Lung and sinus fungal infection imaging in immunocompromised patients.

BACKGROUND: Imaging is a key diagnostic modality for suspected invasive pulmonary or sinus fungal disease and may help to direct testing and treatment. Fungal diagnostic guidelines have been developed and emphasize the role of imaging in this setting. We review and summarize evidence regarding imaging for fungal pulmonary and sinus disease (in particular invasive aspergillosis, mucormycosis and pneumocystosis) in immunocompromised patients. OBJECTIVES: We reviewed data on imaging modalities and findings used for diagnosis of invasive fungal pulmonary and sinus disease. SOURCES: References for this review were identified by searches of PubMed, Google Scholar, Embase and Web of Science through 1 April 1 2023. CONTENT: Computed tomography imaging is the method of choice for the evaluation of suspected lung or sinus fungal disease. Although no computed tomography radiologic pattern is pathognomonic of pulmonary invasive fungal disease (IFD) the halo sign firstly suggests an angio-invasive pulmonary aspergillosis while the Reversed Halo Sign is more suggestive of pulmonary mucormycosis in an appropriate clinical setting. The air crescent sign is uncommon, occurring in the later stages of invasive aspergillosis in neutropenic patients. In contrast, new cavitary lesions should suggest IFD in moderately immunocompromised patients. Regarding sinus site, bony erosion, peri-antral fat or septal ulceration are reasonably predictive of IFD. IMPLICATIONS: Imaging assessment of the lung and sinuses is an important component of the diagnostic work-up and management of IFD in immunocompromised patients. However, radiological features signs have sensitivity and specificity that often vary according to underlying disease states. Periodic review of imaging studies and diagnostic guidelines characterizing imaging findings may help clinicians to consider fungal infections in clinical care thereby leading to an earlier confirmation and treatment of IFD.

Longitudinal multimodal imaging-compatible mouse model of triazole-sensitive and -resistant invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis (IPA) caused by the mold Aspergillus fumigatus is one of the most important life-threatening infections in immunocompromised patients. The alarming increase of isolates resistant to the first-line recommended antifungal therapy urges more insights into triazole-resistant A. fumigatus infections. In this study, we systematically optimized a longitudinal multimodal imaging-compatible neutropenic mouse model of IPA. Reproducible rates of pulmonary infection were achieved through immunosuppression (sustained neutropenia) with 150 mg/kg cyclophosphamide at day -4, -1 and 2, and an orotracheal inoculation route in both sexes. Furthermore, increased sensitivity of in vivo bioluminescence imaging for fungal burden detection, as early as the day after infection, was achieved by optimizing luciferin dosing and through engineering isogenic red-shifted bioluminescent A. fumigatus strains, one wild type and two triazole-resistant mutants. We successfully tested appropriate and inappropriate antifungal treatment scenarios in vivo with our optimized multimodal imaging strategy, according to the in vitro susceptibility of our luminescent fungal strains. Therefore, we provide novel essential mouse models with sensitive imaging tools for investigating IPA development and therapy in triazole-susceptible and triazole-resistant scenarios.

Invasive pulmonary aspergillosis in solid-organ transplant patients in the intensive care unit.

INTRODUCTION: Solid-organ transplantation (SOT) is a well-known risk factor for invasive pulmonary aspergillosis (IPA). We report on the epidemiology and outcome of SOT patients with IPA in an intensive care unit (ICU) setting. METHODS: This is a secondary study based on a subset of SOT patients from a prospective observational multicenter cohort (the AspICU project) including ICU patients with at least one Aspergillus spp. positive culture. Cases were classified as proven, probable, or putative IPA, or as Aspergillus-colonized. Mortality was reported at 12 weeks. RESULTS: The study included 52 SOT patients (of which 18 lung, 17 liver, 12 kidney, and five heart transplants). Sixteen patients had proven IPA, 28 were categorized as putative IPA (of which only five reached a probable IPA diagnosis according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group and Research Consortium criteria), and eight as Aspergillus-colonization. Among patients with IPA, 20 (45.5%) developed IPA during their ICU stay following transplantation whereas 24 patients (54.5%) had a medical ICU admission. Regarding medical imaging, nearly all IPA cases presented with non-specific findings as only nine demonstrated robust findings suggestive for invasive fungal disease. Overall, severity of the disease was reflected by a high prevalence of underlying conditions and acute organ derangements. Mortality among patients with IPA was 68%. Lung transplantation was associated with better survival (50%). CONCLUSION: IPA in SOT patients in the ICU develops in the presence of overall high severity of the disease. It rarely presents with suggestive medical imaging thereby hampering diagnosis. IPA in ICU patients with SOT carries a grim prognosis.

