Although several diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) have been proposed, the disease remains frequently misdiagnosed and underdiagnosed. In 2021, Asano et al introduced new diagnostic criteria for allergic bronchopulmonary mycosis (ABPM), which were found to improve diagnostic sensitivity compared to existing criteria, but the specificity was lower.

To develop revised scoring criteria for ABPA/ABPM diagnosis, delphi surveys were conducted with two rounds in 14 experts. The integer value of the mean importance scores for each item was used as the assigning values of revised scoring criteria. We evaluated the performance of existing diagnostic criteria against revised scoring criteria, using both physician diagnosis and latent class analysis (LCA) diagnosis of ABPM as reference standard.

We screened a total of 168 patients as initial suspected ABPM. Using physician diagnosis as the reference, diagnostic sensitivity for the Rosenberg-Patterson criteria, ISHAM criteria, revised ISHAM criteria, Asano criteria and revised scoring criteria were 39.8%, 51.6%, 64.5%, 76.3% and 86.0%, while the diagnostic specificity was 100%, 100%, 100%, 85.3% and 94.7%, respectively. When using LCA as the reference, the sensitivities of these criteria were 45.1%, 48.0%, 56.7%, 71.0%, and 76.4%, the diagnostic specificity was 100%, 100%, 98.4%, 83.8% and 95.2%, respectively.

Revised scoring criteria showed improved diagnostic sensitivity compared to existing criteria while also enhancing specificity compared to the Asano criteria.

The objective of this study is to in silico predict Aspergillus fumigatus specific B-cell epitopes with a focus on enhancing Allergic Bronchopulmonary Aspergillosis (ABPA) diagnostic precision by using and to validate using molecular docking of Aspergillus fumigatus specific B-cell epitopes, aiming to overcome current serological and clinical method limitations and to support specific therapies and preventive strategies for better ABPA management.

The sequences of Asp f1, Asp f2, Asp f3, and Asp f4 from NCBI were analyzed using IEDB-AR for B-cell epitope prediction. Structural modeling and molecular docking analysis were conducted using MODELER and HADDOCK, respectively, with visualization via PyMOL and PDBe PISA.

For Asp f1, two IgE-specific (40-47) and four IgG-specific (33-76, 125-148) B-cell epitopes were predicted. Asp f3 had one IgG-specific epitope (47-73), and Asp f4 had two IgG-specific epitopes (52-133) with no IgE epitopes. Asp f2 had eight IgE-specific epitopes (56-63, 93-99, 136-146, 153-160, 185-194, 200-206, 229-239) with IgPred scores above 0.931 and no IgG-specific epitopes. Molecular docking with HADDOCK Z-scores showed strong interactions between IgE and Asp f1 and Asp f2 epitopes. PyMOL and PISA-EBI identified key residues: LYS43 in Asp f1 forms a salt bridge with the IgE heavy chain. In Asp f2, out of nineteen identified residues, six residues (LYS 94, ARG 153, ASP 200, ASP 204, ASP 207 and GLU 233) were confirmed as part of the predicted IgE epitopes, exhibiting significant interactions with IgE, in agreement with both PyMOL and PISA analysis.

This study aimed to enhance ABPA diagnostics by identifying key B-cell epitopes of Aspergillus fumigatus through in silico prediction and molecular docking, a way to support personalized therapies and preventive strategies in future.

Allergic bronchopulmonary mycoses, primarily from Aspergillus fumigatus, complicate asthma and cystic fibrosis, presenting diagnostic challenges due to overlapping respiratory symptoms.

A 48-year-old male with asthma and a history of Guillain-Barré syndrome presented with cough, chest pain, dyspnea, and weight loss. He was diagnosed with allergic bronchopulmonary aspergillosis after a series of investigations, including CT scans and bronchoscopy.

Allergic bronchopulmonary aspergillosis (ABPA) is a rare lung disease caused by an immune reaction to Aspergillus fungi in individuals with pre-existing respiratory conditions like asthma or cystic fibrosis. The primary treatment for ABPA involves systemic corticosteroids, often combined with antifungal agents, to reduce the need for long-term high-dose steroid therapy.

This case highlights the need for accurate and early diagnosis of ABPA, especially in patients with asthma or other respiratory diseases, which helps prevent potential complications. Additionally, the case provides valuable insights into how to manage patients with ABPA, contributing to the improvement of protocols and medical care in the future.

Multiple dangerous pathogens from the World Health Organization's priority list possess a plethora of virulence components, including the ability to survive inside macrophages. Often, the pathogens rely on a multi-layered defence strategy in order to defend themselves against the immune system. Here, a minimal model is proposed to study such a strategy. By way of example, we consider the interaction between Pseudomonas aeruginosa and the human host, in which the host and the pathogen counter each other in a back-and-forth interaction. In particular, the pathogen attacks the host, macrophages of the host engulf the pathogen and reduce its access to glucose, the pathogen activates the glyoxylate shunt, which is started by the enzyme isocitrate lyase (Icl), the host inhibits it by itaconic acid, and the pathogen metabolizes itaconic acid using the enzyme succinyl-CoA:itaconate CoA transferase (Ict). The flux through the glyoxylate shunt allows the pathogen to avoid carbon loss and oxidative stress. These functions are of utmost importance inside a phagolysosome. Therefore, the pathogen needs to allocate its limited protein resource between the enzymes Icl and Ict in order to maximize the time integral of a flux through the enzyme Icl. We use both random search and dynamic optimization to identify the enzyme Ict as a cost-effective means of counter-counter-counter-defence and as a possible drug target during the early phase of infection.

