Objectives To investigate interleukin 36γ (IL-36γ) expression, and analyze the influence of IL-36γ to CD8⁺ T cell activity in chronic obstructive pulmonary diseases (COPD) patients with secondary fungal pneumonia. Methods Peripheral blood was collected from 47 COPD patients, 39 COPD patients with secondary fungal pneumonia, and 20 controls. Bronchial alveolar lavage fluid (BALF) was isolated from 27 COPD patients with secondary fungal pneumonia. CD8⁺ T cells were purified. The levels of four IL-36 isoforms in plasma and BALF were measured by enzyme linked immunosorbent assay (ELISA). CD8⁺ T cells were stimulated with recombinant human IL-36γ. The levels of interferon γ(IFN-γ), tumor necrosis factor α(TNF-α), perforin and granzyme B in the cultured supernatants were measured by ELISA. Recombinant human IL-36γ-stimulated CD8⁺ T cells were co-cultured with NCI-H1882 cells in either direct cell-to-cell contact or Transwell^TM manner. The levels of IFN-γ, TNF-α, and lactate dehydrogenase in the cultured supernatants were assessed. The percentage of target cell death was calculated. Results Plasma IL-36α, IL-36β, and IL-36γ levels were significantly elevated in both COPD group and COPD with secondary fungal pneumonia group compared with those in control group. However, only plasma IL-36γ level was higher in COPD with secondary fungal pneumonia group than that in COPD group [(200.11±99.95)pg/mL vs (53.03±87.18)pg/mL, P=0.023]. There was no remarkable difference in plasma IL-36 receptor antagonist level among three groups. IL-36γ level in BALF from infectious site was higher than that from non-infectious site in COPD with secondary fungal pneumonia group [(305.82±59.60)pg/mL vs (251.93±76.01)pg/mL, P=0.011]. IL-36γ stimulation enhanced IFN-γ, TNF-α, perforin and granzyme B secreted by CD8⁺ T cells. When IL-36γ-stimulated CD8⁺ T cells were directly mixed with NCI-H1882 cells for co-culture, the percentage of cell death was increased [(16.06±3.67)% vs (11.47±2.36)%, P=0.002]. When using Transwell^TM plate for non-contact co-culture, IL-36γ-stimulated CD8⁺ T cell-mediated death of NCI-H1882 cells showed no significant difference compared to that without stimulation [(4.77±0.78)% vs (4.99±0.92)%, P=0.554]. Conclusion IL-36γ level in plasma and infectious site is elevated in COPD patients with secondary fungal pneumonia, which enhances the cytotoxicity of CD8⁺ T cells in peripheral blood and infectious microenviroment.
Humans ; Pulmonary Disease, Chronic Obstructive/complications* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Aged ; Middle Aged ; Interferon-gamma/metabolism* ; Interleukin-1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Lung Diseases, Fungal/complications* ; Bronchoalveolar Lavage Fluid/chemistry* ; Perforin/metabolism* ; Pneumonia/immunology* ; Granzymes/metabolism*

Child ; Humans ; Invasive Fungal Infections/diagnosis* ; Lung ; Lung Diseases, Fungal/diagnosis*

Child ; Consensus ; Humans ; Invasive Fungal Infections/diagnosis* ; Lung Diseases, Fungal

