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ABSTRACT Background Methods Results Conclusion The 2015 International Society for Heart and Lung Transplant (ISHLT) fungal guidelines recommend the use of bronchoalveolar lavage (BAL) galactomannan over serum galactomannan for the diagnosis of invasive aspergillosis (IA) in lung transplant (LTx) recipients, based on limited evidence. Galactomannan testing is costly.A single‐center, retrospective cohort study reviewing all 814 serum and BAL galactomannan samples received from 184 LTx recipients in our center between 2021 and 2022 and assessing their diagnostic performance in the diagnosis of IA.Over the study period, 394 serum galactomannan samples were received from 144 patients and 420 BAL galactomannan samples from 143 patients. Using a cut‐off of ≥ 1.0 for BAL galactomannan, the sensitivity and specificity were 65.9% and 98.4%, respectively. In total, 30 patients had positive BAL galactomannan. Antifungal therapy was commenced or continued in 29 of these patients either as targeted or pre‐emptive treatment. Using a cut‐off of ≥ 0.5 for serum galactomannan, the sensitivity and specificity were 9.7% and 99.7%, respectively. In total, four patients had a positive serum galactomannan. All four patients were either already on antifungal treatment for IA or were started before the serum galactomannan result was available, supported by laboratory, clinical, and radiological findings. A positive serum galactomannan was used to monitor treatment response in one patient.Serum galactomannan is not a valuable test in the diagnosis of IA in our LTx recipients, is costly, and does not remove the need for bronchoscopy and BAL galactomannan. This supports the ISHLT recommendation. [ABSTRACT FROM AUTHOR]

Rationale: The influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza-associated pulmonary aspergillosis (IAPA) or coronavirus disease (COVID-19)–associated pulmonary aspergillosis (CAPA) has yet to be explored. Objectives: To explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity, and outcome in severe influenza versus COVID-19 with or without aspergillosis. Methods: We performed a retrospective study in mechanically ventilated patients with influenza and COVID-19 with or without invasive aspergillosis in whom BAL for bacterial culture (with or without PCR) was obtained within 2 weeks after ICU admission. In addition, 16S rRNA gene sequencing data and viral and bacterial load of BAL samples from a subset of these patients, and of patients requiring noninvasive ventilation, were analyzed. We integrated 16S rRNA gene sequencing data with existing immune parameter datasets. Measurements and Main Results: Potential bacterial pathogens were detected in 20% (28/142) of patients with influenza and 37% (104/281) of patients with COVID-19, whereas aspergillosis was detected in 38% (54/142) of patients with influenza and 31% (86/281) of patients with COVID-19. A significant association between bacterial pathogens in BAL fluid and 90-day mortality was found only in patients with influenza, particularly patients with IAPA. Patients with COVID-19, but not patients with influenza, showed increased proinflammatory pulmonary cytokine responses to bacterial pathogens. Conclusions: Aspergillosis is more frequently detected in the lungs of patients with severe influenza than bacterial pathogens. Detection of bacterial pathogens associates with worse outcome in patients with influenza, particularly in those with IAPA, but not in patients with COVID-19. The immunological dynamics of tripartite viral–fungal–bacterial interactions deserve further investigation. [ABSTRACT FROM AUTHOR]

There is clearly a need for novel antifungal agents, not only concerning spectrum, but also oral bioavailability, tolerability, and drug-drug interactions. There is growing concern for antifungal resistance for current available antifungals, mainly driven by environmental fungicide use or long-term exposure to antifungals, in the setting of mould-active prophylaxis or for chronic antifungal infections, such as chronic pulmonary aspergillosis. Moreover, the incidence of breakthrough infections is increasing, because of the introduction of (mould-active) prophylaxis (1-4). There is emergence of difficult to treat invasive fungal infections, such as those caused by Lomentospora prolificans, cryptic species of Aspergillus, Scedosporium and Coccidioides. Olorofim (F901318) is the first-in class of the orotomides, a novel antifungal class targeting dihydroorotate dehydrogenase (DHODH), a key enzyme in the biosynthesis of pyrimidines. Olorofim shows good in vitro and in vivo activity against Aspergillus species, rare and difficult to treat moulds and endemic dimorphic fungi, including azole- and amphotericin-resistant isolates. It lacks activity against yeasts and the Mucorales species. It is only orally available and shows very promising results in ongoing clinical trials. In this review we will describe the mechanism of action of olorofim, the spectrum of activity in vitro and in vivo, pharmacokinetics, pharmacodynamics, drug-drug interactions, resistance, and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the diagnostic and prognostic value of Aspergillus-specific IgG (Asp-IgG) for invasive pulmonary aspergillosis (IPA) in non-neutropenic non-hematologic patients. Methods: Between November 2019 and February 2022, we recruited 40 non-neutropenic, non-hematologic IPA patients from Taiwan and measured serum Asp-IgG levels using Phadia, Thermofisher. A positive Asp-IgG test was defined as a level > 40 mgA/L. We evaluated the association between Asp-IgG levels and overall survival, as well 90-day mortality rate of IPA patients. Results: Of the 40 participants, 11 (27.5%) tested positive for Asp-IgG, while 16 (40%) had positive galactomannan antigen (optical density > 1). Higher Asp-IgG levels were associated with improved overall survival (HR: 0.22, 95% CI: 0.05–0.99, p = 0.035) in multivariable Cox regression. The overall 90-day mortality rate was 65% (26/40). We found that patients with low Asp-IgG levels (≤ 40 mgA/L) had a borderline higher 90-day mortality rate compared to patients with high Asp-IgG levels (OR: 3.15, 95% CI: 0.75–13.28, p = 0.118). Stratifying by serum galactomannan and Aspergillus IgG levels, patients with elevated serum GM and low Asp-IgG had the highest 90-day mortality (80%, 8/10), followed by patients with low serum GM and low Asp-IgG (68.4%, 13/19). Conclusions: Asp-IgG was positive in approximately one-fourth of non-neutropenic IPA patients. Asp-IgG may hold potential as a clinical prognostic factor for IPA. Further studies are required to validate this finding. [ABSTRACT FROM AUTHOR]