Elevated Aspergillus fumigatus (A. fumigatus)-specific Immunoglobulin E (IgE) is recognized as an essential diagnostic criterion for allergic bronchopulmonary aspergillosis (ABPA). However, it remains unknown whether initial A. fumigatus-specific IgE at acute stage has a role beyond diagnostic purposes.

This two-center retrospective study enrolled 149 acute ABPA patients. Risk factors for one-year exacerbation were analyzed using univariate and multivariate logistic regression. Participants were then divided into a discovery cohort (n = 93) to determine the optimal initial A. fumigatus-specific IgE cut-off value via receiver operating characteristic (ROC) curve, and a validation cohort (n = 56) to confirm exacerbation differences based on this cut-off value.

Multivariate logistic regression analysis revealed that female sex (odds ratio (OR) 2.44, 95% confidence interval (CI) 1.15-5.16, P = 0.020), A. fumigatus-specific IgE (OR 1.05, 95% CI 1.02-1.08, P = 0.002), and bronchiectasis (OR 3.61, 95% CI 1.07-12.21, P = 0.039) were independent risk factors for ABPA exacerbation. In the discovery cohort, the optimal initial cut-off value for A. fumigatus-specific IgE was calculated to be 9.88 kUA/L. And, the validation cohort confirmed that patients with A. fumigatus-specific IgE > 9.88 kUA/L were at higher risk of exacerbation (P = 0.005).

This study highlighted the prognostic utility of initial A. fumigatus-specific IgE at acute stage and found that elevated levels, especially those exceeding 9.88 kUA/L, were associated with increased risks of exacerbation in ABPA patients.

In patients with severe asthma with allergic bronchopulmonary aspergillosis (ABPA), a variety of radiological manifestations are seen. Pleural involvement is rare, and a very few case reports of secondary spontaneous pneumothorax have been reported in the literature. Here, we report an even rarer case of secondary spontaneous pneumothorax in a patient of ABPA 'without asthma'.

The distribution characteristics of clinical isolates of A. fumigatus were analyzed to provide the basis for the prevention and control of A. fumigatus infection.

From January 2021 to December 2023, the First Affiliated Hospital of Nanjing Medical University collected clinical isolates of A. fumigatus from hospitalized patients for study. Duplicate strains from the same patient in the same area were eliminated, and community-, hospital-, and colonization infections were grouped.

A total of 561 clinical isolates of A. fumigatus were identified, with 402 (82.35%) originating from male patients and 159 (17.65%) from female patients. The percentage of individuals aged 51 to 90 years was 78.97% (443/561). With the exception of surgery, which predominantly involved colonization, other departments mainly exhibited community-acquired infections (CAI) (P=0.002). The length of hospital stay was less than <15-30 days for most cases in the healthcare-associated infection group (HAI) (P<0.001). Lower respiratory tract infection accounted for the main site of infection across all three groups (95.37%), with ventilator-associated pneumonia being most prevalent in the HAI group (P<0.001). The detection rates of A. fumigatus from 2021 to 2023 were 3.89‱, 7.15‱, and 12.50‱, respectively. The detection frequencies of A. fumigatus throughout the three groups exhibited a year-on-year increase (P<0.001). Sputum samples constituted the main source of clinical isolates for all three groups, accounting for 61 strains (89.71%), 277 strains (78.69%), and 122 strains (86.52%) respectively, followed by bronchoalveolar lavage fluid samples.

The detection rate of A. fumigatus has exhibited a consistent upward trend over the past three years, with varying epidemiological characteristics observed across different infection types. It is recommended that medical institutions develop targeted prevention and control measures for A. fumigatus infections based on these unique characteristics.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease of immunocompetent patients, and invasive pulmonary aspergillosis is seen in immunocompromised patients. Hence, pulmonary Aspergillus overlap syndrome presenting with ABPA and invasive aspergillosis is extremely rare. We report a case of well-controlled bronchial asthma who presented with acute exacerbation and hypoxaemic respiratory failure. The chest imaging showed bilateral patchy consolidation. Sputum culture revealed Pseudomonas aeruginosa Video bronchoscopy showed dense greyish-white membranes studded all over the tracheobronchial tree. On further evaluation and bronchoscopic biopsy, she was diagnosed with an overlap of ABPA and invasive pseudomembranous Aspergillus tracheobronchitis with a secondary P. aeruginosa infection. She responded well to antifungal therapy, resulting in good clinico-radiological resolution, but developed some residual lung damage. Ours is the first report on pseudomembranous Aspergillus tracheobronchitis (a form of invasive pulmonary aspergillosis) with ABPA overlap, although ABPA has been reported with other forms of invasive aspergillosis.

