Left Lung High-Density Shadow Combined with Elevated NSE Ultimately Confirmed as Pulmonary Aspergillosis.

BACKGROUND: Detection of serum neuron specific enolase (NSE) has high sensitivity and specificity in the diagnosis of lung cancer, especially small cell lung cancer, but sometimes serum NSE provides limited help. We report a case of high-density shadow of the left lung and elevated serum NSE which mimicked lung cancer. It was ultimately confirmed to be pulmonary aspergillosis (PA) by bronchoscopic alveolar lavage fluid (BALF) and next-generation sequencing (NGS). METHODS: Appropriate laboratory tests, chest computed tomography (CT) scan, bronchoscopic alveolar lavage fluid, and next-generation sequencing were used to explore latent causes. RESULTS: NSE level was elevated, chest CT scan showed high-density shadow of the left lung, bronchoscopy showed flesh-colored new organisms in the lower lobe of the left lung, BALF and NGS revealed the presence of Aspergillus. CONCLUSIONS: Elevated NSE is not a typical manifestation of lung cancer, and we should perform BALF and NGS early to determine whether there is infection with special pathogenic bacteria.

In situ follicular neoplasm discovered as an enlarging pulmonary nodule complicated by pulmonary aspergillosis.

In situ follicular B cell neoplasm, previously known as follicular lymphoma in situ, is a neoplastic proliferation of follicular lymphoma-like B cells confined to the germinal centers. Herein, we report a case of a woman in her 70s who initially presented with several enlarged abdominal lymph nodes. Seven months later during follow-up, a solitary pulmonary nodule was detected. As it was close to the hilum, lobectomy was performed. The intraoperative frozen section showed fibrosis and a collection of lymphocytes and macrophages. Therefore, the lymph nodes were sampled. Station 4 and 10 lymph nodes exhibited similar tumor cells and were immunohistochemically positive for CD10 and BCL2. Thus, the patient was diagnosed with in situ follicular neoplasm and is currently under observation. In situ follicular neoplasm is typically a slowly progressive neoplasm; however, it can present as a rapidly enlarging pulmonary nodule complicated by pulmonary aspergillosis.

Primary pulmonary leiomyosarcoma with coexistent pulmonary aspergillosis: a case report.

Coexisting primary pulmonary leiomyosarcoma (PPL) with pulmonary Aspergillosis in immunocompetent patients is a rare occurrence. Here, we presented a 54-year-old woman presented with a dry cough for two months. Bronchoscopy revealed pulmonary aspergillosis. The patient was treated with antifungal therapy for one month without improvement. To evaluate further, a chest computed tomography (CT) scan showed a large heterogeneous enhancing mass in the lower lobe of the left lung with left atrium thrombosis. Computed tomography-guided biopsy was performed, and histopathology demonstrated the diagnosis of PPL. The metastasis workup staging showed multiple metastases in vertebrae, scapula, rib, and liver. The patient was treated with chemotherapy followed by tumor bed radiotherapy. Unfortunately, her general condition worsened, and she passed away with overall survival of fourteen months. In conclusion, clinicians should be alert to underlying malignant disease if airway Aspergillus infection is suspicious in patients without strong risk factors for invasive fungal infection.

An Unusual Congenital Heart Disease: Giant Left Atrial Appendage.

A 52-year-old female was admitted to our hospital in April 2021 with dyspnea. She was discharged from the hospital 3 weeks ago due to the diagnosis of pneumonia caused by coronavirus disease 2019 (COVID-19). Physical examination revealed an oxygen desaturation of 82%. The patient underwent computed tomography angiography (CTA) that showed a ground-glass pattern and a giant left atrial appendage ( Figure 1A ). Film array respiratory panel was negative, and pulmonary aspergillosis was diagnosed after bronchoscopy. Cardiac magnetic resonance corroborated the huge left atrial appendage ( Figure 1B ). No other structural or functional heart abnormalities were diagnosed. A giant left atrial appendage is a rare cardiac anomaly that can be congenital or acquired. In the literature, it is called a left atrial appendage aneurysm. The dilatation can be generalized or focused. Although it can occur in all age groups, it is predominant in patients in their 30s to 50s and most common in females.1 Patients can be asymptomatic or present with symptoms such as palpitations, chest pain, or dyspnea. A number of recent cases in the literature have highlighted the diagnostic utility of CTA.2 While there is no standard treatment for this condition, surgical resection is the most frequent therapy. Another option reported in the literature is anticoagulant treatment for select cases.3 Closure of the left atrial appendage is a more recent and emerging intervention that can be considered. In our patient, we initiated anticoagulant therapy to reduce the risk of thromboembolic events; however, we recommended left atrial appendage occlusion or surgical resection after completing the treatment for pulmonary aspergillosis.

