Incidence and risk factors for coronavirus disease 2019-associated pulmonary aspergillosis using administrative claims data.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is one of the noticeable complications of COVID-19 and its incidence varies widely. In Japan, research on the incidence, risk factors and mortality associated with CAPA is limited. OBJECTIVES: This study aimed to explore the incidence and potential risk factors for CAPA in patients with severe or critical COVID-19 and evaluate the relationship between CAPA and mortality of patients with severe or critical COVID-19. METHODS: We investigated the incidence of CAPA in patients with severe and critical COVID-19 using administrative claims data from acute care hospitals in Japan. We employed multivariable regression models to explore potential risk factors for CAPA and their contribution to mortality in patients with severe and critical COVID-19. RESULTS: The incidence of CAPA was 0.4%-2.7% in 33,136 patients with severe to critical COVID-19. Age, male sex, chronic lung disease, steroids, immunosuppressants, intensive care unit admission, blood transfusion and dialysis were potential risk factors for CAPA in patients with severe to critical COVID-19. CAPA was an independent factor associated with mortality. CONCLUSIONS: CAPA is a serious complication in patients with severe and critical COVID-19 and may increase mortality.

Clinical significance of chronic pulmonary aspergillosis in lung cancer patients undergoing anticancer drug therapy.

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.

An immunocompetent lady with invasive aspergillosis presenting as disseminated lesions: a case report.

BACKGROUND: Invasive Aspergillosis is a fungal infection caused by Aspergillus species, typically posing life-threatening risks to immunocompromised individuals. While occurrences in immunocompetent hosts are rare, a recent case report documented fulminant pulmonary aspergillosis in an immunocompetent patient during autopsy. Here, we present a case of invasive aspergillosis in an immunocompetent woman, manifesting with disseminated lesions. CASE PRESENTATION: A 29-year-old Asian woman presented to our hospital in March 2022, reporting chest pain and shortness of breath persisting for two months. Upon examination, she appeared thin and unwell, with no notable abnormalities otherwise. Radiographic imaging revealed an ill-defined lesion in her left lung. Subsequent bronchoscopy and lavage were performed, followed by initiation of empirical antibiotic therapy. Lavage results were negative for gram staining, culture, and ZN staining for AFB, but revealed numerous septate hyphae on fungal smear. Histopathological examination indicated chronic granulomatous inflammation with septal fungal hyphae, indicative of aspergillosis. Subsequent culture confirmed Aspergillus species, prompting initiation of voriconazole therapy. Remarkably, the patient exhibited significant improvement, with weight gain and restored appetite observed within a short period. Within 2 months of treatment, her symptoms resolved, and she resumed near-normal daily activities. CONCLUSION: This case highlights the diagnosis of aspergillosis in an immunocompetent individual presenting with disseminated nodular lesions across the lungs, mediastinum, and abdomen. Clinicians should maintain a high index of suspicion for aspergillosis in cases of non-resolving pneumonia and disseminated nodular lesions, even in patients lacking traditional predisposing factors.

Aspergillus-sensitized asthma in children.

BACKGROUND: Asthma is the most common chronic respiratory disease in childhood. Aspergillus fumigatus sensitivity may be involved in the pathogenesis of asthma by leading to different clinical presentations. OBJECTIVE: To investigate the demographic, clinical, laboratory, and radiological characteristics of A. fumigatus sensitivity in childhood asthma and identify associated risk factors and diagnostic parameters. METHODS: A total of 259 children with asthma were included in the study, 7 (2.7%) with allergic bronchopulmonary aspergillosis (ABPA), 84 (32.4%) with A. fumigatus-sensitized asthma (Af-SA), and 168 (64.9%) with A. fumigatus-unsensitized asthma (Af-UA). RESULTS: Aspergillus sensitivity was associated with early asthma onset and longer asthma duration. Total IgE level and asthma severity are highest in ABPA and higher in Af-SA. Absolute eosinophil count was higher, and FEV1 was lower in Af-SA and ABPA. Aspergillus fumigatus was associated with greater odds of being male (odds ratio [OR], 2.45), having atopic dermatitis (OR, 3.159), Alternaria sensitivity (OR, 10.37), and longer asthma duration (OR, 1.266). The best cut-off values for detecting A. fumigatus positivity were 363.5 IU/mL for total IgE and 455 cells/µL for absolute eosinophil count. In Af-SA compared to Af-UA, centrilobular nodules and peribronchial thickening were more common, and the bronchoarterial ratio was higher. CONCLUSIONS: Aspergillus sensitivity is a strong allergic stimulus in asthma, leading to laboratory, structural, clinical, and functional consequences. Af-SA is a distinct asthma endotype independent of ABPA that is characterized by increased risk of severe clinical presentations and impaired lung function.