Chronic pulmonary aspergillosis (CPA) is a disease commonly caused by Aspergillus fumigatus and other Aspergillus species characterized by cavitary lung lesions. Tea garden population is an agrarian population of Assam, mostly associated with tea plantations. Assam is a major tea-producing state with 803 tea gardens producing approximately 50% of the total tea in India, of which 177 are present in the Dibrugarh district alone. Tuberculosis is common in tea garden workers. This community-based cross-sectional study in the tea garden community of Dibrugarh was done to find the prevalence of Aspergillus IgG antibodies and CPA cases in individuals with chronic respiratory symptoms.

Patients visiting 3 tea garden hospitals and 2 referral hospitals with chronic cough and/or haemoptysis, weight loss/fatigue, and other respiratory symptoms for a duration of 3 months or more were included in this one-year study. Serum samples were tested by Immunocap Phadia 200 for Aspergillus fumigatus-specific IgG antibodies. CPA cases were diagnosed based on clinical, radiological, and serological criteria. Out of 128 samples, seropositivity was seen in 41 (32.0%) patients (cutoff value: 27 mgA/l). Male preponderance (1.6:1) with a mean age of 41.9 (±15.69) was observed. Haemoptysis and fatigue were significant symptoms seen (p-values: 0.0086 and 0.0098, respectively). Aspergillus fumigatus-specific IgG antibody was found to be significantly high in 29 out of 76 patients (38.1%) with a history of tuberculosis. Amongst them, seropositivity with active TB was 5 out of 27 patients (18.5%), and seropositivity with post-TB was 24 out of 49 patients (48.9%). Chronic cavitary pulmonary aspergillosis was the predominant type (38.1%). Proven CPA (clinically, radiologically, and serologically positive) were 22 (17.1%, 95% CI 10.7%-26.0%), and possible CPA (clinically and serologically positive but without radiological data) were 19 (14.8%, 95% CI 8.9%-23.1%).

A high prevalence of CPA (60 per 100 000) was detected. High Aspergillus seropositivity of 48.9% was seen in the post-TB population. Aspergillus-specific IgG antibody testing is the only confirmatory method for diagnosing CPA, which is available in limited centres in India. Aspergillus seropositivity should be detected in post-TB patients presenting with chronic respiratory symptoms.

Susceptibility to relapse is an important feature of allergic bronchopulmonary aspergillosis (ABPA); early identification of patients at high risk of relapse is urgently needed. A practical score that classifies the severity of ABPA according to its prognosis is not available.

We retrospectively reviewed patients with a diagnosis of ABPA at our hospital between January 2010 and December 2022. Logistic regression analysis was used to investigate independent risk factors for ABPA treatment escalation and select the variables included in the final score.

One hundred and three patients with ABPA were enrolled in this study. An eosinophil count >1000/μL, Aspergillus fumigatus-specific IgE (Sp-IgE) >3.5 kUA/L, expectoration of brownish-black mucus plugs, high-attenuation mucus (HAM) and a percentage of the predicted diffusing capacity of carbon monoxide (DLCO/pred) < 60% were independent risk factors for ABPA treatment escalation. Initial treatment with antifungals was an independent protective factor. The final scale, designated HEID, incorporated 4 dichotomized variables: HAM (H, 1 point); eosinophil count (E, cutoff 1000/μL, 1 point); Sp-IgE (I, cutoff 3.5 kUA/L, 1 point) and DLCO/pred (D, cutoff 60%, 1 point). A score of 0-1 point indicated a low relapse risk; 2-4 points indicated a high relapse risk.

This easy-to-use multidimensional grading system was capable of accurately classifying the risk of treatment escalation in ABPA.

Aspergillus fumigatus is a ubiquitous pathogenic mold and causes several diseases, including mycotoxicosis, allergic reactions, and systemic diseases (invasive aspergillosis), with high mortality rates. In its ecological niche, the fungus has evolved and mastered many reply strategies to resist and survive against negative threats, including harsh environmental stress and deficiency of essential nutrients from natural environments, immunity responses and drug treatments in host, and competition from symbiotic microorganisms. Hence, treating A. fumigatus infection is a growing challenge. In this review, we summarized A. fumigatus reply strategies and escape mechanisms and clarified the main competitive or symbiotic relationships between A. fumigatus, viruses, bacteria, or fungi in host microecology. Additionally, we discussed the contemporary drug repertoire used to treat A. fumigatus and the latest evidence of potential resistance mechanisms. This review provides valuable knowledge which will stimulate further investigations and clinical applications for treating and preventing A. fumigatus infections. KEY POINTS: • Harsh living environment was a great challenge for A. fumigatus survival. • A. fumigatus has evolved multiple strategies to escape host immune responses. • A. fumigatus withstands antifungal drugs via intrinsic escape mechanisms.

Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease caused by a hypersensitivity reaction to antigens of Aspergillus fumigatus.

The aim of this study was to evaluate the long-term clinical outcomes of omalizumab use in patients with ABPA.

In this retrospective study, 12 patients diagnosed with ABPA and receiving omalizumab for at least 2 years, and 32 patients diagnosed with severe allergic asthma and receiving omalizumab for at least 2 years (control group) were evaluated.

