Objective: To investigate the clinical characteristics of Aspergillus fumigatus(A.f)-sensitized asthma and allergic bronchopulmonary aspergillosis (ABPA), which provides a foundation for the diagnosis and differential diagnosis of A.f-sensitized asthma and ABPA, as well as the prevention of ABPA. Methods: This was a single-center retrospective case-control study. Collected the clinical data of patients who visited the Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University from December 2018 to May 2022.A total of 122 patients were included, including 64 males (52.5%) and 58 females (47.5%).The age range was 3 to 89 years.The median age was 44 years.The average age was 41.8 years.The patients were divided into three groups (48 ABPA, 35 A.f-sensitized asthma and 39 HDM-sensitized asthma).Analyzed the differences and correlations among clinical indicators in the three groups, and evaluated the risk factors for the development of ABPA in A.f-sensitized asthma.For statistical analysis, metrological data was tested by t-test or Wilcoxon Mann-Whitney. Classification variables by chi-square test or Fisher's exact test. Pearson correlation analysis for normal distribution data.Spearman correlation analysis for skewed distribution data. Influencing factor analysis was performed using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was made, the area under the ROC curve (AUC) was calculated, and the sensitivity and specificity of the model were evaluated. Results: Compared with patients with A.f-sensitized asthma, the fractional exhaled nitric oxide (FeNO) [75.00(52.00, 87.00)ppb vs. 40.00(32.00, 52.00)ppb], eosinophils% (EO%) [10.60(6.75, 13.05) vs. 4.10(1.20, 7.30)], eosinophils (EO) [1.50(1.07, 2.20)×10⁹/L vs. 0.33(0.10, 0.54)×10⁹/L], A.f-specific Immunoglobulin E (sIgE) [10.24(4.09, 22.88)KU/L vs. 1.13(0.53, 3.72) KU/L], and sIgE to total IgE(tIgE) ratio (sIgE/tIgE) [0.0049(0.0027, 0.0100) vs. 0.0008(0.0004, 0.0017)] were higher in ABPA patients, the differences were statistically significant (P<0.001). In all patients, tIgE was positively correlated with EO% (r=0.206, P<0.05) and EO (r=0.302, P<0.001). sIgE/tIgE was negatively correlated with one-second rate (FEV1/FVC%) (r=-0.256, P<0.01). The percentage of predicted forced vital capacity [FVC(%)] was negatively correlated with FeNO (r=-0.184, P<0.05).In the ABPA group, the percentage of predicted peak expiratory flow [PEF(%)] was negatively correlated with FeNO (r=-0.295, P<0.05). In the HDM-sensitized asthma group, FeNO was positively correlated with EO% (r=0.49, P<0.01) and EO (r=0.548, P<0.001).The results of logistic regression analysis showed that FeNO and EO were the influencing factors for the development of ABPA in A.f-sensitized asthma. ROC curve analysis results showed that A.f-sIgE (cut-off, 4.108; AUC=0.749;95%CI, 0.632-0.867), sIgE/tIgE(cut-off, 0.0026;AUC=0.749;95%CI, 0.631-0.868), FeNO(cut-off, 55.5;AUC=0.794; 95%CI, 0.687-0.900), EO% (cut-off, 8.70;AUC=0.806;95%CI, 0.709-0.903) and EO (cut-off, 0.815;AUC=0.865;95%CI, 0.779-0.950) had differential diagnostic value in A.f-sensitized asthma and ABPA.The combination of FeNO, EO and EO% had good diagnostic efficiency in differentiating A.f-sensitized asthma from ABPA, with a sensitivity of 91.4% and a specificity of 84.4%. Conclusion: Compared with patients with A.f-sensitized asthma, patients with ABPA have more severe eosinophil inflammation. The higher the FeNO and EO, the more likely A.f-sensitized asthma will develop into ABPA.sIgE/tIgE may have differential diagnostic value in A.f-sensitized asthma and ABPA.The combination of FeNO, EO and EO% has good diagnostic efficacy in differentiating A.f-sensitized asthma from ABPA.
Male ; Female ; Humans ; Adult ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Aspergillus fumigatus ; Retrospective Studies ; Case-Control Studies ; Aspergillosis, Allergic Bronchopulmonary/diagnosis* ; Asthma/diagnosis* ; Immunoglobulin E ; Nitric Oxide