Occurrence and case fatality rate of invasive aspergillosis in children with acute leukemia: A systematic review and meta-analysis.

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 3,661 ALL patients and 1,728 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.

A retrospective Italian analysis on the characteristics of invasive fungal infections in the intensive care unit setting: CHARTER-IFI study.

BACKGROUND: Invasive fungal infections (IFI), prevalent in critically ill ICU patients, have gained attention due to post-COVID-19 epidemiological shifts. Notably, COVID-19-associated aspergillosis and candidiasis pose significant risks. WHO recognises key fungal pathogens, emphasising the need for enhanced research and interventions. METHODS: The CHARTER-IFI study retrospectively examines 186,310 individuals admitted to ICUs in Italy from 01/01/2012-01/09/2023, utilising administrative databases covering around 10 million inhabitants. Adult patients were included having at least one ICU discharge diagnosis of IFI at their first IFI-related hospitalisation and having at least 12 months of available data prior to this hospitalisation. RESULTS: A total of 746 IFI patients discharged from ICU (incidence of 4.0 per 1000 ICU-hospitalised patients), were included. Median age was 68 years, 63% were males, and the overall Charlson Comorbidity Index was 2.2. The top three diagnoses were candidiasis (N = 501, 2.7/1000 ICU-hospitalised patients), aspergillosis (N = 71, 0.4/1000), and pneumocystosis (N = 55, 0.3/1000). The evaluation of the comorbidity profile in IFI patients revealed the presence of hypertension (60.5%), use of systemic GC/antibacterials (45.3% during 12 months before and 18.6% during 3 months before hospital admission), cancer (23.1%), diabetes (24.3%) and cardiovascular diseases (23.9%). The mean (±SD) length of hospitalisation in ICU was 19.9 ± 24.1 days (median 11 days), and deaths occurred in 36.1% of IFI patients (within 30 days from discharge). CONCLUSIONS: This retrospective analysis among ICU-hospitalised patients described the burden of IFI in ICU, and its understanding could be crucial to strengthen surveillance, investments in research, and public health interventions as required by WHO.

Population prevalence of aspergillus sensitization and allergic bronchopulmonary aspergillosis in COPD subjects in North India.

BACKGROUND: Sensitization to Aspergillus fumigatus (AS) has been recently described in chronic obstructive pulmonary disease (COPD) patients. However, there is no data on the community prevalence of AS in COPD. OBJECTIVES: To assess the prevalence of AS among COPD subjects. The secondary objectives were to (1) assess the prevalence of allergic bronchopulmonary aspergillosis (ABPA) in COPD and (2) compare the lung function in COPD subjects with and without AS. METHODS: We conducted a cross-sectional study in rural (29 villages) and urban (20 wards) communities in North India. We identified individuals with respiratory symptoms (IRS) through a house-to-house survey using a modified IUATLD questionnaire. We then diagnosed COPD through specialist assessment and spirometry using the GOLD criteria. We assayed A.fumigatus-specific IgE in COPD subjects. In those with A. fumigatus-specific IgE ≥0.35 kUA/L (AS), ABPA was diagnosed with raised serum total IgE and raised A.fumigatus-specific IgG or blood eosinophil count. RESULTS: We found 1315 (8.2%) IRS among 16,071 participants >40 years and diagnosed COPD in 355 (2.2%) subjects. 291 (82.0%) were men and 259 (73.0%) resided in rural areas. The prevalence of AS and ABPA was 17.7% (95% CI, 13.9-21.8) and 6.6% (95% CI, 4.4-8.8). We found a lower percentage predicted FEV1 in COPD subjects with AS than those without (p =.042). CONCLUSIONS: We found an 18% community prevalence of AS in COPD subjects in a specific area in North India. Studies from different geographical areas are required to confirm our findings. The impact of AS and ABPA on COPD requires further research.