Evaluation was made of a total of 44 participants, comprising 11 (25%) males and 33 (75%) females, who received omalizumab for at least 2 years with the diagnosis of the control group (n = 32) and ABPA (n = 12). The increase in asthma control test (ACT) score after omalizumab was significant at 12 months and at 24 months in patients with ABPA. After omalizumab, the use of oral corticosteroid (OCS), the annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in patients with ABPA. The increase in forced expiratory volume in 1 s (FEV1) (%) and ACT score after omalizumab were significant at 12 months and at 24 months in the control group. After omalizumab, the use of OCS, annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in the control group.

Long-term omalizumab use in patients with ABPA seems to be an effective treatment for improving pulmonary function and reducing asthma exacerbations and hospitalizations.

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: "type 2-high," characterized by increased eosinophil levels in the airways and sputum of patients, and "type 2-low," distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms.

The impact of sex on allergic bronchopulmonary aspergillosis (ABPA) outcomes remains uncertain. We retrospectively included ABPA subjects per the revised International Society for Human and Animal Mycology ABPA working group criteria over 13 years. We compared the clinical features, lung function, immunological tests, imaging, and ABPA exacerbation rates between men and women. Our primary objective was to assess whether women experience higher ABPA exacerbations than men. We included 731 ABPA subjects (mean age, 34.5 years; 49.5% women). Women with ABPA were older and had underlying asthma more frequently than men. There was no difference in lung function, immunological investigations, and imaging between men and women. ABPA exacerbations occurred in a slightly higher proportion of women than men (44.5% vs. 38.2%) but did not reach statistical significance (p = 0.09). We did not find a significant sex difference in ABPA exacerbation rates. Prospective studies should confirm our findings.

The utility of two disease-severity indices, namely bronchiectasis severity index (BSI) and FACED score in allergic bronchopulmonary aspergillosis (ABPA) remains unknown.

To correlate the BSI and FACED scores with immunological parameters (serum IgE [total and A. fumigatus-specific], A. fumigatus-specific IgG, blood eosinophil count), and high-attenuation mucus on chest computed tomography in ABPA. The secondary objectives were to evaluate the correlation between BSI and FACED scores and correlate the BSI/FACED scores with the bronchiectasis health questionnaire (BHQ) and Saint George's Respiratory Questionnaire (SGRQ).

We included treatment-naïve ABPA subjects with bronchiectasis in a prospective observational study. We computed the BSI and FACED scores for each subject before initiating treatment. The subjects also completed two quality-of-life questionnaires (BHQ and SGRQ).

We included 91 subjects. The mean (standard deviation) BSI and FACED scores were 3.43 (3.39) and 1.43 (1.27). We found no correlation between BSI or FACED with any immunological parameter or high-attenuation mucus. There was a strong correlation between BSI and FACED scores (r = 0.76, p < 0.001). We found a weak correlation between BSI and BHQ/SGRQ and FACED and SGRQ.

We found no correlation between BSI and FACED with immunological parameters in ABPA. However, we found a significant correlation between BSI and FACED and a weak correlation between SGRQ and BHQ. ABPA likely requires a separate disease-severity scoring system.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by Aspergillus fumigatus (Af), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, Af proteases drive a T-helper cell-2 (Th2)-mediated allergic immune response leading to inflammation that contributes to permanent lung damage. Corticosteroids and antifungals are the mainstays of therapies for ABPA. However, their long-term use has negative sequelae. The treatment of patients with CF (pwCF) has been revolutionized by the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Pharmacological improvement in CFTR function with highly effective elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes of pwCF. The mechanism behind the improvement in patient outcomes is a continued topic of investigation as our understanding of the role of CFTR function evolves. As ETI therapy gains traction in CF management, understanding its potential impact on ABPA, especially on the allergic immune response pathways and Af infection becomes increasingly crucial for optimizing patient outcomes. This literature review aims to examine the extent of these findings and expand our understanding of the already published research focusing on the intersection between ABPA therapeutic approaches in CF and the rapid impact of the evolving CFTR modulator landscape. While our literature search yielded limited reports specifically focusing on the role of CFTR modulator therapy on CF-ABPA, findings from epidemiologic and retrospective studies suggest the potential for CFTR modulator therapies to positively influence pulmonary outcomes by addressing the underlying pathophysiology of CF-ABPA, especially by decreasing inflammatory response and Af colonization. Thus, this review highlights the promising scope of CFTR modulator therapy in decreasing the overall prevalence and incidence of CF-ABPA.

This study aimed to comprehensively investigate the prevalence of ABPA and AFRS, scrutinize existing diagnostic criteria and immunoassays, pinpoint their limitations, highlight ABPA as an occupational health implication, and identify suggestive measures to improve ABPA diagnosis in the context of Occupational Health Nursing and primary healthcare.

The data sources such as PubMed, Health and Safety Science Abstracts, OSH Update, Medline, and Google Scholar were searched.

All published studies in the English language from 1990 till Oct, 2023 using Mesh terms keywords "Allergic bronchopulmonary aspergillosis," "Allergic fungal rhinosinusitis," "Signs and Symptoms," "Rapid Diagnostic Tests," "Diagnosis," "Occupational Health," "Occupational Health Nursing," "Prevalence," "Allergens" following "Boolean operators" search strategy were selected.