Thoracic Air Leak Syndrome, Pulmonary Aspergillosis, and COVID-19 Pneumonia After Allogeneic Stem Cell Transplantation in a Child With Myelodysplastic Syndrome.

Thoracic air leak syndromes (TALS) are very rare among the noninfectious pulmonary complications (PCs). They can either be idiopathic or have several risk factors such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft versus host disease and rarely pulmonary aspergillosis. We present a 14-year-old girl with hypoplastic myelodysplastic syndrome who developed graft versus host disease on day 60, TALS on day 150, bronchiolitis obliterans syndrome on day 300, pulmonary aspergillosis on day 400 and COVID-19 pneumonia on day 575 after allo-HSCT. This is the first report of a child who developed these subsequent PCs after allo-HSCT. Therefore, the manifestations of these unfamiliar PCs like TALS and COVID-19 pneumonia, and concomitant pulmonary aspergillosis with management options are discussed.

Lung eosinophils elicited during allergic and acute aspergillosis express RORγt and IL-23R but do not require IL-23 for IL-17 production.

Exposure to the mold, Aspergillus, is ubiquitous and generally has no adverse consequences in immunocompetent persons. However, invasive and allergic aspergillosis can develop in immunocompromised and atopic individuals, respectively. Previously, we demonstrated that mouse lung eosinophils produce IL-17 in response to stimulation by live conidia and antigens of A. fumigatus. Here, we utilized murine models of allergic and acute pulmonary aspergillosis to determine the association of IL-23, IL-23R and RORγt with eosinophil IL-17 expression. Following A. fumigatus stimulation, a population of lung eosinophils expressed RORγt, the master transcription factor for IL-17 regulation. Eosinophil RORγt expression was demonstrated by flow cytometry, confocal microscopy, western blotting and an mCherry reporter mouse. Both nuclear and cytoplasmic localization of RORγt in eosinophils were observed, although the former predominated. A population of lung eosinophils also expressed IL-23R. While expression of IL-23R was positively correlated with expression of RORγt, expression of RORγt and IL-17 was similar when comparing lung eosinophils from A. fumigatus-challenged wild-type and IL-23p19-/- mice. Thus, in allergic and acute models of pulmonary aspergillosis, lung eosinophils express IL-17, RORγt and IL-23R. However, IL-23 is dispensable for production of IL-17 and RORγt.

Pulmonary Aspergillosis: Spectrum of Disease.

Aspergillus species are ubiquitous in the environment. Aspergillosis is acquired by inhalation of Aspergillus spores. In normal hosts, spore inhalation rarely causes lung disease. Pulmonary Aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive Aspergillosis to Aspergillus bronchitis. Invasive Aspergillosis usually occurs in severely immunocompromised patients, typically in neutropenic but also in non-neutropenic patients. Chronic pulmonary Aspergillosis affects patients with chronic structural lung disease such as COPD or previous mycobacterial lung disease, but without other significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such as bronchiectasis. Allergic bronchopulmonary Aspergillosis affects patients with bronchial asthma or cystic fibrosis, and is due to an allergic response to Aspergillus.

A Murine Model for Chronic A. fumigatus Airway Infections.

In addition to causing acute invasive infections in immunocompromised patients, the mold Aspergillus fumigatus causes chronic infections in patients with chronic pulmonary conditions such as cystic fibrosis. Here we describe a non-lethal model of chronic pulmonary aspergillosis in which immunocompetent mice are endotracheally infected with A. fumigatus conidia embedded in agar beads. This approach results in the establishment of hyphal infection within the airways of mice for up to a 28-day period and is amenable to the study of innate and adaptive antifungal responses, fungal mutant strains, and antifungal agents.

Automated Quantitative Analysis of Airway Epithelial Cell Detachment Upon Fungal Challenge.

Host-pathogen interactions involve a complex interplay between host and pathogen factors, resulting in either host protective immunity or establishment of disease. One of the hallmarks for disease progression is host tissue destruction. The first host surface to interact with the opportunistic respiratory fungal pathogen, Aspergillus fumigatus, is the airway epithelium. Unravelling the mechanisms involved in airway epithelial cell damage by A. fumigatus is essential to understanding the establishment and progression of infection in the host. Although host cell damage can be measured in vitro by indirect cell lysis assays, here, we describe an automated, simple, and low-cost assay to directly visualize and quantify epithelial cell line damage after challenge with A. fumigatus. We employ the previously characterized tissue noninvasive A. fumigatus ΔpacC mutant to demonstrate the quantitative difference in cell damage relative to its parental tissue invasive strain. This assay is easily scaled up for high-throughput screening of multiple Aspergillus mutants and can be adapted to suit diverse host cell lines, different time points of infection, challenge with other microbes, and drugs or novel compounds.