Chronic ethanol exposure decreases H3K27me3 in the Il6 promoter region of macrophages and generates persistent dysfunction on neutrophils during fungal infection.

OBJECTIVE AND DESIGN: The aim of this study was to investigate the effects of ethanol exposure on epigenetic markers in bone marrow (BM) and their impact on inflammatory response during Aspergillus fumigatus infection. RESULTS: Chronic ethanol exposure decreased H3K27me3 enrichment in the Il6 promoter region while increased H3K4me3 enrichment in Tnf. Chimeric mice were generated by transplanting BM from mice exposed to ethanol or water. Infection of ethanol-chimeric mice culminated in higher clinical scores, although there was no effect on mortality. However, previous chronic exposure to ethanol affects persistently the inflammatory response in lung tissue, demonstrated by increased lung damage, neutrophil accumulation and IL-6, TNF and CXCL2 production in ethanol-chimeric mice, resulting in a decreased neutrophil infiltration into the alveolar space. Neutrophil killing and phagocytosis were also significantly lower. Moreover, BM derived macrophages (BMDM) from ethanol-chimeric mice stimulated with A. fumigatus conidia exhibited higher levels of TNF, CXCL2 and IL-6 release and a higher killing activity. The Il6 promoter of BMDM from ethanol-chimeric mice exhibited a reduction in H3K27me3 enrichment, a finding also observed in BM donors exposed to ethanol. CONCLUSIONS: These evidences demonstrate that prior chronic alcohol exposure of bone-marrow modify immune effector cells functions impairing the inflammatory response during A. fumigatus infection. These findings highlight the persistent impact of chronic ethanol exposure on infectious disease outcomes.

Outcomes of Patients with COVID-19 and Fungal Coinfections: A Systematic Review and Meta-Analysis Study.

Background & Objective: Fungal co-infections increase the incidence and mortality of viral respiratory tract infections. This study systematically reviews and conducts a meta-analysis to evaluate the prevalence of COVID-19 patients with fungal coinfections. The aim is to provide a concise overview of the impact of these infections on patient outcomes especially association with risk of mortality, informing future research and optimizing patient management strategies. Methods: To identify relevant studies on COVID-19 patients, we conducted a systematic search of databases from the beginning of the year until July 2023, including fungal co-infections, mortality, and sequelae. Eligibility criteria were developed using the PICO framework, and data extraction was carried out separately by two authors using standard techniques. Statistical analysis was performed using the correlation model and differences between studies were evaluated using the I2 test. R and RStudio were used for statistical analysis and visualization. Results: We initially identified 6,764 studies, and after checking for equivalence and consistency, 41 studies were included in the final analysis. The overall COVID-19 odds ratio for people who died from fungal infections was 2.65, indicating that patients infected with both COVID-19 and fungal infections had a higher risk of death compared to patients with COVID-19 alone. Specifically, COVID-19-associated pulmonary aspergillosis (CAPA) has a higher odds ratio of 3.36, while COVID-19-associated candidiasis (CAC) has an odds ratio of 1.84, and both are much more associated with death. However, coinfection of the fungus with other fungal species did not show a significant difference in the risk of mortality. Conclusion: This study identified CAPA and CAC as the most common infections acquired in healthcare settings. Fungal coinfections may be associated with an increased risk of death in COVID-19 patients.

An update on pharmacotherapy for fungal infections in allogeneic stem cell transplant recipients.

