-reactive protein and erythrocyte sedimentation rate. The positive rate of sputum culture, serum galactomannan (GM), and bronchoalveolar lavage fluid GM was 32.7% (36/110), 18.4% (18/98), and 48.7% (19/39), respectively. There were 64.6% (31/48) patients with CCPA and 25.4% (18/71) patients with SAIA who received surgery and the 5-year cumulative survival rate was 92.1 and 66.6%, respectively. SAIA, old age, male, low body mass index (BMI), COPD or emphysema, multiple distribution, low serum ALB, and positive sputum culture were adverse prognosis factors for SAIA and CCPA group, and BMI ≤ 20.0 kg/m2 was independently associated with increased mortality (hazard ratio (HR) 5.311, 95% CI 1.405–20.068, p = 0.014). Multivariable Cox regression indicated that surgery (HR 0.093, 95% CI 0.011–0.814, p = 0.032) and antifungal duration >6 months (HR 0.204, 95% CI 0.060–0.696 p = 0.011) were related to improved survival.ConclusionThe clinical features and laboratory test performance are different among SA, CCPA, CFPA, AN, and SAIA. Low BMI was an independent risk factor for survival. Selective surgery and antifungal duration over 6 months were associated with improved survival.

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.

Clinical study of invasive pulmonary aspergillosis following influenza A H1N1.

This study to analyze the clinical characteristics of patients with invasive pulmonary aspergillosis (IPA) following influenza A (H1N1) infection.We retrospectively analyzed 10 cases with IPA following H1N1 infection. The clinical manifestations, laboratory examination results, chest computed tomography, and treatments were analyzed.Clinical manifestations: all 10 cases had typical flu-like symptoms at the onset of the disease, among which 7 patients developed dyspnea in the late stage, and 8 patients had hemoptysis. Laboratory examination: the absolute and percentage of peripheral blood lymphocytes in all 10 patients were declined, among which 5 cases were with decreased CD3+ CD4+ T cells/lymphocytes; 9 cases with increased bronchoalveolar lavage fluid galactomannan; 6 cases with increased serum galactomannan; 1 case with bronchoalveolar lavage fluid cultured aspergillus fumigatus; and 2 cases with aspergillus by second-generation sequencing. Chest computed tomography: all patients showed multiple diffused ground-glass opacities at the beginning, along with linear or reticular interstitial changes. Two cases had multiple subarachnoid nodules with halo signs, 3 cases had consolidation in multiple segments of both lungs, 2 cases had cavities, and 4 cases were with pleural effusion. Treatment: 10 patients were treated with antiviral and anti-Aspergillus drugs after admission. Four patients received respiratory support. All 10 cases were cured and discharged.Early diagnosis of IPA in influenza A (H1N1) patients is the key to successful treatment.

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...