Objective: To verify whether the bleeding risk assessment guidelines from the 9th American College of Chest Physicians (ACCP) are prognostic for respiratory intensive care unit (RICU) patients and to explore risk factors for hemorrhages, we conducted a secondary data analysis based on our previously published cohort study of venous thromboembolism. Patients and methods: We performed a secondary data analysis on the single-center prospective cohort from our previous study. Patients admitted to the RICU at Beijing Chao-Yang Hospital from August 1, 2014 to December 31, 2020 were included and followed up until discharge. Results: The study enrolled 931 patients, of which 715 (76.8%) were at high risk of bleeding, while the remaining were at low risk. Of the total, 9.2% (86/931) suffered major bleeding, and no significant difference was found between the two risk groups (p = 0.601). High-risk patients had poor outcomes, including higher mortality and longer stays. Independent risk factors for major bleeding were APACHE II score ≥ 15; invasive pulmonary aspergillosis; therapeutic dose of anticoagulants; extracorporeal membrane oxygenation; and continuous renal replacement therapy. Blood transfusion not related to bleeding appeared to be an independent protective factor for major bleeding (OR 0.099, 95% CI 0.045–0.218, p < 0.001). Conclusion: Bleeding risk assessment models from the 9th ACCP guidelines may not be suitable for patients in RICU. Building a bleeding risk assessment model that is suitable for patients in all RICUs remains a challenge. Trial registration ClinicalTrials.gov: NCT02213978. [ABSTRACT FROM AUTHOR]

Introduction: Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant Aspergillus strains can complicate antifungal therapy. In addition, drug-resistant influenza viruses are becoming an increasing concern in clinics. A drug that affects fungal and viral propagation could overcome these disadvantages. Thus, we conducted a study to examine the antifungal and antiviral properties of ProcCluster® and procaine hydrochloride (HCl), which are prodrugs derived from the local anesthetic procaine. Methods: Conidia of different A. fumigatus strains, A. flavus and A. terreus were treated with the test substances in a human cell-free system and antifungal properties were analyzed either by fluorescence microscopy or absorption measurements. Changes in metabolic activity and intracellular Ca2+ distribution during treatment of A. fumigatus with ProcCluster® were observed using fluorescence microscopy. In addition, antifungal and antiviral properties of ProcCluster® and procaine HCl were investigated during in vitro coinfection of lung epithelial cells with A. fumigatus and influenza A viruses (IAV). Analysis was performed by fluorescence microscopy, standard plaque assay and Western blot assay. Results: Both substances inhibited the growth of the fungus, even when applied after germination or in the presence of purified IAV particles. ProcCluster® remained effective against triazole-resistant A. fumigatus strains. However, the addition of CaCl2 reversed the antifungal effect, indicating that ProcCluster® inhibited fungal growth by disrupting fungal Ca2+ homeostasis. Furthermore, in vitro studies showed that ProcCluster® and procaine HCl reduced the pathogen load of IAV and A. fumigatus during coinfection. Finally, the combination of ProcCluster® with the antiviral drug favipiravir exhibited increased antipathogenic activity, particularly against IAV replication. Discussion: This research highlights ProcCluster® and procaine HCl as substances with anti-infective properties against various pathogens. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionThe objective of this study is to in silico predict Aspergillus fumigatus specific B-cell epitopes with a focus on enhancing Allergic Bronchopulmonary Aspergillosis (ABPA) diagnostic precision by using and to validate using molecular docking of Aspergillus fumigatus specific B-cell epitopes, aiming to overcome current serological and clinical method limitations and to support specific therapies and preventive strategies for better ABPA management.The sequences of Asp f1, Asp f2, Asp f3, and Asp f4 from NCBI were analyzed using IEDB-AR for B-cell epitope prediction. Structural modeling and molecular docking analysis were conducted using MODELER and HADDOCK, respectively, with visualization via PyMOL and PDBe PISA.For Asp f1, two IgE-specific (40–47) and four IgG–specific (33–76, 125–148) B-cell epitopes were predicted. Asp f3 had one IgG-specific epitope (47–73), and Asp f4 had two IgG-specific epitopes (52–133) with no IgE epitopes. Asp f2 had eight IgE-specific epitopes (56–63, 93–99, 136–146, 153–160, 185–194, 200–206, 229–239) with IgPred scores above 0.931 and no IgG-specific epitopes. Molecular docking with HADDOCK Z-scores showed strong interactions between IgE and Asp f1 and Asp f2 epitopes. PyMOL and PISA-EBI identified key residues: LYS43 in Asp f1 forms a salt bridge with the IgE heavy chain. In Asp f2, out of nineteen identified residues, six residues (LYS 94, ARG 153, ASP 200, ASP 204, ASP 207 and GLU 233) were confirmed as part of the predicted IgE epitopes, exhibiting significant interactions with IgE, in agreement with both PyMOL and PISA analysis.This study aimed to enhance ABPA diagnostics by identifying key B-cell epitopes of Aspergillus fumigatus through in silico prediction and molecular docking, a way to support personalized therapies and preventive strategies in future. [ABSTRACT FROM AUTHOR]

