Pulmonary Aspergillosis In Patients Research Articles

Clinical Impact of Chronic Pulmonary Aspergillosis in Patients with Nontuberculous Mycobacterial Pulmonary Disease and Role of Computed Tomography in the Diagnosis.

Objective Chronic pulmonary aspergillosis (CPA) is an important complication of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnosis is challenging, as both CPA and NTM-PD present as chronic cavitary disease. The present study evaluated the impact of CPA on the survival of patients with NTM-PD and revealed the key computed tomography findings for a prompt diagnosis. Methods We retrospectively reviewed patients newly diagnosed with NTM-PD in Tenri Hospital (Tenri City, Nara Prefecture, Japan) between January 2009 and March 2018; the patients were followed up until May 2021. Clinical and radiological characteristics were assessed, and patients with CPA were identified. Results A total of 611 patients were diagnosed with NTM-PD. Among them, 38 (6.2%), 102 (17%), and 471 (77%) patients were diagnosed with NTM-PD with CPA, cavitary NTM-PD without CPA, and non-cavitary NTM-PD without CPA, respectively. The 5-year survival rate of the NTM-PD with CPA group (42.8%; 95% confidence interval: 28.7%-64.0%) was lower than that of the cavitary NTM-PD without CPA group (74.4%; 95% confidence interval: 65.4%-84.6%). A multivariate analysis revealed that fungal balls and cavities with adjacent extrapleural fat were significant predictive factors for NTM-PD with CPA. Conclusion NTM-PD with CPA patients exhibited a worse prognosis than cavitary NTM-PD without CPA patients. Therefore, an unerring diagnosis of CPA is essential for managing patients with NTM-PD. Computed tomography findings, such as fungal balls and cavities with adjacent extrapleural fat, may be valuable diagnostic clues when CPA is suspected in patients with NTM-PD.

Prediction of pulmonary aspergillosis in patients with ventilator-associated pneumonia

BackgroundPredictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP.MethodsMechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort.ResultsAmong 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia < 0.5G/L and high-dose steroids ≥ 1 mg/kg/day of prednisolone equivalent) (p = 0.001; score = 1 point) and lymphocyte count at admission < 0.8 G/L (p = 0.019; score = 1 point). Operational values of the predictive score in the learning/validation cohort were 50%/52% sensitivity and 90%/87% specificity, respectively, for high PiPa score (score = 2) and 94%/91% sensitivity and 44%/46% specificity, respectively, for moderate PiPa score (score = 1). Finally, the AUC for the prediction of IPA was 0.783 in the learning cohort and 0.770 in the validation cohort.ConclusionsWe evaluated a clinical score with good predictive value which may help to predict IPA in patient with VAP. External validation will be needed to confirm our preliminary findings.

Microbiological diagnosis of pulmonary invasive aspergillosis in critically ill patients with severe SARS-CoV-2 pneumonia: a bronchoalveolar study

BackgroundDiagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD).MethodsProspective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose.ResultsOf the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%.ConclusionsUsing a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA.

POSTER: AML-366 Invasive Pulmonary Aspergillosis in Patients With Acute Myeloid Leukemia (AML) in Morocco

POSTER: AML-366 Invasive Pulmonary Aspergillosis in Patients With Acute Myeloid Leukemia (AML) in Morocco

AML-366 Invasive Pulmonary Aspergillosis in Patients With Acute Myeloid Leukemia (AML) in Morocco

AML-366 Invasive Pulmonary Aspergillosis in Patients With Acute Myeloid Leukemia (AML) in Morocco

Possibilities of CT in the diagnosis of pulmonary aspergillosis in patients with COVID-19 (literature review)