Characteristics of the Computed Tomography Imaging Findings in 72 Patients with Airway-Invasive Pulmonary Aspergillosis.

BACKGROUND This multiple-center retrospective study aimed to investigate computed tomography (CT) imaging findings in 72 patients with airway-invasive pulmonary aspergillosis. MATERIAL AND METHODS Seventy-two patients with airway-invasive pulmonary aspergillosis confirmed by pathology results were divided into 3 types according to image characteristics. Type I involved the trachea or the main bronchus. Type II involved the lobular and segmental bronchi, which manifested early as bronchial wall thickening, and later development was divided into types IIa and IIb. Type IIa manifested as bronchiectasis, and type IIb manifested as consolidation around the bronchus. Type III involved the bronchioles and pulmonary parenchyma, with tree-in-bud sign and acinar nodules around. CT signs of the various types and their differentiation were investigated. RESULTS The main clinical manifestations of the 72 patients with airway-invasive pulmonary aspergillosis were shortness of breath (55/72, 76.4%), cough (40/72, 55.6%), expectoration (35/72, 48.6%), dyspnea (8/72, 11.1%), weight loss (2/72, 2.8%), and fever (30/72, 41.7%). CT typing identified 3 types: 2 patients (2.8%) had type I, presenting as thickening of trachea or main bronchial walls; 3 patients (4.2%) had early type II, manifesting as thickening of lobular or segmental bronchial walls; 27 patients (37.5%) developed type IIa, manifesting as bronchiectasis; 22 patients (30.6%) had type IIb, manifesting as consolidation around the bronchus; and 18 patients (25.0%) had type III, presenting as nodules and patchy shadows with small cavities in the periphery of the lung. CONCLUSIONS Airway pulmonary aspergillosis has characteristic imaging findings, which can help early clinical diagnosis through classification according to CT imaging characteristics.

Severe Fever with Thrombocytopenia Syndrome Accompanied by Invasive Pulmonary Aspergillosis: An Autopsy Case.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne infectious disease in China, Korea, and Japan caused by the SFTS virus (SFTSV). SFTS has a high mortality rate due to multiorgan failure. Recently, there are several reports on SFTS patients with mycosis. Here, we report a middle-aged Japanese SFTS patient with invasive pulmonary aspergillosis (IPA) revealed by an autopsy. A 61-year-old man with hypertension working in forestry was bitten by a tick and developed fever, diarrhea, and anorexia in 2 days. On day 4, consciousness disorder was appearing, and the patient was transferred to the University of Miyazaki Hospital. A blood test showed leukocytopenia, thrombocytopenia, as well as elevated levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase. The SFTSV gene was detected in serum using a reverse-transcription polymerase chain reaction. On day 5, respiratory failure appeared and progressed rapidly, and on day 7, the patient died. An autopsy was performed that revealed hemophagocytosis in the bone marrow and bleeding of several organs. IPA was observed in lung specimens. SFTSV infection may be a risk factor for developing IPA. Early diagnosis and treatment of IPA may be important in patients with SFTS.

[Assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis in severe patients].

OBJECTIVE: To evaluate the assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis (IPA) in severe patients. METHODS: A retrospective study was conducted. The patients with suspected IPA admitted to intensive care unit (ICU) of Affiliated Hospital of Binzhou Medical College from January 2015 to December 2019 were enrolled. The diagnosis, clinical diagnosis and suspected diagnosis were made according to the grading criteria of Guidelines for the diagnosis and treatment of invasive fungal infection in severe patients (2007). Those who met the criteria were enrolled in the IPA group, and those who did not meet the criteria or other pathogens were enrolled in the non-IPA group. The general data of the patients were collected, and the changes of tracheal and bronchial mucosa under tracheal microscope before and after treatment were recorded, as well as the results of galactomannan (GM) test and aetiology culture of bronchoalveolar lavage fluid (BALF). The baseline, bronchoscopy and pulmonary CT manifestations and their dynamic changes were compared in each group. RESULTS: A total of 142 patients with suspected IPA were finally enrolled. Among them, 12 were pathologically proven IPA, 77 were probable IPA, 22 were possible IPA, and 31 were undefined IPA. Of the 142 patients, 60 had typical manifestations of mucosal injury under bronchoscopy, including 7 proven IPA patients (58.3%), 52 probable IPA patients (67.5%), and 1 possible IPA patient (4.5%), but none undefined IPA patient. The patients undergoing lung CT scan were 12 proven IPA patients (100%), 73 probable IPA patients (94.8%), and 21 possible IPA patients (95.5%), respectively. Most of the Chest CT showed patchy or strip density increasing and other non-specific manifestations. There were 3 proven IPA patients (25.0%), 7 probable IPA patients (9.0%), and 0 possible IPA patient (0%) who had typical IPA CT manifestations (halo sign and cavity or crescent sign). Among the patients of proven IPA and probable IPA (89 cases), there were a total of 35 cases with endoscopic airway mucosal injury and tracheoscopy reexamination ≥ 3 times. All the 35 patients received anti-aspergillus treatment, among which 16 survived and 19 died. Among the 16 patients who survived, the microscopic appearance of mucosal injury was gradually reduced and the clinical manifestations were gradually improved. Of the 19 patients who died, 16 had deteriorated endoscopic airway mucosal injury. CONCLUSIONS: The specific manifestations of severe patients with bronchial mucosal injury are of great significance in the diagnosis of IPA. In the case of severe patients who cannot receive pathological examination or chest CT in time, dynamic observation of the changes of airway mucosal injury is a simple auxiliary method to discover the changes of patients' condition in time, evaluate the effect of antifungal therapy and the prognosis of IPA.