Background: Aspergillomas are globular growths of Aspergillus fumigatus, a benign aspergillosis of the lungs. It usually affects patients who are immunocompromised and have anatomically defective lung structures. The majority of aspergilloma cases are asymptomatic, despite the fact that 10% of cases spontaneously resolve. Most patients do not have any symptoms from their lesions. Direct serological or microbiological evidence of an Aspergillus species along with radiologic evidence is required for the diagnosis of an aspergilloma. Case: We describe a 35-year-old adult Oromo male patient who had been experiencing night sweats, an intermittent productive cough with sparse whitish sputum, loss of appetite, and easy fatigability for 3 months. At 5 years prior, he received treatment for pulmonary tuberculosis that was smear-positive and was subsequently certified healed. Objectively, he was tachypneic and had intercostal, subcostal, and supraclavicular retractions with symmetric chest movement. A high-resolution computed tomography scan revealed bilateral apical cavitary lesions with core soft tissue attenuating spherical masses and an air crescentic sign suggestive of aspergillomas, which were confirmed by sputum light microscopic examination. The patient was managed with antibiotics and antifungals. Conclusion: Aspergilloma is a symptom of chronic pulmonary aspergillosis, a category of lung disorders caused by a persistent Aspergillus infection. Primary aspergillomas are uncommon and frequently occur in people with compromised immune systems. A prolonged cough, fever, chest pain, and hemoptysis are all symptoms of pulmonary aspergillomas. The majority of the time, pulmonary aspergillosis is difficult to identify. Despite high mortality and morbidity rates, surgery is still the most effective treatment for pulmonary aspergilloma. [ABSTRACT FROM AUTHOR]

Background: Invasive pulmonary aspergillosis (IPA) is a serious fungal infection. However, current diagnostic methods have limitations. The purpose of this study was to use artificial intelligence to achieve a more accurate diagnosis of IPA. Methods: Totally 263 patients (148 cases of IPA, 115 cases of non-IPA) were retrospectively enrolled from a single institution and randomly divided into training and test sets at a ratio of 7:3. Clinic-radiological independent risk factors for IPA were screened using univariate analysis and multivariate logistic regression analysis, after which a clinic-radiological model was constructed. The optimal radiomics features were extracted and screened based on CT images to construct the radiomics label score (Rad-score) and radiomics model. The optimal DL features were extracted and screened using four pre-trained convolutional neural networks, respectively, followed by the construction of the DL label score (DL-score) and DL model. Then, the radiomics-DL model was constructed. Finally, the combined model was constructed based on clinic-radiological independent risk factors, the Rad-score, and the DL-score. LR was adopted as the classifier. Receiver operating characteristic (ROC) curves were drawn, and the areas under the curve (AUC) were calculated to evaluate the efficacy of each model in predicting IPA. Additionally, based on the best-performing model on the LR classifier, four other machine learning (ML) classifiers were constructed to evaluate the predictive value for IPA. Results: The AUC of the clinic-radiological model for predicting IPA in the training and test sets was 0.845 and 0.765, respectively. The AUC of the radiomics-DL and combined models in the training set was 0.871 and 0.932, while in the test set was 0.851 and 0.881, respectively. The combined model showed better predictive performance than all other models. DCA showed that taking 0.00–1.00 as the threshold, the clinical benefit of the combined model was higher than that of all other models. Then, the combined model was trained on four other machine learning classifiers, all of which achieved AUC values above 0.80 in the test set, showing good performance in predicting IPA. Conclusion: Clinic, CT radiomics, and DL combined model could be used to predict IPA effectively. [ABSTRACT FROM AUTHOR]