Aim: to analyze the latest research in the field of CT diagnostics of pulmonary aspergillosis in patients with COVID-19 according to domestic and foreign literature.Results. Pulmonary aspergillosis is one of the most common life-threatening fungal diseases that is caused by inhalation of Aspergillus mold spores and affects all parts of the respiratory system. In recent years, there has been a sharp increase in cases of invasive mycotic processes. During the COVID-19 pandemic, according to a number of authors, the incidence of pulmonary aspergillosis reached 34.4%, and the mortality rate was 74%. The World Health Organization calls for “minimizing the disproportionate use of corticosteroids and antibiotics for mild and moderate cases”. She explained that corticosteroids in severe cases do save lives, but their massive use can cause fungal infections. This complication is increasingly common in patients after corticosteroid and antibiotic therapy, with immunodeficiency states, as well as those treated in intensive care units. The COVID-19 pandemic has created additional challenges in the diagnosis, treatment and prevention of fungal complications. The clinical and radiographic features of fungal infections are largely similar to typical pulmonary manifestations of COVID-19. A comparative analysis of CT signs of various forms of pulmonary aspergillosis before and during the COVID-19 pandemic was carried out according to the literature. The main CT symptoms of mycotic lung lesions among patients who have undergone COVID-19 have been identified. Currently, computed tomography is crucial, first of all, to detect and monitor complications of COVID-19, including the addition of a secondary fungal infection.Conclusion. To make a conclusion about mycosis in the early stages, special vigilance and high qualification of the radiologist are required, which in turn will contribute to the timely appointment of antifungal therapy, which will reduce morbidity and mortality.

The dose-response relationship between smoking and the risk factor for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome.

Invasive pulmonary aspergillosis (IPA) is common in immuno-compromised people, and a high incidence of IPA has been found in patients with severe fever with thrombocytopenia syndrome (SFTS). Our study aimed to determine the independent risk factors for IPA and the relationship between smoking status and the risk of IPA in SFTS patients. A retrospective analysis of SFTS patients in the First Affiliated Hospital of Nanjing Medical University from May 2011 to December 2021 was reviewed. The patients were divided into two groups: IPA and non-IPA groups. We compared demographic characteristics, clinical manifestation, laboratory parameters, treatment, and prognosis, and explored the risk factors of IPA using logistic regression and ROC curve. The dose-dependent effect of smoking on the risk of IPA was further estimated, including the age of smoking initiation, daily smoking amount, smoking duration, and pack-years of smoking. In total, 189 individuals were included. Compared with the non-IPA group, the IPA group had higher levels of smoking, drinking, cough, dyspnea, aCCI scores, Dabie bandavirus (DBV) RNA load, ferritin, PCT, IL-6, APTT, LDH, BUN, creatinine, and lower levels of FT4 and TSH. The incidences of MODS, admission to ICU, ventilation, and broad-spectrum antibiotic treatment were significantly higher in the IPA group than in the non-IPA group. Multivariable logistic analysis showed that smoking history, cough, creatinine, admission to ICU, broad-spectrum, and corticosteroid therapies were the independent risk factors for IPA in SFTS patients. We further confirmed that the age of smoking initiation <30 years, smoking at least one pack per day, smoking for at least 40 years, and having at least 40 pack-years of smoking exposure were the independent risk factors for IPA among smokers. The prognosis of SFTS patients in the IPA group is worse than that of the non-IPA group. Attention should be paid to SFTS patients with a smoking history, cough, creatinine, admission to ICU, and broad-spectrum and corticosteroid therapies. There is a strong dose-dependent association between smoking and IPA development in SFTS patients. Prophylactic antifungal therapy should be considered for SFTS patients with these risk factors, but further studies are necessary to determine if it is beneficial for the prognosis of these patients.

Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

COVID-19 Associated Pulmonary Aspergillosis in Patients on Extracorporeal Membrane Oxygenation Treatment-A Retrospective Study.

The incidence and outcome of pulmonary aspergillosis in coronavirus disease (COVID-19) patients on extracorporeal membrane oxygenation (ECMO) are unknown and have not been fully addressed. We investigated the incidence, risk factors and outcome of pulmonary aspergillosis in COVID-19 ECMO patients. In addition, the diagnostic utility of bronchoalveolar lavage fluid and CT scans in this setting were assessed. We conducted a retrospective study on incidence and outcome of pulmonary aspergillosis in COVID-19 ECMO patients by reviewing clinical, radiological, and mycological evidence. These patients were admitted to a tertiary cardiothoracic centre during the early COVID-19 surge between March 2020 and January 2021. Results and measurements: The study included 88 predominantly male COVID-19 ECMO patients with a median age and a BMI of 48 years and 32 kg/m2, respectively. Pulmonary aspergillosis incidence was 10% and was associated with very high mortality. Patients with an Aspergillus infection were almost eight times more likely to die compared with those without infection in multivariate analysis (OR 7.81, 95% CI: 1.20-50.68). BALF GM correlated well with culture results, with a Kappa value of 0.8 (95% CI: 0.6, 1.0). However, serum galactomannan (GM) and serum (1-3)-β-D-glucan (BDG) lacked sensitivity. Thoracic computed tomography (CT) diagnostic utility was also inconclusive, showing nonspecific ground glass opacities in almost all patients. In COVID-19 ECMO patients, pulmonary aspergillosis incidence was 10% and associated with very high mortality. Our results support the role of BALF in the diagnosis of pulmonary aspergillosis in COVID-19 ECMO patients. However, the diagnostic utility of BDG, serum GM, and CT scans is unclear.