INTRODUCTION: Invasive fungal diseases (IFD) constitute a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients. AREAS COVERED: We describe epidemiology, causes and risk factors of IFD in allogeneic HSCT discussing prophylaxis and treatment in various HSCT phases. We present the most recent studies on this thematic area, including novel data on currently available antifungals, i.e. formulations, dosing, safety, efficacy and therapeutic drug monitoring. Finally, we present the most recent relevant recommendations published. Literature search included PubMed, Scopus, and clinicaltrials.gov between January 2014 and April 2024. EXPERT OPINION: The antifungal agents employed for prophylaxis and therapy should be predicated on local epidemiology of IFD. Fluconazole prophylaxis remains a first-line choice before engraftment when the main pathogen is Candida spp. After engraftment, prophylaxis should be with mold-active agents (i.e. triazoles). For candidiasis, echinocandins are suggested as first-line treatment, whereas aspergillosis responds well to mold-active azoles and liposomal amphotericin B (L-AmB). For mucormycosis, treatment of choice includes L-AmB and isavuconazole. Choice between fever-driven and diagnostics-driven strategies remains equivocal. Open research topics remain: 1) optimization of tools to ensure prompt and accurate IFD diagnosis to avoid unnecessary exposure to antifungals, drug interactions and cost; 2) refinement of treatment for resistant/refractory strains.

Aspergillus in the Indoor Air of Critical Areas of a Tertiary Hospital in Brazil.

Airborne Aspergillus spp. are critical pathogens that cause nosocomial infections in hospitals. Despite their importance, little is known about the distribution of Aspergillus species in the indoor air of hospitals in Brazil. We investigated Aspergillus spp. in the indoor air of critical areas in a tertiary hospital in Brazil. Air samples (n = 238) were collected from the intensive care unit (ICU), medical clinic unit (MCU), and urgency and emergency unit (UEU) using an air sampler (100 L/min). Of the 324 Aspergillus isolates, 322 were identified using phenotypic methods, and 37 were identified using DNA sequencing. Aspergillus spp. was grouped into five sections: Fumigati (29.3%), Nidulantes (27.8%), Nigri (27.5%), Flavi (11.7%), and Terrei (3.1%). The predominant species identified via sequencing were Aspergillus sydowii (n = 9), Aspergillus flavus (n = 7), and Aspergilus fumigatus (n = 6). The number of Aspergillus spp. and their sections varied according to the collection day. A. fumigatus was isolated more frequently during winter and in the ICU. This study is the first to demonstrate the diversity of airborne Aspergillus (saprophytic, allergenic, toxigenic, and potentially pathogenic) strains in a hospital located in the Midwest region of Brazil. It contributes to the knowledge of the diversity of cryptic species in the hospital environment.

Invasive Pulmonary Aspergillosis in Patients with HBV-Related Acute on Chronic Liver Failure.

BACKGROUND: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). METHODS: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. RESULTS: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. CONCLUSIONS: The WBC count might be used to monitor patients' progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels.

Atypical Presentation of Invasive Aspergillosis during Treatment with Mogamulizumab.

Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists.

The Expanding Mycovirome of Aspergilli.

Mycoviruses are viruses that infect fungi and are widespread across all major fungal taxa, exhibiting great biological diversity. Since their discovery in the 1960s, researchers have observed a myriad of fungal phenotypes altered due to mycoviral infection. In this review, we examine the nuanced world of mycoviruses in the context of the medically and agriculturally important fungal genus, Aspergillus. The advent of RNA sequencing has revealed a previous underestimate of viral prevalence in fungi, in particular linear single-stranded RNA viruses, and here we outline the diverse viral families known to date that contain mycoviruses infecting Aspergillus. Furthermore, we describe these novel mycoviruses, highlighting those with peculiar genome structures, such as a split RNA dependent RNA polymerase gene. Next, we delineate notable mycovirus-mediated phenotypes in Aspergillus, in particular reporting on observations of mycoviruses that affect their fungal host's virulence and explore how this may relate to virus-mediated decreased stress tolerance. Furthermore, mycovirus effects on microbial competition and antifungal resistance are discussed. The factors that influence the manifestation of these phenotypes, such as temperature, fungal life stage, and infection with multiple viruses, among others, are also evaluated. In addition, we attempt to elucidate the molecular mechanisms that underpin these phenotypes, examining how mycoviruses can be targets, triggers, and even suppressors of RNA silencing and how this can affect fungal gene expression and phenotypes. Finally, we highlight the potential therapeutic applications of mycoviruses and how, in an approach analogous to bacteriophage therapy, their ability to produce hypovirulence in Aspergillus might be used to attenuate invasive aspergillosis infections in humans.

Allergic bronchopulmonary aspergillosis as an initial manifestation of cystic fibrosis: Diagnostic and therapeutic implications in the era of CFTR modulators.