This review succinctly covered signs, symptoms, and prevalence data concerning ABPA and AFRS. It briefly discussed existing diagnostic criteria and immunoassays, highlighted factors influencing the assay's variability, and underscored the role and scope of specific allergens toward improved, simple, and early ABPA diagnosis. ABPA as a neglected occupational health concern was emphasized, and the importance of RDTs in the context of healthcare professionals and OHNs was stated. Finally, this study suggested analyzing the impact of compromised post-pandemic immune status and the use of immunosuppressive drugs on ABPA prevalence among vulnerable communities and occupations.

To conclude, global and Indian ABPA and AFRS prevalence data, factors influencing existing assay variability, and the scope of improvement in RDTs for ABPA diagnosis in the background of primary healthcare professionals and OHNs were addressed.

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced TH2 inflammatory response. Fractional exhaled nitric oxide (FeNO) measurement has been used as a valuable tool in predicting the development and management of asthma, another typical TH2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear.

To investigate the association between FeNO and the prognosis of patients with ABPA to provide a basis for the use of FeNO in evaluating the efficacy of glucocorticoids in ABPA treatment.

This study comprised 2 parts; 58 patients were enrolled in the retrospective study. Clinical indexes in patients with different prognoses were compared, and receiver operating characteristic curve analysis was used to determine the threshold value. The prospective observational study involved 61 patients who were regularly followed up at 4 to 6 weeks and 6 months since the initial treatment. Patients were grouped on the basis of baseline FeNO values; correlation analysis was performed in the clinical data.

Different prognoses were observed between patients with high and low baseline FeNO values, with a threshold value of 57 parts per billion. The percentage of Aspergillus fumigatus-specific IgE, percentage of positive A fumigatus-specific IgG, and relapse/exacerbation rate differed significantly between the high and low FeNO groups. Patients with higher FeNO needed longer treatment duration and showed shorter interval between glucocorticoid withdrawal and the next relapse/exacerbation.

Our findings indicate that the level of FeNO is associated with the prognosis of ABPA. It can serve as an independent and valuable biomarker for evaluating the effectiveness of glucocorticoid treatment.

Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively.

All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396.

A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment.

These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.

This case study describes a unique scenario in which allergic bronchopulmonary aspergillosis (ABPA) was identified following treatment for pulmonary tuberculosis (PTB). ABPA is a complex pulmonary disorder that is often overlooked due to its nonspecific clinical presentation, especially in individuals concurrently diagnosed with tuberculosis (TB). Despite initial TB diagnosis and treatment, a 28-year-old male continued to experience respiratory symptoms, prompting further investigation that revealed underlying ABPA. This case underscores the importance of emphasizing the critical role of maintaining a high level of suspicion for ABPA in TB patients with persistent symptoms, highlighting the need for timely recognition and management to minimize further lung damage and improve patient outcomes.

Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are diseases caused by Aspergillus infection, and CPA can develop from ABPA in some cases. We herein report a patient with CPA overlapping with ABPA. Serum cytokine levels were evaluated at 4 time points: the ABPA diagnosis, CPA diagnosis, 6 months after the start of voriconazole (VRCZ), and 12 months after re-administration of VRCZ. Interleukin (IL)-13 levels decreased upon glucocorticoid treatment, whereas IL-25 and IL-33 levels decreased rapidly with the initiation of antifungals. Early antifungal therapy may be important to control disease progression and prevent CPA overlap.

Radiological imaging has proven to be a useful tool in the assessment of asthma, its comorbidities and potential complications. Characteristic chest radiograph and computed tomography scan findings can be seen in asthma and in other conditions that can coexist with or be misdiagnosed as asthma, including chronic rhinosinusitis, inducible laryngeal obstruction, excessive dynamic airway collapse, tracheobronchomalacia, concomitant COPD, bronchiectasis, allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, and eosinophilic pneumonia. The identification of the characteristic radiological findings of these conditions is often essential in making the correct diagnosis and provision of appropriate management and treatment. Furthermore, radiological imaging modalities can be used to monitor response to therapy.

Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear.

We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured.

ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE.

We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.

Pulmonary infiltrates with eosinophilia are a heterogeneous group of disorders that are characterized by pulmonary infiltrates on chest radiograph and elevated levels of eosinophils in the peripheral blood. Among patients with these disorders, reports of either allergic bronchopulmonary aspergillosis (ABPA) or tropical pulmonary eosinophilia (TPE) are common. However, the simultaneous occurrence of ABPA and TPE is not often reported. We present the case of a young man with a history of asthma who was diagnosed with ABPA and TPE. Initially, the patient exhibited a partial response to treatment of ABPA, but persistent symptoms and eosinophilia led to suspicion and subsequent diagnosis of TPE. With implementation of antifilarials and steroids, the patient experienced satisfactory clinical and serological improvements. This case underscores the importance of considering multiple diagnoses in patients with overlapping symptoms and highlights the need for comprehensive management strategies in complex lung diseases.