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.

COVID-19-associated pulmonary aspergillosis in patients with severe SARS-CoV-2 infection: A single-center observational study from Greece.

COVID-19-associated pulmonary aspergillosis (CAPA) is a serious complication affecting patients with severe SARS-CoV-2 infection, and is associated with increased mortality. The objective of this study was to investigate potential risk factors, and to estimate the incidence and mortality in patients diagnosed with CAPA. A single-center retrospective observational study was conducted on patients admitted to the intensive care unit (ICU) with severe COVID-19 from October 2020 to May 2022. Patients with deterioration of their clinical status were evaluated with serum galactomannan (GM) for probable CAPA. Baseline demographic patient characteristics, vaccination status, and time period during which each patient was infected with SARS-CoV-2 were obtained, and risk stratification according to underlying comorbidities was performed in an effort to assess various risk factors for CAPA. The incidence of CAPA in the entire cohort was measured, and mortality rates in the CAPA and non-CAPA groups were calculated and compared. Of 488 patients admitted to the ICU, 95 (19.4%) had deterioration of their clinical status, which prompted testing with serum GM. Positive serum testing was observed in 39/95 patients, with an overall CAPA incidence in the entire study cohort reaching 7.9% (39/488). The mortality rate was 75% (42/56) in the non-CAPA group that was tested for serum GM, and 87.2% (34/39) in the CAPA group (P = 0.041). Multivariable Cox regression hazard models were tested for 28- and 90-day survival from ICU admission. An invasive pulmonary aspergillosis (IPA) risk-stratified cox regression model corrected for the SARS-CoV-2 variant of the patient identified the diagnosis of probable CAPA and elevated procalcitonin (PCT) levels measured at least 10 days after ICU admission, as significantly associated with death in the IPA-risk subgroup only, with hazard ratio (HR): 3.687 (95% confidence interval [CI], 1.030-13.199, P = 0.045) for the diagnosis of probable CAPA, and HR: 1.022 (95% CI, 1.003-1.042, P = 0.026) for every 1 ng/mL rise in PCT. Patients in the IPA-risk subgroup that were diagnosed with CAPA had a lower 90-day survival when compared to patients in the same group without a CAPA diagnosis.

Impact of revised EORTC/MSGERC 2020 criteria on diagnosis and prognosis of invasive pulmonary aspergillosis in patients with hematological malignancies undergoing bronchoscopy.

The first consensus definitions for invasive fungal diseases (IFD) were published in 2002. Advances in diagnostic tests and a clear need for improvement in certain areas led to a revision of these definitions in 2008. However, growing data on Aspergillus galactomannan (GM) thresholds and the introduction of new polymerase chain reaction-based diagnostic tests resulted in a further update by EORTC and Mycoses Study Group Education and Research Consortium (MSGERC) in 2020. Compared to the 2008 version, the 2020 EORTC/MSGERC criteria have stricter definitions, especially regarding GM levels, which should lead to improved specificity. Thus, our study aimed to evaluate diagnostic changes, based on GM levels, resulting from these new definitions and ascertain the impact of the new classification on mortality rates. Patients hospitalized in a single tertiary care center with hematologic malignancies and undergoing bronchoscopy for suspected IPA between April 2004 and December 2019 were included in this retrospective study. The study population consisted of 327 patients with 31 patients (nine patients with proven IPA and 22 patients with no IPA) excluded from the study. 194 patients were classified as probable IPA cases according to 2008 EORTC/MSG criteria. However, 53 (27.3%) of these patients were re-classified as possible IPA according to 2020 EORTC/MSGERC criteria, due to novel galactomannan cut-off levels. Compared to re-classified possible IPA patients, those remaining in the probable IPA category experienced a higher incidence of septic shock (34.0% vs 16.9%, p=0.02), and required more non-invasive (12.0% vs 0.0%, p=0.004) and invasive (44.6 vs 24.5%, p=0.01) mechanical ventilation. There was a higher in-hospital mortality rate in probable IPA patients than in the re-classified possible IPA group (42.5% vs 22.6%, p=0.01). Patients reassigned to possible IPA had similar underlying diseases, radiological features and prognosis to patients already classified as possible IPA. Independent risk factors for mortality were classification as probable IPA according to 2020 EORTC/MSGERC criteria, lack of remission from hematologic malignancy, and number of nodules in Thorax CT. The use of 2020 EORTC/MSGERC criteria resulted in a 27.3% significant reduction in probable IPA diagnoses and created a more homogeneous category of patients with respect to treatment response, prognosis and mortality. Therefore, 2020 EORTC/MSGERC criteria afford more reliable mortality prediction than 2008 EORTC/MSG criteria.