Clinical utility of the updated European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and the Mycoses Study Group Education and Research Consortium computed tomography criteria of invasive pulmonary aspergillosis in hematological malignancies.

Invasive pulmonary aspergillosis is a life-threatening complication in the cases of patients with hematologic malignancies. In December 2019, the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and the Mycoses Study Group Education and Research Consortium published a revision and an update of the consensus definitions of invasive fungal disease. The aim of this study was to evaluate the signs and radiologic patterns of early-stage invasive pulmonary aspergillosis in computed tomography in patients with hematologic entities according to the latest criteria.This retrospective analysis of a baseline high-resolution computed tomography included neutropenic patients with hematological malignancies and probable invasive pulmonary aspergillosis. The data were collected between the years 2017 and 2019. Computed tomography was performed within 72 h from the beginning of clinical symptoms: fever, dyspnea or nonproductive cough. CT scans were analyzed by two independent radiologists according to the standardized protocol based on predefined criteria.All 35 evaluated patients had typical lesions for early-stage invasive aspergillosis. Wedge-shaped infiltrates were noted in 48.6% of patients. In this group, 40% of patients had coexisting atypical radiological findings. In 11.4% of patients, wedge-shape consolidations were noted as the only type of lesions.Employment of the latest EORTC/MSG criteria increased diagnostic value of the baseline high resolution computed tomography in our study group by 11.4%.

Role of pre-transplant chest high-resolution computed tomography and serum galactomannan index in predicting post-transplant invasive pulmonary aspergillosis in allogeneic hematopoietic cell transplant recipients.

INTRODUCTION: The role of pre-HCT chest high-resolution computed tomography (HRCT) and serum galactomannan index (GMI) in predicting the post-allogeneic hematopoietic cell transplant (HCT) invasive pulmonary aspergillosis (IPA) is debatable. METHODS: This was a single-center, prospective study from 2014 to 2019. The primary objective was to study if pre-HCT chest HRCT and serum GMI predicted IPA post-HCT. The secondary objective was day +100 mortality. All consecutive, consenting patients of ≥12 years of age undergoing allo-HCT were included and had pre-HCT chest HRCT and serum GMI. All patients received mold active antifungal prophylaxis. The EORTC/MSG criteria were used for the diagnosis of IPA. RESULTS: A total of 82 patients with median age 27 years (12-59 years) were included. The underlying diagnoses included hematological malignancies (79%) and aplastic anemia (21%). Fifteen percent of patients was treated for prior history of probable IPA (>6 weeks before HCT). Pre-HCT chest HRCT satisfied EORTC clinical criteria in 24% patients. Serum GMI ≥0.5 was seen in 27% of patients. Post-HCT probable IPA was seen in 24% of patients. There were more patients with pre-HCT chest HRCT findings satisfying EORTC clinical criteria (45% vs. 18%, P = .014) and GMI ≥0.5 (45% vs. 21%, P = .03) in the group with post-HCT IPA compared to those without IPA. There was higher day+100 mortality in patients with post-HCT IPA (55% vs. 18%, P = .001). CONCLUSIONS: The presence of EORTC clinical criteria on pre-HCT chest HRCT, serum GMI ≥0.5, and prior history of IPA predicted post-HCT IPA.

Dynamic monitor of CT scan within short interval in invasive pulmonary aspergillosis for nonneutropenic patients: a retrospective analysis in two centers.