Successful treatment with nivolumab in a patient with lung adenocarcinoma complicated by pulmonary aspergilloma.

Immune checkpoint inhibitors (ICIs) are the key drugs used in patients with non-small cell lung cancer (NSCLC). However, anti-PD-1 therapy might worsen chronic infection by reactivating the immune response to infectious diseases. Here, we describe a case of successful treatment with nivolumab in a patient with NSCLC complicated by pulmonary aspergilloma, which was safely treated by surgical resection before administration of nivolumab. In conclusion, to safely treat patients with locally limited chronic pulmonary aspergillosis (CPA), surgical resection should be considered before ICI therapy.

Chronic granulomatous 'Aspergillus lung mass'.

The diverse clinicopathological spectrum of pulmonary aspergillosis is a consequence of varying levels of invasiveness of this ubiquitous fungus, which largely depends on the host immune response and pre-existing lung disease. The clinical presentation of pulmonary aspergillosis spans a wide spectrum from hypersensitivity to life threatening angio-invasive and disseminated disease. We report the case of a young immunocompetent male with no underlying lung disease, who presented with an incidentally detected 'infective mass' lesion in the lung associated with minimal respiratory symptoms. The diagnostic challenges posed by the unusual clinical, radiological and histological picture as well as the therapeutic dilemmas faced are discussed in this report.

NLRX1 is a key regulator of immune signaling during invasive pulmonary aspergillosis.

Aspergillus fumigatus is an opportunistic fungal pathogen of immunocompromised patient populations. Mortality is thought to be context-specific and occurs via both enhanced fungal growth and immunopathogenesis. NLRX1 is a negative regulator of immune signaling and metabolic pathways implicated in host responses to microbes, cancers, and autoimmune diseases. Our study indicates loss of Nlrx1 results in enhanced fungal burden, pulmonary inflammation, immune cell recruitment, and mortality across immuno-suppressed and immuno-competent models of IPA using two clinically derived isolates (AF293, CEA10). We observed that the heightened mortality is due to enhanced recruitment of CD103+ dendritic cells (DCs) that produce elevated amounts of IL-4 resulting in a detrimental Th2-mediated immune response. Adoptive transfer of Nlrx1-/- CD103+ DCs in neutropenic NRG mice results in enhanced mortality that can be ablated using IL-4 neutralizing antibodies. In vitro analysis of CD103+ DCs indicates loss of Nlrx1 results in enhanced IL-4 production via elevated activation of the JNK/JunB pathways. Interestingly, loss of Nlrx1 also results in enhanced recruitment of monocytes and neutrophils. Chimeras of irradiated Nlrx1-/- mice reconstituted with wild type bone marrow have enhanced neutrophil recruitment and survival during models of IPA. This enhanced immune cell recruitment in the absence of Nlrx1 is mediated by excessive production of CXCL8/IL-8 family of chemokines and IL-6 via early and enhanced activation of P38 in response to A. fumigatus conidia as shown in BEAS-2B airway epithelial cells. In summary, our results point strongly towards the cell-specific and contextual function of Nlrx1 during invasive pulmonary aspergillosis and may lead to novel therapeutics to reduce Th2 responses by CD103+ DCs or heightened recruitment of neutrophils.

Late histopathologic characteristics of critically ill COVID-19 patients: Different phenotypes without evidence of invasive aspergillosis, a case series.

PURPOSE: Pathological data of critical ill COVID-19 patients is essential in the search for optimal treatment options. MATERIAL AND METHODS: We performed postmortem needle core lung biopsies in seven patients with COVID-19 related ARDS. Clinical, radiological and microbiological characteristics are reported together with histopathological findings. MEASUREMENT AND MAIN RESULTS: Patients age ranged from 58 to 83 years, five males and two females were included. Time from hospital admission to death ranged from 12 to 36 days, with a mean of 20 ventilated days. ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. Chest CT in all patients showed ground glass opacities, commonly progressing to nondependent consolidations. We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia. None of the biopsy specimens showed any signs of invasive aspergillosis. CONCLUSIONS: In this case series common late histopathology in critically ill COVID patients is not classic DAD but heterogeneous with predominant pattern of organizing pneumonia. Postmortem biopsy investigations in critically COVID-19 patients with probable COVID-19 associated pulmonary aspergillosis obtained no evidence for invasive aspergillosis.

Detection of anatomical variation during left internal jugular vein cannulation under ultrasound: A case report.