Allergic bronchopulmonary aspergillosis (ABPA) results from complex hypersensitivity reactions to Aspergillus fumigatus, which often occur in patients with asthma, cystic fibrosis (CF), or CF transmembrane conductance regulator (CFTR)-related disorders. Genetic predisposition, particularly variants of the CFTR gene, probably plays a significant role in the development of ABPA. We present the case of a 20-year-old male with ABPA and bronchiectasis that was initially misdiagnosed as a result of normal sweat chloride values and negative first-level genetic testing results. Comprehensive CFTR gene sequencing revealed 2 pathogenic variants, R347H and D1152H, which together with the clinical phenotype and functional tests, supported the diagnosis of CF. Treatment with elexacaftor/tezacaftor/ivacaftor resulted in significant clinical and functional improvement, including a marked decrease in total IgE levels, suggesting a potential role for CFTR modulators in controlling ABPA. This case illustrates the evolving understanding of CF as a spectrum of disorders in which CFTR dysfunction may manifest subtly and variably, necessitating a high index of suspicion and a comprehensive diagnostic approach to ensure timely treatment in the era of highly effective CFTR modulators.

Clinical Characteristics and the Prognostic Impact of Acute Kidney Injury in Critically Ill Patients with Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Retrospective, Single-Center Study.

Introduction: The incidence and impact of acute kidney injury (AKI) in patients with invasive pulmonary aspergillosis (IPA) admitted to the intensive care unit (ICU) are unknown. Methods: This retrospective study included 140 patients who were diagnosed with IPA and admitted to the medical ICU of China-Japan Friendship Hospital in Beijing, China. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. Data on demographic characteristics, comorbidities, laboratory tests, treatments, and prognosis at ICU admission were collected. Results: The rate of AKI was 71.4% (n = 100), and approximately 30% of the patients had preadmission acute kidney dysfunction. Of the 100 patients with AKI, 19, 8, and 73 patients had stage I, II, and III AKI, respectively, and 64 (87.6%) patients required continuous renal replacement therapy. Overall ICU mortality rate was 52.1%. Irreversible AKI was a strong independent risk factor for ICU mortality (odds ratio 13.36, 95% confidence interval 4.52-39.48, p < 0.001), followed by chronic lung disease, use of intermittent positive-pressure ventilation, and long-term corticosteroid treatment within 1 year prior to ICU admission. Higher cardiac troponin I levels at admission and worse volume control during the first 7 days of ICU stay were potential predictive factors of irreversible kidney dysfunction. Patients with irreversible AKI and those who died during the ICU stay had greater volume overload during the first 14 days of ICU stay. Patients who survived received earlier renal replacement therapy support after ICU admission compared to those who died (median, 2 vs. 5 days; p = 0.026). Conclusion: Compared to the patients with IPA in the absence of AKI, those with AKI presented with more volume overload, worse disease burden, and required stronger respiratory support, while experiencing worse prognosis. Irreversible AKI was a strong predictor of mortality in patients with critical IPA. Better volume control and earlier CRRT initiation should be considered key points in AKI management and prognostic improvement.

PANoptosis opens new treatment options for allergic bronchopulmonary aspergillosis.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a rare airway disorder primarily affecting patients with asthma and cystic fibrosis. Persistent airway inflammation brought on by Aspergillus fumigatus exacerbates the underlying condition and can cause significant respiratory damage. Treatments center on reducing inflammation with the use of corticosteroids and antifungals. PANoptosis is a new concept in the field of cell death and inflammation that posits the existence of cross talk and a master control system for the 3 programmed cell death (PCD) pathways, namely, apoptosis, pyroptosis, and necroptosis. This concept has revolutionized the understanding of PCD and opened new avenues for its exploration. Studies show that Aspergillus is one of the pathogens that is capable of activating PANoptosis via the Z-DNA binding protein 1 (ZBP1) pathway and plays an active role in the inflammation caused by this organism. Objective: This article explores the nature of inflammation in ABPA and ways in which PCD could lead to novel treatment options. Method: PubMed was used to review the literature surrounding Aspergillus infection-related inflammation and PANoptosis. Results: There is evidence that apoptosis and pyroptosis protect against Aspergillus-induced inflammation, whereas necroptosis promotes inflammation. Conclusion: Experimental medications, in particular, necroptosis inhibitors such as necrosulfonamide and necrostatin-1, should be studied for use in the treatment of ABPA.