Invasive fungal infections in patients with leukemia carry a high mortality rate, but early diagnosis has the potential to modify this natural history. A novel screening method using Aspergillus droplet-digital polymerase chain reaction in exhaled breath condensate may have a similar performance to serum galactomannan screening. Larger studies, including other molds, are necessary. [ABSTRACT FROM AUTHOR]

Introduction: Although the progression of invasive Aspergillosis (IA) shares some risk factors in the development of active Pulmonary Tuberculosis (PTB), however, the prevalence of IA in PTB remains unclear. Material and methods: 100 consecutive sputum samples with proven PTB between 12.7.203 and 7.12.23 were collected during the study period. All sample were processed for KOH mount followed by culture on SDA, if growth appeared colony were processed by slide culture followed by LPCB. Result: out of 100 sputum samples positive for Pulmonary Tuberculosis, 8 samples were found positive for pulmonary Aspergillosis of which A. fumagatus, A.flavus and A.niger were 4, 3 and 1 respectively. [ABSTRACT FROM AUTHOR]

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disorder characterized by an exaggerated immune response to fungal allergens, particularly from Aspergillus fumigatus. ABPA leads to excessive mucus production and impaired mucociliary clearance. When A. fumigatus conidia are inhaled, they germinate, release exoproteases and other substances that further impede mucociliary clearance, and activate the immune response. The immune response is known by an exaggerated Th2 response to Aspergillus antigens, leading to production of IgE antibodies, eosinophilic infiltration of the lungs, and the formation of immune complexes. These immune complexes can deposit in the lung tissue, leading to airway inflammation, bronchiectasis, and fibrosis. This disease mainly occurs in individuals diagnosed with bronchial asthma and cystic fibrosis. Increased levels of A. fumigatus total IgE and specific IgE, IgG, and IgA antibodies, play a role in diagnosing patients with ABPA. [ABSTRACT FROM AUTHOR]

Introduction: Aspergillus species cause a broad range of infections, from Allergic Bronchopulmonary Aspergillosis (ABPA) to invasive aspergillosis. Accurate species-level identification is crucial for diagnosis and treatment, especially since some rare Aspergillus species exhibit increased resistance to common antifungal agents. Aim: To identify Aspergillus species at the species complex level and determine the emergence of cryptic Aspergillus species using Multilocus Sequence Analysis (MLSA). Materials and Methods: This descriptive cross-sectional study was conducted over eight months, from January 2023 to August 2023, in three tertiary care centres in Chennai, India. Sixty Aspergillus strains were isolated from various clinical samples. The primary inclusion criteria were patients with suspected aspergillosis, categorised based on the European Organszation for Research and Treatment of Cancer Mycoses Study Group (EORTC-MSG) criteria. Isolates were grown on Oatmeal Agar or Sabouraud Dextrose Agar (SDA) and phenotypically identified using tease mount and slide culture techniques. Genomic fungal Deoxyribonucleic acid (DNA) was extracted and amplified using specific primers for Internal transcribed spacer (ITS), beta-tubulin, hydrophobin, and calmodulin genes, followed by nucleic acid sequencing. Results: Among the 60 Aspergillus isolates, the Aspergillus flavus complex comprised 26 (43.3%), the Aspergillus fumigatus complex 16 (26.7%), the Aspergillus niger complex 12 (20%), and the Aspergillus terreus complex 6 (10%). Initial speciation relied on microscopic and cultural characteristics. Isolates were recovered from various clinical specimens: bronchial wash 6 (10%), Bronchoalveolar lavage (BAL) fluid 10 (16.7%), sputum 3 (5%), ear swab 20 (33.3%), endotracheal aspirate 8 (13.3%), pus and tissue from the nasal cavity and paranasal sinus 11 (18.3%), and tissue from other sites 2 (3.3%). MLSA identified common species such as A. flavus, A. fumigatus, A. terreus, and A. niger, as well as rare species including A. awamori, A. carneus, A. lentulus, A. oryzae, A. tamarii, A. tubingensis, and A. welwitschiae. Sequence identity ranged from 99% to 100%, confirming species diversity. Phylogenetic analysis using ITS, beta-tubulin, hydrophobin, and calmodulin genes supported species identification with robust bootstrap support (1000 replications). Conclusion: Cryptic Aspergillus species are prevalent in clinical samples from the South Indian population, with a notable presence from the section Nigri and the first-time isolation of Aspergillus carneus in clinical samples from India. Molecular identification is essential for determining the invasive potential and guiding appropriate antifungal therapy. [ABSTRACT FROM AUTHOR]