BACKGROUND: In nonneutropenic patients with underlying respiratory diseases (URD), invasive pulmonary aspergillosis (IPA) is a life-threatening disease. Yet establishing early diagnosis in those patients remains quite a challenge. METHODS: A retrospective series of nonneutropenic patients with probable or proven IPA were reviewed from January 2014 to May 2018 in Department of Respiratory Medicine of two Chinese hospitals. Those patients were suspected of IPA and underwent lung computed tomography (CT) scans twice within 5-21 days. The items required for IPA diagnosis were assessed by their host factors, mycological findings and CT scans according to the European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria (EORTC/MSG criteria). RESULTS: Together with the risk factors, mycological findings and nonspecific radiological signs on first CT, ten patients were suspected of IPA. With the appearance of cavities on second CT scan in the following days, all patients met the criteria of probable or possible IPA. Except one patient who refused antifungal treatment, nine patients received timely antifungal treatment and recovered well. One of the nine treated IPA cases was further confirmed by pathology, one was confirmed by biopsy. CONCLUSIONS: Dynamic monitor of CT scan provided specific image evidences for IPA diagnosis. This novel finding might provide a noninvasive and efficient strategy in IPA diagnosis with URD.

Antibody-guided in vivo imaging of Aspergillus fumigatus lung infections during antifungal azole treatment.

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of immunocompromised humans, caused by the opportunistic fungal pathogen Aspergillus fumigatus. Inadequacies in current diagnostic procedures mean that early diagnosis of the disease, critical to patient survival, remains a major clinical challenge, and is leading to the empiric use of antifungal drugs and emergence of azole resistance. A non-invasive procedure that allows both unambiguous detection of IPA and its response to azole treatment is therefore needed. Here, we show that a humanised Aspergillus-specific monoclonal antibody, dual labelled with a radionuclide and fluorophore, can be used in immunoPET/MRI in vivo in a neutropenic mouse model and 3D light sheet fluorescence microscopy ex vivo in the infected mouse lungs to quantify early A. fumigatus lung infections and to monitor the efficacy of azole therapy. Our antibody-guided approach reveals that early drug intervention is critical to prevent complete invasion of the lungs by the fungus, and demonstrates the power of molecular imaging as a non-invasive procedure for tracking IPA in vivo.

Guidance on Imaging for Invasive Pulmonary Aspergillosis and Mucormycosis: From the Imaging Working Group for the Revision and Update of the Consensus Definitions of Fungal Disease from the EORTC/MSGERC.

BACKGROUND: Clinical imaging in suspected invasive fungal disease (IFD) has a significant role in early detection of disease and helps direct further testing and treatment. Revised definitions of IFD from the EORTC/MSGERC were recently published and provide clarity on the role of imaging for the definition of IFD. Here, we provide evidence to support these revised diagnostic guidelines. METHODS: We reviewed data on imaging modalities and techniques used to characterize IFDs. RESULTS: Volumetric high-resolution computed tomography (CT) is the method of choice for lung imaging. Although no CT radiologic pattern is pathognomonic of IFD, the halo sign, in the appropriate clinical setting, is highly suggestive of invasive pulmonary aspergillosis (IPA) and associated with specific stages of the disease. The ACS is not specific for IFD and occurs in the later stages of infection. By contrast, the reversed halo sign and the hypodense sign are typical of pulmonary mucormycosis but occur less frequently. In noncancer populations, both invasive pulmonary aspergillosis and mucormycosis are associated with "atypical" nonnodular presentations, including consolidation and ground-glass opacities. CONCLUSIONS: A uniform definition of IFD could improve the quality of clinical studies and aid in differentiating IFD from other pathology in clinical practice. Radiologic assessment of the lung is an important component of the diagnostic work-up and management of IFD. Periodic review of imaging studies that characterize findings in patients with IFD will inform future diagnostic guidelines.

Clinical characteristics and CT manifestations of invasive pulmonary aspergillosis in hospitalised patients with systemic lupus erythematosus.