Performance of the IMMY® sona Aspergillus lateral flow assay for the detection of galactomannan in tracheal aspirate samples from Brazilian patients with COVID-19-associated pulmonary aspergillosis: Cross-sectional and systematic review of literature.

During the COVID-19 pandemic, many patients in intensive care units (ICUs) were affected by invasive fungal infections, including aspergillosis, contributing to a high mortality rate. Diagnosing proven COVID-19-associated pulmonary aspergillosis (CAPA) requires clinical and radiological evaluations, along with laboratory testing of bronchoalveolar lavage samples or lung biopsies. However, these procedures and equipment are often inaccessible in developing countries or regions with limited resources, including Brazil. Consequently, alternative diagnostic methods, such as measuring Aspergillus galactomannan (GM) in tracheal aspirate (TA), have been explored for CAPA diagnosis. Nonetheless, research on the efficacy of TA-based diagnostic tests is limited. This study aimed to assess the performance of the IMMY® Sona Aspergillus lateral flow assay (LFA) for GM detection in TA samples from 60 ICU patients with suspected CAPA at two tertiary hospitals in Campo Grande, Brazil. The ELISA method (Platelia Aspergillus AG, Bio-Rad®) was used to detect Aspergillus GM in TA samples, serving as the microbiological criterion and reference test. Fifteen patients (12.4%) were identified as having possible CAPA. The overall accuracy of LFA was 94%, and the tests demonstrated an agreement of 93.1% (Cohen's kappa of 0.83). Based on our findings, the LFA for Aspergillus GM detection in TA samples exhibited excellent performance, proving to be a valuable diagnostic tool for potential CAPA. In a systematic review, two studies were included, and the meta-analysis revealed pooled estimates provided a sensitivity of 86% (95% CI, 80%-91%) and specificity of 93% (95% CI, 86%-97%). The diagnostic odds ratio (DOR) for identification of Aspergillus using LFA was 103.38 (95% CI, 38.03-281.03). Despite its lower sensitivity compared to our study, the LFA appears to be a promising diagnostic option for CAPA, particularly in suspected cases that have not received antifungal therapy. This enables timely antifungal treatment and could reduce mortality rates in regions where bronchoscopy is unavailable or limited.

A Case Report of Central Bronchiectasis in a Poorly Controlled Asthmatic Adolescent With Allergic Bronchopulmonary Aspergillosis and Secondary Spontaneous Pneumothorax.

Allergic bronchopulmonary aspergillosis (ABPA) is a multifaceted immune hypersensitivity reaction occurring in the lungs and bronchi, triggered by exposure and colonization of Aspergillus species, commonly Aspergillus fumigatus (A. fumigatus). It typically affects individuals who are immunocompetent but predisposed, such as those with bronchial asthma and cystic fibrosis. Diagnosis involves various methods including chest radiography, computed tomography, identification of eosinophilia, elevated serum IgE (immunoglobulin E) levels, and immunological tests for Aspergillus antigen. Left undiagnosed and untreated, ABPA can advance to bronchiectasis and/or pulmonary fibrosis, leading to significant morbidity and mortality.

A Case Report of Navigating Dual Respiratory Challenges: From Pulmonary Tuberculosis (PTB) to Allergic Bronchopulmonary Aspergillosis (ABPA).

This case study describes a unique scenario in which allergic bronchopulmonary aspergillosis (ABPA) was identified following treatment for pulmonary tuberculosis (PTB). ABPA is a complex pulmonary disorder that is often overlooked due to its nonspecific clinical presentation, especially in individuals concurrently diagnosed with tuberculosis (TB). Despite initial TB diagnosis and treatment, a 28-year-old male continued to experience respiratory symptoms, prompting further investigation that revealed underlying ABPA. This case underscores the importance of emphasizing the critical role of maintaining a high level of suspicion for ABPA in TB patients with persistent symptoms, highlighting the need for timely recognition and management to minimize further lung damage and improve patient outcomes.