Understanding the immune response to Aspergillus fumigatus, a common cause of invasive fungal infections (IFIs) in immunocompromised individuals, is critical for developing effective treatments. Tcells play a critical role in the immune response to A. fumigatus, with different subsets having distinct functions. Th1 cells are important for controlling fungal growth, while Th2 cells can exacerbate infection. Th17 cells promote the clearance of fungi indirectly by stimulating the production of various antimicrobial peptides from epithelial cells and directly by recruiting and activating neutrophils. Regulatory T cells have varied functions in A.fumigatus infection. They expand after exposure to A. fumigatus conidia and prevent organ injury and fungal sepsis by downregulating inflammation and inhibiting neutrophils or suppressing Th17 cells. Regulatory T cells also block Th2 cells to stop aspergillosis allergies. Immunotherapy with CAR T cells is a promising treatment for fungal infections, including A. fumigatus infections, especially in immunocompromised individuals. However, further research is needed to fully understand the mechanisms underlying the immune response to A. fumigatus and to develop effective immunotherapies with CAR-T cells for this infection. This literature review explores the role of Tcell subsets in A.fumigatus infection, and the effects of CAR-T cell therapy on this fungal infection.

The filamentous fungus Aspergillus causes a wide spectrum of diseases in the human lung, with Aspergillus fumigatus being the most pathogenic and allergenic subspecies. The broad range of clinical syndromes that can develop from the presence of Aspergillus in the respiratory tract is determined by the interaction between host and pathogen. In this review, an oversight of the different clinical entities of pulmonary aspergillosis is given, categorized by their main pathophysiological mechanisms. The underlying immune processes are discussed, and the main clinical, radiological, biochemical, microbiological, and histopathological findings are summarized.

Aspergillus fumigatus is a common causative pathogen of aspergillosis. At present, triazole resistance of A. fumigatus poses an important challenge to human health globally. In this study, the biological characteristics and mechanisms of azole resistance of five A. fumigatus strains (AF1, AF2, AF4, AF5, and AF8) were explored. There were notable differences in the sporulation and biofilm formation abilities of the five test strains as compared to the standard strain AF293. The ability of strain AF1 to avoid phagocytosis by MH-S cells was significantly decreased as compared to strain AF293, while that of strains AF2, AF4, and AF5 were significantly increased. Fungal burden analysis with Galleria mellonella larvae revealed differences in pathogenicity among the five strains. Moreover, the broth microdilution and E-test assays confirmed that strains AF1 and AF2 were resistant to itraconazole and isaconazole, while strains AF4, AF5, and AF8 were resistant to voriconazole and isaconazole. Strains AF1 and AF2 carried the cyp51A mutations TR34/L98H/V242I/S297T/F495I combined with the hmg1 mutation S541G, whereas strains AF4 and AF8 carried the cyp51A mutation TR46/Y121F/V242I/T289A, while strain AF5 had no cyp51A mutation. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed differences in the expression levels of genes associated with ergosterol synthesis and efflux pumps among the five strains. In addition, transcriptomics, RT-qPCR, and the NAD+/NADH ratio demonstrated that the mechanism of voriconazole resistance of strain AF5 was related to overexpression of genes associated with energy production and efflux pumps. These findings will help to further elucidate the triazole resistance mechanism in A. fumigatus.

A 55-year-old female presented with recent exacerbation of the chronic cough, dyspnea, and copious expectoration. The symptoms worsened during the winter months. In the past, she was misdiagnosed with pulmonary tuberculosis. A computed tomography scan revealed bronchiectasis changes, high attenuated mucus, and hypereosinophilia. The diagnosis of Allergic Bronchopulmonary Aspergillosis (ABPA) with subacute invasion was confirmed through bronchoscopy and fungal culture. Treatment with oral voriconazole significantly improved lung function and quality of life. This case highlights the importance of considering invasive pulmonary aspergillosis in patients with exacerbations of asthma and bronchiectasis. Early diagnosis and appropriate treatment are essential for improved outcomes in such cases.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus that occurs in patients with asthma or cystic fibrosis. Here, we report a case of a young female with bronchial asthma who presented to our hospital with worsening breathlessness on exertion. She was diagnosed to have ABPA and was initiated on oral itraconazole while continuing inhaled long acting beta-2 adrenergic agonist and medium dose inhaled corticosteroid (ICS) for her asthma. Three months after initiation of therapy, the patient had significant improvement in breathlessness. However, she had weight gain, facial puffiness, increased facial hair and development of striae on her inner thighs, calf and lower abdomen. Her serum cortisol levels were found to be suppressed and hence a diagnosis of iatrogenic Cushing's syndrome was made. Our case describes the potentially serious interaction between ICS and oral itraconazole, a treatment very commonly prescribed in patients with ABPA.

Hitherto, the bulk of diagnostic criteria regards Aspergillus-specific immunoglobulin E as a key item, and regard IgG as an auxiliary method in diagnose. Nevertheless, there is no conclusive study in summarize the performance of IgG and IgE diagnosing ABPA.

We conducted a systematic review to identify studies report results of IgE and IgG detection in diagnosing ABPA. QUADAS-2 tool was used to evaluate included studies, and we applied the HSROC model to calculate the pooled sensitivity and specificity. Deeks' funnel was derived to evaluated the public bias of included studies, and Cochrane Q test and I2 statistic were used to test the heterogeneity.