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Aspergillus fumigatus ; Cytokines ; Humans ; Interleukin-1beta ; Keratitis ; Receptors, IgE ; Tumor Necrosis Factor-alpha ; Tumor Necrosis Factors

Aims: This study examined the mycosynthesis of phosphorus nanoparticles (PNPs) and its application as a fertilizer for flax plant. Methodology and results: A total of thirty eight fungal isolates were isolated and screened for their abilities to synthesize PNPs. The fungal isolate was determined and identified as Aspergillus fumigatus (NCBI GenBank accession No. MN610566-MN610567). The biosynthesized nanoparticles were characterized by particle size analyzer, UV-visible spectrophotometer, transmission electron microscope (TEM), energy-dispersive X-ray spectroscopy (EDX) and fourier transform infrared spectroscopy (FT-IR). They were found to have an average diameter of 45.1 nm, regular round shape, EDX confirms the 54.63 atom % of phosphorous. The cytotoxicity of produced nanoparticles was performed to determine the safe dose that will be applied in agricultural experiment and was found to be 12.5 μg/mL. Pot experiment was performed to determine the fertilizing impact of mycosynthesized PNPs on flax plant and to equate their influence with granular single super phosphate. Results revealed that growth parameters, phosphorus content and microbial activities in the rhizosphere of flax plants were highly significantly (p ≤ 0.05) affected by foliar application of PNPs in presence of half dose of super phosphate. The TEM-micrographs of stained ultrastructural leaves showed that the PNPs treated leaves in the presence of half dose of super phosphate had normal cell structure similar to control, while the cell structure of leaves treated with PNPs but did not receive super phosphate were adversely affected. Conclusion, significance and impact of study This study clearly indicated that the application of low cost biosynthesised PNPs could save about 50% of recommended dose of phosphorus fertilizer. This study also demonstrates that it is not preferred to use PNPs as a fertilizer alone without adding super phosphate. Hence, this investigation suggests that further studies should be established to detect the safety of this nanofertilizers.
Nanoparticles--chemistry ; Aspergillus fumigatus

PURPOSE: Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease with skin barrier defects and altered immune responses. Chronic inflammation leads to irreversible fibrosis in the skin and there is no treatment to completely abolish the inflammation and fibrosis. To prevent or treat the chronic process of AD, it is necessary to develop a murine model of AD that reflects the chronic process to identify the mechanism. The aims of this study were to develop a chronic AD model with a crude extract Aspergillus fumigatus (Af) antigen. METHODS: We applied Af extract (40 µg) epicutaneously to the dorsal skin of BALB/c mice for 5 consecutive days per week during a period of 5 weeks for a chronic AD model, and 5 consecutive days repeatedly with 2 weeks interval for an acute AD model. RESULTS: The clinical score and transepidermal water loss were more increased in the chronic AD model than in the acute AD model. Histologic findings showed that more increased epidermal thickness, neutrophil infiltration and hyperkeratosis in the chronic model than in the acute model. Skin fibrosis was more prominent in the chronic model than in the acute model. The mRNA expression levels of transforming growth factor (TGF)-β, thymic stromal lymphopoietin, and interleukin-33 were increased in the skin of the chronic model compared to the acute model. The levels of total IgE, Af-specific IgE, IgG1, and IgG2a were significantly increased in the chronic model compared to controls. CONCLUSION: The Af-induced chronic AD model showed prominent fibrosis and increased TGF-β expression in the skin, which suggests that these models may be useful in the research for the mechanism of the chronic process in AD.
Animals ; Aspergillus fumigatus ; Aspergillus ; Dermatitis, Atopic ; Fibrosis ; Immunoglobulin E ; Immunoglobulin G ; Inflammation ; Interleukin-33 ; Mice ; Neutrophil Infiltration ; RNA, Messenger ; Skin ; Skin Diseases ; Transforming Growth Factors ; Water

