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*

Aspergillosis, Allergic Bronchopulmonary ; complications ; diagnosis ; Humans

Severe asthma is a heterogeneous disease entity to which diverse cellular components and pathogenetic mechanisms contribute. Current asthma therapies, including new biologic agents, are mainly targeting T helper type 2 cell-dominant inflammation, so that they are often unsatisfactory in the treatment of severe asthma. Respiratory fungal exposure has long been regarded as a precipitating factor for severe asthma phenotype. Moreover, as seen in clinical definitions of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS), fungal allergy-associated severe asthma phenotype is increasingly thought to have distinct pathobiologic mechanisms requiring different therapeutic approaches other than conventional treatment. However, there are still many unanswered questions on the direct causality of fungal sensitization in inducing severe allergic inflammation in SAFS. Recently, growing evidence suggests that stress response from the largest organelle, endoplasmic reticulum (ER), is closely interconnected to diverse cellular immune/inflammatory platforms, thereby being implicated in severe allergic lung inflammation. Interestingly, a recent study on this issue has suggested that ER stress responses and several associated molecular platforms, including phosphoinositide 3-kinase-δ and mitochondria, may be crucial players in the development of severe allergic inflammation in the SAFS. Defining emerging roles of ER and associated cellular platforms in SAFS may offer promising therapeutic options in the near future.
Aspergillosis, Allergic Bronchopulmonary ; Asthma* ; Biological Factors ; Endoplasmic Reticulum* ; Fungi ; Immunity, Innate ; Inflammation* ; Mitochondria ; Organelles ; Phenotype ; Pneumonia ; Precipitating Factors

No abstract available.
Allergens ; Food Hypersensitivity ; Asthma ; Invasive Pulmonary Aspergillosis ; Aspergillosis, Allergic Bronchopulmonary

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) in children with asthma, not associated with cystic fibrosis, is yet to receive the recognition it deserves. OBJECTIVE: To highlight the presentation of ABPA in children with asthma. METHODS: This retrospective review documents the occurrence of pediatric ABPA over a period of 31 years in one unit. Children with asthma, eosinophilia and infiltrates on chest radiograph were screened for ABPA. In these patients, demonstration of immediate hypersensitivity response against Aspergillus species along with serological profile and pulmonary function testing were done. Bronchography/computed tomography (CT) of the chest demonstrated central bronchiectasis (CB). CT of the paranasal sinuses was done in patients with upper airways symptoms. In those suspected with allergic Aspergillus sinusitis (AAS) consent was sought from the parents for the invasive procedure needed for the diagnosis of AAS. RESULTS: Of the 349 patients with ABPA diagnosed, 42 (12.03%) were in the pediatric age group. The mean age on presentation was 12.9 ± 4 years with a male preponderance. All patients had asthma and positive intradermal/skin prick test against Aspergillus species. Ring shadows, the most common radiological presentation, were seen in 28 of 42 patients. Bronchography/CT of the chest demonstrated CB, a feature pathognomic of ABPA, in 32 of 42 patients. High attenuation mucus plugs was observed in 7 of 36 patients while ABPA-seropositive was diagnosed in 10 of 42 patients. On imaging, sinusitis was seen in 20 of 30 patients with upper airways symptoms of whom eight had suspected AAS. Three parents consented for surgery, which confirmed the diagnosis. CONCLUSION: This study highlights the need to evaluate asthmatic children for ABPA as also to exclude AAS.
Aspergillosis, Allergic Bronchopulmonary ; Aspergillus ; Asthma ; Bronchiectasis ; Child ; Cystic Fibrosis ; Diagnosis ; Eosinophilia ; Humans ; Hypersensitivity, Immediate ; Male ; Mucus ; Paranasal Sinuses ; Parents ; Radiography, Thoracic ; Respiratory Function Tests ; Retrospective Studies ; Sinusitis ; Thorax