Objectives: Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendations. Methods: We extracted key recommendations from the updated 2024 ISHAM‐AWG guidelines, focusing on critical areas: screening and diagnosis of ABPA, managing acute and treatment‐dependent ABPA, and monitoring treatment response. Each item was assigned a score ranging from zero to three. We assigned negative scores to interventions not recommended by the guidelines. Results: We identified 38 items indicative of optimal clinical care for patients with ABPA. The score for screening asthmatics for ABPA was set at three points. For diagnosing ABPA, 16 items were included, with a score ranging from 12 to 16 points, depending on the specific components used (predisposing conditions, serum A. fumigatus‐specific IgE and IgG, serum total IgE, blood eosinophil count and chest computed tomography). The management of acute ABPA comprised 11 items, with a maximum score of three points. For treatment‐dependent ABPA, there were nine items (scores ranging from −3 to 6). Follow‐up care comprised 10 items with a maximum score of 10–13 points, covering imaging, spirometry, testing serum total IgE levels and therapeutic drug monitoring. Conclusions: The EQUAL ABPA score has been developed as a comprehensive tool to quantify guideline adherence. Future studies will evaluate to which extent guideline adherence is associated with improved clinical outcomes for patients with ABPA. [ABSTRACT FROM AUTHOR]

Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large‐subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult‐to‐culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non‐tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and β‐D‐glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway‐derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections. [ABSTRACT FROM AUTHOR]

Objectives: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection characterised by the slowly progressing destruction of the lung parenchyma and has four main subtypes. The objective of this work was to evaluate the epidemiology of CPA in our area and evaluate the involvement of the different subtypes in mortality. Methods: This was a descriptive longitudinal retrospective study developed in three tertiary hospitals in Spain. Among all patients admitted with a pulmonary aspergillosis diagnosis, we selected those who fulfilled the criteria for chronic aspergillosis according to the criteria of Denning, excluding those with a haematological disorder. Results: Among 409 inpatients recorded as having a pulmonary aspergillosis infection, only 76 (18.5%) fulfilled the criteria for CPA, with an estimated incidence of 0.67 cases/100,000 inhabitants/year. The subtypes detected were subacute invasive aspergillosis (SAIA) in 33 (43.4%) patients, simple aspergilloma (SA) in 25 (32.9%) patients, cavitary chronic aspergillosis (CCPA) in 13 (17.1%) patients, and chronic fibrosis (CFPA) in five (6.5%) patients. The overall three-month mortality rate was 23%, which was higher in SAIA patients. The predictors of early mortality were age > 65 years (OR 3.0 CI 95 1.0–9.5 p = 0.043) and the SAIA subtype vs. other subtypes (OR 3.1 CI 95 1.0–9.5 p = 0.042). Conclusions: The incidence rate estimated was inferior to that previously reported. The three-month mortality in patients with CPA was high, with older age and the SAIA subtype being the variable independent predictors of a worse prognosis. [ABSTRACT FROM AUTHOR]

This article explores the use of biologic therapies such as dupilumab, mepolizumab, and benralizumab in treating severe asthma, emphasizing their efficacy and safety in improving symptoms and disease control. The studies underscore the benefits of personalized treatment approaches and combining different biologic therapies for optimal outcomes. Additionally, the article discusses the immunogenic properties of Bet v 1 conjugated with the TLR7-agonist TL7-887, suggesting a potential for enhanced allergy vaccines. The study on hereditary angioedema in Belarus sheds light on the challenges faced by patients in accessing effective treatments, while a case report highlights the efficacy of targeted therapy in managing mastocytosis. Lastly, the article emphasizes the importance of recognizing emerging allergens like fenugreek and managing drug-induced skin reactions like acute generalized exanthematous pustulosis. [Extracted from the article]

Background: Invasive aspergillosis affects solid organ transplant (SOT) recipients, carrying a high risk of mortality and morbidity in this population. Rapid and accurate diagnosis is essential to ensure the initiation of correct antifungal therapy. We aimed to evaluate the performance of the bronchoalveolar lavage (BAL) Eurofins Viracor Aspergillus PCR (AspPCR) in diagnosing invasive pulmonary aspergillosis (IPA) in SOT recipients. Methods: We conducted a multicenter retrospective study of SOT recipients in Arizona from February 2019 to December 2022 who had AspPCR done at the time of the clinical encounter. Probable IPA was defined as a positive BAL culture with Aspergillus spp. with clinical and imaging findings of IPA per EORTC/MSGERC criteria. Results: Ninety‐nine SOT recipients with 131 encounters with BAL AspPCR testing were included. The median age was 66, the majority were White, non‐Hispanics (60%), and males (66%). Among the participants, 93 lung transplant recipients with 87 of the encounters received antifungal prophylaxis active against Aspergillus spp. Sixty‐four encounters had BAL galactomannan (GM), all of which had BAL GM <1 OD, and one case had a serum GM of 10 OD. Nine cases met the definition of IPA. The sensitivity of the BAL AspPCR was 67% (95% CI 30%–93%), and the specificity was 98% (95% CI 93%–99%). Conclusion: BAL AspPCR had moderate sensitivity and high specificity in identifying IPA in our cohort of SOT recipients. Further studies in populations with a higher prevalence of IPA are needed to evaluate the performance of this test. [ABSTRACT FROM AUTHOR]