Adult ; Alternaria ; immunology ; Alveolitis, Extrinsic Allergic ; immunology ; Animals ; Antibodies ; immunology ; Antibodies, Bacterial ; immunology ; Antibodies, Fungal ; immunology ; Antigens ; immunology ; Antigens, Bacterial ; immunology ; Antigens, Fungal ; immunology ; Aspergillus fumigatus ; immunology ; Asymptomatic Diseases ; Candida albicans ; immunology ; Cladosporium ; immunology ; Columbidae ; immunology ; Female ; Healthy Volunteers ; Humans ; Immunoglobulin G ; immunology ; Male ; Melopsittacus ; immunology ; Middle Aged ; Mucor ; immunology ; Nocardia ; immunology ; Parrots ; immunology ; Penicillium chrysogenum ; immunology ; Stachybotrys ; immunology ; Thermoactinomyces ; immunology

This research was carried out to study the secondary metabolites of endophytic fungus Aspergillosis fumigatus from Euphorbia royleana. The endophytic fungus A. fumigatus was fermented by solid fermentation,and purified by various chromatographic methods after extraction. The structures of the compounds were identified by1 H-NMR,13 C-NMR and HSQC,HMBC spectra and physicchemical properties. Three compounds were isolated and their structures were identified as 3-( 3,4-dihydroxybenzoyl)-5-( 3,4-dihydroxyphenyl)-6-methyl-5,6-dihydro-2 H-pyran-2-one( 1),hydroxysydonic acid( 2) and 11-hydroxysydonic acid( 3). Compound 1 is a new compound.
Aspergillus fumigatus/chemistry* ; Endophytes/chemistry* ; Euphorbia/microbiology* ; Fermentation ; Phenols/isolation & purification*

Among the various drug induced dermatological entities toxic epidermalnecrolysis (TEN) and Stevens-Johnson syndrome (SJS) occupy a primary place in terms of mortality. Toxic epidermal necrolysis also known as Lyell's syndrome was first described by Lyell in 1956. Drugs are by far the most common cause of toxic epidermal necrolysis, in which large sheets of skin are lost from the body surface making redundant the barrier function of the skin, with its resultant complications. Drug-induced toxic epidermal necrolysis are severe adverse cutaneous drug reactions to various precipitating agents that predominantly involve the skin and mucous membranes. Toxic epidermal necrolysis is rare but considered medical emergencies as they are potentially fatal. Drugs are the most common cause accounting for about 65%-80% of the cases. The most common offending agents are sulfonamides, NSAIDs, butazones and hydrantoins. An immune mechanism is implicated in the pathogenesis, but its nature is still unclear. There is a prodormal phase in which there is burning sensation all over the skin and conjunctivae, along with skin tenderness, fever, malaise and arthralgias. Early sites of cutaneous involvement are the presternal region of the trunk and the face, but also the palms and soles, rapidly spread to their maximum extent, the oral mucosa and conjunctiva being affected. Initial lesions are macular, followed by desquamateion, or may be from atypical targets with purpuriccenters that coalesce, from bullae, then slough. The earlier a causative agent is withdrawn the better is the prognosis. Several treatment modalities given in addition to supportive care are reported in the literature, such as systemicsteroids, high-dose intravenous immunoglobulins, ciclosporin, TNF antagonists. Recovery is slow over a period of 14-28 days and relapses are frequent. Mortality is 25%-50% and half the deaths occur due to secondary infection. Here we report a 50-year-old female of drug-induced toxic epidermal necrolysis. She was admitted to the dermatology ward with extensive peeling of skin over the trunk and limbs. She had taken alamotrigine for epilepsy. A week after taking the tablets, the patient developed a severe burning sensation all over the body and followed by a polymorphic erythematous dermatitis and widespread peeling of skin. We treated this patient with high dose corticosteroids, high-dose intravenous immunoglobulins and etanercept, but eventually she died of secondary aspergillus fumigatus infection.
Adrenal Cortex Hormones ; Aspergillosis/diagnosis* ; Aspergillus fumigatus ; Cyclosporine ; Female ; Humans ; Middle Aged ; Skin ; Stevens-Johnson Syndrome/microbiology*