Research progress on pulmonary aspergillosis in patients with bronchiectasis

Research progress on pulmonary aspergillosis in patients with bronchiectasis

P262 Clinico- microbiological profile of post-COVID pulmonary fungal infections encountered during the second wave of COVID-19 pandemic at a tertiary care teaching hospital in the Himalayas

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectiveThe study aims to generate preliminary data about post-COVID pulmonary fungal infections in the Himalayas and analyze patients’ micro-radio-clinical profiles and outcomes.MethodologyWe conducted a retrospective study at a tertiary care teaching hospital in the Himalayas to generate preliminary post-COVID pulmonary fungal infection data. Sputum, Endotracheal Tube (ET), and Bronchoalveolar lavage (BAL) samples of patients sent to the Mycology laboratory were subjected to KOH mount and aerobic inoculation on Sabouraud dextrose agar plates at 37°C. The patients’ symptoms, diagnosis, clinical-radiological profile, and outcome were collected from the hospital database.ResultsAmong n = 16 cases of post-COVID pulmonary fungal infections aged 53 +/- 13.38 years, n = 7 (43.75%) had Pulmonary Aspergillosis (n = 5 A. fumigatus, n = 1 A. flavus, n = 1 A. niger), n = 5 (31.25%) had Pulmonary Mucormycosis (Rhizopus arrhizus), and n = 4 (25%) had mixed infection. In 2 of 4 mixed infection patients, R. arrhizus was identified on KOH microscopy and A. fumigatus on SDA Agar. Both A. fumigatus and R. arrhizus were identified on KOH Microscopy of the third patient, while only A. fumigatus was cultivated on his SDA Agar. Aspergillus flavus and R. arrhizus were isolated simultaneously from the sample of the last patient, but only R. arrhizus was identified on KOH Microscopy.Clinical symptoms were similar among Pulmonary Aspergillosis and Mucormycosis patients, but hemoptysis was reported only among Pulmonary Aspergillosis patients. Pre-existing co-morbid end-organ damage, AKI, CKD, CLD, COPD, and CAD was more common among Pulmonary Mucormycosis patients and rare among Pulmonary Aspergillosis patients. Treatment requirements and clinical outcomes of patients infected with either mold were similar. The clinical profile of mixed infection patients was notably different from the others. All the patients were males, none complained of chest pain or expectoration, and none had a history of PTB, AKI, CKD, CLD, COPD, or CAD. Only 2 (50%) mixed infection patients needed supplemental high flow oxygen, unlike all (100%) patients diagnosed with single mold infection. None of the mixed infection patients required steroids. Moreover, none of the mixed infection patients died, unlike 60% mortality in cases of single-species infections.On radiological investigation, n = 6 had typical thick-walled cavitary lesions with air-fluid levels and multiple centrilobular nodules giving a tree in bud appearance, of which n = 4 had bilateral lung involvement, and n = 2 had only one lung involved. n = 1 patient had a well-circumscribed lung abscess.ConclusionCOVID patients from the Himalayas had a higher prevalence of invasive pulmonary fungal infections, probably due to the dense surrounding vegetation. The immuno-compromised state following COVID-19 infection/treatment might be responsible for the progression of regular exposure to invasive pulmonary infection.

Metabolomic profiling of exhaled breath condensate for the diagnosis of pulmonary aspergillosis.