Eleven studies were included in this study (1127 subjects and 215 for IgE and IgG). Deeks's test for IgE and IgG were 0.10 and 0.19. The pooled sensitivity and specificity for IgE were 0.83 (95%CI: 0.77, 0.90) and 0.89 (0.83, 0.94), and for IgG were 0.93 (0.87, 0.97) and 0.73 (0.62,0.82), with P value < 0.001. The PLR and NLR for IgE were 7.80 (5.03,12.10) and 0.19 (0.13,0.27), while for IgG were 3.45 (2.40,4.96) and 0.09 (0.05,0.17). The combined diagnostic odds ratio and diagnostic score were 41.49 (26.74,64.36) and3.73 (3.29,4.16) for IgE, respectively, and were 38.42 (19.23,76.79) and 3.65 (2.96,4.34) for IgG.

The sensitivity for IgG diagnosing ABPA is higher than IgE, while the specificity for IgE is higher. IgG might be able to play a more important role in filtering ABPA patients.

Fungal sensitization is highly prevalent in severe asthma. The relationship between fungus and asthma, especially Aspergillus fumigatus, has been the subject of extensive research. The ubiquitous presence of A. fumigatus, its thermotolerant nature, the respirable size of its conidia, and its ability to produce potent allergens are pivotal in worsening asthma control. Due to the diverse clinical manifestations of fungal asthma and the lack of specific biomarkers, its diagnosis remains intricate. Diagnosing fungal asthma requires carefully assessing the patient's clinical history, immunological tests, and imaging. Depending on the severity, patients with fungal asthma require personalized treatment plans, including inhaled corticosteroids and bronchodilators, and antifungal therapy. This review provides a comprehensive overview of the association between Aspergillus and asthma by reviewing the relevant literature and highlighting key findings. We discuss the diagnosis of various entities included in fungal asthma. We also debate whether newer definitions, including allergic fungal airway disease, offer any additional advantages over the existing ones. Finally, we provide the current treatment options for the individual entities, including A. fumigatus-associated asthma, severe asthma with fungal sensitization, and allergic bronchopulmonary mycoses.

Allergic fungal airway diseases are associated with asthma exacerbations and poor control. However, the early identification of allergic Aspergillus airway diseases can be challenging, especially in resource-poor countries. We aimed to evaluate the clinical utility of the point-of-care Aspergillus IgG-IgM lateral flow assay in diagnosing Aspergillus airway diseases in patients with moderate-severe asthma. Patients with moderate-severe asthma, severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) were recruited. Clinical information was extracted from clinical records. Blood samples were collected for serological tests. Serum samples were evaluated using Aspergillus immunochromatographic test (ICT). A total of 65 patients were recruited into the study, of whom 23.1% had clinical diagnosis of ABPA, 18.5% had SAFS and 58.5% had moderate-to-severe asthma who did not fit ABPA or SAFS criteria. The ICT test gave a sensitivity of 69 [95% confidence interval: 51-88]% and a specificity of 77 [60-88]% in predicting a positive Aspergillus IgG test. The sensitivity and specificity for a positive Aspergillus IgE were 77 [59-88]% and 86 [71-94]%, respectively. The majority (sensitivity: 87 [62-96]%) of patients with ABPA had positive ICT results, with a specificity of 70%. The negative predictive value was high (95 [82-99]%) with a low negative likelihood ratio (< 0.2), making it potentially useful in ruling out ABPA. The ICT assay may be valuable in ruling out ABPA in resource-limited countries where serological investigations are less feasible. The ICT assay may be particularly useful in ruling out ABPA and warrants further validation.

Patients with allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity reaction to Aspergillus fumigatus, typically present with asthma; the common imaging findings are central bronchiectasis, mucoid impaction, and tree-in-bud opacities. In this report, we discuss the case of a heavy smoker who presented with a large pulmonary mass that was initially presumed to be primary lung cancer and who was ultimately diagnosed with ABPA, which responded favorably to steroid treatment.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic fungal disease that commonly complicates the natural course of patients with asthma and cystic fibrosis. Patients with ABPA commonly present with recurrent pulmonary infiltrates or bronchiectasis. They also experience difficulty treating asthma. Characteristic radiological findings include central bronchiectasis and high-attenuation mucus. Complete unilateral lung collapse is an uncommon presentation of ABPA, with few cases reported in published literature. We present a case of a man in his mid-40s, with acute cerebrovascular disease, who subsequently developed neurological deterioration, compounded by development of respiratory failure attributed to a complete left lung collapse, requiring invasive mechanical ventilation. Initially suspected to have aspiration pneumonia, he was eventually diagnosed with ABPA and was treated accordingly. This case illustrates an uncommon aetiology for complete lung collapse in this clinical setting and serves to remind us to consider ABPA as a differential diagnosis in such patients as well.