Background: This retrospective observational study was conducted to study the clinical profile, indications, post-operative complications and long-term outcome of patients having pulmonary aspergilloma. Methods: From January 2013 to October 2023, 25 patients underwent surgery for pulmonary aspergilloma at our tertiary care institute. Patients were broadly classified into simple and complex Aspergilloma based on clinical and CT findings. Results: The group consisted of 16 males and 9 females with a mean age of 41 years for 10 years. The most common indication for surgery was Heomptysis (76%). The underlying lung diseases were tuberculosis (76%), bronchiectasis (8%), and lung abscess (4%). The procedures performed were lobectomy (88%), pneumonectomy (4%), Cavernostomy (4%) and segmental resection (4%). The post-operative mortality was 4% (one patient). Overall complications occurred in 12 (23.07%) patients. The complications included prolonged air leak (32%), bleeding (12%), repeated pneumothorax (4%), and wound dehiscence (4%). Conclusion: Pulmonary aspergilloma, a fungal infection frequently encountered in developing countries like India with high rates of tuberculosis, can be effectively treated through surgical resection. This procedure is considered the gold standard for preventing recurrent symptoms, especially hemoptysis. Early surgical intervention, accompanied by thorough preoperative preparation, meticulous surgical technique, and diligent postoperative chest physiotherapy, can significantly reduce the rate of complications. While complications may still arise, particularly in cases with underlying lung pathology, the long-term prognosis for patients undergoing surgical resection of pulmonary aspergilloma is generally positive. [ABSTRACT FROM AUTHOR]

Purpose: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. Methods: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. Results: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/μL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. Conclusions: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management. [ABSTRACT FROM AUTHOR]

Background: The utility of two disease-severity indices, namely bronchiectasis severity index (BSI) and FACED score in allergic bronchopulmonary aspergillosis (ABPA) remains unknown. Objective: To correlate the BSI and FACED scores with immunological parameters (serum IgE [total and A. fumigatus-specific], A. fumigatus-specific IgG, blood eosinophil count), and high-attenuation mucus on chest computed tomography in ABPA. The secondary objectives were to evaluate the correlation between BSI and FACED scores and correlate the BSI/FACED scores with the bronchiectasis health questionnaire (BHQ) and Saint George's Respiratory Questionnaire (SGRQ). Methods: We included treatment-naïve ABPA subjects with bronchiectasis in a prospective observational study. We computed the BSI and FACED scores for each subject before initiating treatment. The subjects also completed two quality-of-life questionnaires (BHQ and SGRQ). Results: We included 91 subjects. The mean (standard deviation) BSI and FACED scores were 3.43 (3.39) and 1.43 (1.27). We found no correlation between BSI or FACED with any immunological parameter or high-attenuation mucus. There was a strong correlation between BSI and FACED scores (r = 0.76, p < 0.001). We found a weak correlation between BSI and BHQ/SGRQ and FACED and SGRQ. Conclusion: We found no correlation between BSI and FACED with immunological parameters in ABPA. However, we found a significant correlation between BSI and FACED and a weak correlation between SGRQ and BHQ. ABPA likely requires a separate disease-severity scoring system. [ABSTRACT FROM AUTHOR]

The article presents a case study of unresolved pneumonia in a 43-year-old male admitted to the ICU due to an endobronchial mass obstructing the left main bronchus. Typically, patients with community-acquired pneumonia show improvement within 3-5 days; however, persistent symptoms or radiologic infiltrates indicate non-resolving pneumonia, necessitating the ruling out of alternative diagnoses such as tuberculosis or cancer, and assessment of treatment efficacy and patient compliance.

Background: Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. Methods: We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. Results: The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57–73% response rate). Conclusions: We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections. [ABSTRACT FROM AUTHOR]

Background: Clinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined. Case presentation: A 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient's respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, βD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis. Conclusion: The patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected. [ABSTRACT FROM AUTHOR]