ObjectiveThis study aims to ascertain the unique metabolic profile of exhaled breath condensate (EBC) samples in pulmonary aspergillosis (PA) patients, and explore their usefulness for the diagnosis of PA.MethodsA total of 133 patients were included in the study, including 66 PA patients (invasive pulmonary aspergillosis, n=3; chronic pulmonary aspergillosis, n=60; allergic bronchopulmonary aspergillosis, n=3) and controls (n=67). Ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS) was used to analyze EBC samples. Metabolic profiling of EBC samples that were collected from 22 CPA patients at various times during treatment (before treatment, <1 month, 1–2 months, 2–3 months, 3–6 months, and ≥6 months after treatment initiation) were performed using UHPLC-HRMS. Potential biomarkers were evaluated using cluster analysis, Venn diagram and receiver operating characteristic analysis (ROC).ResultsA total of 47 metabolites of potential interest were detected in the EBC samples. Further investigation showed that Asperpyrone C, Kotanin, Terphenyllin, Terrelumamide B, and Cyclotryprostatin D could be used as a diagnostic biomarker for PA. The classification between metabolic profiling of EBC samples from PA patients and controls was good with a sensitivity of 100%, specificity 89.6% for patients with PA, respectively. Venn diagram analysis of these biomarker candidates displayed three main types of compounds, which could be used for the further discrimination of aspergilloma and chronic cavitary PA. In addition, antifungal treatment had a limited influence on the value of the EBC results.ConclusionsThis metabolomic approach using UHPLC-HRMS could be used as a noninvasive method for the diagnosis of PA.

Invasive pulmonary aspergillosis in critically ill patients with pneumonia due to COVID-19, influenza, and community-acquired pneumonia: A prospective observational study.

Influenza A and SARS-CoV-2 are risk factors for invasive pulmonary aspergillosis. Both influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis result in high mortality and poor clinical outcomes. No prospective study has so far compared the features, treatment, and outcomes of influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis within a similar time frame. Therefore, this study aimed to determine the frequency, risk factors, and outcomes of invasive pulmonary aspergillosis in critically ill patients with influenza, COVID-19, and community-acquired pneumonia. This prospective study included adult patients with pneumonia and was conducted at The Aga Khan University Hospital in Karachi, Pakistan. Patients were divided into three groups, including community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia. The data collected included information on demographic characteristics, comorbidities, clinical features, laboratory results, treatment, and outcomes. A total of 140 patients were included in this study. These included 35 (25%), 70 (50%), and 35 (25%) patients with community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia, respectively. In addition, 20 (14.2%) patients were found to have invasive aspergillosis, of whom 10/35 (28.5%), 9/70 (12.8%), and 1/35 (2.8%) patients were in the COVID-19, influenza, and community-acquired pneumonia groups, respectively. Moreover, nine (90%) COVID-19-associated pulmonary aspergillosis patients required vasopressors, compared to three (33%) patients with influenza-associated pulmonary aspergillosis (P=0.020). In total, seven (70%) COVID-19-associated pulmonary aspergillosis patients required invasive mechanical ventilation compared to four (44%) influenza-associated pulmonary aspergillosis patients (P=0.37). The mean±SD length of hospital stay was highest in the COVID-19-associated pulmonary aspergillosis patients (18.3±7.28 days) compared to influenza-associated pulmonary aspergillosis patients (11.7±5.34 days) (P=0.036). The number of deaths in influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis patients was three (33.3%) and five (50%), respectively (P=0.526). A higher proportion of patients with COVID-19 developed invasive aspergillosis compared to those with influenza. Although the mortality rate in COVID-19-associated pulmonary aspergillosis was comparable to that in influenza-associated pulmonary aspergillosis patients, COVID-19-associated pulmonary aspergillosis patients had a significantly longer stay in the hospital.

Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study.