AIM: To investigate clinical and computed tomography (CT) findings of invasive pulmonary aspergillosis (IPA) in patients with systemic lupus erythematosus (SLE) and to explore the relationships of CT findings with clinical characteristics and outcomes. MATERIALS AND METHODS: Clinical and CT findings of 14 SLE patients with proven (n=4) and probable (n=10) IPA between January 2006 and April 2013 were reviewed retrospectively and related to patients' outcomes. RESULTS: All patients (mean age, 42.3 ± 15.1 years; 11 women, three men) had active SLE, prior corticosteroid, and/or immunosuppressive therapy. Dominant CT findings performed within 10 days of the clinical onset consisted of nodules/masses (100%, 14/14), consolidations (92.9%, 13/14), and ground-glass opacity (85.7%, 12/14). Bilateral, multilobar, and upper-lobe involvement was common. Regardless of dominant patterns, the halo, reversed halo, air-crescent, hypodense, and feeding vessel signs were found in 12 (85.7%), one (7.1%), three (21.3%), seven (50%), and seven (50%) patients, respectively. There was no significant difference in CT findings between the IPA alone (n=5) and co-infection (n=9) groups and between survived (n=4) and non-survived (n=10) patients. The IPA-alone group more frequently had alcohol consumption (p=0.018), haemoptysis (p=0.023), and disseminated aspergillosis (p=0.027) than did the co-infection group. Non-survived patients tended to be older and have a history of recent hospitalisation. CONCLUSIONS: IPA is a rare, life-threatening disease affecting SLE patients in the early course of disease with high disease activity requiring corticosteroid and/or immunosuppressive therapy. Dominant CT findings are characteristics of angio-invasive form with a high frequency of the halo sign and bilateral, multilobar, and upper-lobe involvement.

Invasive pulmonary aspergillosis associated with COVID-19 in a kidney transplant recipient.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might increase the risk of invasive pulmonary aspergillosis (IPA). Although several case reports and small series have been reported in the general population, scarce information is available regarding coronavirus disease 2019 (COVID-19)-associated IPA in the setting of solid organ transplantation. We describe a case of a kidney transplant recipient with severe COVID-19 that was subsequently diagnosed with probable IPA on the basis of the repeated isolation of Aspergillus fumigatus in sputum cultures, repeatedly increased serum (1 â†’ 3)-ß-d-glucan levels, and enlarging cavitary nodules in the CT scan. The evolution was favorable after initiation of isavuconazole and nebulized liposomal amphotericin B combination therapy and the withdrawal of immunosuppression.

Short course of voriconazole therapy as a risk factor for relapse of invasive pulmonary aspergillosis.

To investigate associations of the duration of voriconazole treatment and radiological response with relapse of invasive pulmonary aspergillosis (IPA) in immunocompromised patients, we explored the risk factors for IPA relapse after successful initial treatment. All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography. Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2-17.5; P = 0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors. Longer duration of therapy should be considered for those at higher risk of relapse.

CT features and clinical characteristics of invasive pulmonary aspergillosis complicated with hematopathy. / è¡€æ¶²ç— å¹¶å‘ä¾µè¢­æ€§è‚ºæ›²éœ‰èŒç— çš„CT表现及临床特点.

OBJECTIVES: To analyze the CT manifestations,clinical symptoms, laboratory test and the interrelationship of them with secondary invasive pulmonary aspergillosis (IPA) in hematologic patients so as to improve the diagnosis and prognosis of this disease. METHODS: A total of 37 hematologic patients suspected of IPA in a tertiary referral center were selectedfrom Jun. 2004 to Sep. 2016 and the CT characteristics, clinical manifestations, laboratory test of these patients were retrospectively analyzed. RESULTS: There were 8 patients confirmed as IPA by sputum culture or bronchoalveolar lavage fluid culture among the 37 hematologic patients.The sensitivity of CT in the diagnosis of IPA was 75.0%, the specificity was 79.3%, the positive predictive value was 42.9%, and the negative predictive value was 91.3%. Multiple patchy shadows in both lungs were the most common CT signs of suspected and confirmed patients, followed by nodules, air bronchogram, cavitary lesions, consolidation, mass shadows, halo, and crescent sign. Cough, expectoration, and fever were the most common symptoms among the suspected and confirmed patients. ß-D-glucan (G)/galactomannan antigen (GM) tests for the most patients were negative, but the number of people with elevated procalcitonin (PCT) in the confirmed patients (57.1%) was higher than that in the suspected patients (31.4%). Results of sputum culture, PCT, G/GM test, and clinical manifestations were compared between the CT lesion progression group and the absorption group, and no significant difference was observed. CONCLUSIONS: Hematologic patients are susceptible to IPA. CT features showed no obvious specificity, and the G/GM test was normal in most patients. So when hematologic patients have clinical symptoms such as cough, expectoration and fever, the possibility of combination with IPA should be considered as soon as possible, and relevant examinations such as sputum culture, bronchoalveolar lavage fluid culture and pathological examination should be completed for early diagnosis and treatment to improve the prognosis of patients.