In our previous studies, Bacillus megaterium KU143, Microbacterium testaceum KU313, and Pseudomonas protegens AS15 have been shown to be antagonistic to Aspergillus flavus in stored rice grains. In this study, the biocontrol activities of these strains were evaluated against Aspergillus candidus, Aspergillus fumigatus, Penicillium fellutanum, and Penicillium islandicum, which are predominant in stored rice grains. In vitro and in vivo antifungal activities of the bacterial strains were evaluated against the fungi on media and rice grains, respectively. The antifungal activities of the volatiles produced by the strains against fungal development and population were also tested using I-plates. In in vitro tests, the strains produced secondary metabolites capable of reducing conidial germination, germ-tube elongation, and mycelial growth of all the tested fungi. In in vivo tests, the strains significantly inhibited the fungal growth in rice grains. Additionally, in I-plate tests, strains KU143 and AS15 produced volatiles that significantly inhibited not only mycelial growth, sporulation, and conidial germination of the fungi on media but also fungal populations on rice grains. GC-MS analysis of the volatiles by strains KU143 and AS15 identified 12 and 17 compounds, respectively. Among these, the antifungal compound, 5-methyl-2-phenyl-1H-indole, was produced by strain KU143 and the antimicrobial compounds, 2-butyl 1-octanal, dimethyl disulfide, 2-isopropyl-5-methyl-1-heptanol, and 4-trifluoroacetoxyhexadecane, were produced by strain AS15. These results suggest that the tested strains producing extracellular metabolites and/or volatiles may have a broad spectrum of antifungal activities against the grain fungi. In particular, B. megaterium KU143 and P. protegens AS15 may be potential biocontrol agents against Aspergillus and Penicillium spp. during rice grain storage.
Aspergillus flavus ; Aspergillus fumigatus ; Aspergillus* ; Bacillus megaterium* ; Bacillus* ; Fungi ; Germination ; In Vitro Techniques ; Penicillium* ; Pseudomonas*

Allergic bronchopulmonary mycosis (ABPM) develops mainly in patients with asthma or cystic fibrosis via types I and III hypersensitivity reactions to filamentous fungi. Aspergillus spp., especially Aspergillus fumigatus, is the major causative fungus because of its small conidia, thermophilic hyphae, and ability to secrete serine proteases. The cardinal histological feature of ABPM is allergic (eosinophilic) mucin-harboring hyphae in the bronchi, for which the formation of extracellular DNA trap cell death (ETosis) of eosinophils induced by viable fungi is essential. Clinically, ABPM is characterized by peripheral blood eosinophilia, increased IgE levels in the serum, IgE and IgG antibodies specific for fungi, and characteristic radiographic findings; however, there are substantial differences in the clinical features of this disease between East and South Asian populations. Systemic corticosteroids and/or antifungal drugs effectively control acute diseases, but recurrences are quite common, and development of novel treatments are warranted to avoid adverse effects and emergence of drug-resistance due to prolonged treatment with corticosteroids and/or antifungal drugs.
Acute Disease ; Adrenal Cortex Hormones ; Antibodies ; Asian Continental Ancestry Group ; Aspergillus ; Aspergillus fumigatus ; Asthma ; Bronchi ; Cell Death ; Cystic Fibrosis ; Diagnosis ; Eosinophilia ; Eosinophils ; Extracellular Traps ; Fungi ; Humans ; Hypersensitivity ; Hyphae ; Immunoglobulin E ; Immunoglobulin G ; Invasive Pulmonary Aspergillosis ; Recurrence ; Serine Proteases ; Spores, Fungal