RATIONALE: The left internal jugular vein has a higher possibility of anatomical variation than the right side. Therefore, the complication risk during cannulation is expected to be higher. PATIENT CONCERNS: A 74-year-old woman was scheduled for elective surgery for left upper lobe wedge resection. We observed an anatomical abnormality at the location of the common carotid artery (CCA) and left internal jugular vein (IJV). DIAGNOSIS: During the ultrasound, the left IJV was detected at the medial side of the CCA, and this anatomical variation was confirmed by color Doppler ultrasonography. Enhanced chest computed tomography showed that the left CCA ran across the left IJV from medial to lateral at the level of the clavicle. INTERVENTION: A triple-lumen central venous catheter was inserted at the right IJV to avoid complications caused by the anatomical variation. OUTCOMES: There were no intraoperative or postoperative complications. LESSONS: Anesthesiologists should consider anatomical variation during central venous cannulation, especially with the left IJV approach. Because of anatomical variation, ultrasound-guided intervention is highly recommended to prevent procedure-related complications.

Platelets are critical for survival and tissue integrity during murine pulmonary Aspergillus fumigatus infection.

Beyond their canonical roles in hemostasis and thrombosis, platelets function in the innate immune response by interacting directly with pathogens and by regulating the recruitment and activation of immune effector cells. Thrombocytopenia often coincides with neutropenia in patients with hematologic malignancies and in allogeneic hematopoietic cell transplant recipients, patient groups at high risk for invasive fungal infections. While neutropenia is well established as a major clinical risk factor for invasive fungal infections, the role of platelets in host defense against human fungal pathogens remains understudied. Here, we examined the role of platelets in murine Aspergillus fumigatus infection using two complementary approaches to induce thrombocytopenia without concurrent neutropenia. Thrombocytopenic mice were highly susceptible to A. fumigatus challenge and rapidly succumbed to infection. Although platelets regulated early conidial phagocytosis by neutrophils in a spleen tyrosine kinase (Syk)-dependent manner, platelet-regulated conidial phagocytosis was dispensable for host survival. Instead, our data indicated that platelets primarily function to maintain hemostasis and lung integrity in response to exposed fungal antigens, since thrombocytopenic mice exhibited severe hemorrhage into the airways in response to fungal challenge in the absence of overt angioinvasion. Challenge with swollen, heat-killed, conidia was lethal in thrombocytopenic hosts and could be reversed by platelet transfusion, consistent with the model that fungus-induced inflammation in platelet-depleted mice was sufficient to induce lethal hemorrhage. These data provide new insights into the role of platelets in the anti-Aspergillus host response and expand their role to host defense against filamentous molds.

Madelung's disease and pulmonary aspergillosis: a case report and literature review.

BACKGROUND: Madelung's disease (MD) is a rare disorder of fat metabolism, which is usually associated with diabetes, hyperuricemia, liver disease, nevertheless there is no report of a patient with MD and pulmonary aspergillosis (PA). This article aimed to enhance the awareness of this two diseases and discuss the possible mechanism of the combination of them preliminarily. CASE PRESENTATION: In this case, we described a 56-year-old male patient with cough, expectoration and dyspnea. His neck has a very peculiar appearance. Chest enhanced CT scan showed there were multiple nodules in both lungs, some of which had cavities and the mediastinal lymph nodes were swollen. Ultrasound scan of the neck showed diffuse hyperplasia of subcutaneous fat in neck and bilateral supraclavicular fossa. Fortunately, after performing pulmonary wedge resection aimed at pathological examination and giving relevant treatments, this patient was finally diagnosed as MD with PA, and his symptoms were significantly relieved. CONCLUSIONS: MD is rare, the phenomenon that MD combined with PA is rarer. Immune disorder may be the possible mechanism.

Fatal Hemoptysis Due to Endobronchial Aspergilloma in the Hyperinflated Native Lung after Single-Lung Transplantation for Lymphangioleiomyomatosis: A Case Report.

Pulmonary lymphangioleiomyomatosis accounts for the majority of cadaveric lung transplantation cases. Post-transplantation management is continuingly necessary not only to prevent the progression of LAM but also to address complications. A woman with lymphangioleiomyomatosis underwent cadaveric lung transplantation. She developed post-operative native lung hyperinflation and hemoptysis with cavity shadow in the native lung on computed tomography. Isolated Aspergillus from her sputum and positive Aspergillus galactomannan antigen in the blood led to a diagnosis of aspergillosis. Despite the reduction of hemoptysis by antifungal medication, she developed fatal hemoptysis. An autopsy showed an Aspergillus fungal mass in the bronchus in the native lung whilst the lung graft was free from lymphangioleiomyomatosis lesions. Endobronchial aspergilloma was suggested to be a cause of hemoptysis. This fatal clinical course suggested that hemoptysis due to endobronchial aspergilloma in the native lung should have been considered native lung pneumonectomy as a further intervention.