Background: Idiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL. Case Presentation: We herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis. Conclusions: Nocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Invasive pulmonary aspergillosis (IPA) typically occurs in immunocompromised individuals. Severe fever with thrombocytopenia syndrome (SFTS) patients are typically characterized by fever, thrombocytopenia, and leukopenia. These patients typically present with dysregulation of cellular and humoral immunity, which may predispose them to IPA. Our study aimed to identify risk factors for SFTS-associated invasive pulmonary aspergillosis (SAPA) and evaluate its associated prognostic impact. Methods: We conducted a cohort study between January 2017 and December 2022 in a tertiary hospital in Wuhan City, China. All SFTS patients hospitalized in our department who formally consented were divided into a SAPA group and a non-SAPA group according to whether they were coinfected with aspergillosis or not. The independent risk factors for the SAPA group were determined by multivariate logistic regression. Receiver operating characteristic (ROC) analysis was used to assess the statistical value of parameters to predict SAPA patients. The survival analysis was carried out using the Kaplan--Meier (KM) method. Results: Of the 269 hospitalized SFTS patients enrolled in the study, 118 (43.87%) cases were diagnosed with SAPA with an average age of 65.71 ± 9.7 years. Multivariate logistic regression analysis revealed that age, neurological complications, serum severe fever with thrombocytopenia syndrome virus (SFTSV) RNA loads, the white blood cell (WBC) count, platelet (PLT) count, albumin (ALB) and globulin (GLB) concentrations, and cardiac troponin I (cTNI) were complementary risk factors for the development of IPA in SFTS patients. The risk score is calculated as 5 times age, plus 6 times neurological complications, plus 10 times RNA (log), plus 5 times WBC, minus 5 times PLT, minus 5 times ALB, plus 5 times GLB, and plus 6 times cTNI. ROC curve analysis showed that the area under the receiver operating characteristic (AUROC) curve represented a risk score of 0.837 (95% CI: 0.789--0.885, p < 0.001) for predicting IPA in SFTS patients. The average length of hospitalization in the SAPA group was more prolonged than non-SAPA. SAPA and non-SAPA groups had significantly different mortality rates: 25.42% (SAPA) and 3.97% (non-SAPA) (p < 0.05). Conclusion: SFTS patients with IPA have high morbidity and mortality. Early monitoring of neurological complications, SFTSV RNA loads, WBC, PLT, ALB, GLB, and cTNI in SFTS patients may be useful in predicting the occurrence of IPA. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a refractory chronic respiratory infectious disease and its prevalence is increasing globally. The standard treatment regimen for NTM-PD involves long-term multidrug therapy including macrolides. The incidence of adverse events is high given the advanced age of many NTM-PD patients. In addition, drug-drug interactions under coexisting conditions add additional complexity. Despite guidelines advocating multidrug therapy for NTM-PD, low adherence rates probably owing to the relatively frequent adverse events and drug interactions. An appropriate treatment regimen can improve the bacteriological response rates, reduce the development of macrolide resistance, and mitigate adverse events. Of particular concern are the interactions arising from new complications that develop with NTM-PD. Notably, chronic pulmonary aspergillosis occasionally co-infects NTM-PD, which can lead to poor prognosis. The primary therapeutic modality for chronic pulmonary aspergillosis is the azoles. However, the interaction with rifamycin is problematic, making it challenging to continue standard treatment for NTM-PD and requiring drug adjustments. The implications of rifamycin extend beyond chronic pulmonary aspergillosis, impacting various other diseases such as those requiring immunosuppressive agents and AIDS patients requiring antiretroviral therapy. Hence, a comprehensive consideration of drug interactions is imperative for the initiation of NTM-PD treatment. This mini-review focuses on drug-drug interactions in a multidrug regimen for NTM-PD and discusses the essential points to be considered in the treatment of NTM. [ABSTRACT FROM AUTHOR]

Background: Advances in anticancer drugs for lung cancer (LC) have improved the prognosis of LC. Chronic pulmonary aspergillosis (CPA) is a progressive and often exacerbating respiratory disease with a poor prognosis. To date, the prognosis of LC complicated by CPA has not been elucidated. This study investigated the clinical implications of concomitant CPA in patients with LC undergoing anticancer drug treatment. Methods: Between January 2010 and May 2020, we consecutively enrolled patients with LC complicated with CPA at five different institutions in Japan. We analyzed patients with LC complicated by CPA who received anticancer drug treatment. Results: A total of 10 patients with LC complicated by CPA received anticancer drug treatment. The median overall survival (OS) was 14.57 months (95% confidence interval [CI]: 5.37–21.67). The cause of death in all patients was LC. Six of the seven patients with LC did not show worsening pulmonary aspergillosis lesions during the anticancer drug treatment. Although two patients discontinued anticancer drug treatment due to pneumonitis, CPA complications did not interfere with the continuation of anticancer drug treatment. In univariate analyses, squamous histology (p = 0.01) and body mass index (<18.5 kg/m2) (p = 0.0008) were significantly associated with poorer OS. Conclusions: This study demonstrated that the cause of death in LC patients with concomitant CPA who received anticancer drug treatments and effective antifungal treatment was LC progression. Further large‐scale studies are needed to identify the effect of CPA in patients with LC. [ABSTRACT FROM AUTHOR]