Allergic bronchopulmonary aspergillosis (ABPA) is an underdiagnosed lung condition in patients with asthma and cystic fibrosis. Its clinical and diagnostic manifestations result from an allergic response to multiple antigens expressed by Aspergillus fumigatus, which colonize the bronchial mucus. This report presents the case of a 73-year-old female patient referred to our hospital for uncontrolled asthma for 35 years. The diagnosis of ABPA was made on the basis of clinical symptoms, peripheral blood eosinophilia, elevated total serum immunoglobulin E, positive aspergillus serology, and bronchiectasis with mucoid impaction. Systemic corticosteroids and antifungal therapy came up with satisfactory clinical results.

Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p < 0.01), and improved pulmonary function (p = 0.01). Mucus plugs in the bronchi shrank or diminished in 18 patients (82%). Despite the clinical/radiographical improvement, serum levels of total IgE, the key biomarker for the pharmacological response in ABPA, were unchanged. Anti-IL-5/IL-5Rα mAbs that directly target eosinophils are promising candidates for the treatment of patients with ABPA, especially those with mucus plugs in the bronchi.

An unmet clinical need exists in the management of treatment-refractory allergic bronchopulmonary aspergillosis (ABPA). Omalizumab has shown promising effects in case series and cohort studies; however, evidence to support its routine clinical use is lacking.

The aim of this systematic review and meta-analysis was to evaluate the clinical effectiveness and safety of omalizumab in patients with ABPA.

We conducted a systematic search across standard databases using specific key words until May 13, 2021. We performed a meta-analysis to compare the effectiveness (exacerbations, oral corticosteroid [OCS] use, lung function, and patient-reported asthma control) and safety of pre- and post-omalizumab treatment. Subgroup analyses were performed for treatment duration and underlying disease.

In total, 49 studies (n = 267) were included in the qualitative synthesis and 14 case series (n = 186) in the quantitative meta-analysis. Omalizumab treatment significantly reduced the annualized exacerbation rate compared with pretreatment (mean difference, -2.09 [95% CI, -3.07 to -1.11]; P < .01). There was a reduction in OCS use (risk difference, 0.65 [95% CI, 0.46-0.84]; P < .01), an increase in termination of OCS use (risk difference, 0.53 [95% CI, 0.24-0.82]; P < .01), and a reduction in OCS dose (milligrams per day) (mean difference, -14.62 [95% CI, -19.86 to -9.39]; P < .01) in ABPA patients receiving omalizumab. Omalizumab improved FEV₁ % predicted by 11.9% (95% CI, 8.2-15.6; P < .01) and asthma control, and was well-tolerated.

Omalizumab treatment reduced exacerbations and OCS use, improved lung function and asthma control in patients with ABPA, and was well-tolerated. The results highlight the potential role of omalizumab in the treatment of ABPA.

A male patient in his 20s presented with a cough and a small volume of haemoptysis that lasted a year. He had no other constitutional symptoms and a respiratory examination was suggestive of a consolidation. A chronic infection, such as tuberculosis, was suspected. The routine evaluation showed peripheral eosinophilia with raised serum total IgE. Sputum examination for tuberculosis was negative; hence, a high-resolution CT of the thorax was performed, which revealed bilateral bronchiectasis with high-attenuation mucus plugging. The imaging and blood profiles were in favour of allergic bronchopulmonary aspergillosis, but there was no history suggestive of asthma, and the pulmonary function test was normal. The patient underwent a skin prick test and an allergen-specific IgE test for Aspergillus fumigatus, and both were positive. His bronchoalveolar lavage cultures also grew A. fumigatus, and he responded well to antifungal therapy. This case illustrates the presentation of a rare entity-allergic bronchopulmonary aspergillosis sans asthma.

Background: Eosinophils have a double-edged role in the human body, being essential in important physiologic functions but whose presence is conspicuous in a variety of diseases characterized by a T2 inflammation phenotype. Eosinophils are exquisitely sensitive to corticosteroids, and the latter have, until recently, represented the cornerstone of treatment of eosinophilic diseases. However, most patients remain dependent on oral corticosteroids, with a notable adverse effect burden and experience a chronic relapsing disease that leads to high morbidity and mortality. Treatment prospects have changed with the advent of biologic drugs that target the eosinotropic cytokine interleukin (IL) 5 or its receptor. The success of the latter drugs in severe eosinophilic asthma has paved the way for their use in other, rarer, eosinophilic lung diseases. Recently, mepolizumab, a humanized monoclonal antibody that works against IL-5, was approved for the add-on treatment of relapsing-remitting or refractory eosinophilic granulomatosis with polyangiitis (EGPA) in patients ages ≥ 6 years. Benralizumab, a humanized antibody that binds to the α portion of the IL-5 receptor, is also being tested for its efficacy in EGPA in two clinical trials, after a growing number of case reports and case series supported its use as a steroid-sparing agent in the treatment of EGPA. Methods: In this review, we summarized the scientific literature evaluating the efficacy of benralizumab treatment in patients afflicted with rare primary eosinophilic lung diseases. Results: The literature we found, largely case reports, reported that the use of benralizumab in EGPA, chronic eosinophilic pneumonia (CEP) and allergic bronchopulmonary aspergillosis (ABPA) often led to a depletion of eosinophils, less exacerbations and a decreased systemic corticosteroid burden. No adverse effects were reported. Conclusion: Benralizumab has a prospective role in the treatment of rare eosinophilic lung diseases, which needs to be further elucidated in randomized controlled trials.