Objective To analyze the CT characteristics of consolidation type of pulmonary cryptococcosis in immunocompetent patients,and thus improve the diagnosis of this disease. Methods A total of 20 cases with consolidation-type pulmonary cryptococcosis confirmed by pathological examinations were studied.Each patient underwent breath-hold multislice spiral CT,and 10 patients underwent contrast enhanced CT.The data including lesion number,lesion distribution,lesion density,performance of enhanced CT scan,accompanying signs,and prognosis were analyzed. Results The occurrence rates of single and multiple lesions were 80.0%(n=16)and 20.0%(n=4),respectively.In all the 16 multiple-lesion patients,the occurrence rate of unilateral lobar distribution was 56.0%(n=9).The 76 measurable lesions mainly presented subpleural distribution(71.1%,n=54)and lower pulmonary distribution(75.0%,n=57).A total of 39 lesions were detected in the 10 patients received contrast enhanced CT,in which 31 lesions(79.5%)showed homogeneous enhancement,34 lesions(87.2%)showed moderate enhancement,and all the lesions manifested angiogram sign.Consolidation lesions were accompanied by many CT signs,of which air bronchogram sign had the occurrence rate of 63.2%(n=48),including types Ⅲ(n =37)and Ⅳ(n=11).Other signs included halo signs(43/76,56.6%),vacuoles or cavities(9/76,11.8%),pleural thickening(14/20,70.0%),and pleural effusion(2/20,10.0%).After treatment,the lesions of 7 patients were basically absorbed and eventually existed in the form of fibrosis. Conclusions The lesions in the immunocompetent patients with consolidation type of pulmonary cryptococcosis usually occur in the lower lobe and close to the pleura,mainly presenting unilateral distribution.The CT angiogram signs,proximal air bronchogram signs,and halo signs are the main features of this disease,which contribute to the diagnosis.
COVID-19 ; Cryptococcosis/diagnostic imaging* ; Humans ; Lung ; Lung Diseases, Fungal/diagnostic imaging* ; Retrospective Studies ; Tomography, X-Ray Computed

Pulmonary cryptococcosis(PC)is a fungal infection that can be easily misdiagnosed due to its non-specific clinical features and imaging findings.This article reviews the imaging findings of PC,their relationships with pathology and immune status,and differential diagnosis of PC with other disease,so as to improve the clinical management of PC.
Cryptococcosis ; Diagnosis, Differential ; Humans ; Lung Diseases, Fungal ; Tomography, X-Ray Computed

OBJECTIVE: To study the clinical features of children with bronchial asthma complicated by pulmonary fungal infection and the risk factors for pulmonary fungal infection. METHODS: A retrospective analysis was performed for the clinical data of 150 children with bronchial asthma who were admitted from January 2015 to June 2018. Among these children, 75 had pulmonary fungal infection (fungal infection group) and 75 did not have such infection (control group). The distribution of pathogenic fungi, clinical symptoms/signs and treatment outcome were recorded for the fungal infection group. The multivariate logistic regression analysis was used to investigate the risk factors for pulmonary fungal infection. RESULTS: A total of 69 pathogenic fungi were detected in 75 children in the fungal infection group, among which Candida albicans had the highest detection rate of 61%. Major clinical symptoms were cough (93%), persistent high fever (56%), wheezing (49%) and dyspnea (48%). Major signs were dry and moist rales (43%) and moist rales (29%). Parts of children had hepatosplenomegaly. Among the 75 children in the fungal infection group, 39 were markedly improved, 26 were improved, 7 had no response, and 3 experienced aggravation and then died. Age <3 years, comorbidities of nasosinusitis and/or allergic rhinitis, asthma attacks of >3 times during hospitalization, intravenous administration of glucocorticoids, non-rational use of antibiotics, mechanical ventilation and prolonged hospital stay were independent risk factors for pulmonary fungal infection in children with asthma (OR=4.865, 3.241, 2.255, 3.725, 3.568, 1.549, 3.808; P<0.05). CONCLUSIONS Pulmonary fungal infection should be considered for asthmatic children with cough, persistent high fever, obvious dry and moist rales and hepatosplenomegaly. The asthmatic children with an age of <3 years, comorbidities of nasosinusitis and/or allergic rhinitis, asthma attacks of >3 times during hospitalization, intravenous administration of glucocorticoids, non-rational use of antibiotics, mechanical ventilation or prolonged hospital stay have a higher risk for secondary pulmonary fungal infection.
Asthma ; Child ; Humans ; Lung Diseases, Fungal ; Retrospective Studies ; Rhinitis, Allergic ; Risk Factors