Introduction: Chronic obstructive pulmonary disease is a lung condition characterized by chronic respiratory symptoms (breathlessness, cough, and expectoration). In the advanced stages, patients often report to the Accident & Emergency department due to worsening of symptoms. Because of the repeated exposure to corticosteroids during the management of exacerbations, these patients are susceptible to super additional infections. Pulmonary aspergillosis can be divided into three main categories: invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. Aspergillus overlap syndrome is defined as the presence of more than one form of Aspergillus in a single patient. However, coinfection with Klebsiella and pulmonary aspergillosis overlap syndrome is rare and poses a treatment challenge. As per a pub med search, no such case report has been reported in a case of chronic obstructive pulmonary disease. Case report: We report the case of a 66-year-old male, Punjabi Hindu by ethnicity, who was a reformed smoker with a known case of COPD. He presented with a history of breathlessness (mMRC grade 4) associated with cough with expectoration and wheezing for 15 days and intermittent episodes of hemoptysis for more than 6 months. The examination revealed tachypnea and wheezing throughout the lung fields. He was initially managed with parenteral steroids and frequent nebulization with bronchodilators. On day 5 of hospitalization, the patient experienced worsening of symptoms and cardiac arrest; he was intubated and return of spontaneous circulation was achieved within 5 minutes of cardio pulmonary resuscitation. Tracheal aspirate and culture revealed Aspergillus fumigatus and Klebsiella pneumoniae respectively. He underwent chest CT, which showed features suggestive of allergic bronchopulmonary aspergillosis and invasive pulmonary aspergillosis. He was found to have elevated β-d-glucan, galactomannan, and aspergillus IgE and IgG. Severe pneumonia and pulmonary Aspergillus overlap syndrome were managed with antibiotics, steroids, and antifungals. Over the next 15–20 days, his general condition improved. He was discharged after 45 days of hospitalization and continued on oral corticosteroids, antifungals, and inhaled bronchodilators. Conclusion: Coinfection with bacteria and fungi worsens the outcome. Clinicians should be aware of the polymicrobial manifestations and various drug interactions involved. Timely diagnosis aids in better management strategies and improved patient outcomes. [ABSTRACT FROM AUTHOR]

COVID-19 associated pulmonary aspergillosis (CAPA) had been reported, and raised concern about this secondary infection due to the high mortality. This study aimed to investigate the risk factors for CAPA. The enrolled 114 COVID-19 patients were further divided into CAPA group and non-CAPA group. Demographic characteristics, underlying diseases, laboratory parameters and therapeutic schedule between the two groups were compared to identify the independent risk factors for CAPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent risk factors were confirmed by receiver operating characteristic (ROC) curve analysis. Univariate analysis showed that renal transplant, IL-6 and CRP levels, decreased CD4 + T cell and CD8 + T cell, duration of antibiotics therapy, and prolonged mechanical ventilation were risk factors for development of CAPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that elevated IL-6 level, decreased CD4 + T cell and prolonged mechanical ventilation could be recognized as independent risk factors for CAPA in COVID-19 patients. Identification of these risk factors is essential to initiate antifungal therapy as soon as possible to improve outcome of patients with CAPA. [ABSTRACT FROM AUTHOR]

Fungal pathogens exhibit extensive strain heterogeneity, including variation in virulence. Whether closely related non-pathogenic species also exhibit strain heterogeneity remains unknown. Here, we comprehensively characterized the pathogenic potentials (i.e., the ability to cause morbidity and mortality) of 16 diverse strains of Aspergillus fischeri, a non-pathogenic close relative of the major pathogen Aspergillus fumigatus. In vitro immune response assays and in vivo virulence assays using a mouse model of pulmonary aspergillosis showed that A. fischeri strains varied widely in their pathogenic potential. Furthermore, pangenome analyses suggest that A. fischeri genomic and phenotypic diversity is even greater. Genomic, transcriptomic, and metabolic profiling identified several pathways and secondary metabolites associated with variation in virulence. Notably, strain virulence was associated with the simultaneous presence of the secondary metabolites hexadehydroastechrome and gliotoxin. We submit that examining the pathogenic potentials of non-pathogenic close relatives is key for understanding the origins of fungal pathogenicity. Examination of Aspergillus fischeri, a non-pathogenic close relative of the major fungal pathogen Aspergillus fumigatus, revealed extensive strain heterogeneity in virulence and identified an association with specific metabolic differences. [ABSTRACT FROM AUTHOR]

Background: Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians' understanding of the disease and to facilitate early diagnosis and treatment. Case presentation: A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. infection. Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates. Conclusion: Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) is a potentially life-threatening complication of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). We conducted a systematic review and meta-analyses of studies on acute leukemia in children aged 0–17 years since 2000. Findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We included 24 studies with 3661 ALL patients and 1728 AML patients. IA cumulative incidence varied (0%–10% for ALL and 0%–18% for AML) across the studies. Pooled cumulative IA incidences were estimated at 3.2% (95% CI: 1.8%–5.8%) in ALL and 5.2% (95% CI: 3.1%–8.6%) in AML, with corresponding case fatality rates of 13.3% (95% CI: 6.3%–25.9%), and 7.8% (95% CI: 0.7%–51.2%), respectively. Our analysis highlights the impact of IA in childhood leukemia, underscoring the need to address strategies for prevention, early detection, and treatment of IA in pediatric leukemia. [ABSTRACT FROM AUTHOR]