This study aimed to obtain further in-depth information on the value of metagenomic next-generation sequencing (mNGS) for diagnosing pulmonary aspergillosis in non-neutropenic patients. We did a retrospective study, in which 33 non-neutropenic patients were included, of which 12 were patients with pulmonary aspergillosis and 21 were diagnosed with non-pulmonary aspergillosis. Fungi and all other co-pathogens in bronchoalveolar lavage fluid (BALF) (27 cases), blood (6 cases), and/or pleural fluid (1 case) samples were analyzed using mNGS. One of the patients submitted both BALF and blood samples. We analyzed the clinical characteristics, laboratory tests, and radiologic features of pulmonary aspergillosis patients and compared the diagnostic accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value of mNGS with conventional etiological methods and serum (1,3)-β-D-glucan. We also explored the efficacy of mNGS in detecting mixed infections and co-pathogens. We further reviewed modifications of antimicrobial therapy for patients with pulmonary aspergillosis according to the mNGS results. Finally, we compared the detection of Aspergillus in BALF and blood samples from three patients using mNGS. In non-neutropenic patients, immunocompromised conditions of non-pulmonary aspergillosis were far less prevalent than in patients with pulmonary aspergillosis. More patients with pulmonary aspergillosis received long-term systemic corticosteroids (50% vs. 14.3%, p < 0.05). Additionally, mNGS managed to reach a sensitivity of 91.7% for diagnosing pulmonary aspergillosis, which was significantly higher than that of conventional etiological methods (33.3%) and serum (1,3)-β-D-glucan (33.3%). In addition, mNGS showed superior performance in discovering co-pathogens (84.6%) of pulmonary aspergillosis; bacteria, bacteria-fungi, and bacteria-PJP-virus were most commonly observed in non-neutropenic patients. Moreover, mNGS results can help guide effective treatments. According to the mNGS results, antimicrobial therapy was altered in 91.7% of patients with pulmonary aspergillosis. The diagnosis of Aspergillus detected in blood samples, which can be used as a supplement to BALF samples, seemed to show a higher specificity than that in BALF samples. mNGS is a useful and effective method for the diagnosis of pulmonary aspergillosis in non-neutropenic patients, detection of co-pathogens, and adjustment of antimicrobial treatment.

MAVS Expression in Alveolar Macrophages Is Essential for Host Resistance against Aspergillus fumigatus.

Our recent data demonstrate a critical role of the RIG-I-like receptor family in regulating antifungal immunity against Aspergillus fumigatus in a murine model. However, the importance of this pathway in humans and the cell types that use this innate immune receptor family to detect A. fumigatus remain unresolved. In this study, using patients who underwent hematopoietic stem cell transplantation, we demonstrate that a polymorphism in human MAVS present in the donor genome was associated with the incidence of invasive pulmonary aspergillosis. Moreover, in a separate cohort of confirmed invasive pulmonary aspergillosis patients, polymorphisms in the IFIH1 gene alter the inflammatory response, including IFN-responsive chemokines. Returning to our murine model, we now demonstrate that CD11c+ Siglec F+ alveolar macrophages require Mavs expression to maintain host resistance against A. fumigatus. Our data support the role of MAVS signaling in mediating antifungal immunity in both mice and humans at least in part through the role of MAVS-dependent signaling in alveolar macrophages.

Malignant course of invasive pulmonary aspergillosis in the new coronavirus infection COVID-19

Respiratory infections caused by fungal pathogens are the main cause of death in immunocompromised patients. During the COVID-19 pandemic, the registration of respiratory fungal pathology, especially pulmonary aspergillosis, has increased significantly.&#x0D; We present a histopathologically confirmed case of fatal invasive pulmonary aspergillosis complicating COVID-19. A 65-year-old patient with long-term diabetes backgrounded with a severe course of COVID-19 (the virus was identified ICD-10 code U07.1) described. During the illness bilateral polysegmental pneumonia of fungal-bacterial (Klebsiella pneumoniae) etiology with necrosis and sequestration of the affected tissue the lower lobe of the right lung with the formation of a fungal ball and the development of a right-sided pneumothorax was developed. In other parts of both lungs, focal destruction of the interalveolar septa was determined with the formation of small cavities filled with detritus and accumulations of segmented neutrophils, with the proliferation of fungal mycelium, positively stained in the PAS reaction. Fungal hyphae and conidial heads were also found in the lumens of individual bronchi and vessels with invasion of their walls. Long-term (more than one month) course of the disease, clinical and radiological dynamics, and detection of a forming connective tissue capsule along the periphery of the necrosis zone during microscopy testifies in favor of the subacute nature of the infection.&#x0D; The presented clinical case, as well as a review of current publications and meta-analyses on invasive pulmonary aspergillosis, point to diagnostic problems and poor outcomes of invasive pulmonary aspergillosis in patients with COVID-19.&#x0D; Pulmonary aspergillosis associated with COVID-19 is a serious and potentially life ― threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment. Early diagnosis of fungal infections is crucial to ensure the survival of such patients. Targeted biopsy examination with microscopy and/or seeding of a lung biopsy allows not only to establish the diagnosis of aspergillosis, but also to determine the presence of tissue invasion.&#x0D; Further research should include approaches aimed at developing an effective diagnosis of fungal tissue invasion and respiratory tract damage, determining the patients immune status in order to conduct personalized immunotherapy.