BACKGROUND: The complication rate of fungal disease is higher among patients with hematological malignancies. We investigated the clinicobacteriological outcomes of resected pulmonary fungal infections complicating hematological malignancies. METHODS: Between 2001 and 2017, 21 patients with pulmonary fungal infections complicating hematological malignancies underwent resection, and their clinical records and survival were retrospectively reviewed. RESULTS: The median age of the patients was 47 years, and 13 were male. The histological diagnoses were pulmonary aspergillosis (19 cases), mucormycosis (1 case), and cryptococcosis (1 case). The indications for surgery were resistance to antifungal therapy and the necessity of surgery before hematopoietic stem cell transplantation in 13 and 8 cases, respectively. The diagnoses of the hematological malignancies were acute myelogenous leukemia (10 cases), acute lymphocytic leukemia (5 cases), myelodysplastic syndrome (3 cases), and chronic myelogenous leukemia, malignant lymphoma, and extramedullary plasmacytoma (1 case each). The surgical procedures were partial resection (11 cases), segmentectomy (5 cases), lobectomy (4 cases), and cavernostomy (1 case). The size of the lesions was 0.9–8.5 cm. Fourteen cases had cavitation. There were no surgical-related deaths or fungal progression. CONCLUSION: Pulmonary fungal infections are resistant to treatments for hematological malignancies. Since the treatment of the underlying disease is extended and these infections often recur and are exacerbated, surgery should be considered when possible.
Cryptococcosis ; Diagnosis ; Hematologic Neoplasms* ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Lung Diseases, Fungal* ; Lymphoma ; Male ; Mastectomy, Segmental ; Mucormycosis ; Mycoses ; Myelodysplastic Syndromes ; Plasmacytoma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Pulmonary Aspergillosis ; Retrospective Studies ; Thoracic Surgery

OBJECTIVE: To improve the understanding of the clinical features of pulmonary cryptococcosis in non-human immunodeficiency virus (non-HIV) infection patients and reduce delay in diagnosis, or misdiagnosis. METHODS: The clinical features, imaging characteristics, laboratory examinations, treatment and prognosis of 34 cases of pulmonary cryptococcosis were retrospectively analyzed. The data were collected from Peking University First Hospital from June 1997 to June 2016. RESULTS: There were 34 cases diagnosed with pulmonary cryptococcosis, including 22 males and 12 females, aged from 20 to 75 years [average: (50.1±15.0) years]. There were 16 cases with host factors and (or) underlying diseases named immunocompromised group. In the study, 67.6% patients had clinical symptoms while 32.4% patients had no symptoms. The most common symptoms included cough, fever, chest pain, shortness of breath, and hemoptysis in sequence. Common chest imaging findings were patchy infiltrates, consolidation, single or multiple nodular or masses shadows. Among the 20 cases with cryptococcal capsular polysaccharide antigen detection, 19 were positive. Eleven cases underwent routine cerebrospinal fluid examination, and 3 cases complicated with central nervous system cryptococcal infection. At first visit, 24 cases were misdiagnosed, among which, 11 cases were misdiagnosed as lung cancer. The diagnosis of 15 cases was proved by percutaneous lung biopsy and 11 were confirmed by surgery, while 8 were diagnosed clinically. Then 11 cases were treated by surgical resection, and in median 4 years' followp, there was 1 case of recurrence. And 23 cases were treated with antifungal therapy, and in median 8 years' follow-up, 3 cases lost to the follow-up and 1 case of recurrence. Compared with normal immune group, immunocompromised patients had higher ages (P=0.017), more crackles (P=0.006) and more percentage of increase of peripheral white blood cells or neutrophils (P=0.003), but no significant difference in symptoms, imaging characteristics or hospitalization time. CONCLUSION There were no specific clinical symptoms and signs for pulmonary cryptococcosis in non-HIV patients. Diagnosis of pulmonary cryptococcosis depends on pathology. Percutaneous lung biopsy was mostly recommended for clinical highly suspected patients. Cryptoeoccal capsular polysaccharide antigen detection had a high sensitivity for the clinical diagnosis. Antifungal drug therapy was the major treatment, and the prognosis of the most patients was good.
Adult ; Aged ; Cryptococcosis/pathology* ; Delayed Diagnosis ; Diagnostic Errors ; Female ; Humans ; Lung Diseases ; Lung Diseases, Fungal/pathology* ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