In susceptible individuals, inhalation of Aspergillus spores can affect the respiratory tract in many ways. These spores get trapped in the viscid sputum of asthmatic subjects which triggers a cascade of inflammatory reactions that can result in Aspergillus-induced asthma, allergic bronchopulmonary aspergillosis (ABPA), and allergic Aspergillus sinusitis (AAS). An immunologically mediated disease, ABPA, occurs predominantly in patients with asthma and cystic fibrosis (CF). A set of criteria, which is still evolving, is required for diagnosis. Imaging plays a compelling role in the diagnosis and monitoring of the disease. Demonstration of central bronchiectasis with normal tapering bronchi is still considered pathognomonic in patients without CF. Elevated serum IgE levels and Aspergillus-specific IgE and/or IgG are also vital for the diagnosis. Mucoid impaction occurring in the paranasal sinuses results in AAS, which also requires a set of diagnostic criteria. Demonstration of fungal elements in sinus material is the hallmark of AAS. In spite of similar histopathologic features, co-existence of ABPA and AAS is still uncommon. Oral corticosteroids continue to be the mainstay of management of allergic aspergillosis. Antifungal agents play an adjunctive role in ABPA as they help reduce the fungal load. Saprophytic colonization in cavitary ABPA may lead to aspergilloma formation, which could increase the severity of the disease. The presence of ABPA, AAS, and aspergilloma in the same patient has also been documented. All patients with Aspergillus-sensitized asthma must be screened for ABPA, and AAS should always be looked for.
Adrenal Cortex Hormones ; Antifungal Agents ; Aspergillosis ; Aspergillosis, Allergic Bronchopulmonary* ; Aspergillus ; Asthma ; Bronchi ; Bronchiectasis ; Colon ; Cystic Fibrosis ; Diagnosis ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Inhalation ; Paranasal Sinuses ; Respiratory System ; Sinusitis ; Spores ; Sputum

Allergic bronchopulmonary aspergillosis is one of major pulmonary fungal diseases. Although it is not a rare in clinical settings,the misdiagnosis rate is high and the treatment effectiveness remains unstable. This article reviews the recent advances in the diagnosis and treatment of this disease.
Aspergillosis, Allergic Bronchopulmonary ; diagnosis ; therapy ; Humans ; Treatment Outcome

Allergic bronchopulmonary aspergillosis (ABPA) is infrequently documented in children with asthma. Although collapse is not uncommon, middle lobe syndrome (MLS) as a presentation of ABPA is rather a rarity. A 9-year-old female child with asthma presented with increase in intensity of symptoms along with a right midzone patchy consolidation on a chest radiograph. In addition, an ill-defined opacity abutting the right cardiac border with loss of cardiac silhouette was noted. A right lateral view confirmed a MLS, which was further corroborated by high resolution computed tomography. Central bronchiectasis was also observed, which prompted a work-up for ABPA. The child met 7/8 major diagnostic criteria for ABPA. She was then initiated on oral prednisolone that resulted in a marked clinical improvement within a fortnight. Radiological clearance occurred at 3 months with inflation of the middle lobe. ABPA presenting with MLS in a child is yet to be reported. A high index of suspicion is required to establish the diagnosis of ABPA in a child presenting with MLS. This would obviate the invasive investigations usually done to ascertain the cause of MLS.
Aspergillosis, Allergic Bronchopulmonary ; Asthma ; Bronchiectasis ; Child ; Diagnosis ; Female ; Humans ; Inflation, Economic ; Middle Lobe Syndrome ; Prednisolone ; Radiography, Thoracic

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease with small prevalence. Exposure to aspergillus mold causes immunologic hypersensitivity and may cause ranges of symptoms from minimal to detrimental outcomes. Diagnosing and treating the disease before the development of bronchiectasis may save the patient from poor outcomes. This report presents a case of recurrent ABPA without any symptom of asthma, which impeded the correct diagnosis even after numerous hospitalizations.
Aspergillosis, Allergic Bronchopulmonary ; Aspergillus ; Asthma ; Bronchiectasis ; Delayed Diagnosis ; Diagnosis ; Fungi ; Hospitalization ; Humans ; Hypersensitivity ; Lung Diseases ; Prevalence