PURPOSE: Infection and malignancy represent two common complications after solid organ transplantation, which are often characterized by poorly specific clinical symptomatology. Herein, we have evaluated the role of 18F-fluoro-2-deoxy-Dglucose (FDG) positron emission tomography/computed tomography (PET/CT) in this clinical setting.METHODS: Fifty-eight consecutive patients who underwent FDG PET/CT after kidney, lung or heart transplantation were included in this retrospective analysis. Twelve patients underwent FDGPET/CT to strengthen or confirma diagnostic suspicion of malignancies. The remaining 46 patients presented with unexplained inflammatory syndrome, fever of unknown origin (FUO), CMVor EBV seroconversion during post-transplant follow-up without conclusive conventional imaging. FDG PET/CT results were compared to histology or to the finding obtained during a clinical/imaging follow-up period of at least 6 months after PET/CT study.RESULTS: Positive FDG PET/CT results were obtained in 18 (31 %) patients. In the remaining 40 (69 %) cases, FDG PET/CT was negative, showing exclusively a physiological radiotracer distribution. On the basis of a patient-based analysis, FDG PET/CT's sensitivity, specificity, PPV and NPV were respectively 78 %, 90 %, 78 % and 90 %, with a global accuracy of 86 %. FDG PET/CT was true positive in 14 patients with bacterial pneumonias (n = 4), pulmonary fungal infection (n = 1), histoplasmosis (n = 1), cutaneous abscess (n = 1), inflammatory disorder (sacroiliitis) (n = 1), lymphoma (n = 3) and NSCLC (n = 3). On the other hand, FDG PET/CT failed to detect lung bronchoalveolar adenocarcinoma, septicemia, endocarditis and graft-versus-host disease (GVHD), respectively, in four patients. FDG PET/CT contributed to adjusting the patient therapeutic strategy in 40 % of cases.CONCLUSIONS: FDG PET/CT emerges as a valuable technique to manage complications in the post-transplantation period. FDG PET/CT should be considered in patients with severe unexplained inflammatory syndrome or FUO and inconclusive conventional imaging or to discriminate active from silent lesions previously detected by conventional imaging particularly when malignancy is suspected.
Abscess ; Adenocarcinoma ; Diagnosis ; Electrons ; Endocarditis ; Fever of Unknown Origin ; Follow-Up Studies ; Graft vs Host Disease ; Hand ; Heart Transplantation ; Herpesvirus 4, Human ; Histoplasmosis ; Humans ; Kidney ; Lung ; Lung Diseases, Fungal ; Lymphoma ; Organ Transplantation ; Pneumonia, Bacterial ; Positron-Emission Tomography and Computed Tomography ; Retrospective Studies ; Sensitivity and Specificity ; Sepsis ; Seroconversion ; Transplants

Differential diagnosis of invasive aspergillosis from other pulmonary fungal infections including mucormycosis is important because the treatment is pathogen-dependent. Clinically, invasive aspergillosis is often discriminated from other mold infections on the basis of typical histopathologic features in the biopsy specimen. However, biopsy alone is not always complete because different fungal species can display similar histopathologic features. Surrogate markers or molecular-based assays can be useful when the results of conventional diagnostic modalities are conflicting. Here, we present a case of invasive pulmonary aspergillosis histologically mimicking mucormycosis, which was confirmed by fungal polymerase chain reaction.
Aspergillosis ; Biomarkers ; Biopsy ; Diagnosis, Differential ; Fungi ; Invasive Pulmonary Aspergillosis* ; Lung Diseases, Fungal ; Mucormycosis* ; Polymerase Chain Reaction